Bradykinin-like immunoreactive neuronal systems localized histochemically in rat brain. Bradykinin-like immunoreactive structures were localized in rat brain by the indirect immunofluorescence method. Specificity of staining was demonstrated by: (i) the absence of fluorescence when preimmune serum was used, (ii) the disappearance of fluorescence when sera were preadsorbed with bradykinin, and (iii) the presence of identical staining with two different antisera. Immunoreactive neuronal cells are observed only in the hypothalamus, with especially dense clusters overlying the periventricular and dorsomedial nuclei. Fibers and varicose processes are observed in the periaqueductal gray matter, hypothalamus, perirhinal and cingulate cortices, the ventral portion of caudate-putamen, and the lateral septal area.


Myelin-associated glycoprotein demonstrated immunocytochemically in myelin and myelin-forming cells of developing rat. The unlabeled peroxidase-antiperoxidase method has been used with antiserum against "myelin-associated glycoprotein" to establish the presence of the glycoprotein in myelin and myelin-forming cells of the developing rat nervous system. Myelin-associated glycoprotein is found in oligodendroglial cytoplasm before the beginning of myelination. Staining intensity of oligodendroglia increases during early development and slowly declines during the period of rapid myelination. Myelin staining is confined to the periaxonal region of the myelin sheath and does not increase as large, compact sheaths are formed. Antiserum to central nervous system myelin-associated glycoprotein also stains Schwann cells in developing trigeminal ganglia and the periaxonal region of peripheral myelin sheaths.


Effects of goldthioglucose lesions on central catecholamine levels in the mouse. Male and female C57 B1/6J mice were injected with goldthioglucose (GTG) to induce an obesity syndrome. Significant increases in body weight were inversely correlated with pituitary dopamine (DA) levels. Significant reductions in hypothalamic norepinephrine (NE) and DA were also noted; however, these reductions did not appear to be related to body weight gain. The GTG injections did not produce any significant alterations in telencephalic NE or DA. The damage to catecholamine neurons is discussed in relation to the endocrine abnormalities of the GTG mouse and some current hypotheses on the control of food intake.


Studies in potential organo-fluorine antibacterial agents. Part 2: Synthesis and antibacterial activity of some new fluorine-containing 3.5-disubstituted isoxazoles. A series of new fluorine-containing 3,5-disubstituted aryl/alkylisoxazoles has been synthesized by the condensation of hydroxylamine with appropriate beta-diketones in the presence of pyridine and characterized by IR and 1H NMR spectral studies. These isoxazoles have been screened for their antibacterial activity against the gram positive bacteria, Staphylococcus albus, Streptococcus nonhemolyticus and the gram negative bacterium Escherichia coli.


Control of acetylcholine receptors in skeletal muscle. An ACh receptor is the molecular entity that, in its native habitat, possesses the binding sites for ACh and all the other components required to generate the ion channels mediating the ACh response. Narrower definitions of an ACh receptor (as the binding site for ACh or the polypeptide chain that is folded to form the binding site) could lead to semantic arguments about receptor structure. Experimentally, ACh receptors are defined by their total function (when electrophysiological tests are used) or by ligand binding. There is no evidence that the ligand-binding portions of ACh receptors ever exist in vivo without the associated channel-forming mechanism and vice versa. Most data are consistent with the idea that detergent-solubilized glycoproteins retaining the ACh binding sites of the receptor also include the channel-forming components, although it appears that the mechanism is prone to denaturation or proteolytic damage. Studies of receptor-rich membranes and of solubilized receptor glycoprotein have not yet yielded a totally satisfactory image of receptor structure. Most evidence favors an ACh receptor composed of three or four different types of glycosylated polypeptide chains organized into a unit of aggregate molecular weight about 300,000--400,000 daltons. Plasma membranes are dynamic structures in two different ways. First, their constituent molecules are in rapid thermal motion and, when these molecules are not tethered to extramembranous structures or mired in large aggregates, they fairly rapidly change their position in the plane of the lipid bilayer. Second, all membrane components are continually being synthesized and degraded. Acetylcholine receptors participate in both aspects of this dynamism. In this review it is proposed that the number and the distribution of ACh receptors in skeletal muscle are controlled by modulation of receptor metabolism and modulation of associations between receptor molecules or between receptors and other, as yet unidentified, elements in neuromuscular junctions and at extrajunctional sites where receptors are clustered. The arrangements of receptors in skeletal muscle and the total number of receptors in skeletal muscle may be regulated by separate mechanisms. Clusters of ACh receptors apparently can form spontaneously in extrajunctional areas of denervated muscles and in tissue-cultured embryonic muscle. Such clusters may be positionally stable and the receptor molecules in them may be highly restricted in mobility. Nevertheless, these receptors have average lifetimes on the order of 20 h, just like the nonclustered, mobile extrajunctional receptors. Receptor clusters also form at sites of innervation. In the chick embryo the junctional receptor molecules remain short-lived. The metabolism of ACh receptors is highly regulated. The biosynthesis of receptors commences during myogenesis at about the time myogenic cells become competent to fuse. Later, biosynthesis is dramatically repressed by muscle activity and possibly by other factors...


Complicated neck contracture treated with a pectoralis major myocutaneous flap. A case is presented which demonstrates the use of a pectoralis major myocutaneous flap for repair in a heavily radiated neck and chest, with neck contracture and a tracheocutaneous fistula.


[Diagnosis and therapy of neurotic depressions]. The causes of depressive syndroms differ from case to case. Frequently, the cause of disease cannot be reliably determined from the cross-sectional picture alone. Rather, it is necessary to give careful consideration to heredity, longitudinal analyses, and psychodynamics. The etiopathogenesis of neurotic depressions is discussed for the four different forms of neurosis by reference to the classification of neuroses recommended in Bad Elster in 1969. To make the psychodynamics of neurotic depressions understandable, loss of object, oral regression, pathological narcissism, and defense against aggressions are used in the sense of metaphoric model concepts and discussed in detail. Psychotherapy and its principal objectives are not only discussed in respect to genuine neurotic depressions, but it is also shown how it can be made an integral part of a differently accentuated, predominantly somatic therapy.


[Meningoencephalitis in Behçet's disease--review and clinical-morphological case report]. The paper describes the neuropathological findings in the seven-year case history of a male patient who died at the age of 29 of Behçet's disease with initial iridocyclitis and neurological complications. In the author's opinion, the presence of any one of the three cardinal symptoms of the muco-cutaneo-ocular syndrome and its manifestation on the CNS is sufficient to suppose Behçet's disease. Affectation of the eye is a significant and usually the first symptom. The case history and the typical morphological findings give rise to the assumption of a special ophthalmomeningoencephalic variety of Behçet's disease.


The influence of the psyche and the brain on immunity and disease susceptibility: a critical review. In critically reviewing the sources of evidence connecting psyche and brain with the immune system, the authors include a brief review of current knowledge of the immune system, its interactions with the neuroendocrine system, and other factors influencing its regulation. These include developmental stages, aging, rhythmicity, and a variety of exogenous influences. The need for developing further information about normal base lines is emphasized. Against that background, many sources of data demonstrating connections between the central nervous system and the immune system are presented: indirect evidence from clinical and experimental illnesses involving the immune system, and direct changes in either humoral or cellular immunity after natural or experimental stress, conditioning, hypnosis, and direct brain stimulation. Possible mechanisms are discussed, as well as some important methodological issues for further research.


Primary IgA glomerulonephritis and Schönlein-Henoch purpura nephritis: Clinicopathological and immunohistological characteristics. A comparative analysis on clinicopathological and immunohistological characteristics was performed of 205 cases with primary IgA nephritis and 35 with Schönlein-Henoch purpura nephritis (purpura nephritis). Diagnostic criteria for primary IgA nephritis were set out so that IgA was either the most prominent immunoglobulin or, at least, equal to IgG and/or IgM, if present, irrespective of mesangial or peripheral localization. In primary IgA nephritis, one half of the cases were discovered by asymptomatic proteinuria, and one-third presented recurrent upper respiratory tract infection and gross hematuria, one-fourth abdominal pain and a few cases joint pain, while purpura nephritis was associated with a significantly higher incidence of such systemic symptoms as abdominal and joint pains, in addition to purpura. Both diseases shared a tendency toward conspicuous hematuria in contrast to the modest proteinuria, with normal renal function in three-fourths to two-thirds. Moreover, four of 35 with purpura nephritis showed preceding proteinuria and had been regarded as primary IgA nephritis until purpura appeared. The glomerular pathology had a common feature in that there was frequent occurrence of mesangial proliferative and focal and segmental lesions. The immunohistology in the two diseases was indistinguishable with regard to the glomerular immunoglobulins and mediators, whether purpura was present or absent. Thus, we propose a unifying concept that, by analogy with SLE, primary IgA nephritis may be regarded as 'sine lupo,' lying on one side of the nosological spectrum with less systemic symptoms, whereas purpura nephritis may occupy the other side with more systemic aspects. Furthermore, we confirmed the epimembranous granular deposition of IgA in both diseases as the most characteristic morphological expression of circulating immune complexes.


[Early diagnostic imaging of rheumatoid arthritis (RA) (author's transl)]. The respective diagnostic value each of diagnostic radiology and nuclear medicine in the detection of early rheumatoid arthritis is being demonstrated--with close correlation to its clinical presentation and course. Diagnostic radiology is found to be specific and nuclear medicine to be highly sensitive, with the latter giving better diagnostic information at an earlier time about the activity of the disease than the former--including soft tissue technique. Nuclear medicine further--more will be helpful for appropriate timing of diagnostic radiology evaluations of this disease.


Increased perinephric activity in 99mTc-DTPA studies of renal transplants. All 99mTc-DTPA studies of renal transplant patients whose grafts infarcted during a three-and-one-half-year period were reviewed. Four patients demonstrated absent renal perfusion and clearance and absent bladder activity. Three of these exhibited increased perinephric 99mTc-DTPA activity and never regained renal function. The fourth patient did not demonstrate increased perinephric activity, and some return of graft function appeared in a subsequent 99mTc-DTPA study. The pathogenesis of increased perinephric activity is unknown, but may signify renal infarction, and its absence may indicate potential renal viability.


