Influence of anti-rheumatic drugs on human lymphocytes in vitro. Influence of anti-rheumatic drugs on human lymphocytes, especially T and B cell membranes, was studies with D-penicillamine, aurothiomalate, dexamethasone, cyclophosphamide, mitomycin C and aspirin. Peripheral blood obtained from five healthy individuals and lymphocytes were separated by centrifugation with Lymphoprep. The separated lymphocytes were adjusted to 5 X 10(6)/ml in PBS. The suspension of lymphocytes was mixed with equal volume of each concentration of the above drugs. After suspensions, we investigated the percentages of T -and B-cells, compared to control. The results are as follows: 1. Drugs which act only on the T cell membrane: D-penicillamine, aurothiomalate. 2. Drug which acts only on B cell membrane: dexamethasone. 3. Drugs which act on both T- and B-cell membrane: mitomycin C, cyclophosphamide and aspirin.


[Analysis of the causes of the predominant localization of macular cerebral vessel and tissue lesions following an acute rise in arterial pressure]. In acute experiment on rabbits a rise in arterial pressure was induced by intravenous administration of noradrenaline with simultaneous recording of the changes in the vessel diameter on the surface of the brain in arterial bordering zones and in the basin of the middle cerebral artery and permeability of the hematoencephalic barrier to Evans blue. Autoregulation disorder manifesting itself in dilatation of the arteries and spreading out of their enternal elastic membrane developed first of all in arterial bordering zones, appeared earlier and was marked mainly in the anastomoses of the major type and small arteries lying at an acute angle which are more often detected in the occipital regions of the blood supply area. Similar results were obtained with an analysis of 3-section cases of hypertensive encephalopathy.


Effect of alpha-MSH on the tyrosinase activity and the rate of melanin accumulation of melanoma cells in vitro. A stimulation of the tyrosinase activity was observed when melanoma cells isolated from transplantable mouse melanomas were incubated at 37 degrees C for 6 h in the presence of 1-10 X 10(-6) M alpha-MSH. All strains of mouse melanomas studied (B-16, Cloudman S-91 and Harding-Passey), exhibited similar responses. It was also observed that the intact cellular structure of melanoma cells was not required for the ability to respond to alpha-MSH. The stimulation of the enzymic activity was accompanied by an increase of the rate of incorporation of radioactivity into melanin from L-[U-14C]tyrosine, indicating an enhanced melanogenesis of tumour cells under in vitro conditions.


Serum prolactin in patients with "functionless" chromophobe adenomas before and after therapy. The immunoreactive serum human prolactin (PRL) level was measured before and after intravenous administration of 500 mug of thyrotrophin-releasing hormone (TRH) in 11 patients with "functionless" chromophobe adenomas before and after surgery and after radiotherapy in 6 of these patients. The results were compared to other pituitary function tests. Two of the patients studied had recurrent disease after previous pituitary surgery and radiotherapy. Five patients had pituitary surgery through the transfrontal route, while 6 had adenoma removal via the transnasal transsplenoidal route. Before surgery, the serum PRL concentration was abnormally high in 4 patients, before and after TRH administration. It was normal in 6 and subnormal in 1 patient who had had previous therapy. Two of the patients studied showed high serum thyroid-stimulating hormone (TSH) levels in the presence of low serum T3 and T4 suggesting primary hypothyroidism with a secondary TSH-producing pituitary tumour. After surgery all patients showed a significant decrease of the serum PRL level. This contrasts with more variable results in the measurements of other pituitary hormones. Post-operative radiotherapy produced no significant additional change in serum PRL levels in 5 of the 6 patients measured 6 months to 4 years after radiotherapy. Five of the 6 patients who had adenoma removed via the transsphenoidal route required no cortisol replacement and 4 remained euthyroid, whereas all 5 patients after transfrontal surgery required both cortisol and thyroid hormone replacement. These results indicate: (1) that measurement of serum PRL levels at basal and after TRH administration in patients with "functionless" chromophobe adenomas before and after treatment may be the best index for evaluating the effect of therapy; (2) that adenoma removal may be followed by preservation of normal pituitary function, but this is more likely to occur if the transsphenoidal approach is used; and (3) that primary thyroid insufficiency may be associated with a pituitary adenoma.


Electron microscope and high resolution autoradiographic studies of megaloblastic erythropoiesis. Bone marrow fragments from 10 patients with a megaloblastic anaemia due to vitamin B12 or folate deficiency were studied by electron microscopy and electron microscope autoradiography. A proportion of the erythroblasts showed ultrastructural abnormalities. Some of the cells containing autophagic vacuoles, large siderosomes, iron-laden mitochondria, irregularly shaped nuclei, membrane-bound nuclear clefts, or incomplete nuclear membranes were found to be capable of DNA, RNA and protein synthesis. Other cells showed advanced degenerative changes such as the distension of the perinuclear space, the clumping of cytoplasmic organelles near the nucleus and a reduction in the electron density and ribosome content of the cytoplasm. Most of these grossly abnormal cells suffered from either a marked depression or an arrest in protein and RNA synthesis, and were presumably destined for phagocytosis by reticulum cells.


Idiopathic acquired refractory sideroblastic anemia: Banded chromosome analysis in six patients. Chromosome analyses with banding were performed on six patients with idiopathic acquired refractory sideroblastic anemia (IARSA). One patient was found to have an extra chromosome No. 8, but had a normal level of red cell glutathione reductase. Bone marrow chromosomes from the other patients showed a normal karyotype. 28 patients with IARSA, including our 6 patients, have had chromosomal analyses. Two consistent chromosomal abnormalities have been described: a + 8 in three patients and a 20q- in three others. Despite the presence of chromosomal abnormalities in abouut one half of the patients, no patients has yet developed acute myelogenous leukemia. Several have died of hemochromatosis. The presence of a chromosomal abnormality appears to have no influence on the early course of IARSA.


Quantitation of Hb a2 with DE-52 microchromatography in whole blood as screening test for beta-thalassemia heterozygotes. HB A2 was assayed by means of DE-52 microchromatography in hemolysates from 285 normal subjects and 223 beta-thalassemia heterozygotes. No overlap was found between both groups. Comparable results were observed analyzing whole blood samples collected in capillary tubes from 550 normal subjects and 295 beta-thalassemia heterozygotes. Our results demonstrate that this technique is useful in a screening program for beta-thalassemia trait.


Tetraploid cell line in a girl with acute leukaemia. In a girl with atypical acute leukaemia the malignant cell line in peripheral blood and bone marrow during these relapses was found to be tetraploid. The abnormal cells were more proliferative than those usually present in acute leukaemia. The tetraploid DNA content of the blast cells distinguished them from other cells in blood and bone marrow from this patient and from the blast cells found in other instances of acute lymphoblastic leukaemia.


Interaction of haemoglobin E with alpha-thalassaemia and haemoglobin Constant Spring. The combination of Hb E,alpha-thalassaemia and Hb CoSp was found in a 20-year-old female Malay who presented with a moderately severe haemolytic anaemia. The findings in the patient and her family from which this diagnosis was arrived at are discussed. Although this is the first report of this condition in this country it is pointed out that one may see more such cases in the future if one is aware of this condition since Hb E, alpha-thalassaemia and Hb CoSp all occur at significant frequencies in this country.


Red cell pyruvate kinase deficiency: adverse effect of oral contraceptives. Erythrocyte enzymopathies are being detected with increasing frequency. The homozygous state for pyruvate kinase (PK) deficiency usually causes chronic non-spherocytic haemolytic anaemia. Aggravation of the condition by a variety of extrinsic factors has been reported, but drugs have rarely been incriminated. A case of severe PK deficiency is presented in which an anovulant drug upsets the usual haematologic balance. This strengthens the suspicion that contraceptive pills may be hazardous in such patients.


Effect of blood transfusion on the immune response of children with thalassaemia. The effect of blood transfusions on the immune response of 46 thalassaemic children was studied. Cell-mediated immune response was evaluated by performing skin tests to specific (streptokinase-streptodornase and candidin) and nonspecific (dinitrochlorobenzene and phytohaemagglutinin) antigens. Antibody response to specific antigen (tetanus toxoid) was estimated by measuring the tetanus antitoxin titre before and after vaccination. No gross impairment of cell-mediated immunity was elicited. The larger proportion of negative phytohaemagglutinin skin tests found in thalassaemic patients does not necessarily suggest a cell-mediated immunity impairment, since this skin reaction is also affected by other factors, especially the inflammatory skin response. The transfused antibodies may inhibit the recipient's sensitization and primary immune response to the homologous antigen, especially when the antibody level in the transfused blood is high whereas the secondary immune response is not affected.


A simplified one-step procedure for the simultaneous determination of complement receptor lymphocytes and lymphocytes with membrane-bound immunoglobulins. A simple one-step procedure for the demonstration of complement receptor lymphocytes (CRL) with complement-coated bacteria (BC) as indicator particles is described. With this assay the percentage of CRL in normal peripheral blood ranged between 6 and 21% (mean 11%). In a separately performed combined assay for lymphocytes with membrane-bound immunoglobulins (M-Ig) and lymphocytes, which form rosettes with complement-coated bacteria (BC-RFC), four different fractions of lymphocytes could be detected: (M-Ig+-BC+, M-Ig+-BC-,M-Ig--BC+, M-Ig--BC-). These results suggest that the subpopulation of lymphocytes with complement receptor sites overlaps with, but is not totally identical with the lymphocyte subpopulation bearing Ig on the surface.


Histogenesis of myeloid metaplasia in the spleen. Hemopoietic activity in the spleen is caused by the proliferation of the RE cells of the red pulp, lining the sinusoids and the endothelial cells lining the venous channels and their vasa vasora. The RE cells of the marginal zone do not contribute. As the cells involved line blood spaces, and the immature cells are washed into the circulation hemopoiesis appears to be intravascular. Different agents produce different effect: copper sulphate an early proliferation of both the red pulp and venous cells, phenylhydrazine a red pulp proliferation and antiserum a high venous endothelial activity.


Circulating platelet aggregates and thrombocytopenia induced by intravenous infusions of arachidonic and lauric acids in guinea pigs. Slow intravenous infusion of Na laurate (NaL) into guinea pigs caused a rapid appearance of platelet aggregates in the arterial blood and a precipitous fall in platelet counts. During the infusion of Na arachidonate (NaA) thrombocytopenia developed slowly, and few and smaller platelet aggregates appeared in the arterial blood. Considerably more guinea pigs died during or after the NaA infusion than after administration of NaL. The possibility that arachidonic acid and other long-chain fatty acids may play a role in the development of thrombosis and thromboembolism is discussed.


