[Mature benign teratomas with malignant tumors and malignant monodermal ovarian teratomas. Anatomo-clinical presentation of 10 cases]. The clinicopathologic features are presented of 8 malignant neoplasms occurring in adult teratomas, and of 2 malignant monodermal teratomas found in a continuous series of 1029 cases of ovarian adult teratomas. The age of the patients was 44--76 years. The first 8 observations included 6 epidermoid carcinomas, 1 undifferentiated carcinoma and 1 strumal carcinoid. In the epidermoid carcinomas malignancy was recognized peroperatively only in three instances. One tumor had infiltrated the broad ligament on one side and another the urinary bladder. The neoplasm appeared as a mass which thickened the wall of a typical dermoid cyst. Four patients died of the tumor from 3 months to 1 year after operation; one is alive more than 19 years later and one is lost to follow-up. The crucial factor in prognosis is the integrity of the ovarian capsule. The undifferentiated carcinoma, which had infiltrated the pelvic walls, could only be incompletely resected and caused death within 3 1/2 months. The strumal carcinoid was discovered by chance during laparotomy for a far-advanced adenocarcinoma of the pancreas which led to death within 2 months. The two cases of malignant monodermal teratoma comprised 1 thyroid papillary carcinoma and 1 carcinoid. Both patients are alive more than 8 and 5 years after operation. The carcinoid manifested itself by persistant diarrhea which ceased soon after operation and did not recur subsequently.


[Severe hemolytic anemia after mitral valvuloplasty]. A patient with mitral insufficiency is described who developed severe hemolytic anemia six months after mitral valvuloplasty. Various laboratory tests suggested that the cause of the hemolysis was mechanical. A second heart operation was therefore performed which revealed intact valve function. In view of the mechanical cause of hemolysis a bioprosthesis was implanted but the patient died shortly after this operation. Since similar cases are not found in the literature the authors invite discussion of the course in this case.


[Near-drowning in children].

[Near-drowning in children]. From 1971 to 1977 a total of 32 nearly-drowned children were admitted to the University Pediatric Hospital, Berne, and the Children's Hospital, Lucerne. 5 died within 15 h to 10 days. Neurological damage was seen in 5 cases. 20 children were under 5 years of age and only 8 over 7 years. All cases with fatal consequences or severe cerebral sequel had cardiac arrest on admission. A maximal possible submersion time for survival without consequences has not been found. The pathophysiology of fresh water drowning and current treatment are summarized. Situations leading to near drowning are specified and some aspects of prognosis discussed.


[The echocardiogram in mitral anulus calcification]. In agreement with the known high incidence of mitral anulus calcification in elderly patients, the authors have found corresponding calcifications in echocardiographic examinations in 61 patients as the single or additional cause of an abnormal systolic or diastolic murmur. The intracardiac calcifications were known of from the chest X-ray only in 6 patients. The echocardiograms served to locate and estimate the amount of the calcification. Calcifications of the aortic cusps, found in 75% of patients, may be of degenerative origin. The echocardiographic presentation of the degenerative calcifications can be misinterpreted either as postrheumatic valvular disease, posterior pericardial effusion or hypertrophic cardiomyopathy. Registration by continuous sector scan was necessary to differentiate these entities.


[Kirner's deformity: an isolated malformation of the third phalanx of the little finger]. A typical growth deformity of the third phalanx of the 5th finger known in the literature as "Kirner's deformity" has been observed over 5 years in 4 patients (there are now 5 patients) at the Clinic for Hand Surgery in St. Gall. Almost all reports (39 cases) are in the English-language literature. It is felt that apart from esthetic problems functional deficiency is of considerable relevance, and the only existing therapy mentioned in the literature (osteotomy) has been supplemented by localized partial epiphysiodesis by microsurgical operative technique.


[Dissociation of human factor VIII and recombination of the fragments VIII-C and VIII-AG]. Human factor VIII has been dissociated into fragment VIII-C and fragment VIII-AG in the presence of calcium chloride (0.25 M). After removing the calcium, recombination of the molecule is obtained. Fragment VIII-C can be activated by thrombin in a similar manner to the coagulant activity of whole factor VIII. This activation is calcium-dependent. In rabbits immunized against purified F VIII, VIII-C and VIII-AG specific antisera against these three entities were obtained.


[Sacroiliac changes, HLA-B27 negative, in primary hyperparathyroidism and osteomalacia]. Radiological sacroiliac (SI) changes were found in 3 patients, 2 with primary hyperparathyroidism (1 also with associated chondrocalcinosis) and 1 with osteomalacia. Osteomalacia was due to celiac disease. None of the 3 patients, all females, had a history of psoriasis, urethritis, iritis or chronic colitis. There was no renal function impairment. Peripheral joints were affected in the patient with associated condrocalcinosis. HLA B 27 was negative in all cases. Low back pain and vertebral stiffness were present in the patient with osteomalacia. A dramatic improvement in pain and stiffness ensued after vitamin D injections. These SI lesions, which may simulate ankylosing spondylitis, were attributable to subchondral bone changes related to the metabolic bone diseases. In the case of osteomalacia the SI lesions were predominantly on the right side, where there was a Looser's zone on the ischial ramus suggesting that pseudofractures could be a cause of SI changes. Metabolic osseous diseases such as osteomalacia or primary hyperparathyroidism should be investigated in cases of HLA B 27 negative radiological "sacroiliitis".


[Clinical pathology of colonic mucosal polyps]. Of 636 polyps removed during endoscopy between 1973 and 1975 at the University Hospital, Zurich, 36 (5.5%) were of the hyperplastic and 18 (2.8%) of the juvenile type. One polyp was seen in a female patient with Peutz-Jeghers syndrome. The vast majority of the polyps (581, 91.5%) were neoplastic in origin; 70% were tubular adenomas, 16% villous adenomas, and 14% intermediate forms or tubulo-villous adenomas. On the basis of a continuous spectrum in histologic structure and similar cellular dedifferentiation, these three types of adenoma may be viewed as different forms in the development of the same neoplastic process. Hyperplastic and hamartomatous polyps are innocuous, whereas the neoplastic forms may well turn aggressive. Malignant change was observed in 5.1% of our material, particularly in villous adenomas and in polyps exceeding 1 cm in diameter. The presence or absence of invasive growth through the muscularis mucosae is of prime importance for therapy. In accordance with WHO nomenclature, the term carcinoma is used only in the presence of such infiltration. If, in addition, the tumor tissue is not well differentiated, additional segmental resection may be required. The term "focal carcinoma" is no longer in use and has been replaced by "severe focal atypia". In these cases, primary polypectomy for diagnostic purposes is also the optimal therapy, and is as effective here as in cases of benign adenoma.


Dynamics of skeletal pattern formation in developing chick limb. During development of the embryonic chick limb the skeletal pattern is laid out as cartilaginous primordia, which emerge in a proximodistal sequence over a period of 4 days. The differentiation of cartilage is preceded by changes in cellular contacts at specific locations in the precartilage mesenchyme. Under realistic assumptions, the biosynthesis and diffusion through the extracellular matrix of a cell surface protein, such as fibronectin, will lead to spatial patterns of this molecule that could be the basis of the emergent primordia. As cellular differentiation proceeds, the size of the mesenchymal diffusion chamber is reduced in descrete steps, leading to sequential reorganizations of the morphogen pattern. The successive patterns correspond to observed rows of skeletal elements, whose emergence, in theory and in practice, depends on the maintenance of a unique boundary condition at the limb bud apex.


Nonpneumonic, short-incubation-period Legionellosis (Pontiac fever) in men who cleaned a steam turbine condenser. Pontiac fever affected ten men who had cleaned a steam turbine condenser with compressed air. Previous epidemics of Pontiac fever and Legionnaires' disease--both caused by Legionella Pneumophila (proposed sp. nov.)--involved "airborne spread" from air-conditioning cooling towers or evaporative condensers. Aerosols of contaminated water in heat-rejection systems appear to be important sources of epidemic legionellosis.


4-aminobutyrate:2-oxoglutarate aminotransferase in blood platelets. Platelet lysates obtained from blood of humans, dogs, and rats catalyzed the transamination of 4-aminobutyrate with 2-oxoglutarate as cosubstrate. Human platelet 4-aminobutyrate:2-oxoglutarate aminotransferase (36.5 +/- 3.2 picomoles per minute per milligram of platelet protein) resembled the brain enzyme in kinetic properties and in response to cofactors and inhibitors.


Development of the rat's uncrossed retinotectal pathway and its relation to plasticity studies. In the normal newborn rat the retinotectal pathway from each eye distributes across the whole area of both the ipsilateral and contralateral superior colliculus. Most of the ipsilateral projection retracts during the first ten postnatal days to produce the normal adult pattern, but retraction fails to occur if one eye is removed at birth.


Synaptic proteins after electroconvulsive stimulation. Quantitative immunoelectrophoresis of rat brain synaptic proteins following a series of electroconvulsive stimulations demonstrated changes suggestive of an increase in the number of synaptic vesicles, in a preparedness for glycolytic demands, and a delayed development of a certain area in the brain. The increased synaptic remodeling may be important for the action of electroconvulsive therapy.


Differential behavioral and biochemical effects of right and left hemispheric cerebral infarction in the rat. Following ligation of the right middle cerebral artery, rats were hyperactive for 2 to 3 weeks whether activity was measured by running wheel revolutions or open field observations. Assays of brain catecholamines revealed 30 percent reductions of norepinephrine in the injured and uninjured cortex and locus coeruleus and a 20 percent reduction of dopamine in the substantia nigra. In contrast, rats with left middle cerebral artery ligations did not become hyperactive and did not show any significant change in catecholamines in any of the brain areas studied. Right and left hemispheric infarctions were comparable in their locations and extent of tissue damage. This lateralization of behavioral and biochemical response to cerebral infarction may be the consequence of anatomical or physiological asymmetries in the brain.


