[Results of treatment of primary bone neoplasms of the sacrococcygeal region]. In the clinic 53 patients with primary bone tumors of the sacrococcygeal region and sacroiliac junctions were observed. Surgical methods of treatment were used in 33, combined--in 7, radiation therapy--in 10, drug therapy--in 3. Recurrences developed in 7 cases, metastases were revealed in 14. The results of treatment in patients with neoplasms in this region were studied. Twenty five patients died from generalization of the process, metastases, intestinal obstruction and uremia. The remaining 28 patients have been followed up within the terms from 1 to 5 years and longer.


[Results of bone homoplasty in ununited fractures, pseudarthroses and defects of the long tumular bones]. In the article, observations on application of bone homoplasty in 99 patients with unhealing fractures, pseudarthrosis and defects of long tumular bones are described. Homoplasty per se was performed in 22 cases, in combination with autoplasty--in 3, with metallic osteosynthesis--in 74. Tubular homografts were used in 14 cases, grafts in a kind of cortical plates--in 85. Postoperatively, the patients were followed within the terms up to 5 years. In 88 cases the results of surgery were satisfactory, in 11--poor. An analysis of the material concerned have shown that issues of bone homoplasty are greatly effected by the character of the graft, surgical technic and the state of a recipient bed.


Factors influencing occurrence of colibacillosis in calves. This investigation describes some of the husbandry factors influencing the occurrence of colibacillosis in calves. Diarrhoea and mortality were usually associated with an increase in the proportion of "pathogenic" to total E coli to about 50 per cent in the faeces although there were occasions when the proportion of "pathogenic" E coli increased but no disease occurred. These increases often followed changes of diet which appeared to be more important than environmental conditions. The use of uncontaminated houses to break the cycle of infection appeared to have the greatest influence on the disease pattern.


Chromosomes of cattle: present clinical status and promise. Current information on cytogenetics in veterinary medicine is presented as a resume for the veterinarian in cattle practice; previous reviews of the subject are recorded. The literature depicting the recognised chromosome abnormalities in cattle is breifly reviewed. It is suggested that chromosome screening already has a role to play in the economics of cattle production.


[Specific binding of progesterone to the proteins of human endometrial cells]. A specific complex of protein-receptor with hormone, which had a sedimentation coefficient 3.8S, was formed in cell nuclei on incubation of endometrial tissue from pregnant woman with 3H-progestrone at 37 degrees C in vitro. In cell cytoplasm of endometrium the progesterone-protein complex was observed which sedimented at 6.8S and 4.2S. Progesterone was accumulated mainly in nuclei; lower concentrations of the hormone were found in cell cytoplasm of endometrium. Fractions of mitochondria, microsomes and ribosomes also bound the hormone but less distinct as compared with the nuclei. The formation of cytoplasmic complex of progesterone with protein-receptor occurred on incubation of endometrial cytoplasmic fraction with 3h-progesterone at 4 degrees C.


[Metabolic stability of the protein-synthesizing system of the myocardium in compensatory cardiac hyperfunction in actinomycin D block of RNA synthesis]. Under conditions of complete actinomycin block in rat heart muscle an inhibition of protein synthesis and dissociation of myocardial polyribosome structures were observed (half-life was equal to 6.5 hrs). In compensatory hyperfunction of heart muscle, caused by stenosis of aorta, the inhibitory effect of actinomycin D on the protein synthesis was manifested earlier than in control and was exhibited more distinctly. In myocardium under compensatory hyperfunction of heart muscle the protein synthesis was decreased by 50% within 4 hrs after administration of actinomycin into animals and it was completely inhibited within 10 hrs after the antibiotic administration. The alteration in stability of polyritobosomes under compensatory hyperfunction of heart muscle was specific for myocardium and was not observed in liver tissue.


[Noncoagulative catabolism of fibrinogen]. In catabolism of fibrinogen a function of Cupfer endothelial cells isolated from dog and rabbit liver tissue, was studied. In lysosomal-mitochondrial fraction of Cupfer cells and activator of plasminogen was found. Proteolytic and esterase (hydrolysis of benzoyll-agronine methyl ester) activities were the most typical for lysosomal-mitochondril and supernatant fractions of Cupfer cells. The enzymatic hydrolysis of fibrinogen was not observed in cytoplasmic matrix. The data obtained suggest that under the physiological conditions non-coagulational catabolism of fibrinogen occurred mainly intracellularly.


[Blood proteolytic enzyme inhibitors and their clinical study]. Data on biochemistry, physiological significance and clinical investigations of two main inhibitors of proteinases in human blood serum (alpha 1-antitrypsin and alpha 2-macroglobulin) are reviewed. Physico-chemical properties of the inhibitors, mechanisms of their interaction with proteinases and methods for determination are discussed. Modification of the specificity of some proteinases by alpha 2-macroglobulin, which probably plays a significant role in the regulation of enzymatic systems of proteolysis in blood, is considered. The use of the inhibitors of proteolysis for diagnostics of pathological processes is discussed. Data on the alpha 1-antitrypsin deficiency and its relation to the development of degenerative diseases in lungs are reviewed.


[Napkin thrush clinical picture, mycology, histology, therapy (author's transl)]. A well-defined, characteristic disease has been observed in babies at the Department of Dermatology, Innsbruck University, over the past 7 years. On account of the localisation and probable pathogenesis of the condition the term "Windelsoor" (napkin thrush) has been coined by us for it. The clinical picture, the mycological and histological findings, the therapeutic results and the follow up are reported and the aetiology and pathogenesis of this disease discussed.


The measurement of hypothalamic releasing hormone content and activity in the unanaesthetized rat by means of carotid artery cannulation. To gain insights into quantitative changes in hypothalamic substances which affect the function of the anterior hypophyseal lobe, we developed a technique for carotid cannulation allowing sequential measurements of plasma levels of an affected hormone after injection of such a factor. The principle involves the use of a previously cannulated rat in an unanaesthetized unstressed condition. The hypothalamic extract or LH-RH injected into the cannulas of such animals leads to rapid peaks of LH in peripheral blood removed from the same cannulas within 6 to 8 min, followed by a slow decrease. At least 50% of the peak value is usually found within 3 min. The technique yields quantitatively reproducible results, and appears suitable for measuring relative potencies of test extracts against pure standards and, within as yet undetermined limits, for kinetic studies.


Measurement of rat LH with a double-antibody solid-phase radioimmunoassay: effect of LH-RH and of testosterone oenanthate in castrated animals. A double-antibody solid-phase radioimmunoassay for the measurement of rat LH was described. The use of a solid-phase method for the second incubation resulted in a considerable saving of time as compared to the conventional double-antibody method. The sensitivity and accuracy of the method were not affected by this modification. It was found that there was a cross-reaction between the NIAMD-anti-rat-LH-serum-1 used and NIAMD-rat-FSH-RP-1. This indicates that the test system does not specifically measure rat LH but gonadotrophic activity. The RIA was tested under different experimental conditions. In male rats, the effect of castration and of subsequent treatment with testosterone oenanthate upon serum LH, and upon the weight of the seminal vesicles, the ventral prostate, and the levator ani, was examined. Serum LH rose rapidly after castration and reached 2 to 4 weeks after orchidectomy a maximum (8-9 fold increase). Subsequent treatment with testosterone oenanthate caused a rapid decrease of serum LH. The accessory sex organs showed reciprocal changes of weight. In oophorectomized rats whose pituitaries had been blocked with oestradiol monobenzoate and progesterone, a linear log-dose response of plasma LH was found after administration of various doses of synthetic LH-RH.


Studies on the inhibitory effect of somatostatin on glucose induced insulin release in the isolated perfused rat pancreas. Somatostatin, the recently discovered growth hormone release-inhibiting hormone in the hypothalamus, also inhibited glucose induced insulin release from the isolated perfused rat pancreas. The lowest effective dose of somatostatin was 1 ng/ml of perfusate. By increasing the dose to 100 ng/ml an almost complete inhibition of basal as well as stimulated insulin release was obtained. The inhibition of glucose stimulated insulin release mediated by somatostatin might be of competitive nature since somatostatin seemed to dislocate the glucose-insulin dose-response curve to the right.


Studies on the mechanism of somatostatin action on insulin release in man. I. Effect of blockade of alpha-adrenergic receptors. The present studies have demonstrated that the growth hormone releaseinhibiting factor of the hypothalamus, somatostatin, exerts a prominent inhibiting action on glucose induced insulin release in man. This inhibition of insulin release could not be reversed by infusion of the alpha-adrenergic blocking agent, phentolamine. Our findings therefore suggest that the inhibiting effect of somatostatin on glucose induced insulin release is not mediated by the alpha-adrenergic receptors.


Insulin components released by the normal and subtotal degranulated perifused islets of Langerhans of the rat. The insulin components released from normal and tolbutamide treated islets of the rat were studied in a perifusion system. The treated islets showed diminished quantities of insulin secreted as compared to the controls and an increase in the proportions of "big insulin" secreted during the second phase of this release. On the other hand, the main component of insulin released during the first phase was "little insulin". These studies confirm that the subtotally degranulated islets are less efficient than the controls in producing insulin release.


Clinical and pharmacological evaluation of the effects of piribedil in patients with parkinsonism. Nine patients with Parkinsonism were studied before and after treatment with piribedil, a dopamine-receptor stimulator. Piribedil appeared to have a slight anti-Parkinsonism effect upon bradykinesia, and possibly upon tremor, but did not improve rigidity. The chief toxic effects were drowsiness and confusion, and two patients experienced nausea. Changes in homovanillic acid in the cerebrospinal fluid indicated that the drug reduced the turnover of endogenous dopamine. In spite of this definite neuropharmacological action, no clear-cut associated clinical benefit was demonstrated. The significance of these findings is discussed.