Freeze-fracture of circulating human eosinophils. Freeze-fracture has been carried out on peripheral blood from three patients with eosinophilia. Eosinophil granule membranes are characterized by intramembranous particles (IMP) with diameters of 80-150 A. These particles of the granule membrane are consistently larger than the IMP of the plasma membrane which are approximately 80 A in diameter. Cross-fractures of granules showed no evident subgranular inclusions. The difference in size between granule and plasma membrane particles observed in freeze-fracture suggests that studies of eosinophils may be an approach to membrane alterations during phagocytosis.


A study of folic-acid-binding protein in normal subjects. 6 normal females were found to have a level of folic-acid-binding protein (FABP) in their sera (mean level 345 pg/ml). Lysates of their various leucocytes were assayed and FABP found exclusively in the polymorph fraction. The sera and lysates were fractionated by Sephadex G-200 gel column chromatography and the molecular weight of the FABP appeared to be approximately 40,000. A hitherto unreported inhibitory effect of heparin on folate binding was noticed. Studies have been performed on folic-acid-binding protein (FABP) in various pathological states, but the levels found in normal people are usually considered too low to permit investigation. In an earlier study [3], 6 normal females were found to have levels in excess of 300 pg/ml whilst the mean level of 94 controls was 76 pg/ml. Sera and leucocyte lysates from these people have been  used to estimate the molecular weight of FABP in normal people.


Membrane deformability of erythrocytes with glucose-6-phosphate dehydrogenase Hamburg. Deformability of erythrocytes of a patient with chronic nonspherocytic hemolytic anemia caused by a G-6-PD variant (G-6-PD Hamburg) in red cells was studied. The flow rate of erythrocytes from this patient through 5 mum polycarbonate sieves was higher than that of red cells from healthy adults. Even under oxidative stress in vitro, the deformability of erythrocytes of the patient was only slightly decreased. The residual hemoglobin content of red cell membranes (ghosts) from this patient was lower than that of ghosts from healthy adults and of ghosts prepared from comparable reticulocyte-rich blood withoug G-6-PD deficiency. In contrast to the low enzymatic activity of G-6-PD Hamburg in the hemolysate, a high activity of this enzyme could be demonstrated in the ghosts from the patient. In view of the flexibility of this patient's erythrocytes splenectomy is not to be recommended.


Chronic idiopathic myelofibrosis. A reversible disease?. A patient with chronic idiopathic myelofibrosis was subjected to splenectomy 1 year after diagnosis. As a clinically unexpected finding, lymph node biopsy suggested the presence of non-Hodgkin lymphoma. The patient was subjected to intensive combined cytostatic therapy. In the following months, signs and symptoms of myelofibrosis regressed remarkably. The patient died 31 months after splenectomy in massive gastrointestinal bleeding. At post-mortem, myelofibrosis could not be detected in three bone marrow areas and a regular, fat-containing, hypercellular marrow was present. The nature of the previous lymph noede pathology was reconsidered, and angioimmunoblastic lymphadenopathy was diagnosed.


In vivo behaviour of neuraminidase-treated rabbit erythrocytes and reticulocytes. 51Cr rabbit erythrocytes were treated with different amount of neuraminidase and reinjected into the animal. The survival curves after the removal of more than 50% membrane sialic acid show a characteristic behaviour: after a rapid decrease, blood radioactivity increases again reaching a maximum level 50-80 h after reinjection, then tends to decrease with a slope similar to that of control curves. Liver radioactivity determined before the rise of blood radioactivity is evidently higher than the value determined after radioactivity elevation. Similar results were obtained with phenylhydrazine-induced young erythrocytes.


Treatment of vasomotor rhinitis with intranasal disodium cromoglycate (SCG). Results from a double-blind cross-over study. The effect of SCG powder (Lomudalr, Intalr) intranasally in vasomotor rhinitis has been studied on 49 adult volunteers in a double-blind cross-over study during 13 weeks in January--April 1973. The dose of SCG was 40 mg/day. Although a substantial number of results were obtained, no significant difference between the effects of SCG and placebo treatment, on variables measured, was detected. However, some patients experienced relief with, and preferred, the treatment with SCG. The results from this investigation are discussed in comparison with those from other studies including patients with vasomotor rhinitis.


The need for halothane supplementation of N2O-O2-relaxant anaesthesia in chronic alcoholics. The demand for intermittant halothane supplementation during N2O-O2-relaxant anaesthesia was studied in 25 alcohlics (annual consumption over 15 1 pure alcohol) scheduled for biliary or gastric surgery. The controls were 45 non-alcoholics and 43 patients with an annual consumption of between 1 to 15 1. Thiopental (3 mg/kg/min) was given for induction. After intubation, halothane supplementation was given in 0.5% concentration for 10-min periods. Standardized criteria for halothane supplementation were various motor and autonomic responses to painful stimuli. Muscular relaxation was kept fairly constant (roughly 90%), as assessed visually with the aid of a peripheral nerve stimulator. The total time for which halothane supplementation was given, expressed as a percentage of the total anaesthesia time, was used as an indication of the need for halothane supplementation. The need for thiopental for induction was not increased to a statistically significant extent in alcoholics, but signs of excitation did occur in 40% as compared with 11% in non-alcoholics (P less than 0.01). The demand for halothane supplementation was higher in alcoholics (47 +/- 4.8%, s.e. mean) than in non-alcoholics (33 +/- 2.3%). This difference, however, was partly due to the higher incidence of gastric surgery, which required more supplementation than biliary surgery. Analysis of the different criteria indicating the need for halothane supplementation revealed that an increase in blood pressure or heart rate was more common in non-alcoholics, whereas motor irritability, sweating and lacrimation were more frequent in alcoholics. Management of the anaesthetic posed no special difficulties in the alcoholics with an estimated mean annual consumption of 32 +/- 4 (s.e. mean) litres of absolute alcohol. Three patients (5% of the alcohol consumers) reported dreams or recollections, suggesting that this mode of halothane supplementation does not guarantee an adequate anaesthetic depth. The difficulties and biases associated with this type of analysis are discussed.


The analysis of collagen in glutaraldehyde-fixed, osmicated peripheral nerve. Glutaraldehyde fixation and osmication of rat sciatic nerve and human sural nerve did not appreciably alter the apparent weight of collagen in nerve fasciculi as determined by hydroxyproline analysis of hydrolysed samples. The collagen content of autopsied peripheral nerve is unaltered at least up to 24 h after death. The mean endoneurial weight of collagen per fascicle in rat sciatic nerve was 123 mug (all results expressed for 1 cm length). In human sural nerve the mean weight was 57 mug and the mean fascicular volume 1.75 mm3. Human endoneurial collagen fibrils gave a unimodal distribution of diameters with a peak at 40 nm.


Heterologous growth of human ovarian cancer. A new in vivo testing system. Successful heterotransplantation of ovarian cancer in the mouse mutant, nude is described, with serial transmission, in one case to date. Light and electron microscopic examination of this tumour, a poorly differentiated adenocarcinoma, has not revealed any alteration in its morphology after six passages. Tumour-bearing mice have been treated with ThioTEPA or 5-Fluoro-Uracil, in an attempt to see if they show a similar effect to that seen in the patient. ThioTEPA resulted in a marked regression, whilst there was no effect from 5-Fluoro-Uracil, on tumour growth--confirming the ThioTEPA effect seen in the patient.


Pilocarpine-induced subsensitivity to carbachol and pilocarpine of ciliary muscle in vervet and cynomolgus monkeys. Vervet monkeys were given unilateral treatment for two weeks with one 2% pilocarpine eye drop three times daily between 8 a.m. and 6 p.m. (night interval 14h) and were then subjected to anterior chamber perfusion 20 mug pilocarpine intracamerally caused similar and substantial increases in outflow facility in both eyes. Cynomolgus monkeys were unilaterally treated with continuous release of 33 mug/h of pilocarpine for 5-6 days. The facility response to 1 mg/kg pilocarpine iv was small or absent on the treated side. Iridectomized cynomolgus monkeys responded with 12.6+/-5.2 (SD) diopters accommodation to 1.5 mg/kg pilocarpine im, with very similar responses in the two eyes. During continuous release of 30 mug/h pilocarpine, accommodation of the treated eye dropped grdually and after 4-8 days treatment the accommodative response was markedly reduced to pilocarpine 1.5 mg/kg im or 100 mug topically. The degree of subsensitivity was much less when tested with either systemic or topical carbachol. This was also the case in a few vervet experiments. Recovery of full pilocarpine sensitivity took several weeks in the cynomolgus monkey. As an explanation for the excessive subsensitivity and large interindividual differences found with pilocarpine, an individually variable, nonmuscarinic relaxant action counteracting the muscarinic excitatory action is suggested. Clinical implications of this hypothesis are discussed.


Ultrastructure and distribution of intercellular junctions in corneal endothelium. The intercellular junctions of the corneal endothelium has been studied in rabbit, monkey and human eyes. A union of apposing outer leaflets (tight junction) is usually found near the apical end of the intercellular clefts. However, evidence from lanthanum tracer studies indicates that the tight junctions do not seal the intercellular clefts completely. In addition to tight junctions, the presence of gap junctions or nexuses is demonstrated in all three species studied.


C-peptide in juvenile diabetics beyond the postinitial remission period. Relation to clinical manifestations at onset of diabetes, remission and diabetic control. A group of 58 diabetics, age 6-17 years and with a duration of diabetes of 3-14 years was studied in order to show whether the nature of the clinical manifestations and the treatment at the onset of the disease are related to the subsequent C-peptide production and also whether remaining C-peptide production is related to better diabetic control. The relations between a number of clinical and laboratory variables were analysed including the degree of ketosis and the insulin dose given at onset of diabetes, the incidence of postinitial remission period, the fasting C-peptide level after the remission period, the level of insulin antibodies and the actual diabetic control expressed as the degree of glucosuria in the patients' urine tests at home. Multiple regression analysis was the main method used. Postinitial remission was positively correlated to initial insulin dose and negatively correlated to duration of ketonuria at onset. C-peptide, which was found in 24.1% of the patients was positively correlated to age at onset and initial insulin dose, but negatively correlated to ketonuria at onset. Diabetic control was positively correlated to insulin dose at onset and to C-peptide level, but negatively correlated to insulin antibodies. It could further be shown that patients who had received a more vigorous treatment immediately at onset had both a higher incidence of postinitial remission and a better diabetic control. The results suggest that an early diagnosis followed by rapid normalization of the metabolism at the onset of juvenile diabetes increase the possibility of preservation of some of the endogenous insulin production, which seems to facilitate diabetic control.