Transdiaphragmatic jejunal duplication: a report of five cases. Five infants with intrathoracic transdiaphragmatic duplication cysts are presented. Diagnosis was possible from the combination of several features on plain chest radiographs: (a) right-sided cystic areas lying posteriorly in the chest, (b) lower cervical or upper dorsal spinal dysraphism, and (c) unusual gas collection beneath the right hemidiaphragm. Barium studies, positive-contrast myelography, and computed tomography were helpful in preoperative assessment.


Gray scale ultrasonic appearances of renal transplant rejection. Ultrasonic examination of renal transplants with special attention to the parenchymal echo pattern has been undertaken in 43 patients. In the normal renal transplant, the pyramids, cortex and renal sinus can be distinguished. Renal transplant rejection is manifested by swelling and decreased echogenicity of the pyramids and hyperechogenic cortex. In addition, large anechoic areas due to hemorrhagic infarcts and necrosis are seen. In long-standing rejection, a normal or small-sized kidney with an irregular intrarenal echo pattern is observed. In 13 cases of acute tubular necrosis, none of the above appearances could be demonstrated. Serial ultrasonic scans are essential to reveal evolutionary changes of the rejection process.


Prostaglandins, their intermediates and precursors: cardiovascular actions and regulatory roles in normal and abnormal circulatory systems. The characterization of newly found unstable metabolites of arachidonic acid has provided new perspectives for cardiovascular regulatory mechanisms and new insights into disorders of the circulatory system. Since these intermediates are often more potent on and more specific for cardiovascular structures than the classical prostaglandins, they are more likely candidates as physiologic mediators of circulatory events. Their instability in vitro need not preclude these roles; on the contrary, the limited pharmacology described to date suggests that they function purely as local hormones. As such, changes in the rate of generation of these unstable but potent compounds would provide an excellent control system. The stable prostaglandins may represent only overflow of degradation products of the active mediators associated with pathologic events. For example, the dicovery of prostacyclin and the realization that this prostaglandin and not PGE2 is the primary metabolite of arachidonic acid in blood vessels emphasizes the need to reinterpret many of the previously held hypotheses that proposed that prostaglandins of the E series contributed to the regulation of vessel tone and blood pressure, Moreover, the contribution made by abnormal prostaglandin mechanisms to hypertensive disease should now take into account that a deficiency of prostacyclin and not PGE2 could be a major factor causing the elevated tension developed in vascular smooth muscle and the augmented vessel responsiveness to stimuli associated with hypertension.


Aureobasidium pullulans metabolism of prostaglandins of the A-type. Aureobasidium pullulans, originally introduced as an inadvertent contaminant in solutions used for evaluating the stability of prostaglandins, proved to lead to the rapid disappearance of the cyclopentenone unit of PGA2 (as monitored by circular dichroic spectroscopy). The cyclopentenone unit is converted, in various metabolites, to a 9-keto, 9 alpha or 9 beta-hydroxy group lacking the ring unsaturation. The major EtoAc-soluble 9-hydroxy metabolite (Compound-I) was shown to be 9 alpha, 15 alpha-dihydroxy-2, 3, 4, 5-tetranor-13-trans-prostenoic acid. Similar tetranor 9-hydroxy metabolites with one additional degree of unsaturation, and with a 9 beta-hydroxy group, also occur but these have not been fully characterized. Only two of the wide range of 9-keto metabolites are fully characterized by mass spectral (MS) data: 9, 15-oxo-2, 3, 4, 5-tetranorprostanoic acid and 9, 15-oxo-2, 3, 4, 5-tetranor-13-trans-prostenoic acid. The water soluble metabolites have not been characterized further. The fully characterized metabolites together with MS data from mixtures of minor metabolites indicate that A. pullulans can perform the following transformation: beta-oxidation, dehydrogenation at C-15, reduction of the enone carbon-carbon double bonds (both delta 10,11 and delta 13,14), reduction of the 9-ketone, and possibly migration of the cyclopentyl double bond (delta 10, 11 leads to delta 11, 12). A. pullulans metabolizes 15-epimeric PGA2 equally readily with the production of similar products. PGA1 affords less 9-keto metabolites with compound I constituting 33% of the product by HPLC analysis. A. pullulans displays some enantioselectivity, PGA2 and 15-epi-PGA2 are each metabolized more rapidly than their enantiomers. Other prostaglandins appear to be less readily metabolized.


The renal haemodynamic and excretory actions of prostacyclin and 6-oxo-PGF1 alpha in anaesthetized dogs. Intrarenal arterial (i.a.) infusions of prostacyclin (PGI2) at 30-300 ng/min to anaesthetized dogs reduced renal vascular resistance (RVR) and filtration fraction (FF), increased mean renal blood flow (MRBF) but did not alter mean arterial pressure (MAP)or glomerular filtration rate (GFR). The urinary excretion of sodium (UNaV), potassium (UKV) and chloride ions (UC1V) were increased through inhibition of net tubular ion reabsorption. PGI2 (3000 ng/min, i.a.) reduced MAP and increased heart rate. Intravenous (i.v.) infusions of PGI2 (3000 gn/min) reduced MAP, GFR, FF, urine volume and ion excretion, with elevation of heart rate. The measured variables were unaltered by 6-oxo-PGF1 alpha (10,000 ng/min i.a.). Treatment of the dogs with the PG synthetase inhibitor meclofenamic acid (2.5 mg/kg i.v.) did not antagonise the elevation of MRBF to PGI2 (300 ng/min i.a.). Thus the renal effects of PGI2 were due to a direct action rather than through conversion to 6-oxo-PGF1 alpha or through stimulation of endogenous renal PG biosynthesis and release.


The action of prostacyclin (PGI2) on the contractility of the isolated circular and longitudinal muscle layers of the human oviduct. Small strips from the circular and longitudinal muscle layers of the ampullary-isthmic portion of the human oviduct were mounted in organ chambers for recording of their spontaneous contractility. Concentrations in the order of 1-300 ng/ml of PGI2 were tested and compared with similar concentrations of PGE2 and PGF2 alpha. It was found that PGI2 contracted the longitudinal muscle layer in the same manner as did PGE2. The spontaneous activity of the circular layer was markedly suppressed by PGE2 but only moderately inhibited by PGI2 even at high concentrations.


[Microbiologic quality of fish on sale in the City of Guatermala]. A sanitary microbiological survey of fresh and processed fish on sale in Guatemalan markets and supermarkets was carried out. Samples of tables, floor and freezer surfaces, and of the water, ice and liquid drippings of the different stands were also taken and analyzed. Aerobic counts exceeded 10(6)/g in 72% of the samples, and 16% had more than 40 fecal coliforms/g. Coagulase-positive Staphylococcus aureus were never higher than 100/g in fish. The bacterial counts were higher in the ice and liquid drippings.


Bacteriophage specificity in the identification of Yersinia pestis as compared with other enterobacteria. Bacteriophage typing of Yersinia pestis and the specificity of the phage among Enterobacteriaceae were investigated. The bacteriophage used for rapid identification of Y. pestis reacted with representative strains of all recognized species of Shigella as well as with Salmonella cholerae-suis. Reactive Shigella serotypes were Sh. dysenteriae 1 and 9, Sh. flexneri 2a, Sh. boydii 1 and 6, and Sh. sonnei. Patterns consisting of isolated plaques (two cases) or absence of plaques were observed when the routine test dilution (RTD) of the phage was used. Results were independent of the incubation temperature (20, 28 or 37 degrees C). Representative strains of Escherichia, Proteus, Providencia and Klebsiella were resistant to the bacteriophage even at 1000 X the RTD established for Y. pestis.


[Correlations between variations in vigilance, E.E.G. activity, respiration, and clonicity in a case of Jakob-Creutzfeldt's disease (author's transl)]. Diurnal polygraphic recordings in a 72 year old women with Jakob-Creutzfeldt's disease (confirmed by anatomical and pathological examinations), showed correlations between modifications in respiration and myoclonic activity, and somnolent episodes. Falling asleep was marked by the replacement of periodic paroxystic activity by diffuse and irregular theta activity; the brusts of clonicity were interrupted at the same time as the paroxystic complexes; a more or less marked hypopnea accompanied most of these episodes, but the bradycardia was inconstant. The close temporal correlations between the variations in vigilance, respiration, periodic E.E.G. activity, and clonicity suggested the existence of a common triggering mechanism, the nature of which has still to be elucidated.


Influence of the adrenal cortex on allograft rejections in rats. I. The bibliography about corticosteroid influence on immune response is briefly reviewed. Generally, it is admitted that corticosteroids are immunosuppressive when administered in large amounts. Divergent opinions are recalled. II. The aims of the experiments are summarized: A) Investigate on the influence of corticoids (given in just substitutive amounts) on skin allograft rejection. B) Investigate on possible interactions between adrenal cortex and thymus with this test. III. It was observed, that A) Adrenalectomy resulted in a significant delay of allograft rejection. B) This could be suppressed partially by administering aldosterone, corticosterone, and desoxycorticosterone and completely by administering at least two of these hormones. C) Cortisol had shown a minor inhibitory influence. D) There was no obvious difference between adrenalectomized and thymectomized rats and those adrenalectomized only. IV. These observations are replaced in the context of bibliography and their significance is discussed.


[Experimental study on tissue and cell reactions after implantation of xenogeneic collagen sponges (author's transl)]. 164 inbred Wistar rats received subcutaneous and intraperitoneal implants of xenogeneic collagen sponges and were examined by light- and electron microscopy as well as immunohistologically, to establish tissue and cell reactions and the time of collagen reabsorption. 4 to 5 weeks after implantation the xenogeneic collagen sponge was completely absorbed. All the inflammatory and reparative reactions were non-specific. Granulation tissue appeared soon (3 days after implantation) with new synthesis of fine collagen fibrils, mainly of type III, followed by type I collagen fibers. Myofibroblasts, with intracellular evidence of myosin and collagen (Type I and III) were sporadically present in the granulation tissue after day 5 and regularly after day 10. Small scar granulomas without xenogenic collagen were detectable even 4 to 6 months after collagen implantation. Reabsorption and regression of collagen granulomas occurred faster after xenogeneic collagen implantation than after using surgical cat sutures. From the morphological point of view, there is no indication of specific sensitization against xenogeneic collagen or of a specific immunologic process.