Plasma and erythrocyte magnesium levels in patients with primary affective disorder during chronic lithium treatment. Plasma and erythrocyte magnesium concentrations were measured in 79 clinic outpatients who had histories of bipolar or unipolar primary affective disorder and who were being chronically treated with lithium carbonate (60 patients) or placebo (19 patients). Although slight differences in the mean concentration of magnesium in plasma and erythrocytes were noted with lithium treatment, diagnosis, and sex, the differences overall failed to achieve statistical significance. In contrast to prior reports demonstrating increases in plasma magnesium during acute lithium carbonate treatment of affectively ill patients, these data suggest that the pre-lithium steady state is achieved during chronic lithium treatment.


A comparative trail of fluphenazine decanoate and flupenthixol decanoate. A double-blind cross-over study is reported which compares the antipsychotic properties and the side effects of depot flupenthixol with fluphenazine decanoate in chronic schizophrenic inpatients. Special emphasis was laid on examining changes in the target symptoms of apathy/anergia and depression in which flupenthixol has been claimed to be particulary effective. No significant differences were found between treatments on schizophrenic symptoms, or as regards the extrapyramidal side effects produced by equipotent doses of the two drugs. Reasons for the essentially negative results are discussed against a background review of earlier optimistic studies of flupenthixol.


Age-related changes of cells involved in immune responses. The interaction between T- and B-lymphocytes in the immune response to sheep reythrocytes was revealed by estimating the direct plaque-forming cells in mice CMA of various age. Investigations with a transfer of cells to irradiated and intact recipients were performed. We found a 23-fold diminution of the immune response in mice aged 26-28 months, when compared with that in mice aged 8 months. The first signs of a disturbed activity of the immune system were found in animals whose age did not exceed the half of their average lifespan. The injection of B-lymphocytes from young animals does not give rise to the immune response of old nonirradiated recipients. The injection of young b-lymphocytes to old irradiated recipients, being primed by antigen using Playfair's technique before irradiation, results in the highest response than it is in other combinations. The effect of disturbances in the interaction between  T- and B-cells on the mechanism of age-related changes of the immune response is discussed.


Effect of clofibrate on progression of coronary disease: a prospective angiographic study in man. Lowering blood lipids has been invoked as a means of controlling future coronary events.  In this prospective study, the effect of a lipid-reducing agent clofibrate (2 gm. daily) on extent of coronary artery disease was investigated.  Forty patients, 32 having aortocoronary bypass, six having Vineberg operations, two having neither, were placed double-blind in placebo (24 patients) and clofibrate (16 patients) groups, and restudied by selective coronary angiography one year later.  An additional 24 patients dropped from the study due to adverse drug reactions in eight.  Each patient's right, left, anterior descending, and circumflex coronary arteries (with their branches) were separately rated according to degree of obstruction.  The clofibrate group showed a significantly greater fall in triglyceride than did the placebo group (minus 13.7 per cent versus plus 2.3 per cent; p equal to 0.45).  In the clofibrate group, 19 out of 64 coronary arteries (29.6 per cent) showed progressive coronary narrowing, not significantly different from the placebo group (24 out of 96 coronary arteries narrowed, 25 per cent; p equal to 0.26).  No significant differences between drug groups emerged when the data were corrected for degree of fall of blood lipids, initial lipoprotein type, or effect in bypassed versus nonbypassed vessels (p always greater than 0.2).  Regression of coronary artery disease was not seen.  We conclude that clofibrate did not significantly influence the rate of progression of coronary artery disease in a one-year period.


Ultrasound in the diagnosis of congenital heart disease. In addition to recording the motion of the mitral, tricuspid, aortic, and pulmonic valves, echocardiography can identify right and left ventricular cavities and the interventricular septum.  Disorders such as atrial-septal defect, valvular and subvalvular aortic stenosis, pulmonic stenosis, Ebstein's anomaly of the tricuspid valve, and the hypoplastic left-heart syndrome can readily be evaluated by echocardiography.  In tetralogy of Fallot and truncus arteriosus, discontinuity between the anterior aortic wall and septum with overriding aorta has been demonstrated.  Doubleoutlet right ventricle is associated with posterior aortic wall and mitral valve discontinuity.  In disorders such as single ventricle, tricuspid atresia, and endocardial cushion defect with common A-V canal, echocardiographic demonstration of the absence of the interventricular septum has provided the clinician with valuable information.  Newer techniques such as compound-B ultrasonography, which produces a two-dimensional cross-sectional image of intracardiac structures, and multiscan echocardiography will enhance the use of conventional echocardiography by providing a more accurate anatomic display of cardiac chambers and outflow vessels.


Electrophysiology and pharmacology of cardiac arrhythmias.  VI.  Cardiac effects of verapamil. It is clear from clinical and experimental data that have been reported thus far that verapamil is highly effective in the therapy of cardiac arrhythmias, and that it acts by a different mechanism than most of the commonly used antiarrhythmic drugs.  The available clinical data indicate that on intravenous administration verapamil is as good as and perhaps superior to quinidine, procainamide and propranolol for the therapy of many atrial arrhythmias.  Unfortunately the extent to which it is useful as longterm prophylaxis has not yet been reported, nor has its toxicity during protracted oral administration.  The effects of verapamil on cardiac action potentials clearly indicate that it modifies the slow response to a much greater extent than the fast response.  Studies of cardiac tissues from diseased human atria have indicated that slow response action potentials occur frequently.  It is possible that such action potentials are responsible for the reentrant and automatic arrhythmias which occur in association with clinical cardiac disease.  Whether the efficacy of verapamil in the therapy of atrial arrhythmias is primarily due to abolishing slow response activity in diseased atrial tissues or to suppression of propagation through the atrioventricular node is uncertain.  However, it is likely that the therapeutic action of the drug may result from altered propagation of an arrhythmia through the atrioventricular junction as well as from the effects of the drug on diseased atrial and ventricular tissues.


Effects of alpha-tocopherol acetate on the swimming endurance of trained swimmers. Well-trained, competitive swimmers were divided into two groups. Group A was given 900 IU alpha-tocopherol acetate daily for 6 months while group B was given placebos. A swimming endurance test was given before the start of supplementation and after 1, 2, 5 and 6 months. No difference in swimmers' endurance was observed between the two groups during the 6-month period. There was also no difference in postexercise serum lactic acid levels. Younger, less well-trained, competitive swimmers were also divided into two groups. Group A received 900 IU alpha-tocopherol acetate daily while group B received placebos. Swimming times for these swimmers were erratic, reflecting a lack of training. alpha-Tocopherol did not appear to have any effect on their swimming endurance.


Physiology of the menstrual cycle.

Physiology of the menstrual cycle. Modern techniques of bioassay have permitted correlation of hormonal secretion with genital tissue changes during the normal menstrual cycle. During the follicular phase, estrogen secretion rises while other hormone levels are low. At ovulation luteinizing hormone and follicle-stimulating hormone surges are associated with falling estrogen levels. Secretions of progesterone and estrogen again are characteristic of the luteal phase ending with menstruation. Gonadotrophin-releasing hormones are detectable just before the luteinizing hormone and follicle-stimulating hormone surges. Basal body temperature rises with ovulation and is still the most reliable clinical indicator, although ferning and spinnbarkeit (when present) are also quite helpful. Vaginal smears are probably less useful except in the hands of experienced observers.


Oral contraceptive hormones, folate metabolism, and the cervical epithelium. The currently available evidence concerning disorders of folate metabolism in women taking oral contraceptives has been reviewed. A disturbance in folate balance serious enough to cause symptoms (i.e., megaloblastic anemia) occurs very rarely. In some series, but not in others, serum and/or red cell folate concentrations have been reduced in oral contraceptive users. It is doubtful whether sex steroids affect polyglutamate folate absorption. About 20 percent of women taking contraceptive hormones manifest mild megaloblastic changes on Papanicolaou smears of the cervicovaginal epithelium which disappear after folic acid therapy. The current evidence, however, would not indicate that any significant benefit would ensue from routine folate supplementation in women on oral contraceptives.


Adverse reactions, contraindications and complications of acupuncture and moxibustion. This article discusses the various adverse reactions, contraindications and complications of employing acupuncture and moxibustion in therapy. A historical review of these phenomena is also presented, as well as a section on the side effects of auriculotherapy.


Diagnosis of human rabies by the cornea test. The second death due to rabies encephalitis occurring among American servicemen stationed in the Republic of Vietnam is reported. The clinical diagnosis was confirmed by performing the direct fluorescent antibody test for rabies on smears of corneal epithelial cells obtained on the second day of hospitalization. The reliability of various laboratory procedures in confirming the diagnosis of human rabies early in the course of clinical illness is discussed. The cornea test is a useful and rapid method of diagnosing human rabies prior to the development of significant serum antibody titers.


Detection of bacteriuria by dip-slide. Routine use in a large general hospital. The use of a dip-slide (Uricult) procedure for the culture of voided urine specimens in a large general hospital was found to give equivalent results to those obtained by conventional culture technics. There was a significant decrease in the number of unsatisfactory speciments that needed to be repeated. The dip-slide procedure was readily accepted by physicians, nurses and laboratory personnel, and significant savings for the institution were realized.


Computer data processing of medical diagnoses in pathology. Modes of insertion of pathology diagnoses into a computer data storage and retrieval system are reviewed. The conversion of free-flowing diagnostic sentences into internal code is considered, and the advantages of coding are discussed from two aspects: (a) to minimize storage, and (b) to help alleviate difficulties in retrieval of synonymous terminology. Methods of manually pre-coding diagnoses into Systemized Nomenclature of Pathology (SNOP) code are discussed. Data encoding produces a fixed format record which provides significant economy in data handling. The potential use of a real-time visual display unit in data gathering and automatic coding is presented.


Dietary supplement and nutrition in children with cystic fibrosis. Assessment of nutritional status of patients with cystic fibrosis of the pancreas (CFP) showed that poor growth was associated with low concentrations of albumin, urea nitrogen, and cholesterol in serum and with elevated white blood cell (WBC) counts. Patients with CFP maintained weight approximately 1 standard deviation below the mean until 8 years, after which there was a progressive decline in growth rate compared to normal. A complete dietary supplement consisting of a beef serum hydrolysate, a glucose polymer, and medium-chain triglycerides was given to 15 patients for a year. Patients who received the diet showed significant gains in weight, significant increase in clinical score, significant increase in serum albumin level, and a significant drop in the WBC count compared to control patients who did not receive the supplement.


