Conjugate lateral gaze nystagmus and free phenytoin concentrations in plasma: lack of correlation. Electrooculographic recordings during left and right conjugate lateral gaze fixation from 10 degrees to 50 degrees were made in 29 patients being treated with phenytoin. At the time of electrooculographic recordings, venous blood samples were drawn for analysis of total and free phenytoin plasma concentrations. Rhythmic horizontal nystagmus occurred in 7 patients, and only at extreme (40 degrees, 50 degrees) later gaze in 6 of these. Measurable free phenytoin levels in the 29 patients ranged from 0.2 to 3.2 mug/ml, and in the 7 patients with nystagmus were 0.6, 0.8, 1.0, 1.0, 1.7, 1.8, and 3.2 mug/ml. Neither the occurrence of nystagmus nor the degree of lateral gaze at onset could be correlated with free phenytoin concentrations in plasma.


Mannosidosis: separation and characterization of two acid alpha-mannosidase forms in mutant fibroblasts. Two acidic forms of alpha-mannosidase activity, A and B, are separated and characterized in fibroblasts from controls and patients with mannosidosis. In normal cells, A and B differ in adsorption on DEAE-cellulose, electrophoretic mobility, stability at 70 degrees C and resistance to freezing at --20 degrees C. In 5 of 6 mutant cell lines, A and B both exhibit altered Km's for artificial substrates and decreased thermal stability. Zn2+ has no effect on A or B in mutant or normal cells. In contrast, Co2+ slightly inhibits B in normal cells but markedly enhances the activity of B in mutant cells. The mutation in mannosidosis clearly results in an alteration in the biochemical characteristics of both major acidic forms of alpha-mannosidase.


Adenyl cyclase in normal and denervated skeletal muscles. Adenyl cyclase (AC) has been studied in homogenates and crude plasma membranes from normal and denervated red and white skeletal muscle from male rats. Basal-, NaF- and epinephrine-stimulated activities were increased in homogenates of both types of muscles after nerve transection, supporting a possible role of the cAMP-AC system in the neurotrophic control of skeletal muscle. AC-specific activity was increased 10 times in crude plasmic membranes from normal muscle if compared to that of homogenate. It was decreased in crude plasmic membrane from denervated muscle. The correlation of our results with other results on cAMP concentrations and cAMP phosphodiesterase (PDE) activities in denervated muscle suggests that factors other than AC and PDE might control the synthesis and degradation of cAMP.


Uterine total lactic dehydrogenase and isozymes of rats administered steroids. Endometrial scrapings from intact immature and adult rats as well as from ovariectomized series injected subcutaneously daily for 4 days with estradiol benzoate (0.053 mumol/rat/day) displayed marked increases in total LDH and LDH5 over the controls. The uterine luminal fluids from the estrogen-treated animals were lower in total enzyme and, of the isozymes, LHD5 occurred at levels higher than in the scrapings, and LHD1--LDH3, inclusive, were very low to absent. A few of the fluids which were purulent contained greater total LDH contents. Progesterone (19.1 mumol/rat/day) depressed the control LDH in intact adults but had very little influence on an ovariectomized series, and the distribution of isozymes followed the control patterns. However, estradiol benzoate + progesterone elicited overall LDH levels exceeding the respective controls, being more in the range of the estrogen-treated groups and with a trend toward decreases in LDH5 relative to the estrogen-injected rats.


Fatty acid, 3-beta-hydroxysterol, and ketone synthesis in the perfused rat liver. Effects of (--)-hydroxycitrate and oleate. The effects of oleate and hydroxycitrate on the rate of long-chain fatty acid and 3-beta-hydroxysterol synthesis were measured in perfused rat livers. Metabolite measurements show that in livers from fed animals inhibition of fatty acid synthesis by oleate or hydroxycitrate is associated with an increase in the tissue content of glucose 6-phosphate and fructose 6-phosphate, and a diminution in glycolytic intermediates from fructose diphosphate to phosphoenolpyruvate. Oleate also causes an increase in the tissue content of long-chain fatty acyl-CoA and citrate. The increase in long-chain fatty acyl-CoA is larger in livers from starved as compared to fed rats, while the increase in citrate is larger in livers from fed as compared to starved rats. However, the increase in the citrate content of livers from fed rats occurs in a range where it causes no further activation of acetyl-CoA carboxylase in vitro. Ketogenesis by livers from fed rats perfused without free fatty acids is strongly inhibited by hydroxycitrate. However, ketogenesis is not inhibited by hydroxycitrate when livers from starved rats are perfused with oleate, and ketogenesis is increased somewhat by hydroxycitrate when livers from fed rats are perfused with oleate. These results are interpreted in terms of an extramitochondrial pathway of ketogenesis which operates in carbohydrate-fed animals. The intramitochondrial pathway predominates in starved animals, or when the concentration of fatty acids is high, or both. Other interpretations, which cannot be ruled out at present, are also considered.


