[Arguments for a hesitamt attitude in the management of retroflexion of the pregnant uterus].

Among 5036 pregnant patients under prenatal care of a gynecologist, a retroflexion of the pregnant uterus was found in 438 cases (8.7%). The incidence of spontaneous abortion in the cases with retroflexion was 10.4%. This corresponds to the expected mean incidence of spontaneous abortion. In a control group of 1000 pregnancies without retroflexion of the uterus, the incidence of spontaneous abortion was 9.2%. The rate of premature delivery in cases with retroflexion was 5.3% and showed no difference to the control group without retroflexion (5.5%). Spontaneous anteflexion was awaited in all cases with retroflected pregnant uterus. Because of overflow incontinence manual anteflexion of the uterus at 15 weeks of gestation became necessary in one case. This pregnancy went to term. Because of our good results, we make a plea for expectant management of retroflexion of the pregnant uterus. Regular control examinations are necessary so that the lack of spontaneous anteflexion is not overlooked. Among 378 cases with a retroflected pregnant uterus which were followed to term, manual anteflexion became necessary in only one case.


[Contraception with the intrauterine pessary Progestasert].

A prospective study was carried out from June 1973 to August 1976 in 131 women fitted with a newly developed IUD (Progestasert). The IUD's were removed as planned after 12 months with the exception of 4 cases in which they were retained for up to 17 months. The evaluation of the trial was performed according to the Life Table Analysis and the usual statistical methods. 1496 application months were evaluated. One case each of intrauterine and extrauterine pregnancies were observed. One patient experienced spontaneous expulsion of the IUD. In 9 cases medical reasons led to the removal of Progestasert at an earlier date. Duration, intensity, and interval of menstruation as well as frequency of spotting and dysmenorrhea were recorded. A slight increase in duration and interval of menstruation was seen whereas bleeding intensity was reduced. Increased spotting, especially during the first month after insertion, and a significant reduction of dysmenorrheal complaints were noted after 2 months. In addition to 8 removals due to bleeding disturbances, 6 other patients experienced spotting throughout the entire treatment period. Laboratory tests such as ESR, WBC, hemoglobin, hematocrit and cytological smear determinations were carried out. No pathological alterations of these parameters were found.


[Diagnosis in diseases of the eye and orbit. Indications and value of ultrasonic diagnosis and radio computer tomography].

The principles of diagnostic ultrasound and computed X-ray tomography are briefly described. The informations to be expected can be derived. First, the clinical use in determination of size and localization of the bulbus is discussed. This proved helpful in follow-up studies of buphthalmos, localization of intraocular foreign bodies and differentiation of pseudo-protrusion and protrusion (ultrasound exophthalmometry). The differentiation and localization of intraocular disorders (e.g. retinal detachment, intraocular tumors, vitreous hemorrhages, aqueous cysts) is facilitated. In space-occupying orbital disorders both methods complement but cannot replace each other. Therefore it appears that further development of ultrasonic diagnostic techniques should be promoted to reach at least the standards which are nowadays already achieved in computed X-ray tomography.


[Plasmacytoma].

Plasmocytoma is generally a systemic disorder and has to be differentiated from solitary plasmocytoma of bones and connective tissue. Diagnosis is based on the typical bone marrow findings, the demonstration of monoclonal paraprotein and the radiological skeletal changes. Prognosis is poor, life expectancy limited to about 18 months. Specific therapy with cytotoxic drugs leads in many cases to marked improvement of the general condition, relative freedom of pain and a decreased complication rate.


[Inhibition of cancer cell stickiness, a model for the testing of in vivo thrombocyte aggregation inhibitors. IV. Effect of sulfinpyrazone].

It has been shown that sulfinpyrazone is able to interfere with the dynamic interaction between sticky Walker-256-carcinosarcoma cells and the vascular endothelium. This effect is due to a dose-dependent inhibition of platelet adhesiveness and aggregation to sticky circulating tumor cells and their consequent attachment to the vascular endothelium as observed by means of intravital capillary microscopy in the mesentery of rats. Further proof of these investigations was that sulfinpyrazone led to a dose-dependent inhibition of the immediate drop of circulating platelets and reduced significantly the lethal pulmonary tumor cell embolism which occurred in 57.5% of the controls within 5-10 minutes after intravenous transplantation of 1 X 10(6) Walker-256-carcinosarcoma cells. These results are interpreted in an inhibition of platelet adhesiveness and aggregation in vivo by sulfinpyrazone.


[The patho-anatomical Regional Cancer Registry of North Baden].

Since the middle of 1976, after approximately one year of preparation, the regional cancer registry of gastrointestinal tumors in the district of North Baden has been fully in operation. Meanwhile approximately 15,000 cases of cancer have been registered retrospective including 1971. Reasons for the maximum size of a population-based registry and the method of efficiently procuring the necessary data are shown.


[Polymyalgia arteriitica].

A description of the polymyalgia arteriitica is presented: preference of beginning in higher age, leading symptom being muscular pain at the back of the neck, around the shoulders, the upper arms, the buttocks and thighs as well as the visibly augmented erythrocyte sedimentation rate. The arteriitic manifestation being considered, the necessity of adequate corticosteroid therapy is accentuated. Prognosis depends on both factors, localization of the arteriitis and efficient corticosteroid treatment.


[Carcinoembryonic antigen in gynecological oncology].

169 CEA-determinations in sera from 119 patients with gynecologic malignancies and 30 healthy women as controls are reported. The highest percentage of positive results was found in patients with cancer of the ovaries (62%). This result is followed by 60 per cent in cancer of the collum uteri, 50 per cent in cancer of vulva and vagina and 42 per cent in cancer of the breast. Very low CEA-titers have been found in cases with cancer of corpus uteri. This method is not reliable enough for very early detection of gynecological cancer, it may be a useful help in the supervision of cancer patients who already have been treated.


[Bloom syndrome: review and definition].

The cases of Bloom-syndrome as described in the literature (till...) are reviewed and this syndrome is discussed as a defined entity which can be separated from congenital poikilodermias. The prognosis of this autosomal recessive disease is dubious.


[Relationship between immunoglobulin levels in cerebrospinal fluid and serum].

By means of radial immunodiffusion, immunoglobulins A, G, M and albumin were determined in serum and unconcentrated cerebrospinal fluid from 182 controls and 141 patients. Concentrations in cerebrospinal fluid and serum of patients did not correlate, not even in those groups whose elevated immunoglobulin and albumin concentrations in cerebrospinal fluid resulted from damage to the blood-cerebrospinal fluid barrier, as in inflammatory diseases and neoplastic processes of the central nervous system or of the meninges.--Concentrations of immunoglobulins in cerebrospinal fluid should therefore be evaluated independently of the serum concentrations. Cerebrospinal fluid and serum constitute samples from two separate compartments which are capable of independent immune reactions.


[Epidemiology of mental disorders and psychiatric care. Part 2. Discussion of results].

A prior analysis of treated patients is required in order to develop effectively a system of psychiatric health services. Data are presented respectively for a rural small town area of Upper Bavaria with 424,000 residents. Incidence and prevalence rates of treated mental illness are considered according to various criteria, especially diagnosis. Morbidity rates for localities of varying size are cited as an example of ecological approach. When planning, one must conclude the necessity for differentiated psychiatric treatment within the community, with emphasis on outpatient services.


[Studies on nucleic acid metabolism. Molecular biology and clinical significance].

All known nucleic acids contain varying amounts of modified nucleosides. In contrast to the standard nucleosides, the modified nucleosides and their nucleobases as minor nucleic acids components cannot be recycled. Only part of them can be catabolized. Therefore, many modified catabolites of nucleic acids are enriched in urine. They can be measured at the picomole level by cation exchange HPLC. Plotted against age, the excretion curves of the modified nucleobases are in accordance with the shape of the known growth velocity curve. Aberrant nucleobases excretion patterns are found in very young children, probably resulting from a specific nucleic acids equipment as well as from different relative growth velocities of different organs. In the urine of patients with neoplasms, often extremely disturbed nucleobases excretion patterns are found which can be normalized by successful cytostatic therapy. From the published and our own results it is concluded that modifications of nucleic acids should play an important regulatory role. Therefore, the analysis of modified nucleobases excretion patterns will open new diagnostic approaches.


[Pharmacokinetics of piracetam during delivery].

The excretion of Piracetam was monitored by measuring the concentrations in maternal and fetal substrates during labor in nine volunteers. Piracetam was tolerated without side-effects and injected in the maternal cubital vein. Consecutively, maternal plasma and urine samples as well as amniotic fluid portions were collected during labor. at delivery, fetal blood from placenta and the first fetal urines were collected. Biostatistical methods showed that approximately 50% of Piracetam were eliminated 80 minutes after the injection of the drug. In amniotic fluid a continuous rise of Piracetam concentrations was monitored until delivery. In fetal plasma and urines the substance could be detected. The rapid excretion of Piracetam during labor was obviously typical for the situation sub partu; reasons are discussed.


[Vertebrogenic dizziness, etiology and differential diagnosis].

Cervical-induced vertigo may be caused by degenerative or functional disorders of the cervical spine. Explaining its pathophysiology, disorders of the cervical spine itself, the vertebral artery and the entire cardiovascular system must be taken into account. 66 patients with signs of cervical-induced vertigo were examined neuro-otologically, the function of the cervical spine was judged by X-ray and clinical examination. Moreover, a special provocation of the cervical spine was made--when patients were sitting and in supine position with the head in different directions--including simultaneous ENG recording. With regard to the complaints of the patients and all clinical findings, a selection could be made in 3 groups of signs: A = the degenerative cervical syndrome, B = the irritative cervical syndrome, C = the vertebralis-basilaris syndrome.


[The problem "diagnosis" demonstrated on the example of farmer's lung].

Using the farmer's lung as an example, the various problems in establishing a diagnosis are discussed. The "instruments" of diagnosis such as history (exposition), functional parameters, macro- and micromorphology, and laboratory findings are described. The different criteria and their value, the compatibility of informations, and the quality of definitions ("fuzzy sets") are analytically evaluated--all this finally leading to the "quality" of diagnosis and of subsequent decisions.


[Chronic septic granulomatosis imitating exogenic allergic alveolitis (farmer's lung)].