The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on meal-stimulated elevations of circulating glucose, insulin, and triglyceride levels in man. In blind studies the effects of a new alpha-glucosidase inhibitor (BAY g 5421) were tested in normal weight and overweight male volunteers after oral application of 75, 150, or 300 mg of BAY g 5421 or placebo per os before three standardized main meals of one day. Before and three hours after each meal blood glucose, serum insulin, and serum triglyceride levels were determined. In addition, safety studies were performed. BAY g 5421 induced a statistically significant, in part dose-dependent inhibition of the postprandial increase of blood glucose- and serum insulin levels. The reduction of the postprandial increase of serum triglyceride levels was variable. Routine blood chemistry and hematology tests have revealed no adverse side effects; but the application of the drug was frequently associated with intestinal effects, such as flatulence and diarrhea, which were substrate (carbohydrate) and, in part, dose-dependent.


The effects of the alpha-glucosidase inhibitor BAY g 5421 (Acarbose) on postprandial blood glucose, serum insulin, and triglyceride levels: dose-time-response relationships in man. In a double-blind quadruple cross-over study the effect of a new alpha-glucosidase inhibitor (BAY g 5421) on postprandial blood glucose, serum insulin, and serum triglyceride increases was tested in 24 male healthy volunteers. They received before a standardized breakfast 50, 100, or 200 mg of BAY g 5421 or a placebo per os. The dose-time-response relationships were calculated and the drug tolerance was assessed. There was a statistically significant inhibition of the postprandial increases of the blood glucose, serum insulin, and triglyceride values. Further analysis showed no dose-dependent effect of the drug on the blood glucose values, whereas the serum insulin and triglyceride values were affected in a dose-dependent fashion. The maximal inhibitory effect on the serum insulin levels occurred 69 min after breakfast and on the serum triglyceride levels 104 min after breakfast. One hundred and 200 mg of BAY g 5421 were equally inhibitory-effective on the serum insulin levels, whereas the highest dose used was markedly more effective on serum triglyceride values than lower doses. Based on these results, a dosage of 100--200 mg of BAY g 5421/meal is recommended for clinical trials in metabolic diseases.


Farmer's lung disease in Vermont.

Farmer's lung disease in Vermont. Several Vermont population groups were surveyed for the occurrence of antibodies to thermophilic actinomycetes. Antibodies to M. faeni and T. vulgaris were measured by the precipitin method in all subjects and, in 124 subjects, M. faeni antibodies were also measured by the indirect fluorescent antibody (IFA) technique. There was relatively good correlation between the two techniques (r 0.48, p less than 0.01). Hospital employees, blood donors and patients with chronic bronchitis were generally negative for precipitins to thermophilic actinomycetes. Of the 258 Vermont dairy farmers surveyed, 14 (5.4%) had precipitins to M. faeni, 3 (1.2%) had precipitins to T. vulgaris but only 1 farmer with antibodies to M. faeni had symptoms of possible farmer's lung disease (FLD). On the other hand, 10 (4.1%) precipitin-negative farmers had symptoms possibly consistent with FLD. The IFA test did not correlate any better with symptoms. 7 (5.6%) patients with pulmonary fibrosis had precipitins to M. faeni 5 of these were diagnosed as having FLD. 18 (14.4%) had precipitins to T. vulgaris and only 3 of these patients were felt to have hypersensitivity pneumonitis. Patients with pulmonary fibrosis and FLD hat IFA titers of greater than or equal to 1/128, but so did asymptomatic farmers.


Radioisotope synoviorthesis in rheumatoid arthritis. Synoviorthesis with radioisotopes is indicated when joint inflammation is not totally controlled by drug prescription. Synoviorthesis should prevent osteoarticular destruction, especially in those cases where the patient does not feel any pain while taking analgesic and anti-inflammatory drugs. Several publications have shown the value of 90Y for treatment of the knee in rheumatoid arthritis. A dose of 4 mCi seems to be sufficient. For digital joints 169Er, a much weaker isotope, is used. Excellent and good results are obtained in 54.6% of cases. A recent double-blind study demonstrated a highly significant difference with saline (+ prednisolone acetate). Other joints, such as the wrist, elbow, shoulder, ankle or hip, can be treated with 198Au or, better, with 186Rh, which is an almost pure beta-emitter. Excellent and good results are seen in 50--60% of cases, depending on the joint. Treatment is well tolerated but patients younger than 40 years should not receive isotopes and the total dose administered should be less than 15 mCi.


[Use of the computer in teaching rheumatology. Trial application in the diagnosis of an adult polyarthritis]. The immense possibilities offered by the computer can be utilized in medical education, through a free dialogue between the student and the machine thanks to a terminal. A diagnostic simulation program has been carried out in diagnosing adult polyarthritis. This program neccesitates an analysis of diagnostic behavior and, on this basis, the preparing of a diagnostic tree or graph. The reasons leading to the plan adopted in constructing the graph, are discussed. Cases of increasing difficulty are proposed to the student, who must follow the course plan in order to arrive at a diagnosis. This teaching method, applied for thing pedagogical advantages both for the teacher and the student. The operating cost seems reasonable.


Morphometric electron and light microscope analysis of lymphoid cells in coeliac disease. Lymphocytes in jejunal biopsies from normal subjects and from untreated, treated, and gluten-challenged coeliac patients were examined by accurate morphometric methods. There was no significant difference between lymphocytes from different sources and those in the jejunum. Transforming lymphocytes were ultrastructurally quite different from non-transforming lymphocytes. The appearance of transforming lymphocytes in the lamina propria in different groups of coeliac patients is in accordance with the increase in the number of plasma cells. In treated patients the results indicate a rapid humoral response to gluten challenge.


Antral G- and D-cell counts in chronic renal failure. Antral somatostatin- and gastrin-producing cells (D and G cells) were studied in a group of patients with chronic renal failure (CRF) in comparison with a control group. Gastric acid secretion and serum gastrin, phosphate, and parathormone (PTH) levels were also evaluated in every patient. The group with CRF showed a mild increase both in G- and in D-cell denisty. In this group serum phosphate and PTH levels were higher than normal, showing hyperparathyroidism in every patient. A direct correlation was found between G-cell density and parathyroid function in patients with CRF. Hyperparathyroidism, therefore, seems to play a role in the mechanism of increased serum gastrin levels in CRF.


The inhibitory effect of 15(R)15 methyl prostaglandin E2 and the interaction with atropine on stimulated gastric acid secretion in man. The inhibitory effect of 15(R)15 methyl prostaglandin E2 (Me PGE2) on the gastric acid response to pentagastrin stimulation, 0.6 micrograms.kg-1.h-1, was examined in healthy male volunteers. Each subject underwent a control test and tests with intragastrically administered graded doses of 15(R)15 Me PGE2 as free acid (80, 140, 200, and 400 micrograms, n = 5) and as methylester (80, 140, and 200 micrograms, n = 6). The percentage inhibition of the acid output during 2 h after increasing doses of the free acid was 24 +/- 11, 49 +/- 7, 44+/-9, and 76 +/- 12%. Corresponding figures for the methylester were 35 +/- 2, 54 +/- 5, and 64 +/- 8%. Both volume and acidity were reduced. Side effects did not occur, except for moderate diarrhoea in one subject after 400 micrograms of the free acid. In a third series (n = 6) the combined effect of 80 micrograms methyl ester (44 +/- 5% inhibition) and 1.5 mg atropine sulphate was studied. Atropine alone gave a 43 +/- 6% inhibition by lowering the secreted volumes. For the combination the inhibition was 82 +/- 3%. Intragastric 15(R)15 Me PGE2 inhibited dose-dependently the pentagastrin-stimulated gastric acid response. Differences between the free acid and methyl ester of the analogue were not significant. Compared with other Me PGE2 compounds, 15(R)15 Me PGE2 was less effective per dose, but the dose range was broader and side effects were slight. Concomitantly given atropine had a significant additive inhibitory effect.


Effect of cimetidine on histamine- and pentagastrin-stimulated gastric secretion in healthy subjects. Cimetidine-induced inhibition of gastric acid and pepsin secretion in response to histamine and pentagastrin simulation was studied in four healthy young subjects. Different doses of histamine and pentagastrin were administered alone and in combination with cimetidine on separate days; the order of administration was randomized. As the dose of histamine increased, the inhibitory effect of 0.6mg.kg-1h-1 of cimetidine on acid output decreased. With supramaximal histamine stimulation the inhibition was completely overcome. These results are consistent with competitive inhibition of histamine-stimulated acid output by cimetidine in man. After pentagastrin stimulation inhibition of acid output by cimetidine could not be overcome by increasing the dose of the stimulant, suggesting a noncompetitive inhibition of pentagastrin-evoked acid output. It is concluded that the kinetics of cimetidine-induced inhibition of histamine- and pentastrin-stimulated gastric acid output are different. At approximately half maximal stimulation of acid secretion, cimetidine was a more potent inhibitor of histamine than of pentagastrin. Pepsin output in response to both histamine and pentagastrin stimulation was also inhibited by cimetidine.


Hepatitis B virus markers among family contacts of asymptomatic HBsAg carriers. A study was undertaken to establish the risk of family contacts of HBsAg carriers acquiring a hepatitis B virus (HBV) infection. About one-third of all household contacts of asymptomatic HBsAg carriers had signs of past or ongoing HBV infection. Family contacts of HBsAg carriers with high numbers of circulating Dane particles were shown to have a higher risk of developing HBV infection than family contacts of HBsAg carriers without serological evidence of HBV synthesis. The probability of acquiring HBV infection was not different between spouses, parents, children, and brothers and sisters, respectively of asymptomatic HBsAg carriers.


Properties of antinuclear antibodies that cross-react with plasma membranes. Certain human antinuclear antibodies (ANA) cross-react specifically with the surface membrane of human leucocytes. In the present work these cross-reacting (X) ANA could be eluted directly from viable leucocytes isolated from three patients. The plasma membrane antigen recognized by X-ANA appeared phylogenetically highly conserved since it was present on viable HeLa cells and cells from mouse and rabbit spleen, rat liver, and the slime mould Physarum polycephalum. X-ANA did not react with the plasma membrane of nucleated bird erythrocytes or human erythrocytes or thrombocytes. The same X-ANA subset reacted with the various cells. The presence of X-ANA correlated strongly (P less than 0.01) with antibodies against a HeLa cell surface antigen. The nuclear antigen recognized by X-ANA was present in all species examined, including bird erythrocyte nuclei and nuclei of Physarum polycephalum. Native or denatured DNA, RNA or a saline extract of nuclei did not inhibit the binding of X-ANA to cell nuclei.


