Adrenergic mechanisms in the hepatic arterial circulation of baboons.

The effects of intra-arterial injections and infusions of three adrenergic amines upon hepatic arterial blood flow were measured in anesthetized baboons before and after alpha and beta adrenergic blockade with intravenous phenoxybenzamine and propranolol. Injections of norepinephrine or epinephrine caused dose-dependent decreases in hepatic arterial blood flow. These responses were attenuated by alpha adrenergic blockade and were unchanged by beta adrenergic blockade. Injections of isoproterenol caused dose-dependent increases in hepatic arterial flow. These increases were relatively small and were reversed to constriction at low doses and attenuated at high doses of the agonist by beta adrenergic blockade. Intrahepatic arterial infusions of constrictors were unaccompanied by autoregulatory excape. The degree of constriction was attenuated by alpha adrenergic blockade but was not potentiated by beta adrenergic blockade. Intrahepatic arterial infusion of a relatively large dose of isoproterenol was required to evoke a relatively modest, but sustained, increase in hepatic arterial blood flow. This response was not potentiated by alpha adrenergic antagonism, but was attenuated by beta adrenergic blockade. These observations suggest an apparent and relative decrease in beta adrenergic receptor activity in the hepatic arterial bed of the baboon when compared to other regional circulations such as the mesenteric and femoral beds. These beta receptors are relatively resistant to both stimulation and blockade.


Vascular prosthetic infections: collected experience and results of treatment.

A review of 178 published cases of infected vascular prosthetic grafts through 1974 disclosed 164 sufficiently well documented for review. The time and manner of presentation depended on location and most commonly included localized wound infection with graft exposure. Staphylococcus aureus was the most common organism cultured and predisposing infection in the foot or opposite groin was significant. The over-all mortality rate was 52 of 153 patients (33.9 percent), separating into 47.9 percent at the aortofemoral (AF) level and 9.9 percent for femoropopliteal (FP) infections. Amputation rate was 23 percent for AF and 36 percent for FP infections. Of five treatment plans utilized. best results were obtained with early exploration and revascularization. Conservative treatment of FP grafts was successful when the graft was patent. At the Medical College of Virginia, the graft infection rate was 2.6 percent and the mortality rate was 36 percent. Conservative treatment efforts without revascularization resulted in a 57 percent amputation rate and justifies a more aggressive approach to suspected graft infection.


Reconstruction of the cervical esophagus by transplantation and revascularization of a small intestinal segment: ten year follow-up.

This study represents a 10 year follow-up of one case of cervical esophagus reconstruction by transplantation of a small intestinal segment. The graft was of normal configuration in esophagoscopy, radiography, and biopsy. The patient is well now and is able to have any food she likes, but she finds it somewhat difficult to take liquid foods. This may be one of the longest recorded follow-up cases in medical history.


Midgut volvulus with secondary thrombosis of superior mesenteric vessels in a pregnant woman.

An anomaly of the position of the midgut in a pregnant woman predisposes to volvulus. Vascular repair, despite the abdominal catastrophe, sometimes allows parts of the intestine to be saved. A case of volvulus in a pregnant woman is described. At operation, 18 hours after onset, two anomalies were found: reverse rotation of the midgut and an anomaly of the collecting system of the superior mesenteric vein. Most of the midgut was infarcted. Thrombi were removed from the superior mesenteric vessels, and a portion of the anamalous superior mesenteric vein was reconstructed. All but 3 M. of the small bowel and the entire right colon were resected. Prolonged treatment with parenteral hyperalimentation enabled us to control the appearance of a moderate degree of malabsorption. To our knowledge, no similar case has been reported previously in the literature.


The value of endoscopic retrograde pancreatography in the management of pancreatic ascites.

A case of pancreatic ascites is presented in which the preoperative use of endoscopic retrograde cannulation of ampulla of Vater (ERCP) precisely located the site of pancreatic duct disruption and thus directed the choice of operation best suited to this patients. We suggest that in this form of ascites preoperative ERCP may aid in the selection of those patients whose lesions are surgically correctable.


Pancreatic ascites: diagnosis of leakage site by endoscopic pancreatography.

A case with pancreatic ascites is presented in which the site of leak from a pancreatic pseudocyst was identified by oral endoscopic pancreatography. It is suggested that this procedure be done early in the clinical course of most patients with pancreatic ascites, since the information obtained will facilitate medical and surgical management.


Thallium-induced achondroplasia in chicken embryos and the concept of critical periods during development.

Achondroplasia was induced in chicken embryos by in ovo application of 0.6 mg/egg thallium sulfate. The critical (sensitive) period for production of achondroplasia began on day 5 of incubation and ended at the start of HH stage 35 (8.5 days). The end of the critical period was accurately timed and found to be 205-207 hours of incubation and to coincide with a 66% decrease in growth rate of the embryos. Treatment resulted in reduced tibial growth one day later, tibial angulation two days later, and chrondrocytic necrosis four days later. The last was therefore not the cause of the angulation. Tibias were taken from thallium-treated and control donor embryos of various ages and grafted to the chorioallantoic membranes of treated and control host embryos of various ages during and outside the critical period and achondroplastic changes induced in grafted tibias exposed to thallium while on the chorioallantoic membrane. The critical period was extended into day 10 of incubation in such grafted tibias. Tibias maintained for seven days in organ culture were achondroplastic if pretreated with thallium at seven or eight days of incubation but not at ten days. Exposure of as little as 0.5 hour was sufficient to elicit micromelia when the tibias were grafted or organ cultured. Thallium therefore rapidly binds to skeletal tissues during a critical period of embryonic development but this critical period may be extended when tibias are removed from the embryo.


Epithelial breakdown in the palatal processes of mouse fetuses with spontaneous cleft lip and palate.

Contact and fusion of the palatal processes are prevented by mechanical obstruction in A/J mice with spontaneous cleft lip and palate. Histological examination of cleft-lip fetuses revealed a very thin epithelial covering on the tip of the palatal process at day 15 1/2 of gestation, when the palate normally undergoes fusion, but at day 16 the palatal epithelium was completely disrupted, exposing the underlying mesenchyme. This epithelial discontinuity lasted only one day--by day 17 epithelial continuity was reestablished. These findings support the hypothesis that contact between the palatal shevles is not a prerequisite for epithelial degeneration.


Prenatal toxicity of medroxyprogesterone acetate in rabbits, rats, and mice.

Medroxyprogesterone acetate (MPA) was given once daily sc at 0.1-3,000 mg/kg/day for 3, 6, or 9 consecutive days during gestation days 7 to 15 to CD1 and A/J mice, and New Zealand (NZ) and Dutch Belted (DB) rabbits, and during days 8 to 16 to CD rats. Malformations attributable to MPA did not occur in fetuses of mice or rats exposed to the largest dosage tested. However, 1, 3, or 10 mg/kg on days 13 to 15 to NZ rabbits resulted in 6, 28, and 42% cleft palate, respectively. Comparable cleft palate frequencies were seen in DB offspring.


Vater syndrome: hypothesis and report of two further cases.

Two cases are reported of the association of a group of abnormalities defined as the Vater syndrome, together with a hypothesis, based on the presence of normal cell death during embryogenesis, on how they occur together so frequently. Although the mechanism of normal cell death is unknown, adjacent cells are probably affected sublethally and subsequently recover. A teratogenic situation introduced simultaneously with the occurrence of normal cell death may further diminish the viability of those adjacent cells, causing increase in the necrotic zone and loss of both normal tissue and growth potential.


Possible teratogenic effect of phenothiazines in human beings.

A prospective survey was carried out by the French National Institute of Health and Medical Research (INSERM) in 12 University hospitals in Paris and included 12,764 women; 189 gave birth to babies with unequivocal, non-chromosomally based, malformations. There was a significant excess of malformed infants when women had taken phenothiazines during the first three months after the last menstrual period. This association did not seem due to chance or to bias and could not be explained by the influence of the outcome of previous pregnancies. These data are to be added to results of recent surveys showing a significant increase of malformations in children exposed in utero to anticonvulsants, carbamates, benzodiazepines, tricyclic antidepressants, and amphetamines.


Embryotoxicity of the folate antagonist methotrexate in rats and rabbits.

The prenatal effects of methotrexate (MTX) in rats and rabbits were assessed. It was found highly embryotoxic in postimplantation rat embryos; 0.3 mg/kg ip or less caused nearly total embryolethality with slight teratogenicity. Rabbit embryos were far more resistant to small doses of MTX than rats, but 19.2 mg/kg iv, when given during days 10 to 15 of gestation, produced little death and a constant spectrum of malformation in a high percentage of offspring. Cleft palate, skull defects, and severe fore- and hindlimb dysplasias, occurred with a high degree of regularity and were strongly dose and developmental-stage specific.


Temporal, morphological, and genetic responses of avian embryos to Azodrin, an organophosphate insecticide.

The effect of Azodrin on avian development was studied using a bobwhite quail line and two chicken lines--a single comb White Leghorn (SCWL) and an Australorp line. The bobwhite quail embryos did not respond to injections of Azodrin until stages 22 to 23 (6 days of incubation); the SCWL embryos, not until stage 18 (3 days of incubation) with increasing susceptibility through stage 20. The threshold concentration, at stage 19, for the SCWL was 0.4 mg/kg, for the Australorp, less. Within one hour of treatment stage-20 embryo shape was altered. There was, however, no immediate response from embryos treated earlier. The effect appeared as a reduced growth rate in the cervical flexure, and may be mediated by interference with the normal energy balance. The response, once initiated, was continuous through 10 days of incubation.


Digital anomalies of mouse limbs induced by treatment with urethan in vitro.

The effects of urethan on ICR/JCL mouse limbs were examined in forelimbs of day-11 embryos cultured in concentrations of 0, 50, and 100 mug/ml for one to four days, and in forelimbs of day-12 embryos and in fore- and hind limbs of day-13 embryos in 0, 10, 50, and 100 mug/ml for one to four days. Urethan did not cause digital malformations on day-11 limbs but induced syndactyly in day-12 forelimbs and polydactyly in day-12 forelimbs and day-13-fore- and hind limbs. The polydactyly may have been due to effects on mesenchymal cells producing localized cell proliferation, whereas syndactyly may have been due to effects on precartilage cells, resulting in excess migration of mesenchymal cells toward the digits, leaving the connective tissue at the interdigital space to develop inadequately.


Haemothorax after subclavian vein cannulation.