A 17-year-old boy demonstrated clinical and immunological signs of exogenic allergic alveolitis (farmer's lung). The patient grew up in the country and suffered from recurrent "pneumonia." In his serum precipitins were detected against Micropolyspora faeni, Aspergillus fumigatus and hay. Transbronchially obtained lung tissue showed histologically an inflammation of the epitheloid-cell-granulomatous type with fibrosis. A congenital defect of the neutrophilic function was suspected in view of the recurrent infections with significant polyclonal hypergammaglobulinemia, accompanied by leucocytosis and neutrophilia. In vitro studies of isolated patient's neutrophils showed that he suffered from chronic granulomatous disease. CGD should be considered in adolescents and adults with a history of severe infections and unexplained pulmonary fibrosis or pulmonary fibrosis simulating exogen allergic alveolitis.


[Familial sarcoidosis. 4 cases in 2 families].

Among the patients of the Bundeswehrzentralkrankenhaus Koblenz two new cases of familial sarcoidosis with two cases each became known from Nov. 1977 to Feb. 1978. These cases are reported with typical x-ray-findings. The above mentioned short period of time for finding two new cases of familial sarcoidosis seems extraordinary, as in the world literature on sarcoidosis until today only 114-150 cases are reported. "Sarcoidosis" is described referring to the newer literature. Possible causes for acquiring sarcoidosis are discussed. Specific research by the disciplines social medicine, genetics, and hygiene of the families suffering from familial sarcoidosis is proposed, in order to analyze genetic disposition and/or environmental factors. Long-term supervision of the families afflicted with familial sarcoidosis is proposed.


[Alcohol abuse in children and adolescents].

There is a strong increase in the misuse of alcoholics by children and adolescents. The different phases of development towards an adolescent alcoholic are discussed. Possible causes are shown. It is especially important that children with minimal cerebral dysfunction seem to be more inclined to a later development towards alcoholism. Identification with the adult world seems to be the main reason for adolescents to drink alcohol excessively. Methods of identifying young alcoholics are discussed, preventive methods are shown. A discussion of therapeutical possibilities follows.


[Bile acids in the intestinal juice of infants and children with malabsorption and maldigestion syndromes].

43 gastroenterologically healthy infants and children as well as 45 patients with different malabsorption and maldigestion syndromes were investigated during the basic secretion and after injection of secretin and pancreozymin in order to establish the total quantity and also the distribution of the secreted bile acids. The total concentration and quantity were determined enzymatically; column and thinlayer chromatography were utilized to separate the bile into 30 different bile acids. While the total quantity of bile acids was found to be independent of age, the compounding of bile changed during the first years of life. Patients with coeliac disease reacted to injection of peptide hormones by producing a larger volume of secretion than did the control group. Despite the increased secretion there was at the same time a significantly higher concentration of bile acids in the duodenal juice. In this group the analysis of the bile acid distribution indicated no abnormality but striking changes were found in patients with cystic fibrosis, biliary atresia, M. Wilson, and in children after subtotal resection of the small bowel.


[Procetofen, a new lipid- and urine-acid-reducing substance].

23 patients with different forms of hyperlipidemias received procetofen (3 X 100 mg/day) over a period of fourteen days. The cholesterol concentration in blood showed a significant reduction from 322 +/- 30 mg/dl to 227 +/- 37 mg/dl, triglycerides dropped from 221 +/- 84 mg/dl to 129 +/- 34 mg/dl and uric acid diminished from 6,1 +/- 1,4 mg/dl to 4,6 +/- 0,8 mg/dl.


[Experiences with substitution therapy using a new pancreatic enzyme of plant origin].

The indication field of Nortase, a combination of microbial lipolytic and proteolytic enzymes, comprises the replacement therapy of maldigestion and insufficiency of pancreas. Its efficacy and tolerance were tested in 100 patients in an open study under the conditions of general practice. During the 15-day treatment the following symptoms were evaluated: anorexia, flatulence, pressure and pain in the epigastrium, nausea after the meals, belching, pyrosis, the quality of feces and the body weight. 96% of the patients showed relief of the symptoms after treatment, 65% a therapeutic result ranging from very good to good. In 53% an improvement of the quality of feces was observed and 76% reached an increase in weight. 6 patients had some small side effects, in 1 case the treatment had to be interrupted. The altogether good results confirmed the results of former investigations on the acid stability and the high lipolytic activity of lipase from Rhizopus arrhizus.


[Prognosis of idiopathic scoliosis].

The prognosis of the scoliosis is determined by early and exact treatment, which depends on the degree of curvature, age, localization and expected of deviation. Scoliosis up to 30 degrees is treated by physical therapy. Between 30-50 degrees an active treatment with the Milwaukee-brace is recommended. Over 50 degrees surgery is required, because further progression is to be expected. The Harrington procedure should now be used in all centers of scoliosis. Paraplegia is seen in 0,5%. Minor complications and better correction can be expected by surgery carried out in special centers.


[The congenital club foot].

The congenital clubfoot of infancy to-day is curable in 90% of cases. Aim of the treatment is normalization of form, function and growth. With combined therapy according to Imhäuser optimal results are possible: 1. Immediately after birth--depending on the general condition of the newborn--reposition of all components without the talipes equinus component; plastercasts are changed frequently till the third or fourth month of life; 2. surgical development of the heel; calcaneal equinus is corrected by elongating the tendocalcaneus combined with arthrolysis of the ankle joint; 3. intensive clinical treatment by physiotherapy; 4. ambulant orthopedic controls at regular intervals till the end of skeletal growth.


[The fixed lumbar lordosis due to slipped disks].

The fixed lumbar lordosis is represented by a group of characteristic symptomes; they specifically happen to the LWS of adolescents which are in a specific pathogenic situation. The cause of the fixed lumbar lordosis is almost a slipped discus. The case of an adolescent is presented, who had two operations because of twice slipped discus in one year.


[The irritable colon syndrome. New therapeutic possibilities in the treatment of a frequent syndrome].

A double-blind clinical longterm trial with the musculotropic agent Mebeverine in 30 patients, suffering from the irritable colon syndrome, is reported. In 70% of patients, treated by this new antispasmodic preparation, most symptoms, related to the irregular activities of the lower alimentary tract--as abdominal cramps and distrubance of bowel habit--improved.  Female patients were superior in getting symptom-free. No unpleasant drug-related side effects were seen. The double-blind controlled trial showed Mebeverine to be superior to a placebo preparation regarding relief of symptoms and demonstrates this agent to be a useful drug for controlling the symptoms of this functional disorder. The usefulness is enhanced by the fact that most of the patients studied had been pretreated by other preparations with low or limited therapeutic effectiveness. Despite facing the difficulties in documenting objective criteria of improvement in a condition such as the irritable colon, defined as a "collection of functional disorders of the colon of mixed aetiology" (Truelove), our results demonstrate that Mebeverine is able to improve abdominal cramps and disturbances of bowel habit in this common disorder without side effects, as seen with standard anticholinergic preparations.


[Carcinoembryonic antigen as a control parameter in cryosurgical treatments of patients with rectal carcinoma].

The monitoring power of CEA during cryotherapeutic management was investigated in a group of 39 patients with inoperable cancer of the rectum. By the results it is concluded that the determination of serial serum CEA levels during cryosurgery is not only a useful parameter of the results of local treatment but also a sensitive indicator of tumor metastases.


[Synchronous and metachronous processes in colo-rectal carcinoma].

Polyps are often associated with carcinoma in the colon. The incidence of colorectal polyps with single carcinoma is up to 25% and with multiple carcinoma up to 75%. Not infrequently both synchronous and metachronous carcinoma are found in the colon and rectum. These findings emanate from a sample of 367 patients (in this hospital) with colorectal carcinoma during the period 1973 to 1977. The incidence of synchronous and metachronous carcinoma as well as severe dysplasia (focal carcinoma) in adenomatous polyps was nearly 8%. In slightly more than 50% of cases involving a single carcinoma, there was no evidence of an accompanying condition or later development. In more than 20% of the cases single carcinoma was accompanied by synchronous and metachronous polyps. These figures eloquently illustrate the necessity for closely coordinated postoperative care of patients with colorectal carcinoma.


[Heart rhythm during esophago-gastro-duodenoscopy].

The ECGs of 157 patients were registered continuously during the oesophago-gastro-duodenoscopy with a R-R intervall monitoring system. The behavior of frequencies and cardiac arrhythms of 53 patients with and 104 patients without heart diseases is reported. 32 patients were premedicated with 0,5 mg Atropin intravenously, 121 patients received intramuscular premedication. The influence of the vegetative nervous system is discussed in view of the heart actions during the diagnostic procedure. A clinically relevant danger for the heart and circulatory system caused by oesophago-gastro-duodenoscopy was not observed.


[Inhibition of gastric acid secretion and motility with trospium chloride].

The present study demonstrated a significant inhibition of gastric acid secretion and gastric motility by parenteral and oral application of trospiumchloride. Oral application of a dose inhibiting gastric acid secretion was not associated with the known side effects of anticholinergic therapy like tachycardia, reduction of salivary secretion and impairment of visual accommodation.


[Therapy of reflux esophagitis. Manometric determination of the effect of bromoprid on the lower esophageal sphincter].

The effect of bromopride (4-amino-5-bromo-N-(2-diethyl-aminoethyl)-2-methoxy-benzamide) on the pressure amplitude of the lower oesophageal sphincter was examined in ten healthy subjects and fifteen patients suffering from peptic oesophagitis. Diagnosis of peptic oesophagitis was based on the histological study of a sample of the lower oesophageal mucosa.


Morphological patterns of the liver in South American blastomycosis.

Histological features were semi-quantitatively analysed in 60 livers, obtained by necropsy, from patients who died of South American blastomycosis. These findings were classified and correlated with duration of the disease and treatment. Bile-duct lesions were prominent and a particular pattern was found in which segments of bile ducts were "disrupted" and replaced by inflammatory reaction. A classification of the lesions is proposed: Class o--near normal livers; Class I--predominance of necrosis and suppuration; Class II--predominance of tuberculoid granulomas; Class III--portal fibrosis and non-specific infiltrate. There has been no evidence that treatment could induce bile-duct proliferation, fatty change of liver cells, or cholestasis. On the other hand, less fibrosis was found in treated patients. Pathogenesis of the bile-duct lesions is discussed.