Methodological issues in tardive dyskinesia research. Research into tardive dyskinesia, an involuntary movement disorder secondary to chronic neuroleptic treatment, has so far produced conflicting results with no clear clinical applications. Heterogeneous diagnostic criteria, research designs, and rating scales, plus an emphasis on single-drug trials, are probably responsible. A strategy of developing pharmacological response profiles for patients participating in tardive dyskinesia research is suggested as one way to produce meaningful data, which may delineate pharmacological and clinical subtypes that would respond to different treatment approaches. Further suggestions are made about future trends in this area of research.


Is borderline a distinct entity?

Is borderline a distinct entity? There is no agreement in American psychiatry as to whether borderline should be regarded as a distinct entity. A review of the major viewpoints in the field reveals that borderline is variously used to designate: (1) a clinical disorder distinguishable by behavioral criteria; (2) a milder form of schizophrenia; (3) a nonspecific term encompassing several atypical affective disorders; (4) a psychostructural distinction. When the St. Louis approach to diagnostic validity is used as a guideline, the conclusion reached is that available data do not weigh conclusively for or against borderline's status as an independent entity. In particular, borderline, as defined by several investigators, appears distinct from schizophrenia, but requires further delimitation from the affective disorders.


Borderline schizophrenia: evidence of its validity. Borderline schizophrenia is held to be a valid entity that should be included in the DSM-III. It is a chronic illness that may be associated with many other symptoms but is best characterized by perceptual-cognitive abnormalities. It has a familial distribution and a genetic relationship with schizophrenia. The term schizotypal personality is an acceptable alternative to borderline schizophrenia, but given the apparent genetic relationship with schizophrenia, and given that we are dealing with a vulnerability to episodic symptoms more than personality traits, we prefer the older term.


Genetic determinants of borderline conditions. Evidence about the genetic determinants for borderline conditions is reviewed. The research data are too limited and the diagnostic practices followed in existing studies are too varied to allow firm conclusions to be drawn. Thus, the need for new studies starting with well-defined samples of borderline patients is clear. Previous work implicates genetic factors in the etiology of at least some borderlines, but it is unclear that borderlines by any definition will, as a group, have uniformly strong and specific genetic determinants. With further research, partially overlapping subgroups might be defined on the basis of careful examination of borderline patients' clinical characteristics and family histories. Such characterization could have potential clinical value since there may be subgroups of borderlines who respond differently to various psychopharmacologic treatments (Klein 1975) or to exploratory versus ego supportive psychotherapy (Stone 1977). Characterizations based on genetic considerations may have their limitations, since the genetics of these disorders probably involve complex interactions of a variety of factors that may be more or less specifically related to other major diagnostic groups.


Was Thomas Wolfe a borderline?

Was Thomas Wolfe a borderline? The distinction between the two types of borderline proposed by Spitzer, Endicott, and Gibbon--the Schizotypal Personality type of borderline and the Borderline Personality type of borderline--suggests an advance in our thinking about the borderline concept. However, it can be shown, at least in the case of Thomas Wolfe, that an appreciable amount of overlap exists between the two borderline types, in the sense that the same person can load substantially on items from both types. Such findings may tend to blur the distinction between the two types. Also, Wolfe, hailed as a genius, manifested unusual behaviors which are rarely observed and may constitute a form of borderline condition that challenges current diagnosis.


Post-mortem inflation, radiography, and fixation of human lungs. A method for radiological and pathological correlations and morphometric studies. A method is described for correlative radiological and pathological studies of the lung post mortem, including radiography after air inflation, fixation with formalin-polyethylene glycol-alcohol solution, air drying and systematic histological sampling of lung tissue. For morphometric studies the total lung capacity during life is determined from radiograms and compared with the volume of the excised lung after fixation. The method is simple, relatively inexpensive, and with some experience gives good results both in radiography and histology. With this method the test lungs seemed to assume during fixation a fairly constant volume, a little higher than functional residual capacity.


Humidifier-associated extrinsic allergic alveolitis. Three cases of allergic alveolitis due to indoor humdification systems are described. Thermoactinomyces vulgaris precipitins were detected in the serum of a 37-year-old female patient who had typical febrile attacks during exposure to cool-mist from a home humidifier. When the cause was detected and eliminated, the symptoms and signs disappeared and the woman's gas transfer factor improved from 56% to normal within six months. In a printing office a 60-year-old woman had had febrile attacks with cough for more than a year. The patient herself associated the respiratory disease with a cool-mist humidifier sometimes used at work. The water reservoir was heavily contaminated with amoebas (Amoeba proteus), which might have been the causative organisms in this case. Aspergillus fumigatus precipitins were found in the serum of a 53-year-old female printer with the clinical picture of occupational allergic alveolitis. The same organism was detected in the ambient air of the printing office.


[Thrombangiitis obliterans: diagnosis and therapy in light of new immunological findings]. Thrombangiitis obliterans, a segmental, multilocal, inflammatory disease of the small and medium-sized arteries and veins, is characterized by the relatively juvenile onset of the disease, the peripheral localization of the arterial occlusions and by phlebitis saltans. Other diagnostic criteria are the absence of risk factors typical of atherosclerosis (except smoking), strictly localized occlusion on angiography, phasic clinical course, and exclusion of either collagen disease or essential thrombocytosis. A possible immunopathogenesis for the disease is increasingly favored. In our own study of 33 patients the complement factor C4 was increased in 54.6%, the antielastin antibodies were found at a titre of 1:8 in 57.1% and the immuncomplexes in 23.3%. In only 1 case was the histocompatibility antigen HLA B 12 absent. In view of these immunologic findings and also the fact that phlebitis saltans as a symptom of the disease can be suppressed by salicylates and corticosteroids, but not by anticoagulants, the following therapy is proposed: high doses of acetylsalicylic acid during the acute stage of the illness, or, if this regimen fails, a trial with corticosteroids or immunosuppressive agents.


Potential halogenated industrial carcinogenic and mutagenic chemicals. IV. Halogenated aryl derivatives. A variety of halogenated aryl derivatives possess significant activity as solvents for pesticides, heat transfer agents, pesticide intermediates, additives for rubber products, intermediates in organic synthesis and as insect repellants and deodorants. Ortho- and para-dichlorobenzenes; 1,2,4-trichloro- and hexachlorobenzene, as well as bromobenzenes and benzylchloride were reviewed principally in terms of their synthesis, areas of utility, stability, distribution, reactivity, levels of exposure, populations at risk, metabolism, carcinogenicity and mutagenicity.


Extrapituitary action of gonadotropin-releasing hormone: direct inhibition ovarian steroidogenesis. Gonadotropin-releasing hormone (GnRH) and its agonistic analogs inhibited the follicle-stimulating hormone (FSH)-induced increase of estrogen and progesterone production in vitro by rat ovarian granulosa cells. Likewise, GnRH analogs inhibited FSH-induced changes in ovarian function in hypophysectomized rats in vivo. These results indicate that GnRH, in addition to its well-known gonadotropin-releasing action in the pituitary, exerts a direct inhibition of ovarian steroidogenesis.


Physical factors affecting the mutagenicity of fly ash from a coal-fired power plant. The two finest, most respirable coal fly ash fractions collected from the smokestack of a power plant were more mutagenic than two coarser fractions. Mutagenicity was evaluated in the histidine-requiring bacterial strains TA 1538, TA 98, and TA 100 of Salmonella typhimurium. Ash samples collected from the hoppers of an electrostatic precipitator in the plant were not mutagenic. The mutagens in coal fly ash were resistant to x-ray or ultraviolet irradiation, possibly as a result of stabilization by fly ash surfaces. All mutagenic activity is lost with heating to 350 degrees C.


[Family tree of the historically oldest Premysl dynasty in the light of serological group properties as determined from their skeletal remains]. The determination of group family properties assayed in individuals of five of the historically eldest generations of the Premysl dynasty, who reigned in the 9th and 10th centuries, contributed to: 1. the corroboration or refutation of possible kinship among the individuals under investigation, 2. supporting the identification of some of the individuals as established by other methods, using the above independent methodology, 3. the purification of fragments of anatomically unconnectable parts of the postcranial bones by eliminating fragments of other group properties. In conclusion, the joint anthropological and forensic effort can be said to have contributed to a large extent to obtaining more historical knowledge of personalities associated with the very beginnings of the history of the Czech nation and statehood.


Renal tubular dysfunction in transplanted kidneys. We studied 15 renal transplant recipients for evidence of tubular dysfunction. Eight patients were hypophosphatemic, and two had systemic acidosis with a urinary acidification defect. Mild aminoaciduria and bicarbonaturia were present in four and 14 patients, respectively. Elevated parathyroid hormone level was found in only one patient. Tubular reabsorption of phosphorus was depressed in all eight hypophosphatemic patients, while no such abnormalities were observed in 14 control subjects. Defective tubular reabsorption of phosphorus was the most striking abnormality. None of the parameters studied, including immunosuppressant therapy, parathyroid hormone levels, creatinine clearance, or acid-base balance, clearly account for the pathogenesis of this abnormality.


Retrograde jejunogastric intussusception. Jejunogastric intussusception is an infrequently reported complication of gastroenterostomy. Prognosis and treatment are functions of the anatomic type (Shackman's classification). Gastroscopy and sometimes roentgenograms are the major diagnostic tools. Surgical treatment is required in the acute types where incarceration or strangulation occurs, and in the chronic types when function or quality of life is impaired.


Preventing disruption of abdominal wounds. The use of silver wire retention sutures requires added operating room time and expense, and it incurs the potential hazards of caught viscera, the possibility of more adhesions, leakage of intraperitoneal fluid through the exit wound, mild infection of exit wounds, and, on removal of the sutures, pain despite sedation, cutting of viscera, and a residual cross-hatched scar. Nevertheless, we believe that use of the technic is amply justified by the prevention of abdominal wound disruption, ease in visualization of the wound, ease in providing equal distribution of wound tension and periodic adjustment of it, and in reapproximation of superficial tissues in the event of wound breakdown, as well as in the elimination of need for any external supportive device. The existence of a voluminous literature on the placing, making, and closing of abdominal incisions suggests that no single ideal method exists. Major disruption of abdominal wounds continues to be a serious problem, despite the infrequency of its occurrence. The use of through-and-through semirigid silver wire retention sutures with adjustable tension as a complement to the routine layered closure can prevent disruption of abdominal wounds while causing only minor complications.


