Attitudes of health science students towards teaching practices, examinations, and other related issues.

A brief multiple choice questionnaire explored the attitudes of students enrolled in several health science faculties (medicine, pharmacy, nursing, and physical and health education). A substantial proportion indicated a wish for more challenging lectures. On the other hand, the majority of students devoted less than one hour of personal study per week to required 'courses', interest in health-related 'courses' being particularly weak. Small textbooks with minimal references were desired, and relatively little use was made of free lecture handouts. Financial constraints had little influence on personal study, but affected textbook purchase. The demand for 'handouts' would have been reduced by a charge. Frequent term examinations as a stimulus to learning were favoured by all groups, as were full or challenging presentations by instructors. Team teaching, although favoured generally, was not equally appealing to all groups.


The influence of a lecture course in loss and grief on medical students: an empirical study of attitude formation.

In this study the results of a questionnaire administered to medical students attending a lecture course on loss and grief are analysed. The focus of the inquiry was to determine whether attitudes towards death, dying and loss could be influenced by confrontation with factual information on bereavement. The results showed that the original idealized attitudes underwent a reality correction due to increased factual knowledge of bereavement processes. The defensive attitudes of students who experienced death in their family during the course are discussed. Intensity and temporality of one's involvement with death appear to be a determining factor in the formation of attitudes towards death. Typical male and female attitudes are also presented. It is concluded that the institutionalization of education in bereavement processes should receive priority in medical programmes and that the classical lecture deserves its place therein.


Differential evaluation of students' performance in histology. All questions are equal but some are more equal than others.

Construction of multiple choice questions in histology is often hampered by the difficulty in finding alternatives to the correct answer which will be neither trivial nor ludicrous. An additional problem appears when the student performance on the morphological and the functional aspects needs to be assessed. A method of test construction is presented which includes 'multi-dimensional' questions. The questions reflect the objectives of the course and performance is evaluated differentially according to the importance attributed to their content. 'Essential knowledge' is more highly rewarded than knowledge deemed secondary by the course's planners.


Teaching communication skills to pre-clinical medical students: a general practice based approach.

This paper describes a method of teaching communication skills to pre-clinical medical students in the setting of general practice. By focusing on the nature of the patient's problem this teaching tries to place interviewing and diagnostic procedures in their proper context in the doctor-patient relationship.


A preliminary investigation of three types of multiple choice questions.

The present study reports the results of an evaluation of three types of multiple choice questions--the five choice completion, and assertion-reason. Fifty-four questions, eighteen of each type and measuring the candidate on the same scientific principle and classified as either factual or comprehension, were developed and included in the General Surgery certifying examination of the Royal College of Physicians and Surgeons of Canada. In addition to using descriptive statistics, the multitrait-multimethod technique was used to investigate whether the item types measured different aspects of examinee capabilities. Results indicated that performance on the five choice completion and the multiple completion type questions was roughly the same, whereas performance on the assertion-reason type was lower. The results of the multitrait-multimethod validation revealed that the three item types were unable to discriminate between the two traits of factual and comprehension.


Introducing students to the medical literature.

It is extremely difficut to determine if it really makes a difference to provide a medical journal to medical students. Does it alter their reading habits? Does it indeed form the basis for learning? In 1976 84% of the third year class and in 1972 69% (n=97), personally subscribed to a Journal designated. In the fourth year class, 75% (n=149) subscribed in 1976 and 58% (n=82) in 1972. The conclusion is that the New England Journal of Medicine Project can be viewed as an endeavour which meets the need of students.


Behavioural self-analysis in the medical curriculum: a comparison of Malaysian and American experiences.

Behavioural self-analysis projects were introduced into the second year medical curriculum in behavioural sciences at the University of Malaya. Students performance and evaluation of the experience were compared with those of American medical students. It was concluded that receptivity of medical students to principles of behaviour therapy is relatively similar in the two societies.


Monitoring and recording clinical trials.

A procedure based on the use of on-site monitoring has been developed for managing clinical testing programs. The procedure involves orientation meetings, forms specifically designed for good record-keeping, staff instruction, the establishment of normal laboratory values and criteria for patient selection, and prescribed monitoring functions. This procedure has proved successful in improving the performance of the physician-investigator, maintaining investigator interest, and enhancing the value of program results.


An automatic cardiac resuscitator for emergency treatment of cardiac arrest.

A new, portable, automatic resuscitator seeks respiratory signals and electrocardiogram of a victim in cardiac arrest through an intrapharyngeal sensor and a lingual-epigastric skin pathway. The resuscitator then assesses the status of the patient and delivers either an electric impulse to defibrillate or a pacing pulse, as indicated by an algorithmic logic circuit gated by respiratory rate and ECG. Field testing the device on 21 patients in ventricular fibrillation resulted in 35 successful conversions to sinus rhythm and 1 long-term survivor. Pacing was accomplished in two humans. Such a device has great potential for saving lives by eliminating crucial time now spent waiting for skilled help and equipment to arrive.


Safe and effective use of ethylene oxide.

Reports of potential hazards inherent in the use of ethylene oxide as a sterilant have inspired repeated inquiries and concern. Thus we publish herein two items to help clarify aspects of the safe and effective use of this sterilant. These should be disseminated among all hospital sterilization unit personnel.


Oculoplethysmography and carotid phonoangiography for the noninvasive detection of extracranial carotid occlusive disease.

Clinical applications of imaging techniques and noninvasive physiological vascular evaluations provide useful assistance in the detection and management of stroke-prone patients by minimizing unnecessary carotid arteriography and surgery. Two such evaluation techniques are oculoplethysmography (OPG) and carotid phonoangiography (CPA). Developed, used, and proved highly reliable at the Tucson (Arizona) Medical Center, the techniques have been documented in 12,000 tests on approximately 8500 patients. OPG simultaneously records the bilateral ocular pulses concomitantly with external carotid pulses. Delays in timing of these pulses reflect reduction of flow in the internal and/or external carotid arteries, respectively. CPA consists of electronic stethoscopic auscultation, direct visualization, and photographic recording of carotid bruits or blood flow sounds.


Supraorbital Doppler evaluation in vascular surgery.

Directional Doppler examination of the supraorbital vessels is an effective, noninvasive method of evaluating patency of the internal carotid artery. In the presence of occlusive disease in the internal carotid artery, flow in the superficial temporal and frontal artery is reversed so that blood flows in a retrograde fashion into the orbit, providing valuable collateral circulation to the brain. Using these basic anatomical and physiological facts, the direction of arterial flow in the supraorbital vessels and the response to compression of the superficial temporal and facial arteries were measured with the directional Doppler. Evaluation of 125 carotid arteries in 63 patients by both arteriography and Doppler examination established an overall accuracy of 87 percent by the Doppler supraorbital test. This study demonstrated the value of carotid Doppler examination in the evaluation of extracranial cerebral circulation.


"Barbiturate burns" caused by glutethimide.

A case of glutethimide overdose associated with skin lesions resembling burns is reported. These characteristic skin lesions are usually ascribed to barbiturates. Their aetiology, incidence, and association with other drugs and neurological disorders are discussed.


Clinical application of electrical impedance for the study of arterial insufficiency.

A four-electrode impedance plethysmography containing a dedicated computer has been developed for evaluating arterial insufficiency in the clinical noninvasive vascular laboratory. Measurements obtained by the impedance plethysmograph were compared with measurements obtained by the Doppler ultrasound technique. Five case reports demonstrate that electrical impedance measurements can feasibly be obtained in the clinical setting and that the information is useful in treating patients with arterial insufficiency. Results indicate that electrical impedance data correlate better with the clinical symptoms reported by the patient than do the Doppler systolic pressure data. The impedance plethysmography measurements are particularly useful when considered in conjunction with the Doppler measurements.


Null cell chronic lymphocytic leukaemia.

Lymphocytes lacking receptors for sheep erythrocytes and surface immunoglobulin were present in the blood in large numbers at some stage in four cases of chronic lymphocytic leukaemia (which included a mother and son), and formed a substantial proportion of the circulating lymphocytes in other cases. These null cells possessed receptors for mouse erythrocytes. Other B-cell markers were also found on these cells. Serial studies showed a great variation in the number of null cells during the course of the disease (which may be associated with treatment), suggesting variation in the the maturation of leukaemic cells, and indicating that the surface marker complement may not reflect the constitution of the cell undergoing the original malignant change.


Intracranial abscess.

Thirty-one patients with intracranial abscess who were treated at Royal Perth Hospital during the past 10 years are reviewed. There were 17 males and 14 females with a mean age of 39.2 years. Fifteen deaths indicate an over-all mortality of 45%. However, the mortality was 62% in the first five years, and 39% during the latter five years. The clinical features of the patients are reviewed. Factors contributing to the high mortality were severe local and multisystem disease, delay in diagnosis and surgical drainage, and inappropriate or inadequate antibiotic therapy. The use of high doses of antibiotics is suggested and recommendations are made concerning appropriate regimens.


Clinical use of cefamandole: a new cephalosporin.

Cefamandole, a new cephalosporin derivative, has been used in treatment of six patients who had diminished renal function and respiratory infections, and of 14 patients with urinary tract infections (UTI). Infection was eliminated in all patients with respiratory infections, and in seven of the patients with UTI. No serious side effects were encountered and, even in patients with pre-existing renal dysfunction, no reduction in renal function occurred.


Clinical measurement of pain.

The problems of clinical measurement of pain are considered. Various adjuncts to the standard clinical interview are proposed. These are: written reports, visual analogue scales, McGill's Pain Assessment Questionnaire, and a weekly pain chart. The advantages and disadvantages of each are discussed. Correlations between various pain measures are shown. The use of the weekly pain chart by doctors is recommended in cases of chronic pain.


Infant strabismus: a 25-year review of 750 cases.

The review demonstrates that there is no justification for delay in treating babies who present with strabismus. A survey of 750 infants aged from 0 to 36 months among 5497 cases seen by an individual orthoptist over 25 years shows a decreasing use of surgery and an increasing proportion of fully functional results over this time. It emphasizes that no infant is too young for assessment and treatment.


