The therapeutic community: multivariate prediction of retention. Multiple regression procedures were employed to study the profile of resident time in program, demographic, sociobackground, and psychological variables in relationship to retention. The sample consisted of 809 Phoenix House residents who were primarily male (81.4%) and Black (64.9%). A psychological battery was administered on a cross-sectional basis. The multiple R of .44 and R2 of .19 were large for this type of research. Time in program accounted for over half the variance explained. Ten other measures contributed significantly to the explained variance. Residents who dropped out were less likely to be Blacks and more often came from lower SES families but with less family deviance; they made fewer prior attempts at giving up drugs and had lower education levels. Psychologically, they were generally more defensive and disturbed.


A survey of substances use among junior and senior high school students in New York state, Winter 1974-75. A survey designed to assess drug and alcohol use among the 1,600,000 students in Grades 7 through 12 who attend New York State public schools was administered in 10i schools during the winter of 1974-75. Findings indicate that over 80% of the students have used alcohol and that almost one-third of the students have used marijuana at least once. In addition, 60% of the marijuana users have used no other substance, with the possible exception of alcohol. Also, if a student has used a substance, he is likely to have used it within the last 6 months. Finally, multiple substance use is not predominant among marijuana users, but is predominant among users of other substances.


A follow-up of admissions to the California Civil Addict Program. A follow-up interview study of early admissions to the California Civil Addict Program found that those continuing in the program performed substantially better during the commitment period than did a comparable group discharged shortly after admission. To a lesser extent, the program also appeared to have had some impact subsequent to discharge. Those program discharges defined as successes tended to do relatively well until the time of interview. Comparisons under the strict (pre-1970) and more lenient regimens showed roughly comparable behavior, but the availability of methadone maintenance was also a significant factor in reducing heroin use during the latter period.


A comparison of recidivism rates for alcoholic detox residents referred to hospitals, halway houses, and outpatient facilities. Recidivism rates were studied for alcoholics referred to treatment facilities from a detoxication center. The aims were to examine (1) the proportions of clients who arrived, (2) whether similar clients were referred to different facilities, and (3) whether different facilities had different recovery rates. Only a minority improved in terms of recidivism. There were no differences for those referred to halfway houses, hospitals, and nonresidential programs. Those who arrived for treatment or completed it did not have higher improvement rates than those who did not.


Follow-up evaluation of drug abuse treatment. Several fundamental issues in the design and planning of a follow-up evaluation are introduced. Many factors, including the design of the questionnaire, relationship to the subject, and confidentiality policies, determine  both the rate and validity of the responses. Utilizing the described planning the supervision, staff time can be minimized, and estimates are given for both mailed and personal interviews. A variety of specific tracking techniques is outlined which facilitate the location of subjects who cannot be found at formerly listed addresses.


The effect of marijuana on small group process. In a research group setting, marijuana increased social-emotional interpersonal communication and decreased task-oriented behavior. Following a frustration stimulus, groups of marijuana smokers appeared nonintoxicated and showed improvement in consensus problem solving. Interpersonal behavior with marijuana may depend in part, on the presence or absence of demand characteristics for task performance. Creativity in group problem solving was not improved by marijuana.


The use of an alcoholism screening test to identify the potential for alcoholism in persons on methadone maintenance. Alcoholism has become a problem of increasing prominence in persons enrolled in methadone maintenance programs. Since early identification of the potential problem drinker may result in successful intervention, a method to screen individuals applying for admission to methadone maintenance who have a proclivity toward alcoholism would be of great value. A modified self-administered alcoholism screening test (SAAST), previously confirmed to identify "hidden alcoholics" in a general nonnarcotic-using population, was utilized as a screening device in three groups of narcotic-dependent persons on methadone maintenance: 30 individuals who had a known problem with alcoholism, 30 individuals without any history or signs of alcoholism over an extended time period, and 80 persons entering methadone maintenance who initially denied any problems with excessive drinking. The ability of the modified SAAST to separate the alcoholic from the nonalcoholic narcotic addict was confirmed (p less than 0.001). This test was also found to have considerable predictive value in determining those individuals initially denying a history of excessive alcohol intake who become problem drinkers.


The reluctance to combine.

The reluctance to combine. The shifting of substance abuse in this country away from a pattern of single substance dependence toward multiple substance abuse has been accompanied by renewed interest in the possibilities of so-called combined treatment and its ideological base, a generic conceptualization that encompasses and integrates into a unitary theory all types of substance abuse. This view maintains that many of the differences separating alcoholic persons from other substance abusers have more to do with factors like age, ethnic, social and cultural background--and prejudice--than with real differences in the addictive processes or therapeutic needs. Some careful studies of combined treatment have found it no less effective than substance segregated treatment. Some persons are helped, others are not. Until we have reliable ways to select out those who would benefit form combined treatment from those who would not, the method remains experimental, not yet to be advocated for mass use. What is needed at once is a generic concept of substance abuse. This would prepare the way for planning, legislation, program organization, national data systems, and research that could be designed for the most effective response to today's needs and problems. An especially pressing need is for generic training and credentialling of workers in the alcohol and drug fields. As the many questions raised by a generic viewpoint are considered, one can observe that much of the resistance to this concept among professionals is attributable to fear of the unfamiliar, protection of vested interest, misapprehension about consequences and, not least, prejudice reflecting the stereotyped ideas of the general population.


Experimental heroin users: an epidemiologic and psychosocial approach. An interview study was conducted on a sample of experimental heroin users involved in an adolescent heroin epidemic. Results showed that heroin use patterns varied, with high users stabilizing at a low frequency of use over a long period of time. Results also showed that experimental users were more likely to occur in the late phase of a local heroin outbreak. Psychosocial data indicated that high users differed from low users in that they had less supportive family experiences, more experience with the criminal justice system, and less positive feelings about self and future.


The characteristics of Cuban Immigrant inhalant abusers. The characteristics of Cuban immigrant inhalant abusers admitted to the Spanish Family Guidance Clinic during a 1-year period were studied. Not surprisingly, this group was found to be similar to inhalant abusers in the national picture. The inhalers in this study were all males, mostly very young, from very low socioeconomic levels, largely from disrupted family backgrounds and disrupted neighborhoods. They showed poor school and/or employment performance, serious anti-social behavior, and occasional hallucinatory experiences. This group of inhalers was found to be multiple substance abusers and more likely to be characterized by a pattern of polydrug abuse than by their abuse of inhalants per se. This finding confirms a general national trend toward the abuse of multiple rather than single substances. A comparison of inhalers with a carefully chosen control group of clients admitted into the Clinic during the same period of time, matched by nationality, sex, and age, indicates that the two groups are similar in important ways. Both groups present general profiles of acting out adolescents, and tend to come from low socioeconomic, disrupted families and poor neighborhoods.


Risk-taking related to drug use: an application of the shift-to-risk design. The utility of the shift-to-risk design for studying the influence of peer groups on drug taking was investigated. Two studies using this design with drug content were conducted, varying the level of information provided about a drug. Subjects were from two college classes consisting of 26 and 28 students. Results indicated that the specification of possible harmful drug effects which are somewhat minimal lead to a significantly greater willingness to recommend trying the drug. In addition, a tendency for a shift-to-caution was found. It was concluded that the shift-to-risk designwas useful for studying decision-making regarding drug use, and that both users and nonusers of drugs should be included in future research.


Personality characteristics of students who became heavy drug users: an MMPI study of an avant-garde. A psychometric study assessed the possibility of a preexisting personality configuration in students who became heavy drug users. We compared the MMPI profiles of 33 Carnegie Institute of Technology students who became heavy users of marijuana and hallucinogenic drugs and 33 peer control subjects. All subjects had been given the MMPI as entering freshmen in the years 1962-1965. The preuser sample constituted an avant-garde of drug-oriented counterculture in this setting. Profiles for both groups were well within normal limits yet unique in respective configurations. Preusers appeared to be socially skillful, adventorous, impulsive, and resistant to authority, while control subjects seemed less socially skilled, reserved, compulsive, and compliant. Significant scale differences appeared on Hy, Pd, and Ma, all being higher for preusers, and Es which favored the controls.


Trends in drug use and crime and their relationship in an arrested population. Trends in drug use and criminal charges of 44,223 consecutive admissions to the District of Columbia Superior Court lock-up between December 1971 and April 1975 were analyzed. While the number of persons arrested and admitted to the lock-up remained relatively constant during this time, drug use as measured by positive urinalysis declined substantially in 1973 and remained at a lower level through 1975. Heroin use showed a decline similar to the overall trends in 1973, but began to increase in mid-1974. Arrestees who were drug positive were generally less likely to be charged with major crimes of violence than those who were drug negative. Exceptions to this pattern as well as trends in drug use and crime in the arrested population are discussed.


Colonoscopic polypectomy.

Colonoscopic polypectomy. A total of 87 polyps were treated during 62 colonoscopic examinations on 60 patients; 69 polyps were resected and 18 were fulgurated with the hot-biopsy forceps. Fifteen patients were under 13 years old, and the average age was 38 years. Twelve patients had more than one polyp. There were no complications and the method could be carried out in all patients, whenever it was indicated. Sixteen polyps were hamartomas, 13 shistosomatic, six hyperplastic, two lymphoid and 36 adenomas. Among these adenomas, six showed evidence of foci carcinoma, one in situ and five, invasive. Surgical resection was indicated in only one patient with sessile polyp with invasive focus of carcinoma. No metastasis was detected whatsoever.


Endoscopic retrograde cholangiopancreatography. Evaluation based on experience with 805 examinations. ERCP was evaluated on the basis of 805 examinations. Visualization of the common bile duct and the pancreatic duct was possible in 44%, of the common bile duct in 22% and of the pancreatic duct alone in 24.6% of the cases. The ductal systems were not opacified in 9.4% but the failure rate decreased from 18.2% to 5.4% within increasing experience. Pathological changes were found in both ducts in 2%, in the common bile duct in 42.2% and the pancreatic duct in 11.4% of the cases. Diagnostic information was supplied by ERCP in 84.4% of the cases. Complications developed in four cases (acute pancreatitis in three and cholangitis in one). There was no mortality in the entire series. It is concluded that ERCP is a valuable diagnostic method that is frequently successful and reasonably safe.