Oxidase positive rods from cases of suspected gonorrhoea. A comparison of conventional, gas chromatographic and genetic methods of identification. Genito-urethral specimens from 3260 women and 1170 men, with ailments suggestive of gonorrhoea, were examined for growth of oxidase positive rodshaped bacteria, as well as of gonococci. Moraxella osloensis was identified in 26 cases (0.64 per cent of women and 0.43 per cent of men). Three patients harboured phenylalanine negative (or weakly reacting) and tryptophan deaminase negative M. phenylpyrouvica and, in three cases, a Flavobacterium species was detected. Among six oropharyngeal specimens from patients suspected of gonorrhoea, two yielded growth of oxidase positive rods, Kingella kingae and Neisseria elongata, respectively, N. gonorrhoeae was isolated from 537 patients, i.e., 12.1 per cent of all cases. The isolates of oxidase positive rods were in most cases completely identified by streptomycin resistance transformation. On this basis, the diagnostic reliability of some morphological and cultural-biochemical tests and gas chromatography was examined. Gas chromatographic analysis of fatty acid and alcohol composition of whole cells proved distinctive of species defined genetically, irrespective of confusing behaviour of some strains in other tests.


Sorption of Streptococcus faecium to glass. A method has been developed by which to study the sorption of Streptococcus faecium to soda-lime cover glasses. Conditions were chosen to minimize the influence on sorption of bacterial polymer production, passive sorption being studied rather than attachment mediated by metabolic activities. Sorption of S. faecium increased with increasing temperature (to 50 degrees C), time, and cell concentration, but equilibrium apparently was not reached even after incubation for 8 hours or at a cell concentration of 3 X 10(10) per ml. Sorption increased with solute molarity up to 0.1 M concentration of NaCl and KCl, indicating an effect of the electrical double layers on the apposition of cells to the glass surface. Desorption of bacteria could be obtained after multiple washings of the glasses in buffer or by the action of Tween 80, but not if sorbed bacteria were left in distilled water, various salt solutions, urea, or in suspensions of unlabelled bacteria. It was concluded that sorption occurred as a result of chemical interactions between the glass and the cell surface. Tween 80 at a concentration of 1 per cent inhibited sorption to 26 per cent of buffer controls, 2 M urea was less effective, and 1 M NaCl was without effect. It is suggested that hydrophobic interactions may be of importance in the binding of S. faecium to glass.


Sorption of Streptococci to glass: Effects of macromolecular solutes. Macromolecular solutes (albumin, concanavalin A, whole saliva, serum) caused impaired sorption of Streptococcus faecium and Streptococcus sanguis to glass. The inhibitory effect resided chiefly with interactions of the solutes with the glass surface. In the case of sorption of S. sanguis to glass in the presence of parotid fluid, the inhibitory effect was counteracted by a specific attachment of S. sanguis cells mediated by some component(s) of the parotid fluid. Agglutination of the test organisms was in general accompanied by inhibition of sorption. However, when small or unstable aggregates were formed, the number of cells adhering on the glass surface was increased. The findings are discussed with reference to the colonization of teeth by oral bacteria.


The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo(b)furan-m-carboxamido)-ethyl)-benzenesulphonyl]-N'-cyclohexylurea (NOVO CS 476). I. Pharmacological studies on the hypoglycaemic effect. The new sulphonylurea CS 476 has been shown to be a potent hypoglycaemic agent. In normal fasting dogs, rabbits, rats and mice the maximal hypoglycaemia produced by intravenous administration of CS 476 was comparable on a weight basis to that produced by glibenclamide. Randomized Latin square experiments in dogs showed that 0.03 mg/kg orally of CS 476 and of glibenclamide caused the same maximal decrease of blood glucose and that CS 476 had the shorter duration of action. CS 476 had no hypoglycaemic effect in totally pancreatectomized dogs nor in streptozotocin diabetic dogs and rats. The insulin releasing activity was studied in dogs after intravenous and oral administration of equipotent doses of CS 476, tolbutamide and glibenclamide. It was found that the insulin curves after CS 476 tended to have a plateau-like maximum like those after glibenclamide although the duration of effect was shorter.


The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo(b)furan-7-carboxamid o)-ethyl)-benzenesulphonyl]-N'-cyclohexlurea (NOVO CS 476). III. General pharmacological studies. The new sulphonylurea CS 476 was tested for positive iontropic effect on the isolated cat papillary muscle. Unlike tolbutamide CS 476 had no positive inotropic effect. CS 476 had no adverse effect on blood pressure in dogs, cats and rats nor on the electrocardiogram of dogs in doses up to ten times the therapeutic dose. Unlike chlorpromide CS 476 did not potentiate the effect of exogenous antidiuretic hormone in hydrated dogs. In therapeutic concentrations the drug had no effect on smooth muscle preparations. 1,000-10,000 times therapeutic concentrations had a papaverine-like effect - similar to therapeutic concentrations of tolbutamide.


The in vivo toxicity of CS2 to liver microsomes: binding of labelled CS2 and changes of the microsomal enzyme activities. The binding of 35S and 14C labelled CS2 to liver microsomes was studied in control and phenobarbitone pretreated rats 3 and 6 hrs after an intraperitoneal injection. The level of hepatic cytochrome P-450, the activities of epoxide hydratase and UDP-glucuronosyltransferase were analyzed in the same animals. The binding of the sulphur label was considerably higher than that of carbon 3 hrs after the injection, the difference being less evident at 6 hrs.T he measurable P-450 declined after the CS2 injection. It was approximately 40% in the phenobarbitone pretreated rats and 60% in control rats of the values of animals which were not treated with CS2. CS2 did not affect microsomal epoxide hydratase activity, while it increased the measurable activity of UDP-glucuronosyltransferase. The increase was evident 3 hrs after the injection of CS2 in the phenobarbitone pretreated rats. It could also be detected in the control animals 6 hrs after the injection. The present data suggest that the change in the measureble P-450 results from the binding of the metabolite(s) of CS2 to the cytochrome, and its subsequent degradation. The increase in measurable UDP-glycuronosyltransferase activity results probably from the activated perturbation of the structure of microsomal membrane by the metabolites of CS2 in vivo.


Thyrotropin-releasing hormone (TRH) inchronic schizophrenia. A controlled study. A controlled study on the effect of synthetic Thyrotropin-Releasing Hormone (TRH) versus placebo in 10 drug-free chronic schizophrenics is presented. TRH 600 mug or placebo was administered intravenously on 4 consecutive days in a double-blind cross-over design and the schizophrenic symptoms were scored daily by use of two rating scales (CPRS and NOSIE). Blood samples were taken before and 30 and 45 minutes after the first and the fourth injection and analyzed for TSH. No changes in symptom intensity were found during the TRH or placebo treatment period and no difference was obtained between the two treatments. The dose of TRH used caused a significant increase in the plasma level of TSH which indicated a normal pituitary responsiveness to TRH. The data do not support the notion that TRH has a beneficial effect in chronic schizophrenic patients.


Treatment of endogenous depressions with thyrotropin-releasing hormone (TRH) under oral administration. In a double-blind study among six patients suffering from endogenous depression, three patients received thyrotropin-Releasing Hormone (TRH) administered orally in doses of 20 mg three times a day for 3 weeks. In an open controlled study of three patients suffering from endogenous depression, two patients received oral TRH 20 mg four times a day for 2 weeks. Degree of depression according to Hamilton's Rating Scale measured during the study showed that TRH had no antidepressant effect. Thyroxine concentration in serum (T4) increased during the period of TRH treatment.


Multidisciplinary meetings with relatives of elderly hospital patients in continuing-care wards. A series of multidisciplinary meetings with the relatives of elderly patients in continuing-care wards is described. The enthusiasm engendered and the amount of useful information obtained left no doubt that the time was well spent. Meetings of this type are considered to be a valuable instrument for highlighting matters relevant to quality of care.


The effects of discontinuing long-term diuretic therapy in the elderly. The effects of discontinuing long-term diuretic therapy were investigated by means of a double-blind randomized controlled trial. A total of 141 elderly patients in the long-stay wards of six hospitals were found to be taking maintenance diuretics, and for 33 of these the drugs were judged to be mandatory. Of the remaining patients, 52 continued to receive diuretics while 54 were given matching placebo tablets. Eight in the latter group required diuretic therapy to be resumed during the following 12 weeks. The main change observed in patients who completed the trial was a slight increase of ankle oedema in the placebo group. Plasma potassium levels below 3.5 mEq/1 were found in some patients taking diuretics but not when the drugs had been withdrawn for 12 weeks. Blood pressure rose slightly in the placebo group and plasma urea rose slightly in the diuretic group. It was concluded that old people receiving long-term diuretic therapy without obvious current indication should have the drugs withdrawn under careful supervision so that those needing them could be identified.


Transient asymptomatic S-T segment depression during daily activity. The significance of asymptomatic episodes of ischemic type S-T segment depression was studied in 20 patients with coronary heart disease. Continuous 10 hour electrocardiographic recordings accompanied by detailed daily diaries of activity and symptoms were obtained periodically during a mean time of 16 months. All patients had ischemic type S-T depression associated with angina pectoris during treadmill exercise. Measurements of heart rate, S-T depression and exercise level at the onset of angina obtained during repeated controlled exercise tests at the start of each study period were compared with the measurements recorded during daily activity. After 2,826 hours of recording, 411 transient epidsodes of ischemic type S-T depression were noted during usual daily activity. Only 101 (25 percent) of these episodes were associated with angina. The remaining episodes were unrelated to other symptoms or to posture. All occurred at heart rates significantly lower than those observed at the onset of angina during exercise testing. Of these episodes of asymptomatic S-T depression, 72 percent occurred only at rest or during very light activity such as slow walking or sitting. Nitroglycerin administered hourly significantly reduced the frequency of these episodes, thus supporting the concept that they represent painless ischemia. Because the episodes of asymptomatic ischemic type S-T depression occurred more frequently than angina during usual daily activity and were evident at heart rates and activity levels well below those expected to evoke ischemia, they may be caused by factors other than those that cause angina.