A patient in whom pulmonary arterial bleeding occurred during percutaneous supraclavicular puncture of the subclavian vein is described. A retrospective survey of over 600 subclavian venepunctures disclosed seven patients in whom serious traumatic complications occurred, six of them in the hands of inexperienced operators.


Severe mycoplasma pneumonia.

A patient who developed who developed a protracted illness following severe mycoplasma pneumonia is described. The acute phase of the infection was complicated by myocarditis and haemolytic anaemia. The respiratory symptoms abated and lung function tests improved with the administration of systemic and inhaled corticosteroids.


Tumour size as a prognostic factor after resection of lung carcinoma.

Two hundred and ninety-five patients who underwent resection for carcinoma of the lung are reviewed, with a particular view to size of tumour and survival rate. The carcinomas were divided into four groups by size. It was found that the larger the tumour the worse was the prognosis. The prognosis in large carcinomas could not be directly attributed to a preponderance of an unfavourable cell type, lymph node metastasis or mediastinal extension. Vascular dissemination at the time of operation is believed to be a major factor for the poor prognosis in this group of carcinomas. Radiotherapy before operation and early ligation of the pulmonary veins might improve the results of resection of large carcinomas.


Asthma deaths in children--a continuing problem.

The clinical and pathological features of five children who died of asthma over a recent 12-month period are reported. All had severe, chronic asthma requiring maintenance corticosteroid therapy. Three had been receiving beclomethasone dipropionate by inhalation and these had acute inflammation of the tracheobronchial tree at necropsy. Adrenal atrophy was found in all four cases examined histologically, despite normal short tetracosactrin tests in three of these shortly before they died. The need for high-dose corticosteroid by mouth for exacerbations of asthma in those weaned from oral steroids is emphasized by these deaths. The introduction of beclomethasone dipropionate by inhalation has led to an increase in the number of children in this high-risk group.


Clinical improvement of patients with emphysema after radiotherapy.

In advanced emphysema the reduced lung retractive force permits dynamic compression of the airways during expiration; this gives rise to breathlessness which is often refractory to conventional remedies. Radiotherapy causes shrinkage of lung tissue and has therefore been given as treatment to 10 patients with emphysema. They have been followed for two years, during which time three have died from various causes, but no adverse effect of radiotherapy has been observed. All the patients at some time experienced a reduction in breathlessness on exertion and an increase in the range of their daily activities; the distensibility of their lungs was on average reduced but the response to test exercise was not altered. The possibility that the clinical improvement may have been a placebo effect is now being investigated.


Regional lung function in asbestos workers.

Regional lung function was measured using radioactive xenon-133 in a group of normal subjects and in two groups of asbestos workers. When compared with the normal group, patients with pulmonary asbestosis showed impaired ventilation of the lower zones. Subjects with calcified pleural plaques without radiological evidence of lung parenchymal fibrosis did not show this abnormality.


Serial pulmonary function tests in patients with asbestosis.

Serial lung function tests were performed on 17 patients with asbestosis. A marked fall in the transfer factor often preceded any significant decline in the vital capacity. Changes in vital capacity and transfer factor did not appear to give any indication of the prognosis in these patients. Death was more commonly due to carcinoma of the lung than to the effects of the lung fibrosis.


Further observations on luminal deformity and stenosis of nonrespiratory bronchioles in pulmonary emphysema.

In an endeavour to elucidate the anatomical basis for the increased resistance to airflow which characterises the most peripheral conducting air passages in pulmonary emphysema, lumina of nonrespiratory bronchioles of lungs with mainly centrilobular disease were assessed for two- and three-dimensional features by: (1) determination of percentage conformity of the lumina of individual bronchioles in histological sections to hypothetical planes through cylinders (ie, ellipses with the same areas and circumferences), and (2) comparison of luminal areas at regular intervals along bronchiolar longitudinal axes. The lumina of most nonrespiratory bronchioles from normal lungs conformed closely to their respective ellipses, thus corroborating previous observations that they are normally cylindroid. In contrast, there was a substantial excess of plane section deformities in the lumina of nonrespiratory bronchioles from the emphysematous specimens. The incidence of stenotic bronchioles (by both diameter and area determinations) was also greatly increased in emphysema. Since there was a strong positive association between such stenotic lesions and bronchiolar deformity, the latter was concluded to be a major factor in bronchiolar restriction. Furthermore, these characteristics seemed to have three-dimensional expression, for the lumina of stenotic bronchioles in emphysema were irregular in a longitudinal fashion.


A comparison of manual and automated methods of measuring airway resistance and thoracic gas volume.

An automated method of measuring airways resistance (Raw) and thoracic gas volume (Vtg) by whole body plethysmography using a digital computer is described. The results obtained by this method are compared with those obtained by an experienced observer and the results of consistency tests on the two methods are given. There was wide variability in the values of Raw obtained using each method, and no significant differences were found between the two methods. The values of Vtg obtained by them were highly correlated, but the results obtained manually were higher than those obtained automatically by an amount proportional to the volume. The consistency of the computer measurements was shown to be greater than that of the manual method. A significant decrease between successive measurements of Raw in some subjects was noted in the manual observations but not in those derived from the automated method. The new method is suitable for the rapid determination of Raw and Vtg.


Variation between observers in the estimation of airway resistance and thoracic gas volume.

Variations in the estimation of airway resistance (Raw) and thoracic gas volume (Vtg) made by different observers using body plethysmography have been investigated. Five observers determined Raw and Vtg in normal subjects using prerecorded signals so that intrasubject variations were eliminated. The slopes of the oscillography tracings required to make the determinations were assessed using a cursor and a scale fitted to the oscilloscope. Significant and consistent differences in Raw determined by different observers were found,with a mean range of 37%. Great care should therefore be taken when comparing results obtained by different observers. The variation between observers measuring Vtg was significant and consistent but of much smaller magnitude than was the case for Raw, having a mean range of 12%.


Lymphomatoid granulomatosis--a condition with affinities to Wegener's granulomatosis and lymphoma.

A case of lymphomatoid granulomatosis of the lung is described in which the presenting features were a skin eruption and peripheral neuropathy. The onset of the pulmonary symptoms of breathlessness and productive cough was delayed nine months but, when apparent, the extent of the radiological changes contrasted with the mildness of the symptoms and the triviality of the physical signs. Biopsy of the affected lung revealed a mixed lymphocytic, plasma cell, and histiocytic infiltrate following a perivascular distribution. This combination of clinical and pathological findings is in every detail that of lymphomatoid granulomatosis as recently identified by Liebow et al. (1972). Additional, previously undescribed, and unexplained findings in this case were persistent hypercalciuria and the presence in three axillary lymph nodes of subcapsular groups of cells resembling those of a benign naevus. This is the first case described in the British literature, and it is important that more cases be reported in order that the prevalence, prognosis, and aetiology of the condition should be further established.


Pulmonary gas transfer 20 years after pneumonectomy for pulmonary tuberculosis.

The changes in pulmonary function after pneumonectomy in 13 patients with pulmonary tuberculosis have been studied. The data at the time of two follow-up studies are compared with those obtained before the pneumonectomy. The first follow-up was carried out between 5 and 30 months postoperatively and the second between 20 and 24 years later. The results of this second follow-up show a relatively normal arterial oxygen saturation and gas transfer factor but an increased residual volume which cannot be explained by increasing age alone.


Familial pneumothoraces and bullae.

The cases of three sisters who presented with spontaneous pneumothoraces are described. In two of the patients large bullae were clearly demonstrable. No recognisable associations of bullae or pneumothorax were present and there was no evidence of generalised emphysema. The cases suggest a familial predisposition to the development of bullae in otherwise apparently healthy lungs.


Penumopericardium and tension pneumopericardium after closed-chest injury.

Three recent cases of pneumopericardium after closed-chest injury are described. The mechanism of pericardial inflation suspected in each was pleuropericardial laceration in the presence of an intrathoracic air leak. Deflation of the pericardium was achieved by underwater seal drainage of the right pleural cavity in the first patient, during thoracotomy for repair of tracheobronchial rupture in the second, and by subxiphoid pericardiotomy in the last. Haemodynamic changes after escape of air from the periion pneumopericardium and air tamponade.


Chylothorax: diagnosis by lipoprotein electrophoresis of serum and pleural fluid.

This report describes a 31-year-old woman who underwent a technically difficult left pneumonectomy for tuberculosis and developed thereafter a large left pleural effusion which was milky in colour. A traumatic chylothorax was suspected, and the diagnosis was confirmed by simultaneous fasting pleural and serum lipid studies and lipoprotein electrophoresis. The latter study was especially helpful in confirming the chylous nature of the fluid in that it revealed a marked chylomicron band at the origin; this was not present in the patient's serum nor in the pleural fluid of five patients with other disease states studied as controls.


Hereditary angioneurotic edema (HANE): Lack of close linkage between HLA haplotypes and C1 esterase inhibitor deficiency.

The HLA haplotypes were defined in a series including 11 patients with hereditary angioneurotic edema (HANE), five symptom-free subjects with pathological laboratory findings characteristic of HANE, and their 33 healthy kinsmen. The subjects belonged to two Finnish families representing the more common form of HANE which is recognized by the immunochemically observed decrease of the inhibitor (C1-INH) blocking the esterase activity of the first complement component. No linkage between HANE and the HLA system was found.


The effect of water-soluble chemicals on the growth and mitosis of primary newborn rat kidney cells in culture.

Mass cultures of primary rat kidney cells were exposed briefly to aqueous solutions of 20 chemicals and their subsequent growth rate and mitotic activity measured. Proximate carcinogens, and some chemicals with a defined inhibitory action biochemically, depressed the growth and division of the cultures. Non-carcinogenic compounds and precarcinogens did not interfere with the subsequent growth rate and mitotic activity of the cultures. It is suggested that the possession of growth inhibitory properties could give an indication of the carcinogenic activity of a chemical on a short-term basis.


Influence of oral contraceptives on the acute effect of amphetamine on the hepatic endoplasmic reticulum of the rat.