Ulcerative esophagitis and colitis in a pediatric pantient with Behcet's syndrome. Response to steroid therapy. The gastrointestinal manifestations of Behcet's syndrome including colitis and esophageal ulceration have been recognized in recent years. In the present case, a girl with Behcet's syndrome was followed since age 11 for oral, vaginal, perianal ulcers and neurological involvement. At age 16 she developed esophageal ulceration and colitis, was treated with steroids and improved. Endoscopic and radiographic findings are presented, previously reported cases are reviewed and treatment is discussed.


Effect of antrectomy and vagisecretion on gastric acid output and gastrin secretion. In three dogs with denervated Heidenhain pouches, ingestion of cooked beef liver caused increased acid output and gastrin secretion. After antrectomy and gastrojejunal anastomosis, ingestion of the liver did not increase serum gastrin levels throughout the experiment. Acid output, however, although markedly reduced, was elevated over basal levels during the last three hours of the four-hour experiment. Total abdominal vagotomy did not alter gastrin secretion but further inhibited acid output in response to the test meal. These results indicate that in the dog intestinal gastrin is not released in response to a beef liver meal. Acid output postantrectomy, although reduced, does respond to the meal and is further decreased after vagotomy. A hormonal mechanism other than the release of intestinal gastrin is responsible for the intestinal phase of gastric acid secretion.


Multiple sclerosis and malabsorption.

Multiple sclerosis and malabsorption. Malabsorption tests were studied in 52 patients with multiple sclerosis. The stools were examined microscopically for fat and undigested meat fibers and were found to be abnormal in 41.6 and 40.9% respectively. Abnormally low five hour excretion of d-xylose was demonstrated in 26.6% cases. Malabsorption of Vitamin B12 was found in 11.9% cases. The jejunal mucosa was examined histologically and by tissue immune technic including viral studies. Histology showed normal mucosa in all except seven patients in whom an increased inflammatory infiltrate was present. Fluorescent antibody studies revealed the presence of measles virus antigen in all patients and immunofluorescent studies showed a variable degree of immune reaction in the majority of cases. The significance of these findings in the pathogenesis of multiple sclerosis is discussed.


Scleroderma and intestinal perforation.

Scleroderma and intestinal perforation. We report four cases of scleroderma and intestinal perforation. There were three instances of colonic perforations, two associated with fecal impaction and stercoral ulceration and one with evidence of vasculitis. The fourth patient was an unusual instance of spontaneous perforation of the small intestine in scleroderma.


Tumor-associated hyperamylasemia.

Tumor-associated hyperamylasemia. Studies were made in eight patients with hyperamylasemia associated with cancer of the lung, pancreas or colon. Isoamylase analysis, conducted in seven of the eight patients revealed that the dominant isoamylase component was S-type in three and P-type in three; in one patient both isoamylases were elevated about equally. Examination of the serum or urine of the same seven patients for subcomponent isoamylase disclosed the presence in two of the seven of an unusual isoamylase designated "Y-type". This subcomponent isoamylase was also found in some samples of human milk, but not in normal persons or in patients with a variety of disorders other than cancer. The significance of hyperamylasemia occurring in association with cancers, the factors responsible for the variability in isoamylase pattern in those with hyperamylasemia, and the relationship, if any, of the "Y" isoamylase form to cellular growth and replication are all presently obscure and remain to be elucidated.


Percutaneous transhepatic cholangiography and needle biopsy in the differential diagnosis of obstruction of bile flow. Twenty-four patients with clinical evidence of obstructive jaundice were examined by percutaneous transhepatic cholangiography (PTC) and needle biopsy (NB) of liver. The presence of extrahepatic bile duct obstruction was confirmed by surgery in 21 cases. PTC and the combination of both methods were superior to NB alone in the differential diagnosis between extra- and intrahepatic biliary obstruction. Sampling bias added to the difficulties of NB in distinguishing beween these two types of obstruction. The combination of both precedures proved most useful in three cases with intrahepatic obstruction, in which the patients were spared unnecessary surgery. In five cases the NB provided additional information about the nature of the tumor metastases and gave suport to the clinicians in their therapeutic approach.


Gastritis varioliformis. Chronic erosive gastritis with protein-losing gastropathy. A patient with chronic erosive gastritis and protein-losing gastropathy is reported. Presentation was with weight loss and abdominal discomfort. There were endoscopic and radiological features of erosive gastritis. Radioactive chromium studies confirmed that the low serum albumin was associated with fecal protein loss. No improvement occurred with bed rest or Caved S but coincided with DeNol therapy.


Eosinophilic gastroenteritis with ascites and colon involvement. The case of a 39-year old white man with eosinophilic gastroenteritis is presented. The major clinical features were gastric outlet obstruction, diarrhea and massive ascites. At surgery, significant involvement of the entire gastrointestinal tract from the gastric antrum to the sigmoid colon was found. Histologic documentation of colon involvement was obtained. The response to corticosteroids was prompt and sustained. At present, he is maintained on an alternating day schedule of steroid administration.


The radiology corner. Neonatal small left colon syndrome. The signs and symptoms of intestinal obstruction in the newborn infant often present a difficult diagnostic problem. Plain films often fail to differentiate small from large bowel obstruction. Contrast studies may be decisive and indicate the site of obstruction and its etiology. This is especially important in nonsurgical conditions as the following case of the "neonatal small left colon syndrome" illustrates.


In acute pancreatitis the decrease of villous activity, the damage of the intestinal mucosa might be induced by agents produced during pancreatitis or by trypsin. If injected into the blood circulation, pancreatitic abdominal exudate significantly reduces villous activity and blood pressure. A relationship can be established between the log of the exudate doses and their effects.


Measured and laboratory-stated parameters of hydrophilic contact lenses. One hundred thirty-one new hydrophilic lenses made by 3 manufacturers were randomly selected from an optometry clinic for measurement and inspection. Approximately 60% of the base-curve specifications fell within the following ranges for the measured dimensions: Bausch & Lomb Soflens contact lenses, less than 0.150 mm; Milton Roy Naturvue lenses, less than 0.375 mm; Soft Lens Inc. Hydrocurve, less than 0.225 mm. More than 65% of the lenses supplied by all the manufactures were within 0.25 D of the power specification. About two-thirds or more of all lenses had a central thickness and overall diameter within 0.04 mm and 0.40 mm, respectively, of the manufacturers' specifications, although there were notable differences among manufacturers. Most of these new lenses exhibited surface scratches and other surface defects, and many lenses had edge defects.


Stereoacuity in mentally retarded and intellectually normal adolescents. Stereoacuity was measured in 30 intellectually normal and 30 mentally retarded adolescents, matched for age and sex, using the Titmus stereo test to provide nasalward and temporalward target disparities. The intellectually normal group had significantly better stereoacuity for both types of disparity. No statistically significant differences between nasal and temporal disparities were found within groups. A learning effect is shown for the mentally retarded.


Dimensional stability of several hard contact lens materials. Hard contact lenses of identical specification, but manufactured from different materials, were immersed in water for up to 168 hours. The back central optic radius of each lens was periodically measured. The magnitude and time course of curvature change during hydration were found to vary with the material.


Applanation tonometer correlations.

Applanation tonometer correlations. The Goldmann, Mackay-Marg, and Non-contact tonometers were compared on 25 subjects to establish correlations between measurements of intraocular pressure by these instruments. Topical anesthetic was used for the Goldmann and Mackay-Marg readings only. Correlations were high: between the Goldmann and the Non-contact, +0.93; between the Mackay-Marg and the Non-contact, +0.81; and between the Goldmann and the Mackay-Marg, +0.87.


Red (rust) spots in hydrogel contact lenses. The red spot phenomenon was investigated by examining sagittal sections of corroded ferrous particles embedded in the matrix of hydrogel contact lenses and also by analyzing the incidence of this contamination. The incidence of the red spot phenomenon was found to be 4.4% and was unrelated to the method of manufacture or whether the lens was new or used. The ferrous particles are of probable exogenous origin, introduced by environmental or aqueous debris, and the subsequent corrosion is accelerated by heat disinfection.


Reaction time to scotopic flashes of light. Reaction time (RT) to scotopic flashes of light presented at various locations along the horizontal meridian near the fovea was measured. RT progressively decreased from a maximum near the fovea to a near-asymptotic value at an eccentricity of 12 deg in both the nasal and the temporal retina.


A marble used as a low-vision reading aid: a case report. An unusual low-vision remedy was encountered in which a simple dime-store marble was used in near vision tasks. Although the marble was found satisfactory as a low-vision aid, the patient could be better assisted with a commercially available magnifier of lesser dioptric power. This case serves to demonstrate a patient's ingenuity in independently solving his own low vision problem.


An optometry course on quality assurance. The Pennsylvania College of Optometry, in response to an increasing demand for accountability from many segments of society, has initiated a course for first-year students on quality assurance. The course covers the concept of peer review, the principles of evaluating optometric care, the rationale of ambulatory records, and the concepts of optometric diagnosing and problem solving. We believe that the need to expose optometric students to basic quality-assurance principles will increase with future third-party payment programs and consumer-rights movements.


Transient endothelial changes soon after wearing soft contact lenses. Changes in the appearance of the corneal endothelial mosaic have been observed within minutes after insertion of soft contact lenses in unadapted patients. The changes consist of increased separation between cells and circumscribed black zones (endothelial "blebs") obscuring or displacing the mosaic.


[Hodgkin's disease with epithelioid cells. Study of 56 cases having undergone an exploratory laparotomy]. Histological examination of the various specimens taken during an exploratory laparotomy for Hodgkin's disease revealed the presence of epithelioid cells in 56 cases out of a total of 235 patients (i.e. 23.8 p. 100). These cells were disseminated throughout the lymphoid tissue or grouped in clumps, in plaques or, more rarely, as true follicles. They were found either in contact with Hodgkin's lesions or at a distance in organs free of disease. They were found in Lukes-Rye histological types 1, 2 and, above all, 3. Their significance remains unknown. The most likely hypotheses would appear to be those of a response to the accumulation of substances to be eliminated (tumour antigens?) or those of a disorder in cellular immunity.