Comparison of butorphanol and pentazocine as postoperative analgesics. Sixty patients with moderate or severe postsurgical pain were randomly divided into three equal groups for a double-blind comparison of the analgesic effectiveness of intramuscular butorphanol (2 and 4 mg) and pentazocine (60 mg). The groups were demographically similar. Pain intensity and pain relief were scored at 10, 20, 30, 60, 120, 180, and 240 minutes after administration of the drug. All treatments provided significant analgesic activity (P less than .05) within ten minutes. However, both doses of butorphanol reached their peak effect at 30 minutes, in contrast to 60 minutes for pentazocine. The duration of effect appeared somewhat longer for butorphanol, though this did not achieve statistical significance. Butorphanol (4 mg) had a significantly greater (P less than .05) analgesic effect at ten minutes than pentazocine (60 mg), and both butorphanol treatments (2 and 4 mg) were significantly better than pentazocine, according to many parameters at 20 and 30 minutes. Side effects, chiefly sleepiness and dizziness, were seen in 15% of the patients, with no significant difference between the treatment groups.


Notes on the history of leprosy in Louisiana. In the late 1880s it became apparent in Louisiana that leprosy was endemic in the southern part of the state. Initially, the intention was to establish a leprosy hospital in the city of New Orleans, close to medical facilities, and where the bulk of the patients were to be found. The establishment, instead, of an isolated leper colony at the run-down plantation at Carville, 85 miles up-river, was the result of community indifference, misunderstanding of the nature of the disease, and expected depreciation of property values. Fear of the disease was a secondary matter. The practice of locating residential facilities for the chronically ill at long distances from the centers of physician practice and medical research continues to this day. Interestingly, the arguments that permit this to happen have not changed appreciably from those of a century ago.


Distribution and prevalence of cases of microfilaraemia in Indonesia. Blood smear surveys were conducted in principal villages on the major islands of Indonesia to determine the microfilarial rates presently existing in the populations. A total of 163,454 persons were examined and 10.8 percent found positive for microfilariae of Wuchereria bancrofti, Brugia malayi or Brugia timori. The highest prevalence rates were found in Nusatenggara-Maluku-Irian Jaya (15.5%) followed by Sulawesi (13.7%) Kalimantan (10.8%) Sumatera (8.9%) and Jawa and Bali (1.7%). Many areas endemic for filariasis are used for the settlement of transmigrants from non-filarial endemic areas. Control program must therefore be implemented to prevent filarial infections in these new susceptible population groups.


Occurrence of coliform bacteria other than Escherichia coli in foods. An evaluation of the BGLB (44 degrees C) confirmation test for the enumeration of E. coli as an index of sanitary quality of some foods was made. Out of 70 samples tested, 43 (61.4%) samples contained E. coli. A total of 347 BGLB gas positive cultures obtained were subjected to the IMViC procedure. It was found that 42.7% of these BGLB gas positives were E. coli and 57.3% were ten other coliform bacteria giving the following IMViC patterns: 31.4% --++, 6.3% -+-+, 4.3% each of +-++ and -+++, 3.2% ++-+, 2.9% ++++, 2% ---+, 1.4% +++-, 1.2% --+- and 0.3% -++-. Some of the possible reasons for obtaining low recovery of E. coli in foods by the BGLB test have been discussed. The various fields to be investigated for the improvement of the test procedure and thus the elimination of false positives have been suggested.


Aetiologic agents of septic sore throat in Thai children. A bacteriological study of children with respiratory infections in Bangkok during January to November 1976 revealed that 37% of the patients had symptoms and sign of bacterial pharyngotonsillitis. Twenty-six per cent of these children harboured Streptococcus pyogenes in their throats. The numbers of streptococci other than group A and Staphylococcus aureus were increased in the children with respiratory infections. However, Staph. aureus was found as the sole organism in children with exudate more often than in the children with only URI. The possible role of Staph. aureus in bacterial pharyngitis should not be ignored. Penicillin remains a drug of choice for the treatment of streptococcal pharyngitis. If penicillin is contraindicated, erythromycin should be preferred over lincomycin as a second choice of drug in order to avoid treatment failure if lincomycin resistant streptococci are present.


Levamisole and mebendazole in the treatment of bancroftian infection. Levamisole and mebendazole, broad spectrum anthelminthic compounds were tested against microfilaria of Wuchereria bancrofti, and the results were compared with similarly treated diethylcarbamazine and untreated group. Levamisole at a dosage of 3 mg/kg daily for 8 days showed marked reduction in both microfilaria rate and microfilaria density and immediately thereafter mf-rate steadily increased almost up to pre-treatment level, the mf-density however showed only marginal increase. Mebendazole at dosage of 6 mg/kg daily for 10 days following 8 days treatment of levamisole also showed marginal increase of mf-rate but no increase of mf-density. Treatment with DEC at a dosage of 6 mg/kg daily for 12 days showed comparatively better results both in respect of reduction in mf-rate and mf-density. The reactions - severity and duration were more among levamisole treated groups as compared to DEC treated group. Thus with the dosages tried, DEC could be considered as a better drug than levamisole and mebendazole. Both the latter compounds had no or very limited effect on the adult worms of W. bancrofti.


Gentamicin and penicillin in the treatment of severe respiratory infections. A combination of penicillin and gentamicin has been used for severely ill patients in a respiratory intensive care ward. It has been shown that predictable mean blood levels of gentamicin can be obtained in these patients by relating the dose to surface area (60 mg/m2/8 h). When renal function was initially normal it did not deteriorate during the course of therapy (10 days); gentamicin assays are not essential for safe treatment. In patients with renal failure, increasing the interval between doses also resulted in satisfactory levels, but close monitoring of the serum creatinine level is considered necessary. No clinical difference could be detected when gentamicin was given by constant or intermittent infusion.


Desensitization of patients with bee sting allergy using pure bee venom. Forty patients who had previously experienced severe systemic reactions after a bee sting were desensitized using pure bee venom. A modified 'Rush' regimen was employed whereby patients received two injections a week and reached maximal desensitization in 5 weeks. Eleven patients have subsequently been stung again and have developed no generalized reaction. Although this form of desensitization is considered to be highly effective in protecting sensitive patients, both generalized and local side-effects were frequent. Maintenance desensitizing injections are required every month for an indefinite period. It is concluded that desensitization with pure been venom should be undertaken only in highly selected sensitive patients, and should be performed under strict control.


Atenolol as primary therapy in previously untreated hypertensives and as an adjuvant to other therapy. A South African Multicentre Study. A series of 50 previously untreated hypertensives (group A) were treated with atenolol 100 mg daily and matching placebo in a double-blind cross-over study. A series of 60 hypertensives who were poorly controlled on non-beta-adrenergic receptor blocking drugs, as evidenced by a diastolic blood pressure of between 100 and 120 mmHg inclusive (group B), were treated in the same manner as group A except that they continued to take their previous non-beta-adrenergic receptor blocking drugs throughout the trial. The large majority of patients in both groups (95% and 72%) experienced a fall in blood pressure to satisfactory levels with no significant additional side-effects when compared with placebo treatment.


Healing of peptic ulcers on conventional antacid therapy with or without butriptyline. A group of ulcer patients taking conventional doses of antacids were subjected to a double-blind randomized trial to examine the possible effect of butriptyline on ulcer healing. The study failed to show any advantage of butriptyline over placebo, but this may well have been due to the very success of antacid therapy. The healing rates of gastric and duodenal ulcers in patients on conventional antacid therapy were found to be comparable to those reported with many of the newer ulcer preparations. This study also showed that larger ulcers tend to take longer to heal than small ones.


In vitro survival of human pathogenic fungi in seawater. The survival of propagules from 4 pathogenic fungi, Trichophyton mentagrophytes, Trichosporon cutaneum, Candida albicans, and Microsporum gypseum was studied in seawater subjected to different temperature (20--35 degrees C) and salinity (6--50%) levels in diurnal rhythm of 12 h cycles. Survival was measured by viability of propagules over a period of 52 weeks. All fungi, except T. cutaneum at 35 degrees C survived the experimental conditions for 52 weeks. Temperature was the most influential factor. When temperature increased, M. gypseum responded with enhanced viability whereas survival for C. albicans and T. cutaneum was inhibited. At 35 degrees C, T. cutaneum was not viable after 6--7 weeks even though it survived the initial 5 weeks with less loss of viability than the other test organisms. No correlation was seen between salinity level and loss of viability. Diurnal light had an inhibitory effect on T. cutaneum and C. albicans survival under in vitro conditions approximating those of seawater in Hawaii. M. gypseum had the highest level of survival over 52 weeks under usual in situ conditions simulated in vitro, followed by T. mentagrophytes, T. cutaneum, and C. albicans. Survival for 52 weeks even when salinity and temperature levels exceed those of the natural habitat indicates that seawater which washes sand beaches can be an environmental niche for potentially pathogenic fungi.


In vitro survival of human pathogenic fungi in Hawaiian beach sand. In vitro studies utilizing 4 pathogenic fungi, Trichosporon cutaneum, Candida albicans, Microsporum gypseum and Trichophyton mentagrophytes, all known from Hawaiian beaches, indicate that they survive in the fluctuating beach habitat where they can serve as potential sources of infection for significant periods of time. Survival was measured by testing the viability of propagules at intervals for 6 months. All species survived 6 months under 1 or more experimental conditions. Survival patterns showed both increases and decreases depending upon the given parameters designed to simulate various beach conditions. Propagules inoculated on hair and horn (keratinized inoculum) did not remain viable longer than propagules from pure culture suspensions (non-keratinized). Microbial antagonism was not a major factor in survival. All species survived at least 1 month in non-sterile sand inoculated with keratinized propagules. This condition approximated the natural sand habitat. Alternate wetting and drying of sand caused an overall decrease in survival time except for M. gypseum (non-keratinized inoculum) at 37 degrees C in sterile sand and T. mentagrophytes (keratinized inoculum) at 37 degrees C in non-sterile sand. Temperature was important: increasing temperature resulted in a general decrease in survival time; 45 degrees C was definitely inhibitory, with the exception of T. cutaneum which survived that level for 6 months (keratinized inoculum). Salinity did not influence survival.