A comparison of the use of the "Tru-Cut" needle and fine needle aspiration cytology in the pre-operative diagnosis of carcinoma of the breast.

Two methods of obtaining a pre-operative diagnosis of carcinoma of the breast are compared. Tru-Cut needle biopsy was carried out on 368 consecutive patients with palpable breast lumps, and both Tru-Cut biopsy and fine needle aspiration cytology were performed during part of this study on 163 of the patients. A final histological diagnosis was obtained in each patient, at excision biopsy or mastectomy. There were 278 patients with carcinoma and 90 with benign breast disease. A correct positive diagnosis of carcinoma was made by the Tru-Cut method in 73.5% of cases, but in only 52% of cases by aspiration cytology. More importantly, there were no false positive diagnoses of carcinoma with Tru-Cut biopsy, but five cases of benign breast disease were incorrectly diagnosed as carcinoma by aspiration cytology. It is concluded that Tru-Cut biopsy is sufficiently reliable to be able to proceed direct to mastectomy following a positive diagnosis of carcinoma, in distinction to aspiration cytology with which an unacceptably high number of false positives occurs. The benefits of a pre-operative Tru-Cut biopsy diagnosis are identified.


The "Scrimp" technique--a method for the rapid diagnosis of surgical pathology specimens.

A rapid cytological method for the diagnosis of surgical pathology specimens is reported. This procedure consists of a scrape of the tissue and an imprint of the cells and has therefore been termed the "Scrimp" technique. It is simple, inexpensive and accurate and is of value in routine surgical pathology in the separation of benign and malignant lesions and particularly in the determination of the adequacy of surgical excision of skin tumours.


Chondroectodermal dysplasia (Ellis--van Creveld syndrome) with dysplasia of renal medulla and bile ducts.

A case of a 28-month-old boy with chondroectodermal dysplasia (Ellis-van Creveld syndrome) is reported. Besides polydactyly, ectodermal dysplasia, acromelic dwarfism and congenital heart defect, which are characteristic morphologic features of the syndrome, additional dysplastic developmental defects were discovered in the kidneys, liver, and lungs. Detailed histopathologic studies of the growth plates of tibia, femur and ribs disclosed an irregular, partly hyperplastic, partly dystrophic appearance of the epiphyseal cartilage, which was not resorbed properly by the invading blood vessels. Focal areas of necrosis occurred and barriers of tongue-shaped cartilaginous peninsulas persisted. Regular enchondral ossification was hindered and compensatory membrane ossification was found in the fibrosing metaphyseal bone marrow adjacent to the cartilage. Dysplasia and fibrosis of the renal medulla plus interstitial fibrosing nephritis in the cortex resulted in kidney contraction and renal failure. Hepatomegaly, portal fibrosis and bile duct hyperplasia and dysplasia were detected at autopsy, but did not have any clinical significance. These findings once again emphasize that derivatives of all three germ layers are involved in the Ellis-van Creveld syndrome. The possibility that a single metabolic or structural abnormality of the mesenchymal tissues could be responsible for the various organ dysplasias is discussed.


Endocardial fibrosis in apparently normal infant hearts.

A classification of the histological appearance of the endocardium in infants, and observers' reproducibility tests have been carried out. In a retrospective survey of 262 overtly normal hearts, what is considered to be abnormal thickening of the endocardium was found in 3.4%, and probably significant thickening in 20%. The changes occurred in unexpected home deaths as well as in hospital deaths and the lesions may be a contributing factor in some cot deaths, but a prospective study is required to confirm this.


Blue naevus of the cervix: report of two cases and review of the literature.

Two cases are described of blue naevi occurring in the uterine cervix. These showed a histological appearance identical to that seen in the commoner cutaneous examples. Electron microscopy of both lesions showed the presence of melanosomes in the dendritic cells. No Schwann cell elements were identified. Previous reports of cases are reviewed and discussed.


Multiple vascular malformation in the "blue rubber bleb naevus" syndrome: a case with aneurysm of vein of Galen and vascular lesions suggesting a link to the Weber-Osler-Rendu syndrome.

A case of Bean's syndrome is reported in which a wide variety of vascular malformations are illustrated. Among these were multiple arterio-venous malformations including a so-called vein of Galen aneurysm. A comparison of this case with those in the literature suggests that the pathology in patients with Bean's syndrome may be more varied than heretofore recognized, and that an overlap between this syndrome and the Osler-Weber-Rendu syndrome may exist.


Community residential treatment for schizophrenia: two-year follow-up.

Two-year outcome data from a study comparing two kinds of treatment given similar groups of young, newly diagnosed, unmarried schizophrenic patients deemed in need of hospitalization are reported. The experimental program, Soteria, is a nonmedical, psychosocial program with minimal use of antipsychotic drugs; it is staffed by nonprofessionals and located in a home in the community. The control program is a short-stay, crisis-oriented inpatient service in a community mental health center where neuroleptic drugs are the principal treatment. The experimental group had significantly longer initial stays, and only 8 per cent received neuroleptics during their initial admission. Over the two-year follow-up period, there were no significant differences between the groups in readmissions or levels of symptomatology. However, experimental subjects significantly less often received medications, used less outpatient care, showed significantly better occupational levels, and were more able to live independently.


Psychiatric education in the emergency room: must teaching stop at 5 p.m.?

The authors surveyed psychiatric residency programs to see what educational resources were available to residents assigned to provide emergency services during evening and nighttime hours. Almost half the sample of 89 programs assigned first-year residents to provide emergency care. The primary immediate means of support for the residents was telephone assistance, in 49 per cent of the programs, or the presence of a non-psychiatrist professional, in 35 per cent. The general lack of educational resources reflects the traditional dispositional model of emergency psychiatry, the authors say, with its emphasis on briefly evaluating the patient and referring him elsewhere for services; current training practices cannot meet the goals of the crisis system model in which a comprehensive treatment program is begun in the emergency room.


Overnight admission for psychiatric emergencies.

Patients identified as psychiatric cases on the emergency ward of a 1036-bed teaching hospital are handled in one of three ways: released with outpatient referral, admitted to a psychiatric inpatient facility, or hospitalized in a general medical holding unit with a 24-hour stay. The authors obtained demographic and diagnostic data on 377 psychiatric patients seen consecutively on the ward and then compared those admitted to the holding unit (83) with those released (193) or hospitalized (101). The three groups were demographically similar but the patients in the holding group fell between the other two groups in severity of psychopathology. More than half the patients admitted to the holding unit were released the following day. The authors discuss the advantages of overnight admission as an alternative to hospitalization or release.


Ex-patient visitors to the hospital psychiatric unit.

An informal study of visits to an inpatient psychiatric unit by former patients indicated that such visiting was a common occurrence, more prevalent than staff realized. Most ex-patient visitors were chronically impaired individuals who were making a marginal community adjustment and did not use aftercare services. Of 29 expatient visitors, some of whom made multiple and even daily visits, more than half appeared to use the visits as an indirect, symbolic way of asking for help. For some the brief contacts with treatment personnel seemed to have therapeutic value. The authors suggest that, although such visits may be troublesome to staff, expatient visitors should be welcomed and offered informal brief supportive contacts when feasible.


Differential diagnosis of the disturbed elderly patient.

Disturbed elderly patients too often receive a general and rather automatic diagnosis of senility when a differential diagnosis, made by a multidisciplinary team, could identify their problems more specifically. The Gerontological Treatment Center of the Psychiatric Institute of Washington, D.C., has been making such differential diagnoses for the past four years and has returned nearly 80 per cent of its 300 patients to community living after six to eight weeks at the center. The most common problem found in the patients is depression. Case examples demonstrate the need for an understanding of both physical and mental problems that elderly patients face.


Movement therapy with geriatric patients in a convalescent home.

After several weeks of orientation with staff, the author, a registered dance therapist, established a movement therapy group for long-term geriatric patients in a convalescent home. The purpose was to promote socialization and expression of feelings, partly by recognizing even the most minimal participation in the group. Many patients were severely depressed and disoriented; most were in wheel chairs. Three months later a second group, functioning at a higher level, was formed. During the first six months, patients showed increases in verbalization and spontaneous expression of feelings, in interaction, and in assertiveness.


Obtaining informed consent for mental health treatment.

A series of forms has been developed by staff at the Veterans Administration Hospital in Seattle in response to a Washington state law requiring that patients give informed consent to treatment. The forms, which describe the nature of the treatment and possible risks and benefits, follow four models: a single consent form that meets all the needs of a clinical unit; separate consent forms for various services of a clinical unit, such as medication or group or individual therapy; a limited-consent form combined with a brochure or fact sheet; and a consent form combined with a treatment contract. The authors report that use of the forms has required very little additional staff time and has not discouraged patients from entering treatment.


Cardiac rehabilitation program focuses on total patient.

One hospital's attempt to combat the nation's leading cause of death is presented here. This medium-sized community hospital has initiated a cardiac rehabilitation program that encompasses the psychosocial as well as the physical well-being of the patient. The three-phase plan involves regular physical examinations, educational counseling for patients and families, and individualized inpatient and outpatient exercise regimens.


Automated system upgrades personnel and payroll records.

A hosital implemented a computer-based system that produces highly detailed and accurate automated personnel files, weekly time sheets, employee attendance records, itemized weekly paychecks, and other special reports. The system has reduced the time, labor, space, errors, and costs associated with producing and storing these personnel records.


Hospital structures guidelines for coping with snowstorms.

When a snowstorm not only paralyzes a community but also isolates its hospital or hospitals, contingency plans and procedures ensure the effective administration and operation of a health care facility during the emergency. In retrospect, Massachusetts General Hospital, Boston, has developed specific policies, procedures, and mechanisms to identify and deal with logistical and organizational problems that MGH experienced during the 1978 blizzard.


Patient drug self-administration improves regimen compliance.

Through a hospital's three-phase program, inpatients learned about their medications and gradually accepted responsibility for self-administration of these medications, for developing their schedules, and for adhering to their regimens. A postdischare follow-up study showed that the program had substantially improved patient compliance with medication regimens.