[Woringer-Kolopp syndrome. Histological and ultrastructural study of a case]. The authors report a case of Woringer-Kolopp syndrome. This was a rare form with multiple cutaneous features with a typical clinical and histological appearance. Ultrastructural study revealed the presence of granules with an opaque centre in the cytoplasm of the abnormal cells, and the close relationship of the latter with neurites. On the basis of these characteristics, they may be likened to the Merkel cells of the epidermis. Thus Woringer-Kolopp disease could be related to the proliferation of Merkel cells.


[Mullerian adenosarcoma and uterine adenofibroma]. Description of a case of a mixed Mullerian tumour of the body of the uterus, with histologically benign epithelial and connective components, developing in a 72-year-old woman. A cervical recurrence and perineal metastasis were solely leiomyomatous in terms of their structure and were associated with peritoneal carcinomatosis and pulmonary involvement. Death occurred three years after subtotal hysterectomy and five years after the first clinical manifestations.


[Cerebral fat emboli. Apropos of a case of a peroperative complication associated with the use of a bone cement in orthopedic surgery]. A case of a per-operative complication associated with the use of a bone cement in orthopaedic surgery is reported. Pathological study revealed the presence of massive fat emboli : pulmonary and cerebral. There were recent infarcts throughout the cerebral cortex, unrelated to arterial topography. The physiopathology of these unusual cerebral lesions ;n association with fat emboli is discussed. They would appear to be related to the particularly abundant and voluminous nature of the fat emboli.


[Idiopathic liquefying panniculitis with fatal outcome]. A 34 year's old female patient died of nodular liquefying panniculitis after a six months evolution. The only systemic lesions found at post mortem histological examination were an involvement of both pleural cavities with an oily fluid. This seemed to have been the cause of death. This symptomatology was not observed in any of the 26 fatal cases of Weber-Christian disease published in the literature among which 11 cases with no other lesions than adipous tissue lesions, 6 cases where death was related to secondary effects of panniculitis and 9 cases where death was related in intercurrent diseases.


[Kogöj's spongiform pustule; ultrastructural results]. The authors demonstrate, with the help of electron microscopy, the location of the polymorphonuclear neutrophils and of the keratinocytes in the Kogöj's pustule. Unlike to the classical ideas, the polymorphonuclear neutrophils are not located in the epidermal cells but in the intercellular spaces. The lesions of keratinocytes, the content of the spaces and the histogenesis have been studied. The results of this study are compared to thoses formed in the literature.


[An case of acute diffuse seleroderma in an infant]. The authors report a case of diffuse scleroderma in a 15 months old infant. Dermatologic (clinical and pathological) findings are quite typical of the disease. On the other hand, in this case some particularities were observed: the age of the infant (second published case beginning before the age of two); the presence of a durable eosinophilia, the absence of visceral lesions and of biological abnormaliteis (of auto-immune nature specially), the evolution towards athrepsica and death within one year. Thus, because of these particularities, the diagnosis of scleroderma remains questionable and the diagnosis of progeria has been considered. The affection appeared in the course of a hepatitis leaving a hepatic fibrosis without inflammatory signs; no conclusion can be drawn about the relations between the hepatic affection and the fatal dermatologic disease.


[Lichen aureus or lichen purpuricus; about 5 cases; ultrastructural study]. Clinical, histological and ultrastructural features in five cases of lichen aureus are descirbed. This rare condition with ages ranging here from 6 to 31 consists of a pigmented papular and purpuric eruption. Unilaterally, trunk or limb may be involved, in a possible systematized distribution. The microscopic picture is characterized by a dense histiocytic and lymphocytic infiltration in the upper part of the dermis; extravasation of erythrocytes and iron pigment in the histiocytes are often noticed. In fine structure most cells of the dermal infiltrate are histiocytes (or macrophages) with numerous worm-like structures and even typical Langerhans granules in three cases; histiocytic cells; histiocytes are frequently seen in apposition to lymphocytes. In all these cases, no sign of histiocytosis X is found. Classification of lichen aureus in the group of idiopathic pigmented purpuric eruption is proposed.


[Acrodermatitis enteropathica; zinc sulfate therapy]. We present the case of two siblings with acrodermatitis enteropathica. Zinc levels were low. Oral administration of 100 mg of zinc sulfate allowed total regression of all signs. When zinc therapy was interrupted, the manifestations reappeared and disappeared again when treatment was resumed. A defect of genetic origin in digestive zinc absorption is suggested. Mohnahan's advocated zinc treatment of acrodermatitis enteropathica in 1973; it is a non-toxic treatment, which is always active and be considered as a diagnostic test.


[Gold therapy in pemphigus].

[Gold therapy in pemphigus]. According to works of Penneys and Eaglstein on the management of pemphigus with gold compounds, the authors report one observation of chronic pemphigus, in which steroid therapy caused severe psychiatric disorders. The use of gold compounds permitted reduction of the dose of steroids and control of the pemphigus.


[Oestriol effect upon prolactinaemia in postmenopausal women (author's transl)]. Six postmenopausal women were treated at two ocasions with an oral dose of, respectively, 2 mg and 6 mg oestriol per day for 14 days; at least one month interval separated the two treatment periods. Blood was collected for prolactin measurement (homologous human radioimmunoassay) every other day during each treatment period as well as during a 14 days control period in the same subjects. Mean prolactin level during oestriol administration, regardless of the dose, was statistically not significantly different from that observed during the control period.


[Experimental data on estradiol 3,17-diethers (author's transl)]. Estradiol ethers reveal a biological activity in female rats which decreases according to the length of the side chain at position 3. Further, percutaneous injections have an activity which is 6 to 30 times greater that subcutaneous ones. This suggests that de-etherification could occur, leading to estradiol. After percutaneous administration of tritiated promestriene (3-propyl ether, 17-methyl ether estradiol) and estradiol, a comparison of the uptake on the uterus and of uterotrophic effects as well as an analysis of radioactivity taken up indicates that a cleavage of both ether groups of promestriene occurs leading to estradiol. This de-etherification takes place in the liver, as demonstrated by perfused liver experiments. With promestriene, antagonist activity is shown on the seborrheic androgen-stimulated rat and on 5-alpha-reductase activity in vitro and in vivo.


[The steroidogenic sites in the Peking, Barbary and hybrids (Peking male X Barbary female) ducks: histochemistry, ultrastructure, biochemical complements (author's transl)]. The follicular theca steroid cells are much more numerous in the Peking female than in the Barbary female. Biochemical analyses show that the transfromation percentage of pregnenolone in progesterone is higher in the first than in the second (73% greater than 52%); in the same way, we dose more plasmatic oestradiol in the Piking than in the Barbary female (160 pg/ml greater than 69 pg/ml). In the hybrid female, resulting from the crossing of Peking male X Barbary female, many steroid cells are destroyed during the aging process; the transformation percentage in then 14,50% (30% in the young females) and the seric concentration is 7 pg/ml (59 pg/ml in the young females).


[Estrogen receptors and nuclear translocation in C3H independent mouse mammary tumors (author's transl)]. In C3H independent mouse mammary tumors, estrogen receptors were characterized and analyzed using dextrancoated charcoal, protamine sulfate and hydroxyapatite assays. The mean concentration of cytosol receptors was of 18.5 +/- 3.5 femtomoles per mg of protein stating that C3H tumor was a "receptor-positive" tumor. The cytosol estrogen-receptor complexes were translocated in vivo to the nucleus thus suggesting that the hormone-independency of the C3H tumor should be searched in later steps of the estradiol mechanism of action.


[Neuroendocrine investigation of the follicular phase: spontaneous and after estrogen stimulation (author's transl)]. Estrogen stimulation on days 7, 8, 9 of the menstrual cycle induces disturbances of the usual clinical and hormonal patterns. Alpha rythm (8-12 Hz) variation curve, studied by mathematical analysis, is modified, and delayed ovulation happened at its nadir. It is concluded that EEG appears as a tool for clinical neuroendocrine correlations and that this preliminary study may indicate that this estrogen positive feedback is received at the neurovegetative level.


[Comparison of effects of ingestion of Si on the content of Ca and Mg of different tissues of female rats normal or receiving oral oestrogen-gestogens (author's transl)]. In the adult normal the ingestion of silicon modifies the concentration of Ca and Mg of plasma and tissues most often opposite ways according to the mineral (silicate Na) or organic form (SMTO) of the administration. In the female adult under oestroprogestative traitment the organic Si is more active than the silicate to suppress the calcico-magnesic modifications caused by both oestroprogestatives (Norethisterone, Mestranol).


[In vitro studies of the effect of temperature on insulin secretion in the rat, the active and the lethargic hedgehog (author's transl)]. The study of insulin secretion by the technic of perifusion of pieces of pancreas at increasing temperature allowed us to point out that the pancreas of the lethargic hedgehog is more sensitive to temperature than that of the active hedgehog or that of the Rat.


[Exchangeable electrolytes, glycoregulation and growth hormone in one case of Bartter's syndrome (author's transl)]. Total body water (T.B.W), extra-cellular fluid volume (E.C.F.), exchangeable sodium (NaE) and potassium (KE) were measured in one typical case of Bartter's syndrome with growth retardation. Intracellular potassium depletion was associated with a slight impaired carbohydrate tolerance and with decreased growth hormone response to arginine infusion and insulin-induced hypoglycemia. These observations demonstrate that impairement of growth hormone responses to stimulation occur in Bartter's syndrome with potassium depletion.


[Human fetal antehypophysis in vitro. II. Immunocytological study and radioimmunoassay of LH and FSH (author's transl)]. Human fetal antehypophysis (16 males, 16 females and 4 unknown sex) were cultivated during several weeks. By immunocytochemistry LH gonadotroph cells were determined with anti-hTSH and anti-pLH serum. The release in vitro of LH and FSH was studied by radioimmunoassay. At the first medium change, the quantity of LH and FSH release was related to the gestational age and sex. A rapid decline of both LH and FSH occured over the 10 first days. There after, a basal release of LH was maintained during several months; the release of FSH was generally maintained at the lower limit of the assay. After 1 month in vitro, the level of LH could not be related to the sex. Release of LH was stimulated by synthetic LRF. A significant increase was observed independently of the sex and age of the fetuses studied.