Protection of the eyes against damage by light activated psoralen.

It is current practice to order eye protection while patients are under treatment with psoralen. There is considerable variation in the protection against long wave light provided by different sunglasses, therefore, it is necessary to write a specific prescription for sunglasses for these patients. We have found Noir Model 102 or 109 with side flaps or the Rayban dark green glass to be the most effective.


Laryngeal cancer and alcohol consumption in Australia.

Whereas lung cancer is strongly associated with cigarette smoking, and upper alimentary tract cancers with both alcohol and cigarettes, the situation has been less clear-cut for laryngeal cancer. This century's time trends in laryngeal cancer death rates in Australia follow those of oesophageal cancer rather than lung cancer. Further, the trends correlate with those for alcohol consumption rather than cigarette consumption. The separate analyses of trends in age-specific death rates for men and women reveal a pattern of laryngeal cancer risk variation between successive generations which is consistent with a causal role of alcohol consumption. Biological mechanisms, and synergism, between alcohol and cigarette consumption are discussed.


Mebendazole therapy of whipworm infestation: a clinical trial.

Mebendazole, a new broad-spectrum oral anthelmintic for nematodes, was given to patients harboring whipworm in a hospital for the mentally retarded. A three-day regimen (100 mg twice a day) dewormed 75% of the subjects, a five-day regimen cured 95%. The remaining patients excreted strikingly lesser amounts of the parasites' eggs after therapy. No untoward effects were noted clinically. It is the drug of choice in mixed worm infestations.


Acute glomerulonephritis in an adult with infected ventriculoatrial shunt.

A case of acute glomerulonephritis occurring during Staphylococcus albus infection of a ventriculoatrial shunt is described. It is the first case in which renal biopsy was repeated after clinical cure by shunt removal. This indicates that isolated haematuria and some histopathological changes may persist for at least a year.


[Spontaneous coronary spasm with reversible occlusion of the left coronary artery: a case report (author's transl)].

A spontaneous coronary spasm with a complete but reversible occlusion of the left coronary artery could be demonstrated by coronary arteriography in a patient with angina pectoris at rest and during exercise. This will prove that spasms of coronary arteries can cause angina pectoris or even acute myocardial infarction if the spasm is persisting for long enough and if there is no sufficient supply by collateral vessels. This can be a possible reason for akinesia or dyskinesia of the left ventricle associated with normal or near normal coronary arteries.


[Sensitivity of creatine kinase and creatine kinase MB in myocardial infarction. Evaluation of a new optimized standard method (author's transl)].

In 70 patients with confirmed transmural myocardial infarction the sensitivity of creatine kinase and creatine kinase MB at different times after admission was investigated by 364 measurements. Beside the number of correctly positive results the optimized standard method hitherto used was compared with the new optimized standard method with N-acetylcystein as activator. During the first 12 hours after admission the percentage of correctly positive results was 64,4% for creatine kinase (GSH) and 86,7% for creatine kinase (NAC). The sensitivity of cretine kinase MB, however, was found to be 71,1% (GSH) and 86,7% (NAC). With respect to the poor specifity of creatine kinase the sensitivity of creatine kinase MB, especially when using the new optimized standard method is superior. Similar results were established 24 and 48 hours after admission. Creatine kinase MB only fails in detection of myocardial infarction if the stroke is older than 3 days or if the enzyme activity determination intervals are too long.


[Infections in man induced by Yersinia enterocolitica serovar 09 and 04 (author's transl)].

Yersinia enterocolitica serovar 09 was isolated from stool specimens of two patients suffering from serious enteritis and pseudo-appendicitis, respectively. Both patients exhibited high titers of serum-agglutinins against the isolated strains. The Widal reaction against brucella-antigens was also found positive. In addition, the isolation of Yersinia enterocolitica serovar 04 from a suppurating wound is reported.


[Penetration activities of cefoxitin into different human tissues. An experimental study (author's transl)].

Subject of the following study was the penetration activity of cefoxitin into different human tissues. The authors obtained material of the cutis, subcutis, fascia, muscle, spongy bone and compact bone during orthopedic surgery on 20 patients. Cefoxitin was administered by means of a continual infusion of a dose of 45 mg per kg body weight per hour. Tissue and serum levels were studied after infusions lasting 15, 60, 90 and 120 minutes. Altogether the results of 215 specimens of serum and 132 specimens of tissue are recorded. The evaluation showed the following mean tissue levels of cefoxitin: 6.6 micrograms/g in compact bone; 14.4 micrograms/g in spongy bone; 23.3 micrograms/g in muscle; 64.2 micrograms/g in fascia, 69.9 micrograms/g in cutis and 21.7 micrograms/g in subcutis.


Influenza virus infection of the guinea pig: immune response and resistance.

Guinea pigs were inoculated by intranasal inoculation with unadapted, influenza virus A/England/42/72, and virus was recovered from nasal washings between 3 and 10 days post-inoculation. Infected animals did not exhibit a febrile response to infection, did not produce local antibody and produced only relatively low levels of serum antibody. However, they developed delayed-type hypersensitivity to influenza virus, demonstrable by both skin tests and macrophage migration inhibition tests, which was similar to that of man. The relevance of the influenza virus specific delayed hypersensitivity in immunity to infection was examined in this model. Guinea pigs previously infected with virus or passively immunized with hyperimmune serum were relatively resistant to reinfection with influenza virus A/England/42/72. Inoculation of guinea pigs with spleen cells from immune donor animals, together with or without immune serum, did not give or enhance resistance to challenge virus infection. The results do not suggest a role for delayed hypersensitivity response in immunity to influenza virus infection.


Measurement of regional cerebral blood flow by intravenous injection of Xe133.

Clearance of Xenon 133 following intravenous injection has been used to perform atraumatic measurements of regional cerebral blood flow (rCBF). rCBF was computed by a two-compartmental analysis of the clearance curves associated with a correction for Xenon recirculation based on the end-tidal tracer concentration. Direct comparison was made between the results of this method and those obtained from the reference intracarotid method. A systematic analysis has shown that the results of the non-invasive method depend on the part of the clearance curves chosen for computation of rCBF. The best concordance with the intra-carotid method was found when the analysed part of the curve was situated between 3 and 11 min. after the beginning of the injection. Under these conditions, the differences between the results from the two methods did not exceed 10% of the flow values even for low flows. Such precision makes the atraumatic measurements of rCBF by intravenous injection of Xenon valuable for clinical applications.


Recognition of the pattern in ultrasonic sectional pictures of the prostate for tumor diagnosis.

To diagnose tumorous alterations of the prostate, we examined the organ with ultrasonics by scanning directly from the abdominal wall through the filled bladder (transvesical). The research is aimed at: 1) improvement and mathematical preparation of the ultrasonic pictures to assist the physician in his diagnosis. 2) ascertainment of significant parameters which allow the classes "normal prostate", "adenoma" and "carcinoma" to be distinguished in screening examinations. The results show that with ultrasonics, adenomas and carcinomas are recognizable in 96% of the examined patients and can be differentiated from normal prostate tissue. The palpation finding was used as a reference in most cases.


Sensory feedback for artificial limbs.

Over the years various approaches have been made to help solve the problem of replacing mechanical function of a lost limb, but there has been little direct interest in the associated problem of replacing the sensory function also lost in the amputation. Psychological rejection of electrically powered hands (despite their good cosmesis) suggests that greater attention should be given to the provision of sensory feedback on artificial limbs. Myoelectrically controlled electric hands fitted with a sense of touch have been fitted to two patients and in a nine month trial period they reported favourably on these fittings. There has not been any adverse skin reaction to the application of the electrical feedback stimulus and the patients say that because of the feedback they have an increased level of confidence in using the prosthesis.


[Comparative electron microscopic studies on benign liver tumors and jaundice associated with contraceptive drugs].

Author compared the ultrastructure of the hepatic tissue in 6 cases with benign hepatic tumours revealed in women taking oral contraceptives and in 3 cases with icterus. The majority of the ultrastructural changes were alike in cases with- or without tumours. Deposition of filamentous material of unknown nature in the biliar canaliculi and Disse-space associated with the damage to the cell membrane author believes to have a significance. Ultrastructure of the sinusoid endothel indicate an increased protein synthesis. The most striking feature of the tumours: formation of continuous capillaries in the place of sinusoids. Author emphasizes that systematic electron microscopic studies may contribute to our knowledge concerning the question of the effect of oral contraceptives on hepatic cells.


[Changes in the nucleus ruber in 3-acetyl pryridine poisoning following unilateral ligation of the carotid artery].

A single-approximately LD50-dosis of the 3-AP given to white rats following the unilateral ligature of the carotid artery in almost 70 percent of the animals caused hydropic-vacuolic degeneration and cell necrosis in the nucleus ruber. Similar changes were quite infrequent in the mesenphalic nuclei. The regressiv changes can be prevented by nicotinamid. When smaller doses are given they do not occur at all. Electronmicroscopic findings help to explain some aspects of the pathogenesis of these rather selective changes.


[Demonstration of hypnotic agents in bone tissue].

Investigating the skeletons of 25 suicide victims the authors have found that the toxic materials taken can rather comfortably and safely be detected in the compactbony substance. Especially important that the poisonous drug residues can remain in the bones for a long time, even for years after death.


[Sudden death due to unusual developmental anomaly of the coronary artery].

In a case of the sudden death of a child, parents were suspected of negligence. At the autopsy anomaly of the coronary artery as the cause of severe damage to myocard and sudden death was revealed.


Timing of oocyte maturation in the mouse and its relevance to radiation-induced cell killing and mutational sensitivity.

Timing oocyte development by labeling the zona pellucida indicates that it takes 6 weeks (possibly a few days more) for a stage 3b oocyte to reach ovulation. Thus the shift in mutation frequency with time after irradiation occurs in an oocyte stage that is comparable in all mammals so far investigated, and in the mouse low-mutational sensitivity is not restricted to the arrested dictyate oocyte stage. Some oocytes with nuclear morphology similar to the arrested human oocytes give low mutation rates. Degree of chromosome condensation in early oocytes does not appear to be a reliable criterion of oocyte sensitivity to either cell killing or mutation induction, and genetic data on mouse oocytes may be more generally applicable than commonly thought.