Characterization of alfalfa-mosaic-virus protein polymerization in the presence of nucleic acid. The polymerization of alfalfa mosaic virus (AMV) protein in the presence of homologous nucleic acids and a number of other natural and synthetic nucleic acids was studied. The conditions for optimal assembly were found to be pH 6.0 and low ionic strength (I = 0.1 M) at room temperature, irrespective of the type of nucleic acid. The resulting nucleoprotein particles exhibited the same structural characteristics as the virus. This information emerged from optical diffraction and computer filtering of electron micrographs from the reconstituted particles. Irrespective of the type of nucleic acid present the polymerization of the protein resulting in a nucleoprotein particle is a cooperative process. Evidence for this was obtained by nitrocellulose filter binding assay, sodium dodecylsulphate/polyacrylamide gel electrophoresis, sedimentation velocity and electron microscopy of the reaction mixtures. The rates and efficiencies of reconstitution were of the same order of magnitude for a number of ribonucleic acids. Sedimentation data derived from AMV protein and AMV RNA mixtures suggested the existence of a specific nucleation product in the first stage of assembly. The results are discussed in terms of a tentative model of the assembly, in which at least two different steps (nucleation and elongation) can be distinguished, each characterized by an association constant.


Kinetic studies of glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle. Initial rate studies at pH 7.6 with three aldehydes, product inhibition patterns with NADH and dead-end inhibition with adenosine diphosphoribose show that the kinetic mechanism of glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle cannot be ordered, and support an enzyme-substitution mechanism. Deviations from Michaelis-Menten behaviour are consistent with negative interactions in the binding of NAD+ and instability of the species E(NAD)3 and E(NAD)4. Inhibition with large concentrations of phosphate and arsenate indicates competition for a binding site for glyceraldehyde 3-phosphate, and is not found with glyceraldehyde as substrate.


The amino-acid sequence of chicken fast-skeletal-muscle troponin I. The amino acid sequence of troponin I from chicken breast and leg muscle has been determined using tryptic and CNBr peptides. The protein contains 182 residues and has a molecular weight of 21136. The N-terminus is blocked and is probably acetylated. 35 of the residues have acidic and 45 have basic side chains giving an overall net positive charge of 9. The CNBr peptides from both breast and leg troponin I have been shown to be identical and no heterogeneity has been found in the tryptic peptides isolated from a mixture of the two proteins. It may thus be taken that the two proteins are identical. Comparison with the sequence of troponin I from rabbit fast skeletal muscle shows strong homology with 34 differences out of 182 residues. The major difference is in a deletion of three residues, from 152 to 154, in the rabbit protein.


Brown-adipose-tissue mitochondria: photoaffinity labelling of the regulatory site of energy dissipation. Brown-adipose-tissue mitochondria possess an energy-dissipating ion uniport which is inhibited by purine nucleotides. The regulatory nucleotides bind to a high-affinity site on the outer face of the inner membrane which is independent of the adenine nucleotide translocator. A direct correlation between affinity for the regulatory site and ability to inhibit the ion uniport is demonstrated for a number of nucleotide analogues. 8-Azido-adenosine 5'-triphosphate, a photoaffinity label, also competes with GDP for the binding site and induces respiratory control. 8-Azido-adenosine [gamma-32P]triphosphate was prepared and covalently bound to hamster brown-adipose-tissue mitochondria by near-ultraviolet irradiation. Two major radioactive bands were identified of apparent molecular weight 30000 and 32000, representing 6% and 10% of the inner membrane protein respectively. Selective labelling enabled the 30000-Mr protein to be identified as the carboxyatractylate binding component of the adenine-nucleotide translocator and the 32000-Mr protein to be identified as the regulatory site of the energy-dissipating ion uniport. The levels of the 32000-Mr protein in the inner membrane of guinea-pig brown-adipose-tissue mitochondria correlate with the degree of thermogenic adaptation of the animal.