Differences in neural organization between individuals with inverted and noninverted handwriting postures. Levy's hypothesis that movements of the distal musculature are controlled by ipsilateral motor projections in subjects with inverted writing posture was tested in a reaction-time experiment with lateralized auditory, tactual, and visual stimulation. Subjects were required to depress a response key with the left or right index finger when they detected a stimulus in either the left or right sensory field. Writers with noninverted posture responded quickest to stimuli on the same side as the responding hand in all modalities tested, whereas inverted writers showed this pattern only in auditory and tactual modalities. In the visual modality, they responded quickest to stimuli on the side opposite the responding hand. Because Levy's hypothesis predicts the latter effect in all modalities for inverted writers, it is challenged by our results, which suggest that inverted writers may be characterized by anomalous visual or visuomotor organization.


Delayed neurotoxicity of phenylphosphonothioate esters. Administration of a single oral dose of five phenylphosphonothioate esters produced delayed neurotoxicity in hens; their potency was, in descending order, cyanofenphos, EPN, desbromoleptophos, leptophos, and EPBP (Seven). Histological examination showed that in some hens there was marked axonal and myelin degeneration in the spinal cord and peripheral nerves. The results suggest that delayed neurotoxicity may be a general feature of phenylphosphonothioate insecticides.


Drug discrimination training with progressively lowered doses. Rats were trained to discriminate drug from no-drug conditions in a two-lever operant task. Moderately high dosages were used initially. Whenever the discrimination was learned, training was continued with progressively reduced dosages. Eventually the rats discriminated extremely low doses of phenobarbital, chlordiazepoxide, cyclazocine, and fentanyl.


Superstitious bar pressing in hippocampal and septal rats. Unlike normal animals or those with sham lesions, rats with hippocampal and septal lesions behaved in an operant chamber as if a dependency existed between pellet delivery and their behavior, despite the fact that reinforcement was based on time, not behavior, and was therefore free. This superstitious behavior did not result from a general inability to inhibit responding, as responding rapidly ceased when the pellets were discontinued. These findings suggest that the hippocampus integrates information regarding response-reinforcer relations, which in the normal rat permits superfluous operant behavior to be eliminated.


Metabolic mapping of functional activity in the hypothalamo-neurohypophysial system of the rat. Physiological stimulation of the hypothalamo-neurohypophysial system by salt loading of rats resulted in a dramatically increased glucose utilization in the posterior pituitary but not in the paraventricular or supraoptic nuclei. The good correlation between glucose utilization and neural activity in the posterior pituitary (that is, nerve terminals) contrasted with the lack of correlation in the paraventricular and supraoptic nuclei (that is, the sites of the cell bodies of the same neurons). This difference in the metabolic response to functional activity between the two regions of these neurons can be explained by the differences in surface-to-volume ratios of these regions.


Assessment of diagnostic technologies.

Assessment of diagnostic technologies. A general protocol for rigorous evaluation of diagnostic systems in medicine was applied successfully in a comparative study of two radiologic techniques. Accuracies of computed tomography and radionuclide scanning in detecting, localizing, and diagnosing brain lesions were assessed with a sample of patients in whom tumor had been suspected. The principal means of analysis was the "relative operating characteristic," which is unique in providing a measure of accuracy that is largely independent of decision biases. Computed tomography was found to be substantially more accurate than radionuclide scanning.


Retinotectal projection in goldfish to an inappropriate region with a reversal in polarity. An abnormal, ipsilateral projection was formed by deflecting optic fibers that normally innervate the posterior part of one tectum into the anterior end of the opposite tectum. When anterior recipient tectum was simultaneously denervate, the deflected fibers formed a retinotopic map in this region that was reversed with respect to the anterior-posterior tectal axis.


GABA receptors in clonal cell lines: a model for study of benzodiazepine action at molecular level. A "recptor unit" for gamma-aminobutyric acid (GABA), which includes brainlike receptor binding sites for tritium-labeled GABA and benzodiazepines (diazepam, clonazepam, and flunitrazepam) and a thermostable endogenous protein (GABA modulin) that inhibits both GABA and benzodiazepine binding, has been demonstrated in membranes prepared from NB2a neuroblastoma and C6 glioma clonal cell lines. In these cells, as in brain, diazepam (1 micromolar) prevents the effect of GABA modulin, and in turn GABA (0.oma and, to a lesser extent, the glioma cells represent a suitable model to study the interactions and the sequence of membrane and intracellular events triggered by the stimulation of benzodiazepine and GABA receptors.


Menopausal flushes: a neuroendocrine link with pulsatile luteninizing hormone secreation. Menopausal flush episodes were found to be invariably associated with the initiation of pulsatile pituitary release of luteinizing hormone. This was not accompanied by a significant change in circulating catecholamine or prolactin concentrations. Since pulsatile luteinizing hormone release results from episodic secretion of luteinizing hormone releasing factor by the hypothalamus, these findings suggest a link between the neuroendocrine mechanisms that initiate such episodic secretion and those responsible for the onset of flush episodes.


alpha-Melanocyte-stimulating hormone: reduction in adult rat brain after monosodium glutamate treatment of neonates. Intraperitoneal injection of monosodium glutamate in neonatal rates resulted in a 90 percent loss of alpha-melanocyte-stimulating hormone in hypothalamic and extrahypothalamic areas of the brain, whereas the amount of hormone in the pituitary gland did not change. The dramatic reduction of alpha-melanocyte-stimulating hormone in the brain suggests that is primary source there is the neuronal perikarya of the arcuate nucleus.


Preparing the health professional for community health. An assessment is made of an initial experience of undergraduate and postgraduate preparation increasingly directed to priority areas in community health. It is measured against set objectives, interrelated factors and a WHO viewpoint of target areas.


[The contributions of homeland health services to plural development]. A brief outline is given of the impact of health services on plural development in the self-governing Black states of South Africa. The importance of community involvement and primary health care in the development process is emphasized. The concept of sustained interterritorial co-operation in health matters in Southern Africa provides the only effective means of dealing with problems which ignore political boundaries.


Trends in four major communicable diseases. The official notifications of the Department of Health pertaining to typhoid fever, tuberculosis, poliomyelitis and malaria are reviewed. Major findings of the epidemiological analysis of the data include the need for establishing the exact mode of transmission of typhoid, the need for assessing upper and lower limits of the expected case load in respect of tuberculosis over the next 5--10 years, the demonstration of the dramatic decline in the number of cases of poliomyelitis and the equally dramatic upsurge of malaria in 1977 and 1978. The need for an integrated, responsive and fully co-ordinated epidemiological service for the Republic of South Africa is emphasized.


[The protection of health in a changing environment]. One of the main functions of the Department of Health is to 'take steps for the promotion of a safe and healthy environment'. Air and water pollution, unhygienic conditions, incorrect use of radiation equipment, detrimental working conditions together with injudicious use of consumer products are but a few facets which have to be attended to in this all-embracing brief of the Health Act No. 63 of 1977. This is achieved by giving attention to scientific principles and effective co-operation between central and local authorities as well as the private sector.


Health education--quo vadis?

Health education--quo vadis? Various implications for health education in relation to current approaches to community medicine are reviewed. Health education activities and needs in the Republic of South Africa are surveyed. Suggested solutions to existing problems include the development of more co-ordinated planning and implementation and evaluation of health education programmes. The urgent need for both undergraduate and postgraduate teaching facilities is stressed. It is suggested that the role and services of the South African National Council for Health Education should be reviewed, so that the Council's resources can in future be better utilized.


Effects of metronidazole on certain functions of human blood neutrophils and lymphocytes. The effects of metronidazole at varying concentrations (10(-7)M - 10(-2)M) on certain cellular immune functions were assessed in vitro. Neutrophil chemotaxis to endotoxin-activated autologous serum, random motility and postphagocytic metabolic activity (hexose monophosphate shunt activity, myeloperoxidase-mediated protein iodination and glycolysis) were unaffected. Likewise, metronidazole had no detectable effects on lymphocyte-active E-rosette formation, mitogen-induced DNA synthesis and mitogen-induced protein synthesis.


Rare and unusual manifestations of Crohn's disease with pyoderma gangrenosum and sclerosing cholangitis. Crohn's ileocolitis manifested in 2 Black patients with the exceptionally rare complications of pyoderma gangrenosum and sclerosing cholangitis. It is emphasized that Crohn's disease is very rare in the Black population of sub-Saharan Africa, and, as far as we are aware, no patient with large-bowel involvement has hitherto been reported.


Benign duodenocolic fistula. A report of 3 cases. Duodenocolic fistulae, although often malignant in aetiology, may result from a wide range of relatively benign disease processes. A report is given of 3 patients with benign duodenocolic fistulae, in 2 on the basis of tuberculosis and in 1 after a duodenal ulcer. The subject is reviewed and the ease of management and good prognosis are stressed.


Diagnosis of upper gastro-intestinal lesions by endoscopy, cytology and biopsy. A prospective consecutive series of 210 upper gastrointestinal endoscopic procedures, at which material for both cytological and histopathological examination was obtained, was conducted at Baragwanath Hospital. The purpose of the study was to determine the respective and combined diagnostic value of endoscopic visualization, cytological brushings and histological sections in benign and malignant lesions of the oesophagus and stomach; and in particular to assess the contribution, if any, of exfoliative cytology to the diagnostic regimen. Endoscopic visualization alone was inconclusive or incorrect in 13% of procedures, cytology alone in 9%, and biopsy alone in 12% (the latter 2 figures corrected for adequacy of material submitted). When assessed together, the diagnostic accuracy achieved by all 3 techniques was 99%. The major contribution of cytology was the correct positive diagnosis in 20% of procedures, performed on patients with malignant lesions, whose initial biopsy specimen was inadequate or normal. It is concluded that for maximal diagnostic accuracy of upper gastro-intestinal lesions, a combined approach, utilizing endoscopic examination, lesion-directed brushings and biopsy specimens, is required.