Does continuing education improve nursing practice?

Is a one-time mandated license enough to ensure competent, up-to-date nursing practice in today's hospital? Are present continuing education programs for nurses adequate? Is mandatory relicensure for nurses necessary? The author looks at these questions and provides some thoughtful and thought-provoking answers.


Hospital offers cardiac crisis program to industry.

A university medical center has initated a cardiac crisis plan that reaches out to industry to promote preventive health care among employees. The program described here served as a marketing tool for the medical center to establish its credibility among business leaders.


Central service guidelines present challenges for in-house packaging.

New standards and guidelines for in-house packaging present perplexing issues and questions regarding types of materials, procedures, and handling of packs to achieve and maintain sterility.


Local vs. regional planning: a delicate balance.

Planning at the institutional level is crucial if hospitals are to influence the initiatives of government regional regulatory agencies. Given the current intensive regulatory environment, the absence of an effective planning process could pose a threat to the very survival of some health care institutions. But most importantly, planning is necessary for every hospital, large or small, because it is the principal management tool that helps hospitals define and meet community needs. The author offers some fundamental principles and practical advice for the development of new directions in hospital planning.


Medical malpractice suits can be avoided.

As medical treatment has become increasingly complex over the years, patient care has become more and more dehumanized. The author explains how this feeling of dehumanization can cause patients to file malpractice suits and explores ways in which hosptial administrators can attempt to remedy the situation.


The hospital system takes a look at 'shrinking' itself.

Health care planning mechanisms and the dangers of the "survival of the fittest" method of reducing the size of the hospital system have led some hospitals and hospital associations to undertake programs of conversion of acute care beds, long-range citywide and statewide planning for reduction in the number of beds, and multiple use of beds, units, or entire hospitals.


Do administrators' views show why hospitals do or don't use unit doses?

A survey of hospital administrators showed some expected correlations and some surprising contradictions between their opinions of the unit dose system and their institutions' policies on use of the system. The survey indicated that hospital administrators need to be better informed about many of the advantages and disadvantages of the unit dose system and that communication with the hospital pharmacists strongly influences their opinions.


Cleaning, disinfecting procedures help control spread of infection.

The spread of nosocomial infection connected with the use of the fiberoptic bronchoscope can be controlled if hospital personnel are taught clear, specific procedures for the cleaning, disinfecting, and/or sterilizing of these instruments. Infection control authorities recommend that the scopes be sterilized between each patient use, but many hospitals find this to be an impractical practice. As an alternative, fiberoptic bronchoscopes can be disinfected with alkaline gluteraldehyde, a process that takes approximately 10 minutes.


Increase control of operations to reduce linen costs.

Hospital linen managers can reduce costs most effectively by devising and imposing controls on linen operations rather than by merely limiting linen usage. Such controls include use of work load timetables for the laundry department, an itemized charge system for each linen-using department, standards for daily usage, and immediate investigation of deviations from the standards.


Reducing excess hospital capacity is a tough but necessary job.

Developing and implementing an effective program to reduce excess hospital capacity is an extremely difficult and complex task. But it is clearly a logical means to contain health care costs and to develope a cost-effective health system.


The end of the line: when a hospital closes.

Seven hospitals that closed between 1974 and 1977 were forced to shut down by a variety of factors. Several of the closings were accomplished in a relatively painless fashion. Others were difficult and created many problems. The individuals involved in the closings and their aftermath learned many lessons, the chief among which is the critical need for communication among all parties involved.


Wide range of causes found for hospital closures.

Survey conducted by the American Hospital Association has determined where hospitals have closed, what types of hospitals close, and the reasons for closing. Comparative data for a three-year period are used to show trends in a variety of factors affecting hospital closings.


Impact of hospital closures on nearby hospitals studied.

An AHA study showed that hospital closures during 1975 significantly affected utilization of other hospitals in the vicinity of the closures. The degree of impact on the affected hospitals varied widely according to certain factors, such as urban or rural setting, bed size, and number of other nearby hospitals.


Planning with the community in mind can prevent hospital closings.

A study of 46 closings and mergers in New York City over a 15-year period shows the importance of public funding for the viability of hospitals and the need for sound institutional planning for hospital survival. Regulatory agencies may deny hospitals public funds if they do not respond to their communities.


There's more to it than people shuffling.

If personnel administrators are to gain their rightful place on the hospital management team, they must be prepared to offer services well beyond the traditional, technical aspects of the personnel function. To begin to provide these services, they must be willing to make difficult choices.


Catholic health care systems: a sign of the times.

Fundamental changes have been taking place both within society and within the Church and religious communities in relation to the delivery of health and hospital services. Consequently, serious attention should be given to an indepth exploration of the potential for religious congregations to continue to vitally witness to the health ministry through the alternative of a systems approach.


Justice, a goal of coordinated Christian health care.

Different systems will be needed to bring order and unity to the many health care activities existing in American dioceses. Three underlying principles, however, should direct any efforts at unification: (1) the centrality of the parish to the development of health care programs, (2) the lay ministry of the health care apostolate, and (3) the reforming role of the ministry in attempting to change society to obtain justice for all.


Dealing confidently with IRS, Part II: IRS audit and postaudit procedures.

Preparation enables an administrator to control the hospital's participation in IRS audit procedures, to fulfill the requirements essential to the institution's tax-exempt status, and to choose the most appropriate alternative at the postaudit conference.


Help for the nonpromotable employee.

Over a period of time individuals become aware of their own nonpromotability, the causes of which are many and not all based in their inherent capacities. A concerned, skillful supervisor can help such employees to avoid counterproductive behavior and to experience satisfaction through restructuring positions and career paths and through counseling.


Anatomic and chromosomal anomalies in 944 induced abortuses.

A total of 944 induced abortuses, 922 of which apparently were anatomically normal and 22 of which were anatomically abnormal, were set up in culture. Of these abortuses, 910 (96.4%) were successfully karyotyped. The study can be divided into two periods. In the initial period, specimens without recovered fetal tissues were excluded, and no chromosome anomalies were found among the 182 abortuses karyotyped. In the later period of study, abortion specimens both with and without recovered fetal tissues were included, and 23 chromosomally abnormal abortuses, 9 of which were without recovered fetal tissues, were found among the 728 abortuses karyotyped. This gives a chromosome abnormality rate of 3.2%. The mean ovulation age for the 728 abortuses was 63.4 days (range 33--109 days). The mean maternal age was 28.4 years (range 15--48 years). The chromosomally abnormal abortuses included 13 (10 nonmosaic and 3 mosaic) trisomics, 7 triploids, 2 abortuses with balanced D/D translocations and an abortus with an XXq- karyotype. Among the 616 abortuses in which both amniotic and fetal tissues were karyotyped, there was complete karyotypic agreement between the two tissues. Among the 339 abortuses in which tissue samples from both sides of the body were analyzed, complete agreement was also found. Factors that may influence the prevalence of abnormal karyotypes in induced abortuses are discussed.


An extra band in human 9qh+ chromosomes.

Chromosome analysis of G-banded cells from nine individuals showed that 9qh+ chromosomes have an extra band in the h region in approx. 3 to 50% of the cells.


Preferential X inactivation in human placenta membranes: is the paternal X inactive in early embryonic development of female mammals?

In placenta membranes of newborn girls carrying electrophoretically distinguishable G6PD alleles, the maternally derived isozyme is expressed preferentially. This phenomenon cannot be explained by allelic differences in enzyme activity or by somatic selection directed against cells with particular G6PD phenotypes. Instead, it may be that in this tissue X inactivation is nonrandom. Preferential expression of the maternal X chromosome, as has been shown in marsupials and in extraembryonic membranes of rodents and now in man, may reflect the state of activity of the X chromosomes in the early stages of female embryonic development.


The relation of sex, smoking status, birth rank, and parental age to beta2-glycoprotein I levels and phenotypes in a sample of Australian Caucasian adults.

The serum level of beta2-glycoprotein I has been measured in a sample of 532 healthy, unrelated Caucasians resident in Melbourne. The distribution of levels is bimodal but lacks complete separation of the two modes. Samples with levels below 14.0 mg/100 ml are considered to be type I, and those above this level to be type N. The present sample contains 42 subjects of the former phenotype and 490 of the latter. The phenotypes are distributed equally between males and females and between smokers and nonsmokers and are unrelated to age, birth rank, or parental age. The gene frequencies for the Melbourne sample are compared with those found in various European samples. The beta2-glycoprotein I level of type N males is higher than that of females, and smokers have a higher level than nonsmokers. The positive regression of level on age is significant when corrections are made for sex and smoking status. beta2-glycoprotein I level is highly correlated with pseudocholinesterase activity. The pattern of inheritance of phenotypes has been examined in 17 families with a total of 56 children. In all families, this pattern is consistent with the currently accepted mode of autosomal codominant transmission.


The gene for human peptidase A is on band 18q23 and shows triplex and uniplex dosage effect.

Gene dosage effect for the enzyme peptidase A was studied in the red cells of subjects trisomic (seven cases) or monosomic (five cases) for the segment of chromosome 18 carrying the gene. The individual levels of enzyme activity in both groups were differen from those of the controls, but with a wide overlap. The use of the ratio of the activity of each subject to the midparent activity eliminated the overlapping. The mean ratio was 0.94 for the controls, 2.36 for the trisomics, and 0.41 for the monosomics. The trisomic ratio is higher than expected on the assumption of a linear effect. Correlation with the cytogenetic data in four cases of ring 18 and one of 18q- firmly places the gene for peptidase A on band 18q23.


Isoelectric focusing of human red cell phosphoglucomutase: the distribution of variant phenotypes in a village population from the Gambia, West Africa.

A total of 637 individuals from the rural village of Keneba in The Gambia, West Africa, have been typed for red cell PGM using isoelectric focusing (pH 5--7) in polyacrylamide gels. Eight different phenotypes have been detected. The frequency of the four alleles at the PGM1 locus was found to be PGM1+(1) 0.795, PGM1-(1) 0.053, PGM2+(1) 0.133, AND PGM2-(1) 0.019. A study of the PGM phenotypes in 89 families confirmed the simple Mendelian codominant inheritance of the four alleles. Comparative population data suggest that red cell PGM typing by isoelectric focusing might prove to be a useful genetic marker in anthropological studies.