Effects of DNA damaging agents on cultured fibroblasts derived from patients with Cockayne syndrome.

The cytotoxic action of physical and chemical agents on 10 skin fibroblast strains in culture derived from individuals with Cockayne's syndrome was measured in terms of colony-forming ability. As compared to fibroblasts from normal donors, all Cockayne cell strains tested exhibited a significantly increased sensitivity to UV light and a normal sensitivity to X-rays. Cells from two sets of parents of unrelated Cockayne children showed an intermediate level of UV sensitivity. There was no effect of 0.5 mM caffeine on UV survival in normal and two Cockayne strains tested, indicating that postreplicational repair in Cockayne cells as measured by caffeine sensitivity was probably normal. Sensitivity of normal and Cockayne cells to the chemical carcinogens and mutagens 4NQO, N-AcO-AAF, ICR-170 and EMS was also compared. An increased sensitivity of Cockayne cells to 4NQO or N-AcO-AAF, but not the ICR-170 or EMS, was observed. However, unlike the intermediate UV sensitivity, the cell strains from two parents of Cockayne patients showed the same sensitivity to N-AcO-AAF or 4NQO as fibroblasts from normal individuals. Quantiation of damage to the DNA after 20 J . m-2 UV irradiation indicates normal levels of [3H] thymidine incorporation in the Cockayne cells, in contrast to UV-irradiated xeroderma pigmentosum cells (XP 12BE) in which there was a very low level of repari synthesis. Moreover, we have shown previously that excision of UV-induced pyrimidine dimers in 2 of the 10 Cockayne cell strains was normal.


Translocation yield from mouse spermatogonial stem cells following unequal-sized x-ray fractionations: evidence of radiation-induced loss of heterogeneity.

Previous work has shown that a high yield of genetic damage can be recovered from stem spermatogonia exposed to a high (900 R) X-ray dose, despite extensive cell killing, when this follows 24 h after a smaller (100 R) radiation exposure. This differs from the response of the normal stem-cell population and has been interpreted to mean that the more radio-resistant cells surviving the first exposure become sensitive both to radiation-induced killing and genetic damage after this time interval and, as a consequence, lose the heterogeneity in radio-sensitivity that typifies a normal stem-cell population. Similar results have now been obtained with doses of 600 and 800 R given in fractions of 100 + 500 R and 100 + 700 R 24 h apart. Yields of translocations among spermatocytes were higher than obtained with the single doses and responses consistent with the fractions acting additively were obtained when the fractions were given in reverse order. Further analyses of the data provided support for the concept that 24 h after a radiation exposure there is a loss of heterogeneity in radio-sensitivity in the surviving stem-cell population.


Cell-cycle dependency of BUdR-induced mutation for six genetic markers in cultured mammalian cells.

Synchronized mouse L5178Y cells were treated with BUdR during each one of four sequential periods of the cell cycle (M-G1, early S, middle S and late S-G2). Among the 6 markers examined, asparagine independence (Asn+), 6-thioguanine resistance (TGr) and excess thymidine resistance (TdRr) showed maximal induction of mutation rates in the early S period, methotrexate resistance (MTXr) gave maximal induction during the middle S period, and two other markers [arabinosylcytosine resistance (Ara-Cr) and ouabain resistance (Ouar)] showed little mutation induction in any period under the experimental conditions. These results suggest that (i) genes responsible for Asn+, TGr and TdRr activity may be replicated in the early S period and the gene for MTXr activity replicated in the middle S period, and (ii) the mechanisms of mutation induction for the Ouar and Ara-Cr markers may be essentially different from those for the Asn+, TGr, TdRr and MTXr markers.


Failure of caffeine to influence induced mutation frequencies and the independence of cell killing and mutation induction in V79 Chinese hamster cells.

Using V79 Chinese hamster cells and a replating assay, no effect of caffeine post-treatment on spontaneous or UV- or EMS-induced mutation frequencies to 8-azaguanine resistance was demonstrable. However, considerable potentiation of cell killing was observed. Previous reports that caffeine enhances induced mutation frequencies are explained by an artefact in the situ method used; a similar artefact may also explain the cumulative in situ mutation dose-response curves. Furthermore, the relationship between mutation induction and dose has been shown to be qualitatively distinct from that between cell killing and dose. These differences suggest that cell killing and mutation induction are mediated via independent mechanisms and that pre-mutational lesions may be qualitatively distinct from pre-lethal lesions.


Cytogenetic investigation of occupational exposure to epichlorohydrin.

Cytogenetic evaluation of peripheral lymphocytes from 93 workers currently exposed to epichlorohydrin has revealed an increase in aberration rates as compared to that of a 75-person group seen for preemployment examination. Statistically significant differences were found in the distribution of individuals with chromatid breaks, chromosome breaks, severely damaged cells, and total abnormal cells. These results confirm the observations of Kucerova et al. in a similar occupational group.


Prenatal diagnosis of classic hemophilia.

Prenatal diagnosis of classic hemophilia (hemophilia A) in mid-trimester was achieved by means of immunoradiometric assays for factor VIII on fetal plasma and amniotic-fluid mixtures obtained by fetoscopy. Samples were analyzed from six male fetuses at risk for severe hemophilia and from nine control fetuses for which fetoscopy was carried out to attempt prenatal diagnosis of other genetic disorders. The factor VIII coagulant-antigen values for the control (non-hemophilic) samples were 17 to 94, and the factor VIII related-antigen concentrations were 50 to 155 U per deciliter. Three of the fetuses at risk for hemophilia had factor VIII values in the control range, and these infants were normal at birth. The other three fetuses had low concentrations of factor VIII coagulant antigen but normal concentrations of factor VIII related antigen. These values and the diagnoses of severe hemophilia were confirmed with blood from the abortuses.


Non-diabetic retinal abnormalities in chronic pancreatitis.

To determine whether retinal abnormalities occur in patients with chronic pancreatitis, ophthalmoscopic and retinal-function evaluation was performed in 28 patients with chronic pancreatitis and 19 healthy subjects. The final threshold of dark adaptation was significantly increased 40 per cent (P less than 0.001) in patients with pancreatitis, whether or not they had steatorrhea. Patients with steatorrhea had a significant decrease of about 42 per cent (P less than 0.001) in the b-wave of the electroretinogram, a measure of both rod and cone function. Seven of the 28 patients complained of difficulty with hight vision; six of these seven had morphologic lesions on ophthalmoscopic examination, confirmed by fluorescein angiography. No correlation was found between any of the retinal abnormalities and the serum vitamin A or zinc levels or glucose tolerance. Non-diabetic retinal lesions and retinal-function abnormalities are common in patients with chronic pancreatitis, even in the absence of steatorrhea.


Clinical implications of sickle-cell trait and glucose-6-phosphate dehydrogenase deficiency in hospitalized black male patients.

To determine whether sickle-cell trait and glucose-6-phosphate dehydrogenase deficiency influence the course and fatality rates of certain diseases requiring hospitalization, especially those associated with thrombotic phenomena, we conducted a co-operative study of 65,154 consecutively admitted, black male patients in 13 Veterans Administration hospitals. The overall frequency of sickle-cell trait was 7.8 per cent and of glucose-6-phosphate dehydrogenase dificiency 11.2 per cent. Both conditions were present in 0.9 per cent of those examined. There were regional, but no age-dependent, differences in the frequency of sickle-cell trait. Sickle-cell trait had no effect on average age at hospitalization or death, overall mortality, length of hospitalization on medical and surgical wards and frequency of any diagnosis, except essential hematuria and pulmonary embolism. Although statistically significant (P less than 0.001), the differences for the latter were small (1.5 per cent of all patients with normal hemoglobin and 2.2 per cent of patients with sickle-cell trait). Glucose-6-phosphate dehydrogenase deficiency had no adverse effect.


Evidence against transmission of Hodgkin's disease in high schools.

A survey in Greater Boston identified 1577 new cases of histologically diagnosed Hodgkin's disease between 1959 and 1973. Of these cases, 448 were of ages such that the patients might have attended high school during 1960-73. For 96 per cent of these persons high-school attendance was ascertained. First of all, we studied Hodgkin's disease at high schools in two time periods. The 13 high schools with cases present in 1960-64 were matched with 26 schools that had no cases in this period, and we compared these two groups for the occurrence of Hodgkin's disease during 1965-69. The proportion of "exposed" high schools that had cases diagnosed in the second period was 0.62, and that for the matched high schools was 0.65. We performed this two-time-period analysis for 25 additional combinations of time periods; in none of them did we find a statistically significant positive result. Secondly, we studied the risk of Hodgkin's disease among persons who had attended high school at the same time as a diagnosed case. We followed these "exposed" persons through 1973 and observed 12 cases among them, whereas the expected number of cases was 13.9. Thirdly, we evaluated the extent to which members of all possible pairs of cases had attended the same or nearby high schools at the same time. We found no excess of classmate pairs than might have occurred by chance alone. These data suggest that there is no transmission of an etiologic agent for Hodgkin's disease at high schools.


Hypothalamic-pituitary-gonadal dysfunction in men using cimetidine.

We studied the effect of cimetidine therapy (1200 mg per day by mouth for nine weeks) on the hypothalamic-pituitary-gonadal axis of seven men. There was a 43 per cent mean reduction in sperm count after therapy. The luteinizing hormone response to luteinizing hormone releasing factor was also reduced, and a statistically significnat rise in plasma testosterone occurred, although it was less than that before therapy. Gonadotropin responses to provocative clomiphene stimulation were inadequate when compared with those of controls. Cimetidine did not affect the responses of thyroid-stimulating hormone, prolactin, growth hormone and thyroxine to thyrotropin releasing factor. Caution is advisable in administration of cimetidine for prolonged periods to young men.


Persistence of middle-ear effusion after acute otitis media in children.