Infective endocarditis at the Johannesburg Hospital. A retrospective analysis of 40 patients. The records of 40 patients admitted to the Johannesburg Hospital with a total of 44 episodes of endocarditis were analysed. Pyrexia, albeit often low grade and intermittent, was the most consistent physical sign. The classic symptoms and signs of infective endocarditis were uncommon. Blood cultures were positive in 56% of episodes. However, in 6 out of 9 patients with 'culture-negative' endocarditis, infective endocarditis was confirmed at surgery or necropsy. For haemodynamic reasons, 10 patients (25%) were subjected to valve replacement and 1 to a mitral valvuloplasty. In 2 of these the infection was still active at the time of surgery. Five patients (12,5%) died; in 4 the cause of death was neurological and in the remaining patient the aortic valve ruptured and he died within 30 minutes.


[The effect of rooibos tea on iron absorption]. A study was carried out to determine if rooibos tea (Aspalathus linearis) has a deleterious effect on iron absorption similar to that of ordinary tea (Camellia sinensis). Three groups of volunteers, each consisting of 10 healthy young men comparable with regard to iron status and body dimensions, were studied. After ingestion of 1 muCi 59Fe and 16 mg of elemental iron, group A drank rooibos tea, group B ordinary tea and group C boiled water. Iron absorption was measured 14 days later with a whole body counter. Mean iron absorption after ingestion of rooibos tea, ordinary tea, and water was 7,25%, 1,70% and 9,34% respectively. In contrast to ordinary tea (P less than 0,0001), rooibos tea did not affect iron absorption significantly. The ascorbic acid content of rooibos tea varies between 121,8 and 154,9 mumol/l, depending on the method of preparation. Rooibos tea contains small amounts of iron, magnesium, phosphorus, sodium, chloride and potassium. These findings have practical nutritional and therapeutic implications.


[Muscle injuries].

[Muscle injuries]. A short summary of the most common muscle injuries is given, as well as a classification into three grades with the corresponding treatment. The common problem of shin splints is dealt with, and a possible explanation of the pathology and the treatment thereof is given.


Haematological differences in three population groups. The increased absolute lymphocyte counts of Indians and Blacks in comparison with Whites, observed in a former study, were shown, in a study on blood donors, to occur in women rather than men of these two groups. Neutrophil counts showed no sex differences, but were significantly highest in Whites and lowest in Blacks. Indians of both sexes had significantly higher mean red cell counts, together with smaller red cells, than subjects in the other two groups. In no group was a significant correlation observed between body mass and haemoglobin level.


Cockroaches in relation to bronchial asthma in the Durban area. Thirty patients from the White and Coloured asthma clinics were subjected to skin prick tests with various antigens. Although the house-dust mite was found to be the main offender, 9 of the 30 patients showed a significant reaction to cockroach antigen. It is felt that cockroaches play a role in the pathogenesis of asthma in the Durban area and that this fact should be considered in desensitization programmes.


Systemic histoplasmosis with oesophageal obstruction due to Histoplasma granulomas. Successful treatment with rifampicin and amphotericin B. A patient with oesophageal stenosis caused by Histoplasma granulomas is reported. He was treated with an initial combined course of intravenous amphotericin B and oral rifampicin. Complications included adrenal insufficiency, operative perforation of the oesophagus, amphotericin nephrotoxicity and tuberculosis. The histoplasmosis has not recurred for over 3 years.


Acute confusional states and depression treated with maprotiline mesylate. Report of 4 patients successfully treated in an intensive care unit. Four patients admitted to hospital with multiple injuries developed psychiatric symptoms after an initially favourable response to intensive therapy. Alterations in the level of consciousness and behavioural pattern were observed, associated with the presence of acute depression, possibly endogenous in origin. Within 24--48 hours of intravenous administration of maprotiline mesylate (Ludiomil, Ciba), a tetracyclic antidepressant drug, considerable improvement was noted in all 4 patients, with regard to both the depressive state and the clouding of consciousness. The importance of recognizing psychiatric disorders in severely ill patients in an intensive therapy environment is stressed.


Overwhelming pneumococcaemia 17 years after splenectomy. A case report. We present a case of fulminant pneumococcaemia and disseminated intravascular coagulopathy in a young adult man 17 years after splenectomy. The clinical presentation, laboratory and postmortem findings are discussed. The diagnosis, management and prophylaxis of overwhelming infections in splenectomized patients are reviewed. The advent of pneumococcal and other vaccines could contribute significantly to the successful protection of asplenic patients against certain severe infections.


Osteopetrosis in South Africa. The benign, lethal and intermediate forms. Osteopetrosis is an unusual bone disorder in which the skeleton is radiographically dense. The condition is conventionally subclassified into a benign autosomal dominant adult form and a malignant autosomal recessive variety. Among 14 affected individuals whom we have studied, 4 adults had an intermediate type of osteopetrosis in which serious complications included osteomyelitis, pathological fractures and dyshaemopoiesis. The fundamental biochemical relationship of this disorder with the classic forms of osteopetrosis is uncertain. The osteopetroses must be distinguished from other sclerosing bone conditions which have a different course and prognosis. Sclerosteosis and craniometaphyseal dysplasia, both of which occur in South Africa, are of practical importance in this context.


Prolonged atrioventricular conduction in young children and adolescents. The role of increased vagal tone. Prolonged atrioventricular (A-V) conduction is often an apparently normal finding in children with or without congenital heart disease. The mechanism is probably vagally mediated and appears to be benign in the majority of cases. Eleven children with first-degree and/or second-degree Mobitz type 1 A-V block were studied by intracardiac His bundle electrocardiography with atrial pacing. Six children had congenital heart disease with left-to-right shunts and 5 had normal cardiac anatomy. In all the patients studied, the A-H intervals were longer than normal. Wenckebach periodicity appeared at relatively long cycle lengths, and in 5 of the 6 patients in whom values could be determined, atrioventriculonodal effective and functional refractory periods were prolonged. With atropine and isoproterenol conduction intervals returned to normal. There was no tendency to develop echo beats with atrial extrastimuli, even when A-H intervals became markedly prolonged. The results of this study suggest that vagal tone plays a significant role in the prolongation of A-V conduction, even in congenital heart lesions that are known to be associated with a long PR interval.


A community psychiatric programme for Soweto. Report on a pilot study. A pilot study was done on 50 patients in a community psychiatric programme in Soweto. The organization was based on the principles of mental health consultation and the treatment was based on primary, secondary and tertiary prevention. The role of the multidisciplinary staff is outlined and the role of maintenance pharmacotherapy for the ex-schizophrenic patient is stressed. The efficacy of the programme could be improved by an increase in the staff-patient ratio.


Factors involved in the acceptance of voluntary female sterilization among Indians in Natal. The sociological characteristics of 200 Indian women admitted for voluntary sterilization to King George V and R. K. Khan Hospitals, Durban, were investigated. Factors involved in the decision to be sterilized were analysed, as well as socio-economic motives found to be of major significance in the desire to limit family size. A control group of 200 Indian women, none of whom had been sterilized, was interviewed, and responses revealed a very favourable attitude towards the acceptance of female sterilization once the family is complete.


A new universal anaesthetic circuit using a preferential-flow T-piece. A new co-axial anaesthetic circuit, employing a preferential-flow T-piece which eliminates the need for valves in the circuit, has been designed. Its efficiency has been shown to compare favourably with that of conventional circuits for use in spontaneous respiration and under conditions of controlled ventilation. The proposed system has the advantage of convenience, in that there is no need to disconnect the system from the patient nor from the anaesthetic machine when it is necessary to change from spontaneous to controlled ventilation or should a circle absorber be incorporated within the circuit. The system has been shown to offer lower resistance than the Mapleson A circuit.


Two simple inexpensive photographic methods for viewing ECG-gated radionuclide blood pool images. Although the ECG-gated radionuclide blood pool scan (GBPS) has become an established method for studying regional myocardial wall motion, it is usually performed with the aid of an expensive computer system. A simple, inexpensive method was developed to view gated radionuclide blood images by a film loop and a photographic motion detection (PHOMOT) technique. These techniques were compared with left ventricular cine angiography in 15 patients. Segmental wall movement (78 segments) showed identical results in 92% of cases. In all patients the same diagnosis was arrived at by GBPS and cine angiography. The photographic techniques developed offer a simple screening procedure to reduce cardiac catheterization in patients with suspected abnormalities of left ventricular wall contraction.


The first published chemical analyses of smoke from South African cigarettes. The smoke of 69 brands of cigarettes sold in South Africa in March 1978 was analysed for its content of tar, nicotine, carbon monoxide and carbon dioxide. The average yield of tar per cigarette varied between 30 and 38,5 mg in 27 brands and between 20 and 30 mg in all but one of the other 42 brands. The nicotine yields with one exception varied between 1,0 and 2,40 mg per cigarette and generally correlated well with those of tar (r = 0,75). The yields of carbon monoxide per cigarette generally ranged from about 14 to 32 mg, and those of carbon dioxide from about 50 to 85 mg. The results of this analysis, the first to be published with regard to South African cigarettes, are very disturbing. In particular, the tar yields are unacceptably high by international standards. They demand urgent action including (a) regular cigarette analyses by the Government, and publication of the results by the mass media, especially the SABC; (b) compulsory printing of the results of analyses on every cigarette pack and advertisement; (c) education of the public with regard to the meaning of the analyses; and (d) a programme designed to replace more dangerous cigarettes with less hazardous ones. Most important, all these measures must be implemented within the framework of a really meaningful, systematic, continuous and appropriate campaign aimed at combating the tobacco hazard at every level in all population groups.


Progesterone in obese patients with respiratory failure. Two obese patients with acute respiratory failure are described. Both required mechanical ventilation to reverse the respiratory acidosis. On recovery, the major abnormality was failure of ventilatory response to inhaled carbon dioxide. After oral progesterone (100 mg/day and 20 mg/day, respectively) the slope of the carbon dioxide response line increased from 0,02 to 1,14 I min-1 mmHg-1 and from 0,04 to 1,14 I min-1 mmHg-1, respectively. This was associated with sustained clinical remission in 1 patient.