Computer-assisted pediatric diagnosis.

Computer-assisted pediatric diagnosis. A system for computer aid to diagnosis was tested on 90 children hospitalized with systemic illness and discharged with a final diagnosis. A medical secretary and a pediatrician were equally successful (78% vs 77%) in having the system list the main final diagnosis when each independently supplied a list of details extracted only from the pediatric intern's admission notes. Even when the final diagnosis was not considered by the pediatric house staff and attending physicians caring for the patient until after the day of admission, the system was accurate in listing the diagnosis (or in raising the correct line of diagnostic inquiry) in at least 85% of the patients.


Impact of a system of computer-assisted diagnosis. Initial evaluation of the hospitalized patient. Computer assisted diagnosis was evaluated for its ability to hasten the time to initial diagnosis and reduce laboratory studies. The time to diagnosis averaged 2.8 days for a control group and 1.9 days for the group in which the computer printout was made available. In a small group in whom the diagnosis was not established until after 48 hours, there was a further trend to reduction in number of days to diagnosis and irrelevant laboratory studies. The ability of the computer to include the final diagnosis in the initial list of differential diagnoses remained unchanged for patients whose conditions were diagnosed before or after 48 hours, while the physicians' ability decreased. In a university hospital setting, computer-assisted diagnosis may be most beneficial for patients whose conditions have not been diagnosed within 48 hours of admission.


Shunt fluid aspiration: an adjunct in the diagnosis of cerebrospinal fluid shunt infection. Bacterial isolates were obtained from 42 of 59 cultures of shunt fluid aspirated from patients with infected cerebrospinal fluid shunts. The etiologic agent was recovered from 24 to 25 aspirates from patients who were not receiving antibiotics and from 18 of 34 aspirates from patients who were receiving antibiotics. Aspiration, culture, and Gram stain of shunt fluid should be considered in patients suspected of having a shunt infection.


Thoracic arteriovenous fistula: venous connection to right iliac vein. A 5-year-old boy had clinical, cardiac catheterization, and operative findings of a thoracic arteriovenous fistula arising from the right subclavian artery. The venous connection was to the paravertebral plexus with eventual drainage into the inferior vena cava through the right common iliac vein. To our knowledge, this type of fistula has not been reported previously and is believed to represent embryological defects of the first or second posterior intercostal arteries as well as maldevelopment of the venous connections of azygos vein to the superior vena cava, which resulted in the observed caudal venous pathways becoming operative.


The use of antibiotics in biliary tract disease. Antibotics are often used in the treatment of patients with biliary tract disease. Certain drugs are relatively contraindicated if there is preexisting liver dysfunction. Not all antibiotis achieve a high level in bile, and  knowledge of their individual excretion rate is important for intelligent use.


The use of metoclopramide in acute pyloric obstruction.  A clinical trial. Twelve patients with complete, or nearly complete, pyloric obstruction due to duodenal ulcer, were treated conservatively with metoclopramide.  The purpose of this therapeutic trial was to avoid emergency operations in these patients and to enable a better radiological evaluation and clinical preparation before surgery.  The treatment, in addition to the usual gastric decompression and fluid and electrolyte replacement therapy, was effective in 10 patients (83.4 percent).  In eight of these patients the results of the trial was regarded as "very good".  Six of them were operated upon electively later and two were not operated upon at all.  In two patients the results were regarded as "good".  These patients underwent early elective surgery.  In the remaining two patients (16.6 percent) the trial failed and semiurgent operation could not be avoided.  As no side-effects are evident following the administration of metoclopramide and no harm is done by delaying surgery for three days, it is suggested that this therapeutic trial should be undertaken in every case of pyloric stenosis or obstruction.  This may markedly reduce the need for emergency operation and prevent many postoperative complications which not uncommonly follow emergency surgery for pyloric stenosis.


Female excess in anencephaly and spina bifida: possible gestational influences. Data are presented on th sex-specific frequency and the sex ratios of anencephaly and spina bifida from 1945 through 1971. Dramatic changes in the overall rate of these malformations occurred during that period. The purpose of this study was to evaluate the concept of sex-specific thresholds for an unidentified environmental teratogen, a concept which had recently been proposed. The observed epidemiologic relationship between the frequencies and the sex ratios of these malformations is too complex to reconcile with the action of a single teratogen. On hypothetical grounds, a deficiency of human chorionic gonadotrophin (HCG) could explain the sex ratio pattern. These malformations might be caused by yet unidentified factors which produce a deficiency in HCG function. These factors could be placental teratogens, or they could be some other type of environmental agent which is capable of producing a long-term effect on maternal endocrine function.


The effectiveness of human placental lactogen measurements as an adjunct in decreasing perinatal deaths. Results of a retrospective and a randomized controlled prospective study. Serum human placental lactogen (HPL) levels were measured in high-risk pregnancies. A retrospective analysis of 101 gestations with a perinatal loss showed that the 71 stillbirths had abnormally low fetal-danger zone (F-D zone) HPL levels (50.7%) before the fetus died (normal smaller than 1%). With severe hypertension, 85.7% of the cases had F-D zone HPL values prior to fetal death. Abnormal low F-D zone HPL values were found in 20% of the 30 neonatal deaths. A 3 year randomized controlled treatment series was done with 2,7333 women (1,362 treatment and 1,371 control) who had serial serum HPL measurements performed at each prenatal visit. The frequency of F-D zone HPL values was similar (8.6% treatment and 8.2% control). The results showed that although the neonatal mortality rates were similar, the HPL treatment group had a significantly lower fetal death rate (2.6 vs. 14.2%) and thus perinatal mortality rate (3.4 vs. 15.0%). This study supports the usefulness of routine prenatal HPL measurements in the management of high-risk pregnancies.


Guidelines for antibiotic prophylaxis in gynecology. Using a random table of numbers, 100 premenopausal women undergoing vaginal hysterectomy were assigned to a short-term or long-term antibiotic prophylaxis regimen. The short-term regimen patients received a total of 3 Gm. of cephaloridine in divided doses on the day of operation, while the long-term regimen patients also received oral cephalexin postoperatively. The preoperative profiles of the two study groups were similar, and the postoperative results were not significantly different. A quantitative evaluation of aerobic and anaerobic bacteria recovered from the surface of the vagina was done, and cephaloridine content of vaginal washings, serum, and vaginal tissue was determined. This information was utilized to suggest guidelines for antibiotic prophylaxis in gynecology.


Cooperative clinical trials. The Second Ticho Memorial Lecture. As exemplified by the collaborative Diabetic Retinopathy Study, all the appropriate techniques involved in a clinical trial-random assignment of treatment, appropriate controls, and avoidance of investigator bias-should be incorporated during the earliest testing of a new therapy for a chronic disease, for the sake of the patient and for the progress of medical science. This approach to clinical trials in the testing of new ocular therapies can provide the most scientifically sound and rational therapy to the patient.


Intravenous adenine arabinoside against herpes simplex keratouveitis in humans. Adenine arabinoside possessed all of the desirable characteristics for an antiviral agent: (1) not incorporated into host DNA; (2) broad spectrum activity against the DNA family of viruses; (3) lack of resistance in vitro; (4) rapid excretion; (5) did not cause immunosuppression; (6) low toxicity in significantly effective doses; and (m7) relatively inexpensive. Adenine arabinoside employed in 20 mg/kg1day intravenous infusions for seven days in a controlled series of patients was clearly effective in treating herpetic keratouveitis with only minimal adverse reactions. For the first time there may be an effective specific treatment for herpetic stromal disease and iritis. Further controlled studies comparing the effectiveness of adenine arabinoside with and without concommitant topical corticosteroid therapy are necessary.


Metabolic bone disease in chronic renal failure. II. Renal transplant patients. Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy.


Effects of intravascular clotting on the activation of the complement system: The role of the platelet. Total hemolytic complement activity and the third component of complement were found to be significantly depressed in vivo in rabbits following the induction of disseminated intravascular coagulation by both thrombin and thromboplastin. Production of severe thrombocytopenia by the administration of platelet antiserum prior to the infusion of thrombin or thromboplastin partially prevented complement activation. The data show that, when clotting is triggered, complement activation takes place and that platelets are required to some extent for this reaction.


Pancreatic insulin release and peripheral tissue resistance in Zucker obese rats fed high- and low-carbohydrate diets. An effort was made to determine to what degree the hyperinsulinemia found in the genetically obese Zucker rat is the result of the carbohydrate content of the diet. When Zucker obese rats are fed precisely the same amount of carbohydrate as lean controls and allowed to become obese by drinking vegetable oil, their pancreatic islets still release 59% more insulin than do those from lean controls. When their diet contains even more carbohydrate, fed from weaning, and they become equivalently obese, their islet insulin release is increased by an additional 46%. An obese Zucker rat fed a high-carbohydrate diet possesses muscle sensitivity to insulin and enlarged adipocytes undergoing active lipogenesis. A rat becoming equivalently obese on a high-fat diet has an absence of insulin sensitivity in muscle and diminished lipogenesis in  adipocytes. Clearly, the composition of the diet plays an important role in the metabolic consequences of obesity, but neither  diet nor changes in peripheral glucose metabolism can completely explain the hyperinsulinemia.


Psychotherapy: historical roots, universal elements, and cultural variations. The authors review various forms of traditional psychotherapeutic interventions to trace the historical development of psychotherapy, which demonstrates a shift in focus from the supernatural world, to the natural world, to the physical person, then to the psychological person. The basic processes of identifying problems, providing explanations, and prescribing for change are observed among various kinds of treatment systems. Universal elements fundamental to successful treatment can be identified in each of these processes, and each is strongly modified by cultural factors. The authors conclude that the special cultural dimension of psychotherapy consists of defining cultural norms, reinforcing culturally sanctioned coping mechanisms, and providing "time out" from usual cultural expectations.