The interaction between amphetamine and synthetic oral contraceptive steroids have been studied in the female rat. A progestational agent, quingestanol acetate, and a standard combination contraceptive (quingestanol acetate/ethynyl estradiol) were given with and without the concurrent administration of amphetamine. Steroid treatments increased the activity of some drug-metabolizing enzymes (aminopyrine N-demethylase, coumarin 3- hydroxylase, hexobarbital oxidase). Other parameters measured remained unaltered (glucose-6-phosphatase, aniline hydroxylase, cytochrome c reductase, cytochrome P 450, microsomal protein and phospholipid contents). Amphetamine treatment alone raised some drug-metabolizing enzymes (coumarin 3-hydroxylase, hexobarbital oxidase), increased microsomal phospholipid content and de novo synthesis, but elicited no effect on other enzymes measured. Amphetamine and quingestanol acetate given together significantly increased some drug metabolizing enzymes while the simultaneous treatment with combined steroids and amphetamine showed the most pronounced action. These experiments thus revealed that at least in the liver of the female rat, amphetamine elicited no overt hepatotoxicity, rather, brought about a weak inductive action of drug metabolizing enzymes. The application of steroid hormones also raised drug metabolism and the interaction between amphetamine and contraceptive steroids showed additive effects.


Short-term toxicity of strontium chloride in rats.

A range-finding experiment with strontium chloride hexahydrate (0, 3, 30, 300 and 3000 ppm in the diet) and subsequently a 90-day test with the same compound at dose levels of 0, 75, 300, 1200 and 4800 ppm in a semipurified diet was carried out with SPF-derived Wistar-rats. The diet contained adequate levels of Ca, Mg, P and Vit.D3. Growth, food intake, behaviour and mortality were measured, extensive haematology and clinical biochemistry carried out, organ weights determined, X-ray photographs of the bones taken and complete histopathological examination was performed. In addition Sr-content of blood, bone and muscles was determined. Thyroid weights were significantly increased in the males of the 1200 and 4800 ppm group. Histological evidence for increased thyroid activity was noticed in the males of the 4800 ppm group. Pituitary weights were significantly decreased in the females of the 300 ppm and 4800 ppm group, but not of the 1200 ppm group. A histologically confirmed glycogen depletion of the liver was noted biochemically in the highest dose group (4800 ppm). Sr-content in bone was increased at all dose levels having a constant level from 4 weeks onwards, thus indicating that a no effect level cannot be established. If the increased Sr-concentration in the bone can be considered a non-toxic effect, the non-toxic effect level appears to be 309 ppm.


[Effects of methylcyclopentadienyl manganese tricarbonyl (MMT) of rat liver mitochondria. I. Effects, in vitro, on the oxidative phosphorylation (author's transl)].

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an effective inhibitor of mitochondrial respiration associated with NAD+-linked substrates. At concentrations which inhibit glutamate-malate oxidation (over 80% inhibition) succinate and tetramethylphenylenediamine (TMPD)-ascorbate are inhibited less than 25%. MMT inhibits both electron and energy transfer in mitochondria as revealed by the partial release of MMT inhibition by 2,4-dinitrophenol (DNP). The data indicated that the effects of MMT are supported by energy conservation at site I of the respiratory chain.


The absorption and metabolism of methyl cinnamate.

Analysis of the gut contents of rats killed at intervals after dosage with methyl cinnamate or cinnamic acid suggested that both ester and acid were rapidly absorbed; at no time was more than 5% of the dose detected in the lower part of the gut. Not more than 9% of the administered methyl cinnamate was detected in the stomach as cinnamic acid whereas at least 40% of the small amounts of the dosed ester detected in the lower part of the gut was present as cinnamic acid. No ester was detected in the peripheral blood of dosed rabbits or rats and only traces were detected in portal and heart blood samples taken from dosed rats. Cinnamic acid and methanol were readily detected in the blood of rabbits and rats which had been dosed with methyl cinnamate. No qualitative or significant quantitative difference was detected in the metabolism of the ester as compared with the parent acid. In addition to the metabolites of cinnamic acid described in the literature p-hydroxyhippuric acid was excreted as a minor metabolite of both cinnamic acid and methyl cinnamate.


Reversal of the toxicity of hydrazine an analogues by pyridoxine hydrochloride.

Single subcutaneous injections of each of five substituted hydrazines were given alone and jointly with pyridoxine hydrochloride (PH) to Swiss mice. The convulsive, toxic, and lethal effects of four compounds--methylhydrazine (MH), ethylhydrazine hydrochloride (EH), n-butylhydrazine hydrochloride (BH), and beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine--were successfully prevented by administering PH before and/or after injection. The toxic symptoms caused by N-methyl-N-formylhydrazine (MFH) were, however, only slightly inhibited by this vitamin.


Biocompatibility and bioabsorption of microfibrillar collagen hemostat in experimental animals.

The effects of Microfibrillar Collagen Hemostat (MCH) and Gelfoam after surgical implantation into incision sites of the liver, kidney, and brain were studied in beagle dogs, rabbits, and beagle dogs, respectively. The results of these experimental animal studies suggest that MCH is comparable to Gelfoam with respect to biocompatibility, rate of bioassimilation, and a lack for adverse systemic effects. The brain, liver, and kidney tissues responded comparably to MCH and Gelfoam with a mild to moderate infiltration of macrophages and mononuclear cells. Most of the hemostatic compound had disappeared from the incision sites by Day 28 and completely disappeared by Day 84. The tissue degree response was interpreted as a factor in the process of bioassimilation of the two hemostatic materials. Both hemostatic compounds contributed to adhesion formation in the experimental models. The incidence of adhesions was somewhat lower for MCH than for Gelfoam, but both produced more adhesions than were found at the control sites. The adhesions were only to the adjacent structures and always localized to the surgical site. When MCH or Gelfoam is used under conditions similar to those in the present experimental study, where tissue approximation is impaired, and where growth of granulation tissue is stimulated by the physical presence of the hemostatic compound, there is the possibility for increased incidence of adhesion formation. However, when an intraperitoneal absorbable hemostatic compound is desired, the present studies in experimental animals suggest that MCH will be safe by exhibiting minimal tissue reaction.


The effect of chronic underfeeding on organ weights of rats. How to interpret organ weight changes in cases of marked growth retardation in toxicity tests?

Growing male rats were kept on a restricted feed intake. After 13 weeks they reached a final body weight of 250 g in comparison with 366 g of their ad lib. fed controls. The relative weights of the heart, kidneys, spleen, pituitary and prostate/seminal vesicle were not altered by underfeeding. The relative weights of the brain, adrenals and tests were increased by 30 to 40% in the feed-restricted groups, the thyroid by about 20%. The relative weight of the liver was decreased by about 30%. When growth is markedly reduced in a toxicity experiment alterations of this kind in the organ weight: body weight ratios have to be expected as a physiological response of the organism to decreased feed intake. They must be differentiated from organ weight changes resulting from primary toxic influences of the drug tested.


Toxic effects of Iomex on rat after repeated oral administration.

Administration of Iomex, petroleum fraction, at a dose level of 1 ml/kg for a period of 4 weeks did not produce any toxic symptoms in albino rats. At higher doses, however, the animals showed high incidence of mortality, reduction in food and water intake and loss in body weight. At necropsy, lungs were found to be congested and intestines hyperaemic. Histopathological examination revealed slight abnormalities in lungs, liver and kidney. The absolute organ weights decreased (liver, kidney, heart, spleen, lung, gonad, brain and adrenal), whereas relative weights increased. There was a significant fall in total erythrocyte (RBC) and total leucocyte (WBC) counts and haemoglobin content (Hb) was reduced. Increased lymphocytes with correspondingly decreased neutrophils were also observed. Serum and liver transaminases (GOT and GTP) showed enhanced activity.


Evaluation of freshly irradiated wheat for dominant lethal mutations in Wistar rats.

Three independent, serially performed experiments involving acute and chronic feeding of freshly irradiated wheat (75 krad, gamma-irradiation) were carried out in Wistar rats. In the first experiment groups of 10 males were given wheat for 1 week; irradiated wheat was consumed by the animals within 24 h or irradiation. In the other two experiments feeding of males was continued for 6 (10 males per group) and 12 (13 males per group) weeks, respectively, and the irradiated wheat was fed within 7 days of irradiation. At the end of each treatment period each male was paired with 3 females for 7 days and sequentially at weekly intervals for 5 or 8 weeks. Females were killed and examined for live and dead implantations and corpora lutea. There were no differences between groups with regard to fertility nor was there any inter-group differences as regards pre- and post-implantation losses whether the rats were fed irradiated or non-irradiated wheat. This suggested that even feeding of freshly irradiated wheat does not induce any dominant lethal mutations in rats.


Effect of amphetamine on the hepatic endoplasmic reticulum of the pregnant rat.

Search for the elucidation of the mode of action of amphetamines has revealed that this drug brought about changes in the activity of some enzymes bound to the hepatic endoplasmic reticulum of the pregnant and non-pregnant rat. Amphetamine administration caused loss of appetite and changes in enzyme activity due to starvation, however, its effects were assessed applying pair-feeding conditions. Drug-metabolizing activity was increased by amphetamine as measured by coumarin 3-hydroxylase and aminopyrine N-demethylase in both pregnant and non-pregnant animals; aniline hydroxylase was elevated only in pregnant rats. These changes were associated with the enhanced synthesis of microsomal phospholipids as indicated by the increased activity of [14C-Me]S-adenosyl-L-methionine : microsomal phospholipid methyl transferase, de novo synthesis and levels of microsomal phospholipids. These effects were mainly manifest in phosphatidylethanolamine and phosphatidylcholine fractions. Glucose-6-phosphatase activity remained unaltered by amphetamine. Pregnancy alone brought about a reduction of all these microsomal parameters. The rise of hepatic drug metabolism following the administration of amphetamine indicated a compensatory mechanism by means of stimulating enzyme induction processes.


[Wood's alloy, a material suitable for quick production of individualized shielding blocks in the mantle technique (author's transl)].

The extended radiation therapy of lymphogranulomatosis by means of the mantle technique requires individualized focussed satelittes. The production of such individualized, ray divergences considering "lead mantles", however, needs some technical expenditure and causes loss of time. Using Wood's alloy, which has a shielding capacity similar to lead but is well and easily workable because of its low melting point, it is possible to obtain individually adjusted shielding blocks by casting.


[Radiation therapy of an inoperable giant cell tumor (author's transl)].

The case of a patient showing an inoperable giant cell tumor in the right wing of the ilium, with extension to the sacrum, is reported. Following radiation therapy with 7000 rd from telecobalt a complete regression of the tumor could be represented angiographically.


[Construction of tissue compensating filters for extended areas in Hodgkin-irradiation on the basis of moiré topography (author's transl)].