Intestinal parasitic infestation in urban and rural Xhosa children. A comparative study. Evidence of helminthic intestinal parasites was found in 97,0% of stools of 544 Xhosa schoolchildren living in Cape Town. The commonest parasite was Trichuris trichiura, which infested 89,9% of the children. In contrast, only 9,8% of 387 Xhosa children living in the Tsolo district, Transkei, had evidence of intestinal parasites in their stools, Hymenolepis nana being the commonest. In spite of the unsatisfactory sanitary conditions in the Tsolo area compared with those in Guguletu, Cape Town, where all sewage is waterborne, few rural children were infested. The high prevalence of infestation in the Guguletu children suggests extensive contamination of the soil in the area by parasitic ova. In view of the magnitude of the extent of parasitic infestation in the Guguletu children, a vigorous and sustained programme of medication and education will have to be undertaken if the problem is to be resolved.


Serum ferritin concentrations in black miners. Serum ferritin concentrations were measured in 651 Black male miners who originated from rural areas throughout southern Africa and who were aged between 17 and 57 years. The mean serum ferritin concentration of 229 microgram/l was above the normal range reported for White subjects, and in 52,8% of the subjects the values were greater than 200 microgram/l. The serum ferritin concentration rose with age, as did the proportion of subjects in each age group who exhibited high values (more than 200 microgram/l). The lowest mean ferritin concentration (112 microgram/l) as well as the lowest proportion of high values (22,9%) were found in subjects from the most northerly area studied. Similarly, the highest mean proportion of high values (66,3%) was seen in the most southerly group studied. Calculations from the present data suggest that the degree of iron overload is currently greater in rural than in urban Black male subjects.


Women doctors wasted.

Women doctors wasted. The problem of wastage of women doctors has exercised the minds of South African medical planners very little. Numerous articles have appeared in the English literature, but we have been able to find only two editorials in semi-facetious vein in the South African Medical Journal over the last 20 years. We have looked at some trends, and believe that there is a need for further investigation, because there are important implications concerning future medical manpower resources in this country.


Endoscopic retrograde cholangiopancreatography in the management of traumatic pancreatic pseudocysts. A report of 2 cases. The results of endoscopic retrograde cholangiopancreatography (ERCP) in 2 patients with traumatic pancreatic pseudocysts are described. As a pre-operative procedure, this investigation provided useful information on the exact site of duct disruption. In both patients, the pancreatic pseudocysts were drained via a posterior cyst gastrostomy, and they have remained well since surgery. Follow-up ERCP at 6 and 12 months demonstrated complete stenosis at the site of duct disruption. The value of ERCP in the pre-operative and follow-up management of traumatic pancreatic pseudocysts is discussed.


The recognition of lesions on chest radiographs. An approach to the recognition of lesions on chest radiographs is outlined. Four basic groups of abnormalities by means of which lesions can be recognized are mentioned and are briefly described, namely an opacity, an area of increased translucency, a combination of an opacity and an area of increased translucency, and, especially, an alteration in normal radiological anatomy.


Radiological features of pulmonary oedema. A clinical classification embracing most of the causes of pulmonary oedema is given, as well as a radiological classification, and the different ways in which pulmonary oedema may present radiologically are briefly described.


The first symptoms of carcinoma of the oesophagus, with particular reference to amaqhakuva. A report from the Republic of Transkei. The first symptoms of cancer of the oesophagus in 82 Xhosa patients were found to be dysphagia (43%), interscapular back pain (23%), sore throat (21%) and epigastric pain (11%). More than half of the patients in whom a sore throat was the first symptom of the disease described the simultaneous occurrence of oropharyngeal lesions (amaqhakuva). No correlation could be found between the first symptoms and the characteristics of the oesophageal carcinoma at the time of presentation.


The comparative efficacy and safety of aminoglycoside antibiotics. In this article a report submitted to the Director of Hospital Services of the Cape Provincial Administration is summarized. The object of the report was to make firm recommendations where possible as to the use of the aminoglycosides in the Cape hospitals, taking into account considerations of comparative efficacy, safety and cost.


Incidence of heart disease in pregnancy. A study done at Peninsula Maternity Services hospitals. A detailed retrospective analysis was made of the records of 697 women with heart disease who were delivered between 1972 and 1976 and who accounted for 0.83% of all deliveries during this time. Rheumatic heart disease accounted for 65%, congenital lesions for 14% patients who had had cardiac surgery 12%, and miscellaneous heart conditions for 10% of cardiac lesions. The maternal mortality rate in these women was 7,17/1,000 deliveries, compared with 0.46/1,000 deliveries during this time. Cardiac disease was found to be the most important non-obstetric cause of maternal death. The perinatal mortality rate was not significantly higher than that in the total population. The high incidence of cardiac disease in pregnancy is unlikely to be significantly reduced until effective contraception is more widely practised in our community.


Mandating private pensions: experience in four European countries. This study examines the experience of four countries--the Netherlands, Sweden, Switzerland, and the United Kingdom--in which the mandating of private pensions exists or has been considered. Proposals to mandate private pensions in the United States have been introduced in Congress several times. The analysis of foreign thinking presented here provides a background on the reasoning behind such a policy and on the integration of private and public systems and the problems involved. A prime reason for mandating private pensions--instead of seeking higher social security benefits or additional social security layers--has been the pressure to avoid higher payroll taxes. Some countries already had such high contribution rates that they sought other means to improve benefits. Adding a layer of private pensions, it was thought, does not involve Government mechanisms and keeps the money in the private sector. Yet mandating by law creates many problems, and no country has fully implemented such legislation.


Effect of substantial gainful activity level on disabled beneficiary work patterns. Analysis of disabled beneficiaries' earnings records from the 1-percent Continuous Work History Sample over a 15-year period indicates that increases in the substantial gainful activity (SGA) level in 1966, 1968, and 1974 were not followed by incremental increases in beneficiary earnings. This article examines the flow of disabled-worker beneficiaries through the disability program in relation to their work history and earnings patterns. The recovery rate dropped steadily during the late 1960's and early 1970's. The earnings patterns indicate that about 10 percent of the beneficiaries were employed; about 3 percent had earnings above the SGA level. Median annual earnings remained well below $1,000, whatever the SGA level. Findings of the study suggest that policy considerations on changing the SGA level should not center on the implications for marginal part-time employment. Most of the evidence from beneficiary work and earnings patterns indicates that the SGA level has not operated as an effective work incentive. The program-flow analysis suggests that the allowance process rather than termination of benefits for recovery after sustained work holds the key to controlling program growth.


Appeals under the SSI Program: January 1974-August 1976. This study of appeals under the supplemental security income (SSI) program has several purposes: (1) To describe the appellate process and provide information on those requesting appeals (including reason for eligibility, program status, and age) and (2) to determine the relationship between these characteristics and the decisions at the three stages of the appellate process. About 312,000 reconsideration requests were processed from January 1974 to August 1976. These requests had been filed by adult and child SSI applicants who disagreed with the initial determinations of the Social Security Administration. Disabled persons requested nearly 95 percent of these reconsiderations. Approximately one-third of the applicants whose initial determination was reaffirmed after reconsideration then requested a hearing. Ninety-seven percent of these requests were filed by disabled persons. For those cases in which the earlier decisions were reaffirmed after hearings, 9,300 applicants requested a review by the Appeals Council. Eighty-two percent of these requests were denied.


Recovery of disabled beneficiaries: a 1975 followup study of 1972 allowances. In recent years, the number of persons awarded disabled-worker benefits has rapidly increased, but no corresponding rise has occurred in the number leaving the rolls for recovery. A comparative analysis has been made of the demographic, disability, and benefit characteristics of a sample of disabled workers awarded benefits in 1972 who left the rolls for recovery and the characteristics of those who remained on the rolls. For most beneficiaries, recovery appeared unlikely. A large proportion of those awarded benefits were older middle-aged workers with chronic progressive diseases. About 7 in 10 were aged 50 or over at allowance; one-fifth had died by the end of 1975. Younger beneficiaries, those with more education, those disabled by injuries, and residents of Western States were most likely to recover. Persons with higher benefit amounts had a high rate of recovery, but this finding appeared to reflect the effects of their being younger and more skilled. The level of earnings replacement appeared to have little independent effect on recovery. Among workers with conditions most subject to medical improvement, however, those with high replacement rates were less likely to leave the rolls.


Dagnostic imaging of the upper part of the abdomen. The new diagnostic procedures developed during the last several years present a confusing dilemma. The state of the art of ultrasound, computed tomography and nuclear scintigraphy is progressing so rapidly that what one says today is generally out of date tomorrow. However, certain guidelines should be followed in evaluating various organ systems. Generally, ultrasound is the procedure of choice in the upper part of the abdomen in most patients who are not extremely obese or filled with intestinal gas. A sonogram is less expensive than computed tomography and, at the present time, is considered noninvasive compared with compound tomography, which produces a small, but significant, radiation exposure. The accuracy of the two modalities is quite similar. Using the slight advantage that computed tomography may have in a given organ system does not generally override other factors, such as cost and radiation dose. However, mitigating factors, such as obesity, presence or absence of intestinal gas or barium, should be taken into account when selecting patients for either procedure. In many clinical situations, neither computed tomography nor ultrasound should be used until other modalities, such as conventional radiography or scintigraphy, have first been tried. Should the problem not be resolved by these more conventional techniques, an ultrasound or computer tomographic examination may be indicated to delineate further the pathologic condition of the abdomen.


Effect of Corynebacterium parvum in prevention and reversal of atrophy of the liver following portacaval shunt. Since it has been demonstrated that the administration of Corynebacterium parvum is associated with increased hepatocyte proliferation in both normal and regenerating livers, it seemed appropriate to determine whether the use of this agent would affect the hepatic atrophy which occurs following end-to-side portacaval shunts. When administered at shunting, liver weight and liver deoxyribonucleic acid failed to decrease to the same extent as that occurring in untreated, shunted rats. An increase in liver deoxyribonucleic acid synthesis was observed following portacaval shunt only in treated rats. Corynebacterium parvum administration to portacaval shunt rats with livers demonstrating marked atrophy 15 to 18 days following shunting resulted in the reversal of such atrophy. There was an increase in liver weight and deoxyribonuclei acid to the extent that those values were equal to, or greater than, those of livers from nonshunted rats. By increasing the number of cells within liver, Corynebacterium parvum administration prevents or reverses the decrease in liver size, that is, atrophy, which occurs after portacaval shunts were performed.