A comparison of hyphal growth of Candida albicans in six liquid media. Six liquid media were compared for their ability to promote hyphal growth of Candida albicans. The two clinical isolates used in this study reacted similarly. The proportion of hyphal growth and the time at which hyphal development reached a peak varied in the media tested. All media produced secondary growth characteristics of lateral budding after peak hyphal development. The Lee-Buckley-Campbell (LBC) synthetic medium induced the highest proportion of filaments; which were also longer than in the other media tested.


Antifungal activity of transferrin.

Antifungal activity of transferrin. Inhibitory effects of transferrin on fungal growth were successfully estimated by measuring fungal ATP content. By this method, it was demonstrated that both human and rabbit transferrin possessed the inhibitory effect in the absence of any other factor on yeast-like and filamentous fungi. However, rabbit stimulation factor enhanced the inhibitory effect. The inhibitory effect of transferrin was nonspecific and correlated with unsaturated iron binding capacity (UIBC) of transferrin. Human transferrin was more inhibitory than rabbit transferrin.


Predicting infection in surgical patients. To date, simple skin testing using recall antigens has proved to be the most accurate method of assessing preoperative risk for serious infectious complications. When used in conjunction with measures to control the microorganisms and the environment, evaluation of host defense mechanisms with skin testing can aid in reducing postoperative infectious morbidity and mortality.


Recent advances in human cellular immunobiology. Several recent advances in human cellular immunology will have increasing impact on surgical science. First, lymphocytes are composed of diverse subpopulations with different biological properties. Second, lymphocytes and phagocytes expressed distinctive cell surface markers that reflect the specialized function of each cell. Third, different subpopulations of lymphocytes probably have one or only a few specific functions rather than being multipotential. Despite the seemingly complex heterogeneity of the immune system, the component parts collaborate in a highly integrated fashion. The recent elucidation of suppressor cells and their interaction with effector cells, for example, is a major conceptual advance. Fourth, the technology of immunologic science has advanced significantly. More discriminating methods for detecting lymphocyte markers and the ability to physically separate and analyze lymphocyte subpopulations will permit increasingly more refined insights into normal and abnormal immune responses. A number of important advances at the molecular level involving the disciplines of immunogenetics and immunochemistry have also been described but are beyond the scope of this review. Much work remains, however, in correlating these in vitro observations in the laboratory with in viro activity in the patient. It is now evident that the outcome of an immune response (or lack of it) represents a net balance of different components in the immunologic network that determine the time course, intensity of response, and the actual mechanisms of antigen elimination. A better understanding of these component parts of a normal immune response, and their deviations in disease states, is essential for designing more sophisticated therapeutic manipulations of the immune system. Attempts at "immune manipulation" aimed at stimulating or depleting the entire system are no more likely to be successful or reproducible than are attempts to "manipulate" the entire endocrine system. More meaningful results will occur when one can deal with individual components of an immune response (such as suppression or killing) and can precisely monitor the consequences of altering them.


Reduced incidence of cerebral ischemia following rupture of intracranial aneurysms. A randomized study was carried out to determine if the administration of reserpine and kanamycin to lower the concentration of vasoactive biogenic monoamines would reduce the incidence of cerebral vascular ischemic complications and death following the rupture of intracranial aneurysms. Twenty-six treated and twenty-eight control (untreated) patients were studied. In the preoperative period, eight control (untreated) patients developed symptomatic cerebral ischemia as opposed to one treated patient. There was no correlation between the preoperative clinical findings of ischemia and angiographic evidence of vasospasm. In the post-operative period four control and one treated patient developed symptomatic cerebral ischemia; vasospasm, as demonstrated by cerebral angiography, paralleled these findings.


Migration of ventriculo-peritoneal shunt into lateral ventricle of an adult. Migration of an entire ventriculo-peritoneal shunt into the lateral ventricle of an adult patient with chronic hydrocephalus is presented. The possible causes are reviewed.


Anticoagulants in the treatment of small cell carcinoma of the bronchus. The object of this study was to see if the addition of anticoagulants to a regimen of cytotoxic drugs would improve the prognosis in patients with small cell carcinoma of the bronchus. Twenty-four patients were randomly allocated to receive chemotherapy or chemotherapy plus anticoagulants. The median survival in the group receiving the anticoagulants was not improved.


Levamisole and surgery in bronchial carcinoma patients: increase in deaths from cardiorespiratory failure. Life table analysis of early entry to this randomised blind trial of 318 patients has shown a significantly poorer survival for resected lung cancer patients treated with levamisole for three days before operation and three days a fortnight thereafter than for placebo-treated controls. This excess was largely due to deaths that had been attributed to operation or other causes (non-cancer deaths), most occurring in the six weeks after operation. In the 99 resected patients treated with levamisole there was a 15% excess of deaths in this category, compared with the placebo-treated controls. Extensive analysis excluded maldistribution of patients between the groups as a cause of this difference. Many more died in respiratory distress, mostly without clear cause, in the levamisole group. Antibody (lgG) reacting with myocardial sarcolemma or sarcoplasm was found in the only serum samples available for testing which were drawn from patients during the syndrome. The findings are in keeping with a primary effect on the heart, possibly involving an autoimmune mechanism. The effect has not been noted in other trials.


A comparative study of atropine methonitrate, salbutamol, and their combination in airways obstruction. Dose-response relationships of the cholinergic antagonist, atropine methonitrate, and the beta-adrenergic agonist, salbutamol, were examined by cumulative dose techniques. A wet aerosol, 1.5 mg atropine methonitrate produced a maximum response. The response to 200 microgram of salbutamol from a pressurised aerosol was close to maximum. Secondly, the bronchodilator response of salbutamol microgram was compared with atropine methonitrate 2 mg and placebo in 18 asthmatic patients in a randomised crossover study. In 11 of them the bronchodilator response of the combination of salbutamol and atropine methonitrate was evaluated. Atropine methonitrate produced a similar peak bronchodilator effect to salbutamol, but its effect was more prolonged, the response being significantly greater at four and six hours than with salbutamol. The combination of drugs produced a significantly greater and more lasting bronchodilatation than either of the drugs alone. Despite mild side effects, atropine methonitrate, either alone or in combination with an adrenergic drug, appears to have a place in the treatment of sever reversible airway obstruction not adequately controlled by conventional treatment.


Separation of human cells bearing HLA-DR antigens using a monoclonal antibody rosetting method. A technique is described for enriching, from human blood, cells bearing HLA-DR antigens. The method depends on the use of monoclonal mouse antibody which reacts with HLA-DR structures. Cells to which this antibody has bound can be separated after rosetting with bovine erythrocytes coated with anti-mouse immunoglobulin. The cells thus enriched may be used for HLA-DR typing by standard cytotoxicity methods with allogeneic sera.


Acidic glycosaminoglycans in human esophagus tissue. The constitution of acidic glycosaminoglycans (AGAG) in the normal human esophagi which were obtained at autopsy from 13 female subjects, from 30 to 59 years old, was biochemically analyzed by the procedures such as resin chromatographic separation, electrophoretic characterization in 3 buffer systems and enzymic assay with chondroitinases and hyaluronidase. The main AGAG was hyaluronic acid which amounts to a half of total AGAG, followed by heparan sulfates and dermatan sulfate one fifth of total AGAG each, and small amounts of chondroitin-4- and -6-sulfates and oversulfated chondroitin sulfate. Heparin was not detected. A possible role of the esophageal AGAG was discussed.


Vibratome sections of difficult tissues. After 1 hours of aldehyde fixation, 4 to 20 hours of soaking in 2% BSA (bovine serum albumin) solution and another 17 hours in the same fixative, the vibratome will produce smooth, even sections from agar embedded guinea pig thyroid, skeletal muscle or larynx with the same ease as it will from soft, homogeneous tissues such as liver or spleen.


A method for orienting cryostat sections for three-dimensional reconstructions. Tissue for cryostat sectioning is embedded together with reference tissue impaled on the needles of a specially constructed trident. To maintain spatial orientation, reference and experimental tissue are frozen in Tissue-Tek O. C. T. compound in the manner usual for enzyme histochemistry using a simply constructed carrier. The trident is removed by heating its handle, thus leaving holes in the reference tissue which in turn are used as reference points to orient successive sections with respect to each other.


Postembedding adjuvants in routine microtomy of paraffin-processed tissues. Soaking the exposed face of routine paraffin-processed tissue blocks from human autopsies in solutions containing either 60% ethyl alcohol-glycerol 9:1; glycerol-aniline 9:1; 5% aqueous phenol; 5% aqueous Photo-flo, or 10% aqueous ammonium hydroxide for 2--4 hours at 0--4 C resulted in greater ease of ribboning and overall improvement of slide quality in the majority of sections compared to the results with the same blocks soaked only in water at 0--4 C. The use of postembedding adjuvants, especially 10% aqueous ammonium hydroxide, presents a simple, convenient, inexpensive means of increasing section quality with routine as well as refractory paraffin-embedded tissue without sacrificing tissue adhesion, staining qualities or cellular detail.


Transmission and scanning electron microscope preparations of the same cell culture. A technique has been developed which allows transmission electron microscopy and scanning electron microscopy to be performed on the same cell culture sample. The technique uses the Costar 3,393 Leighton Tube containing a plastic insert, which does not stick to epoxy, for transmission electron microscopy. A cut piece of the plastic insert can be critical point dried, sputter coated and viewed under high vacuum with the scanning electron microscope.


A sensitive solid phase enzymeimmunoassay for testosterone in plasma and saliva. A sensitive, solid phase enzymeimmunoassay suitable for determining testosterone concentrations in samll aliquots of plasma (20 microliter) and saliva (200 microliter) has been developed. A solid phase antiserum raised against a testosterone-11 alpha-hemisuccinate/bovine serum albumin conjugate was prepared by coupling to cyanogen bromide activated cellulose. The "enzyme label" was a covalently linked testosterone/horseradish peroxidase conjugate. The assay had a lower limit of sensitivity of 4pg/assay tube and satisfied accepted criteria of specificity and precision. Testosterone concentrations determined by enzyme-immunoassay were in excellent agreement not only with a gas liquid chromatography/mass spectrometry procedure (r=0.96, n=12) but also with the radioimmunoassay in routine use (r=0.95, n=12). The EIA can therefore replace RIA in both the small clinical laboratory and high throughput service centres for determining plasma and salivary testosterone concentrations. In normal males salivary testosterone concentrations reflected circulating steroid levels and indicated the possibility of assaying saliva rather than plasma in clinical studies.