[Apparent internal male pseudo-hermaphroditism. Gynecomastia. Negative gonad surgical research. Caryotype 46, XX. Presence of H-Y antigen (author's transl)]. Boy 15. Aspect of delayed puberty with empty scrotum and gynecomastia. Caryotype 46, XX. Presence of H.Y. Antigen. Plasmatic testosterone 1 020 pg/ml. Normal plasmatic FSH and LH. Hypotrophic uterus and tubes. No gonad found. Small right epididymis. Complete virilization by testosterone.


[Study on deshydrogenases implicated in control of farnesol and juvenile hormone metabolisms in Pieris brassicae (author's transl)]. Activity of ODH is high during larval development on pars intercerebralis which is releasing its allatotropic neurosecretion towards 4 th day of 5 th instar under photophase 16 h. ADH is inhibited during the same period and then activated at the time of spinning when the level of JH I and II is falling; by oxidization of JH I and JH II, possibly JH III is produced.


[Hormonal control of the ovarian cycle in Labidura riparia (author's transl)]. The ovaries in female Labidura riparia undergo cyclical development. They require approximately 10 days to complete one vitellogenesis. During this period the Insect eats and and also mates. About 7 to 9 follicles in each ovariole are loaded progressively with vitellus and secrete a chorion. Before each oviposition degenerative phenomena appears in immature follicles. The ovaries remain at a less developed stage during the 10 days of maternal eggs cares. The follicles at the base of each ovariole degenerate. The cerebral neurosecretory centers and the corpus allatum are active during each vitellogenesis and inactive during each period when follicles degenerate and when the female cares her eggs. An experimental study shows that neurosecretory centers control the activity of the corpus allatum which itself influences the evolution of the vitellogenesis.


Comparative studies on activities of gentamicin, sisomicin, tobramycin and amikacin (BB-K8) against Pseudomonas sp. Activities of gentamicin, sisomicin, tobramycin and amikacin against 561 strains of Pseudomonas sp. bacilli were evaluated. Tobramycin was from two to eight times more active against Pseudomonas sp. than gentamicin. No strains resistant to amikacin were encountered. Correlation between the size of the growth inhibition zone and minimal inhibitory concentration was determined as regression lines for all the tested antibiotics. Sisomicin and tobramycin showed lowest correlation, and gentamicin and amikacin good correlation.


The effect of cytostatic drugs on collagen metabolism in guinea pigs. Azathiprine (0.25 mg/100 g body wt.) and cyclophosphamide (0.2 mg/100 g body wt.) were administered to guinea pigs, orally every day during 4 weeks. Azathioprine caused a decrease in total collagen content in skin, liver and bone and decreased hydroxyproline and hydroxylysine concentration in blood serum, and urinary excretion of collagen catabolites. No effect of cyclophosphamide on total collagen in skin and liver was observed. An increase in collagen content in bone in cyclophosphamide-treated guinea pigs was found. A decrease of hydroxyproline and hydroxylysine in blood serum and urine was observed after cyclophosphamide treatment. The results support the view that cytostatic drugs inhibit collagen metabolism, and azathioprine significantly affects collagen biosynthesis, and cyclophosphamide influences inhibition of catabolic processes of collagen.


Histopathological changes in experimental drug-induced collagen disease-like syndrome. Prolonged administration of 1-hydrazinophthalazine (hydralazine) to guinea pigs stimulated the development of collagen disease-like syndrome. Inflammatory changes were found in the heart, kidneys and skin.


The influence of imipramine on the circulatory system and some other parameters of arterial hypertension. Imipramine in doses of 0.35-0.45 mg/kg body weight usually induces a drop in arterial blood pressure; the drop is statistically significant in patients with essential hypertension. In these patients, a significant increase in excretion of catecholamines in urine was observed when compared with a control group. In both groups no changes in heart action were found.


The influence of chlorpromazine, diazepam and imipramine on the central action of ethanol. In experiments with white rats, chlorpromazine, diazepam and imirpramine injected intraperitoneally in the dose of 20 mg/kg and imipramine and diazepam in the dose of 50 mg/kg did not enhance the acute toxicity of ethanol expressed as LD50. Only chlorpromazine in the dose of 50 mg/kg i.p. increased toxicity of ethanol. However, the aforementioned drugs intensified the central action of ethanol by prolonging (except imipramine) duration of narcotic sleep and motor incoordination, and potential ethanol-induced hypothermia.


Studies on derivatives of phenyltetrahydrofuranone-2-carboxylic acids. VI. Derivatives of beta-phenyltetrahydrofuranone-2-beta-carboxylic acid. Proceeding with the studies on derivatives of pheyl-tetrahydrofuranone-2-carboxylic acids the authors have stated that the reaction of hydroxymethylation of ethyl ester of beta-phenyl-beta-cyanopropionic acid I gives transitionally beta-phenyl-beta-cyano-beta-hydroxymethylpropionic acid II which, after a long time, transforms into an amide of beta-phenyl-tetrahydrofuranone-2-beta-carboxylic acid (III). Amide III is tranformed, through acid IV, into acid chloride V that gives a number of derivatives: amide III, substituted amides (VI-IX), methyl ester X, ureide XI, and aminomethylamides (XII, XIII). The chemical structure of these compounds has been confirmed by elemental analysis and IR and PMR spectra. The compounds newly obtained were invested pharmacologically. It has been found that some of the derivatives (III, VI, VII, VIII, XII, XIII) exert a depressing action on the central nervous system.


Changes in chondroitin sulfate concentration in rabbit blood plasma depending on the method of its administration. Glycosaminoglycans were determined in the blood plasma of rabbits as a function of time after intravenous, intramuscular and intragastric administration of chondroitin sulfate preparation. After intravenous administration two phases of chondoitin sulfate elimination from the blood with T1/2 131-135 min and 8.5-9.5 min, respectively were observed. The level of the blood plasma glycosaminoglycans did not increase after intragastric introduction of the chondroitin sulfate preparation. Excretion of glycoaminoglycans in the urine was also determined.


The identification of Babesia equi in Australia. A Babesia parasite, isolated from the blood of a horse at Bowral, New South Wales, was identified on the basis of its morphological features, host specificity and serological reactions, as Babesia equi (Laveran 1901). The case was originally reported by Churchill and Best (1976, Aust. vet. J. 52: 487) and is the first record of equine babesiosis in Australia. In preliminary studies, the organism produced only a mild disease in an intact horse, but caused the typical clinical syndrome of acute babesiosis in a splenectomised horse, which died 19 days after the intravenous inoculation of the parasites.


A dual vaccine for the immunisation of cattle against vibriosis. Single subcutaneous injections of a mineral oil adjuvant vaccine containing 20 mg dry weight of Campylobacter fetus subsp fetus biotype venerealis cells and 20 mg dry weight of C. fetus subsp fetus biotype intermedius cells per 5 mil dose protected 2- and 3-year-old heifers and 3- and 4-year-old cows against genital infection with either organism.


Bovine vibriosis vaccination: immunity conferred by a single biotype. An adjuvant vaccine was prepared from an Australian isolate of Campy-lobacter fetus subsp fetus biotype intermedius and injected into 23 virgin Guernsey heifers. Ten nonvaccinated animals served as controls. When challenged by the intravaginal route with a culture of either the homologous strain or biotype venerealis, weekly swabs from the anterior vagina continued to yield either biotype in 8 of 10 nonvaccinates at 6 weeks as compared with 3 of 23 vaccinates. Serology in vaccinated heifers and rabbits showed that the vaccine produced high titres of antibody against both homologous and heterologous strains.


Comparison of three sampling methods for the diagnosis of genital vibriosis in the bull. Three different methods of collecting preputial material for bacteriological examination were compared using 3 bulls infected with Campylobacter fetus subsp. fetus. The first method utilised a specially designed instrument to scrape the preputial and penile mucosa, int he second method plastic pipettes were used to aspirate material and the third method involved washing the preputial cavity with sterile peptone water. Bacteriological examination of the samples showed conclusively that scraping was the method of choice because more C. fetus positive samples were identified and there was less interference from contaminating organisms.


Treatment of diaphragmatic hernia in buffaloes. The surgical treatment of diaphragmatic hernia attempted on 19 lactating buffaloes is described. Thirteen cases recovered uneventfully, 1 recovered after developing brisket oedema and 5 died, 3 during surgery and 2 postoperatively. The desired depth of anaesthesia was achieved by the administration of 6% chloral hydrate followed by 5% thiopentone sodium. A postxiphoid approach and the use of a continuous lock stitch suture were preferred to repair the vent in the diaphragm. Pre- and post-operative use of hydrocortisones and fluids and sufficient tissue oxygenation by controlled positive pressure respiration are believed to be keys to the success of the treatment adopted.


The effect of testosterone and an anti-oestrogen on hypertrophy of bulbourethral glands of wethers grazing oestrogenic pastures. Testosterone implants (70 mg), but not an oral anti-oestrogen, prevented hypertrophy of the bulbourethral glands of wethers grazing oestrogenic pastures for 18 weeks.


The effect of Eperythrozoon ovis infection on the glucose level and some acid-base factors in the venous blood of sheep. Eperythrozoon ovis infected sheep have low venous blood glucose levels and correspondingly increased blood lactic acid levels as compared with control sheep. Acid-base studies showed that these changes were accompanied by significant falls in venous pH, and standard bicarbonate as well as a negative base excess. All these changes were considered to result from the increased alvcolytic activity of infected erythrocytes. The acidosis and hypoglycaemia associated with E. ovis infection, while not having any apparent effect on young, well-fed sheep, could be potentially serious in pregnant ewes and in sheep on a low plane of nutrition.


White muscle disease of sheep and associated tissue selenium levels in Western Australia. White Muscle Disease of sheep occurs in Western Australia as distinct syndromes in lambs and weaner sheep. Mean liver selenium concentrations of lambs and weaners with WMD and unaffected by WMD were 0.19 and 0.46 ppm, and 0.20 and 0.41 ppm (dry weight) respectively. There was considerable overlap between levels suggesting that selenium status was not the only factor involved in the development of WMD.


The use of simulation modelling in the management of brucellosis eradication. Problems faced by Government veterinarians in the planning and implemention of the national bovine brucellosis eradication campaign are described. These problems stem from the uncertainty associated with the epidemiology of the disease and its initial status in eradication areas. They are compounded by contraints on abattoir capacity, finance and time. A computer stimulation model is discussed which is designed to assist campaign organisers to cope with these problems. Inputs related to expected test and slaughter rates, district disease prevalence and proposed campaign intensity are entered into the model. Output from the model inlcudes distributions giving predicted testing workloads, cattle slaughtered and disease status over the course of the campaign. The operation of the model is illustrated using data from the Bangalow district of New South Wales.