In order to obtain a homogeneous distribution of the dose over extended fields in radiotherapy of Hodgkin's disease, for an exact dosage within the irradiated region it is necessary to consider the topography of the patient. The skin protective build-up effect due to the use of bolus materials would be lost with telecobalt irradiation, and therefore tissue compensating filters with a large surface are to be preferred. A simple method of making such filters by means of the moirétopography is described. The way to obtain a compensation filter for extended areas is demonstrated by an example showing how to construct it from lead plates correct in scale and layerwise.


[A simple method to evaluate the composition of tissue-equivalent phantom materials (author's transl)].

A description is given of a method to calculate the composition of phanatom material with given density and radiation-physical parameters mixed of components, of wich are known their chemical composition and their effective specific volumes. By an example of a simple composition with three components the method is illustrated. The results of this example and some experimental details that must be considered are discussed.


[Depth therapy with electrons in the thoracic region. V. Dosimetric studies with telecentric small-angle pendulous irradiation (author's transl)].

The conditions of dose distribution in telecentric small-angle pendulous electron irradiation of the thoracic region are reported on the basis of isodoses experimentally found using a phantom. Electron energies from 20 to 42 MeV were used, the axial depth amounted to 20 to 30 cm, the pendulous angles to 30 degrees, 40 degrees, or 60 degrees and the field breadth was 3 or 4 cm. Irradiations were performed monaxially as well as biaxially. The influences of single variables upon the dose distribution and especially on the radiation load to skin, lung and spinal cord are discussed.


Trials of new forms of radiotherapy for locally advanced bronchogenic carcinoma. Irradiation under 95% O2 plus 5% CO2 inhalation, uneven fractionation irradiation and intraoperative irradiation.

In order to improve the survival rate of patients with clinically inoperable but localized bronchogenic carcinoma, we have developed the following three forms of radiotherapy and analyzed the results in comparison with those obtained by conventional radiotherapy: 1. Irradiation under 95% O2 plus 5% CO2 inhalation, 2. Uneven fractionation irradiation, 3. Intraoperative irradiation. The tumor regression rate was most pronounced in the 95% O2 plus 5% CO2 breathing group and the one-year survival rate was significantly increased. However, the longterm survival rate was almost the same as that of patients treated by conventional radiotherapy. In uneven fractionation irradiation, the follow-up period is short, but the preliminary results seem most encouraging. Intraoperative irradiation is well indicated for patients with poor pulmonary functions, in whom the localized malignant lesions were left behind following excision of the main mass. The reason is that a cancerocidal dose can be delivered directly to the unresectable remnants without affecting normal structures.


Preoperative radiotherapy of cancer of the larynx.

A series of 128 patients was treated with preoperative radiotherapy, 3000 to 4500 rd, and surgery in 1968 to 1972 at the Radiotherapy Clinic and Otolaryngological Clinic, University Central Hospital, Helsinki. The absolute three-year and five-year survival rates for the total material were 71.1 and 53.2 per cent, respectively. The postoperative complications were two deaths from pneumonia, one of them after aspiration. In addition, 21.3 per cent of the patients had a postoperative fistula. All the fistulae healed spontaneously.


[The incidence of new (second) lesions after surgery and irradiation (author's transl)].

A comparative analysis of 1286 patients with squamous cell carcinomas of the upper respiratory and digestive tracts successfully treated either by surgery, irradiation or a combination of both showed that the incidence of new (second) lesions in these regions is practically identical with the different treatment modalities up to 25 years following treatment. Only within five years following surgery the incidence of new cancers in the vicinity of the original cancer is statistically significantly higher than in patients treated by irradiation alone or in combination with surgery. This is explained by probable eradication of in situ carcinomas or microscopic foci of invasive cancer located in the vicinity and hence receiving a significant dose of irradiation. These new (second) lesions occur about 1000 times more frequently than it would be expected from the estimated cancer-incidence in these sites and are to be separated from the extremely rare therapeutically induced malignancies.


[Radiation therapy in syringomyelia (author's transl)].

It is tried to summarize the different opinions concerning the pathogenesis, radiobiology and techniques of irradiation in the treatment of syringomyelia. The results obtained at the Radiotherapeutic Clinic of the University of Vienna are reported. Between 1969 and 1974 a total of 25 patients with this disease were treated with doses of 500 to 1500 rd SD. In 15 patients (60%) an improvement of symptoms occurred. Long time remissions could be observed in six out of 11 patients.


[In-vivo-examinations of the relative radiosensitivity of hypoxic tumor cells (author's transl)].

The rate of cellular losses of hypoxic respectively euoxic cells of the solid experimental tumor "sarcoma 180" was examined in vivo after irradiations with gamma rays, 15 MeV neutrons, and alpha particles. The tumor cells were labeled in vivo, at first with 125I-UdR and after 50 hours with 131I-UdR. After a further interval of about 20 hours the tumor was irradiated. This method of double labeling makes it possible to determine externally the rates of cellular losses in the labeled zones of tumor cells presenting different partial oxygen pressures. The increase of the rates of cellular losses among the euoxic and hypoxic tumor cells induced by the gamma radiation differs by 2.6; it decreases, however, to 1.5 after injection of nitrofurazone prior to the irradiation. After irradiation with 15 MeV neutrons, a difference of only 1.4 was observed. If the tumors were irradiated internally with alpha particles from the reaction 10B(n,alpha) 7Li, there was no difference between the two rates of cellular losses. As far as the above mentioned kinds of radiation are concerned, the ratios from the increase of the rates of cellular losses induced by radiation are well corresponding to the oxygen enhancement found by other authors during their examinations in vitro.


[Pharmacodynamics of technetium-99m phosphatic compounds in the course of radiation therapy (author's transl)].

Based on a case suffering from an extraosseous tumor infiltrating the mandibula, the behaviour of 99mTc phosphatic compounds in the course of radiation therapy is described. Own measurements are confronted with results from literature. Thus it turned out that a valid interpretation of the late response was not possible, further studies undoubtedly being necessary.


Effects of low doses of DTPA on the excretion and organ retention of 144Ce in the rat.

Single doses of 5, 15 or 50 mg of Na3Ca-DTPA per kilogram of body weight were intraperitoneally injected 1 hour (prompt treatment) or 3 days (delayed treatment) after the intravenous injection of 144CeCl3 in the rat. The daily urinary and fecal excretion of 144Ce was determined for 15 days post 144Ce injection. The retention of 144Ce in the several organs 15 days after the 144Ce injection was also determined. A method to assess the DTPA-enhanced amount of urinary excretion of 144Ce from the early urinary excretion of 144Ce post therapy was proposed.


The effect of erythromycin and its thiocarbamide derivative on the induction of meiotic chromosome rearrangements in irradiated male mice.

Antibiotics, erythromycin and a thiocarbamide derivative of erythromycin were tested for their ability to induce chromosome translocations in whole-body irradiated mice with a dose of 600 r. The aim of the present paper was to determine whether these antibiotics might induce by themselves, chromosomal translocations and whether these agents have a protective effect against X-rays-induced chromosomal translocations in the spermatocytes at the first meiotic metaphase. The incidence of translocations in irradiated animals was 9.07%; in animals treated with erythromycine after irradiation it was 3.80%; and in those treated with a thiocarbamide derivative of erythromycin following irradiation was 3.20%. Not a single chromosome rearrangement was scored among the non-irradiated animals, treated with the mentioned antibiotics.


Effects of estradiol-17beta on cholesterol metabolism in the rat: a study using a deuterium label and mass spectrometry.

The effect of estradiol-17beta (E2) on several important aspects of cholesterol metabolism were examined in the rat. Ovariectomized rats were implanted subcutaneously with 1 or 4 cm. of silastic tubing packed with E2, and were also given 2% D2O in their drinking water. The E2 diffused slowly out of the implants and the two different lengths of tubing resulted in constant E2 blood concentrations of either high (4.0 cm) or physiological (1.0 cm) levels. By measuring the rate of incorporation of deuterium into plasma cholesterol by mass spectrometry over a period of 42 days, we determined the rate constant of cholesterol synthesis and cholesterol turnover time and rate under two E2 dosage conditions. E2 treatment did not affect the rate constant of cholesterol turnover rate (mg synthesized/day) showed a dose dependent reduction with increasing doses of E2. This may be secondarily caused by E2's suppression of both food intake and subsequent weight gain; E2 treated animals are smaller and, therefore, synthesize less cholesterol per day. Additionally, E2 treated animals showed a rise in plasma cholesterol levels and in the fraction of labeled cholesterol appearing in the plasma.


Androgens on the estrogen receptor. II--Correlation between nuclear translocation and uterine protein synthesis.

In the immature rat uterus, occupation of the androgen and estrogen receptor sties after injection of 5 alpha dihydrotestosterone (DHT = 17beta - hydroxy-5alpha-androstan-3-one) were compared to the biological responses induced by the androgen on protein synthesis. Injection of 100 mug DHT induced a maximal occupation of androgen receptor sites (RA) but was totally ineffective in translocating the estrogen receptor sites and in increasing general protein synthesis. Conversely, high doses of androgen (greater than or equal to 3 mg) translocated the estrogen receptor (RE) and stimulated general protein synthesis. In addition, these high doses induced a specific uterine protein undistinguishable from that induced by estradiol treatment (IP). These results strongly suggest that the uterotrophic response of the uterus to androgen is correlated with the nuclear transreceptor which is present in much smaller amounts.


Synthesis of a disulfide affinity adsorbent for purification of estrogen receptor.

Synthesis of an estrogen affinity adsorbent containing a disulfide linkage between the steroid and stationary matrix permitted facile purification of high affinity estrogen binding proteins. Following affinity chromatography of either antibody directed against estrone 17-carboxymethyloxime - bovine serum albumin or immature calf uterine cytoplasmic estrogen receptor proteins, the specifically bound mercaptoethanol. Crude antibody and uterine cytosol was 10(-3) to 10(-2)M cystamine (S-S) to block SH-containing proteins, in order to protect the adsorbent against protein-mediated S-S in equilibrium SH exchange. Cystamine was found to markedly stabilize crude cytosol receptor protein by 200-300% compared with preparations obtained under ordinary conditions. Disulfide affinity adsorbents are versatile in that they can be used either under conventional conditions of specific protein recovery, or with 2-mercaptoethanol which removes the ligand and bound protein from the stationary matrix quantitatively.