We observed the frequent occurrence of persistent middle-ear effusion in children with acute otitis media and followed them according to standard procedures for otologic diagnosis. We performed a life-table analysis to identify risk factors for such persistent disease. Sixty-two patients were free of middle-ear effusion at one or more clinic visits two to 13 weeks after presentation and were considered cured; 45 had effusion at all clinic visits during this period and were defined as having persistent effusion. The life-table analysis showed that the relative risk for persistence was 3.8 times higher in children less than 24 months of age as compared with children 24 months of age or older (P less than 0.001) and that this risk was 2.8 times greater for white as compared with black children (P less than 0.01). Other factors examined were not identified as significant risk factors. Persistent middle-ear effusion may be associated with impaired hearing and appears to be the most important sequela of otitis media.


Immune response of a patient with deficiency of the fourth component of complement and systemic lupus erythematosus.

The clinical details of a five-year-old boy with systemic lupus erythematosus and an inherited deficiency of the fourth component of complement (C4) have been reported elsewhere. In this study of his immune responses, immunization with bacteriophage phi X 174 demonstrated diminished antibody formation, abnormal immunologic memory and failure to switch from IgM to IgG during secondary response. We also noted persistent lymphopenia and reductions in peripheral-blood T lymphocytes, lymphocyte responses to mitogens and allogeneic cells and granulocyte chemotaxis. Kinetic studies revealed that delayed activation of the alternative pathway was corrected by purified C4 only if the classical pathway was not blocked. This finding is consistent with the concept that minute amounts of C3b provided through the classical pathway are necessary to prime the properdin system. Inability to activate the classical complement pathway, abnormal kinetics of alternative-pathway activation and depressed antibody responses to a T-cell-dependent antigen may predispose C4-deficient patients to viral infection or immune-complex formation.


Intramuscular pressures with limb compression. Clarification of the pathogenesis of the drug-induced muscle-compartment syndrome.

To study muscle necrosis due to prolonged limb compression, we measured intramuscular pressure by inserting wick catheters into 10 volar forearms and 10 anterior tibial compartments of adult volunteers. We then placed the subjects in positions in which victims of drug overdose are commonly found. Intramuscular pressures in the area of direct compression on hard surfaces ranged from 26 to 240 mm Hg, and averaged 101 mm Hg. Most remarkable was a mean pressure of 180 mm Hg on compression of the forearm by the rib cage. These pressures are sufficient to cause muscle and capillary ischemia and necrosis by local obstruction of the circulation. This local injury by limb compression may produce edema sufficient to start compartment tamponade and consequent muscle-compartment and crush syndromes.


Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5alpha-reductase deficiency.

To determine the contribution of androgens to the formation of male-gender identity, we studied male pseudohermaphrodites who had decreased dihydrotestosterone production due to 5 alpha-reductase deficiency. These subjects were born with female-appearing external genitalia and were raised as girls. They have plasma testosterone levels in the high normal range, show an excellent response to testosterone and are unique models for evaluating the effect of testosterone, as compared with a female upbringing, in determining gender identity. Eighteen of 38 affected subjects were unambiguously raised as girls, yet during or after puberty, 17 of 18 changed to a male-gender identity and 16 of 18 to a male-gender role. Thus, exposure of the brain to normal levels of testosterone in utero, neonatally and at puberty appears to contribute substantially to the formation of male-gender identity. These subjects demonstrate that in the absence of sociocultural factors that could interrupt the natural sequence of events, the effect of testosterone predominates, over-riding the effect of rearing as girls.


Digoxin-quinidine interaction Pharmacokinetic evaluation.

Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine.


A new design for randomized clinical trials.

This paper proposes a new method for planning randomized clinical trials. This method is especially suited to comparison of a best standard or control treatment with an experimental treatment. Patients are allocated into two groups by a random or chance mechanism. Patients in the first group receive standard treatment; those in the second group are asked if they will accept the experimental therapy; if they decline, they receive the best standard treatment. In the analyses of results, all those in the second group, regardless of treatment, are compared with those in the first group. Any loss of statistical efficiency can be overcome by increased numbers. This experimental plan is indeed a randomized clinical trial and has the advantage that, before providing consent, a patient will know whether an experimental treatment is to be used.


Nontreatment of fever in extended-care facilities.

In a study of decisions not to treat febrile patients, we reviewed the medical records of 1256 people admitted to nine extended-care facilities in Seattle during 1973. Fever, defined as two temperatures of 38.33 degrees C to 38.83 degrees C (101 to 101.9 degrees F), within 24 hours or one temperature greater than or equal to 38.88 degrees C (102 degrees F), developed in 190 patients before two years of stay. Active treatment, defined as antibiotics or hospitalization (or both), was ordered for fever in 109 patients, of whom 10 (9 per cent) died. Active treatment was not ordered for 81 patients, of whom 48 (59 per cent) died. The pre-decision factors that showed a significant relation (P less than 0.05) to such nontreatment were: diagnosis, mental status, mobility, pain, narcotics prescribed, size of the facility, relation of the physician to the patient and medical-record statements documenting the patient's deterioration or plans for nontreatment in general. This pattern of nontreatment suggests that physicians and nurses did not intend to treat these patients actively and that high mortality was expected.


Construction of a site-specific, deletion-frameshift mutation in an essential gene of bacteriophage phiX174.

By in vitro methods, we have deleted 80 nucleotides from a preselected site in the coding sequence of gene G of bacteriophage phiX174. This mutant (Gdelta/FS ZH1) also carries a--2 frameshift. The mutation is lethal, but mutant virus can be stably maintained on host strains bearing plasmids carrying phiX gene G.


Thrombin-stimulated cell division involves proteolysis of its cell surface receptor.

A cell-surface component of molecular weight 43,000 is cleaved by thrombin on cells that divide after thrombin treatment, but is not cleaved on cells that are unresponsive to its mitogenic action. Studies with a photoreactive derivative of thrombin showed that its cell surface receptor has a molecular weight of 43,000. This indicates that thrombin must cleave its receptor to stimulate cell division.


BCG vaccination  in Hodgkin's lymphogranuloma.

Results of active non-specific immunotherapy in 25 patients suffering from Hodgkin's disease are given. All of them, being at the stage of a complete remission (residual disease) were divided into two groups according to the clinical stage: group 1 at the stage I and II and group 2 at the stage III and IV. To each vaccinated patient a non-vaccinated control, being at the same stage of disease and of approximately the same age, was selected by applying the method A--B. Results as to the survival time and the remission duration were in both vaccinated groups significantly longer although less significant in patients with an advanced stage of the disease. The present report is to be considered preliminary and the research work is carried on.


Carcinogenicity and polarographic behaviour of dibenzo[a,h]pyrene, 4,11-diazadibenzo[a,h]pyrene and 7,14-diazadibenzo[a,h]pyrene.

In a simultaneous test of carcinogenicity the writers have studied the activities of dibenzo[a,h]pyrene (I), 4,11-diazadibenzo[a,h]pyrene (II) and 7,14-diazadibenzo[a,h]pyrene (III). These compounds were dispersed in paraffin disks and subcutaneously implanted in rats. Each experimental group consisted of 30 animals. The number of sarcomas induced by (I) and (II) was 23 and 16 respectively. The compound (III) has proved wholly inactive. Tumorigenicity of (I) and (II) was found to be proportional to their electron donation and inversely proportional to their electron acceptance in the performed polarographic test. Inactivity of (III) is being discussed from the aspect of molecular geometry.


Biosynthesis of cholesteryl 14-methylhexadecanoate in the liver of rats bearing transplantable tumors and during chemical carcinogenesis.

Biosynthesis of cholesteryl 14-methylhexadecanoate, cholesteryl palmitate and cholesteryl stearate was studied in the liver of rats bearing the Walker 256 carcinoma. Zajdela hepatoma and during chemical carcinogenesis following the administration of benzo[a]-pyrene. An up to 9-fold enhanced production of all these esters was found in liver homogenate during the 10--16th day after Walker tumor transplantation. Only the enzyme system esterifying cholesterol in the cytosol at pH 6.5 was stimulated while the activity of similar enzymes in mitochondria, microsomes and cytosol at an acid pH were not affected. Activity of the cytosol enzyme esterifying cholesterol at pH 6.5 was also enhanced during the active growth of Zajdela hepatoma and during the period of chemical carcinogenesis characterized by the appearance of first palpable subcutaneous tumors. Enhanced activity of cholesterol esterifying enzymes in the liver exactly coincided with periods of elevated levels of cholesteryl 14-methylhexadecanoate in the liver and blood plasma as described earlier. An increased demand of the tumor-bearing host for this cholesteryl ester utilized as a co-factor for enhanced protein synthesis is obviously met by its stimulated production in the liver tissue.


Morphologic changes in the gastric mucosa of rats after administration of N-methyl-N'-nitro-N-nitrosoguanidine. Electronmicroscopic study.

Electron microscopic findings of the effects of exposure to the cancerogenic substance N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) upon the gastric mucosa of rats are presented. MNNG was administered in drinking water at a concentration of 83 mg/l over a period of eight weeks. The resulting findings included occurrence of myelin figures in membrane structures of epithelial cells, occasional disappearance of nuclear membrane, numerous intranuclear cytoplasmic pseudoinclusions, and increased number of perichromatin and interchromatin granules and of nuclear corpuscles. Narrowing of the layer of peripheral condensed chromatin and broadening of the layer of dispersed chromatin were frequently observed. In the cytoplasm of epithelial cells, production of autophagous vacuoles was detected in differentiated types of cells, the presence of great amount of polysomes and profiles of rough endoplasmic reticulum diversely deformed was seen in the undifferentiated neck cells. These cells presented a marked proliferative activity. Some of the changes described in the nuclei of epithelial cells were also observed in different mesenchymal elements in the lamina propria mucosae. The demonstrated changes are indicative of both regressive and progressive effects of the cancerogen used in our experiment.


Acid hydrolases in the extracellular medium of Ehrlich ascites tumor cells.