Hyperammonemia following ureterocolostomy in the rat. Following ureterosigmoidostomy, encephalopathy with hyperammonemia may occur in the presence of cirrhosis, and the same complication was also observed in a few patients without liver damage. This suggests overloading of normal liver ureagenisis by an increased portal ammonia supply. To test this hypothesis and to try to produce an experimental model of chronic hyperammonemia without portal or hepatic damage, ureterocolostomies were performed in rats. These rats were compared with sham operated upon rats and with rats having chronic uremia induced by subtotal nephrectomy. Rats having a ureterocolostomy had chronic, but moderate, systemic hyperammonemia without any histologic hepatic damage and without gross behavioral modifications and slight uremia with only inconstant pyelonephretic lesions. In these rats, hyperammonemia results from hepatic overloading by the increased portal ammonia supply which is a consequence of both intestinal absorption of some urinary ammonia and increased intestinal ammoniagenesis induced by hydrolysis of urinary and circulating urea.


Clinical implications in bacteroides bacteremia. The clinical presentation and results of treatment of 98 patients with documented bacteroides bacteremia have been reviewed. Surgically treatable causes were documented in three-quarters of the patients. No one antibiotic or combination thereof significantly influenced survival. Patterns of death from sepsis were through multiple organ failure. Early recognition, or surgical drainage or debridement, or both, and specific aerobe directed antibiotic therapy remain the first line of therapeutic endeavor.


Relationship of burn size to vascular permeability changes in rats. Studies to determine the relationship between increased vascular permeability, water content and protein leakage, and burn size were performed on rats. Partial thickness scald burn covering 10, 20, 30 and 40 per cent of the rats' body surface area were induced in four groups of rats. A fifth group of rats served as the controls. Following the burn, all rats received intravenously fluid resuscitation. Burn edema was maximal at three hours postburn for the 30 and 40 per cent groups. The edema persisted throughout the 24 hour study period. No significant change in water content of unburned skin was demonstrated. Albumin leakage into injuried tissues was maximal at 30 minutes and disappeared by 12 hours postinjury. The size of the burn had no effect on 131Risa leakage into injuried tissues. Albumin leakage into noninjured tissues occurred only in the 30 and 40 per cent burn groups was mild compared with that in burned tissues and also disappeared by 12 hours postburn. Extravasation of albumin in lung, liver, spleen, kidney and muscle was mild and seen only in the 30 and 40 per cent burn groups. Except for a mild increase in water content of lung tissue in the 30 and 40 per cent groups only, no consistent increase in the water content of other organs was observed. While the size of the burn appears to have some influence on capillary permeability, burns up to 40 per cent of the body surface have only a mild and transient effect upon capillaries distant to the site of injury. This observation supports the concept of a humoral mediator for capillary permeability and suggests that more pronounced changes can occur with larger burns. Nonetheless, extravasation of albumin appears to be short-lived.


Salivary gland drainage into the thyroglossal duct. The clinical entity described consists of intralingual ectopic salivary glands and ducts draining into the thyroglossal duct. The value of preoperative sinograms to demonstrate the condition is important; the use of methylene blue at operation is advocated to ensure complete removal.


Prevention of radiation enteritis after abdominoperineal resection and radiotherapy. The method described, aimed at preventing radiation enteritis in patients undergoing radiotherapy, postabdominoperineal resection is simple enough, does not materially prolong the time of operation and in our experience, thus far, seems to be effective.


Clinical aspects of grave pyogenic abscesses of the liver. Solitary hepatic abscess has a favorable prognosis in contrast with multiple abscesses which generally are fatal. As compared with the classical cause of appendicitis, at present, abscesses are frequently related to biliary tract and diverticular disease. Occult or temporally remote processes are responsibile for many solitary abscesses. Lethality of multiple abscesses is related to fulminant hepatic and source sepsis, atypical syndromes, late diagnosis and difficult, complex treatment. Causative organisms are predominantly gram-negative and increasingly anaerobic, requiring special bacteriology for isolation. Various laboratory data are useful in diagnosis and prognosis, but liver scans and celiac angiography are critical procedures. Treatment aimed at lowering the mortality of multiple liver abscesses includes early diagnosis, surgical exploration and abscess drainage, direct bacterial identification emphasizing anaerobic techniques, intense specific antibiotic therapy and identification and definitive therapy of the seeding focus with special attention being given to the biliary tract.


Changes in the coagulation of blood during resection of the abdominal aorta. In 33 patients, a significant fall in the fibrinogen level occurred during an operation to replace the abdominal aorta by a bifurcated prosthesis. There was a similar, but less marked, fall in the fibrinogen level of ten patients having a femoropopliteal vein bypass. A concomitant drop in the plasma plasminogen value was also found. Results of specific laboratory tests for intravascular clotting and activation of fibrinolysis were negative. This suggests that fibrinogen may be removed by physical means. The fall in fibrinogen was so low in some patients that the routine administration of a conventional dosage of heparin could be dangerous.


Microbiology of superficial and deep tissues in infected diabetic gangrene. In the current study, it is shown that, in the lesions of diabetic gangrene, there are usually mixed flora of two or more organisms. The organisms isolated from the presenting lesion may only partially reflect the organisms found in the deep tissues. Of the 58 cultures from the deep tissues, 11 of the isolates were anaerobes, but those anaerobes were never isolated as a pure culture. Bacterial synergism probably plays a role in infected diabetic gangrene. Maximizing the reduction of systemic infection and local cellulitis by elevation and appropriate antibiotic therapy results in improved wound healing in amputations of the lower extremities in patients with diabetic gangrene. However, apparent from this study, antibiotic therapy does not eradicate the organisms in the deep tissue, and surgical procedures are usually required for definitive treatment. Material from the surgically removed infected tissue should always be cultured for identification of existing organisms. When indicated, appropriate adjustment of antibiotic therapy, based upon these findings, should be prescribed.


The use of radioactive oxygen to study muscle function in peripheral vascular disease. We have use 15O to study the relationship between blood flow and oxygen utilization in the limbs of patients with peripheral vascular diseases. This technique is noninvasive and provides a useful method of studying the function of ischemic limbs.


Primary adenocarcinoma of the vagina.

Primary adenocarcinoma of the vagina. The characteristics and treatment of eight patients with primary adenocarcinoma of the vagina were reviewed. Cytologic smears of the vagina aided in the diagnosis of adenocarcinoma but, less often, detected vaginal adenosis. Good correlation existed between the degree of differentiation of the primary tumor and the tendency toward lymphatic spread. The clinical stage, size of the primary lesion, presence and duration of symptoms and lymphangiographic findings were not helpful in this regard. Pretreatment lymphadenectomy as a basis for operative staging demonstrated the critical importance of the status of the lymph nodes in the planning of therapy and determination of prognosis. Vaginal reconstruction and ovarian preservation facilitated rehabilitation.


Comparative results of three different techniques for colonic anastomosis in the dog. Three different techniques of colonic anastomosis were evaluated in the dog. Left hemicolectomy and two layer anastomosis were performed in ten dogs, one layer anastomosis in ten dogs and sleeve anastomosis in ten dogs. In each group, five dogs were sacrificed on the second postoperative day, and the anastomotic specimen was studied by a bursting test. The remaining five dogs were sacrificed seven days after operation, and the specimen was studied by hydroxyproline dosage and by microscopy. The bursting test showed a significant difference between sleeve anastamosis and other techniques. The results of hydroxyproline dosage showed no significant differences between the different anastamotic techniques.


Microsurgical removal of lumbar herniated nucleus pulposus. An operating microscope and special instruments make it possible to remove a herniated nucleus pulposus without laminectomy through a 1 inch skin incision. In a follow-up study of 200 patients operated upon over a two and three-fourths year period, the cure rate has been 96 per cent and the postoperative stay reduced to less than three days. One year after operation, all noncompensation patients were working as were 80 per cent of the compensation patients.


A new vascular access procedure for immediate as well as chronic hemodialysis. A new vascular access procedure consists of attaching an arteriovenous shunt to a subcutaneous arteriovenous fistula. The procedure was designed for patients who need immediate as well as long term hemodialysis and in whom the Brescia-Cimino type of fistula could not be done. Secondary objectives for this new procedure were a prolonged patency interval and a lower complication rate of arteriovenous fistulas. Six patients underwent this procedure and were observed from two to five months. Five shunts remained patent for a minimum of two weeks. Five patients have presently functioning fistulas, and in three of these, both shunts and fistulas remain patent. Two of the presently functioning shunts required declotting. Two shunts were removed when neither declotting nor revision was possible, and one shunt was removed because of infection. One fistula was lost due to a technical error, and two of the five presently functioning fistulas have required declotting. We believe clotting was due chiefly to the fact that patients selected for this procedure were from the group who had multiple previous clotting episodes and vascular access procedures. It remains to be seen whether or not more careful patient selection will accomplish the secondary objectives.


Choroidal occlusive disease in sickle cell hemoglobinopathies. Two distinct episodes of posterior ciliary artery occlusion were studied in a 32-year-old man with hemoglobin SS disease and multiple episodes of amaurosis fugax. Although posterior ciliary artery occlusions have been observed following photocoagulation of sickle cell retinopathy, their spontaneous evolution in patients with sickling hemoglobinopathies has received little attention. The manifestations of posterior ciliar artery occlusion seen in this case and in other clinical and experimental situations are reviewed. Histopathologic examination of three additional eyes of patients with sickle hemoglobinopathies revealed changes which may have been the result of previous small posterior ciliary artery occlusions or small vessel occlusive disease related to the sickling hemoglobinopathies; these cases are also reported.