Intra-ocular pressure during retrobulbar injection. It was found that the use of retrobulbar injections can cause quite large transient rises in intra-ocular pressure which can be significantly reduced by using local anaesthetic in the injected saline, and by injecting in small steps, typically 0.2 to 0.3 mls/kg body weight at 1 minute intervals for a total of not more than ten steps. After a moderate retrobulbar injection, the intra-ocular pressure was found to return to near normal in a few minutes, but with some decrease in anterior chamber volume.


An outbreak of anal fibropapillomatosis in cows following rectal examinations. An outbreak of fibropapillomatosis following rectal examination for pregnancy and involving the anus and to a lesser extent the rectum in a herd of beef heifers in western Victoria is described. Almost half the herd were involved at one time; most lesions regressed with the following 16 weeks. Lesions varied from 0.2 mm diameter polyps up to large multiple lesions up to 7 x 5 x 2 cm with a broad base. The presence of lesions did not affect the body condition or health of the animals.


Ataxia and urinary incontinence in cattle grazing sorghum. After grazing forage sorghum and grain sorghum regrowth, 54 of 330 breeding cows became ataxic and developed urinary incontinence. Three cows became recumbent, 2 of which died and the third was killed and autopsied. Wallerian degeneration of the white matter of the spinal cord, cerebellar peduncles and cerebellum was seen histologically. Other affected animals began to recover on removal from the crop, complete clinical recovery taking from a few days to over a month. About 5% of affected cows develped purulent cystitis.


Gnathostomiasis in three cats.

Gnathostomiasis in three cats. A fatal infection with Gnathostoma spinigerum causing a perforated stomach is described in a 3-year-old cat. In a second debilitated case a small serosal perforation was found on a gastric lesion, while a third cat in good condition is described with a well developed stomach lesion but without perforation. Histopathological changes in the stomach were found in the submucosa and consisted of marked proliferation of fibrous tissue containing foci of inflammatory cells, necrotic tracts and a cavity in which the adult nematodes were found.


Some toxicity aspects of dichlorvos flea collars in cats. The effects of the application of a single dichlorvos flea collar containing 500 mg of the insecticide were observed in 23 growing cats for periods of from 1 to 15 weeks. No overt signs of toxicity occurred and weight gain in young growing animals was not significantly affected. Whole blood cholinesterase was reduced within the first week of application of the collar and remained below pretreatment levels for 5 to 8 weeks before returning to normal presumably as the insecticide concentration in the resin was progressively reduced. Signs of systemic organophosphate toxicity did occur within 1 week of the application of three collars to each of two cats kept in the same cage. This suggested that the likelihood of toxicity occurring in cats following the use of dichlorvos flea collars depended mainly on the degree of exposure to the insecticide. Considering recent reports in the literature it was proposed that the environmental conditions of temperature (11 degrees to 23 degrees C) and relative humidity (50 to 65%) under which the experiments were carried out would have promoted a relatively low atmospheric concentration of dichlorvos in the near environment of the test animals and hence generally prevented occurrence of clinical signs. Under most conditions of keeping domestic cats in Australia the use of a single dischlorvos flea collar should therefore be without any untoward effect although some initial and transient inhibition of whole blood and nervous tissue cholinesterases would be expected.


Ecology of mycoplasmas in clinically healthy cats. Mycoplasmas were isolated from various sites and organs of a series of 319 clinically healthy cats. They include M. felis, M. gateae, M. Arginini, A. laidlawii, feline ureaplasmas, M. pulmonis, M. arthritidis, and M. gallisepticum. In addition, there were 10 strains of mycoplasmas which could not be identified with the specific antiserums by growth inhibition tests. Antibody against M. felis was demonstrated by haemagglutination-inhibition and complement-fixation tests in cats which were over 6 months of age. However, no such antibody against M. felis was detected in animals which were less than 6 months old. No antibody against A. laidlawii, M. gateae, M. arginini and feline ureaplasmas was demonstrated by the same serological methods. The significance of these mycoplasmas in cats is described.


The plasma zinc concentration of nonpregnant, pregnant and parturient Hereford cattle. Studies were made on several groups of Hereford cattle to determine the plasma zinc concentration at various phases of their reproductive life. In nonpregnant heifers a major cause of variation was due to differences between individual animals. Seasonal changes were also evident but little difference was noted in the zinc levels of cattle sampled at particular stages of the oestrous cycle or over a 24-hour period. Following conception, the plasma zinc levels remained relatively constant until late in pregnancy when a decline occurred. A more marked decline occurred during the periparturient period although the trends observed differed between animals that calved normally and those that suffered from dystocia. Samples obtained from calves approximately 24 hours after delivery contained zinc at concentrations of more than double that recorded for their dams.


Management factors and grass tetany in dairy cattle. The relationship between intensity of production and the occurrence of hypomagnesaemia and grass tetany in dairy cattle was investigated from 1966-1970 at the Ellinbank Dairy Research Station, Warragul, Victoria. Hypomagnesaemia and/or grass tetany occurred in cows grazing at both high (3.2 cows/hectare) and low (2.2 cows/hectare) stocking rates over the four-year period. Pasture Mg concentrations remained relatively high (0.2% dry matter) throughout this period, except in the low stocking rate pastures in one year, 1967. It is concluded that hypomagnesaemia and grass tetany was precipitated by a combination of low dry matter intake in winter and the effects of a gradual increase of K concentration in autumn and winter pastures, following the heavy application of K fertilizer. Under these conditions, MgO supplementation was inadequate to prevent grass tetany occurring in some animals.


The New South Wales mastitis control program. 1. Field aspects and their effect on clinical and subclinical mastitis. A mastitis control program based on teat dipping and dry cow therapy was evaluated in 35 herds over a 3 year period. The incidence of subclinical mastitis as detected by the Rapid Mastitis Test (RMT) fell from 34% to 12% quarters positive, a reduction of 65%. Clinical mastitis was reduced from 37 clinical cases per 100 cows in the first 3 month period to 12 clinical cases per 100 cows in the last 3 month period, a reduction of 68%. Variations in response to the program in the reduction of subclinical and clinical mastitis are discussed and the results compared with similar trials conducted overseas. The Modified Whiteside Test was used on bulk milk samples from the control herds and these results were significantly correlated with the prevalence of subclinical mastitis assessed by RMT individual quarters.


Observation on the bacterial population of the os cervix of the ewe before and after embryo death. Bacterial samples were isolated from the os cervix of mature Merino ewes during a normal oestrous cycle and after colchicine treatment which killed the 25-day old embryos. The population of bacteria was small during the oestrous cycle and consisted of Achromobacter spp. Alcaligenes spp, Corynebacterium spp, Bacillus spp and Escherichia coli. There was a significant increase in the numbers of bacteria isolated and a change in the proportions of the bacteria isolated from ewes after embryo death. Much greater numbers of potentially pathogenic organisms, including Pasteurella multocida, Corynebacterium pyogenes, Staphylococcus spp and Streptococcus spp were isolated after embryos were killed. It is suggested that persistence of potential pathogens in the vagina may impair fertility in ewes at the first oestrus after embryo death.


Paroxysmal atrial fibrillation in a racehorse. A 4-year-old thoroughbred stallion with a history of loss of racing form was studied over a period of approximately 7 months. At the initial examination he showed positive T waves in 1 chest lead and wandering of the pacemaker. This was followed by an episode of paroxysmal atrial fibrillation which disappeared spontaneously and was replaced by significant T wave changes in all the chest leads. During a period when these changes persisted, there was progressive lengthening of the P wave and the P-R interval. Because the last ECG showed evidence of intra-atrial block, first degree A-V block and T wave changes, the owner was advised that a fluctuating myocarditis was affecting the horse's performance and it was retired to stud. This appears to be the first report of paroxysmal atrial fibrillation in Australia, and it demonstrates the value of regular follow-up examinations in horses with initial electrocardiographs showing only minor departures from normal. The case also suggests that when sharp reversals of racing form occur, the possibility of paroxysmal atrial fibrillation being the cause should be kept in mind.


Realtion of heart rate control to heartbeat perception. The relation of heartbeat perception to voluntary control of heart rate (HR) and to learning of enhanced HR control during feedback was studied in three experiments. In Experiment I heartbeat perception was unrelated to voluntary control of HR but was negatively correlated with HR learning. Experiments II and III showed that heartbeat perception was unrelated to either initial voluntary control or learning and suggested that sampling error accounted for the negative correlation in Experiment I. Experiment I also demonstrated that learned increases in HR are retained for at least 10 weeks following feedback training. Autonomic Perception Questionnaire scores were not predictive of voluntary HR control or learning.


Effects of biofeedback on the discrimination of electrodermal activity. Twenty-four subjects were tested on their ability to discriminate between the presence and absence of negative skin potential responses before and after training to control skin potential. Training consisted of 52 discrete 30-second trials during which subjects were asked either to increase or to inhibit palmar sweating. Subjects in groups N and P were provided with analogue feedback on their skin potential activity. Group N was correctly informed that increases in sweating were indicated by increases in the negativity of skin potential; group P was misinformed that these were indicated by increases in the positivity of skin potential. Subjects in the control (C) group received no feedback. Reliable evidence of discrimination was obtained only in groups N and P, following training. However, reliable evidence of control was obtained only in group N. Thus, training to control skin potential led to an ability to identify afferentation associated with the more common (i.e., negative) skin potential responses, even though biofeedback training appeared unsuccessful in the case of group P. These findings are discussed in the context of "discrimination" or "awareness" accounts of the process of acquiring control of internal response.