Glutaraldehyde fixative tonicity for scanning electron microscopy of delicate chick embryos. Fresh pullet eggs (White Leghorn strain) were incubated from 19-2ldium-gold and observed in a Cambridge S4 scanning electron microscope. Shrunken cells with intracellular yolk granules embossed on the surface are produced by the strongly hypertonic Karnovsky's fixer (Final: 2010 mOsm). Embryos fixed with modified Karnovsky's fixer (Final: 373 mOsm) possess surfaces with irregular microappendages. Swollen cells with few microappendages are observed when embryos are fixed in a hypotonic environment (Final: 250 mOsm or less). Ideal fixatives preserve a relatively flat surface, with cells bordered by smoothsurface microappendages. For adequate SEM fixation, fixative vehicle should be approximately isotonic for tissue, with aldehyde (2% or less) added to vehicle.


3H-fucose incorporation into glycoproteins of toad bladder epithelial cells. Electron microscope autoradiography was used to detect the incorporation of 3H-fucose into glycoproteins of toad bladder epithelial cells. After short exposure to 3H-fucose, without a chase period, the Golgi regions of all four cell types were labeled. When exposure to 3H-fucose was followed by chase periods (1,3,4 and 6 hours) the apical and basal-lateral plasma membranes of granular cells were heavily labeled. Apical granules and the cytoplasm of granular cells were also labeled, suggesting that they both provide the means for glycoprotein transfer from the Golgi to the plasma membranes. The heaviest labeling in mitochondria-rich cells, after the 1- and 3-hour chase periods, was over the apical tubules, although the apical and basal-lateral plasma membranes were also heavily labeled. After 4- and 6-hour chases, the labeling of the apical tubules decreased, whereas the labeling of the plasma membranes increased, strongly suggesting that in these cells apical tubules play a major role in the transfer of glycoproteins from the Golgi to the plasma membrane. Our results demonstrate that the route of 3H-fucose incorporation into plasma membrane glycoproteins and the rate of glycoprotein synthesis and breakdown are not the same in the two major epithelial cell types in toad bladder.


Hemodynamic findings in servere protein-calorie malnutrition. This study was undertaken because circulatory distrubances had been advanced as a possible cause of death during initial renourishing of protein-calorie deprived children. Body weight, plasma albumin concentration, intravascular volumes (radiochromium), cardiac index (dye dilution technique), intravascular pressures (flow-guided catheterization), and related hemodynamic parameters were determined at rest in 43 infection-free African children with a form of protein-calorie malnutrition known as marasmic kwashiokor, and were compared with values observed in 24 convalescent children. The malnourished children showed a prolonged circulation time with a tendency to bradycardia and hypotension; cardiac index, stroke index, and heart work were significantly reduced, as were the intravascular volumes. Hemodynamic data correlated with either body weight or plasma albumin and cardiac index bore a direct relation to red cell volume. In the most severely malnourished subjects, ventricle filling pressures were low and vascular resistances were high. It is inferred that most patients were in an adaptive hypocirculatory state comparable to hypothroidism, while the most severely malnourished children showed frank peripheral circulatory failure comparable to hypovolemic shock. Circulatory failure on admission was associated with high death rate during treatment but the relation between cause and effect could not be clearly demonstrated.


Blood volume changes during treatment of protein-calorie malnutrition. Intravascular volmes were sequentially determined in 13 African children recovering from protein-calorie malnutrition. The red cell volume was measured by a radiochromium technique; the total blood volume and the plasma volume were calculated. The absolute volumes were related to body size and were compared with the control values. Before treatment, the total blood volume was low per unit of body size, the red cell volume was more reduced than the plasma volume. On the 20th realimentation day, the absolute red cell volume had increased less than the absolute plasma volume, the total blood volume was almost normal per unti of body size. On the 60th realimentation day, near recovery, the absolute red cell volume had again increased, but again less than the absolute plasma volume, and the venous hematocrit was lower than on admission; the total blood volume was normalized per unit of body size, the red cell volume was low with a supranormal plasma volume. The rehabilitation period was characterized by an aggravation of the hemodilution already present before treatment. The significance of the changes in volemia per unit of body size was unclear because of the changing body composition.


Protein and calorie malnutrition in infant cebus monkeys: growth and behavioral development during deprivation and rehabilitation. The growth and development of 32 cebus monkeys were studied during a period of insult in nutritional or rearing conditions and after rehabilitation. Eight experimental groups of four animals each were subjected to one of four diets--control, protein restricted, calorie restricted, and protein-calorie restricted, and one of two rearing conditions-partial isolation or a comparatively enriched condition-in a 4 x 2 factorial design. The period of insult from 2 to 6 months of age was followed by 6 months of rehabilitation in both diet and rearing conditions. It was found that only diet affected physical growth, but both diet and rearing affected behavioral development and exploratory behavior. Whereas calorie deficiency produced a direct effect on behavior independent of rearing conditions, protein deficiency produced an effect only in combination with rearing restriction. The effect of protein-calorie deficiency had some characteristics in common with each of the other deficiencies. Retardation in rate of behavioral development was less severe than retardation in growth, most notably in the protein-restricted, enriched-rearing group, producing animals who were behaviorally mature for their size. All groups caught up in physical growth during rehabilitation but the protein-calorie restricted groups failed to recuperate completely in exploratory behavior.


Absence of the biochemical symptoms of essential fatty acid deficiency in surgical patients undergoing protein sparing therapy. The biochemical symptoms of essential fatty acid deficiency appear within 7 to 10 days of fat-free total parenteral nutrition using glucose-amino acid mixtures. The linoleic acid (C18:2W6) content of all plasma lipid fractions decreases greatly and plasma eicosatrienoic acid (C20:3W9) increases. We have measured the fatty acid composition of the plasma lipid fractions in six surgical patients receiving parenteral nutritional solutions containing only amino acids, and completely free of glucose, before and after 10 to 14 days of such therapy. Biochemical symptoms of essential fatty acid deficiency did not occur. The fatty acid composition of all plasma lipid fractions remained unchanged after this time period. Mobilization of linoleic acid from the adipose tissue occurred with this treatment in contrast to the inhibition of lipolysis of adipose tissue triglyceride produced by continuous infusions of hypertonic glucose-amino acid mixtures.


Low-dose intravenous insulin therapy for diabetic ketoacidosis in children. Fourteen pediatric patients were successfully treated for diabetic ketoacidosis with continuous low-dose intravenous insulin. The average admission blood glucose concentration was 717 mg/100 ml and the mean admission capillary blood pH was 7.13. The insulin dosage was 0.25 units/kg every four hours. The average total insulin dose for recovery was 0.6 units/kg. No complication was observed. The method is effective, safe, and simple to administer.


Menopause in rhesus monkeys: model for study of disorders in the human climacteric. Hormonal and menstrual patterns were studied in rhesus monkeys 22 years of age or older. Sustained elevations of serum gonodotropins, low circulating levels of estradiol and progesterone, associated with oligomenorrhea or amneorrhea, were similar to changes reported for peri- and postmenopausal women. During the menopausal transition, pituitary FSH appears to be modulated independently of LH. These observations suggest that the rhesus monkey may be a suitable model for study of disorders afflicting women in the climacteric.


Dentofacial changes produced by extraoral forward force in the Macaca irus. Eleven Macaca irus monkeys with a mixed or a permanent dentition were used in a study of the possible effects of extraoral forward force on the growth of the dentofacial skeleton. An intermittent forward force of 300 Gm. per side was applied, and the effects were analyzed by means of model casts, cephalometric radiographs, tetracycline bone marking, microradiographs, and histologic preparations. The results obtained were as follows: 1. An extraoral forward force caused significant changes in the circum-maxillary sutures and the maxillary tuberosity. 2. It was found that intermittent force of 300 Gm. per side resulted in desirable reactions in the sutures in young monkeys. 3. It was suggested that reactions in the suture might occur as a result of (1) an opening of the suture, (2) stretching of sutural connective tissue fibers, (3) new bone deposition along the stretched fibers, and (4) homeostasis which maintained the sutural width. 4. The maxillary complex showed a positional change with a little counterclockwise rotation. 5. A local reaction was observed histologically in the adult, but the degree was less than that seen in the young monkey. 6. It was considered that a forward movement of the maxillary complex would readily be accomplished by increasing sutural activity as early as possible. 7. Clinically, it was assumed that the hooks attached to the intraoral appliance should be placed as far frontally as possible. The present study seemed to indicate that forward movement of the maxillary complex would be performed with an extraoral anterior-pull appliance. Further investigation should be designed to evaluate a possible skeletal relapse after an orthopedic approach.


Chagasic cardiopathy. Immunopathologic and morphologic studies in myocardial biopsies. Immunopathologic and morphologic studies at the light and transmission electron microscope levels were carried out in myocardial biopsies of 4 chagasic individuals with circulating antibodies reacting with plasma membrane of striated muscle and endothelial cells (EVI antibody). Two cases did not present clinical evidences of heart involvement, and 2 cases showed chronic heart disease. In viv deposits of immunoglobulins were found at the plasma membrane of working myocardial cells and endothelial cells. The cytologic location of the in vivo bound gamma-globulin was coincident with the specificity of the EVI antibody. Ultrastructural studies showed intracellular alterations compatible with hypoxia of the fibers; these lesions, although they were more severe in the 2 cases with heart disease, were also present in the asymptomatic individuals. These results are congruent with a possible pathogenic effect of the EVI antibody. In 2 patients with Chagas' heart disease, foci of mononuclear infiltrates were examined by transmission electron microscopy. At that level, a close relationship between lymphoctes and muscle cells was observed, with imbrication of the plasma membranes and disappearance of the basal laminae. In the neighborhood of the lymphocytes, definite muscle cell abnormalities were found. These observations are also congruent with the recently suggested possibility that a lymphocyte-mediated immune response against heart tissue may participate in some of the pathogenetic mechanisms of chronic chagasic cardiopathy.


Experimental toxemia of pregnancy in the monkey, with a preliminary report on renin and aldosterone. Experimental toxemia of pregnancy was induced in 8 pregnant monkeys (Macacamulatta) by reducing the abdomiinal aorta to one-third of its original diameter during the last month of gestation. It was characterized by hypertension and proteinuria. In the kidney, light and electron microscopy and immunofluorescence revealed findings similar to those in human toxemia. Focal necrosis in the liver and diffuse hemorrhagic infarctions in the placenta were also observed. Plasma renin activity and aldosterone levels, as determined in blood from the uterine vein, were elevated. None of these changes were found in 4 control animals.