Current and emerging models of residential psychiatric treatment, with special reference to the California situation. The author reviews the steps that have led to the progressive deemphasis of psychiatric hospitalization in California and surveys the empirical basis for rejecting the usefulness of hospitalization. He discusses the four alternative residential models that have emerged in California as substitutes for state mental hospitals--general hospital psychiatric units, board and care homes, private psychiatric facilities available through vendor contracts, and convalescent hospitals. The author also touches briefly upon some important problems, including the possible fate of public general hospital psychiatric units, community mental health services, and the commitment law in California.


Depression and anxiety in heroin addicts: a placebo-controlled study of doxepin in combination with methadone. Narcotic addicts may manifest symptoms of depression that aggravate their addiction. In this double-blind study of 35 mildly depressed patients in a methadone maintenance program, subjects who received doxepin improved significantly more than control subjects. Even in this short-term study, the reduction in depression was associated with a trend toward better performance in other areas of rehabilitation.


The prevalence and relationships of malaria, anemia, and malnutrition in a coastal area of El Salvador. To study the relationships between malaria, anemia and malnutrition, 853 school-age children from a high malaria incidence area and an adjacent low incidence area were surveyed in September 1972. For the high incidence area the malaria slide positivity rate was 3.5%, spleen rate 7.6% and malaria (indirect fluorescent antibody) serology positivity 24.7%. Contrasted to this, no positive slides, only 3 palpable spleens and a 3.4% serology positivity rate were found for the low incidence area. Twenty-three percent of those studied were anemic, but the prevalence of anemia was the same in both the high and low incidence areas. However, a selected group of children with known history of recent or actual malaria was found to be more likely to have deficient hematocrit values than were children without such history. Hypochromia and microcytosis were prominent morphologic findings in children with anemia, suggesting a diagnosis of iron deficiency. Weights and heights for age were considerably below those of a U.S. reference population but similar to nationwide Salvadoran figures. In both the high and low incidence groups, 62% had arm circumference values below 90% of standard. The distribution of weight-to-height ratios was also similar for both groups. No difference in nutritional status between the two groups could be found.


Rodent systems (Plasmodium berghei-Anopheles Stephensi) for screening compounds for potential causal prophylaxis. An in vivo screening system is described in which drugs administered to rats or mice and challenged with sporozoites are evaluated for their antimalarial properties (causal prophylaxis, suppression, therapy) by the presence or absence of exoerythrocytic forms and parasitemia. The system is composed of A/J mice, Sprague-Dawley rats, Plasmodium berghei, and Anopheles stephensi. Good correlation has been found between test results and practical application.


A prospective study of the effects of ultralow volume (ULV) aerial application of malathion on epidemic Plasmodium falciparum malaria. I. Study design and perspective. A large-scale prospective study was designed to test the effects of aerial ultralow volume (ULV) application of malathion on epidemic Plasmodium falciparum malaria. The study was conducted during 1972 to 1973, in the Miragoane Valley of Haiti, an area having annual anticipated outbreaks of malaria, which allowed prospective assessment. Spraying of malathion at a dosage of 4.5 fluid ounces per acre reduced populations of adult Anopheles albimanus to less than 1% of prespray levels and interrupted epidemic transmission of P. falciparum malaria. No change was measured in susceptibility of the vector mosquito to malathion after six applications of spray during a period of 50 days. Ecologic study revealed no significant impact on nontarget vertebrates. Factors that contributed to the success of this method in Haiti were: 1) a susceptible population of mosquitoes; 2) suitable topography and climate conditions for spraying; and 3) treatment of an area sufficiently large to minimize the influence of immigration of mosquitoes from unsprayed areas.


A prospective study of the effects of ultralow volume (ULV) aerial application of malathion on epidemic Plasmodium falciparum malaria. II. Entomologic and operational aspects. In a large-scale study in the Miragoane Valley of Haiti, designed to test the effects of aerial ultralow volume (ULV) malathion on epidemic Plasmodium falciparum malaria, spray operations resulted in an immediate and sharp decline in numbers of the vector, Anopheles albimanus. The adult population of this mosquito remained at less than 1% of previous levels until several weeks after a 50-day spray period (27 October-16 December 1972) during which six cycles were completed. The study area offered ideal conditions of wind, temperature, humidity, and mountain barriers. Mosquitoes in the area were highly susceptible to malathion. Results indicated that aerial ULV treatment with malathion can reduce A. albimanus populations rapidly and effectively when applications are made over an area as large as 20,000 acres. Preliminary results showed that effective control was not achieved in areas one-quarter that size; these areas were not sufficiently large, and infiltration of mosquitoes from adjacent untreated areas was possible.


A prospective study of the effects of ultralow volume (ULV) aerial application of malathion on epidemic Plasmodium falciparum malaria. III. Ecologic aspects. The effects of aerial ultralow volume (ULV) malathion on selected species of nontarget animals in Haiti are reported. Mortality of certain groups of insects such as bees, flies, beetles, and butterflies was observed immediately following spray application. Minor fish mortality occurred only in shallow water exposed to direct spray. The brain acetylcholine esterase levels of living fish, tree lizards, birds and bats collected from treated areas were not significantly reduced. No ill or dead animals, besides the few fish, were seen even when maximum exposure occurred. Only minor changes in the feeding behavior of some insectivorous birds were observed. The relative bird density decreased substantially for only one species during the study, and other factors besides treatment were considered to be the reasons for the decline. Aerial applications of ULV malathion at dosages sufficient to dramatically reduce anopheline populations did not significantly affect nontarget vertebrates in this tropical environment.


A prospective study of the effects of ultralow volume (ULV) aerial application of malathion on epidemic Plasmodium falciparum malaria. IV. Epidemiologic aspects. In the Miragoane Valley of Haiti a consistent pattern in the incidence of Plasmodium falciparum malaria over a 10-year period made it possible to predict an annual outbreak and perform a prospective study to test the effects of aerial ultralow volume (ULV) malathion on epidemic levels of this disease. At the end of October 1972, after epidemic levels (100 cases/month/10,000 population) had been reached, spray operations were begun. The first spray cycle produced a sharp and immediate drop in populations of the vector Anopheles albimanus, followed 4 weeks later by a decrease in the incidence of malaria throughout the valley. Although the incidence of malaria was similar in sprayed and unsprayed areas prior to the effect of ULV malathion (176.1 and 198.7 cases/month/10,000 population, respectively), it was significantly different during the subsequent 3 months (16.8 cases/month/10,000 population in sprayed areas and 65.4 in unsprayed; p less than 0.001). Travel histories indicated that only 4% of all cases had spent a night away from home during the 4 weeks prior to onset of symptoms; therefore, we concluded that these incidence data represent malaria transmission in the valley. Results of the study indicate that aerial spraying of ULV malathion can interrupt epidemic transmission of P. falciparum malaria by a susceptible vector.


Attempted prevention of diarrheal disease in Apache children with a non-absorbable broad-spectrum antimicrobial. A double-blind study was conducted to test the prophylactic effect of a non-absorbable broad-spectrum antimicrobial (oral colistin sulfate) against acute diarrhea in Apache children. Children 1 to 6 months old had over twice the morbidity from diarrhea if assigned to the antimicrobial group as compared to placebo, while the toddler group (7-30 months) taking the antimicrobial had somewhat less diarrhea. Enteropathogenic E. coli were significantly more often isolated from the antimicrobial group (but only in well children). No special effect on the children's growth by the antimicrobial was discerned.


Antimalarial effects of clindamycin in man. Clindamycin 450 mg every 8 hours for 3 days cured three non-immune patients of falciparum malaria, although the response was slow. The addition of quinine to this regimen provided an accelerated response and cured 3 of 5 other patients. Single doses of clindamycin given daily for 3 days, with or without quinine, cured 1 of 3 patients. Gastric intolerance to the drugs, probably accentuated by the clinical condition, was pronounced in some cases, the course of treatment being interrupted in three patients for this reason. Chesson strain Plasmodium vivax relapses in man were not inhibited by ingestion of 450 mg of clindamycin every 6 hours for 14 days.


Gastrointestinal and hepatic complications affecting patients with renal allografts. Of 126 renal allograft recipients, 34 were found to have gastrointestinal and hepatic complications. In order of frequency, these included: mild liver dysfunction, severe hepatitis usually associated with cytomegalovirus infection, peptic ulceration complicated by bleeding, intestinal obstruction, and pancreatitis. These complications did not appear to influence the long-term survival or function of the renal allograft, but proved to be fatal when massive infection of cytomegalovirus affected the gastrointestinal tract and especially the liver. Gastrointestinal and pancreatic complications occurring in renal allograft recipients can be managed in the same manner as in patients who are not receiving immunosuppression. When surgical intervention is required, it should be performed promptly. The fact that these patients are receiving immunosuppressive therapy should not be a contraindication to early surgical intervention. When the presence of ulcerative lesions of the gastrointestinal mucosa, pancreatitis, or hepatitis is confirmed, the possibility of these lesions being caused by viral agents, especially cytomegalovirus, should be considered and attempts to confirm this diagnosis should be made. If cytomegalovirus infection is confirmed and the patient is experiencing rejection of the allograft, careful consideration should be given to immediate discontinuation of immunosuppressive therapy followed by removal of the renal allograft. In this way the relentless and fatal course of the cytomegalovirus infection seen in some of the patients reported in this study may be avoided.


Hereditary polypoid diseases of the gastrointestinal tract: a working classification. Almost all published cases of hereditary intestinal polypoid diseases can be meaningfully classified into a relatively few distinct syndromes including familial polyposis of the colon, Peutz-Jeghers syndrome, and juvenile polyposis. Familial polyposis is characterized by the development of numerous adenomatous polyps of the colon and subsequent development of colorectal carcinoma in nearly all patients. Extracolonic manifestations are common but do not influence the premalignant nature of this syndrome. Peutz-Jeghers syndrome is identifiable by a combination of circumoral melanin pigmentation and hamartomatous polyps. These polypoid lesions have an unusually wide distribution and may occur in the respiratory, gastrointestinal, or genitourinary tract. There is a small but definite increased incidence of gastrointestinal cancer in these patients. Juvenile polyposis presents a more variable spectrum. In one form there is extensive intestinal involvement leading to diarrhea, inanition, and increased susceptibility to infection. Another form is limited to the colon and easily confused with familial polyposis. With the third form, there is involvement of the stomach, intestines, and colon, which makes it easily mistaken for the Peutz-Jeghers syndrome.