Treatment of vivax malaria with sulfadoxine-pyrimethamine and with pyrimethamine alone. The effect of pyrimethamine and the combination of pyrimethamine-sulfadoxine (Fansidar) upon the termination of the acute attack of vivax malaria was studied in Thailand. Pyrimethamine was found to be ineffective, providing clearance of parasitaemia in only two of six patients by the end of seven days following treatment. The combination, administered in a two-tablet single dose (sulfadoxine 1 gm, pyrimethamine 50 mg) eliminated parasitaemia in only six of ten patients within seven days. Three tablets (sulfadoxine 1 . 5 gm, pyrimethamine 75 mg) given to 11 patients, provided clearance of parasitaemia in all within seven days; however, mean parasite and fever clearance times in this group were prolonged at 90 and 50 hours respectively. Chloroquine remains the drug of choice for the termination of the acute attack of vivax malaria. Subsequent primaquine is necessary for the prevention of relapse.


Immunosuppression in bancroftian filariasis. Immunological function in Filipino patients with bancroftian filariasis, manifested as either asymptomatic microfilaraemia or chronic obstructive disease, was compared with that found in healthy control subjects living in the same area. As a group, patients with filariasis had raised serum IgG levels, impairment of antibody responses to tetanus and typhoid vaccines, and suppression of delayed hypersensitivity skin reactions to heterologous antigens. This immunosuppression in filariasis may result from antigenic competition and may contribute to the development of secondary infections.


Serum immunoglobulin levels and malaria antibodies in Burkitt's lymphoma. Data are presented to support a relationship between malaria infection and Burkitt's lymphoma in African children. IgG, IgM and IgA levels were measured in sera from Burkitt's lymphoma patients and from sex- and age-matched, nearest-neighbour controls. All three classes of immunoglobulins were present in significantly lower amounts in the sera from Burkitt's lymphoma patients than in the sera from controls. The mechanism of this apparent B-cell suppression is not yet clear. Malaria-specific IgG and IgM antibody titres were determined in the indirect immunofluorescence test. No significant difference in the IgG malaria-specific antibodies was detected between the two groups of sera. Malaria antibody levels measured using IgM specific conjugates were significantly lower in the sera from Burkitt's lymphoma patients in reactions with Plasmodium falciparum antigen. No significant difference was observed when P. malariae was used. Confirmation of this finding would serve as a positive link between Burkitt's lymphoma and P. falciparum infection.


Lethal post-transplantation calcinosis.

Lethal post-transplantation calcinosis. The case studies of four patients with post-transplantation calcinosis are presented. Three of the four patients died of inanition and sepsis secondary to infection of extensive soft tissue ulcers and diffuse cutaneous vascular calcification with gangrene. The fourth patient survived following removal of all four parathyroid glands and autografting of approximately one-half of one gland. Common to the patients was secondary hyperparathyroidism, elevated mean serum calcium levels after transplantation, and radiographic evidence of small and medium vessel calcification. No other differences could be found between these patients and other patients with post-transplantation hyperparathyroidism without calcinosis. In the face of apparently minor complaints of lower extremity discomfort, elevated parathyroid hormone levels (PTH) and positive xerography may indicate subtotal parathyroidectomy regardless of the serum calcium level.


Pregnancy in renal transplant patients: a review. A questionnaire survey and review of the literature show that pregnancy can be well tolerated in most women with renal transplants. Fifty-two per cent of the renal transplant recipients who became pregnant had full-term infants with no serious complications. With therapeutic abortions, excluded, 71% of the 308 pregnancies permitted to continue resulted in full-term infants. Rejection episodes were occasionally a serious problem, occurring in 9% of the pregnancies. Mechanical interference with renal excretion or preventing vaginal delivery occurred in 5.6% of the cases. Hypertension and proteinuria, often existing prior to pregnancy, became frequently increased during pregnancy. Infections not associated with rejection were common but easily controlled in most cases. Prematurity was frequent but related to renal function and the time interval from transplant to conception. The most serious infant complications were related to prematurity. Unknown is the future of these infants and their progeny because of their intrauterine exposure to immunosuppressive drugs.


100 second renal allografts from a single transplantation institution. Between January 1, 1968 and March 1977, 100 of 131 patients who lost their first transplant at the University of Minnesota received a second renal allograft. Overall patient survival in the retransplanted group was 10% less than that in the dialysis group. The best results (graft function and patient survival were seen in young patients, nondiabetics, patients who received two sequential living related groups, and in those whose first graft was lost secondary to chronic rejection. The poorest results were seen in older patients (greater than 40 years), diabetics, and patients with acute rejection during the initial graft. Shared donor antigens do not affect graft outcome. These findings, although not the product of a randomized prospective study, may be useful in advising patients of the relative risks of retransplantation or hemodialysis.


Do blood transfusions enhance the possibility of a compatible transplant? Blood transfusions prior to first cadaver kidney transplants have a significant beneficial effect on graft survival and, in this sense, appear to enhance the possibility of a compatible transplant. This desirable effect, however, occurs concomitantly with an increased degree of sensitization, which in turn reduces the likelihood of identifying a compatible kidney by direct crossmatch testing. This report illustrates that the beneficial effect is achieved with one to five transfusions prior to transplantation, but that more transfusions afford no additional benefits. In addition, the presence of cytotoxic antibodies per se does not have an adverse influence on graft survival. Liberal transfusion policies are therefore indicated in cadaver transplant candidates, but more than five transfusions prior to transplantation should probably be avoided unless clinically necessary.


Prognosis after renal transplantation: cumulative influence of combined risk factors. Seven hundred sixty-seven primary renal allografts from a single center were divided into subgroups according to combinations of several major risk factors: donor source and histocompatibility match, age, and presence or absence of diabetes. The relative effect of diabetes on patient and graft survival decreased as histocompatibility differences increased. The influence of recipient age, however, dramatically decreased as histocompatibility differences decreased. In all groups donor source and histocompatibility match had the strongest relative effect in determining subsequent 2-year patient and graft survival.


Rejection of C57BL/6 skin grafts by (C57BL/6 X Mus musculus castaneus)F1 hybrids. Hybrid offspring from C57BL/6(B6) females mated to males of the subspecies Mus musculus castaneus received B6 skin grafts. No strong Y chromosome-linked histocompatibility genes were detected, although occasional rejection of parental grafts by both male and female hybrids was observed after long periods. Rejection was attributed to interaction of B6 and Castaneus-derived genes in the hybrids.


Diversity of expression of H-2 antigens on mouse liver cells demonstrated by immunoferritin labeling. Antigens of the mouse H-2 locus were studied on isolated liver cells by immunoferritin labeling. Cell suspensions were obtained by gentle homogenization of mouse livers that had been perfused with hypertonic sucrose to loosen cell junctions. Hepatocytes showed sparse labeling of H-2 antigens on the order of 1% of that present on peritoneal monocytes. The slight hepatocyte labeling appeared to be specific for the H-2 locus, since there was essentially no label on congenic control hepatocytes. Other cells in the liver cell preparations were more heavily labeled. Bile duct epithelial cells showed heavy labeling on their lateral surface membranes, but none on their apical brush borders. The preparations contained another nonparenchymal cell type that was densely labeled, but it was not positively identified. Spleen lymphocytes added to liver homogenates and carried through the cell isolation procedure with liver cells showed typically heavy ferritin labeling. These observations suggest that the expression of histocompatibility antigens by tissue cells is likely to be quite variable.


Possible involvement of the central nervous system in graft rejection. Electrolytic lesions were produced in the tuberal hypothalamus and amygdala of male Fischer and female BNLF1 rats, and in male Fischer and female BNLF1 rats that had received antecedent hypophysectomies. Skin grafts from Lewis rats survived less well on tuberal-lesioned male Fischer rats than similar grafts on sham-operated and amygdala-lesioned male Fischer rats. Lewis skin graft survival was also curtailed in male Fischer rats that had received hypophysectomies followed by tuberal lesions. These differences were not apparent across the male to female (H-Y) BNLF1 histocompatibility barrier. We conclude: (1) that tuberal hypothalamic lesions stimulate allograft reactivity in rats, (2)that this response is greater when the immunogenetic disparity between donor and host is greater, and (3) that the mechanism governing this response involves a direct neural pathway which bypasses the hypothalamic-hypophyseal axis.


Antibody-dependent cell-mediated cytotoxicity tests for immunosuppression monitoring of transplant patients. The antibody-dependent cell-mediated cytotoxicity (ADCC) effector activity and phytohemagglutinin (PHA) response of kidney transplant patients were monitored by a new whole blood microassay that permitted performance of 20 tests using only 1 ml of blood. Eleven patients were followed on as many as 55 different occasions with these tests. The ADCC activity of dialysis patients was essentially the same (78% chromium release as compared with 83% in normal controls). However, patients with kidney transplants undergoing immunosuppression had approximately one-half the chromium release (40%). Daily fluctuation in the chromium release could not be used as a predictor of subsequent rejection. The PHA response was as much as 50-fold less in the immunosuppressed patients. Both values also tended to be slightly higher among patients who were doing well than those who were doing poorly. This may reflect the need for greater immunosuppression in the rejecting patients.


Influence of previous immunization on skin graft survival. The results of skin grafts transplanted in immunized and nonimmunized recipients was analysed. Specific sensitization for HLA-A or B determinants shortens graft survival if the recipients were immunized by s.c. injections of leukocytes. When the recipients had been pregnant, no such influence of specific HLA-A or B sensitization could be demonstrated. The variance in mean survival times of grafts exchanged between mixed lymphocyte culture (MLC)-positive donor-recipient combinations was significantly smaller than the variance in mean survival time (MST) of grafts exchanged between MLC-negative combinations. This difference could be the result of the influence of allograft immune-activating determinants of different strength in the MLC-negative donor-recipient combinations. Also the variance in MST of grafts in immunized recipients was significantly larger than the variance in MST of grafts in nonimmunized recipients. Apart from the obvious effect of HLA-A and B sensitization, other less well documented factors must have influenced graft survival. We did not find evidence for a graft enhancing effect of B cell-specific antibodies.