The hydrolytic activities released to the extracellular medium by tumor cells could be related to the fundamental mechanisms of invasion and metastasis. This paper deals with a study of the extracellular release of several enzymatic activities by Ehrlich ascites tumor (EAT) cells maintained in vitro. The activities of acid hydrolases increase during the first 30 minutes of in vitro incubation to levels significantly higher than those of cytoplasmic enzymes. The presented results are consistent with the hypothesis of the existence of a mechanism in these cells for the specific release of lysosomal contents.


Cobalt-activated acylase from human uterine myoma.

Cobalt-activated acylase was isolated from human uterine muscle and myoma. The enzyme was purified by ammonium sulphate precipitation, and subsequent chromatography on DEAE-cellulose, Sephadex G-150 and DEAE-Sephadex. The comparison of muscle acylase and acylase obtained from myoma has shown differences in the enzyme stability, the dependence of activity on pH and in the susceptibility to the effect of activators and inhibitors. Only one molecular form of cobalt-activated acylase has been found in both tissues.


Chromosomal analysis on Yoshida tumor cells sensitive and resistant to dibromodulcitol.

Yoshida ascites tumor in Wistar rats was rendered resistant to dibromodulcitol. The modal number of chromosomes in the parent line was reduced from 39 to 36 in the resistant one. The parent tumor was a mixed cell population, containing large subtelocentric (LST) chromosome in 65 per cent of the cells, while in the remaining 35 per cent the LST chromosome was absent. In the resistant tumor line, however, the LST marker chromosome was present only in a few cells. The resistant line preserved this new karyotype throughout the 5 months of passaging even without dibromodulcitol, however, parallel to the loss of resistance this tumor line regained the original number of chromosomes, i. e. 39. Selection of a cell population with reduced number of chromosomes seems to be associated to the development of drug resistance.


Combined therapy of leukemia La with Damvar and cytostatics.

The new cytostatic drug Damvar, delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl)valeric acid, is not effective in La leukemia system. Damvar given in combination with 5-fluorouracil enhanced the anti-La effect of 5-Fu. There was also enhancement of the antileukemic effect of suboptimal and optimal doses of cyclophosphamide with the addition of Damvar.


Vacuolation in the human cerebral cortex and its relationship to the interval between death and autopsy and to synapse numbers: an electron microscopic study.

Vacuolation in the human cerebral cortex resulting from swelling of cell processes after death was measured in electron micrographs in material obtained up to 69 hours post mortem from subjects with no known neurological abnormality. Vacuolation was found to increase significantly up to 30--35 hours after death and then to decrease. Accompanying this change was a significant reduction in the numbers of recognizable synapses which probably resulted from compression due to the vacuolation rather than from post-mortem disintegration.


Protein and nucleic acid content in the aging human brain.

The frontal cortex, white matter, cerebellum, caudate nucleus, thalamus and putamen of human brains, ranging from 16 to 91 years, were assayed for protein and nucleic acids. In all these areas the protein content decreased by 5--15% between 30 years and 90 years-of-age. The nucleic acid content, however, did not show any significant change. During a post-mortem interval of 6--25 hours there was no significant decrease found in either the protein or the nucleic acid content of brain tissue.


Evidence of vasopressin in adenohypophysis: research into its role in corticotrope activity.

The presence of vasopressin (VP) in pars distalis of rats and pigs was investigated. Using radioimmunoassay and bioassay of VP, a substance with immunological and biological properties of this hormone was found. This substance was not detected in the adenohypophysis of rats with diabetes insipidus. A partial purification of the VP-like peptide showed that it had the chromatographic and electrophoretic properties of VP. It could be identified with arginine vasopressin (AVP) in the case of the rat and lysine-vasopressin (LVP) in the case of the pig. In the Wistar strain, adrenalectomy induced progressively increasing concentrations of adenohypophysial VP. This increase was significant 15 days after surgery. It could be prevented by treatment with dexamethasone. These results indicate that the presence of VP in the anterior pituitary is related to the regulation of ACTH secretion.


Restitution of bromodeoxyuridine-induced changes in cerebellar development.

Previously, it was shown that bromodeoxyuridine (BrdU) in 2-day-old rats caused hypoplasia of the external cerebellar granular layer. Significant restitution was achieved after removal of BrdU by an increase in the rate and duration of proliferative activity of the EGL cells, but abnormal cerebellar cytoarchitecture remained detectable at 35 days of age due mainly to polarity changes in the regenerated cells. The present report concerns repair of the EGL after giving BrdU to 7-day-old rats i.p. (15 mg/100 g body weight) twice daily for 3 days and killed at 15 days-of-age. Now, the regenerative capacity of the EGL was severely curtailed. The proliferative activity of the EGL of the treated animals was similar to normal controls and there was no change in the orientation of either the EGL cells or the parallel fibers. The only noticeable differences were a decrease in the width of the molecular layer and the presence of unusually elongated primary dendrites in many Purkinje cells of the BrdU treated rats. It was concluded that lengthening of the cell cycle time had slowed down the removal of BrdU and thus reduced the regenerative potential of the EGL at this age.


Pinealectomy-induced changes in blood and pituitary luteinizing and prolactin levels during the last phase of pregnancy in rats.

Serum LH levels were higher in pinealectomized than in sham-operated control rats during all 4 of the last days of pregnancy studied, although reaching significance only during the final 2 days, 21 and 22. Prolactin (Prl) levels in the serum on the final day of pregnancy, and its contents in the pituitary throughout the entire study period, were significantly lower in pinealectomized rats. Pituitary weights were lower in pinealectomized than in control animals during days 21 and 22 of pregnancy, but no differences were found between the 2 groups in the average number of living foetuses and resorptions. The results presented would seem to indicate that during the last phase of pregnancy the pineal gland plays a role in the modification of gonadotropin synthesis and release. It appears that with LH the release, and with Prl mainly the synthesis, is being affected by the pineal, although the release of Prl may be influenced as well.


Identification of neurophysin-like proteins in the posterior pituitary gland of the chicken (Gallus domesticus).

Chicken posterior pituitary tissue was partially fractionated by extraction with 0.1 M HCl followed by gel exclusion chromatography. Two fractions, B and C, bound oxytocin. Two components of fraction B and at least 1 component of fraction C had properties characteristic of mammalian neurophysins: they appeared to be synthesized in the hypothalamus, were depleted upon osmotic stress, were rich in residues of cysteine and the 2 components of B bound to [8-lysinel]-vasopressin coupled to Sepharose.


Plasma testosterone and LH levels in male quail bearing hypothalamic lesions or radioluminous implants.

Radioluminous material (RLM) was implanted in either the infundibular complex or the preoptic area of sexually immature quail exposed to short days. Direct selective photic stimulation of the infundibular complex resulted in testicular growth (3,300 mg) and increase in levels of plasma testosterone (T, 23 ng/10 ml) and luteinizing hormone (LH, 4 ng/ml). Direct selective photic stimulation of the preoptic area did not induce any testis enlargement (84 mg) and plasma T and LH levels remained low (1.4 ng/10 ml and 0.9 ng/ml). However, preoptic as well as infundibular lesioning completely suppressed any gonadotropic and testicular responses to environmental photic stimulation. The respective and possibly differential roles played by these 2 structures in the photosexual reflex are discussed.


Plasma corticosterone levels and ulcer formation in rats with hippocampal lesions.

In order to examine the effects of hippocampal lesions on plasma corticosterone levels and ulcer formation, 4 conditions were studied: (1) unrestrained nondeprived (2) unrestrained 24 h food-deprived (3) simple restraint and (4) restraint plus intermittent shock. In the unrestrained and unrestrained plus 24 h food-deprived conditions, neither animals with hippocampal lesions nor control animals developed ulcers. In both instances plasma corticosterone levels were similar in experimental and control animals. Differences appeared in the simple restraint and restraint plus intermittent shock conditions. In both of these conditions animals with hippocampal lesions developed more ulcers and had a higher corticosterone level than controls. It is concluded that animals with hippocampal lesions show an enhanced reaction to stress.


Ultrastructural changes of oligodendroglia and myelin sheaths induced by ethidium bromide.

Intracisternal injection of ethidium bromide, an inhibitor of mitochondria associated RNA, DNA and protein synthesis, produced status spongiosus in the subpial surface of the CNS of rats. Ultrastructurally, numerous intra-myelinic vacuoles and prominent degenerative changes of oligodendroglia were observed. The vacuoles were formed between the myelin lamellae by splitting of the intraperiod lines, between the axolemma and the innermost myelin lamellae, and/or between the inner tongue of oligodendroglia and myelin lamellae. In the degenerating oligodendroglia, proliferation and alteration of the endoplasmic reticulum were prominent. In places, altered membranes of the endoplasmic reticulum formed concentrical scroll-like structures. These ultrastructural changes in ethidium bromide treated rats were compared with other similar previously described changes in animals treated with TET, cuprizone, hexachlorophene, hypocholesterolaemic drugs and actinomycin D.


Effects of thiophene on the Purkinje cell dendritic tree: a quantitative Golgi study.

A quantitative analysis was made of alterations in the dentritic organisation of Purkinje cells in the cerebellum of the adult rat following the administration of the degranulating agent, thiophene. This substance completely eliminated the granule cell population in a number of regions of cerebellar cortex. Purkinje cell dentdritic trees in these regions were markedly reduced in size when compared with control cells and provided evidence for a non-random loss of dentritic segments. Other dendritic abnormalities were noted. These results were discussed in relation to current theories of neuronal maintenance, and the feasibility of using toxic degranulating agents, such as thiophene, was considered.


Effects of dopaminergic antagonist and agonist on oxytocin release induced by various stimuli.

(1) Haloperidol, a dopaminergic antagonist was injected i.p. or into the 3rd ventricle (i.c.v.) of lactating rats to determine whether or not a dopaminergic component was involved in the reflex release of oxytocin (OT) induced by (a) vaginal dilatation (Ferguson reflex), (b) vagal stimulation (vago-pituitary reflex), (c) suckling (milk-ejection reflex). Moreover, we examined the effect of a dopaminergic agonist, apomorphine, on the milk-ejection (ME) reflex. (2) I.c.v. injection of 20 microgram haloperidol inhibited the vaginal and vagal reflexes. The inhibition of the ME reflex produced by 2, 5 or 8 mg/kg i.p. or by 20 and 40 microgram i.c.v. haloperidol was dose-dependent. Apomorphine (10 mg/kg i.p.) had no effect. (3) The results suggest that a dopaminergic component must be involved in OT release whatever the peripheral stimulus.