Patterns of cellular proliferation in normal and tumor cell populations. Three types of cell mosaics have been used in mammalian studies: hemopoietic shimeras, mosaics formed by aggregation of preimplatation embryos, and mosaics resulting from X-chromosome inactivation. The problems investigated with these cell mosaics have included normal tissue orgaization, cell selection, primordial cell pool sizes, and tumor cell kinetics. The emphasis in this review is on the application of X-chromosome inactivation mosaics to the analysis of tumor cell proliferation. The first application of mosaicism to tumor ontogeny involved leiomyomas and demonstrated single cell and independent origin of the tumors. Other tumor studies are reviewed including those of presumed multiple cell origin, especially those of hereditary origin and viral  etiology. The concept of target size is invoked to explain these multiple cell origin tumors. The recent reports on the clonal nature of atherosclerotic plaques is also discussed. Emphasis is placed on resolving the relationship between the multiclonal underlying fatty streak and the clonal plaque in order to understand the implications of the clonal plaques.


Renal electrolyte circadian rhythms: independence from feeding and activity patterns. The interrelationships between urinary electrolyte circadian rhythms and rhythms of feeding, drinking and activity were studied in six conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) kept in temperature-controlled isolation chambers on a light-dark (LD) 12:12 h cycle. With lights on (600 lx) from 0800 to 2000 h and off (less than 1 lx) from 2000 to 0800 h, renal potassium excretion in monkeys fed ad libitum fell to a daily minimum of 64 +/- 6 mueq/h at 0500 h and rose to a maximum of 274 +/- 13 mueq/h at 1700 h. Sodium excretion fell to a minimum of 13 +/- 2 mueq/h at 1000 h and rose to a maximum of 43 +/- 6 mueq/h at 2100 h, while water excretion fell to a minimum of 869 +/- 63 mul/h at 0500 h and rose to a maximum of 2,307 +/- 222 mul/h at 1700 h. Feeding, drinking, and activity occurred only during the lights-on period. Independence of the urinary rhythms from diurnal variations in feeding, drinking, and activity was established a) by depriving monkeys of food, b) by depriving monkeys of water, and c) by training monkeys to perform a 2-hourly schedule of feeding, drinking, and activity throughout day and night. None of these three regimens resulted in major reductions of the amplitude, or changes in the phase of the circadian rhythms of urinary electrolyte or water excretion. These findings indicate that the circadian rhythms of urinary potassium, sodium, and water excretion are controlled by mechanisms that are not passively dependent on the behavioral patterns of feeding, drinking, and activity.


Simultaneous regional myocardial blood flows by tritiated water and microspheres. Regional myocardial blood flow (RMF) was measured simultaneously by use of labeled 8-mum microspheres and the constant-rate infusion of 3H2O in 22 open-chest dogs (Na pentobarbital anesthesia) under markedly different hemodynamic conditions. Following cardiac excision, three adjacent 80-mg tissue samples were taken from the subendocardial, mid-wall, and subepicardial layers of quadrantal left ventricular (LV) segments of the basal and midventricular cardiac slices, and from one segment of the apical slice, totaling 81 samples per LV. RMF was calculated by the microsphere reference-flow technique and by two 3H2O tissue-uptake models. Good agreement between techniques (r=0.9-0.96) was found in comparing flows to the myocardial layers. Using Kety's "single-mixer" model of 3H2O tissue uptake, fairly good agreement was found between techniques in the 80-mg tissue samples; the cofficient of variation from regression was 18.5% which improved markedly to 12.3% when the flow values for each technique were averaged in the three adjacent samples. Analysis of variance showed that flow to the various LV subdivisions (layer, segment, slice) of control animals was heterogeneous.


Detection of contraction of isolated smooth muscle cells in suspension. A Coulter counter has been utilized to assess the contractile state of suspensions of isolated smooth muscle cells prepared by enzymatic digestion of stomach muscularis of Bufo marinus. Pulse-duration and pulse-hieght histograms were constructed from the pulses that occur as cells pass through the Coulter counter orifice. Contraction of cells in suspension causes shifts in these pulse histograms to a greater percent of shorter duration pulses and of larger pulse heights. These shifts are consistent with teh assumption made in out studies that the duration and amplitude of the pulses generated are related to the length and cross-sectional area (or square of the diameter), respectively, of the cell. Shifts in the pulse-height histogram were found to be more reliable. The results of a calibration experiment in which shifts in the histograms of pulse heights were linerrly related to shifts in the histograms of all lengths measured from photomicrographs suggested that the shifts in the pulse-height histogram could be used as a continuous index of changes in the contractile state of a population of cells in suspension.


Characteristics of response of isolated smooth muscle cells to cholinergic drugs. The contractile responses of suspensions of isolated smooth muscle cells from the stomach muscularis of Bufo marinus were assessed with a Coulter counter. Contractile responses of strips from the same tissue were recorded isotonically. Suspensions of isolated smooth muscle cells exhibit a dose-dependent graded response to cholinergic agonists. The intact tissue has a lower sensitivity than the isolated cells to acetycholine but a higher sensitivity to carbachol. The higher sensitivity of isolated cells to acetycholine probably reflected decreased efficiency of cholinesterases upon removal of diffusion barriers. Because the isolated smooth muscle cells have affinity constants for atropine (K1 equals 0.07 +/- 0.02NM) and carbachol (9.5 +/- 3.7 muM) similar to that in this and other intact tissues, the affinity of the cholinergic receptor appears unaffected by cell isolation. The rate constant for dissociation (k2) of atropine was estimated from the slowing of response to carbachol by atropine; k2 in the isolated cells is 100 times larger than seen in intact tissues. Further insight into the interaction of cholinergic substances with their smooth muscle receptors might by obtained using this system. The isolated cells contain intact receptors, and diffusion limitations inherent to intact tissue have been removed.


Converting enzyme activity in endothelial cells isolated from pig pulmonary artery and aorta. Converting enzyme activity was studied in endothelial cells, isolated from pig pulmonary arteries and aorta by exposure to collagenase. The measure was based on the release of His-Leu from Z-Phe-His-Leu was related to the DNA content of the cellular suspension. The same activity was found in the two types of endothelium: 1 nmol His-Leu/mug DNA per 30 min. Subendothelial cells showed a very low activity, amounting to 10% of the value found for the endothelium. The enzyme activity was 2inhibited by the nonapeptide SQ 20881, EDTA, and the lack of Cl- in the same fashion for the two types of endothelium. The presence of another enzyme hydrolyzing His-Leu was detected in both endothelial populations. Isolated fragments of plasma membrane, however, exhibited only converting enzyme activity. It can be concluded that endothelial cells isolated from large vessels of the pulmonary and the systemic circulations have similar properties when dipeptidyl carboxypeptidase activity is measured.


Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats. Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) is known to inhibit the crystallization of calcium phosphate salts in vitro. Large doses of EHDP administered in vivo inhibit skeletal mineralization, decrease intestinal calcium absorption, and produce hypercalcemia. In the present study, EHDP or one of 13 other phosphonates were given to rats at 10 mg P/kg-day sc for 7 days in order to better define the nature of the relationship between bone mineralization, intestinal absorption, and plasma calcium in the regulation of calcium homeostasis. Each of the phosphonates which inhibited skeletal mineralization in vivo also inhibited crystallization in vitro, but the converse was not true. A very close correlation was found between inhibition of skeletal mineralization, decreased intestinal calcium absorption, and slight hypercalcemia. A dose-response study with two compounds also revealed the same close correlation. It is argued that the impairment of intestinal calcium absorption in phosphonate-treated rats may represent a secondary homeostatic response to the primary effect of the drugs on bone mineralization. This response may be mediated by an elevation of a fraction of plasma calcium.


Potassium activity and plasma membrane potentials in epithelial cells of toad bladder. Intracellular potassium activity (aki), mucosal and serosal membrane potential (mEm, sEm), short-circuit current (Isc), and transepithelial potential difference in the epithelium of the toad bladder were measured with a potassium-sensitive liquid ion exchanger and an ordinary microelectrode. Under basal conditions, aki was 41.2 +/- 0.5 mM, corresponding to 54.4 mM in free potassium concentration, so half or more of the intracellular potassium may be of bound form or sequestrated within subcellular organelles. The sEm cannot be explained by only the potassium equilibrium potential (Eeq), because the sEm was markedly lower than the Eeq and no relation was found between them. Ouabain and rotenone decreased the aki, but ethacrynic acid, which also inhibited the Isc and the membrane potentials, did not show any effect on aki. Vasopressin decreased aki with an elevation in mEm, whereas prostaglandin E1 increased the aki with elevation in the sEm. These characteristic changes may afford an insight into the mechanisms by which transcellular electrolyte transport occurs.


Bicarbonate ions in active sodium transport across toad bladder. The conductance, ga, and electromotive force, E, of active ion transport across toad bladders mounted as sacs were estimated from electrical measurements made before and after addition of sufficient ouabain (1.89 X 10(-3) M) to eliminate spontaneous potential. The ratio of net sodium transport (estimated from bidirectional fluxes) to external current in bladders voltage clamped to 0 mV was significantly less than unity in a normal medium containing HCO3- and Cl- ions, and also when Cl- was replaced with SO42-. However, when acetazolamide was added or when HCO3- was replaced by phosphate, short-circuit current and net sodium transport became equal. Spontaneous potential, E, and ga were all reduced about 20% by these maneuvers. The response of bidirectional sodium fluxes to voltage clamping at 0 mV or 120 mV in a bicarbonate-free medium was otherwise similar to that observed in a normal medium: net flux varied linearly with potential and calculated fluxes in the active transport path indicated a value significantly greater than unity for the empirical constant Q in the equation for change in the flux ratio, f, with change in potential, psi, viz., delta ln f = Q(ZF/RT)delta psi, similar to the high value for this constant that we have found in a bicarbonate-containing medium. We conclude that bicarbonate ions facilitate active sodium transport and also may be actively transported from serosa to mucosa in Dominican toads. However, coupling between bicarbonate and sodium fluxes does not account for the high value for Q for sodium in the active transport path.