Relationship of B cell alloantibodies to renal allograft survival. To define the relationship of donor-specific B lymphocyte alloantibodies to renal allograft survival, longitudinal serum samples obtained pre- and post-transplantation were examined for antibodies cytotoxic to donor B lymphocytes. Ten of 17 renal allograft recipients had antibodies to donor B lymphocytes but not T lymphocytes either pre- and/or post-transplantation. Three patients underwent successful transplants despite preformed B cell antibodies; however, seven who developed B cell antibodies only after transplantation are either undergoing chronic rejection (4) or have had severe rejection crisis (3). Seven patients with no B cell antibodies have functioning grafts. In all cases, B cell antibodies were detected before biochemical and clinical evidence of rejection. Similar findings were noted when sera of 38 renal transplant recipients were examined for B cell antibodies cytotoxic to an unrelated panel of B lymphocytes. These results demonstrate that the development of B cell alloantibodies after transplantation is often associated with rejection and that successful renal transplantation can be performed across a positive B cell crossmatch.


Significance of migration stimulatory factor in human renal allotransplantation. Seventy-four recipients of related donor renal allografts were tested for the presence of cellular immunity to specific donor lymphocyte antigens using the direct migration inhibition factor (MIF) assay. Responses on the assay fell into one of the following three statistically distinct groups: (1) greater than 20% inhibition of macrophage migration, (2) nonresponsiveness,  +/- 10% of control migration, and (3) greater than 12% stimulation of macrophage migration. Migration stimulation was shown to be reproducible and to correlate well with a very benign post-transplant clinical course. The production of migration stimulatory factor appears to be an immunological response analagous to the production of migration inhibition factor.


[Further observations of the course of Plasmodium berghei infection in the mouse]. Invasion of immature and mature erythrocytes by merozoites of Plasmodium berghei seems to obey the following rules: Merozoites prefer unparasitized immature erythrocytes. Multiple infections of immature erythrocytes occur in conditions of high merozoite production and low concentration of unparasitized immature erythrocytes, when frequently repeated contacts between merozoites and unparasitized or freshly parasitized immature erythrocytes become increasingly probable. Mature erythrocytes are invaded when the relative density of unparasitized immature erythrocytes drops below 0.2--0.5%, in other words, when merozoites do not meet unparasitized immature erythrocytes in 200--500 erythrocytes. Failure to invade mature erythrocytes is obviously not due to inability of the merozoites to penetrate the erythrocyte membranes.--Merozoites of Plasmodium vinckei, on the other hand, show random invasion of parasitized and unparasitized mature erythrocytes, leading to frequencies of unparasitized and singly or multiply parasitized erythrocytes approaching a Poisson distribution.--The Plasmodium berghei infection regularly leads to a lowered density of polychromatophilic erythrocytes in the peripheral blood. This depression of polychromatophilic erythrocytes uses to be of very different duration, form and intensity. The relative density of immature erythrocytes may show pronounced fluctuations in this phase. As has been seen in one animal, even monocytes and polymorphonuclear leucocytes may, alongside with the immature erythrocytes, for some time totally disappear from the peripheral blood. The depression of polychromatophilic erythrocytes evidently goes along with pronounced alterations of the erythropoesis in spleen and bone marrow. Leucocytes in the peripheral blood generally show rather uncharacteristic alterations of their concentration, they may form very high concentration peaks.


Chemotherapy of echinococcosis with mebendazole: clinical observations of 7 patients. The effect of high dosage therapy with Mebendazole was studied in 5 patients with cystic echinococcosis and 2 patients with alveolar echinococcosis involving several organs. Follow-up studies at regular intervals from 7 to 20 months indicated an improvement of the pathological findings initially observed. This could clearly be demonstrated by the radiographic findings in cases with pulmonary involvement. The desintegration or dissolution of pulmonary cysts was observed within a few months after treatment with Mebendazole had begun. However, consolidation of previously emptied cysts occurred during the follow-up later. Allergic reactions were observed after commencement of drug therapy in two cases. These were probably due to spillage of antigenic material. The following treatment periods were tolerated well. No serious toxic side effects were observed in the other cases described here.


Studies on Dipetalonema viteae (Filarioidea) 3. Antibody-dependent cell-mediated destruction of microfilariae in vivo. Antibody-dependent cell-mediated destruction of Dipetalonema viteae microfilariae could be demonstrated in the golden hamster using a micropore chamber technique. Microfilariae were eliminated within 24 hours in chambers of 3.0 and 5.0 microm pore size when implanted into amicrofilaremic hamsters (week 30 post infection). At peak microfilaremia (week 12 post infection), only some hamsters could efficiently destroy microfilariae. In chambers with 0.3 microm pore size, microfilariae survived for more than 3 weeks in all hamsters. In uninfected hamsters, microfilariae could only be eliminated if they had been preincubated with serum or its 19S fraction containing antibodies to the cuticle of microfilariae. The opsonizing activity of the serum was abolished by 2-mercaptoethanol treatment. The composition of cells adhering to microfilariae was always significantly different from the composition of cells which migrated into a chamber. The adhesion patterns on individual microfilariae indicated that no single effector cell type was responsible for the destruction of microfilariae. The eosinophil was the predominant cell type but neutrophils, lymphocytes and monocytes also adhered to the microfilariae. Cellular adhesion led to the immobilization of microfilariae and subsequently to their disintegration within large cell clusters. During the final stages of destruction the contribution of the monocyte became more pronounced.


Notes on nematode larvae others than microfilariae found on filter membranes in blood surveys for bancroftian filariasis. Among 741 people examined in a rural area in Liberia for microfilariae of Wuchereria bancrofti 39 (5,3%) were found to be infected with nematode larvae others than microfilariae. These larvae had more developed inner structures than microfilariae and could be classified into two different types, differing in length and shape. The larvae have not been identified yet, but it is believed that they have to be associated to parasitic nematodes of the intestine.


Effect of polyamines on protein kinases activities from Trypanosoma cruzi. An interaction of polyamines with protein kinases activities from T. cruzi epimastigotes is demonstrated. Spermine and spermidine and less pronounced putrescine are found to inhibit protein kinases activities. In the extract of T. cruzi three protein kinases are distinguished on account of molecular weight (greater than 200 000, 95 000 and 40 000) and preference for acceptor proteins (phosvitin and histones). Especially the activity of the high molecular weight protein kinase which phosphorylates phosvitin is strongly inhibited by spermine and spermidine. The type of inhibition by both polyamines is found to be non-competitive with respect to ATP as well as phosvitin. The inhibition constants for spermine and spermidine are determined to be 1.4 mM and 2.0 nM, respectively.


Studies on Bancroftian filariasis in Liberia, West Africa. I. Distribution and prevalence in the north-western savanna area. A nightblood survey was carried out in 17 villages in the savanna area in Upper Lofa in Liberia. A total of 1968 people was examined for the prevalence of microfilariae of Wuchereia bancrofti and for clinical symptoms of filariasis. 279 (14,2%) persons proved to be microfilaria carriers. Men were almost twice (19,0%) as much infected than women (10,4%). Only two cases of leg elephantiasis and one breast elephantiasis were found. Enlargements of scrotum were seen in 60 men (6,9%). The scrotal enlargement rate increased steadily with age.


Electron microscopical studies on onchocerciasis. II. Skin and microfilariae after treatment with metrifonate. Skin snips of six patients with manifest onchocerciasis treated with a single dose of metrifonate (10 mg/kg) were examined by electron microscopy one, three, five and ten days after application of the drug. Compared to untreated cases 24 hours after treatment there is a marked increase in the extend of perivascular infiltrates which are composed not only of macrophages, lymphocytes and plasma cells, but also of eosinophils. Infiltrates directly around dead microfilariae are seen infrequently. This pattern of cellular reaction remains constant for the first ten days after treatment. Metrifonate obviously kills the microfilariae rapidly, already 24 hours after its application totally disintegrated parasites are to be found. On the other hand always a few intact microfilariae are seen, possibly they just hatched after treatment.


Serodiagnosis of infection with Trypanosoma evansi in camels in the Sudan. Five diagnostic tests for infection with Trypanosoma evansi have been compared in groups of camels experimentally infected or exposed to natural infection in the Sudan. The correlation of positive results obtained by assays of IgM levels, the mercuric chloride test and the formol gel test with the presence of active infection was unsatisfactory, but there was a good correlation between results obtained using IFAT and ELISA and proven infection. Sera from a high proportion of apparently uninfected camels from endemic areas gave positive reactions with all 5 tests, possibly indicating inadequate parasitological diagnosis or persistence of antibody after unsatisfactory chemotherapy. It was concluded that serological tests using trypanosomal antigens to detect antibodies were more sensitive for diagnosis than indirect tests based on raised euglobulin levels. Serodiagnostic tests may therefore have a place in future programmes for surveillance and control of T. evansi infections in camels.


Effects of prolonged luteinizing hormone-releasing hormone therapy on follicular maturation, ovulation and corpus luteum function in amenorrhoeic women with anorexia nervosa. Nine amenorrhoeic women with anorexia nervosa (AN) were given long-term treatment with 500 microgram of synthetic luteinizing hormone-releasing hormone (LRH) every 8 h. All the women had impaired luteinizing hormone (LH) secretion and no evidence of endogenous oestrogen production. Three of them also had deficient follicle-stimulating hormone (FSH) secretion. The pituitary reserve capacity for gonadotrophin secretion was normal but the response pattern to LRH was similar to that described in prepubertal girls. The constant administration of LRH normalized basal LH and FSH secretion and induced a cyclical gonadotrophin secretory pattern with differential changes of the LH and FSH responses to LRH during the treatment. LRH-induced gonadotrophin secretion produced follicular growth and maturation in all the women. Presumptive ovulation also occurred during the 8 treatment courses in which only LRH was administered. However, inadequate luteal phases were observed during 6 of these 8 cycles. Combined therapy with LRH and human chorionic gonadotrophin (HCG) during 5 treatment courses resulted in normal ovulatory cycles with adequate corpus luteum function.


Differential effect of cupric ions on the in vitro utilization of glucose by blastocysts and pancreatic islets. To evaluate a possible interference of cupric ions on the trophoblast cell metabolism, glucose utilization was studied in mouse blastocysts delayed in utero and later activated by oestradiol for 18 h. Isolated pancreatic islets from guinea pigs were used for comparative purposes. The pancreatic islets were not affected when the copper concentration was 0.1 mmol/l whereas for the blastocysts a marked effect was found already at a concentration of 0.01 mmol/l. This indicates that copper concentrations even lower than that of the uterine secretion in presence of a Cu-IUD might affect different enzymes linked with the glucose metabolism of the trophoblast cells.