Progesterone in the uterus. VII. Uptake of cortisol and incorporation of progesterone under simultaneous application of cortisol into rat uterus.

After injection of radioactively labelled cortisol, the distribution of the radioactivity in the subcellular fractions of the rat uterus (nuclei, mitochondria, microsomes and 105 000 X g supernatant) was studied. In all fractions, radioactivity was observed and maxima were found 10, 20 and 50 min. after injection of the labelled hormone. Radioactivity was measured in all subcellular fractions even 180 min. after application of labelled cortisol. Additionally, radiolabelled progesterone and unlabelled cortisol in the ratio 1:1 or 1:2 (moles:moles) were injected into the animals. Studying the uptake of labelled progesterone in the subcellular fractions of the uterine tissue, revealed that no competition of unlabelled cortisol could be observed 10, 20 and 50 min. after application of the hormone mixture, compared with the control experiments. The results of this study give evidence that the progesterone uptake into rat uterus is specific and cannot be influenced by unlabelled cortisol.


Sterol and bile acid metabolism during development. 1. Studies on the gallbladder and intestinal bile acids of newborn and fetal rabbit.

Bile acid composition and content in the intestine and gallbladder of newborn and fetal rabbits were investigated. Unlike the circumstances in adult rabbits, the bile acids were conjugated with both taurine and glycine. The major bile acids of the fetus and newborn rabbit were cholic acid, chenodeoxycholic acid, and deoxycholic acid. This is different from the known bile acid composition of adult rabbits, in which deoxycholic acid is the major bile acid (greater than 80%). The proportion of chenodeoxycholic acid was higher in the fetal than in the newborn tissues. The total bile acid pool in the newborn was higher than in the fetus. In the fetus, large proportions of bile acids (60.9%) were associated with the gallbladder fraction, whereas in the newborn the bulk of the bile acids were found with the intestinal fraction (64.4%).


Synthesis of new steroid haptens for radioimmunoassay. Part III. 15beta-Carboxyethylmercaptosteroid-bovine serum albumin conjugates. Specific antisera for radioimmunoassay of 5alpha-dihydrotestosterone, 5alpha-androstane-3beta, 17beta-diol and 5alpha-androstane-3alpha, 17beta-diol.

The syntheses of 15beta-carboxyethylmercapto-5alpha-dihydrotestosterone, 15beta-carbosyethylmercapto-5alpha-androstane-3beta, 17beta-diol and 15beta-carboxyethylmercapto-5alpha-androstane-3alpha, 17beta-diol and the preparation of their bovine serum albumin (BSA) conjugates are described. These conjugates were employed for the generation of specific antisera suitable for radioimmunoassay (RIA) of 5alpha-dihydrotestosterone (5alpha-DHT), 5alpha-androstane-3beta, 17beta-diol (3beta-diol) and 5alpha-androstane-3alpha, 17beta-diol (3alpha-diol).


Determination of rat muscles androgen-receptor complexes with methyltrienolone.

In the present study, "in vitro" evidences are shown for the existence of a highly active 3alpha-hydroxysteroid dehydrogenase in the crude cytosol of rat muscle homogenates; the use of 5alpha-dihydrotestosterone (DHT) is therefore compromised in receptor binding measurements because of its extensive metabolism. The synthetic anabolic androgen, methyltrienolone (MT) palliates this disadvantage of DHT. Both steroids, as well as testosterone, appear to be bound to an 8 - 8.5 S androgen receptor on sucrose density gradient. The androgen receptor in the vastus and the levator ani bulbocavernosus complex (LA/BC) shows similar association constants, but the number of binding sites in LA/BC is about 5 times higher than in vastus. Otherwise, the total number of muscle androgen receptors seems to be invariant in adult and aged rats. The binding to these macromolecules can thus be measured "in vitro" provided specific and sensitive methods are utilized.


Estradiol-17beta receptors in the immature rat ovary.

Estradiol binding components in the cytosol and nuclear fractions of the ovary from immature rats (22-28 days old) were characterized by in vitro methods. Several of the biochemical characteristics of the estradiol binding components in the ovarian tissue were compared with the estradiol receptor from the uterus. The results suggest that the ovarian estradiol binding components are similar to the specific high affinity estradiol receptors in the uterus. In the cytosol of intact rat ovary a significant fraction of the total binding sites was found to be occupied, presumably by the endogenous estrogen. Following hypophysectomy there was a significant increase in the available cytosol binding sites. Evidence for translocation of cytosol receptor-estrogen (RE) complex to the nucleus was obtained for the ovary. The sedimentation properties of the RE complex of the ovary and the uterus are similar. The ovarian cytosol RE complex sediments at 7-8S in glycerol gradients at low ionic strength and at 4S in sucrose gradients at high ionic strength. Following extraction with 0.4 M KCl the ovarain nuclear RE complex sediments at 5S in sucrose gradients which is identical to that of the uterine nuclear receptor.


Stimulation of hepatic cholesterol 7alpha-hydroxylase activity by administration of an estrogen (17beta-estradiol-3-benzoate) to female rats.

Adult female rats were given daily subcutaneous injections of 17beta-estradiol-3-benzoate, 25 mug/day for twenty days. Rats were then killed under four different experimental conditions: (1) Fasting, killed in the morning (FM), (2) Non-fasting, killed in the morning (NFM), (3) Fasting, killed at night (FN), and (4) Non-fasting, killed at night (NFN). Estradiol induced a three-fold increase in hepatic cholesterol 7alpha-hydroxylase activity in group FM and a significant increase in group NFN. Although increases in 7alhpa-hydroxylase activity might be associated with lower serum cholesterol levels (by increasing the rate of conversion of cholesterol to bile acids), serum cholesterol concentrations were, in fact, elevated in all rats given estradiol.


A steroid structure which refutes the isolation of C(17)-C(20) rotational isomers.

Isolation of two C(17)-C(20) rotamers of 20-methyl-20-(2-hydroxyethoxy)-5-pregnene-3beta, 17alpha-diol has been reported. X-Ray analysis of a diacetate derivative of one of the "rotamers" shows that the actual structure is 3beta-acetoxy-17aalpha-(2-acetoxyethoxy)-17alpha,17abeta-dimethyl-D-homo-5-androsten-17beta-ol (C28H44O6). Thus, although this investigation refutes the existence of C(17)-C(20) rotamers, it suggests a possible new pathway for D-homo steroid synthesis.


Epimerisation of 3beta-ol to 3alpha-ol steroid alkaloids by Nocardia restrictus.

(22S,25S)-5alpha-tomatanin-3beta-ol, N-acetyl-(22S,25S)-5alpha-tomatanin-3beta-ol, (22R,25R)-5alpha-tomatanin-3beta-ol and (22R, 25S)-22, 26-epimino-5alpha-cholestane-3beta, 16beta, 16beta-diol are transformed by Nocardia restrictus into corresponding 3alpha-ol compounds with yields from 7o to 5%.


Life-table analysis of IUDs: problems and recommendations.

Two major prospective studies of copper-bearing IUDs showed substantial changes in termination rates when calculated at different dates. One of the studies employed the Tietze life-table method and showed progressive increases in termination rates with the passage of time. The other study used the Potter life-table method and showed sharply decreased termination rates at later assessments. In investigating the reasons for these changes, it was noted that the data collected for periodic analyses during the studies violated the assumptions underlying the life-table technique. It was discovered that as a result of these violations the Potter and the Tietze life-table calculations based on the same set of data produced markedly different estimates of IUD termination rates during the course of a study. Underlying these differences, and the reason for the apparent changes in termination rates, was a large set of incomplete observations. Neither of the two life-table methods was able to deal adequately with the biases arising from these incomplete observations. The "anniversary method," devised to overcome the perceived problems of the Potter and Tietze methods, also proved inadequate to deal with the incomplete observations. Only vigorous and active follow-up, together with ample time to complete data collection, editing, coding, and key punching, is likely to reduce the proportion of women with incomplete observations and is likely to minimize the biases attendant upon incomplete or partial observations of acceptors in prospective clinical studies of IUDs.


Studies on onchocerciasis in the United Cameroon Republic. III. A four year follow-up of 6 rain-forest and 6 Sudan-savanna villages.

After an interval of four years the same observers used the same standardized techniques to re-examine 1,016 people in 12 heavily infected rain-forest and savanna villages in Cameroon. The changes in the number of nodules and in the concentration of microfilariae in the skin and eye are described. These latter changes are correlated with the development and/or deterioration of eye lesions and visual impairment. In both the rainforest and the savanna there was a strong association between the development of eye lesions and a high concentration of microfilariae, not only in the eye but also in the skin, and more so at the shoulder than at the buttock. The importance of these findings for the prevention of blindness is discussed.


Pathology of ocular onchocerciasis: human and experimental.

Involvement of the outer eye in Onchocerca volvulus infection is characterized by an inflammatory process around degenerating microfilariae. Individual microfilariae in the cornea may be associated with localized punctate lesions or, especially when present in large numbers, may provoke a sclerosing keratitis due to invasion by fibrovascular pannus from the limbal conjunctiva. Anterior uveitis develops in some patients and can be either granulomatous, probably as a result of direct microfilarial invasion of the iris and ciliary body, or non-granulomatous, in which case the inflammation is likely to be a response to free microfilarial antigens. Posterior segment involvement takes the form of either inflammatory or atrophic lesions, or both. It is possible that the marked atrophy of the retina and choriocapillaris seen in some cases is largely attributable to preceding choroiditis and that the optic nerve atrophy has a similar pathogenesis.


Growth of Zambian children.

In order to identify as early as possible those children who may later develop malnutrition, a sample of Zambian copper-miners' children of known age and birth weights were measured at the age of one year and again at 18 months. By this time, their mean weight, height, triceps skin-fold, arm circumference and developmental progress were less than expected and many were, or had been ill, with malnutrition and infections. The slower growth corresponded significantly with lower development scores. The mean values of the physical measurements resemble those previously observed in Zambia, and it is concluded that the "Harvard" and Tanner standards are suitable for use in this country. The mid upper arm circumference is the easiest and cheapest measurement to make and it compares closely with other measures. A value of 15 cm or less from the age of seven months onwards in young children should arouse suspicion that their nutrition is at risk.


Ethnic differences in growth potential of children of African, Indian, Chinese and European origin.