Fine body movement during autogenic training. Longitudinal and short-term changes. A sensitive electronic device (static sensograph) was used to record fine body movement in two similar groups of normal high school girls at intervals over a few months. One group received weekly instructions in the technique of autogenic training (AT) and was urged to practice it daily, whereas the other (control group) received no such instrutions. In the AT group mean body movement (eyes closed, sitting position) decreased with every session. At 3 and 4.5 months after training was begun (session 3 and 4, respectively) mean body movement of this group was significantly lower than in the first session, before training was begun. In the fourth (but not earlier) sessions the AT group also showed a significant decrease in mean body movement during AT compared with the periods immediately preceding and following it. In contrast, the control gorup showed no significant differences in means between any sessions or periods within a session. The results suggest that fine body movement as measured by a static sensograph is a useful parameter for studying AT and probably other relaxation procedures.


The effects of the distribution of training on learning feedback-assisted cardiac acceleration. In order to test a hypothesis derived from a motor skills learning model of cardiac acceleration control, groups of subjects were given biofeedback training for four sessions to learn cardiac acceleration under four different training schedules: (1) all sessions in one day, (2) daily sessions, (3) sessions every other day, and (4) weekly sessions. Ability to accelerate heart rate both with and without feedback was determined at each session. Also ability to accelerate heart rate without feedback was determined 1 week after the last training session as a measure of retention. Although there was highly significant (p less than.0001) evidence of heart rate control both with and without feedback, there were no differences in degree of control attributable to distribution of training sessions. There was, however, a trend (p less than .10) for subjects trained under the most distributed training schedule (weekly) to show more retention than subjects trained under a less distributed schedule (daily).


Blood pressure tracking systems and their application to biofeedback. Two automatic electronic systems for tracking diastolic or systolic blood pressure (BP) and their use in biofeedback experiments are described. Both systems are based on the use of an arm cuff and the recording of Korotkoff sounds with a microphone. An electronic control system receives input from the microphone and provides output to several solenoid valves that control compressed airflow to the cuff. For one of the tracking systems we devised, the cuff is alternately inflated for 45 sec and deflated for 45 sec. During inflation, small increments and decrements in cuff pressure, based on the occurrence of Korotkoff sounds, are used to track BP. The other tracking system is slower but provides more continuous measurements: The cuff is alternately inflated to approximately the BP level for 5 sec and then deflated for 5 sec. During each inflation, the number of Korotkoff sounds is recorded by the system and according to this number, the amount of inflation on the next trial is automatically adjusted so that the cuff pressure follows BP. Both systems have been used successfully in biofeedback applications.


CT evidence of grey matter calcification secondary to radiation therapy. There are four previously reported cases of post-irradiation calcification in the basal ganglia as demonstrated on the conventional skull roentgenograms. We have described two additional cases with grey matter calcification, which were demonstrated 10 and 14 yr after radiation therapy for an optic glioma and a medulloblastoma, respectively. The calcification was clearly demonstrated on CT scan, although it was not apparent on the skull roentgenogram. The extract pathogenesis of this condition is not clear. It appears, however, to be related to radiation vasculitis of the small vessels of the brain with resultant hyalinization and calcification. A long-term follow up study would be necessary to evaluate the significance and implication of post-irradiation calcification of the grey matter. CT is the most sensitive method of demonstrating the intracranial calcification in vivo.


The value of computed tomography in the radiotherapeutic management of juxtasellar tumors. Computerized tomography has proven to be extremely useful for accurate tumor localization and precise assessment of tumor extent in the juxtasellar region. A reconstruction and display system with ACTA scanner provides three-dimensional images from the serial two-dimensional sections. With this method, one can determine the volume and actual contour of the tumor. Using the ACTA scanner, both transaxial and coronal sections of the tumor can be precisely portrayed with accurate dimensions. With the aid of CT treatment planning, we have been successfully treating such radiocurable tumors as pituitary adenomas, germinomas, craniopharyngiomas and optic gliomas.


A forthcoming cross-sectional atlas correlating CT scans with anatomical structures. With the development of the whole-body CAT (computerized axial tomographic) scanner, a need has arisen for a cross-sectional anatomy book that correlates acutal CT scans with detailed anatomical structures. This article describes a forthcoming cross-sectional atlas using CT scans of normal living human volunteers. After a preliminary discussion of such considerations as some fundamental differences between cross-sectional anatomy and conventional anatomy and the relationship between cross-sectional anatomy and computerized tomography, there is an explanation of the textual format. This section includes a description of the presentations on the pages, the use of color in the scans, and the use of certain advanced features of the ACTA-Scanner, the scanner used for the atlas. The final part of the article illustrates sample scans and a diagram from the forthcoming test.


Radiological methods of studying the orbit. The orbit is a challenge diagnostically to the ophthalmologist and the radiologist because of its small size and enclosed nature. As a result, a variety of radiological tests have been devised to study the orbit, although no one test is entirely definitive. Conventional X-rays, the use of ultrasound techniques, and the injection of contrast into either the orbit per se or the vasculature of the orbit are extremely useful. However, none of these techniques can produce clear, cross-sectional and unsuperimposed images, such as those obtained from computed tomography. The use of color-coding is useful in enhancing even high quality gray-scale scans. Above all, the technique of computed tomography offers the advantages of noninvasive study.


ACTA scanning in the diagnosis of abdominal aortic aneurysms. The presently available diagnostic methods for abdominal aortic aneurysms are reviewed. The application of ACTA scanning for this diagnosis in 35 patients is described. In all cases the presence of an aortic aneurysm was confirmed, even when calcification of its wall was absent. Contrast enhancement demonstrated that aortic lumen not otherwise visualized. In some instances the iliac arteries were clearly seen and more readily so when calcified. Estimates of aneurysm size were compared with measurements taken at surgery with a relatively close correlation. This technique seems to be useful in the differential diagnosis with tortuous abdominal aorta or as a screening procedure. Patients with minimal ectasia of the aorta can be followed by scanning. The planned addition of shorter scanning times and sagital scans with allow the fast evaluation of the longitudinal dimension of the abdominal aortic aneurysm, which is difficult to obtain with the present technique.


The diagnosis of hypertensive intracerebral hemorrhage: the contribution of computed tomography. Sixty-eight cases of hypertensive intracerebral hemorrhage were reviewed and the CT scans studied. The CT scan was accurate in localizing and measuring intracerebral hemorrhage. There were three cases of pontine hemorrhage which did not appear on the CT scan. Hemorrhages at other sites were always seen on the CT scan. The size of putaminal and thalamic hemorrhage as calculated from CT scan allowed accurate prognosis to be made at the onset. CT scanning has become the diagnostic test or first choice when intracerebral hemorrhage is suspected.


Computed tomography of cerebral infarction: hemorrhagic, contrast enhancement, and time of appearance. Large confluent petechial hemorrhages and/or hemorrhage within infarct may be seen on CT scan. Small petechial hemorrhages are not resolved by current equipment and techniques. Elevation of absorption values of an infarct following contrast media primarily occurs in the first month after onset, and may be occasionally confused with a tumor. Sequential CT changes in infarcts correlate well with established pathologic changes. Cerebral infarction may be seen on CT scan in some cases as early as 24--48 hr after its onset.


Cerebral metastasis--a study of computerized tomography. Sixty-eight cases of metastases affecting 34 patients were studied by computerized tomography (CT) before and after the injection of an iodinated contrast medium. CT data provided a diagnosis in most cases. After injection of the contrast medium, a ring aspect was found in half the cases. This morphological feature is a sign of blood-brain barrier impairment crossed by the contrast medium. The low density area inside the ring is not caused by central necrosis, nor is it caused by too little contrast medium. The increase in density is a sign of extra-vascular loss of iodinated molecules in the peritumoral cerebral tissue. Performance of CT should be improved using specific tracers of the tumoral cells.


Children at risk: performance of three-year-olds and their mentally ill and well mothers on an interaction task. Fifteen mothers previously hospitalized for mental illness (psychosis) and 15 well mothers were observed with their 3-year-old children. While mentally ill mothers expressed less positive affect than well mothers, there were no other respects in which the two groups of mothers and their children differed. There were differences in the pattern of intercorrelations among these interaction variables between the two groups, which appear to reflect differences in the degree of flexibility between mothers in the two groups.


Some milestones in premature infants at 6 to 24 months. The onset of 12 milestones that occur from 6 to 24 months of age was studied in premature and full-term infants. The milestones are: sitting, crawling, teething, walking, pursuit of a hidden sound-making object, stranger anxiety, separation anxiety, "no" gesture, words, phrases, speech "no," and speech "yes." It was hypothesized that premature infants would show delay in acquiring milestones related to time separated from mother. Compared to full-terms, the prematures had no significant difference in the means for the onset of the milestones except for: sitting, crawling and walking related to maternal separation; and crawling and teething, related to birth weight.


Children's response to their true and distorted mirror images. In order to study the development of body image, 16 children aged 2 months to 8 years were tested to determine their levels of cognitive development on the basis of Piaget's theory, and their responses to their true and distorted mirror images. The study indicates a definite characteristic response by children according to their levels of cognitive development. This corresponds to infantile anxieties appropriate to the psychoanalytic theory of object relationships. The theoretical and clinical implications of the study are discussed.


Capillary filtration coefficient in the canine hindpaw at different levels of venous pressure. Capillary filtration coefficient (CFC) was determined in 12 dog's hindpaw preparations following elevation of venous pressure. From the quotient of slow component tissue volume change divided by the change in capillary pressure, the CFC averaged 0.027, 0.028 and 0.038 ml/min/mm Hg/100 gm respectively with an elevation of venous pressure from 0 to 15, 30 and 45 mm Hg. As compared with the previous determinations of CFC in the other tissues, the CFC of canine hindpaw was approximately in the same order of magnitude as that of the hindlimb, and was much less than those of the lung, intestine and heart. At venous pressure below 30 mm Hg, the CFC did not alter significantly with the level of venous pressure. This finding indicated that neither "stretched pore phenomenon" nor myogenic sphincter constriction occurred in response to a moderate increase in intramural pressure. The slight increase in CFC when venous pressure was elevated to 45 mm Hg suggested slight change in capillary permeability at high venous pressure, presumably due to the presence of stretched pore phenomenon.