Photographic investigation of the human lens and cataract. Slit-image photography of the anterior segment of the eye can provide important information about the dimensions and optical densities of the refractive structures. It is crucial that the slit-image photograph be in perfect focus and that the slit-beam cut in exactly the same section (along the optic axis) on each occasion. The equipment, principles and techniques which make such precision slit-imagephotography possible  are discussed. Clinical and research applications, especially regarding the human lens and cataract, are summarized.


Pseudotumor cerebri.

Pseudotumor cerebri. The authors evaluate the case of a 20-year-old, four-month-pregnant woman who presented with papilledema and visual field loss, and developed headache, intermittent diplopia and impairment of color vision over the next month. The procedures and considerations leading to the diagnosis of pseudotumor cerebri are discussed, as are the various modes of therapy and their indications.


The nonportal origin of the factors initiating hepatic regeneration. To determine the site of origin of the factors that initiate deoxyribonucleic acid (DNA) synthesis in the liver after partial hepatectomy, normal rats were cross-circulated with totally hepatectomized rats. Half of the hepatectomized rats had also undergone excision of all of the portal organs. After 48 hours of cross-circulation, active DNA synthesis and other evidences of hepatic regeneration were found in normal rats cross-circulated with the hepatectomized portally eviscerated rats. This demonstrates that a blood-borne factor that does not arise from the portal organs is capable of initiating hepatic regeneration. When a normal rat was cross-circulated with a hepatectomized rat with the portal organs still present, hepatic regeneration occurred but was significantly less than when the portal organs had been removed. It is postulated that under these experimental conditions portal factors from the normal rat have a permissive role that allows active regeneration when initiating factors are furnished from the hepatectomized rat. Additional portal organs in the hepatectomized rat decreased DNA synthesis, possibly by alterations of the insulin/glucagon ratio.


Serum ribonuclease elevations and pancreatic necrosis in acute pancreatitis. Pancreatic necrosis is a principal determinant of the severity, duration, and infectious complications of acute pancreatitis. There has been no objective index for pancreatic necrosis, and its recognition has necessarily rested upon nonspecific clinical signs, including later deterioration or appearance of sepsis. In search of such an index, we have measured serum levels of a poly-[C]-specific acid ribonuclease (RNase) in 38 patients with acute pancreatitis, 12 patients with chronic pancreatitis, and 50 control patients. The values in chronic pancreatitis (mean, 52 units; range, 33 to 80 units) were within observed normal limits (mean, 51; range, 17 to 94). The values in acute pancreatitis segregated into two groups, normal values (group A) and high values (group B). Of 25 patients in group A (mean, 46; range, 19 to 87), only one developed evidence of pancreatic necrosis or abscess. In contrast, of the 13 patients in group B (mean, 192, range, 98 to 385), 11 required surgical debridement/drainage for pancreatic necrosis (six) or abscess (five) (P less than 0.001). Each of the other two patients had prolonged pancreatic inflammation with fever and a pancreatic mass which persisted for more than 2 weeks. RNase levels in group B patients rose within a few days after onset of pancreatitis and tended to parallel the clinical course. These findings suggest that measurement of serum RNase in acute pancreatitis gives a reliable indication of pancreatic necrosis. Therefore RNase determinations should be of value for earlier identification and monitoring of patients at high risk of late complications, and for helping to select those who will benefit from early debridement before secondary infection occurs.


Longterm timolol therapy.

Longterm timolol therapy. Of 145 patients registered for an investigation of timolol, 27 patients were dropped for unrelated reasons. Among the remaining 118 patients (212 eyes), a significant reduction in intraocular pressure resulted from twice-a-day topical instillation of 0.25 or 0.5% timolol to ocular hypertensives, primary open-angle glaucoma or aphakic glaucoma patients. Outflow facility improved only slightly, but remained improved throughout the course of this study. A significant reduction in aqueous secretion, however, was the predominant cause of intraocular pressure reduction. Timolol alone controlled intraocular pressure in 87% of ocular hypertensives, in 68% of patients with chronic open-angle glaucoma and in 68% of patients with angle-unobstructed aphakic glaucomas. The addition of epinephrine brought the intraocular pressure to less than 22 mm Hg in 85% of the total group of patients.


Timolol plus maximum tolerated antiglaucoma therapy: a one-year followup study. Thirty-three eyes of 22 patients with primary open-angle glaucoma or severe ocular hypertension had topical timolol maleate added to their maximally tolerated medical regimens. With minimal side effects, 25 eyes (76%) could be treated medically for one year, and only eight eyes (24%) required filtering surgery. Thirteen (39%) of the medically treated eyes achieved intraocular pressures of 21 mm Hg or less. After the addition of timolol, 17 of the 33 eyes (52%) completed the one-year protocol with final mean intraocular pressure decreases of 5 mm Hg or more on medical therapy.


Negative inotropic effect of albumin resuscitation for shock. The inotropic effects of albumin were studied in 94 seriously injured patients who received an average of 14.5 transfusions, 9.2 liters of crystalloid and 0.9 liters of plasma prior to end of operation; 46 patients, by random selection, received added albumin averaging 31 gm during operation, 198 gm during the early postoperative period of extravascular fluid sequestration, and 395 gm during the first 4 days of the later fluid mobilization period. Left ventricular stroke work index (LVSWI) was plotted against pulmonary wedge pressure (Ppw) in 22 patients who had indwelling thermistor pulmonary artery catheters at the time of the first study. Calculated heart work units (WU) were derived from the pulse pressure, mean arterial pressure, pulse rate, and central venous pressure (CVP) in patients without LVSWI measurements. Albumin supplementation increased serum albumin (4.2 vs. 2.9 gm%), plasma volume, CVP (15 vs. 9 cm H2O), but did not alter red cell volume (1,531 vs. 1,519 ml). The ratio of LVSWI/Ppw fell in albumin patients (1.9 +/- 1.6 vs. 4.8 +/- 1.8), and the ratio of WU/CVP was significantly depressed in albumin patients (4.9 +/- 2.3 vs. 7.3 +/- 2.1). The slopes of the LVSWI/Ppw and WU/CVP were shifted to the right in albumin patients. This negative inotropic effect was associated with impaired oxygenation, as reflected by an increased ratio of inspired oxygen per arterial oxygen tension (0.62 +/- 0.06 vs. 0.33 +/- 0.1). Finally, 24 of the 46 albumin-treated patients were digitalized for heart failure, compared to only 11 of the 48 nonalbumin patients. Pending subsequent studies, albumin should be considered a potentially negative inotropic agent.


The role of clinical drug trial methodology with respect to studies of new drugs. Clinical trials of timolol. The use of the Randomized Clinical Trial (RCT) to assess the safety and efficacy of a new drug or treatment can provide a clear evaluation of the relative benefits and risks of the new therapy as compared to the longer-established treatment methodology. In some cases, such as insulin, the benefits are immediately apparent; in other cases, such as photocoagulation for proliferative diabetic retinopathy, the consensus is not so easily obtained, and the clinical trial can supply the answer. Furthermore, the RCT provides the opportunity to identify adverse reactions, in particular those which present with a seemingly unrelated or unexpected set of symptoms. In conducting clinical trials of timolol, researchers must be alert for beta-adrenergic antagonist effects, such as were seen with practolol, and should be especially careful to note early, mild reactions which may be the forerunners of later, more severe or irreversible adverse effects.


Effects of iris pigmentation on response of ocular pressure to timolol. Timolol ophthalmic solution effectively reduced mean intraocular pressure (IOP) in Negro and Caucasian patients with chronic open angle glaucoma and untreated IOP of 22 mm Hg or higher. No differences in pressure lowering response were observed among the races although the Negroes required somewhat higher timolol concentrations to produce similar reductions from baseline IOP. Negro patients also appeared to have a more severe disease as indicated by the number of prior antiglaucoma drugs required and the untreated (baseline) pressures. An unexpected finding was the significantly greater number of Caucasians with dark irides who were discontinued from therapy because of inadequate pressure reduction.


The leukocyte migration inhibition response to certain breast cancer-related antigens (MCF-7 and MuMTV): their potential as discriminants. Certain oncogenic viruses have been implicated in human breast cancer, including the murine mammary tumor virus (MuMTV) and the Mason-Pfizer monkey virus (MPMV). We have used the leukocyte migration inhibition (LMI) response to assay the response to several potential breast cancer-related antigens, including MuMTV, MPMV, and a breast cancer cultured cell line, MCF-7, in 96 breast cancer patients, in 32 women with benign breast disease, and in 67 normal women. The lowest tenth percentile of control (LMI) responses was used as the cutoff point to designate responders. Breast cancer patients showed significant responses to MuMTV (49% and to MCF-7 (50%), but not to MPMV (29%). In a paired-antigen study using MuMTV and MCF-7, 75% of the breast cancer patients responded, versus 18% of the normal women (P less than 0.0050). The potential for this assay to distinguish "normal" from "breast cancer" was analyzed using a migration index derived from discriminant analysis. The ability of the assay to discriminate "normal" from "cancer" was significant (P less than 0.001) and showed a sensitivity of detecting "cancer" of 75%. The overall responses to MuMTV and MCF-7 were analyzed with reference to certain prognostic factors, but showed no relation to age, menstrual status, estrogen receptor status, or stage of disease. The above reactions suggest that a large proportion of breast cancer patients exhibit presensitization to antigenfs found in MuMTV and MCF-7, which may be cross-reactive with antigens in the primary cancer. These responses appear to be independent of major prognostic variables. Further refinement of this assay may yield one which is more highly discriminating for breast cancer.


Patient compliance and the "usefulness product" of timolol. The practical value of any therapy depends upon a combination of effectiveness of the agent (or procedure) and the extent to which the patient complies in its proper administration. Thus, it might be said that the multiple of effectiveness times compliance equals the "usefulness product." Among the various glaucoma therapies, this product seems to range from about 30%--90%. Timolol's effectiveness in lowering intraocular pressure combined with its low incidence of side effects yields a high usefulness product, and this may decrease the incidence of surgery required for the treatment of the open-angle glaucomas.