Community surveys of infants and children of African, Indian, Chinese and European origin in Guyana and Jamaica have been reviewed in order to compare the influence of ethnic origin and environment, including nutrition, on anthropometric measurements used to assess nutritional status. Mean heights and weights of African and European were greater than those of Indian and Chinese children. African had greater weight for height and greater arm circumferences but smaller triceps skinfolds than Indian children. These differences, which cannot be explained by nutritional or other environmental causes, show that ethnic origins cannot be disregarded when assessing nutritional status by anthropometric measurements. Specific adjustments to international standards of height and weight are proposed in order to make them more appropriate for Indian and Chinese children.


Liver disease in early life in Kenya.

A survey of significant pathological abnormalities of liver in the first two decades of life is presented; this is based on biopsy and autopsy specimens received in the histopathology service in Nairobi over five years. It includes conditions which one might expect in a diagnostic service in any country, some of which are attributable to known local conditions, and others which show distinctive features in their occurrence of frequency. There is an unexpected number of cases of chronic aggressive hepatitis and cirrhosis and the latter is notable for its frequency in the first decade of life. Hepatocellular carcinoma also occurs rather commonly, although most often in the second decade and as a complication of cirrhosis. There is a marked male preponderance in chronic aggressive hepatitis, cirrhosis, hepatocellular carcinoma and schistosomiasis. It is unlikely that this is due to selection of cases and the series shows no indication of tribal influence. The possible role of infections and toxins, particularly in the genesis of chronic aggressive hepatitis and cirrhosis, is discussed. In the search for clues to pathogenesis, detailed systematic investigation of children with liver disease is advocated, paying particular attention to cultural background, and exposure to infections and toxic agents.


The protective effect of BCG against Mycobacterium ulcerans disease: a controlled trial in an endemic area of Uganda.

In a BCG vaccination trial in an area of Uganda endemic for Mycobacterium ulcerans disease ("Buruli Ulcer"), 8,856 persons were examined for the disease in mid-1970 and tuberculin tested; BCG was given by intradermal injection to a random 50% of all those with negative, low or middle grade tuberculin reactions; Twelve months later the study group was re-examined for M. ulcerans lesions and, subsequently, new cases of the disease were detected, using a hospital registration system, to December 1974. One hundred and forty-nine patients with onset since July 1970 were thus ascertained and BCG was found to offer an overall protection of 47% against the disease, similar to that observed in a previous smaller trial by the Uganda Buruli Group (UBG, 1969). However, the protective effect was confined to those with tuberculin reactions of less than 4 mm before vaccination and was apparent only in the first year of the study. BCG offered no additional protection to those with previous M. ulcerans disease or an existing BCG scar at entry into the trial, although both these groups appeared to be protected against the disease, the protective effects being 88% and 82% respectively. An initial tuberculin reaction of 4 mm (or greater) offered some protection against the disease (37%). Lesions developing in the vaccinated group, or in those with initial tuberculin reactions of 4 mm or more, were smaller than those in unvaccinated persons. No relationship was found between the protective effect of BCG and either the prevalence of persons with evidence of previous M. ulcerans disease in different geographical areas, or the incidence of new cases in different areas during the first year of the study. A decline in the incidence was observed over the study period. The findings are consistent with BCG producing only short-lasting protection against M. ulcerans disease. However, long-lasting protection and a delay in onset of the disease in vaccinated persons, as suggested by the UBG in 1969, cannot be excluded on the basis of the data currently available from this trial.


Differences between acute hepatitis A and B in Hong Kong,.

Of a consecutive series of 102 patients with acute hepatitis in Hong Kong, 53% had type B infection. Non-Caucasians (Nepalese and Chinese) were more prone to hepatitis B and Caucasians were more prone to hepatitis A. Hepatitis B, but not hepatitis A, appeared to affect Non-Caucasians more severely than it did Caucasians. Possible reasons for this are discussed. A history of previous contact with a case of hepatitis was more commonly given in type A than type B hepatitis. Tattooing may have been a factor in some cases of hepatitis B among Caucasians. Compared with hepatitis A, hepatitis B involved a shorter prodrome (pre-icteric phase) and was a more severe disease. Unexpected differences in the biochemical patterns between the two diseases are demonstrated. Distinctive time-patterns of serum enzyme and serum bilirubin levels for each type are described, and these enable criteria to be devised by which three-quarters of cases can be correctly diagnosed as A or B. Such diagnosis is unrelaible in the individual case, however, except for seven out of every 10 hepatitis A cases which are capable of correct diagnosis on biochemical data alone.


Hepatitis B surface antigenaemia in Kenyans with chronic liver disease.

Fifty Kenyan patients with chronic liver disease or hepatocellular carcinoma were tested for hepatitis B surface antigenaemia by radioimmunoassay. The hepatitis B surface antigen was detected in 77% of the patients with chronic persistent or chronic aggressive hepatitis, or cirrhosis confirmed by liver biopsy, compared with 15% in a control group. All six patients with hepatocellular carcinoma had detectable hepatitis B surface antigen or antibody. 50% of the controls had hepatitis B surface antibody in their plasma detectable by haemagglutination. Auto-immune associated liver disease appeared infrequent. The possibility that the hepatitis B virus is an important cause of cirrhosis in Kenya is discussed.


Analysis of the causes of death on the medical wards of the University College Hospital, Ibadan over a 14-year period (1960-1973).

An analysis was carried out of the mortality rate on the medical wards of the University College Hospital, Ibadan, over a 14-year period (1960-73). A total of 4,568 cases were reviewed with an annual death rate of between 300 and 400. Most of the deaths resulted from cardiovascular diseases, especially hypertension, the mortality rate from which has shown no appreciable decline over the years. Death from cerebrovascular accident is steadily increasing. Infections contribute considerably to mortality from chest and alimentary tract disease, although there has been a progressive decline in mortality rates from infectious diseases such as tetanus and typhoid fever. The standard of death certification needs to be improved upon, especially with respect to the clarification of the primary and the contributory causes of death and whether post-mortem examination was carrie dout or not. It is suggested that more effort should be made to ensure that post-mortem examination is carried out in cases where there is doubt about the ante-mortem diagnosis unless such a request is specifically refused by the relatives of the deceased after explaining to them the value of such an examination to medical knowledge.


The natural history of ocular onchocerciasis over a period of 14--15 years and the effect on this of a single course of suramin therapy.

In 1959 a population of 638 persons over the age of seven years, suffering from heavy endemic onchocerciasis in the Sudan-Savannah of West Africa was examined, and approximately half were allotted to a group for treatment with suramin (up to a total of 4-2 g for healthy adults). In 1973 and 1974 it was possible to re-examine 145 persons allotted to the treatment group and 118 persons allotted to the control group. Measurements were made of the incidence of new "eye lesions", the progress of pre-existing "eye-lesions" and the deterioration in visual acuity. These were greater in men than in women, and increased with age. They were also greater in persons who in 1959 had microfilariae in the anterior chamber, and particularly in those who had already developed "eye lesions". Severe reactions occurred in a significant proportion of patients who received suramin, and one died. However, these was less deterioration in the eyes of persons in the treated than in the control group.


A fatal case of strongyloidiasis with Strongyloides larvae in the meninges.

A case of fatal strongyloidiasis associated with pyogenic meningitis in an adult male African is reported. Strongyloides larvae were present in the purulent exudate in the the meninges, an observation not, to the authors knowledge, hitherto reported in man. Fatal strongyloidiasis due to autoinfection has been reported by several authors and De Paula (1962) reviewed the literature in 40 cases and added 10 others which he had studied. In Uganda fatal cases have been reported by Craven et al. (1971) and Poltera (1974). Although in some cases of fatal strongyloidiasis there was associated pyogenic meningitis (BROWN & PERNA, 1958; WILSON & THOMPSON, 1964; BASSAN-TREMINGER & EL-LANSHAR, 1968) we have not found in the literature any case in which Strongyloides stercoralis larvae or adult worms were found in the brain or meninges. We are, therefore, now reporting a case of fatal strongyloidiasis with pyogenic meningitis in which S. stercoralis larvae were present in the subarachnoid space.


Studies of the neutropenia in kala-azar: results in two patients.

Two patients with kala-azar were studied, one with DF32P (diisopropylfluorophosphate) and one with 51CR (chromate), in an attempt to elucidate the mechanisms producing neutropenia in this disease. The granulocyte half-life was found to be reduced in both patients, with pooling and probable destruction occurring in the spleen and, to a lesser extent, in the liver. Bone marrow neutrophil reserve, estimated by the response to intravenous hydrocortisone hemisuccinate, was found to be markedly reduced in both patients. An enlarged marginal granulocyte pool in one patient indicated that the neutropenia may also be due to altered intravascular granulocyte distribution.


The resistance to human plasma of Trypanosoma brucei, T. rhodesiense and T. gambiense. I. Analysis of the composition of trypanosome strains.

The sensitivity of strains of polymorphic trypanosomes to human plasma was investigated in mice. By measuring the prepatent period an approximate estimate could be made of how many trypanosomes resisted each of a graded series of doses of plasma and survived to produce infection. In this way the composition of typical strains could be analysed. Three types of strains could be recognized: (i) Strains in which all the individuals composing them were sensitive to full doses of plasma, the response to plasma probably having a "normal" distribution. These are termed "sensitive" strains. (ii) Strains composed mostly of sensitive individuals but containing a small sub-population of resistant individuals (perhaps one in a million). These are termed "subresistant" strains. Most of the strains which have been isolated from animals by previous workers and found to be resistant to human serum and/or infective for volunteers are of this type. (iii) Strains composed mostly of resistant individuals. These are "highly resistant" strains and are the type isolated from man. It is postulated that there are one (or two) genes responsible for resistance to human plasma and that the response of a strain in plasma-sensitivity tests depends upon whether the strain contains no trypanosomes with the R gene (sensitive strain), a few trypanosomes with the R gene (subresistant strain) or a jamority with the R gene (resistant strain). This model of a subresistant strain can be reproduced artificially by mixing a few resistant trypanosomes with a large number of sensitive ones. Passage of three resistant strains through mice for six weeks diminished their plasma resistance slightly to moderately, presumably through overgrowth of sensitive individuals. Passage trrough goats for six weeks diminished plasma resistance markedly but did not convert the strains into "sensitive" ones. Repeated exposure of a subresistant strain to human plasma in mice gradually increases the number of resistant trypanosomes present and so the resistance of a strain as a whole is enhanced.