Regional and sexual differences in the size of the neuro-vascular contact surface of the rat median eminence and pituitary stalk.

The size of the neuro-vascular contact surface was estimated along the median eminence (ME) proximal pituitary stalk (PS) of adult rats using serially cut 1 micrometer thick plastic sections. It was found 26% larger in female animals. The dorsal surface of the pars tuberalis was used as reference surface, and its size was estimated in the same way. The average rate of increase of the contact surface with respect to the reference surface was 3.05 and 2.98 in females and 2.34 and 2.35 in males. The reference surface was divided into small components and also the regional distribution of the rate of increase of the contact surface was analyzed. Very folded contact surface areas were found scattered in the rostral half of the ME. Folded areas made up the ME on both sides of the midline and the dorsal and ventral surfaces of the PS, whereas relatively smooth areas are localized along the 2 margins of the ME and the 2 sides of the PS. The results were correlated with the known termination sites of dopamine and various hypothalamic hormone containing pathways.


Intrahypothalamic implants of progesterone inhibit lordosis behavior in ovariectomized, estrogen-treated rats.

Intracranial implants of crystalline progesterone (P) were used to examine in site of action of P's facilitatory and inhibitory effects on lordosis behavior in the ovariectomized, estradiol-benzoate (EB)-primed RAT. P implanted in the medial basal hypothalamus (MBH) 1 h prior to subcutaneous (s.c.) EB injection inhibited lordosis in response to a systemic P injection 44 h after EB (concurrent inhibition). P implanted in the MBH did not facilitate lordosis when implanted 44 h after EB injection, but this same implant of P inhibited lordosis in response to P injection 68 h after EB (sequential inhibition). Cholesterol (Chol) implants in the MBH did not inhibit lordosis behavior in either the concurrent or the sequential inhibition experimental paradigms. The results indicate that the MBH is an important site of P inhibition of sexual receptivity in the rat.


Plasma and erythrocyte cations in affective illness.

Plasma and erythrocyte cations (sodium and magnesium) were studied in groups of patients with an affective disorder and in normal subjects. Baseline determinations were obtained before initiation of treatment for mania or depression. In a subgroup of patients, sequential measurements of cations were made during treatment with lithium carbonate. No differences were found in intraerythrocyte sodium or magnesium among any of the patient groups and controls. Patients with a primary affective disorder had significantly higher plasma sodium than control subjects. Neither baseline cation concentrations nor changes in cation concentration during treatment with lithium correlated with treatment response. Gender was shown to be a significant variable affecting intraerythrocyte cation concentrations.


Correlations between psychiatric diagnosis and some quantitative EEG variables.

Several methods of quantitative analysis were applied to the left parietal 'resting' EEGs of 48 nonpatient controls and 90 undrugged psychiatric inpatients. Patient and control groups, matched for age and sex, differed as follows: (a) Mean frequency was lower and frequency variability was greater in the total patient group than in controls. (b) Mean amplitude was higher and mean frequency lower in chronic schizophrenics than in controls; the amplitude differences were contributed mainly by female patients. (c) Amplitude and frequency means of nonpsychotic patients were intermediate between those of chronic schizophrenics and controls. (d) Mean amplitudes were greater and frequency variability was less in neurotics than in controls.


Serum cholesterol in antisocial personality.

Serum cholesterol fasting concentrations were measured in 274 subjects with personality disorders, who had committed offences. Of these subjects, 139 were found to possess the antisocial personality (sociopathy or psychopathy). With standardized ages, the group of subjects with antisocial personality had a clearly lower mean level of serum cholesterol than the group with other personality disorders which was used as a control group. The use of a mean male population with standardized ages as a control group further emphasized the low values of the serum cholesterol of the antisocial personality group.


Motion sickness: an index of sensory conflict relating to behavior.

Diverse measures of behavior are examined in a student and large patient sample for the purpose of supporting the concept that conflict in sensory mechanisms may contribute to diminished or impaired function. Evidence supports the contention that two patterns of orientation may exist at the extremes of motion sickness susceptibility and that individuals showing transitional patterns of organization may be vulnerable to different kinds of central nervous system disorganization. The authors believe that a consideration of sensory function as it relates to patterns of behavior may contribute to an expansion in the medical model of mental illness.


Motion sickness susceptibility and solution choice in a pragmatic paradox.

This paper reports on an experiment which employed a classic paradox, known as the 'prisoner's dilemma', to explore possible differences in problem solving preference across a spectrum of motion sickness susceptibility. A mathematical form of the problem was used in which the subject was asked to imagine playing a game without communicating with his hypothetical partner. There were three possible solutions to the problem, a win-win, a lose-lose, and a win-lose solution. The results support the contention that a cognitive bias exists across a spectrum of motion sickness susceptibility, highly motion sick individuals having a greater tendency to pick the solution which allows both participants to win. This bias runs counter to that which might be expected on the basis of personality traits (non-motion sick individuals are more socially involved), and suggests that the cognitive tendency may reflect basic problem-solving strategies rooted in orientation process. The potential implications of these findings are discussed.


HLA antigen and affective disorders: a report and critical assessment of histocompatibility studies.

The distribution of 50 HLA antigens, of the A, B and C loci, was investigated in 38 affectively ill Caucasian patients of Eastern European Jewish ancestry. The frequencies found were compared to those of a control population matched for race as well as geographic and ethnic-religious origins. Results indicate that a negative association exists between affective disorders and Cw3 and also suggests a similar negative association between such disorders and A9. A positive association with Bw16, Bw22 and Cw1 is also indicated; Bw16 was increased in those patients with no family history of psychological illness. A review of the available literature in this area shows a glaring lack of agreement among the studies. Methodological problems exist which are likely to contribute to the variable and conflicting results and might make comparison of data irrelevant. The lack of agreement of data among the studies may also indicate that no HLA disease association exists but rather reflect the existence of a defective gene in the HLA complex but not a part of the HLA system. Additional population and family studies are required before any definitive statements can be made.


Possible linkage between alpha-haptoglobin (Hp) and depression spectrum disease.

Depression spectrum disease is an unipolar depressive illness in which at least one member of the family has unipolar depression and at least one other first degree relative has alcoholism and/or antisocial personality; using this definition, 14 depression spectrum disease families are studied. Assuming, among other things, that variability in age of onset is environmentally caused and lognormally distributed, segregation analysis shows that the data are compatible with the dichotomy of 'affected' versus 'not affected' being due to an autosomal dominant gene. A simple environmental hypothesis in which the transmission of the illness does not depend upon the parents' type could be rejected (p less than 0.001). Linkage analysis is performed by the method of maximum likelihood, taking the best fitting Mendelian model found in the segregation analysis. The results show virtually no evidence of linkage between depression spectrum disease and C3, but suggestive evidence (lod score = 1.03) of linkage between depression spectrum disease and alpha-haptoglobin (both these linkages were previously suggested by significant results in sib-pair analyses).


HL-A antigens and the response to prophylactic lithium.

82 consecutive patients checked at the out-patient clinic of the Psychiatric Department of the Umeå University were typed for HL-A antigens. The patients belonged to the diagnostic subgroups: bipolar (manic-depressive) psychosis (n = 33), unipolar recurrent depressive psychosis (n = 29) and cycloid psychosis (n = 20) and all had been on lithium treatment for at least 6 months. By comparing the group of those who did not relapse on lithium therapy (n = 48) with the group of those who did relapse (n = 34) there was a significantly higher frequency of the HL-A A3 antigens among those who did relapse, and none of those who did not relapse were found to have the HL-A B18 antigens. The results suggest a possible interference between HL-A antigens and response to lithium treatment. However, a large number of antigens were tested and a small number of patients.


Suicide in the Lundby study: a comparative investigation of clinical aspects.

28 cases of suicide committed in a Swedish population subjected to repeated psychiatric investigations are described. Two groups of controls were selected from the same population: sex- and age-matched living persons (normal group) and sex-matched persons who had died from organic disease at ages corresponding to those at which the individuals in the suicide group had taken their lives (deceased group). The three groups were compared concerning clinical circumstances regarded to have been of importance for the final suicidal act. Interest was focused on events that had occurred during the year prior to suicide. Psychiatric disorders were diagnosed in 93% of the suicide group, in 60% of the deceased group, and in 32% of the normal group. Depression was the main diagnosis (50%) in the suicide group, organic brain syndrome in decreased and normals. Medical advice was sought more often (75%) by the suicide group than by normal controls (34%) and about equally often as by the deceased control (84%). 10 of the suicide persons with depressive illness had never seen a psychiatrist.


Prediction of antidepressant responses to imipramine.

45 patients hospitalized for depression who had received double-blind trials with imipramine were examined for possible associations between pretreatment responses to the Minnesota Multiphasic Personality Inventory (MMPI) and their behaviorally-rated responses to this drug. Each patient was randomly assigned to one of two groups with the restriction that the number of responders and nonresponders be balanced for sex. Results from the group A patients suggest that responders and nonresponders to imipramine were best identified by using two sex-specific, empirically-derived, MMPI scales. In contrast, 12 of 13 regular validity and clinical scales and all 49 of the selected special scales of the MMPI failed to separate responders from nonresponders. In the cross-validation study with the group B patients, we were able to predict female and male responders from nonresponders by the new imipramine response scale with accuracy rates of 93 and 100%, respectively. The implications of these results are discussed.


Effect of clozapine on apomorphine-induced growth hormone secretion and serum prolactin concentrations in schizophrenia.

Clozapine had no effect on basal serum growth hormone concentrations in 10 schizophrenic patients but significantly inhibited the apomorphine-induced growth hormone increase that occurred in 7 subjects. Clozapine caused a slight (17%) but significant elevation in basal serum prolactin levels. These data suggest that in man clozapine, like other neuroleptics, blocks dopamine receptors, at least in the hypothalamic-pituitary axis.