The effects of early pneumonectomy on the remaining pulmonary parenchyma. To determine the age-related response of the remaining pulmonary parenchyma to lung resection, a matched set of 24 purebred beagle dogs underwent pneumonectomy at 6 to 10 weeks of age (group I) or at 1 year of age (group II). Eight unoperated adult beagles served as controls (group III). One year after pneumonectomy, pulmonary hemodynamics in group I were the same as those in older animals shortly after pneumonectomy and in normal control animals. Functional residual capacity, total lung capacity, single breath diffusing capacity for carbon monoxide, and static lung compliance were measured in all three groups while anesthetized and intubated. Lung volumes and diffusion capacity for carbon monoxide in group I did not differ significantly from those of control animals. Group I animals did have a lower lung compliance than the control group, but significantly greater than the group II adult pneumonectomy dogs. The adult pneumonectomy dogs (group II) had significantly lower values for lung volumes, diffusion capacity, and compliance when compared to the control group. Arterial blood gases were not significantly different among the groups. It is concluded that beagles undergoing early pneumonectomy have an increase of alveoli beyond the normal complement in the remaining lung with concomitant remodeling of the pulmonary capillary bed resulting in normal lung volumes, diffusing capacity, and gas exchange.


Inhibition of basal and meal-stimulated choleresis by somatostatin. The effect of somatostatin, an inhibitor of release of a number of gastrointestinal and other hormones, on choleresis was investigated in chronic, bile fistula dogs with taurocholate-stabilized bile flow. Somatostatin inhibited both fasting and meal-stimulated choleresis, and bile flows during somatostatin inhibition of both fasting and fed dogs were similar, suggesting a complete suppression of factors causing feeding choleresis. Although a transient decrease in bile salt output was observed, bile salt output was unaffected during most of the period of bile flow inhibition. Hormone suppression by somatostatin, indicated by measurement of serum insulin, occurred over a similar time course as inhibition of choleresis. These observations provide further evidence for physiological humoral regulation of choleresis.


The effect of plasma oncotic pressure on the pulmonary microcirculation after hemorrhagic shock. Plasma oncotic pressure is considered to be an important factor in controlling lung water after hemorrhagic shock. However, it is the gradient between plasma and interstitial oncotic pressure which affects the pulmonary transvascular fluid filtration rate, Qf. Our objective was to determine the effect of decreasing plasma oncotic pressure, pip, on Qf, on interstitial oncotic pressure pii, and on the oncotic gradient. Chronic lung lymph fistulas were created in 16 sheep. Lymph flow, a reliable index of Qf, plasma and lymph (equal to interstitial) oncotic pressures, and vascular pressures were monitored in unanesthetized sheep, before and during hemorrhagic shock (50% blood volume), during resuscitation (3 hours), and during recovery (24 hours). Resuscitation was either with shed blood or lactated Ringer's solution in sufficient quantity to return left atrial pressure and cardiac output to baseline levels. During resuscitation with blood, lymph flow increased by 115%. The pip remained constant, while pii decreased, increasing the oncotic gradient. Crystalloid resuscitation produced on increase in lymph flow equal to that in the blood group at 120% over baseline; however, pip decreased by 50%, producing an oncotic gradient 4 mm Hg less than that of blood group. This was not reflected by a difference in Qf between the groups. During recovery Qf returned to baseline in the blood group and in most of the crystalloid group, as the oncotic gradient returned to baseline, despite a significant decrease in pip due to a compensatory decrease in pii. We conclude that during resuscitation Qf does not appear to be increased by a decrease in the oncotic gradient. During recovery a major decrease in pip can be compensated for rapidly by a decrease in pii, leading to no change in interstitial fluid content.


Effect of vagal stimulation on pancreatic secretion and on blood levels of gastrin, cholecystokinin, secretin, vasoactive intestinal peptide, and somatostatin. We investigated in dogs the effect of graded frequencies of electrical vagal stimulation (1.5, 3, 6, and 12 cps) on pancreatic exocrine secretion and on portal blood levels of gastrin, secretin, cholecystokinin (CCK), vasoactive intestinal peptide (VIP), and somatostatin (STS). Stimuli of all four frequencies, each with a duration of 5 minutes, were applied with a secretin background of 0.25 CU/kg-hr, and one stimulatory period of 12 cps was applied without a secretin background. With secretin, a significant, frequency-dependent increase of volume and of pancreatic protein secretion occurred from 3 to 12 cps. Gastrin values increased significantly at all frequencies. VIP and STS increased significantly with 3, 6, and 12 cps. Maximal responses for gastrin, VIP, and STS were observed with 6 cps. Peak values for gastrin and VIP were found during stimulation, whereas STS peaked after the end of the stimulatory period. The integrated responses of gastrin and STS showed significant correlation (P less than 0.01). The results suggest that vagally induced pancreatic response is only partially mediated by gastrin and perhaps VIP, and that endogenous gastrin may be one of the releasing factors for somatostatin. Plasma levels of CCK and secretin did not change after electrical stimulation, which provides direct evidence that their release is unlikely to be under vagal control, and that CCK does not mediate the protein secretion obtained after electrical stimulation of the vagus.


A multifactorial analysis of melanoma. II. Prognostic factors in patients with stage I (localized) melanoma. Stage I melanoma encompasses an extraordinary diversity of biologic behavior. In such a setting where numerous parameters appear to influence survival, a multifactorial analysis using Cox's regression model is a valuable statistical model. Using a computerized data base of 394 clinical stage I melanoma patients treated at this institution during the past 20 years, a multifactorial analysis was used to compare the relative prognostic strength of 11 parameters. Two pathological factors (tumor thickness and ulceration) and two clinial factors (initial surgical treatment and anatomic location) were identified as the dominant prognostic variables. Other factors examined simultaneously that did not provide additional predictive influence on survival included the level of invasion, pigmentation, growth pattern, lymphocyte infiltration, pathological state, sex, and age. Melanoma thickness was the most important factor for predicting survival in patients with stage I melanoma (P less than 10(-8). This parameter is easy to measure and provides a quantitative estimate of clinically occult regional and distant metastases. Contrary to other reports using single factor analysis, the type of initial surgical treatment, in fact, did influence survival after other variables were taken into consideration. Thus the multifactorial analysis supports the observation that patients with intermediate thickness melanoma thickness of 1.5 to 3.99 mm had a 78% 8-year survival rate with wide excision of the melanoma and elective node dissection, while none survived more than 8 years if a melanoma of the same thickness was only widely excised. Multifactorial analysis is a useful and important statistical method when comparing treatment alternatives and prognostic factors in patients with melanoma.


In vivo effect of suloctidil as an antiplatelet agent. The relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5-HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT  after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.


The action mechanism of the purified platelet aggregation principle of Trimeresurus mucrosquamatus venom. The minimal concentration of the platelet aggregation principle (Platelet Aggregoserpentin, PAS) necessary to induce platelet aggregation was 10 ng/ml, about one-hundredth of that of the crude venom. PAS induced the release of platelet factors 3 and 4 from platelets, but the released platelet factor 3 was easily inactivated by the anti-phospholipid effect of PAS. Pretreatment of platelets with neuraminidase potentiated PAS-induced platelet aggregation. PAS-induced platelet aggregation was independent on released ADP; it could occur in the ADP-removing systems, such as apyrase or a combination of phosphoenolpyruvate and pyruvate kinase. However, PAS-induced platelet aggregation could be inhibited by adenine nucleotides and adenosine. PAS-induced platelet aggregation was inhibited by some anti-inflammatory agents, antimalarial drugs, local anesthetics, antihistamine and smooth muscle relaxants. After deaggregation of PAS-treated platelets, thrombin and sodium arachidonate could further induce platelet aggregation, but ADP and second dose of PAS could not. It is concluded that PAS-induced platelet aggregation is due to prostaglandin synthesis. Recent literatures on the mechanism of platelet aggregation were surveyed and the actions of PAS were discussed.


Effects of adenosine diphosphate, colchicine and temperature on size of human platelets. An improved measuring system based on the Coulter principle and developed in our laboratory is used to size human blood platelets. The mean volume of platelets in 24 healthy subjects is found to be 8.45 micron 3 with a standard deviation of 1.07 micron 3; the typical size-distribution curve is unimodal and asymmetrical, with a marked skew to the right. The effects of different reagents on platelet size (shape factor x volume) are evaluated. Platelets increase in size by 23% following suspension in isotonic, phosphate-buffered saline and incubation with 10 microM adenosine diphosphate; no change is observed when the suspending medium is autologous plasma. Cooling the platelets to 0-4 degrees C results in a size increase of 25%; rewarming to 37 degrees C restores them to their initial size within 2 hr. A similar increase occurs when the platelets are incubated with 1-10 mM colchicine. It is proposed that these reagents, which are known to produce changes in the orientation of the marginal bundle of microtubules, cause platelets to undergo disc-sphere transformations. Calculations are made which show that such transformations increase platelet size by 27% as measured electrically, and we conclude that the so-called volume changes reported in the literature reflect shape changes only and that no true volume increase actually takes place.


Direct measurement of the amount of bound collagen which stimulates platelet aggregation. The amount of collagen which binds to platelets has been correlated with aggregating activity in a platelet aggregometer. Aggregating activity requires only 0.22 microgram/ml (0.35 microgram/10(9) cells) of collagen bound, the reaction saturating with 4.9 microgram/ml (7.9 microgram/10(9) cells). On the basis of the fraction of collagen bound and its hydroxyproline/proline ratio, it is concluded that the activity resides in the type I collagen component.