The resistance to human plasma of Trypanosoma brucei, T. rhodesiense and T. gambiense. II. Survey of strains from East Africa and Nigeria.

Tests were made in vivo of the sensitivity or resistance to human plasma of many strains of polymorphic trypanosomes. Five strains of T. gambiense from Nigeria were tested and all were highly resistant. Fifteen strains of T. rhodesiense (isolated from man in East Africa) were tested and they showed great variation in their degree of resistance from high resistance (five strains) to only subresistance (two strains). Forty strains of T. brucei (isolated from animals or tsetse flies) were tested; 20 were sensitive, nine were doubtful (probably sensitive) and 10 were subresistant (i.e., probably only one of a million trypanosomes in them was resistant). One strain (ETAT 10, isolated from tsetse flies) was highly resistant. During this work, tests were made on 14 stains of T. brucei (isolated from animals or fly) which were recorded as having been tested on human volunteers. Six of these strains were sensitive to human plasma and none had infected volunteers. Seven strains were subresistant, and three had infected volunteers. One strain was highly resistant and had infected a laboratory worker. For practical purposes it is advisable to consider that if a strain of polymorphic trypanosomes is plasmasensitive, it is probably not infective for man; if a strain is at all plasma-resistant it is potentially infective for man; and if a strain is highly resistant then it is almost certainly infective for man.


Hepatitis B surface antigen in the Iraqi population.

Using counter immunoelectrophoresis (CIEP), the carrier rate of HBsAg among the Arab Population of Iraq was found to be 2.8% comparted with 5.5% in the Kurd population. The incidence of antigenaemia in laboratory workers, renal dialysis staff and patients, nursing and blood bank staff, and pulmonary tuberculosis and diabetes mellitus patients is also reported. Study of immunoglobulin classes in carriers and in HBsAg-negative controls showed that raised IgG and IgM is more common in the former than in the latter.


The purification of red cells for transfusion by freeze-preservation and washing. V. Red cell recovery and residual leukocytes after freeze-preservation with high concentrations of glycerol and washing in various systems.

Red blood cells freeze-preserved with 40% W/V glycerol in an ionic or low ionic medium at -80 C were washed in one of four commercially available systems: the Haemonetics Blood Processor 15 using a continuous-flow centrifugation procedure, the Fenwal Elutramatic using a continuous-flow centrifugation procedure, the IBM Blood Processor using an automated serial centrifugation procedure, and the Huggins Cytoglomerator using a dilution/agglomeration procedure. Determinations of red blood cell recovery and leukocyte and platelet removal were made for each of these groups. The dilution/agglomeration procedure produced lower red blood cell recovery values and poorer leukocyte and platelet removal than did any of the three wash systems using sodium chloride solutions. The values obtained with the systems using sodium chloride solutions were slightly but significantly different.


Anti-A1 in the plasma of platelet concentrates causing a hemolytic reaction.

A patient with acute leukemia who typed as AintB received 10 packs of platelets of group 0. Subsequent transfusion of A1B blood resulted in a hemolytic transfusion reaction. Anti-A1 was detected in the serum and on the red blood cells of a post-transfusion sample. This anti-A1 reacted with the transfused A1B red blood cells and other A1 cells, but not with the patient's pretransfusion red blood cells. The plasma of the transfused platelet concentrates had a high titer of immune anti-A.


Clinical value of washed-platelet concentrates in patients with non-hemolytic transfusion reactions.

In patients with severe allergic reactions to plasma proteins it is possible to observe such reactions to even the small quantity of plasma contained in platelet concentrates. A platelet washing solution was designed, and platelet concentrates for four such patients were washed before infusion. Transfusion reactions were completely eliminated by the washing procedure. Platelet recovery was equivalent to that of unwashed platelets, and hemostatic effectiveness of the infused platelet concentrates was evidenced by abrupt cessation of bleeding episodes, including purpura and hematuria. Platelet washing represents a valuable, rapid and simple approach to the problem patient with thrombocytopenia and severe reactions to plasma proteins.


The uptake and egress of adenine from human red blood cells in vitro.

The initial uptake of adenine from plasma by human red blood cells was measured at 0, 10, and 20 C. Initial uptake is completed in several minutes as distribution equilibrium is reached; however, total uptake requires several weeks at 4 C. Adenine inside the red blood cell was shown to egress to the plasma if the equilibrium shifted due to plasma dilution or exchange.


Detection of HBsAg in coagulation Factor IX concentrates.

HBsAg was detected in two commercial clotting factor concentrates: Proplex (Hyland) and Konyne (Cutter). HBsAg was positive by RIA in samples of Proplex but not Konyne. Immune-electron microscopy, however, demonstrated clumped small spheres of HBsAg in both preparations, and lamellar-type strands were seen in several preparations.


Independence of Wright from many other blood group systems.

The finding that En(a-) red blood cells are Wr(a-b), and thus probably represent a "null" phenotype of the Wright system, has provided evidence of the independence of the Wright blood group system from many others. Detection of blood group antigens on "null" red blood cells almost certainly indicates that those antigens do not belong to the same blood group system as the "null" cells. In the case of Wright, lack of certainty that En(a-) is the "real", or only, null type slightly reduces the weight of the evidence.


Variations in cryoprecipitate production.

Several variables influencing the recovery of Factor VIII in the cold-precipitated protein fraction were examined. The actual rate at which the physical-chemical conversion of plasma from a solid to a liquid state occurs does not seem to affect the yield. Rather, it is the amount of time immediately postthaw and prior to centrifugation that determines the Factor VIII activity in the cryoprecipitate. With prolonged periods at 4 C the Factor VIII activity leaves the cold precipitate and lifts into the supernatant. Even distribution of the plasma layer and close attention to the thawing procedure facilitate Factor VIII recovery.


Experimental induction of caprylate-dependent albumin antibodies.

To provide evidence for the immune nature of the albumin agglutination phenomenon or caprylate dependent albumin agglutinins (CDAA), rabbits were injected with native serum that had been incubated in a solution of sodium caprylate. Two of three rabbits responded with the production of CDAA, which in vitro behaved identical to human antisera. Human cells were agglutinated only when caprylate stabilized albumin was added to the cell/serum mixture or when caprylate free albumin plus sodium caprylate were used. The CDAA failed to agglutinate rabbit cells, although, both human adult and cord cells were agglutinated. These experiments indicate that the CDAA represent an immune response to native albumin that had been altered by caprylate.


In vivo stability of cryoprecipitate fibrinogen.

Because of its lower hepatitis risk, cryoprecipitate has been advocated as a substitute for commercial fibrinogen. Previous literature on cryofibrinogen has demonstrated a short blood t1/2, rendering it unsuitable for therapeutic use. The in vivo clearance of 131I-cryoprecipitate was compared with that of 125I-standard fibrinogen. A small amount of cryoprecipitate was rapidly cleared and apparently was cryofibrinogen. However, the bulk of the cryoprecipitate was cleared with a normal half life, as was cryoprecipitated that was in 10-bag pools. The data indicated cryoprecipitate was an effective in vivo form of fibrinogen and thus the preferred fibrinogen source because of its combining normal t1/2 with single donor procurement.


Component preparation record.

A card form has been developed to record production and distribution data of non-red cell blood components prepared. This form provides a concise, accurate, and permanent record of each unit of non-red cell blood component produced. The form can be modified to meet local requirements.


Rapid in vivo destruction of Yt(a+) erythrocytes in a recipient with anti-Yta.

A patient with anti-Cartwright (anti-Yta) is reported. Immunohematologic studies showed this antibody to be an IgG immunoglobulin that does not bind complement. A 51Cr red blood cell survival study resulted in a greatly reduced half-life of less than six hours of Yt(a+) cells. The antibody titer increased threefold after the red blood cell survival study. Determination of red cell survival is indicated when crossmatch-incompatible blood transfusion is considered.


Factors affecting the efficiency of filtration leukapheresis.

Continuous flow filtration leukopheresis was performed on normal volunteer donors with and without intravenous administration of dexamethasone. Although granulocyte counts were increased in steroid treated donors and almost 20% more cells were presented to the filters, the final yield of granulocytes was slightly decreased and the efficiency of collection during a two- to three-hour leukapheresis was statistically significantly decreased.


Decreased accumulation of phthalate plasticizer during storage of blood as packed cells.

Accumulation of phthalate plasticizer (di-(2-ethylhexyl) phthalate, DEHP) was markedly reduced in blood stored as packed cells rather than as whole blood. After the first week, the accumulation rate in whole blood was essentially linear, but in packed cells DEHP accumulation was lower, and reached a plateau. At three weeks whole blood contained about three times more DEHP than did packed cells. Smaller amounts of plasma and restricted diffusion probably limited DEHP accumulation in packed cell preparations.


Self-administered blood donor medical history.

An experiment in self-administered blood donor medical histories is described. This history, reviewed by a medical history nurse, was not associated with more rapid donor processing. Donors and medical history nurses reacted positively to self-administration. The quality of the medical history did not appear to be affected by the procedure. The findings suggest that there is value in the self-administration process, and that further trial is warranted.


Chemical analysis of a 30-year-old bottle of lyophilized plasma.

The biochemical constituents of a 30-year-old sealed bottle of lyophilized plasma were analyzed. The results in this communication show that the process of lyophilization and storage has not seemed to cause any great changes in plasma components, including hormones, enzymes, and proteins.


Viability and function of platelets frozen at 2 to 3 C per minute with 4 or 5 per cent DMSO and stored at -80 C for 8 months.

Each of 15 healthy male volunteers was treated with 650 mg of aspirin 24 hours before the autologous transfusion of one unit of freeze-preserved platelets. Freeze-thaw-wash recovery values in vitro, viability and function in vivo, and the bleeding time and platelet aggregation response were measured. The platelets were frozen with 4 or 5 per cent dimethylsulfoxide (DMSO) at an overall rate of 2 to 3 C per minute and were stored at -80 C in a mechanical freezer for up to eight months. They were washed by dilution/centrifugation. The mean recovery in vitro of platelets frozen with 4 per cent DMSO was 76+/-16%; the value was 64+/-16% for platelets frozen with 5% DMSO. The mean in vivo 51Cr recovery of autologous platelets frozen with 4% DMSO was 34+/-6%, and for platelets frozen with 5% DMSO it was 33+/-7%. In both groups the platelet lifespan was normal. There was a significant reduction in bleeding time after the transfusion of a single unit of autologous platelets preserved with either 4 or 5% DMSO, but no improvement in the aspirin-induced platelet aggregation pattern.