Red cell glucose 6 phosphate dehydrogenase genotypes of the population of two West African villages.

Blood samples from 1109 individuals, residents of two villages in The Gambia, West Africa, have been examined for red cell G6PD. Using both starch gel electrophoresis and a spectrophotometric assay, preliminary phenotypes were assigned to the 519 males and 590 females. The G6PD genotypes were established by reference to the family trees of the two village populations. In addition to the G6PD alleles B+, A+ and A-, a fourth allele, representing a new variant of human G6PD was discovered between the two villages, despite their being of the same tribal origin and only five miles apart.


Is there a pattern of gene differentiation in the Indian populations.

Indian populations divided into a number of endogamous groups consisting of different castes, languages, religions, and tribes provide unique opportunities for examining the extent and nature of genetic differentiation at a microevolutionary stage. The genetic relationships between some of these Indian population groups have been examined using electrophoretic data from several biochemical loci in a gene diversity analysis. Does this type of analysis provide any insight into what causes such gene differentiation? What patterns of genetic variation emerge from these empirical findings? Answers are sought by relating the observed heterozygosity, genetic distance, and allied statistics to a mutation-drift hypothesis. The statistics used are: (1) interlocus mean and variance of heterozygosity, (2) mean and variance of genetic distance, and (3) correlation of heterozygosity and gene identity. The observed relationships between these sets of statistics agree well with the ones predicted by the hypothesis that different alleles at protein loci are selectively equivalent and gene frequency change occurs predominantly due to genetic drift.


Ring 10 chromosome: 46,XX,r10(p15q26).

A teenage girl with mild retardation and some clinical features suggestive of the Turner syndrome was found to have an r10(p15q26) in blood and skin cells. Quantitative evaluation of 28 red cell enzymes, including two (hexokinase and glutamic-oxalocetic transaminase) known to be on chromosome 10, gave normal values.


Trisomy 22 in a 20-year-old female.

Trisomy 22 was confirmed in a 20-year-old ambulatory female. Growth and mental retardation plus various dysmorphic features of this syndrome are described and compared with a previous survey. Several interesting unreported findings such as sexual immaturity and gait are discussed in regard to the 22 trisomy syndrome.


The L1210 radioimmune assay for detecting circulating immune complexes.

A radioimmune assay for the detection and quantitation of circulating immune complexes has been developed which employs the L1210 murine leukemia cell. The assay is based upon the binding of immune complexes to the L1210 through its Fc receptor followed by quantitation of the complexes with an 125I-labelled anti-IgG. The radioactivity of the cell pellet is referred to a standard curve generated by incubating the L1210 with known amounts of heat aggregated IgG (AIgG). 7S IgG of three species (human, canine, murine) do not bind significantly to the L1210 in contrast to the respective AIgG. The assay readily distinguishes between sera of healthy individuals and sera of individuals (human and canine) with diseases known to be associated with circulation immune complexes (i.e., systemic lupus erythematosus, HBAg positive acute hepatitis). The L1210 radioimmune assay is capable of detecting as little as 5 micrograms of immune complexes per ml of serum in all three species tested. The assay possesses several advantages over those currently employed, the most notable being the ability of the L1210 cell to detect immune complexes irrespective of their complement fixing properties.


Differentiation and activity of mast cells following immunization in cultures of lymph-node cells.

An extensive clonal differentiation into mast cells from primitive blast cell precursors occurred when lymph node cells obtained from mice immunized with horse serum were cultured on mouse embryonic skin monolayers. Horse serum was always present in the culture as a constituent of the nutritional medium. Mast cells developed to lesser extent also in cultures prepared from non-immunized mice. However, a clear difference in mast cell-granule ultrastructure and in histamine content was noted between the two. In cultures of lymph nodes cells from non-immunized mice the granules were tiny and uniform in size and in staining density; whereas granules in the immune cultures were larger and non-uniform in size and in staining density, and the intragranular organization manifested alterations of various forms. The content of intracellular histamine per 10(6) mast cells was about equal in both cultures. However, much more free histamine (per 10(6) mast cells) gradually accumulated in cultures of the immune lymph node cells, indicating higher rates of synthesis and release of histamine. The mast cells were readily degranulated by heat-inactivated (IgG1) sera of the mice used as donors of the lymph node cells. 92% of the mast cells were degranulated and as much as 80% of the histamine was released. The degranulation was accompanied by an immediate (albeit reversible) response of the fibroblast cells in the monolayer. A shift of the well-stretched cytoplasm of the fibroblasts opened numerous 'window' over the whole monolayer. The degranulated mast cells survived the process and could be maintained further in the cultures. Moreover, they were capable of repeated degranulation, releasing 50% of their histamine, even after four degranulation cycles performed over a 7 days' period of culture. No cytotoxic effect on the mast cells was noted and the histamine content in culture, 3 days after degranulation, seemed to be higher than in the undergranulated control cultures--suggesting an intensified rate of histamine synthesis.


Trichinella spiralis infection in mice. Mechanism of the resistance in animals genetically selected for high and low antibody production.

Mice genetically selected according to their capacity to produce antibody were orally infected with fifty muscle larvae. After 1 month, the number of larvae found in low responder mice was twice the number found in high responder mice. Following a second infection, low responder mice were completely protected while high responder mice showed only partial protection. It is suggested that the better resistance of high responder mice after a primary infection is due to their high and rapid antibody production. However, at the time of a secondary infection both lines of mice possess enough antibody to act on the effector cells (macrophages, eosinophils, etc.) and resistance is then dependent on the metabolic activity of these cells, which is more intense in the low responder mice.


Effect of age on C1q and C3 levels in human serum and their presence in colostrum.

The initiating complement component (C1q) in the classical pathway of 730 subjects and the first essential component (C3) in the alternative pathway of 461 subjects in Japan were examined. The study population consisted of normal healthy newborns, infants, children, adults and the old (from birth up to 75 years of age). In cord sera, both C1q and C3 were about 60% to the total mean level. At 3 days of age, C1q markedly increased to the mean level which remained relatively invariable up to 40 years of age. And above 40 years, the C1q level increased steadily with age up to about 75 years of age. C3 reached the mean level at about 1 month of age, and was highest during infancy. This level declined at about puberty and then continued to increase steadily with age up to around 55 years. In normal healthy subjects, a moderate positive rank correlation was found between C1q and C3 amounts. No significant differences of C1q and C3 levels were evident between male and female. No C1q was demonstrable in the colostrum from which lipids were previously removed, but after concentration by precipitation in a chelating agent with a low ionic strength, C1q, measured immunochemically, was detectable at concentrations of 300 ng/ml of colostrum. C3 was also detected at concentrations of about 200 microgram/ml of colostrum.


Isolation and characterization of Fc-receptors shed from human peripheral mononuclear cells.

Supernatants of human peripheral mononuclear cells containing membrane components shed in consequence of 4--37 degrees temperature shift were used as source for isolation of Fc-receptors (FcR). Aggregated IgG1 myeloma protein and TMV-anti-TMV complexes proved suitable sorbents to adsorb quantitatively and specifically the FcR-s. The isolated FcR interacts only with IgG and not with IgM. No haemagglutination was observed when the isolated FcR was incubated with sensitized human Rh+ red blood cells. Complement dependent lysis of sheep red blood cells was not inhibited by the isolated FcR-s. The interaction between IgG and SpA from Staphylococcus aureus (Cowan I) bacteria was not inhibited when red blood cells sensitized with IgG were preincubated with the isolated FcR-s. The differences between the FcR-like material isolated from supernatants of peripheral human mononuclear cells and those secreted by stimulated T cells or produced by lymphoblastoid cell lines are discussed.


Haemodynamic effects of hypothalamic stimulation on skin and muscle venous beds.

Twenty three points mainly located in the posterior hypothalamus were stimulated to study its effect on the pressures, flows and calculated segmental resistances of the skin and muscle venous beds of hind limbs in the dog. Stimulation of these points produced a uniform pattern of rise in pressures of the muscle veins consisting consisting of a steep rise during stimulation followed by a rapid decline to basal level on its cessation. Skin veins, on the other hand registered a gradual increase in pressure during stimulation followed by a secondary rise during post stimulatory period. Large veins of both muscle and skin exhibited comparatively smaller pressure increases than small vein. These pressure changes were accompanied by a similar marked rise in systemic arterial pressure. Out of 23 points, 21 points produced similar increases in the calculated resistances of skin and muscle veins. Two points produced greater increase of the skin vein resistance. Total venous resistance of the limb was therefore, raised by all the points stimulated. None of these points elicited any fall in the pressures or calculated resistances of either the muscle or skin venous bed. Muscle venous outflow always registered an increase while the skin venous outflow recorded either a small increase or decrease or at times no change during the hypothalamic stimulation. These findings demonstrate that hypothalamic stimulation can profoundly alter the haemodynamics of the hind limb venous beds and actively mobilize the post capillary venous sections of both skin and muscle venous beds.


Evaluation of certain tranquillisers and sedative premedications on the safety index of volatile anaesthetics.

Safety index (S.I.) of ether, chloroform and halothane was determined in mice following premedication with chloral hydrate, phenobarbitone, diazepam and trifluoperazine given alone or in combination with atropine or hyoscine. The S.I. of ether was significantly raised by chloral hydrate and phenobarbitone when combined with atropine while trifluoperazine in combination with atropine or hyoscine lowered it. The S.I. of chloroform and halothane was raised by chloral hydrate, phenobarbitone and diazepam. The S.I. raising effects were augmented in chloroform anaesthesia and reduced in cases of halothane (except diazepam-hyoscine) when these premedications were combined with atropine or hyoscine.


A study of some nitrogenous constituents in the newborn infants and their mothers.

Blood chemistry of 50 newborn infants and their mothers were studied for nitrogenous constituents of blood, i.e. urea, uric acid, creatinine, total proteins and their fractions. Total serum proteins, albumin and fractions of globulin of infants were found significantly lower than their mothers though the cord blood showed direct relationship to that of the maternal serum proteins. Values of total serum proteins of Indian infants were low as compared to their foreign counterparts. By contrast, globulin level was higher. Though the blood urea levels of infants and their mothers were within the normal range, the mean blood urea level of infants was significantly higher than their mothers. No significant difference was found in the mean uric acid and mean creatinine levels of the cord blood and maternal blood.