Myocardial lesions produced by external heat or cold exposure in rats. Three groups of Sprague-Dawley rats were kept at the ambient temperatures of 8, 24 and 32 degrees C respectively for 3 to 7 days. These animals maintained their rectal temperatures within normal limits. However, the animals of either the heat-stressed or the cold-stressed group yielded not only the functional but also the organic effects to their hearts when compared to those of the control group (24 degrees C exposure). Heat exposure produced a lower heart rate and higher cutaneous temperature, while cold exposure produced a higher heart rate and a lower cutaneous temperature. In addition, the ECG recordings showed a predominant S wave and probably a depressed S-T segment in response to either heat or cold exposure. At the end of either 3-day or the 7-day thermal exposure, the animals were subjected to decapitation. Their hearts were sampled for both light and electron microscopic examinations. It was found that the heat-stressed animals shared with the cold-stressed animals a common picture of the myocardial changes. The subcellular changes in the myocardium in response to external heat or cold were characterized by the mitochondrial hypertrophy, the intracellular edema, the destruction of myofibrils, the dilatation of the intercalated discs, and some abnormalities in their capillaries. The data demonstrate that a short term (3 to 7 days) of moderate heat (32 degrees C) or cold (8 degrees C) exposure produces myocardial lesions in rats, although they maintain their body temperatures within normal limits.


Shock avoidance in rats with unilateral lesions in the lateral hypothalamus. Male albino rats bearing unilateral lateral hypothalamic lesions on either side were tested to acquire active shock avoidance in a two-way shuttle box. The retention of this task learned prior to the surgery was also studied. It was found that the unilateral hypothalamic lesion impaired both performance and no difference between sides was observed.


Effect of GABA on the electrical potentials across the mouse small intestine. The effects of gamma-aminobutyric acid (GABA) on transmural potential difference (PD) and radioactive chloride fluxes (J) across the mouse small intestine were studied. It was found that GABA decreased the PD and increased the J in both mucosal-to-serosal and serosal-to-mucosal directions (JMS and JSM) only at a concentration of or higher than 50 mM. The PD was increased by the presence of 10 mM glucose or glycine in bathing solutions. The PD was also decreased by increasing the osmolarity of the bathing solutions with increasing concentration of GABA, mannitol, sucrose, or glucose. Our results suggested that the hyperosmotic effect causes the decrease of PD and the increase of J across the mouse small intestine by GABA.


Recent findings on the carcinogenicity of chlorinated olefins. Data are presented on factors affecting the carcinogenic effects of chlorinated olefins, such as molecular structure, concentration, length of treatment, route of administration and animal species, strain, sex, and age. The observations are based upon carcinogenicity experimental bioassays of vinyl chloride and vinylidene chloride. Early results, which appear to show that some of these factors (particularly species, strain, and sex) act by affecting the metabolism of the tested compounds, are presented, and the need for metabolic characterization of experimental animals in chemical carcinogenesis is stressed.


Irreversible binding of chlorinated ethylenes to macromolecules. Rats have been exposed in a closed system to the chlorinated ethylenes vinyl chloride and trichloroethylene and to carbon tetrachloride as a reference compound. Data of uptake of the compounds, of urinary excretion of metabolites, and of exhalation after exposure show that the chlorinated ethylenes are metabolized much faster than carbon tetrachloride, probably due to their common ethylene structure. To eliminate differences in uptake, calculation of metabolites of the three compounds in tissues was based on the amount actually taken up by the animals. Vinyl chloride, trichloroethylene, and carbon tetrachloride showed irreversible binding of metabolites to tissue proteins, mainly of the liver. Irreversible protein binding of either of these compounds ranged within the same order of magnitude, if related to the amount of compound which had been taken up. Also, no differences in the relative portion of irreversibly bound metabolites were found after exposure to different atmospheric concentrations of the three compounds. As already shown for vinyl chloride, trichloroethylene is metabolized in vitro by rat liver microsomes in presence of NADPH-regenerating system to intermediates that irreversibly bind to proteins. Albumin (bovine and rabbit) was a preferred target for binding. In contrast to vinyl chloride, significant irreversible binding of trichloroethylene metabolites also occurred to non-SH-proteins (gamma-globulin, concanavalin A) and to polylysine. Hence it should be inferred that, unlike vinyl chloride, trichloroethylene metabolites not only bind to sulfhydryl groups but also, to a lesser extent, to free amino groups of proteins.


1,1-Dichloroethylene hepatotoxicity: proposed mechanism of action and distribution and binding of 14C radioactivity following inhalation exposure in rats. 1,1-Dichloroethylene is reported to produce renal tumors in male mice. It is an hepatotoxin in fasted rats after inhalation. We found that trichloropropane epoxide, an inhibitor of epoxide hydrase, enhances hepatic injury as measured by serum sorbitol dehydrogenase elevation. A significant elevation of hepatic citric acid concentration was seen in fasted but not fed rats. We hypothesized that mitochondrial injury was associated with inhibition of the tricarboxylic acid cycle and postulated that monochloroacetic acid was a toxic metabolite of 1,1-DCE. Fluoroacetic acid and chloroacetic acid were similar in their ability to inhibit oxygen uptake when pyruvic and malic acids were substrates in isolated mitochondria supplemented with adenosine diphosphate. In experiments where 1,1-DCE metabolism was estimated, no difference between the rate of uptake in a 2-hr period was detected between fed and fasted animals. Urinary output of radioactivity at 26 hr for fed and fasted rats was similar. Water-soluble (i.e. TCA-soluble) 1,1-DCE metabolites were found in tissues of fasted rats in excess of that seen in fed rats. The kidney had the largest concentration of total metabolites. Tissue-bound, or TCA-insoluble, radioactivity was associated with the mitrochondrial and microsomal fraction of fasted rats in excess of that seen in fed rats. The disappearance of TCA-insoluble radioactivity from the mitochondrial and microsomal fractions was comparable in rate between fed and fasted rats respectively. These results suggest that 1,1-DCE is metabolized quite rapidly in the organism to TCA-soluble components which are excreted by the kidneys. Metabolites of 1,1-DCE may enter the metabolic pool, since a reasonably short turnover of (14)C-labeled, bound material was observed. The metabolite of 1,1-DCE appears to inhibit the mitochondria so that citric acid accumulates. This may occur by a process of lethal synthesis.


Dechloriation mechanisms of chlorinated olefins. The dechlorination of chlorinated hydrocarbons has been examined in detail. The reaction is catalyzed by cytochrome P-450 and occurs optimally in the presence of oxygen although some dechlorination may occur under anaerobic conditions. Halothane has been shown to undergo an oxidative dechlorination and a reductive defluorination. Enzymatic attack of chlorinated olefins and hydrocarbons is not on the carbon--halogen bond. Oxidative dechlorination of hydrocarbons is apparently initiated by an attack on the carbon atom and the halogen is then released from the oxidized carbon. The chlorinated olefins, on the other hand, are not easily dechlorinated enzymatically. The chlorines migrate readily across the double bond, therefore, cyclic chloronium ions must occur as intermediates. It is not clear at this time if epoxides are also intermediates in this conversion.


Effect of various treatments on toxicity of inhaled vinylidene chloride. The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various treatments to alter parameters of toxicity was evaluated. Mice were more sensitive than rats both to the acute lethal and hepatotoxic effects of VDC. Disulfiram treatment reduced the acute lethal and hepatotoxic effects of inhaled VDC and reduced the levels of covalent bound radioactivity in the liver and kidney after the intraperitoneal administration of 14C-VDC. Treatment with diethyldithiocarbamate and thiram also protected mice from the acute lethal effects of VDC.


Damage to hepatic cellular membranes by chlorinated olefins with emphasis on synergism and antagonism. The fundamental reactivity or stability of the chloroethylene molecules affects their hepatotoxic potential. Extent and symmetry of the chlorine substitution, which alters electron delocalization, charge polarization, and solubility, affect biologic response. The most nonsymmetrically depolarized chloroethylene, 1,1-dichloroethylene (1,1-DCE) is the most hepatotoxic and causes a unique pattern of hepatocellular injury involving mitochondria, plasma membranes, and chromatin. The injury caused by the other chloroethylenes examined appears to profoundly affect the structural integrity of the endoplasmic reticulum with toxic potential in the order: trichloroethylene (TRI) greater than vinyl chloride (VCM) greater than perchloroethylene (PER). Pretreatments which increased cytochrome P-450 contents, thus presumably augmenting metabolic activation to a reactive intermediate such as an epoxide, enhanced or were synergistic to the hepatotoxic potential of TRI, VCM and PER but were protective or antagonistic to 1,1-DCE hepatotoxicity. Biologic response to 1,1-DCE may be expressed by a different metabolic pathway. Glutathione appears to be involved in the biologic response to all nonsymmetric chloroethylenes and toact as an antagonist against injury. Marked differences in the patterns of injury and the biologic responses suggest that more than one mechanism is involved in the production of injury by chloroethylenes.


Influence of aliphatic alcohols on the hepatic response to halogenated olefins. The role of alcohols in potentiating the toxicity of halogenated hydrocarbon solvents has been reviewed. The toxicity of carbon tetrachloride and chloroform can be markedly potentiated by prior treatment with ethanol or phenobarbital. Trichloroethylene toxicity may also be potentiated by ethanol ingestion. Prior ethanol ingestion acts by altering biochemical parameters that result in an increased response to subsequent solvent exposure. Simultaneous exposure to both ethanol and trichloroethylene allows for competitive substrate inhibition of metabolism since these compounds share several common enzymatic pathways. Thus the toxic response to multiple exposures varies depending upon the time sequence and the comparative levels of the individual components. Phenobarbital apparently potentiates solvent toxocity by induction of the microsomal mixed function oxidase system. Ethanol, either on a chronic or single dose basis, also has the ability to stimulate this enzyme system. Although alteration of the microsomal mixed function oxidase system by chronic ethanol ingestion may play an important role in potentiation of solvent toxicity, the potentiation seen following a single dose of ethanol cannot be fully accounted for by the known effects of ethanol on the mixed function oxidase system. In addition to ethanol a large number of other alcohols will markedly potentiate the hepatotoxic response to solvents such as carbon tetrachloride and chloroform. The mechanisms involved in such potentiation are not known at the present time.