Silastic T tube splints for biliary repair. Silastic rubber T tubes have been compared with latex rubber T tubes in the biliary system of dogs. It was found that Silastic rubber T tubes evoked a significant foreign body reaction within the biliary system, producing bile salt precipitation and debris. Alarmingly, in these studies in dogs, Silastic rubber T tubes did not cause sufficient intraperitoneal adhesions around the tube to form an intraperitoneal tract walling off the tube from the general peritoneal cavity. Thus, when the Silastic rubber T tube was removed, bile leakage into the peritoneal cavity occurred. Based on studies in dogs, Silastic rubber T tubes should not be used in the clinical situation in which the T tube would be removed postoperatively.


Reduction of acute tubular necrosis (ATN) by furosemide and steroids in cadaveric kidney recovery. One hundred fifty human cadaver kidneys have been preserved by a combination of topical hypothermia and pulsatile perfusion with cryoprecipitated plasma in our laboratory. Post-transplant acute renal failure was reduced from 58 to 21 per cent in those kidneys protected with furosemide and methylprednisolone.


Calculi complicating a renal transplant. Four months after a cadaver kidney transplant, kidney stones were found in the renal allograft. Three major predisposing causes of nephrolithiasis were found in the patient, including hyperparathyroidism, renal tubular acidosis, and urinary tract infection. Hypercalcemia was corrected by parathyroidectomy. During the subsequent three years there was no enlargement of the renal stones and adequate kidney function was maintained. Renal tubular acidosis was not severe and seemed to be related to chronic rejection. Urinary tract infection was readily corrected with antibiotics and did not recur after the immediate post-transplant period. Surgical therapy for nephrolithiasis involving a kidney allograft was defferred since urinary flow was not obstructed. This course of management is recommended for use in patients with calculi complicating renal transplantation.


Skin closure using a new skin clip.

Skin closure using a new skin clip. A new skin clip that allows rapid skin closure with minimal trauma to the skin has been devised. The clip can be used in most conventional incisions on the neck, extremities, thorax, and abdomen. It cannot be used where skin is tightly adherent, as in the scalp, palm, and soles of the feet. Closure with this skin clip has proved to be dependable and to provide an aesthetic hairline scar.


[Further investigations for the demonstration of a specific microorganism in sympathetik ophthalmia]. 19 Following the inoculation of tissue culture cells with material obtained from 3 human eyes suffering from sympathetic ophthalmia (2 sympathizing = sy-l, 1 sympathized = sy-2), no growth of bacteria was observed. On the other hand, changes occurred such as are typical for a massive infection with mycoplasmas. The morphology of these microbes corresponds, down to the details, with micro-organisms which the author has frequently demonstrated and illustrated since 1948 in human, chicken and monkey eyes suffering from sympathetic ophthalmia. 2. With the cultures of mycoplasmas obtained from the eyes of human patients suffering from sympathetic ophthalmia, it was possible to produce the same symptoms in chickens as were described by the author in 1950 in sympathizing and sympathized human eyes, namely: torpid uveitis and papillitis, which dragged on for months, and affected not only the inoculated right eye, but also, after 3 weeks and more, the untouched left eye. 3. Identical phenomena involving both eyes have been observed in chickens, the right eyes of which were inoculated with a strain of mycoplasma hominis orale 1 cultivated from other material in the Institut für medizinische Mikrobiologie der Universität Mainz (Prof. Bredt) and given to the author. A chronic intraocular inflammation, which persisted for several months--up to 6 months and more--developed not only in the inoculated right eye of the animals, but also, after an interval of several weeks, in the untouched left eye. 4. Viewed critically and with due care, these findings suggest that mycoplasmas might well play a role in triggering off sympathetic ophthalmia. 5. The results reported on here indicate that intraocular inoculation with mycoplasmas is of importance both in microbiology and in general medicine.


The immune system of the nine-banded armadillo (Dasypus novemcinctus, Linn). The armadillo is rapidly emerging as an animal for biomedical research. A morphological study of the immune system of the armadillo was undertaken to try to demonstrate a possible defect in the morphogenesis of the lymphoid organs that could account for their susceptibility to leprosy. Blood from 20 domesticated adult armadillos revealed lymphocytes predominated among circulating leukocytes in the majority of animals, whereas in wild animals neutrophils predominated. Necropsies revealed well-developed thymus glands and the thymus-dependent areas in lymph nodes and spleens contained abundant lymphoid cells. Hence, we conclude that the susceptibility of the armadillo to leprosy cannot be explained on a morphological basis.


The use of haloperidol for treatment of postoperative nausea and vomiting--a double-blind placebo-controlled trial. Sixty-two postoperative patients were admitted to a double-blind study to compare the therapeutic effectiveness of a single intramuscular injection of 1 mg of haloperidol with that of a placebo for the relief of vomiting and nausea following surgical procedures. Significantly fewer patients continued to vomit or experience nausea in the haloperidol-treatment group than in the placebo-treatment group. No statistically or clinically significant change in vital signs occurred in the haloperidol-treatment group. No serious side effect occurred in either group.


A computer-assisted instruction course in the diagnosis and treatment of respiratory diseases. A computer-assisted simulation of the 'chart method' of teaching has been developed and was used to provide instruction in clinical decision-making in the diagonosis and treatment of pulmonary diseases. The course requires a student to reach and to defend a diagonisis and to provide appropriate treatment for each of 10 simulated cases. Evaluation of performance and immediate feedback and correction of errors of commission and ommission are an integral part of the course. The course provides a model for development of additional programs in other subject areas.


Effect of prostaglandins F2 alpha and E2 on airway conductance in healthy subjects and asthmatic patients. Effects of aerosol inhalation of prostaglandins F2alpha and E2 on specific airway conductance were studied in 12 healthy subjects and 17 patients with bronchial asthma. Approximately 50 per cent reduction of specific airway conductance was obtained with 250 to 1000 mug of prostaglandin F2alpha in healthy subjects and 4 to 512 ng of prostaglandin F2alpha in asthmatics. In healthy subjects, repeated administration of prostaglandin F2alpha within 1 session elicited nearly identical changes specific airway conductance, whereas a degree of tachyphylaxis possible existed in asthmatics. The sensitivity to prostaglandin F2alpha during a 17 month period remained quite constand; test-retest responses did not differ significantly. Pretreatment with 1 mg of atropine did not modify the effect of prostaglandin F2alpha in health subjects. In contrast. bronchoconstriction in asthmatics was diminished 1 and 5 but not 10 minutes after inhalation prostaglandin F2alpha. Prostaglandin E2 was a bronchodilator in healthy subjects but caused either dilation or constriction (the direction of the change in specific airway conductance being consistent for each subject) in asthamatics.


Subfascial ligation (Linton operation) of the perforating leg veins to treat post-thrombophlebitic syndrome. A series of 71 subfascial ligations of the perforating veins of the lower leg is discussed, and the technique of the operation outlined. Forty-four per cent of the limbs we treated developed a postoperative slough, and 25 per cent required skin grafting. There was an ulcer recurrence rate of 33.8 per cent in our series, but these ulcers usually promptly healed with compression bandaging. In 13 per cent of the limbs, further operative procedures were required. There was no operative mortality in this series.


Decreasing reliability of acid-fast smear techniques for detection of tuberculosis. The ability of any screening test to correctly identify diseased patients is directly related to the prevalence of the disease in question. The continuing use of smears for the detection of acid-fast bacilli when the prevalence of tuberculosis is declining will produce increasing numbers of false-positive results. To determine the usefulness of smear techniques, we carried out a retrospective study of approximately 10 000 consecutive smears and cultures. Positive smears were classified as true- or false-positive on the basis of whether the corresponding cultures grew mycobacteria. The overall incidence of false-positive smears was 0.7%; however, the ratio of the number of false-positive to total positive smear was about 0.5. Thus, for each true-positive result, one false-positive result was obtained. Patients in the true-positive group had clinical and radiological evidence to support the diagnosis of tuberculosis, while those in the false-positive group had new findings of the disease. These data suggest that the smear is a poor screening technique in a population where the prevalence of tuberculosis is low.


Hyperglucagonemia in uremia: reversal by renal transplantation. Chronic renal failure in man is associated with hyperglucagonemia that is not corrected by hemodialysis. Plasma glucagon concentrations were measured in nine patients before and after renal transplantation. Mean plasma glucagon concentration in eight patients with chronic renal failure before transplantation was 295 plus or minus 171 pg/ml (plus or minus SD). After successful transplantation, mean plasma glucagon concentration fell to 134 plus or minus 81 pg/ml (plus or minus SD) (P less than 0.001). Plasma glucagon concentration remained elevated in an additional patient who received a cadaveric graft that never functioned. Immunologic rejection of transplanted kidneys was associated with a dramatic increase of plasma glucagon concentration.