Cytocidal activity and proliferative ability of macrophages infiltrating the EMT6 tumor.

The EMT6 mouse tumor was selected for use in the study of cytocidal activity and proliferative ability of infiltrating macrophages because of its high plating efficiency when explanted to culture. The plating efficiency for cells directly plated in culture from the tumor was 28 +/- 9.3%, irrespective of the size of the tumor. Of the adherent cells derived from the tumor, the fraction that was macrophages increased from 27% at 7 days to 47% at 28 days after initial injection. Time-lapse cinemicrography was used to directly observe adherent cells derived from the tumor, and macrophages were found to be cytocidal. When grown in the presence of L-cell conditioned medium no macrophage colonies were found when cultures were established from untreated mice even though most tumor cell colonies contained macrophages. When mice were first treated with 0.8 mg BCNU prior to establishment of the cultures, in order to reduce the frequency of colony-forming tumor cells, approximately half the colonies found contained only macrophages. These results show that macrophages in this tumor are cytocidal and capable of proliferation.


DNA damage in liver, colon, stomach, lung and kidney of BALB/c mice treated with 1,2-dimethylhydrazine.

DNA single-strand breaks induced in various organs of BALB/c mice by treatment with a single dose of 1,2-dimethylhydrazine (DMH) were studied by means of the alkaline elution method modified in order to allow the evaluation of DNA damage in vivo with no need of radioactive prelabelling. DNA damage was detected in liver, lung, kidney, stomach and colon mucosa, with the liver showing the greatest amount of damage. Its degree was dependent on the dose and route of administration. A differential effect was evident in colon mucosa from Swiss and C57BL/6 mice which are respectively susceptible and resistant to the induction of bowel tumors by DMH. The higher degree of DNA damage found in liver in comparison with colon mucosa is consistent with the previously reported higher degree of DNA methylation, but does not correlate with the specificity of this carcinogen in inducing tumors of the large intestine in mice given repeated subcutaneous injections.


Inhibition by lymphoblastoid interferon of growth of cells derived from the human breast.

Human lymphoblastoid interferon inhibited the growth in vitro of fibroblasts and epithelial cells from normal, hyperplastic and neoplastic human breast tissue. At an interferon concentration of 10(3) inter-national units (IU) per ml, the inhibitory effects on monolayer growth were completely reversible but the growth potential of cells at lower density in colony-forming cultures was not completely recovered. Studies on the cell cycle distribution of interferon-treated cells demonstrated that the growth-inhibitory effect was not due to an effect on one specific phase of the cell cycle, but to a lengthening of all phases.


Failure of selective screening for breast cancer by combining risk factors.

The possibilities of selective screening to reduce the costs of screening programmes for breast cancer were considered. Discriminant function analysis was used in an effort to describe a high-risk group of breast cancer, which will be subjected to screening. The high-risk group consisted of females with a combination of reproductive and hormone use characteristics. One-fifth of the breast cancer cases remained in the low-risk group, when the high-risk group was small enough (two-thirds of the population) to yield a meaningful reduction in costs. Selective screening for breast cancer seems to have only limited applicability and is not effective enough for application in public health work.


Effects of carcinogen dose on the characteristics of the tracheal tumor response induced by N-nitroso-N-methylurea in hamsters.

Tracheal tumors were induced by repeated intratracheal exposures to the carcinogen N-nitroso-N-methylurea (NMU), using a catheter system previously described. Carcinogen concentrations of 0.25, 0.50 and 1.0% were employed in 20 or 30 twice-weekly exposures. Most of the tumors developed in the mid-portion of the tracheas. Virtually all tumors developed after the end of the 10- to 15-week exposure period. Tumor incidence ranged from 20-94% with mean tumor induction times of 13-46 weeks, depending on NMU concentration and frequency of exposure (i.e., dose). At lower doses, mostly non-invasive tumors were induced; at higher doses, mostly invasive carcinomas of various histological types (epidermoid, adeno-, epidermoid-adeno, and anaplastic large- and small-cell carcinomas) were induced. Adenocarcinomas were most frequent at low NMU concentrations. The possible mechanisms of the carcinogen dose effects are discussed.


Inhibition of morphological transformation induced with N-methyl-N'-nitro-N-nitrosoguanidine in cultures of hamster embryo cells by 5'-bromo-2'-deoxyuridine-photolysis.

The present study was performed in order to determine whether type III transformed foci induced by N-methyl-N'-nitro-N-nitrosoguanidine originate from the small subpopulation of cells stimulated by the carcinogen to enter DNA synthesis. During the last 30 min of variable treatment periods using different doses of N-methyl-N'-nitro-N-nitrosoguanidine, administered alone or in association with the thymidine analogue, 5'-bromo-2'-deoxyuridine (0.98 x 10(-5)M), the density-inhibited monolayers of hamster embryo cells were exposed to fluorescent light and then assayed for abnormal growth patterns by the focus formation method. Mock-irradiated cultures as well as monolayers whose medium lacked N-methyl-N'-nitro-N-nitro-soguanidine, 5'-bromo-2'-deoxyuridine, or both, served as controls. The cytotoxicity of 5'-bromo-2'- deoxyuridine + N-methyl-N'-nitro-N-nitrosoguanidine + photolysis (BMP) protocol on confluent as well as logarithmically growing hamster embryo cells was estimated in single-cell survival experiments. Plating efficiency determinations have demonstrated that, unlike their actively growing counterparts, confluent hamster embryo cell monolayers are extremely resistant to the cytotoxic effects of the BMP protocol. The quantitative transformation assays indicated that: (1) in non-illuminated cultures addition of 5'-bromo-2'-deoxyuridine to carcinogen-containing medium does affect transformation frequency of hamster embryo cells in the sense that the incidence of type III foci did not subside at later intervals during the post-carcinogen administration period as it did in the absence of the analogue; (2) irradiation of N-methyl-N'-nitro-N-nitrosoguanidine and halogenated pyrimidine analogue-treated cultures with fluorescent light practically suppressed transformation; (3) analogue-added and analogue-removed experiments pointed out that the event(s) on which 5'-bromo-2'-deoxyuridine fluorescent light sensitization of morphological transformation largely depends, takes place between 5 and 15 h after N-methyl-N'-nitro-N-nitrosoguanidine administration, i.e., during the period of maximal carcinogen-stimulated DNA synthesis; and (4) neither fluorescent light nor 5'-bromo-2'-deoxyuridine, singly or in combination, were able to transform cultures of hamster embryo cells. These findings are strong indirect arguments for the concept that carcinogen-induced DNA synthesis and the initiation of transformed clones are causally related.


Secretion of plasminogen activator by normal, reactive and neoplastic human tissues cultured in vitro.

Plasminogen activator secretion by 39 primary or early-passage cultures of malignant human neoplasms has been compared with that of 16 similar cultures of benign neoplasms and 39 cultures of normal or reactive tissue. While normal cells of mesenchymal or neural origin secreted considerably less plasminogen activator than did cells from frankly malignant tissues, elevated levels of enzyme secretion were also encountered in cultures of benign neoplastic or reactive cells. In the case of epithelial tissue, no consistent relationship between plasminogen activator secretion and neoplasia could be documented. Our failure to observe, for any particular cell type, a reproducible correlation between malignancy and plasminogen activator secretion may be attributable to the artificial conditions of in vitro culture, where normal in vivo regulatory mechanisms do not obtain.


Interferon and spontaneous cytotoxicity in man. I. Enhancement of the spontaneous cytotoxicity of peripheral lymphocytes by human leukocyte interferon.

A purified preparation of human leukocyte interferon used at this hospital in the treatment of malignant diseases was tested for its ability to modify the spontaneous cytotoxicity of peripheral lymphocytes from healthy donors. The inhibitory effect of allogeneic lymphocytes on the (3H)thymidine incorporation of a lymphoblastoid cell line, Raji, was augmented by the presence of interferon or by pretreatment of the lymphocytes with interferon. This form of pretreatment also increased lymphocytes' capacity for reducing the number of surface-adherent tumor cells in a microassay. Moreover, lymphocytes treated with interferon exhibited an enhanced cytotoxic capacity for target cells on incubation with such cells labelled with 51CR.


Nonspecific activation of complement by leukemic cells.

Non-specific activation of complement (NAC) on cell membranes via the alternative pathway was studied by using leukemic cells and cells from a generalized reticulohistiocytosis. The cells were treated with normal human serum in veronal-buffered saline containing ethyleneglycoltetraacetrate and MG++. Since human erythrocytes (HuE) are known to adhere to complement-reacted cell membranes in an immune adherence reaction, complement activation on the cell membrane was confirmed by the rosette formation of HuE which is due to the generation of C3b molecules on the cell membrane. Only cells from Schilling-type acute monocytic leukemias and cells from a generalized reticulohistiocytosis possessed NAC ability. All other leukemic cells tested, as well as normal hematopoietic and lymphoreticular cells, were NAC-negative. Furthermore, none of the mitogens tested generated NAC ability on normal peripheral blood lymphocytes.


BCG treatment of transplanted rat tumours of spontaneous origin.

Six transplanted rat tumours (three mammary carcinomas and three fibrosarcomas), all of spontaneous origin and of limited immunogenicity, have been examined for susceptibility to immunotherapy with BCG (Glaxo). Growth of limited numbers of cells from five tumours was suppressed when cells were injected subcutaneously in admixture with BCG organisms. There was no clear correlation between the immunogenicity of tumour lines and their susceptibility to regionally applied BCG. Active specific immunotherapy, using vaccines of viable or radiation-attenuated tumour cells in admixture with BCG, was reproducibly successful with only one tumour, the mammary carcinoma Sp4, this being the most immunogenic of the tumours examined. These studies indicate that naturally arising tumours are less susceptible to BCG-mediated suppression than carcinogen-induced tumours widely used for experimental immunotherapy, but indicate that local application of BCG may give the best therapeutic response.


Neoplastic transformation of canine embryo cells in vitro by N-methyl-N'-nitro-N-nitrosoguanidine.