Effect of factor XII deficiency on pregnancy and parturition. The clotting parameter of a primigravida with factor XII deficiency was studied during her third trimester of pregnancy, labor and post-partum; and compared with those of her newborn male infant. Sharp increases in factors VII, VIII, IX, X and moderate increases in factors II and XI were documented during pregnancy and at labor. All factors had returned to normal or near normal levels 24 hours after delivery. Factor XII remained at 0.0 level throughout. In the infant the clotting factor levels reflected depression of vitamins K-dependent factors II, IX, and X and a factor XII level of 40.0%. No undue bleeding was noted in the mother at delivery or placental separation, and no bleeding manifestation was apparent in the infant. These findings suggest that factor XII does not play a major role in triggering or modulating the course of normal labor, nor is its absence necessarily associated with bleeding complications during parturition or placental separation.


Studies on a subcellular system for vitamin K-dependent carboxylation. The subcellular localization of acarboxyprothrombin and the vitamin K-dependent carboxylation system has been studied using livers from vitamin K-deficient rats and found to be mainly in the membranes of the rough microsomal fraction. Bovine acarboxyprothrombin or fragment 1 thereof were inactive as substrates in the rat carboxylating system.


Prevention of intravascular thrombus formation on plastic catheters with heparin-benzalkonium complex: in vivo and in vitro studies. A complex of heparin and a quaternary ammonium compound dissolved in an organic solvent was investigated for its potential ability to prevent clotting on the surface of plastic catheters. Despite the complexing of heparin to ammonium, anticoagulant activity remained on in vitro testing. Both the heparin complex and its organic solvent alone partially prevented catheter thrombus formation when tested in an in vivo animal model system. Neither, however, was totally effective in preventing thrombosis.


Plasma thrombin assay using a chromogenic substrate in disseminated intravascular coagulation due to snake bite envenomation. Using the chromogenic substrate, Tos-Gly-Pro-Arg-pNA-HCl (Chromozym TH, Boehringer Mannheim) plasma thrombin was estimated in six cases of envenomation by Australian elapid snakes. All patients manifested findings characteristic of defibrination due to envenomation by these snakes. Fibrin-fibrinogen degradation products were grossly elevated, as was plasma thrombin in all cases. Following treatment with antivenene, all abnormal coagulation parameters returned rapidly towards normal by 24 hours and plasma thrombin disappeared.


Detection and partial purification of a natural heparin inhibitor from hog small intestine. A natural occurring heparin inhibitor was detected and was partially purified from the mucosa of hog small intestine. The mucosa was homogenized and was extracted overnight in 0.15 M NaCl, 0.01 M imidazole, 0.001 M EDTA, pH 6.5. When the extract was made to 85% saturation in ammonium sulfate, a large quantity of heparin neutralizing activity was detected in the precipitate. Each small intestine contains approximately 35,000 units of heparin neutralizing activity. This heparin inhibitor was further purified by the procedures of zinc sulfate precipitation, ammonium sulfate fractionation, ethanol precipitaiton and heparin-sepharose chromatography. A 37 fold partial purification with 15% overall recovery was achieved to yield heparin inhibitor with specific activity of 50-65 units per mg of protein.


A in vivo assay for standardizing heparin preparations. The limitations of currently used in vitro assays of heparin have demonstrated the need for an in vivo method suitable for routine use. The in vivo method which is described in this paper uses, for each heparin preparation, four groups of five mice which are injected intravenously with heparin according to a "2 and 2 dose assay" procedure. The method is relatively rapid, requiring 3 to 4 hours to test five heparin preparations against a standard preparation of heparin. Levels of accuracy and precision acceptable for the requirements of the British Pharmacopoeia are obtained by combining the results of 3 to 4 assays of a heparin preparation. The similarity of results obtained in vivo method and in vitro method of the British Pharmacopoeia for heparin preparations of lung and mucosal origin validates this in vivo method and, conversely, demonstrates that the in vitro method of the British Pharmacopoeia gives a reliable estimation of the in vivo activity of heparin.


Measurement of the heparin neutralizing capacity of protamine. Several methods of estimating the heparin neutralizing capacity of protamine were investigated for their reliability and practicability. The results from two chemical methods were compared with those from two in vitro biological assays, one of which was the method of the British Pharmacopoeia (1973). An in vivo method using mice was used to assess the accuracy of the in vitro test methods. Three standard heparin preparations were tested against the W.H.O. 1st International Reference Preparation for Protamine. Two of the heparin preparations were of mucosal origin, one of which was the 3rd International Standard, and the third heparin preparation was of lung origin (the 2nd International Standard for Heparin). The mean neutralization values (all methods) of heparin by protamine for a House Reference Preparation and the 3rd and 2nd International Standards for Heparin were 95.8, 109.8 and 89.9 units per mg of Protamine, respectively. All methods read the House Reference Preparation to have a lower value than the 3rd International Standard, which had a higher value than the 2nd International Standard for Heparin. There was a constant relationship between the results of any one method and those of another. The chemical and in vitro biological methods gave results of comparable precision although the latter required a greater degree of technical skill and time to perform.


Somatostatin-induced changes in the hemostasis of rats. Somatostatin (SRIF) given intravenously, either as a single bolus or as a 2 hr infusion caused a significant prolongation of partial thromboplastin time (PTT) and depressed platelet counts and platelet aggregation in the rat. Following daily injections of protamin-zinc SRIF for 2 weeks the platelet count returned to normal, PTT remained prolonged and platelet aggregation was enhanced. The doses of SRIF used in this work were adequate to suppress the secretion of insulin and glucagon by the isolated pancreatic islets of treated animals.


The nucleated thrombocytoid cells. I. Electron microscopic studies on chicken blood cells. By analyses of electron micrographs it was investigated whether nucleated thrombocytes of chickens described in the literature can be differentiated from lymphoid cells with sufficient certainty as an independent cell system. The result was negative. The mixture of lymphoid cells and so-called thrombocytes investigated was extremely polymorphous and, unlike mammalian platelets, proved to be one cell system containing younger and more mature cells. In the literature cells with signs of overmaturity or activation are designated as thrombocytes. Our studies suggest that a genuine thrombocyte system of chickens and other birds is not existent. The cell hitherto considered as nucleated thrombocytes seem to belong to the lymphoid system.


[Bone tumours in the shoulder area (author's transl)]. An introduction into the basic principles of radiographic interpretation of bone tumours is presented. Patient material is selected in order to demonstrate the different appearances of bone tumours. The basic patterns of periosteal response are discussed. A short discussion of differential diagnosis is included.


[Mycoplasma synoviae control. II. Treatment of hatching eggs with tylosin tartrate (author's transl)]. Several strains of Mycoplasma synoviae isolated in the Netherlands during the past five years, were found to be sensitive to tylosin tartrate in vitro as well as in vivo. In one of four cases in which laying hens were infected experimentally, vertical transmission of the infective agent was demonstrated by the isolation of Mycoplasma synoviae from hatching eggs laid during the second and third weeks after infection. Treatment of experimentally infected eggs and eggs laid by infected flocks with 2.5 mg. of tylosin tartrate in the aircell on the ninth day of incubation resulted in the elimination of Mycoplasma synoviae. This procedure also underwent large-scale testing in the field. Injection of 0.8 and 1.5 mg. of tylosin tartrate into the albumen of non-incubated chicken eggs or turkey eggs through an area at a distance of approximately 1 cm. from the tapering extremity will probably provide an attractive alternative to egg-dipping in the control of mycoplasma infection.


[Haemoglobin and haematocrit levels in veal calves (author's transl)]. The haemoglobin and haematocrit levels were studied in three groups of about thirty male Dutch-Friesian veal calves. The iron content of the milk replaces was 5, 10 and 25 ppm. During the experiment which was continued for sixteen weeks, the haemoglobin and haematocrit levels decreased in all groups. The decrease was confined to the first six weeks in the calves fed the milk replacer containing 25 ppm of iron. In the two other groups, the decrease of the two criteria continued throuhgout period. Regardless of the iron content of the milk replacer, the decrease of Hb- and haematocrit levels of the individual calves was greater in those having the highest initial level. The borderline for anaemia in a group of sixteen-week-old veal calves is estimated at approximately 10 g. Hb/100 ml. blood. For an individual calf, the borderline is estimated at 8 g. Hb/100 ml. blood.


[Registering, licensing and investigating vaccines in animal disease control (author's transl)]. The registration, licensing and investigation of veterinary vaccines are discussed with reference to the producer, the user and the authorities. The significance of basic research by the producer, of testing by the authorities, of quality control and of evaluation (laboratory and field studies) in the control of animal diseases are examined more closely. The fact is stressed, that legislation concerning veterinary medicines in general and vaccines in particular should be well defined. All this is regarded as an integral part of recent developments in animal farming in the Netherlands.


Recovery of the heart after normothermic ischemia. Part II: Myocardial function during postischemic reperfusion. Contraction and relaxation of the canine myocardium were examined during normothermic ischemia in an isolated heart model. Decrease in the development of tension depends on the duration of ischemia. Deficient functional recovery was observed after ischemic periods extending beyond 30 minutes, in spite of reperfusion periods of over 1 hour. A decrease in compliance was observed during the anoxic period, but a persistent defect of relaxation occurred only after 60 minutes of ischemia. After this period there was also a disturbance in the autoregulative mechanisms of coronary perfusion and an uncoupling of O2-consumption and mechanical efficiency. A prolonged reperfusion period of the heart beating empty allowed ultrastructural recovery of the damaged myocardium. In contrast, functional recovery of the myocardium, as determined by several parameters of contraction and relaxation, did not correlate with ultrastructural recovery and was not improved by prolonged reperfusion.


Inotropic agents and functional recovery from ischemic cardiac arrest. Short periods of ischemic arrest may cause myocardial cell damage so that reperfusion does not result in an immediate return to normal metabolic and contractile activity. Studies have been carried out using a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest in order to determine whether the use of inotropic agents (isoprenaline and dobutamine) to augment contractile activity during the early phase of post-ischemic reperfusion extends pre-existing damage and results in ultimate impairment of contractile activity. The results indicated the existance of a substantial metabolic reserve, capable of providing sufficient energy for a marked increase in dP/dt and heart rate, without inducing tissue damage. However, in this isolated rat heart preparation the use of these agents had relatively little effect upon cardiac output and could be shown to induce a dose-dependent reduction in stroke volume.