Energy metabolism of various substrates and the 2,3-Bisphosphoglycerate bypass in human erythrocytes. 1. Using different experimental conditions and applying various substrates, a wide range of metabolic rates could be observed in incubations with human erythrocytes. 2. Lower rates of substrate utilization resulted in a decrease of the ATP and, more pronounced, of the 2,3-bisphosphoglycerate concentration while carbon utilization rates beyond 14 mumol C/ml packed cells in 120 min yielded constant levels of ATP and 2,3-bisphosphoglycerate indicating that steady state had been achieved. 3. It can be concluded, that a carbon utilization rate of 14 mumol C/ml cells in 120 min is able to cover the energy requirement of the red cells under steady state conditions which could be calculated to amount to 3.6 mumol ATP/ml cells in 120 min at 37 degrees C. 4. The contribution of the 2,3-bisphosphoglycerate bypass to carbon metabolism could be calculated to range between 15--25% at metabolic rates below 14 mumol C/ml cells in 120 min (presteady state). When steady state has been achieved, the share of this bypass increases up to 61% with increasing metabolic rates.


Some properties of sialyltransferase in plasma and lymphocytes of patients with chronic lymphocytic leukemia. Some properties of sialyltransferase activity in plasma and lymphocytes from patients with chronic lymphocytic leukemia were compared. Three distinct enzyme fractions were identified in plasma: (1) cation independent, irreversibly bound to agarose; (2) cation dependent, weakly bound to agarose; (3) strongly bound to agarose, lost upon dialysis. Lowering of the peripheral lymphocyte count by leukapheresis markedly decreased the level of serum sialyltransferase, suggesting the circulating lymphocyte is a source of the serum enzyme. The enzyme solubilized by detergent from lymphocytes showed a substantially lower Km for CMP-sialic acid than did the serum enzyme, was less sensitive to several inhibitors, was not irreversible bound to Agarose, and had a substantial cation requirement. The enzyme solubilized from the lymphocyte therefore generally resembles fraction 2 of serum.


Ionic strength dependence of the oxidation of iodide and ferrocyanide by compound I of horseradish peroxidase. The kinetics of the oxidation of iodide and ferrocyanide by compound I of horseradish peroxidase have been studied at 25 degrees C as a function of ionic strength and pH. The ionic strength dependencies of the second-order rate constants are tested with an extended form of the Debye-Hückel equation for the activity coefficients of the reacting species. For the reaction of iodide with compound I it is shown that the pH variation of the rate constant at zero ionic strength is caused mainly by titrating a catalytically important acid group and not mainly by the varying charge of the protein. The ferrocyanide reaction rate with compound I does not correlate with enzyme net charge, at all pH values. The influence of electrostatic interactions on reaction rates is discussed.


Isolation of messenger RNA coding for eggshell protein of the DNA-eliminating nematode Ascaris lumbricoides. Poly(A)-containing RNA from polyploid uterine epithelial cells of Ascaris lumbricoides has been isolated by poly(U)-Sepharose chromatography. The bulk of poly(A)-containing RNA migrates as 18-S RNA in formamide/polyacrylamide gels. In a cell-free wheat germ system, this RNA directs the synthesis of a polypeptide with identical migration behavior in dodecylsulphate/urea/polyacrylamide gels as the polypeptide isolated from the proteinaceous eggshell. The two proteins reveal almost identical peptide patterns in fingerprint analysis. The authentic eggshell protein has been identified as a glycoprotein with a molecular weight of about 10000, as determined by dodecylsulphate/polyacrylamide gel electrophoresis. The apparent discrepancy between mRNA length and the required coding length for the protein is discussed.


Kinetics of synthesis of cytoplasmic messenger-like RNA not associated with ribosomes in HeLa cells. The turn-over of cytoplasmic messenger-like RNA not associated with polyribosomes as well as that of polyribosomal mRNA was investigated by labelling with [3H]uridine in conditions of arrested ribosomal RNA and mitochondrial RNA synthesis. The synthesis of ribosomal RNA was inhibited with toyokamycin and that of mitochondrial RNA with ethidium bromide. In both accumulation kinetics and actinomycin-D-chase experiments, cytoplasmic messenger-like ribonucleoprotein particles and polyribosomes were fractionated by buoyant density centrifugation in CsCl gradients. The half-life of free m1RNA was found to be of 1--2 h whereas the bulk of polyribosomal mRNA was stable over the time period considered (up to 8 h) but with a minor short-lived component. Purification of RNA from polyribosomes labelled under the same conditions and fractionation of it into polyadenylated and non-polyadenylated fractions showed that this short-lived minor component of half-life less than 1 h is non-polyadenylated.