A review on neurosecretory granules: their contents and mechanisms of release. The available evidence suggests that hormones and neurophysins are associated exclusively with the neurosecretory granules, each of which contains approximately 6 times 10-4 molecules of each. Hormones and carrier proteins are complexed within the granules and the complexes are densely packed. The processes that keep the intragranular space in osmotic equilibrium with the axoplasm require further study. Freeze-fracture data, as well as studies in which histochemical methods for the detection of glycoproteins were used, suggest that the intragranular aspect of the granule membrane mostly resembles the extracellular half of the plasma membrane; on the other hand, the cytoplasmic aspects of plasma and granule membrane have similar characteristics, which may be important in permitting membrane fusion to take place prior to secretion. Little is known about the molecular species involved in this interaction between granule and plasma membrane, except that calcium is a cofactor in this process. Release is triggered in vivo by propagated action potentials which cause an influx of calcium into the secretory endings. Newly formed granules, and other granules located at the periphery of the endings are preferentially released. Irrespective of the type of stimulation of secretion, release involves the diffusion into the extracellular space of granule core constituents. The best evidence so far in support of this view comes from ultrastructural studies showing images of exocytosis, as well as from biochemical studies demonstrating that hormones and carrier proteins are secreted concomitantly in a great variety of experimental or clinical conditions, without an associated release of granule membrane constituents or of enzymes of cytoplasmic origin. Recovery mechanisms following secretion require new synthesis of granule constituents and restoration of the resting internal concentrations of potassium, sodium, and calcium. Membrane surface area is restored following exocytosis by compensatory endocytosis which involves indiscriminate uptake of extracellular medium into the secretory axon terminals. While much progress has been made in research on the cellular and subcellular processes that take place in neurons which produce, store, and secrete neurohypophyseal hormones and their carrier proteins, neurophysins, many pressing questions remain to be answered. New developments, such as organ culture of supraoptic nuclei94-96 and the recent isolation of a clone of mouse hypothalamic cells capable of synthesizing vasopressin and neurophysin,97 will hopefully allow some of these problems to be solved in the future.


[Possible mechanisms of the rifampicin suppression of the conjugation transfer of R-factors in Escherichia coli]. The studies on the effect of a number of antibiotics on transfer of R-factors with the use of a kinetic conjugation system showed that rifampicin inhibited the transfer of various R-factors independent of the microbial host strain and R-factor type (the inhibition coefficient of I infinity equals 7.5-16.8). The early conjugation stages preceding the transfer of R-factor DNA were most sensitive to the antibiotic effect. Decreased number of R+ conjugants observed on the donor strain growth in the presence of rifampicin were due rather to selection of spontaneous R- variants with the antibiotic found in our experiments than to its direct effect on the donor competence of R+ cells. It was also found that exposure of E. coli strains to rifampicin for 30 minutes increased their sensitivity to chloramphenicol and tetracycline, this being more pronounced in the cells which not long ago acquired the R-factor. The mechanism of the phenomenon is not clear yet. It was shown to be not associated with the cell permeability impairement under the effect of rifampicin. It was noted that rifampicin combination with neomycin chloramphenicol, tetracycline or streptomycin had a synergistic effect on the strains of E. coli.


[Recipient capacity of B. alcalescens strains in the conjugation transfer of R-factors to them for E. coli strains]. Unlike many enterobacteria the strains of B. alkalescens isolated from patients with the intestine dysfunction and healthy persons preserved sensitivity to the antibiotics used in the medical practice. This served as a basis for the study of the recipient competence for reception of R-factors from E. coli by 6 strains of the alkali producer. The strains of E. coli with the derepressive R-factors J 5-3 R1, J 5-3 R64 and CSH-2 R1-19 were introduced into the conjugation mixture as the donors. Only I strain of E. coli, i.e. J 5-3 R1 with multiple antibiotic resistance proved to be a competent donor. A possibility of transfering on1 I determinant of resistance (to neomycin) to 3 out of 6 strains of B. alkalescens at a low rate of10-7 and 10-9 was shown. The R+ conjugants appeared to be immune to further reception of R-factors of both the competent and the incompetent donors. The low recipient capacity of the strains of B. alkalescens must, to some extent promote circulation mainly of antibiotic sensitive strains of the microbes under natural conditions.


[Bacteriocinogeny in Yersinia enterocolitica]. Bacteriocinogeny was found in 19.8 per cent of Y. enterocolitica strains tested. It was designated by the authors as enterocoliticacinogeny and the substance produced by the pathogen was named enterocoliticacine. Bacteriocinogeny was found among the collection strains isolated in the South Primorye and not among the strains isolated abroad. Some cultures of Y. enterocolitica isolated abroad and in the South Primorye were used as indicator strains for revealing enterocoliticacinogeny. Enterocoliticacine inhibited growth only of some strains of Y. enterocolitica and had no inhibitory effect on growth of Coli bacteria, plague and pseudotuberculosis microbes. The latter 3 bacterial species did not inhibit growth of the causative agent of gastric yearsiniosis, which may be of some diagnostic importance. The diverse spectrum of enterocoliticacine and the character of inhibition of sensitive culture growth are indicative of the presence of several types of bacteriocines in Y. enterocolitica.


[Effectiveness of prodigiozan in the therapy of chronic nonspecific diseases of the lungs]. The efficiency of the Soviet prodigiozan in therapy of chronic non-specific diseases of the lungs (18 cases with bronchial asthma and 26 cases with chronic pneumonia of the 1st and 2nd stages) in the phase of exacerbation was studied. The results of the treatment were estimated by the clinico-roentgenological pictures. The effect of prodigiozan on breathing and the functional state of the adrenal gland was studied in particular. Satisfactory results were obtained in the patients suffering from chronic pneumonia of the 1st and 2nd stages without clinical signs of the bronchial tree affection and in the patients with infection-allergic forms of bronchial asthma. Modest results were observed in the patients suffering from chronic pneumonia of the 1st and 2nd stages with the bronchial tree affection, especially when exacerbated by the asthma syndrome. In some patients the results of the treatment with prodigiozan were not stable. Prodigiozan improved the bronchial permeability, stimulated the sympatho-adrenal system and had no effect on the adrenal cortex.


[Dynamics of the antibiotic sensitivity of the staphylococci in suppurative, inflammatory foci in patients during the period of the hospital stay]. The dynamics of staphylococci sensitivity to antibiotics in purulent foci of 242 in patients was studied. Two criteria were used for estimation of the above process, i.e. (I) sensitivity to the antibiotics of the whole staphylococcal population isolated and (2) sensitivity to the antibiotics of separate strains isolated from the population. In 10 or more days the number of the in-patients with staphylococci resistant to streptomycin, monomycin or oxacillin in the purulent foci increased. The number of the in-patients with penicillin, neomycin or chloramphenicol resistant staphylocci was statistically doubtful. The average number of the antibiotic resistant microbial cells in the staphylococcal populations of the foci in the patients during their stay in the hospital increased 2-4 times.


[Comparative clinical electroencephalographic study of cycloserine and terizidon tolerance]. The aim of the study was comparative investigation of cycloserin and terizidone tolerance by patients with the lung tuberculosis. The investigation procedure included parallel clinical observations and electroencephalographic studies (EEG) using light and sonic stimulation. Sixty six and 26 patients treated with cycloserin and terizidone respectively were observed. The results of the studies showed that by the mechanism of their action on the central nervous system terizidone and cycloserine were similar and increased the general reactivity of the brain. However, terizidone promoted an increase of the activating effect of the ascending part of the reticular formation of the brain stem to a lesser extent than cycloserine. Terizidone in a dose of 0.25 g 3 times a day was well tolerated by the patients with concomitant psycho-neurological impairements.


Tumor angiogenic factor and human skin tumors. A transparent acrylic hamster cheek-pouch chamber was used to investigate the elaboration of a tumor angiogenic factor (TAF) by human cutaneous neoplasms; direct tumor implantations, transfilter diffusion, and soluble tumor extracts were used in the study. A diffusible and filterable TAF was extracted from cutaneous tumors and produced distinctive patterns of sequential vasodilatation, tortuosity, and neovascular proliferation in the cheek-pouch membrane. Malignant human neoplasms (eg, melanoma, basal cell epithelioma, squamous cell carcinoma, lymphoma) produced striking neovascularization; vascular tumors (eg, Kaposi sarcoma, pyogenic granuloma, vascular histiocytoma) stimulated dramatic hyperemia and ectasia. Angiogenesis was conspicuously absent after implantation of control materials and nevoid or normal cutaneous components (with the exception of epidermis). Tumor angiogenic factor appears to induce direct stimulation of endothelial cell mitosis and may be essential for survival of nutritionally ravenous neoplastic tissues. The interference with TAF has therapeutic implications.


Lupus erythematosus profundus following thrombocytopenic purpura. A patient with thrombocytopenic purpura subsequently exhibited skin lesions of lupus erythematosus profundus, serositis, and serum antinuclear antibodies. Immunoglobulins and complement were found in the dermoepidermal junction of active skin lesions. Also of note was the presence of possible systemic lupus erythematosus in his mother.


Uses for immunofluorescence tests of skin and sera. Utilization of immunofluorescence in the diagnosis of bullous diseases, lupus erythematosus, and certain other dermatoses. Sera and frozen biopsy specimens taken for immunofluorescence can be of diagnostic value in studies of vesiculobullous eruptions and connective tissue diseases. Appropriate handling of specimens is important. In cases of pemphigus and pemphigoid, findings of typical antibodies in sera and immunoglobulin deposits in skin sections serve to establish the diagnoses. Fluctuations in titers of pemphigus antibodies afford a prognistic guide. IgA deposits at the dermoepidermal junction in patients with vesiculobullous eruptions are diagnostic of dermatitis herpetiformis. Elevated titers of antinuclear antibodies, frequently with a peripheral pattern, and DNA antibodies as well as junctional deposits of immunoglobulins or complement or both in the apparently uninvolved skin are highly characteristic of systemic lupus erythematosus, more or less typical patterns of immunoglobulin and complement deposits in the lesion appear in discoid lupus erythematosus, porphyrias, and some other dermatoses.


Controlled double-blind comparative trial with fluprednylidene acetate cream and its base. The effect of combined therapy with fluprednylidene acetate cream applied once daily plus cream base of the same formulation twice daily was tested in controlled double-blind contralateral investigations carried out on 31 in-patients with skin diseases which react to corticoids. Comparison with the 3 times daily application of the cream containing fluprednylidene and the 3 times daily application of a cream containing betamethasone 17-valerate did not show any differences in the result of treatment which was good to very good in each case within a 15-day trial period. No side effects were determined. The combined treatment with fluprednylidene acetate cream (once daily) and the cream base of the same formulation means that by economising on the use of the corticoid the risk involved in treatment is reduced and a therapeutic concept can be propounded which is suitable for all individual circumstances because the cream base used is kept constant.