Insulin-mediated Na+ transport in the toad urinary bladder. The characteristics of insulin-induced Na+ transport in the toad urinary bladder were determined and compared to those of aldosterone. Bladders were mounted in modified Ussing chambers, and standard short-circuit current techniques were employed to measure transepithelial Na+ transport. Insulin added to the serosal medium is much more effective than insulin added to the mucosal medium. Serosal insulin concentrations from 10(1) to 10(3) muU/ml increase both the initial rate and the final level of Na+ transport achieved, whereas concentrations from 10(3) to 10(5) muU/ml increase only the initial rate of Na+ transport. Insulin-induced Na+ transport probably does not require glucose. Both insulin- and aldosterone-induced Na+ transport are directly proportional to serosal (but not mucosal) K+ concentration over the physiologic range (2.0-7.0 meq/liter). However, cycloheximide abolishes aldosterone- but not insulin-induced Na+ transport. In addition, insulin stimulates Na+ transport after a maximal response to aldosterone, and aldosterone stimulates Na+ transport after a maximal response to insulin. Thus, although they have several similar characteristics, insulin and aldosterone have at least partially independent mechanisms of action on Na+ transport in the toad urinary bladder.


Bone extraction and blood clearance of diphosphonate in the dog. The transcapillary extraction of diphosphonate, as [99mTc]EHDP, a substance used in bone scanning and for management of certain metabolic bone diseases, has been examined. The maximum instantaneous extraction for [99mTc]EHDP was 0.27 +/- 0.05 (mean +/- SD, N = 10) and the net extraction at 5 min was 0.18 +/- 0.05 (N = 10). The permeability ratio of [99mTc]EHDP to the freely diffusible compound, sucrose, using the formula PS = -Fs loge (1 - Emax), was 0.71. This is similar to the ratio of diffusion coefficients of EHDP to sucrose, which is estimated to be 0.78. These results suggest that the mechanism by which [99mTc]EHDP passes through the capillaries in bone is passive diffusion. Tissue level estimations of EHDP confirm a rapid blood clearance associated with an increase in the rate of urinary excretion; the level of [99mTc]EHDP in bone, however, remains constant. The fractional excretion of [99mTc]EHDP was 27.3 +/- 2.0% in control dogs and was unchanged by thyroparathyroidectomy and subsequent infusion of parathyroid hormone.


Guide wire thrombogenicity measured by fibrinopeptide A radioimmunoassay. A radioimmunoassay for measurement of canine fibrinopeptide A, which provides a quantitative index of thrombin action on canine fibrinogen, was applied to measurements of the thrombogenicity of angiographic guide wires. Benzalkonium-heparin-treated Teflon-coated, untreated Teflon-coated, and uncoated stainless steel wires were compared in an experiment in dogs which closely simulated the use of these wires in humans. During the first 4 min after insertion, the benzalkonium-heparin-treated Teflon-coated wire was associated with significantly greater systemic levels of fibrinopeptide A than were either Teflon-coated or stainless steel wires. Beyond 10 min, markedly increased levels of fibrinopeptide A were measured in association with these latter two wires compared to the benzalkonium-heparin-treated Teflon-coated wire. Both the early rises in fibrinopeptide A associated with the benzalkonium-heparin-treated Teflon-coated wire and the late increases in fibrinopeptide A associated with the Teflon-coated and uncoated stainless steel wires could be eliminated by prior systemic administration of low dose heparin (40U/kg). These studies suggest that, at least in regard to activation of the plasma clotting system, the benzalkonium-heparin treatment offered no advantages over the other wires tested in terms of reduced thrombogenicity within the critical 10 min following insertion. No difference could be discerned between uncoated stainless steel wires and Teflon-coated stainless steel guide wires in this test.


A new simple power injector.

A new simple power injector. A new simple pneumatic-hydraulic injection device has been constructed, tested, and used in clinical angiography. Is is the only injector which produces a square wave velocity curve with immediate rise time. Disposable plastic syringes are used which convert the velocity profile of the plunger into a smooth buildup time of the injectate, reducing recoil. The unit can be operated by both local or remote triggering. It has numerous advantages over commercially available devices, such as small size, simplicity of design, and safety features which eliminate shock hazards and reduce human error.


Left internal mammary artery--coronary artery bypass anatomy. Bypass coronary surgery has made good use of the anatomic proximity of the internal mammary artery and the left anterior descending coronary artery. In preparing the internal mammary artery for bypass surgery, several of its proximal branches remain intact and are visualized during selective studies of the bypass graft. A brief description of these vessels is presented with specific attention to the branching and position of the pericardial vessels and their relationship to the grafted left anterior descending artery.


Peripheral arterial disease: assessment by arteriography and alternative noninvasive measurements. In most centers arteriography is the sole method used to investigate peripheral arterial disease. In view of the availability of other noninvasive techniques, this practice must be reappraised. Among 3,000 patients with peripheral arterial disease, 40% of those undergoing arteriography were found unsuitable for reconstructive arterial surgery primarily because of poor arterial runoff. Noninvasive assessment techniques are discussed, including sequential arterial scanning with Doppler ultrasound. In a single-blind comparison of Doppler ultrasound scanning and arteriography, findings by ultrasound were confirmed by arteriography in 265 of 267 examinations. Blood pressure measurements in the limbs as well as fluorescence and radioisotope clearance studies also provide valuable information. It is recommended that a more rational approach to the assessment of peripheral arterial disease be considered, particularly in elderly patients, to safeguard against undue discomfort and risk. Arteriography should be reserved for patients undergoing reconstructive surgical procedures.


Combined mammographic-sonographic evaluation of breast masses. Palpable breast masses which have a nondiagnostic appearance on the mammogram often require a biopsy to rule out malignancy. Contact B-scan ultrasonography of such masses were performed in an effort to improve the diagnostic accuracy of mammography and reduce the number of unnecessary biopsies. A total of 200 patients with breast masses of 1-8 cm were examined by both methods. The results of this combined evaluation were compared to those of mammography alone. Of 115 pathologically proven lesions, 44 were fluid-filled cysts. Sonography correctly diagnosed all 44 cysts, while mammography was equivocal in 27 (61%) of them. Of the remaining 71 solid masses, 38 were benign and 33 malignant. Mammography alone correctly diagnosed 31 carcinomas (94%), whereas sonography correctly diagnosed 26 (78.8%). While the infiltrating carcinomas have a typical sonographic appearance, circumscribed carcinomas may have the same sonographic features as fibroadenomas; the value of sonography here was to establish whether the mass was solid. In other solid masses such as those produced by dysplasias, abscesses, and mastitis, sonography was helpful in differentiating between diffuse and discrete lesions. The combined mammographic-sonographic evaluation of breast masses was more accurate than either method alone.


Thoracic and abdominal extravasation: a complication of hyperalimentation in infants. Two infants with five separate episodes of extravasation from hyperalimentation catheters are described. Three were intrathoracic and two were retroperitoneal, one of the latter producing clinical ascites. Clinical respiratory distress or ascites developing in an infant undergoing hyperalimentation may indicate vein wall perforation with extravasation into the pleural or abdominal cavities or the retroperitoneum. Questionable situations may be readily resolved by contrast injection through the catheter. Suboptimal position of the catheter tip and venous thrombosis seem to be major contributors to this problem. Prompt recognition and removal of the catheter are generally sufficient to correct the situation.


Posterior fossa extraaxial cyst: diagnosis with metrizamide CT cisternography. This study describes a new technique for the study of posterior fossa extraaxial cysts. Using metrizamide (Amipaque) CT cisternography, a rapid, simple, low morbidity method is now available which gives both anatomic and physiologic information that may obviate the need for pneumoencephalography and angiography. Two cases are reported; in a third the diagnosis was definitively excluded. By doing serial CT scans following the intrathecal introduction of metrizamide, data concerning the diffusion characteristics of these cysts as well as the accompanying hydrocephalus are obtained.


Ultrasonography in pediatric gynecology and obstetrics. Sonograms were performed on 144 pediatric patients ranging in age from 2 months to 15 years during a recent 26 month period. The main indications for pelvic sonography were to confirm pregnancy prior to elective abortion; to exclude pregnancy in girls with pelvic masses and/or secondary amenorrhea prior to extensive radiographic studies; to confirm or rule out the presence of pelvic masses; to delineate the extent and internal structure of pelvic tumors; and to exclude ovarian tumors in girls with precocious sexual maturation. Normal sonograms in girls with suspected pelvic tumors usually eliminated the need for additional radiographic studies. Because of technical problems and inherent limitations of present imaging techniques, sonography has an ancillary role in the investigation of patients with abnormal or ambiguous genitalia.


Plain film findings in massive gastrointestinal bleeding. The admixture of blood clots and air in the lumen of the stomach or colon produces a bubbly radiolucency on plain films of the abdomen in some patients with massive gastrointestinal bleeding. In 10 patients this radiographic sign served as a clue to the site of bleeding. It is postulated that recognition of this sign on preliminary scout films may facilitate location of the bleeding vessel.


The radiographic spectrum of pulmonary complications in burn victims. The spectrum of pulmonary complications in 28 of 66 burn victims is analyzed according to time of onset and resultant radiographic features. Immediately recognizable pulmonary abnormalities are usually due to chemical pulmonary edema and inhalation pneumonitis. Complications manifested 2-5 days after injury include pulmonary microembolism, adult respiratory distress syndrome, and atelectasis. Delayed complications are major pulmonary embolism, pneumonia, and adult respiratory distress syndrome. In this series, 25 patients (89%) developing pulmonary complications died. The critical role of serial chest radiographs in the evaluation and management of burn victims is emphasized.


Glomerulonephritis and nephrotic syndrome complicated by renal vein thrombosis and pulmonary emboli: report of two cases. Two patients with membranous glomerulonephritis and nephrotic syndrome developed renal vein thrombosis and pulmonary emboli. Renal disease appears to be the initiating event in this syndrome complex. While intravenous urography and radionuclide venography are useful, inferior venacavography followed by pulmonary angiography are the definitive diagnostic procedures. Follow-up cavography is indicated to monitor progress of anticoagulant therapy in clot dissolution or recurrence.


Pneumothorax: a complication of percutaneous aspiration of upper pole renal masses. Pneumothorax is a rare complication of percutaneous needle aspiration of suspected upper pole renal cysts. This complication is of particular concern in elderly patients with compromised cardiopulmonary reserve who undergo this procedure on an outpatient basis. An upright expiratory chest film is recommended following needle aspiration of upper pole lesions for detection of asymptomatic pneumothorax.