Functional interhemispheric differences in relation to various psychopathological components of the depressive syndromes. A pilot international study.

Previous investigations from our laboratory have suggested a possible interhemispheric difference in brain functioning in relation to the severity of a depressive psychopathological process. The present study has been carried out to extend the previous findings to comprise a more detailed symptom analysis of the depressive syndrome, several EEG characteristics, and a new method of EEG analysis. 22 depressed patients, most of them previously untreated, participated in the study. The patients were rated by means of a highly reliable rating scale for depression, and an EEG record was obtained from each of them. Analysis of possible relationships among clinical symptoms and EEG characteristics from different parts of the brain showed a complex pattern, quite different for each symptom. First when a systemic structural analysis of the EEG was performed by means of a special computer program, differential EEG syndromes could be identified. Patients with a high level of anxiety-depression showed a more pronounced functional involvement of the left precentral region than less severely ill patients.


Mortality on lithium.

A register of patients receiving lithium in the Edinburgh and Lothian area of Scotland has been kept by the Medical Research Council Brain Metabolism Unit since 1967. Using this register, information was obtained on 784 patients receiving lithium for a period of up to 115 months (97.4% of the population available for study). 33 patients died during the period of study due predominantly to cardiovascular causes or to suicide. There was nothing to suggest that long-term exposure caused more deaths than short-term exposure and the pattern of mortality resembled that found in other studies of manic-depressive illness, i.e. the majority of deaths occurred in the early stages of follow-up.


[Contribution to the study of "wet lung". Radiological and clinico-functional changes induced by depletion therapy in 5 patients with chronic bronchopulmonary disease].

The Authors consider the global evaluation of clinical and functional data in patients with the following radiological features: 1) X-ray thoracic aspects characterized by marked broncho-vascular bundles and diffusion of reticular nodulation as in diffuse interstitial pulmonary fibrosis; 2) lack of ECG and clinical signs of heart failure. Since a reversibility of radiological alterations was considered a favourable reply to bleeding and diuretic acute and long term therapy the Authors suggest that these patterns should be related to a different distribution of hydric and haematic masses with a decreasing of interstitial pulmonary oedema which contributes to a full interlobar septa like "D" lines shadows, according to Kreel, (1975). The Authors, moreover, relate these clinical, functional and radiological aspects to the patterns of "wet lung" distinguished from the cardiac lung caused by congestive heart failure and from interstitial lung fibrosis.


[Plasma ion changes in venous blood incubated with beta receptor blockers and subjected to tonometry in vitro. 1. Study using propranolol].

The Authors considered the variations in electrolyte plasmatic assessment in blood samples incubated "in vitro" with propranolol (48 gamma/10 cc) and part of sample incubated with propranolol and theophyllin-ethilandiamin. The evaluation of electrolyte assessment was performed at 20'-40'-60' after tonometration. Sodium and potassium values increase in the samples with the beta-blocking agent and are statistically significant only after 20'; in further controls the increasing values persist. Chloride rises too, marked by a low statistic significance. No variations were observed in samples incubated also with propranolol and antiphosphodiestherasic agent. The Authors suggest trat data should confirm ionic transport blockage across the red cell membrane obtained with theophylline.


[Physiopathological and clinical data on post-hypercapnic metabolic alkalosis. A case of severe hypercapnia treated with drugs and in an "iron lung"].

The Authors produce a further contribution on metabolic post-hypercapnic alkalosis on the basis of clinical observation of a patient with severe hypercapnia and respiratory failure undergoing intensive care as well as treatment with iron lung (Pulmolife). The improvement of respiratory acid-base umbalance was associated with alteration of electrolytic assessment, especially of the plasmatic chloride ratio. The Authors consider this remark as a starting point for a physiopathological pattern and a more complete analysis of the pathways which generate the metabolic post-hypercapnic alkalosis condition in such patients.


[Changes in the acid-base equilibrium and the water-electrolyte balance during maximum aerobic work in patients with chronic broncho-pulmonary disease].

The Authors studied the behaviour of acid-base balance in subjects with chronic obstructive lung disease undergoing Maximal Aerobic Work following the method of Pasargiklian e Coll., 1955. For the research two different experimental pattern were adopted: 1) patients were subjected, in two different sessions, to the muscular work in room air and in hyperoxia (60%) breathing for the evaluation of acid-base balance. During hyperoxia Authors observed rising of paO2 and decrease of paCO2, pH and lactic acid concentration. 2) In the second pattern the muscular test was performed in room air only with the use of an antiphosphodiesterasic drug e.v. administration in each patient. Together with acid-base balance behaviour of plasmatic electrolytic assessment was controlled in order to evaluate adaptation to work. The data, although preliminary, show an increase of paO2 with decrease of paCO2 in both test; potassium and bicarbonates concentration increase more in the first test without theophyllin whereas this drug forbid these increments. The Authors even if the experimental program must be developed suggest that the evaluation of these data is interesting in diagnosis and prognosis in chronic lung disease for the cellular adaptation to work and offers interesting elements to carry on the rehabilitation of chronic obstructive lung disease.


[The use of oral potassium chloride (BS 560) in the treatment of mixed acid-base imbalance in patients with chronic broncho-pulmonary diseases].

The Authors, after giving an outline of metabolic alterations on acid-base balance in chronic obstructive lung disease, describe the need of correction of electrolytic umbalance, signally in relationship to metabolic alkalosis dued to hypochloremia. The Authors emphasize the importance of correction of jonic balance during long term therapy in such patients, especially diuretic and steroid long term treatment. The Authors studied the comparative effects on jonic assessment by correction with potassium chloride e.v. and potassium chloride by oral administration with a new capsulate preparation, (BS 560). Last they underline the good tolerance of this preparation and report the favourable effects on electrolytic patterns.


[Medical treatment of hyperammoniemia in the elderly. Controlled clinical study].

After considering the physiopathological mechanisms of ammoniac metabolism and the different causes of hyperammonaemia in subjects whose organisms present the weak biological equilibrium of the elderly, the antiammonaemic activity of gamma-ethylester of glutamic acid and that of arginine have been compared in a controlled double-blind trial. 45 old patients suffering from hepatic insufficiency characterized by hyperammonaemia and correlated neurological symptomatology have been treated. The subjects, subdivided at random into groups of 15, were treated for an average of 8.8 days with gamma-ethylester of glutamic acid, arginine and placebo presented in identical 500 ml bottles. The posology of the active ingredients ranged form a maximum of 25 g to a minimum of 10 g. The results obtained show that gamma-ethylester of glutamic acid and arginine has significantly greater antiammonemic activity than placebo and that gamma-ethylester of glutamic acid is significantly more effective than arginine. As regards the improvement in neuropsychic symptomatology, the clear superiority of gamma-ethylester of glutamic acid versus both arginine and placebo non evident.


[The hyposmolar-hyponatremic syndrome in hepatic cirrhosis. Possible role of ADH].

Following some remarks on the hyposomolar-hyponatraemic syndrome and on the formation of free water, the possible aetiopathogenetic mechanisms of hyponatraemia in ascitogenous cirrhosis of the liver and in particular the role of ADH are considered. 3 cases out of 18 suffering from ascitic phase cirrhosis in whom inability to produce free water was accompanied by conserved urinary excretion of sodium are reported. One explanation might be the intervention of ADH or of an antidiuretic substance.


[Pesticides in rural pathology].

Reference is made to the extensive use of pesticides in agriculture and the fact that many are highly toxic. The lack of information and legislative provisions makes agricultural workers particularly vulnerable to the several categories of poisons contained under the description "pesticides". The chlorinated and phosphoric organic compounds are of especial interest. The former include the derivatives of the phenoxycarboxylic acids, which can give rise to a product (tetrachlorobenzodioxine, or dioxine) that was responsible for the pollution at Seveso. The latter group contains the very commonly employed alkylthiophosphates (malathion, parathion, etc.). These are well-known inhibitors of acetylcholine esterase and thus responsible for harm to the nervous system. A comparable, but less intense effect on this esterase is possessed by the carbamates, which are increasingly being used in agriculture. It is hoped that, as in the past, suitable, oriented epidemiological surveys will be carried out in industry, designed to focus attention on the probable, but not yet documented chronic damage that many of these products cause to the human body.


[Hypouricemia and xanthinuria. Observation of 3 cases].

The Authors refer about three cases of asymptomatic xanthinuria pointed out after the discovery of very low serum uric acid levels (below 1 mg/100 ml). The above-mentioned cases come out from 137.194 evaluation of serum uric acid carried out in a period of about four years. The values of serum and urinary uric acid and those of total oxypurines in urine of same kinsmen of the three patients have been evaluated; all these values were in the normal range.


[Importance of the analysis of the carcinoembryonic antigen in clinical oncology].

330 patients (126 with gastric neoplasms, 204 with large bowel carcinoma) were submitted to serial assays to evaluate the possible relations between C.E.A. levels, pathologic stage and histologictype of the neoplasm and to define the usefulness of the C.E.A. test in monitoring the followup of the patients with gastrointestinal neoplasms. From our experience it ensues that C.E.A. test positivity (C.E.A. greater than or equal to 5 ng/ml, according to the method employed) is higher in colon neoplasms in comparison with gastric neoplasms, in the adenocarcinomas compared with the anaplastic forms. Besides, the study of the relationship with the pathologic stage points out the scanty usefulness of the C.E.A. test in the early diagnosis of gastroenteric neoplasms (Dukes A-B-C1 = 29.2%; CH stage = 88.1%). The use of C.E.A. test during the follow up seemed us of fundamental importance. We observed that: a) after radical surgery, 72% of the patients showed a normalization of C.E.A. values; b) there is a significant relationship between clinical course and C.E.A. as it can predict, sometimes several months earlier, the occurrence of relapses and metastases; c) there is also a close relationship (P less than 0.001) between the modifications of the antigen under chemotherapy and the clinical response. At present, C.E.A. seems to play, above all, fundamental role in choosing a correct treatment after radical surgery or in modifying the chemotherapeutic treatment in non surgical cases or in non radically resected patients.