Evidence for a neuromuscular disorder in methylmercury poisoning. Data suggestive of a neuromuscular disorder responsive to neostigmine was uncovered in the course of electrophysiological testing of Iraqi patients poisoned by methylmercury. Subsequent neostigmine therapy produced a remarkable clinical improvement of the patients. Placebo substitution resulted in a substantial loss of testable strength that was restored when drug therapy was resumed.


Stability of normal human fecal flora during a chemically defined, low residue liquid diet. Ten adult male volunteers (medical students) subsisted for seven days upon a chemically defined, low residue liquid diet, and consumed 1200-1800 calories per day. All stools were collected; three were cultured within the hour-a prediet stool, one collected on the seventh day, and a postdiet stool. Specimens were diluted anaerobically, and anaerobic cultures were streaked upon plates of prereduced agar media and incubated in Brewer jars. During the low residue diet, total fecal mass was relatively small and each subject passed only two or three stools. The mean reduction in daily fecal output was 70%. Mean counts of total aerobes were 10-7/gm throughout the study, and mean counts of total anaerobes were 10-10/gm. There was no overgrowth by opportunistic bacteria or fungi. The low residue food did not alter fecal flora; there was neither disappearance nor reduction of any bacterial group.


Pyeloureterostomy reconstruction in human renal transplantation. Pyelouretersotomy or ureteroureterostomy was the urinary tract reconstructive procedure in 114 of 132 consecutive renal transplants performed at the Massachusetts General Hospital from September 1967 to December 1973. Anastomotic leakage was the only complication related to failure of pyeloureterostomy or ureteroureterostomy. This occurred in nine transplants (7.9%). Since 1970, only four anastomotic leaks have occurred in 79 consecutive pyeloureterostomies or ureteroureterostomies. Six of the nine primary anastomotic leaks were corrected either by retrograde ureteral catheter drainage or re-suturing of the anastomotic defect. Only one patient died as a result of complications following a leak. The operative technique is described with emphasis on the important details believed necessary for consistent success in performing this procedure.


Pneumonectomy by "en masse" stapling of hilar vessels. Since the development of automatic surgical stapling instruments in the Soviet Union in the 1950s and their description in the American literature in 1961, American surgeons have used them for a variety of pulmonary resections. However, there is no account of their use in this country for pneumonectomy by "en masse" stapling of the hilar structures. We have used this whenever it was applicable in 41 consecutive pneumonectomies since 1967. There were 2 postoperative deaths, 1 due to pulmonary embolism and the other to myocardial infarction. There were no complications attributable to the operative technique used. The only empyema developed nine months postoperatively and was not accompanied by bronchial fistula. Cancer-free survival was 43% at two and one-half years and 33% at five years. The technique of en masse stapling of hilar vessels renders pneumonectomy easier, safer, and faster than the technique of individual ligation.


The spectrum concept of schizophrenia. Problems for diagnostic practice. The spectrum concept of schizophrenia posits that a number of psychopathologic states, both psychotic and nonpsychotic, may share some genetic basis with schizophrenia, and may therefore constitute, together with schizophrenia itself, a genetic spectrum of schizophrenic disorders. While this is a valuable and promising research concept, its application to diagnostic practice could broaden the boundaries of schizophrenia to include patients with other conditions, thus rendering a larger population at risk for the untoward effects of the schizophrenia disgnosis itself. This may have already occurred in the Soviet Union, where a diagnostic system derived from a variant of the spectrum concept is used in routine diagnostic practice. The adoption of a spectrum-based diagnostic system should await further research on the boundaries of the spectrum, and more detailed descriptions of confirmed spectrum states.


Sex research and social change.

Sex research and social change. The history of scientific sex research which emerged at the turn of the century with the exemplary work of Sigmund Freud and Havelock Ellis has been complexly interactive with changing general social conditions, specific trends in sexual conduct, the content of sexual ideologies, and the developing techniques of scientific inquiry. The earliest sex researchers, although serving to bring sexuality out of the Victorian cold and into the center of human development based their views of sexuality on control-repression and drive models. The Freudian tradition was especially influential in general intellectual matters and was probably the most important in the development of twentieth-century sexual ideologies. Beginning in the 1920s and culminating in the work of Kinsey in the 1940s and 1950s, a tradiition of social bookkeeping began focusing on the sexual behavior of relatively normal persons. Methodologically such studies moved away from the case history and from populations who were defined as criminal or neurotic. At the same time, general social changes were occurring that were directly affecting the rates and directions of sexual conduct in the society. The work of Alfred Kinsey charted these changes and in turn influenced public attitudes, public policy, and research interests during the 1950s and 1960s. The work of other researchers began to fill in the picture of sexual conduct in the society from a survey point of view, and some workers began studies in sexual deviance that focused anew on homosexuality and prostitution. The work of William Masters and Virginia Johnson served to open the door to studies of sexual anatomy and physiology by applying well-known techniques to the laboratory study of the sexual. While the biological tradition is still strong in the discussion of the sexual, new emphases are being placed on a cognitive-social learning persepctive that emphasizes the nonbiological factors in sexual development. Major changes have occurred in the sexual backdrop of the society in the 1960s, and while changes in sexual conduct have been less than revolutionary, they have occurred in a number of areas (contraception, abortion) that have directly influenced societal practices. Sex research and the sex researcher have played an important role in providing benchmarks for sexual practices, illuminating general understanding, and providing the content for ideiolicaal debates about the right and wrong of sexuality in the society. In few areas of research have researchers had such an important role in the debate over the measning and significance of the behavior they have studied.


Molecular pathogenesis of systemic lupus erythematosus. The study of patients with systemic lupus erythematosus revealed the close association of the disease with measles--or a related virus. High titres of antibodies to measles virus were found in patients that correlated with the course of the disease. Immunofluorescence tests revealed measles virus or a related antigen in lupus-affected tissues. Inclusion bodies consisting of paramyxovirus-like ribonucleoprotein structures were regularly detected in both affected tissues and leukocytes. Molecular hybridization of measles virus RNA with DNA from the affected tissues showed that DNA transcripts of measles or a closely related virus are integrated in the cellular nuclear DNA. Possible pathogenetic mechanisms of the disease are discussed.


Early events in myxovirus replication: immunofluorescent spots. Indirect immunofluorescent staining of Ehrlich ascites tumor cells infected with two influenza A strains, WSA (HON1) and TUR (Hav1 Nav3), revealed early fluorescent spots which became detectable in the cytoplasm within 30 minutes of infection, before the nucleoprotein antigen appeared in the nucleus. These spots seemed to be linked to some structural antigen of the virus not identical with hemagglutinin, neuraminidase, or nucleoprotein. Their formation was not inhibited by actinomycin, p-fluorophenylalanine or amantadine in concentrations sufficient to block viral replication; amantadine led to an altered time course of spot evolution and to the emergence of coarser spots. The exact serologic specificity of early spots remains to be worked out but appears to differ from that of known influenza A antigens.


The lens.

The lens. The subjects to be reviewed are as follows: (1) Anatomy, histology, and pathology. (2) Genetic and congenital anomalies. (3) Cataract. (Under cataract we shall consider the following: incidence and prevention of blindness from cataract; formation of an experimental production of cataract; cataract related to ocular and systemic disease; cataract related to medication, trauma, and radiation; medical treatment of cataract; cataract surgery; complications of cataract surgery; optical correction of aphakia.) (4) Exfoliation syndrome.


Current management of non-Hodgkin malignant lymphoma of the head and neck. Older nomenclature for non-Hodgkin malignant lymphoma has undergone revision to more accurate terminology based on cytology and histological pattern. Presentation of non-Hodgkin malignant lymphoma above the supraclavicular fossa demands through investigation to rule out occult disease in bone marrow and the intra-abdominal space. This is accomplished by appropriate clinical evaluation including lymphangiogram and exploratory laparotomy. However, the value of exploratory laparotomy for staging on increased survival rates in non-Hodgkin malignant lymphoma of the head and neck has not been established.


Transsternal radical neck dissection. Postoperative complications and management. In 1962, Sisson et al reported the use of the transsternal radical neck dissection for carcinoma recurring in the peristomal area after laryngectomy. We have performed over 50 transsternal radical neck dissections in the past 14 years. A significant number of early cases succumbed to the postoperative problems of fistula, infection, and large vessel rupture. Our two cases illustrate intraoperative and postoperative complications. Management of these complications is discussed. Morbidity and mortality has decreased as we have gained experience in the management of these problems.


Repair of extended laryngotracheal stenosis. The most challenging laryngotracheal stenosis are those that exceed 5 cm in length and involve more than one area of the larynx and trachea contiguously. A successful technique for the repair of these injuries with a three-stage laryngotracheal trough was created followed by anterior tracheal wall replacement with a skin-Marlex-muscle pedicle flap.


Surgical repair of facial nerve branches. An analysis of different sheathing and suturing techniques. The distal branches of the facial nerve are sometimes severed in various forms of trauma. These distal branches respond to repair differently than do the main trunk or other peripheral nerves. Actual axon counts must be done to determine the percentage of regrowth rather than measuring nerve diameter. Physiologic and histologic techniques were used to analyze sheathing and suturing techniques in the repair of facial nerve branches in rabbits. Repair sites were examined at various intervals up to four months after repair. Very small suture material (10-0) must be used. Vein sheaths caused decreased axon regrowth, and strictures occurred when silicone elastomer sheaths were used. Seven stitches provided the best results in terms of axon regrowth, prevention of neuromas, and return of function. Three sutures or a continuous stitch produced poorer overall results.


Modified nondelayed forehead flap.

Modified nondelayed forehead flap. The versatility and benefit of the forehead flap need not be lost when the external carotid artery system has been ligated. By basing the forehead flap laterally on the scalp, nourishment from the opposite external carotid artery gives the head and neck surgeon another advantage in reconstruction with nondelayed expedience. We report three cases of wide cheek ablative surgery, external carotid ligation, and utilization of the forehead flap. The occasions to use this modified nondelayed forehead flap are few, but it offers the same advantage without staging. It definitely can be used in any situation requiring a forehead flap when the external carotid artery system has been ligated.


Incus window in transposition.