A cell line derived from a normal beagle embryo was treated in vitro with various levels of N-methyl-N'-nitro-N-nitrosoguanidine or dimethyl sulfoxide (control). Cells treated only with the carcinogen underwent morphologic alteration in vitro, and one of these altered cell lines produced tumors subcutaneously when injected into NIH nude mice. The tumorigenic transformed line formed larger cell aggregates and grew in this aggregate form when suspended in liquid growth medium above an agar base.


Oncogenicity of Friend-virus-infected cells: determination of origin of spleen colonies by the H-2 antigens as genetic markers.

Spleen cells from mice infected with Friend leukemia virus (FLV) inoculated by the intravenous route give rise to macroscopically visible colonies in the spleens of normal F1 histocompatible hybrid hosts. A study of H-2 antigens as generic markers for identification of strains of origin of cells constituting the spleen colonies was undertaken. The standard cytotoxic test was demonstrated to be suitable for characterizing the H-2 antigens present on the surface of spleen cells from normal of FLV-leukemic parents of F1 hybrid mice. Individual colonies dissected out of the spleen of (C3HxC57B6/6) F1 recipients (H-2k/H-2b), 10 days after the intravenous graft of FLV-infected spleen cells of C3H origin (H-2k), were all sensitive to anti-C57BL/6 antibodies. In the same way, colonies obtained from the spleens of (DBA/2xC57BL/10) F1 recipients (H-2d/H-2b) grafted with DBA/2 leukemic spleen cells (H-2d) were all sensitive to both anti-H-2b and anti-H-2d antibodies. These results directly prove that the main cell population constituing a spleen colony arises from the recipient. The authors conclude that the spleen colonies do not result from the neoplastic proliferation of injected donor cells but rather from the multiplication of host cells transformed by Friend virus produced by the grafted cells.


Comparative aspects of circadian rhythms in homeotherms, re-entrainment after phase shifts of the zeitgeber.

Re-entrainment of circadian activity of 3 avian species (Fringillidae: Fringilla coelebs, Carduelis chloris, Pyrrhula pyrrhula) and 4 mammalian species (Rodentia: Eutamias sibiricus, Funambulus pennanti, Glis glis, Mesocricetus auratus), subjected to 12:12 h light-dark (LD) cycles as zeitgeber, was studied after shifting the LD cycle by different amounts (hours) and in different directions (advances and delays). The properties of the zeitgeber were changed by varying light intensity during dark-time (ID) and/or light-time (IL). After 6 and 9-h advance and delay shifts of the LD cycle, the 3 species of finches similarly re-entrained their activity rhythms in the direction of the shifted zeitgeber. After 10.5 and 12-h shifts, the majority of individuals re-entrained by delay phase shifts of the rhythms. After two successive 6-h advance or delay shifts (resulting in inversion of the LD cycle) most finches responded by advances. Generally, the time needed for re-entrainment of 2/3 of the full shift (2/3 tr) in finches dependend on: (a) the direction of the phase shift ('asymmetry effect'), and (b) the phase-angle difference between onset of activity and light-on (psio) before the shift. After 12-h shifts, species-specific differences in the direction of re-entrainment and in the slope of the relationship between 2/3 tr and psio were found. In two rodents, the nocturnal golden hamster and the diurnal Siberian chipmunk, the direction of re-entrainment following inversion of the LD cycle depended on psio. In both species, 2/3 tr after inversion of the zeitgeber was significantly longer than in the common dormouse. In chipmunks, changes in 2/3 tr were correlated with changes in psio due to systematic variation of the zeitgeber properties (range and/or mean level). After 6-h phase shifts, the 'asymmetry effect' was opposite in the two nocturnal rodents, the hamster and the dormouse. It is suggested that the time course (direction and rate) of re-entrainment was influenced by differences in the characteristics of the circadian systems and their responses ('sensitivity') to light changes in the various species of birds and mammals.


Seasonal fluctuations of the circadian changes in rabbit visual evoked potentials.

Two rabbits were exposed for more than a year to the natural cycles of daylight and darkness. At intervals of 2 months and less records were taken of the time course of the 24 hr rhythm appearing in constant conditions in their cortical flash-evoked responses. It appeared that the rhythm can be programmed as well by the natural light-dark alternations as by artificial cycles. In temperate zones this "natural programming" causes large seasonal fluctuations in the time course of the rhythm which reflects, over the major part of the year and with remarkable precision, the times of sunrise and sunset and, in consequence, the length of the day. The possible significance of fixing daylength temporarily in the nervous system is discussed in connection with Bünning's hypothesis on the causation of seasonal photoperiodism.


Circadian variations of ovarian ascorbic acid depletion in response to luteinising hormone in the rat.

The ovarian ascorbic acid (OAA) was titrated, three hours after an I.V. injection of either saline or LH, administered to 46 day-old Sprague Dawley female rats pretreated with P.M.S., H.C.G., and estradiol benzoate (and undecylate). The rats were killed at specific times along the 24-hour scale (L.D. 12:12; L 06(00) to 18(00); Ambient temperature 24 degrees C +/- 2 degrees C). The OAA content varied with a statistically significant circadian rhythm in the controls. The minimum dose of LH effecting OAA depletion varied systematically with the circadian system phase. OAA depletion increases with the dose of LH, and also depends on the circadian time that the animal is killed; it is maximum at the same time that the OAA peak is found in the controls. The slope of the linear regression (quantity of OAA as a function of the logarithm of the LH doses administered) is always significant, but varies over the 24-hour span; in consequence the LH biological titration must be carried out rapidly, the optimal circadian time for killing the animals is about 16(30).


Growth rhythms of the cartilage of the mandibular condyle: effects of orthopaedic appliances.

The growth rate of the cartilage of the mandibular condyle in the young rat exhibits: - a circadian cycle with a maximum of the 3H-thymidine labelled cells around 13(00) and a minimum around 01(00); with a maximum in the number of mitoses around 21(00) and a minimum around 09(00). - a circannual cycle with a maximum in May and a minimum between November and January, and with a difference in rhythms between May and November. The condylar cartilage growth in response to orthopaedical appliances of the mandible is modified and exhibits: - circadian variations. - circannual variations. The responsiveness of the condylar cartilage to orthopaedic appliances is greater when the condylar cartilage growth rate is higher.


Ethical problems in clinical psychopharmacology.

The present article originates from some intriguing problems which the author, working as a clinical pharmacologist and psychiatrist, was faced with during clinical investigations. Practical difficulties appearing at first glance as of a rather methodological nature often reveal themselves as ethical questions. Investigation of psychotropic drugs in normal volunteers as well as in psychiatric patients is taken as a model to exemplify certain fundamental ethical aspects of medical research. It is emphasized that the "solution" of ethical problems cannot be achieved by referring to a given code of norms which themselves depend on certain historical circumstances, but rather by recognizing and reasoning the conflicts which result from various moral maxims. Clinical psychopharmacology should not only be conscious of its methodological shortcomings and future goals but also accept the justification of discussions about the ethical and legal questions involved in its dealings and take an active part in these debates. With regard to the relationship between patient and investigator, "solidarity" [23] instead of ongoing paternalism or legal formalism, appears to be a realistic goal. This is also true in the area of psychopharmacological research.


Effects of extracellular Ca2+ and Mg2+ on nucleic acids and proteins syntheses by tumor and normal liver cells.

The effects of increasing extracellular concentrations of Ca2+ and Mg2+ on the uptake of 14C-thymidine, 3H-uridine and 14C-leucine by Novikoff hepatoma and normal liver cells have been studied. Increasing concentrations of Ca2+ stimulate all the three incorporations while Mg2+ exhibits an inhibitory effect. Liver cells presented a higher cation permeation induced by the extracellular concentration than hepatoma cells which also seems to explain the quantitative differences observed in the studied syntheses. The importance of the extracellular cation-cell membrane interaction in these effects is discussed.


Pharmacological reevaluation of gitoxin in man.

The aim of the present investigation was to reevaluate the pharmacokinetic and pharmacodynamic parameters of gitoxin in man. Gitoxin given as a solution is quasi-completely absorbed after oral administration in a fasting man. A dose of 1.5 mg modifies the left ventricular ejection time index (LVETI) as digoxin or digitoxin does. The biological half-life of gitoxin calculated on the basis of plasma concentrations or urinary data is about one day. The urinary elimination of gitoxin is smaller than 21% of the dose. Therefore the two main advantages of gitoxin versus digoxin or digitoxin are: 1) its short biological half-life and 2) its elimination being less dependent on the renal function of the patient.


Human myocardium and plasma digoxin concentration in patients on long-term digoxin therapy.

Digoxin concentration of 14 left ventricular papillary muscles and 36 right atrial appendages of 45 patients undergoing cardiac surgery were determined by the NEN 125J-radioimmunoassay. Blood specimens for digoxin assay were withdrawn immediately before operation, 12 to 16 hr after the last digitalis dose. Mean papillary muscle digoxin concentration was 76.1 ng/g +/- 25.5; mean ratio to plasma digoxin level, 36.8:1. The mean concentration of right atrial appendages was 41.8 ng/g; mean ratio, 29.9:1. Most of the tissue specimens were examined histologically using Hematoxylin-Eosin and van Gieson stains. No clear relation between tissue digoxin concentration and hisological alteration, i.e., the degree of fibrosis or lipomatosis, could be found, although most severe alterations were found in right atrial appendages corresponding to a higher variation in tissue concentrations and a poorer correlation to plasma digoxin (r = 0.47, respectively for papillary muscle r = 0.73).


Dose equations without protein-binding parameters.

Simple and practical dose equations for oral administration and intravenous infusion are derived by means of pharmacokinetics. These equations have no troublesome parameters for adsorption of drug on protein in blood, as these are eliminated with the help of information obtained by the pilot dosing.


Kinetics of drug interactions in the treatment of epilepsy.

The interactions of antiepileptic drugs in multiple drug treatment have been discussed. Although some combinations may lead to predictable increase or decrease of clearance of the respective drugs, most combinations will individually lead to a reduced predictability. Monitoring plasma concentrations may lead to adaptations of the choice of the drug and of the dosage regimen. Also physiological conditions control the individual clearance of antiepileptic drugs.


Pharmacokinetics of chlordiazepoxide and metabolites following single and multiple oral doses.