Oral toxicity of 1,1-dichloroethylene in the rat: effects of sex, age, and fasting. Mortality curves for groups of fasted male rats treated with single, oral doses of 1,1-dichloroethylene (1,1-DCE, vinylidene chloride) were not monotonically increasing sigmoids, but were complex with maxima or extended plateaus in the region of dose between 100 and 700 mg of 1,1-DCE/kg. The exact shape was a function of the size (age) of the rat used. When groups of rats of various sizes were dosed with 50 mg/kg, mortality and hepatotoxicity were greatest for those groups whose average weight was between 100 and 150 g. Smaller and larger male rats were less susceptible to 1,1-DCE intoxication. The toxicity of 1,1-DCE was less severe in female rats and there was no significant effect of rat size on 1,1-DCE toxicity in females. In rats of both sexes the dose dependence of the hepatotoxic response was complex, possessing a threshold level, a region of precipitous increase, and a plateau, where larger doses were ineffective in increasing hepatotoxicity. The threshold in male rats of 100-150 g occurred near 50 mg/kg, and for females it was closer to 100 mg/kg. Considered in their entirety these data suggest that 1,1-DCE is metabolized to a toxic intermediate via some saturable pathway. Based on the effects of pretreatment with microsomal enzyme inhibitors and activators on 1,1-DCE toxicity in rats of various sizes, it appears that there are at least two microsomal reactions involved in 1,1-DCE metabolism.


Chemical structure, reactivity, and carcinogenicity of halohydrocarbons. This review summarizes studies concerning the covalent binding of [14C]TCE to rat liver microsomal protein and exogenous DNA, in vitro, the enhancement of this binding by inducers of mixed-function oxidases, and inhibition of binding by inhibitors of these enzymes. Furthermore, recent studies on this type of binding in various strains of mice and rats of both sexes and using microsomal preparations from various organs are briefly reviewed. Other work reviewed here concerns the synthesis of TCE epoxide and its reaction with nucleophiles since it is believed that TCE epoxide is the activated carcinogenic intermediate of TCE. The utility of structural prognostication of carcinogenic activity and the importance of considering possible metabolic pathways for other chlorinated olefins is also discussed.


Bioactivation and covalent binding of halothane to liver macromolecules. In this manuscript we report our attempts to determine if 14C-halothane or its metabolites interact with DNA. Three bioactivation systems were used: in vitro microsomal incubations, isolated hepatocytes, and in vivo administration. Even though we used optimal conditions for bioactivation, no significant covalent binding of 14C to DNA was observed. Slight 14C activity above background (6 dpm/0.1 mg DNA) was observed in the microsomal incubations but is considered insignificant because it was not reduced when NADPH was omitted from the incubations. We are able to demonstrate covalent binding to nuclear lipids and proteins when rats were pretreated with phenobarbital and maintained in a hypoxic environment (14% O2). Similarly, these conditions markedly increased covalent binding of 14C from 14C-halothane to microsomal proteins and lipids. Isolated rat hepatocytes proved to be a viable system for studying the bioactivation of halothane. In this system it was also possible to demonstrate increased binding under N2 and/or phenobarbital pretreatment.


Effect of enzyme induction on nephrotoxicity of halothane-related compounds. Nephrotoxicity following administration of methoxyflurane has been shown to be directly related to anesthetic metabolism to inorganic fluoride. Enzyme induction should increase metabolic rate and the amount of inorganic fluoride that is released. In vivo studies in Fischer 344 rats show that enzyme induction with phenobarbital or phenytoin increases defluorination following methoxyflurane anesthesia but not after enflurane or isoflurane. In vitro, methoxyflurane defluorinase activity was increased far more than that of any of the other anesthetics. These data suggest that treatment with enzyme inducing drugs increases the risk of nephrotoxocity only if methoxyflurane is the anesthetic agent.


Halothane hepatotoxicity and the reduced derivative, 1,1,1-trifluoro-2-chloroethane. Halothane (1,1,1-trifluoro-2-bromo-2-chloroethane) is a safe, clinically useful inhalation anesthetic. Rare, unpredictable cases of liver necrosis have been reported following its use. Although the mechanism of this reaction in man is unknown the most plausible is biotransformation to reactive intermediates compounds. The oxidative metabolism of halothane appears to be benign. There is early evidence that reductive (nonoxygen dependent) may be harmful. Since the bromine atom of halothane appears to possess weak bond energy, the reduced,  debrominated derivative of halothane, 1,1,1-trifluoro-2-chloroethane, was synthesized and tested for hepatotoxicity in the rat. The derivative is unstable and thus was prepared anaerobically and trapped in propylene glycol solvent. Injection of small amounts of this compound into the portal vein of rats produces extensive liver necrosis. It is postulated that biotransformation of halothane via a reductive pathway could produce this reactive intermediate metabolite.


Behavioral and neurochemical effects of prenatal halothane. Permanent neurobehavioral toxicological effects have been theorized to occur at the lowest doses of a toxic agent if exposure occurs during early development compared to exposure during adulthood. Data are reviewed showing the exposure to 10 ppm of halothane from conception to day 60 of life post-partum led to adult rats (>/= 135 days of age) which were hyperalgesic to electric footshock and which committed 30% more errors learning a light-dark discrimination to escape footshock, or learning the shortest path to a food reward in a maze. Exposure only during adulthood to 10 ppm of halothane (from day 60 of life onwards) had no effects. To determine prenatal periods sensitive to halothane, rats were exposed to 12,500 ppm of halothane (with 35% oxygen) on day 3, 10, or 17 of gestation. As adults (>/= 75 days of age) day 3- and day 10-exposed rats, but not day 17-exposed rats, were hyperalgesic and committed 40% more errors in learning a visual discrimination to escape footshock. Food and water consumption, body weight, and running wheel activity were unaffected. Finally, adult rats exposed to 10, 50, or 100 ppm of halothane from conception to day 28 postpartum had 15% less 5-hydroxyindoleacetic acid in brain, but normal 5-hydroxytryptophan, noradrenalin, and dopamine. The possibility is discussed that the hyperalgesia noted above results from a permanently reduced turnover of brain serotonin produced by halothane present in brain at days 10-15 of gestation.


Pathologic changes following chronic exposures to halothane: a review. The toxic effects of halothane on the liver, kidney, and brain are reviewed. Increasing evidence has indicated that hepatic degeneration can be induced in several animal speices after exposure to halothane. Recent electron microscopic investigations have also revealed cytological degeneration of the liver cells after chronic exposure to subclinical levels of halothane. Degeneration of the kidney and the nervous system after halothane exposure have also been reported. The pathological effects of halothane on the neonatal (developing) liver, kidney, and brain are also demonstrated by electron microscopy. Although the full significance of these observations on experimental animals in relationship to human exposure is still not known, the indication of the toxic potential of halothane on the biological system is strong and deserves further investigation.


Oxidative metabolism in fetal rat brain during maternal halothane anesthesia. The present study examines the effects of maternally administered halothane on fetal brain metabolism as determined by direct tissue analysis. Term pregnant rats were paralyzed, ventilated, and administered halothane in concentrations of 0.4, 1, or 2%. For comparison of fetal response to anesthetic agents, other maternal rats were administered pentobarbital (50 or 200 mg/kg). Dams receiving 0.4% halothane or 50 mg/kg pentobarbital remained normotensive, whereas 2% halothane or 200 mg/kg pentobarbital led to a 65% reduction in maternal blood pressure and a 3-fold increase in blood lactate. Fetal blood lactate tended to parallel the maternal lactacidemia. Fetuses of dams anesthetized with 0.4% halothane or 50 mg/kg pentobarbital exhibited concentrations of cerebral metabolities comparable to those of control animals. A 2% halothane level was associated with metabolic disturbances in fetal brain, indicative of cerebral hypoxia. Pentobarbital 200 mg/kg, although producing maternal hypotension and lactacidemia to a degree similar to 2% halothane, preserved a more optimal fetal cerebral energy state as reflected in a lower lactate/pyruvate ratio and normal ATP. The metabolic influence of pentobarbital may serve to protect the hypoxic fetus from neurological damage, an effect apparently not shared by maternally administered halothane.


Human exposure to tetrachloroethylene: inhalation and skin contact. There is considerable potential for worker exposure to tetrachloroethylene, both by skin contact and by inhalation, during its use in dry cleaning and degreasing operations. This paper reviews accounts of both accidental overexposures of workers and controlled exposures of human subjects by these two routes of exposure. Several reported cases of accidental overexposure to anesthetic doses of the chemical reveal that recovery was generally complete but prolonged, and accompanied by many days of measurable levels of the chemical in the patient's alveolar breath. Chronic overexposures of workmen have lessened since the general acceptance by the Western world of the recommended TLV of 100 ppm for 8 hr of daily exposure. Controlled inhalation studies with volunteer subjects at this level of exposure revealed no effects upon health but did indicate a slight decrement in performance on a coordination test. Additional behavioral and neurological tests revealed no interactive effects when alcohol or diazepam, two depressant drugs, were added singly to tetrachloroethylene exposures. Individual susceptibility to the vapor of this chemical, as evidenced by subjective complaints, was noted in approximately one of ten subjects. The authors conclude that the TLV concentration of 100 ppm in the workplace has a negligible margin of safety regarding unimpaired performance during repeated exposures which could be especially hazardous if the worker is physically active or is in a situation where skin absorption presents an added burden.


Metabolism of trichloroethylene and tetrachloroethylene in human subjects. A linear correlation exists between the trichloroethylene concentration in the work environments and the level of total trichloro compounds in the urine of the workers, as expressed by the equation: Gamma = 7.25=chi + 5.5, where Gamma is trichloroethylene in air (ppm) is Chi is total trichloro compounds in urine (mg/l). Trichloroethanol level is also linearly related to trichloroethylene concentration, while trichloroacetic acid level deviates from the linear relation when trichloroethylene level exceeds 50 ppm. In the case of tetrachloroethylene exposure, both trichloroethanol and trichloroacetic acid levels, and consequently the total trichloro compound level, reach a plateau at tetrachloroethylene level well below 100 ppm. The mean urinary biological half-life is 41 hr for trichloroethylene and 144 hr for tetrachloroethylene. The two values are the largest of the values so far obtained with organic solvents. The respiratory half-life is shorter than the urinary half-life, both in richloroethylene and in tetrachloroethylene. Applications of the urinalyses in clinical cases are described. In one case of trichlorethylene dependency, a longer urinary half-life of 73 hr was observed. An automated system is presented for the determination of total trichloro compounds in human urine. The system can analyze the samples at the rate of 20 samples per hour with an accuracy comparable to that of the time-consuming manual analysis.