Incus window in transposition. In aiding the positioning of the incus in incus transposition, a hole, the incus window, is drilled completely through the body of the incus. Through the window the surgeon has a visual as well as a tactile reference to the head of the stapes. At one year results show that 182 of 201 patients closed the air-bone gap to within 20 dB of the preoperative bone level.


A quantitative study of the effect of endotoxin on embryonating chicken eggs. A quantitative study of the effect of endotoxin on embryonating chicken eggs revealed the importance of several variables. In the study, the chorioallanotic membrane was detached (i.e.,dropped) from the eggshell membrane on the 9th and 11th incubation days. Various doses of endotoxin in various amounts of diluent were applied on the dropped membrane on the 11th day. Embryo deaths were greater when the membrane was dropped on the 11th day. Within the limits of our trial, the variables were, in decreasing order of significance: 1) the day the membrane was dropped; 2) the amount of endotoxin applied; and 3) an interaction between 1 and 2. The volume of diluent had no significant effect on mortality. The importance of these variables is discussed with reference to the design of additional experiments with endotoxin.


An outbreak of type-C botulism in three-weeek-old broilers. Botulism was diagnosed in 3-week-old broilers from clinical signs, absence of postmortem and histopathological lesions, and demonstration of toxin in the serum of comatose birds. Passive immunization of mice with Clostridium botulinum type-C antitoxin protected against a challenge with serum from comatose birds containing the Cl. botulinum toxin. Total mortality for the grow-out period exceeded 27% and was not altered by water medication with penicillin. Bacitracin at 100 g per ton reduced mortality to 5-7 birds per day.


Plastic embedding of avian tissues for diagnostic histopathology. A series of photomicrographs show the histologic features of avian tissues embedded in plastic and sectioned on glass knives. The techniques described gave superior resolution, less cell shrinkage, and fewer sectioning artifacts than sections prepared with conventional paraffin methods.


Direct immunofluorescent technique in diagnosis of experimental salmonellosis of turkeys. Young turkey poults were experimentally infected with Salmonella heidelberg to evaluate the standard tube agglutination test (TAT) and direct fluorescent antibody test (DFAT), and to correlate results of these procedures with the spread pattern of the organisms in the feces using conventional culture procedures for the detection and isolation of S heidelberg from cloacal swabs. The DFAT test detected fecal excretors considerably longer than bacterial isolation and gave better results. The cultural method was not the most reliable and sensitive method, especially when compared with the DFAT. All control birds remained negative bacteriologically serologically, and with the DFAT during the observation period.


[Pivampicillin and ampicillin in experimental E. coli pyelonephritis]. The antimicrobiol activity of 6-[D(--)-alpha-aminophenylacetamido]-penicillanic acid-(pivaloyloxymethyl)-ester (privampicillin) was tested in comparison to ampicillin during the acute ascending pyelonephritis of the rat caused by E. coli. Two groups of rats were treated with different drug concentrations; group I:3 times 70 mg/kg/day pivampicillin and 3 times 50 mg/kg/day ampicillin, group II: 3 times 70 mg/kg/day pivampicillin and 3 times 150 mg/kg/day ampicillin; controls were inoculated three times daily with 1.0 ml physiological saline. A higher activity of pivampicillin was found in the first group as proved by bacterial counting in the left and the right renal parenchyma as well as in the urine. In the second group the efficacy of ampicillin was increased.


[Cellular kinetics of the primary immune response after application of phytohemagglutinin]. The Jerne technique, a proved method for detecting the number of plaque-forming cells (PFC) in spleen, shows an immunosuppressive effect of phytohemagglutine (PHA) on primary immune response. Kinetic studies are done on 300 NMRI mice, considering the number of PFC/10-8 spleen cells. Significant suppressions of the primary immune response are found if PHA is applied either one day before or together with antigen provided that studies are done 3, 4 or 5 days after immunization with sheep red blood cells (SRBC). The role of activated T-lymphocytes concerning the diminution of immune response is discussed.


[Clinical study on five depot neuroleptics.  Comparison of effective profiles of fluphenazinedecanoate, fluspirilene, penfluridol, perphenazine-enanthate and pipothiazinepalmitate]. Five depot neuroleptics (fluphenazinedeconoate, fluspirilene, pipothiazinepalmitate, penfluridol and perphenazine-enanthate) were compared based on clinical trials in subacute and chronic schizophrenic patients.  The psychopathological symptoms were documented by means of the AMP-system.  Statistical analyses showed several differences between the effects of the five substances.  The AMP-system proved a useful instrument to differentiate similar drugs.


Intermediate coronary care. A controlled trial. A controlled trial of intermediate coronary care was carried out over a five-year period at a district general hospital. One thousand male patients under 65 were allocated at random into a group kept in the same ward as the coronary care unit (CCU) and a control group discharged from the CCU to a general medical ward. The intermediate care patients were nursed by the CCU staff, resuscitation equipment was immediately available and there was an efficient emergency call system. The mortality was the same in both groups and no more patients survived cardiac arrest to leave hospital in the intermediate care group than among the controls, though initial resuscitation was more often successful. The failure of intermediate coronary care was attributed to the rarity of primary ventricular fibrillation after discharge from the CCU.


Maximal intestinal absorption of digoxin, and its relation to steady state plasma concentration. In a group of 8 volunteers, peak plasma digoxin concentrations and areas under 80-hour plasma concentration curves were significantly greater after 1 mg digoxin in paediatric elixir than after 4 0,25 mg tablets. Mean cumulative urinary excretion of digoxin over 12 days was 46.4 per cent after tablets, 53.6 per cent after elixir, and 70.8 per cent after intravenous injection. Mean percentage absorption was estimated to be 63 per cent from tablets and 75 per cent from elixir, but considerable between-subject variation was noted. Individual estimates of percentage absorption were significantly correlated with plasma concentrations in the steady state. Computer programmes to relate steady state plasma concentration to oral digoxin dosage take no account of absorptive capacity, are limited to gross approximations, and cannot replace determination of plasma concentration to assess the degree of digitalization.


Fluorescence energy transfer between ligand binding sites on aspartate transcarbamylase. The method of fluorescence energy transfer is used to measure the distances between several sites on aspartate transcarbamylase. Both fluorescence steady-state and lifetime techniques are used. When the tryptophans on the catalytic subunit are the fluorescent donor groups, either pyridoxamine phosphate, covalently bound to an amino group at the active site, or 8-anilino-1-naphthalenesulfonate, noncovalently bound at the active site, is the acceptor group. The distance between tryptophan and the active site is calculated to be 2e A assuming that the fluorescence of only one tryptophan per catalytic polypeptide chain is quenched by the acceptor or 27 A assuming that both tryptophans on a catalytic chain are equally quenched. The pyridoxamine phosphate label is also used as the fluorescent donor with mercurinitrophenol bound to the sulfhydryl group of the catalytic subunit as the energy acceptor. For this pair of labels the active site is determined to be very close to the sulfhydryl group on the same catalytic chain and 26 A from the sulfhydryl groups on the other chains of the catalytic trimer. In experiments with pyridoxamine phosphate at the active site as the donor and 8-anilino-1-naphthalenesulfonate at the active site as the acceptor, a distance of 26 A between active sites of a catalytic trimer is found. No energy transfer is observed from pyridoxamine phosphate at the active site to a fluorescamine derivative of cytidine 5'-triphosphate at the regulatory site. This implies that these groups are separated by at least 42 A in the native enzyme. All of the distances are calculated using the assumption of rapid rotation of donor and acceptor dipole moments relative to the donor fluorescence lifetime. Fluorescence polarization measurements suggest this assumption does not produce a significant error in the calculated distances. The distances between the various sites are related to the subunit structure of aspartate transcarbamylase.


The quaternary structure of citrate synthase from Escherichia coli K12. A combination of equilibrium ultracentrifugation and polyacrylamide gel electrophoresis techniques has been used to establish the quaternary structure of citrate synthase from acetate-grown Escherichia coli K12 3000. In polyacrylamide gels containing 0.1% sodium dodecyl sulfate (SDS), the pure enzyme showed one major band whose mobility was consistent with a molecular weight of 46,000 plus or minus 2000 g/mol, and a little material of 87,000 plus or minus 5000 g/mol. When first cross-linked with dimethyl suberimidate and then submitted to electrophoresis in SDS, citrate synthase showed six bands, in widely different amounts, whose apparent molecular weights were almost integral multiples of 47,000 g/mol. The dimer was the major product of the cross-linking procedure. In 6 M guanidine HCl at pH 7.0, citrate synthase behaved as a single component in high-speed sedimentation equilibrium experiments, with a weight average molecular weight of 43,400 plus or minus 300 g/mol. The molecular weight of native citrate synthase was investigated by high-speed sedimentation equilibrium ultracentrifugation under different conditions of pH and KCl concentration. In 0.02 M Tris-Cl at pH 7.0 and 7.8, the enzyme was a mixture of oligomers, with species ranging from monomer (47,000 g/mol) to greater than decamer being present. At pH 9.0, only dimer was seen (94,000 g/mol). Large aggregates were present at pH 10.0. The addition of small amounts of KCl, a potent activator of the enzyme, simplified the mixture of oligomers considerably at pH 7.8. A detailed analysis of the data with 0.05 M KCl indicated that dimer and hexamer were the only species present, with marked nonideality. Increasing the KCl concentration to 0.10 M converted all the enzyme to hexamer. The amino acid composition of E. coli citrate synthase was presented. Taken together with peptide mapping experiments of others (J. A. Wright and B. D. Sanwal (1971), J. Biol. Chem. 246 1689), it indicates that the subunits have all the same or very similar amino acid sequences. The dansylation method revealed only methionine at the N-termini of the citrate synthase polypeptide chains. Citrate synthase from E. coli thus resembles the enzyme from eukaryotes in that it consists of subunits weighing just under 50,000 g/mol, although these subunits are more highly aggregated in the bacterial enzyme under most conditions. This conclusion is in disagreement with that of Wright and Sanwal (1971, see above), who reported a subunit size of 62,000 g/mol.