Emergency percutaneous nephropyelostomy: experience with 34 patients and review of the literature. Emergency temporary percutaneous nephrophelostomy was performed 35 times in 34 patients. This procedure was used to relieve urinary tract obstruction when azotemia, infection, sepsis, or associated medical conditions precluded surgical correction of a renal obstruction. In all patients there was excellent clinical response. Supine oblique positioning in ill patients facilitates placement of nephrophelostomy tubes.


Perinephric abscess aspiration using ultrasound guidance. A perinephric is difficult to diagnose by clinical examination and traditional radiographic imaging techniques. Five cases are described in which the sonograms revealed a sonolucent perinephric collection suggestive of perinephric abscess. Diagnostic percutaneous aspiration performed under ultrasound guidance is a rapid, reliable, and safe means of distinguishing an abscess from a noninflammatory collection.


CT detection and aspiration of abdominal abscesses. Computed tomography (CT) is effective in detecting intraabdominal abscesses. Loculations of fluid and extraluminal gas are clearly localized in relation to other organs. Of 22 abscess in this series, CT successfully detected 20; comparative information with gallium, techneticum, and ultrasound scans is presented. In addition to localizing these collections, CT can be used to guide needle aspiration and drainage procedures. Three sizes of needles were used to aspirate specimens and/or provide drainage. This was accomplished successfully in 12 of 14 CT-guided procedures.


The African green monkey as an alternate primate host for studying Machupo virus infection. African green monkeys (Cercopithecus aethiops) are highly susceptible to Bolivian hemorrhagic fever (BHF). Six monkeys were inoculated with 1,000 plague-forming units of Machupo virus, the etiologic agent of BHF. They were observed and monitored for clinical signs, body temperature, viremia, hematologic changes, and virus neutralizing antibody. Onset of fever, anorexia, and depression was noted on days 3 to 6 postinoculation. These and other signs increased in severity and all monkeys died: 5 of 6 died by day 13 and one survived until day 24. The median time to death for the group was 12.5 days. The mean value for hematocrit determinations gradually decreased to 30 on day 10 but subsequently increased. Mean neutrophil and lymphocyte values increased slightly until day 3, and then decreased to minimal values of 3,000 and 2,000, respectively, on day 10. Four monkeys were viremic by day 7 and all were viremic on day 10. The monkey that survived until day 24 had a neutralizing antibody titer of 1:32 on day 14 and appeared to recover from the initial acute illness by day 16. It died following onset of severe neurologic signs on day 23. BHF in the African green monkey is similar to the disease described in two species of macaques.


Sporozoite transmission of falciparum malaria (Burma-Thau. strain) from man to Aotus monkey. A sporozoite-induced infection of Plasmodium falciparum (Burma-Thau. strain) was established in splenectomized Aotus trivirgatus which received prior treatment with dlmethionine as a dietary supplement. This is the first recorded instance of infection of an Aotus monkey with falciparum sporozoites of human origin.


Bronchodilators and physiotherapy during long term mechanical ventilation of the lungs. The effects of physiotherapy and hexaprenaline sulphate administration were studied on 10 patients requiring mechanical ventilation. No significant changes in arterial oxygen tensions were noted, but alveolar pressure fell significantly after treatment, indicating improvement in pulmonary compliance.


Central-nervous-system toxicity of local anesthetic mixtures in monkeys. The central-nervous-system toxicities of local anesthetic mixtures consisting of lidocaine and etidocaine or lidocaine and tetracaine, administered intravenously to four healthy, non-medicated rhesus monkeys, were evaluated. Toxicities were compared by determining seizure dosages for each drug alone and then in a lidocaine-etidocaine-tetracaine mixture. Arterial plasma levels of lidocaine and etidocaine at which electrical seizure activity occurred also were measured when the drugs were administered alone and in combination. The seizure dosages and arterial plasma levels for the drug mixtures studied were equal to the sums of the dosages and thresholds for individual constituents of the mixtures. Under the conditions of this investigation local anesthetic toxicity was additive. (Key words: Anesthetics, local, lidocaine; Anesthetics, local, etidocaine; Anesthetics, local, tetracaine; Brain, seizure thresholds; Toxicity, convulsions.)


Anterior shift of the dominant EEG rhytham during anesthesia in the Java monkey: correlation with anesthetic potency. EEG amplitude dominance in awake man is posterior. During EEG monitoring in patients, the authors observed the abrupt appearance of anterior amplitude dominance during induction of anesthesia with halothane, enflurane, or thiopental. This EEG change is coincident with loss of eyelid reflex and loss of ability to respond to command. This EEG change was studied with several anesthetics in five Java monkeys to determine alveolar anesthetic concentration at which it occurred and to observe the effects of various stimuli on it. EEG recordings were obtained after equilibration at each level with increasing concentrations of halothane, enflurane or isoflurane in oxygen and each agent again in 30 per cent N2O, in separate experiments in the same animals. EEG amplitude dominance became anterior in each animal with each anesthetic and combination at concentrations less than MAC, which was also determined in the same experiments. At lower concentrations, stimulation at equilibrated anesthetic concentrations resulted in abrupt EEG return to posterior amplitude dominance. The end-tidal anesthetic concentration at which persistence of anterior EEG dominance was seen after stimulation was approximately 0.4 MAC for each anesthetic and combination tested. This is interpreted as support for physical solution-lipid solubility theories of anesthetic action. In addition, an EEG change common to various anesthetics may increase the clinical usefulness of EEG monitoring. It is speculated that this EEG change may signal loss of awareness. If so, observance of sustained anterior EEG amplitude dominance may provide assurance of obliteration of awareness during anesthesia.


Animal models of hypersensitivity pneumonitis: a review. The etiology of hypersensitivity pneumonitis has been ascribed to each major type of immune injury. Data obtained from animal models support the spontaneous human situation in which a contunuum of events results in disease. The major attempts at gaining insight into this disease spectrum through animal models are reviewed.


Differing patterns of pulmonary function response to bronchodilators in asthmatics. An analysis of the patterns of pulmonary function response to bronchodilators in 20 adult asthmatics reveal distinct categories of response. It is suggested that the pattern of response is related primarily to the degree of baseline abnormality in pulmonary function rather than to other characteristics of the disease or patient. Thus, one may predict pulmonary function response to bronchodilators in adult asthmatics based solely upon baseline function.


Fate and distribution of inhaled nitrogen dioxide in rhesus monkeys. The intra- and extrapulmonary distributions of inspired nitrogen dioxide (NO2) were studied by exposing rhesus monkeys to air mixtures containing concentrations slightly greater than ambient (0.56 to 1.71 mg per m3, or 0.30 to 0.91 ppm) of NO2 labeled with tracer quantities of NO2 containing nitrogen-13 dioxide (13NO2). The 13NO2 (half-time, 10 min) was synthesized by the oxygen-16 (P, alpha)13N nuclear reaction in an isochronous cyclotron. The intrapulmonary location and concentration of the inspired 13NO2 was detected continuously by external monitoring of the annihilation radiation consequent to positron emissions from disintegrating 13N. The 13N concentration of arterial blood was also measured at intervals, and the blood values were correlated with those from the lung. Chemical measurements of NO2 concentration in inspired and expired air were performed by the Saltman method. Control studies were performed with xenon-125 (125Xe) (halftime, 17 hours). The results demonstrated that 50 to 60% of the inspired pollutant was retained by the primate during quiet respiration; the gas was distributed throughout the lungs. Once absorbed, NO2 or chemical intermediates remained within the lungs for prolonged periods after cessation of exposure, and dissemination of the pollutant or its derivatives to extrapulmonary sites occurred via the blood stream. Indirect evidence indicated the probable reaction of NO2 with water in the nasopharynx and lungs to form nitric and nitrous acids. The reaction of these acids with pulmonary and extrapulmonary tissues probably accounts for the biologic toxicity of NO2.


Stability of bacteriophage type of Mycobacterium tuberculosis: absence of variation caused by experimental chemotherapy in mice and analysis of spontaneous variation. The bacteriophage typing of 54 strains isolated from the tissues of mice infected with the strain H37Rv of Mycobacterium tuberculosis and treated with isonazid and rifampin showed that the bacteriophage type did not change. The fluctuation analysis of populations of the tubercle bacilli demonstrated that the rate of mutation from sensitivity to resistance in respect to the bacteriophage DS6A was less than 1.3 X 10(-8) mutations per bacterium per generation.


Dose-related levodopa-induced haemolytic anaemia. A 71-year-old white man developed direct antiglobulin positive haemolytic anaemia after 16 months of levodopa therapy for Parkinson's disease. Immunoglobulin G autoantibodies directed against Rh antigens were found in the patient's serum and on his erythrocytes. Reduction of levodopa dosage to one sixth with the aid of a peripheral decarboxylase inhibitor (benserazide) largely eliminated autoimmune haemolysis while maintaining adequate control of neurologic symptoms.


Anorectal gonococcal infection.

Anorectal gonococcal infection. Anorectal gonococcal infection is common in women and homosexual men. In women with uncomplicated gonorrhea, the mean prevalence rate of anorectal involvement is 44%, with lone involvement of the anorectum in 4%. Among homosexual men with gonorrhea, anorectal infection occurs in 45%, although more than 90% of all male patients with anorectal gonorrhea admit to homosexual rectal intercourse. This infection is usually asymptomatic but occasionally presents with acute or chronic symptoms that mimic other causes of proctitis. Whereas currently recommended regimens for uncomplicated gonorrhea appear effective for anorectal gonorrhea in women, results in men have not been adequately evaluated. Available data showed failure rates from 7% to 35%; however, only one study used a currently accepted regimen. Further controlled studies in male patients with anorectal gonorrhea are clearly needed to establish optimal therapeutic regimens. Diligent contact tracing of all male homose.xual cases appears to be the only effective means of control at present.


Genetic and environmental determinants of growth of school-aged children in a rural Colombian population. Parent-offspring correlations and heritabilities of body measurements from midparent-offspring regressions are presented for school-aged children from the village of Tenza, Colombia (N = 403 families). Parent-child correlations and midparent regressions in this subsistence farming sample, are similar in magnitude to those for well nourished, urban industrial samples, suggesting that the environmental component of variability in body size is the same regardless of the environment. Tenza children are significantly shorter and lighter than upper class Bogota children, and Tenza parents have mean heights and weights similar to those of other lower class Colombian samples. Thus, chronic undernutrition has affected the growth of parents and continues to affect the growth of the present generation. Although it has been hypothesized that heritability of growth might be reduced in samples experiencing malnutrition and its sequelae, such a reduction may only be observable where environment of parents during their development is different from that of their offspring, which is not the case here. The pattern of heritabilities with respect to different body measurements in Tenza, is similar to that seen in well nourished samples, except that measurements of breadth (biacromial, bicristal, bicondylar) have heritabilities similar in magnitude to those of linear measurements (height, sitting-height, subischial length) especially in males; and heritabilities of some measurements related to adiposity are significantly higher in daughters than in sons.