Three healthy volunteers (2 male and one female) participated in single- and multiple-dose pharmacokinetic studies of oral chlordiazepoxide (CDX) hydrochloride. Following single 50-mg oral doses of CDX.HCl, absorption and elimination proceeded as apparent first-order processes. Values of absorption half-life were: 14.5, 189, and 18.9 minutes; elimination half-lives were: 7.6, 9.8, and 12.6 hours. Disappearance of CDX was mirrored by appearance of its first active metabolite, desmethylchlordiazepoxide (DMCDX). During once-daily ingestion of 50 mg of CDX.HCl, observed values of CDX accumulation half-life (0.0, 5.8, and 52.5 hours) differed substantially from values predicted based upon the single-dose study; pre-dose steady-state CDX blood concentrations also differed from the predicted values. Accumulation half-lives for the metabolite DMCDX were: 17.7, 9.9, and 15.8 hours. Accumulation in blood of a second active metabolite, demoxepam (DMX), proceeded with half-life values of 21.1, 34.2, and 78.5 hours. Minimum steady-state concentrations of DMCDX and DMX exceeded those of the parent compound. Thus accumulation and persistence of at least two active metabolites during long-term treatment with chlordiazepoxide renders the drug suitable for single-daily dose therapy of anxiety.


The estimation of drug plasma levels in epileptics.

The estimation of antiepileptic drugs in plasma is an indispensble resource in the handling of seizure patients in many countries. Using our results, simple methods for the estimation of antiepileptic drugs are discussed.


Problems in the kinetic evaluation of capacity-limited processes by means of the analog computer MEDA 82 T.

A method for the calculation of dose-dependent pharmaco-kinetics by means of a combined zero and first-order model at the analog computer is presented. The results of the combined model can be converted into Michaelis-Menten parameters using simple equations. The method is usable for i.v. injection and for e.v. modes of application in the case of cmax greater than c = co/e.


Effect of antirheumatic drugs on proteinases in synovia of patients with rheumatoid arthritis.

Synovia and synovial fluid proteinases were determined in 21 patients with rheumatoid arthritis who were using different kinds of antirheumatic medications. Significantly lower cathepsin B1-like proteinase activity (only 10% of control) was found in the synovial fluid of patients with chloroquine treatment, and significantly lower neutral trypsin-substrate hydrolysing proteinase activity (about 30% of control) was found in the synovia of patients with phenylbutazone treatment. No significant differences were found with other medications: gold, indomethacin, cortisone, acetylsalicyclic acid. No definitive correlations between disease activity parameters and proteinase activities could be found.


Estimation of pharmacokinetic parameters of digoxin from serum, saliva and urine.

The pharmacokinetics of digoxin was studied in 14 healthy volunteers using concentrations measured radioimmunologically in the serum, saliva and urine. The subjects were given 0.75 mg of digoxin intravenously. Serum and saliva were obtained over a 72 hr period and urinary excretion rates over 6 or 7 days. Binding of digoxin to serum proteins was determined by ultracentrifugalization. A linear correlation between the serum and saliva concentrations was found. Salivary levels were equal to the unbound fraction in the serum. The half-lives of distribution did not differ between the serum and saliva. An erroneously short half-life of elimination was found in the serum, but in the saliva and urine it was found to be in the range previously reported. Salivary level measurements may be useful in pharmacokinetic studies and may have important clinical implications.


Effect of clonidine (Haemiton) on plasma renin level and angiotensin sensitivity in man.

The effect of clonidine and of clonidine + spironolactone on renin activity and angiotensin sensitivity has been studied in 15 persons. Clonidine-induced angiotensin pressor dose and renin level reduction have been abolished by spironolactone. The phenomenon is explained by the contrary effects of the two drugs on renin activity and angiotensin sensitivity. Other possible mechanisms of antihypertensive clonidine effect are also discussed.


Carcinogens and analogs: trace analysis of thirteen compounds in admixture in wastewater and human urine.

A gas chromatographic method is described for determining traces of 13 carcinogens and related compounds (aromatic amines and estrogens) in admixture in wastewater and human urine. This method was developed for use in toxicological research for monitoring the safe disposal of wastewater and to signal any accidental exposure of personnel to hazardous test substances. Salient elements of the procedure are: extraction of phenolic and neutral residues from the acidified sample, liquid--liquid partitioning cleanup and separation of neutral from phenolic residues at pH 14 and 10.2, acid hydrolysis of the neutral component, subsequent alkalinization of the sample and extraction of the basic residues as the free amines, conversion of all residues to the corresponding pentafluoropropionyl (PFP) derivatives and quantification by electron-capture gas chromatography. Residues were detectable in wastewater and urine at the 0.1 and 1 ppb levels, respectively. Additional information is provided concerning partition values for all PFP derivatives in five solvent systems, structure verification of the derivatives by mass spectrometry and the adaption of this method to the monitoring of surfaces and air in potentially contaminated work areas.


N-alkylation of amino acid residues by chloromethyl groups. A potential side reaction in the solid phase peptide synthesis.

A serious side reaction in the peptide synthesis on the Merrifield resin was observed during attempts to synthesize the TMV fragment, Asn-Pro-Thr-Thr-Ala (101--105). The side reaction is consistent with N-alkylation of the amino groups by the residual chloromethyl groups on the resin, which lowers the total yield and complicates evaluation of monitoring data during the synthesis. It is shown that several amino acids can be N-alkylated in different positions in the peptide chain and in different solvents. The extent of N-alkylation is in some cases 50%.


Determination of the intramolecular tyrosine-tryptophan distance in a 7-peptide related to the C-terminal sequence of cholecystokinin.

The solution conformation of a 7-peptide with the C-terminal sequence of cholecystokinin was investigated by evaluation of intramolecular resonance energy transfer between tyrosine (donor) in position 1 and tryptophan (acceptor) in position 4. From the relative enhancement of acceptor fluorescence a transfer efficiency of 0.70 +/- 0.04 was determined. The use of this parameter in Förster's equation permitted the calculation of the average intramolecular tyrosine-tryptophan separation, whereby the assumption of random donor-acceptor orientation was made. The resulting average distance of 10.0 +/- 0.3 A suggests some type of a folded conformation and excludes the existence of a fully extended chain in the N-terminal part of the peptide. A comparison with tyrosine-tryptophan distances observed in other biologically active polypeptides is made.


Solid-phase synthesis of oxytocin, desaminooxytocin and 4-Thr-oxytocin using active esters in presence of 1-hydroxybenzotriazole.

Using appropriate amino acid active esters (3 eq.) in presence of HOBt (1 eq.) and employing DPM protection for the thiol function of cysteine, a rapid synthesis of oxytocin in the solid phase has been accomplished. The DPM group has been removed by sodium-liquid ammonia reduction since boiling TFA is ineffective. Desaminooxytocin and 4-Thr-oxytocin have been synthesized using lesser quantities of amino acid active esters (1.5 eq.) in presence of HOBt (1 eq.), but the durations of coupling are longer. The solid-phase synthesis of desamino-oxytocin using appropriate Boc-amino acids in presence of DCCI in toluene medium has been described. Toluene does not exert any significant accelerating influence on the coupling rate as it does when active esters are employed.


betah-endorphin: antidiuretic effects in rats.

Human beta-endorphin (betah-EP) inhibits urine flow in rats. This antidiuretic effect of the peptide occurs after intravenous and intraventricular injections. Intravenously, betah-EP is 24 times more potent than morphine. Intraventricularly, betah-EP is 24 times more potent than morphine. Intraventricularly, betah-EP is effective at doses (0.45 microgram) which have no antidiuretic activity when injected intravenously. This fact suggests that one site of the antidiuretic action of betah-endorphin may be in the central nervous system. Animals tolerant to morphine are also tolerant to the antidiuretic effects of betah-endorphin.


Teaching psychological medicine on hospital rounds: a liaison experiment.

An unusual version of liaison psychiatry is described in which the object of the liaison is the practicing physician in the hospital setting. Hospital work rounds were used as teaching rounds at frequent intervals over a relatively long time span. The paper demonstrates the usefulness and feasibility of such a project. The processes and principles of teaching psychological medicine in this way are described and exemplified.


Psychiatric and biochemical correlates of respiratory decompensation in a terminal and non-terminal chronic pulmonary disease patient.

A psychiatric and biochemical study was undertaken at the request of two patients who were thought to be terminally ill by the medical staff. One patient accepted dying and expired from her disease. The other patient wished to continue living and did not die. The dying patient exhibited abnormally high levels of catecholamine excretion which were not associated with verbal reports of anxiety or discomfort and did not seem upset or uncomfortable to the physician and nurses caring for her. The patient who lived had relatively low levels of catecholamine excretion and was anxious, irritable and uncomfortable. The behavior of these two patients differed during the period of acute respiratory failure. The dying patient had given up and felt that she was engaging in goal-directed activity which she would or could not shut off. The patient who lived was frightened of dying and felt that she would overcome her current difficulties and that she was not ready or willing to die. The major cardiovascular differences were those of a significantly lower blood pressure and higher heart rate in the patient who died.


Sexual dysfunction in renal failure: a survey of chronic hemodialysis patients.

Eighteen chronic hemodialysis patients were interviewed by staff trained in sex therapy. Compared with the pre-uremic phase, sexual satisfaction was less in nine subjects, greater in four; frequency of intercourse had declined in ten subjects. Dysfunctions of sexual response were reported by five men and six women. Analysis of physical factors, medication and depression showed no clear association with sexual dysfunction, suggesting the importance of psychosocial factors. A trial of sex therapy in renal patients in proposed.


Evaluating liaison program effectiveness: the use of unobtrusive measurement.

The author suggests that the goal of liaison psychiatry as well as its organizational and clinical properties require the use of measures which are non-reactive and developmental in nature. In this paper four categories are theorized as representing the implicit working assumptions of nonpsychiatric housestaff in clinical formulation. By analyzing the overt and latent assumptions of the questions presented to a liaison psychiatrist in patient care conferences, the author illustrates how the assumptions can change through six levels of development. Changes within the assumptions are then used as criteria for program effectiveness since the working assumptions represent preconditions to holistic care. Potential uses of this global scheme for evaluating liaison programs are suggested.