[The behavior of the a and the t indices and the systolic times in myocardial infarct].

A study of the behaviour of the a and telediastolic indices and systolic times in patients presenting the sequelae of myocardial infarction is reported. It is pointed out that the earliness of a and t index variations with respect to those of systolic times is an indication of the sensitivity of the investigation which offers invaluable pointers to subsequent treatment. It is also stressed that previous hypertension and/or coronaropathy are more important than the infarction itself in creating dyskinetic zones of the myocardium and, consequently, the haemodynamic changes observed with phonomechanocardiography.


[The organization of diagnostic exercise tests in a provincial general hospital].

The approach to the diagnostic effort test recently recommended by the A.N.M.C.O. is discussed. The cost of equipment and staff required are examined. Precise data regarding the cost of such a unit in the cardiology department are given and stress is laid on the advisability of confining its use to cases in which clinico-historical investigation and preliminary clinical evaluation point to it as indispensable for cardiology diagnosis.


[Atrial electric stimulation via the esophagus. A promising new method].

Experience acquired in the electrical stimulation of the atrium via the oesophagus in 18 consecutive cases ir presented. An account is given of the technique and the results obtained. These confirm the reliability and simplicity of execution of the entire diagnostic procedure.


[The effect of a beta blocker on various manifestations of hypermetabolism and hypersympathicotonia].

The possible mechanism and the therapeutic activity of a beta-blocking drug (propranolol) in 50 patients with slight "hyperthyroidism" or "dysthyroidism" are examined. In most cases, the laboratory findings were :1) increase (sometimes considerable) of basal metabolism (up to 70% or more); 2) normal, or nearly normal, thyroid scan, iodoproteinaemia, T3 and T4; 3) therapeutic iodine improvement. Prior to the introduction of scanning, these cases would have been classed as "hyperthyroidism" or "dysthyroidism". Observation of a normal scan picture, however, throws doubt on such a diagnosis. Cases have, in fact, been noted in which the syndrome was accompanied by normal RU T3, but a marked increase in RIA T3. Since the latter is five times more active, it might be supposed that its increases was responsible for the symptoms, i.e. there could be an increase in T3 activity, even though its quantity was still within normal limits. In other words, there may be cases of genuine hyperthyroidism due to such a proportional rise in RIA T3. Propranolol had a beneficial effect on a series of manifestations that can be described as "hyperthyroidism" or "hypersympathicotonia".


[Trigeminal neuralgia. Classical clinical and therapeutic aspects. Advantages of a modern method: controlled differential heat coagulation].

The main clinical aspects of essential trigeminal neuralgia are reported and traditional medical and surgical therapy reviewed. Results obtained in 114 patients treated with a modern method, controlled differential thermocoagulation, are then analysed. This consists of percutaneous infiltration of Gasser's ganglion and/or retrogasserian roots and in causing thermolesions by means of radiofrequency, i.e. using constantly controlled and steadily increasing temperatures which selectively damage the finer painful facial fibres without affecting the more resistant tactile fibres. While the principal advantage of this method lies in the elimination of pain with partial saving of facial tactile sensitivity, other practical advantages are of no less importance: these include the fact that the method is so harmless that all patients, even those of advanced age, could leave hospital at the latest one day after treatment.


[Scintigraphy of the bile ducts by means of the Tc-99m-acid N-(2,6 diethyl-acetanilide) iminodiacetic acid in pediatrics].

Results with diethyl-IDA in the diagnosis of dilatation and obstruction of the bile ducts are reported. By comparison with methyl-IDA, the more rapid blood clearance and slower renal excretion of diethyl-IDA do not lead to interference on the part of the right kidney and ureter during the first 30' of scintiscanning. The preparation was employed in 15 subjects with persistent neonatal icterus and clinically suspected diseases of the hepatic bile ducts. Personal experience is cited for the view that, thanks to its almost exclusively biliary excretion and high bile concentration, 99mTc-labelled diethyl-IDA gives better visualisation of the bile ducts than the methyl-IDA complex.


[Automatic method for the evaluation of the extent of myocardial infarct from the serum of CPK curve].

An off-line system for calculating the extent of infarct from serial serum CPK determinations based on Sobel et al.'s compartmental model is presented. Results in 40 patients with acute infarct in a coronary unit showed that the index of infarct extent had an appreciable prognostic significance. Employment of the MB isoenzyme in the calculation could, it is felt improve the sensitivity of the method.


[Clinical use of DDAVP in a case of familial hypothalamo-pituitary diabetes insipidus].

The effectiveness of 1-deamino-8-d-arginine-vasopressin (DDAVP) has been evaluated in a case of insipid hypothalamo-hypophyseal familial diabetes. The polyuric-poly-dipsic syndrome was well controlled and there were no notalbe side-effects. The advantages of this treatment in comparison with more traditional methods are underlined.


[Hemolytic crisis due to a G-6-PD deficiency during the course of viral hepatitis A].

Pathogenetic hypotheses regarding G-6-PD deficiency syndromes are reviewed and a case of viral hepatitis with concomitant haemolytic crisis due to a deficiency in this enzyme is reported. In agreement with other workers, it is noted that viral hepatitis may be one of a variety of factors triggering of the phenomenon and may in such cases present a more serious clinical course.


[Mitral valve substitution, using the Lillehei-Kaster prosthesis].

Personal experience acquired in the course of 177 mitral valve replacements with a Lillehei-Kaster prosthesis up to June 1977 is discussed. Intraoperative mortality was 8.5%. Postoperative mortality (as at 31-12-1976) was 5.3%. The clinical, radiological, and ergometric findings were fully satisfactory. Haemodynamic examination at rest and during effort revealed improved pressure and heart capacity values. The mean transprosthetic gradient at rest was 5.61 and rose to 13.53 (after uncalibrated effort). Thromboembolism was noted in 5 patients (3.1%), as in the literature. The haemodynamic features and low thrombogenicity of the Lillehei-Kaster prosthesis would thus appear to make it a sound replacement for the mitral valve.


[Use of angiopneumography with Tc-99M in 2 cases of pneumopathy caused by anatomical defect].

A parallel study, using traditional angiopneumographic technique with iodate contrast medium and the radioisotopic technique employing 99MTc has been carried out in some cases of bronchopulmonary malformations due to anatomic defect. The purpose of this is to assess the angiographic performance at pulmonary circulation level of an extremely simple radioisotopic technique. Analysis of the two cases presented suggests that although radioisotopic angiopneumography presents lower resolution capacity for viewing small and medium lumen branches of the pulmonary artery, it has the advantage of associating the results of traditional angiopneumography with statis pulmonary scintigraphy in a single exploration. It is considered that this investigation can be used particularly in those patients with severe cardiorespiratory insufficiency, for whom the invasive technique presents some by no means inconsiderable risks.


[Antigens and antibodies in acute viral hepatitis caused by the B virus. Clinical significance].

Three antigen-antibody systems are so far known to be related to viral hepatitis type B. Tests for evidencing HBsAg and antiHBs are easily performed and important for the diagnosis, prevention and study of hepatitis B. The tests for evidencing HBcAg and HBc are still the subject of study and research. The presence of HBsAg in a subject shows he is hosting hepatitis B virus. It may also be present without hepatopathy or it may be associated with acute or chronic hepatitis B. At the present time there is no feasible way of eliminating the chronic carrier condition. The problem represented by healthy carriers as infection risks is currently under study.


[A case of melanoderma erroneously considered to be addisonian].

A case characterized by a dark pigmentation of the skin with an initial hypotension and a lung tuberculosis in the remote anamnesis is described. The skin pigment was formed by lipofuscin and emosiderin, but only the former was found in the liver biopsy. Anyway, the pigment was not melanine and the surrenalic function of the patient was completely normal; therefore, an Addisonism syndrome is excluded. The patient was treated for a very long time with DOCA: this caused hypertension, probably supported by the hypervolemia triggered by the DOCA depending retenction of sodium and water. A sure diagnosis of the case was not made, but an Addisonism syndrome was certainly excluded.


[Chemotherapy of intestinal carcinomas].

It is not easy to weigh up therapeutic and toxic effects in the medical treatment of intestinal cancer. The number of drugs that have demonstrated certain activity in these forms is extremely limited, only 5 FU being definitely active and even this only in a small percentage of patients. 5 FU produces remission in some 20% of cases. It is highly probable that prophylactic treatment with 5 FU increases patient survival as reported by Regelson and other workers, but the resulting damage (hepatic, bone marrow, immunodepression, etc.) must also be assessed and the risk of a second neoplasia should not be forgotten. The personally used association of 5 FU and cyclophosphamide has proved active at least to the same extent as 5 FU alone, while toxic effects were not particularly important. Brilliant but unfortunately temporary results can be obtained by peritoneal PTC in peritoneal carcinomatosis. Good results with respect to the pain symptom have been obtained by associating 5 FU with radiotherapy in non-operable intestinal tumours.


[Clinical and hormonal evaluation of recurrence of goiter after thyroidectomy].

The incidence and features of goitre recurrences were investigated in a sample population of patients operated at the University of Turin Endocrine Surgery Centre. The following parameters were examined: sex, age, familial history of goitre, number of pregnancies, T3 and T4 levels, and TSH levels. Attention is drawn to the finding of significantly higher TSH values in the patients operated for recurrent goitre than in a series of persons free of recurrences after they had been operated on for goitre. Other workers have made the same observation, which is therefore regarded as a pointer to the correct interpretation of the recurrence of goitre.


[Prognosis of acute hepatitis B].

The clinical course, persistance of HBs antigen, and the liver biopsy morphological picture were evaluated in 40 patients with acute viral hepatitis, type B. In 34 cases, the disease ran a satisfactory course and clinical cure was corroborated histologically. In 4 cases, onset was particularly severe and the disease ran a long course. Here the immunological test for HBs antigen was still positive 8 weeks after the disease began, while a biopsy at 4 months showed a morphological picture similar to that of acute hepatitis. Lastly, two cases with a protracted clinical course displayed persistent HBs antigen positivity one year after the acute episode, with a histological finding of persistent hepatitis and cirrhosis of the liver respectively.