Stature and age as factors in the growth of second metacarpal cortical bone in moderately malnourished children. The association of stature and age with measures of second metacarpal cortical bone growth is investigated in a sample of 1586 radiographs taken from Guatemalan Ladino children aged 1-7 years in a setting of endemic mild-to-moderate malnutrition. For given stature, chronological age is positively associated with cortical thickness and cortical area and negatively associated with periosteal and medullary diameter. These different partial correlations are seen as evidence of different kinds of growth. Correlations of cortical bone variables with body size within a chronological age are shown to derive from the overall relationship between age, stature, and measures of cortical bone.


[Antibacterial activity of rifampicin against the causative agents of suppurative, septic diseases]. The antibacterial activity of rifampicin was studied in comparison with other antibiotics with respect to clinical strains isolated from cases with various purulent inflammatory processes caused by Staphylococcus, E. coli, Ps. aeruginose, Proteus. The aim of the study was to define the role of rifampicin in the treatment of the above infections. No rifampicin resistant strains were found among staphylococci belonging to the phenotype carrying the determinants of resistance to 2-8 antibiotics. Rifampicin was less active against gramnegative organisms. High heterogeneity of the microbial population of rifampicin was shown with respect to all microbial strains tested. The rate of the spontaneous mutants was high. The average rate of the mutants was 1-7.7-10-8. The studies on the dynamics of the rifampicin resistance increase in the strains of Staphylococci, E. Coli, Ps. aeruginosa and Proteus showed that the resistance increased after 1-2 passages, which means that one-stage mutation was characteristic rifampicin.


Scanning electron microscopic appearance of rat otocyst of the twelfth postcoital day: elaboration of a method. A method for removal, fixation, microdissection, and drying of early rat otocyst for examination by the scanning electron microscope is elaborated. Tissues were dissected, fixed as for conventional transmission electron microscopy and dried by critical point evaporation using amylacetate as the transitional fluid and carbon dioxide as the pressure head. Otocysts were either dissected at the time of initial fixation, or subsequent to drying. The otocyst of the 12th postcoital day was used as a model system in this preliminary report. Critical point drying retained the overall configuration and the fine ultrastructural detail of the otocyst. The interior otocystic surface was visualized and cilia bearing cells of the luminal surface were identified. Most if not all of these cells had a comspicuous, but short kinocillum which terminated in an ovoid bulb. The scanning electron microscopic appearance was correlated to the transmission electron microscopic image seen in the second paper in this Supplement.


[Antibiotic sensitivity of Proteus, Pseudomonas pyocyanea and staphyloccoci isolated from scleroma and ozena patients]. Antibiotic sensitivity of 292 strains of Proteus, 60 strains of Ps, aeruginosa, 309 strains of S. aureus and 88 strains of S. epidermidis isolated from the upper respiratory tract of patients with scleroma and ozena was studied. The cultures of Pr. mirabilis were sensitive to aminoglucosides (54.9-96.2 per cent) and Pr. morganii were sensitive to levomycetin (81.5 per cent) and neomycin (92.6 per cnet). Sensitivity of Pr. vulgaris and Pr. morganii was reliably higher (p less than 0.001) than that of Pr. mirabilis. The strains of Pr. morganii were less sensitive to monomycin (P less than 0.001) and streptomycin (p less than 0.01) as compared to the cultures of other Proteus species tested. The strains of Ps. aeruginosa were sensitive only to gentamicin (90 per cent) and neomycin (81.1 per cent). Most of the strains of S. aureus (85.4-100 per cent) were sensitive to oleadomycin, erythromycin, olemorphocycline, tetraolean, oxacillin, methicillin ceporin, lincomycin, ristomycin, kanamycin, monomycin and gentamicin. Benzylpenicillin (90.8 per cent of the sensitive strains), ampicillin (67.1 per cent), tetracycline (66.7 per cent), levomycetin (68.6 per cent) and streptomycin (38.1 per cent) were less effective. Antibacterial therapy in cases with scleroma and ozena should be directed not only against causative agents of the diseases but also against the microbes developing due to disbacteriosis. Combination of parenteral and local use of the antibiotics in the treatment of chronic clebsiellesis decreased the isolation rate of Proteus and Ps. aeruginosa in the patients.


Ultrastructural development of the early rat otocyst. The ultrastructural development and differentiation of cells forming the rat otocyst were studied from the 9th to the 13th postcoital day (PCD). The earliest stage investigated was a simple ovoid structure with a connecting stalk to the surface ectoderm. A process of programmed cellular death involving surface ectoderm, connecting stalk, and lateral otocyst wall rapidly detached the otocyst. The cells forming the otocyst were roughly columnar, the organelles were polarized; mitochondria occurred in greatest number basally and in the supranuclear area; Golgi membranes when present were supranuclear. Luminal cells had many microvilli and cilia of various lengths were detected. The shorter, incompletely formed cilia terminated in small knob-like blebs. With each day the otocysts became more complicated and the endolymphatic duct made its appearance as an evagination of the otocyst. Many more cells were seen to have cilia in various stages of development, and by the 12th PCD possibly each cell of the main otocystic cavity had a kinocilium. Growth of the otocyst due to mitosis occurred to a great extent from a single ventromedial center. Cells in mitosis, although seen at other sites, were in greatest abundance in this area; cellular involution apparently was a related function. Together the process of over-production and programmed cellular involution of supranumerary cells not lost to other causes (e.g., environmental) may represent an evolutionary advantage.


Diving injuries to the inner ear.

Diving injuries to the inner ear. Most of the previous literature concerning otologic problems in compressed gas environments has emphasized middle ear barotrauma. With recent increases in commercial, military, and sport diving to deeper depths, inner ear disturbances during these exposures have been noted more frequently. Studies of inner ear physiology and pathology during diving indicate that the causes and treatment of these problems differ depending upon the phase and type of diving. Humans exposed to simulated depths of up to 305 meters without barotrauma or decompression sickness develop transient, conductive hearing losses with no audiometric evidence of cochlear dysfunction. Transient vertigo and nystagmus during diving have been noted with caloric stimulation, resulting from the unequal entry of cold water into the external auditory canals, and with asymmetric middle ear pressure equilibration during ascent and descent (alternobaric vertigo). Equilibrium disturbances noted with nitrogen narcosis, oxygen toxicity, hypercarbia, or hypoxia appear primarily related to the effects of these conditions upon the central nervous system and not to specific vestibular end-organ dysfunction. Compression of humans in helium-oxygen at depths greater than 152.4 meters results in transient symptoms of tremor, dizziness, and nausea plus decrements in postural equilibrium and psychomotor performance, the high pressure nervous syndrome. Vestibular function studies during these conditions indicate that these problems are due to central dysfunction and not to vestibular end-organ dysfunction. Persistent inner ear injuries have been noted during several phases of diving: 1) Such injuries during compression (inner ear barotrauma) have been related to round window ruptures occurring with straining, or a Valsalva's maneuver during inadequate middle ear pressure equilibration. Divers who develop cochlear and/or vestibular symptoms during shallow diving in which decompression sickness is unlikely or during compression in deeper diving, should be placed on bed rest with head elevation and avoidance of maneuvers which result in increased cerebrospinal fluid and intralabyrinthine pressure. With no improvement in symptoms after 48 hours, exploratory tympanotomy and repair of a possible labyrinthine window fistula should be considered. Recompression therapy is contraindicated in these cases...


Precipitation of 125I-labelled IgG aggregates by factors in sera of healthy individuals and of patients with rheumatoid arthritis. Several factors in human serum are capable of precipitating soluble 125I-labelled heat aggregated IgG (agg IgG*). A study of the nature of these factors resulted in the development of two new methods for the detection and assay of anti-IgG-immunoglobulins (rheumatoid factors) in serum. One method detected rheumatoid factors of the IgG and the IgA classes which are capable of binding and coprecipitating with Clq and agg IgG* in an EDTA milieu. In a second method the serum was first heat inactivated and the assay was then made in a polymeric milieu where rheumatoid factors of the IgM as well as the IgG and IgA classes could be detected. 67 sera from patients with rheumatoid arthritis were tested with this method and rheumatoid factors were detected in all seropositive (as assayed with conventional rheumatoid factor tests) sera and in 58% of the seronegative sera. In the presence of certain anti-IgG-immunoglobulins or polymers, the precipitation of Clq and soluble agg IgG* is greatly enhanced, and we suggest that this can be used as a basis of a sensitive method for the assay of agg-IgG-binding activity of Clq.


Effect of intra-articular corticosteroid injections on primate cartilage. An attempt was made to ascertain whether intra-articular corticosteroids exert a harmful effect on primate cartilage. The knee joints of 10 Macaca irus monkeys were subjected to either one, two, or six injections of 20 mg methyl prednisolone or an equal number of control injections over a 12-week period. Minor degenerative changes of many femoral condyles were shown by India ink staining and by a system of histochemical grading. Changes in the joints injected with corticosteroid were not significantly different from those seen in control joints. The findings were in striking contrast to the severe degeneration reported by others in rabbit joints injected with corticosteroid. The experiment did not support the contention that intra-articular corticosteroids invariably have a deleterious effect on primate cartilage.


Evaluation of a new monkey model for the repeated study of bile secretory physiology. An unchaired monkey model for the repeated long-term study of biliary secretory physiology is reported. Postoperative management with cholre recorded. Evaluation was performed by repeated measurement, over a period of months, of bile flow and 14C erythritol clearance at three rates of taurocholate infusion given intravenously in a random order. Response to secretin was tested at the final infusion rate of taurocholate for each experiment. The outcomes of 9 monkeys were described of which 5 were repeatedly studied. They demonstrated an increase in bile flow and 14C erythritol clearance with increasing bile salt output. A dramatic choleresis over a wide range of bile salt excretion was noted with secretin and a linear relationship between bile bicarbonate output and bile salt secretion rate was observed. The new model has several major advantages and gives higher bile flows than previously recorded in the chaired model.