Lymphatic network of kidney. I. Anatomic and physiologic considerations.

A small number of investigators, including our team, has been responsible during the past two decades for many studies focusing on the kidney lymphatics. Interesting new information and concepts have been published, but unfortunately some of these data are scattered in obscure journals. The major purpose of this, and three subsequent reviews, is to present these new concepts in a more organized fashion. The reviews will also allow our group an opportunity to emphasize physiologic principles which have been ignored in the past. In a future review we will emphasize the role of the immunoblast, found only in kidney lymph and responsible for rejecting the renal allograft. Azathioprine (Imuran), if given early and in adequate dosage, will reduce the role of these transformed lymphocytes. Still another review article will emphasize the importance of renal tissue concentrations of antibacteria in eradicating acute pyelonephritis. Blood and urine levels of antibiotics are also important in eradicating pyelonephritis. Since renal lymph represents interstitial fluid, the concentration of appropriate bacteria-sensitive antibacterials is probably more important. We have now evaluated fourteen antibacterials individually in the mongrel dog, comparing plasma, urine, and renal lymph levels during similar time intervals. Finally, we will review the role of diuretics in altering the interstitial gradient of various solutes. Osmotic diuretics of more potent diuretics which affect renal tubular reabsorption manifest their action by different means when renal lymph fluid is evaluated.


Accessory and ectopic scrota.

Two cases of ectopic scrotum are presented, and 12 previously reported cases are reviewed. This anomaly presumably develops secondary to faulty division or abnormal migration of the embryonic labioscrotal swellings.


Ataralgesia in outpatient urology. Clinical evaluation.

The combination of fentanyl citrate (Sublimaze) and diazepam (Valium) was evaluated for efficacy of analgesia, sedation, and safety in 1,008 predominately outpatient urologic procedures. These procedures included prostate biopsies, basket extractions of ureteral calculi, internal urethrotomies, and cystourethroscopies. Ninety-two per cent were judged to be successful with regard to adequate tranquilization and relief of pain. No detrimental effects were seen with the recommmended method and dosage. This drug combination provides the clinician with an effective and safe alternative to local, general, or spinal anesthesia for many routine urologic procedures and allows them to becom true office procedures.


Urolithiasis after intestinal bypass for morbid obesity.

Urinary calculi, predominantly of oxalate composition, have been noted in 10 to 14% of a large series of morbidly obese patients after jejunoileal intestinal bypass at this institution. Physical and metabolic changes after bypass surgery, including the presence of hyderoxaluria, hyperuricemia, and fluid and electrolyte disturbances are reviewed in their possible relationship to this increased incidence of urolithiasis.


Simulated testicular torsion in a neonate: complication of ventriculoperitoneal shunt.

Ventriculoperitoneal shunts are a common form of cerebrospinal fluid diversion in treating hydrocephalus. With their use various complications have been noted. Herein is described a shunt complication which simulated an acute scrotal condition. The operative findings and treatment are discussed. A brief review of the literature is also given.


Renal cortical microabscesses as cause of reversible acute renal failure.

We report a case of renal cortical microabscesses which presented as oliguric acute renal failure. Prior to the biopsy the patient was suspected of having acute pyelonephritis with acute tubular necrosis. Biopsy was performed to rule out rapidly progressive glomerulonephritis as a cause of his renal failure. To our surprise, we found multiple small microabscesses in the renal cortiex. Renal cortical microabscesses should be considered as a reversible acute renal failure.


Severe hypertensive reaction to indigo carmine.

An episode of severe hypertension induced by indigo carmine is herein reported. Treatment with intravenous hydralazine was required to restore systemic blood pressure to a safe level. The reported association of indigo carmine with hypertension is reviewed.


Vesicoureteral reflux associated with intact orthotopic ureterocele.

Two cases of vesicoureteral reflux into intact, orthotopic ureteroceles are described. A review of the literature failed to reveal any similar reports. Insufficient submucosal ureteral length was thought to be the cause in each of the cases. Both patients were satisfactorily managed with standard ureteroneocystostomy after resection of the ureterocele.


Immunoglobulin A in split ejaculates of patients with prostatitis.

7S and 11S IgA (immunoglobulin A) levels in split ejaculates of 17 patients with chronic prostatis and 16 normal subjects were studied by the Hanson radial immunogel filtration method. The results suggest at least in certain cases of prostatitis increase of IgA level involves elevation of both types of IgA, and they are mainly of prostatic origin.


Methyldopa in treatment of neurogenic bladder disorders.

Fifty patients with neurogenic bladder dysfunction were treated with methyldopa (Aldomet). The preliminary results that are presented suggest a beneficial action in patients with upper neuron lesions. The probable mechanism of the drug's action is discussed.


Retroperitoneal fibrosis secondary to metastatic neoplasm.

Retroperitoneal fibrosis may occur secondary to metastatic neoplasm and may simulate the features of the idiopathic variety. A case of retroperitoneal fibrosis due to gastric carcinoma is presented and the historical, physical, cystoscopic, urographic, operative, and pathologic similarities to the idiopathic form discussed. Generous biopsy of retroperitoneal plaques and careful pathologic examination are stressed to avoid missing malignant disease.


Spectrum of ultrastructural patterns of renal cell adenocarcinoma.

The ultrastructure of renal cell carcinoma was studied in 6 patients. This study demonstrated a spectrum of ultrastructural patterns ranging from the classic electron microscopic features of granular cell carcinoma at one extreme, to those of clear cell carcinoma at the other extreme. Other tumors demonstrated intermediate features. There was reasonably good correlation between the light microscopy and electron microscopy. Unusual findings of connective tissue banded structures and basement membrane branching were demonstrated.


Double contrast polycystography: new radiologic procedure.

To plan the treatment of carcinoma of the bladder correctly accurate knowledge of the morphology and degree of infiltration of the tumor is essential. Double contrast cystography and polycystography are radiologic techniques that can provide such information. Hitherto, these two procedures have been performed separately. Herein is described a new method combining these two investigations. Thus maximum information necessary to plan the treatment of bladder tumors is obtained from a single radiograph. The advantages of this procedure are discussed.


Idiopathic pelviureteric varices.

Pelviureteric varices are well-documented sequelae of renal vein thrombosis, but there have been only 10 prior reports of idiopathic renal vein varicosities. Herein we report 3 more cases and review the literature. Two thirds of the patients presented with hematuria; one-fourth had flank pain, and one-third had saphenous vein varicosities. Pyelographic findings include scalloped deformities of the upper ureter and pelvis with displacement and intraluminal filling defects. The diagnosis may be suspected from the excretory urogram, but venography is definitive. Excision and ligation of the varicose veins were curative in all but 3 patients who required nephrectomy for life-threatening hemorrhage.


Avascular renal adenocarcinoma: variations and characteristics.

Six cases (men ranging in ages from thirty-seven to seventy-seven years) illustrate the varied characteristics of avascular renal adenocarcinoma. These tumors frequently stimulat benign lesions. All modalities including intravenous pyelography, nephrotomography, ultrasonography, cyst puncture with cystic fluid assessment, angiography, and operation with tissue specimens submitted for pathologic examination may be required before diagnosis is established. An orderly approach to the evaluation of lesions will allow accurate diagnosis approaching 100% with minimum morbidity. Attention to the finer details of vascular patterns on angiography has proved to be a most helpful diagnostic aid. Cyst puncture with histochemical, cytologic, and radiographic examinations appears to offer additional help in diagnosing these elusive lesions.


Accuracy of bipedal lymphangiography in testicular tumors.

The accuracy of bipedal lymphangiography to evaluate nodal metastases in patients with testicular malignancies is discussed. A total of 108 patients were evaluated. Histologic correlation was available in 45 cases. The over-all accuracy was 89% which compares favorably with other large series.


Renal sinus angiomyolipoma.

The first case of an angiomyolipoma limited to the renal sinus is presented. The radiographic findings were a relatively lucent mass within the renal sinus (extrarenal); neovascularity that did not respond to epinephrine; lack of arteriovenous shunting; a "whorled" venous pattern; and displacement and compression of the renal vein without evidence of invasion. Infusion nephrotomography and renal venography were crucial in the localization and preoperative suggestion of this benign renal sinus lesion. The renal sinus angiomyolipoma was removed by blunt dissection and the kidney preserved.


Seeding mechanism of urothelium over nonepithelialized surfaces.

To study urothelial spreading over nonepithelialized tissue surfaces, bladder defects in rabbits were patched with pedicled prevesical fat. Using serial sections and scanning electron microscopic studies, it was concluded that urothelium in the process of covering nonepithelialized surfaces is able to seed at a distance from the periphery of the defect as one means of epithelializing a defect.


Minimal mortality of renal surgery.

Eight hundred fourteen renal operative procedures were reviewed to determine overall mortality and to identify patients at risk. The over-all mortality was 1.35%, but as high as 30% in patients with uremia and spesis. Carcinomatosis contributed to higher mortality in other groups. In the absence of these three factors renal surgery was associated with very low or no postoperative (thirty day) mortality.


Nonobstructive anuria in children: hemolytic uremic syndrome.

The hemolytic uremic syndrome (HUS) must be considered as a cause of oligo-anuria in a previously healthy young child. This syndrome consists of a viral-like prodromal illness, followed by acute renal failure, thrombocytopenia, and an abnormal blood smear with fragmented erythrocytes. Awareness of this syndrome will permit earlier diagnosis and management and will minimize unneccessary investigation in the anuric child.


Prevention of venous thromboembolism with low doses of heparin in urologic patients.

The effectiveness of low doses of heparin was investigated for the prevention of clinically manifested thromboembolic disease. In the group of 125 patients, who received 5,000 units of subcutaneous heparin two hours before the operation, and postoperatively 15,000 units per day for seven to ten days, deep vein thrombosis was not observed, and in only 1 patient (0.8%) pulmonary embolism was suspected. Of 216 patients from the control group, pulmonary embolism was clinically diagnosed in 4 (1.9%), deep vein thrombosis in 7 (3.4%), and in 2 patients (0.9%) fatal pulmonary embolism was found at autopsy. The difference between total thromboembolic disease of the control group (6.2%) and heparinized group was highly significant (p less than 0.02). Postoperative bleeding was seen two times more often in the heparin group, but bleeding was not severe and was easily controlled.