Parasitic myositis by Echinococcus alveolaris. Report of a family with myotonia congenita. Echinococcus alveolaris infections were found in 5 members of a family and at least 3 of them also suffered from myotonia congenita. A muslce biopsy, performed in 1 case because of a pathological EMG finding allowed a diagnosis of parastic myositis caused by E. alveolaris to be made. In a further case, X-rays demonstrated calcification of an Echinococcus cyst in the thigh. Since is it only on rare occasions that these parasites are found in muscle tissue, factors are then discussed which might in some way be responsible for this high rate of E. alveolaris lesions in the muscles of patients with myotonia congenita.


Mumps meningitis: prolonged pleocytosis and occurrence of mumps virus-specific oligoclonal IgG in the cerebrospinal fluid. A pleocytosis of the CSF occurred in all of 10 children with mumps meningitis and persisted for weeks and months in some patients. Oligoclonal IgG proteins were detected in the cerebrospinal fluid (CSF) during the 2nd week after onset of meningitis or later in 4 out of 10 patients, and could be detected as late as 11 and 12 months after meningitis in 2 patients. Evidence is presented that the oligoclonal IgG represents mumps virus-specific antibody synthesized locally in the brain. Oligoclonal virus antibodies were demonstrated also in serum samples. The persistence for weeks and moths of pleocytosis and oligoclonal IgG virus antibody in the CSF may imply that a virus infection in some cases persists in the brain in spite of apparently complete clinical recovery.


Fibrinolytic activity in blood and cerebrospinal fluid in subarachnoid hemorrhage from ruptured intracranial saccular aneurysm before and during EACA treatment. 10 patients suffering from intracranial aneurysm causing subarachnoid hemorrhage (SAH) have been treated during the acute pre-and postoperatory phase with omega-aminocaproic acid. The blood and the cerebrospinal fluid of the treated patients have been analyzed in order to study fibrin(ogen) degradation products (FDP) and fibrinolytic activity (FA). The results so obtained show only an alteration of local fibrinolytic processes either inside or around the aneurysmatic clot: there were no alterations of the systemic FA. Furthermore, monitoring of FDP and FA was a very useful tool in those patients who took advantage of the treatment with omega-aminocaproic acid which protected them from rebleeding.


Benign intracranial hypertension after minocycline therapy. A case is reported of a young girl who developed benign intracranial hypertension, with severe bilateral papiledema and a left sixth cranial nerve palsy, after minocylcine therapy. This drug is a semisynthetic tetracycline which has proven to pass into the CSF more effectively and to have a greater lipoid solubility than the other antibiotics of the same group.


Paralysis of the deep branch of the radial nerve due of an entrapment neuropathy. The clinical and neurophysiological findings in two cases of spontaneous paralysis of the deep branch of the radial nerve are reported. The patients are sisters and the dominant hand was affected in both. One patient was submitted to surgical exploration, and 'entrapment neuropathy' was found to be the cause. After neurolysis the patient gained complete recovery. The usefulness of the EMG illustrated and stressed.


A case of Sturge-Weber disease with epilepsy and intracranial calcification at the neonatal period. An extremely rare case of Sturge-Weber disease with the early onset of seizure and intracranial calcification at the neonatal period is reported. It is emphasized that computed tomography (CT) is the first choice as diagnostic procedure for this disease, revealing extensive cortical atrophy and calcification which were not detected by other radiological examinations.


The loss of electrically active myocardium in cardiogenic shock. A method of precordial mapping of RS ratio changes and the appearance of Q waves that occur in acute myocardial infarction has been developed. The serial changes of R and Q waves in 40 patients suffering uncomplicated anterior infarction shows that the loss of electrically active myocardium occurs within 6 h from the onset of chest pain. The total precordial ECG changes of R and Q waves in 5 patients suffering anterior infarction and cardiogenic shock showed that the loss of electrically active myocardium continues after 6 h from the onset of chest pain, and is significantly different from the uncomplicated group. This was supported by the serial plasma MBCK activity determinations which suggest more than one episode of necrosis.


The electrocardiographic diagnosis of left septal fascicular block. In 38 anesthetized and intubated dogs QRS features were estimated after incision of the interventricular septum. The left bundle branch system of the excised heart was stained with Lugol solution to visualize the extent and localization of the fascicular section. In 7 dogs the incision reached a part of the septal network; three of them showed incomplete LBBB pattern. In 13 dogs a major part of the septal network and the posterior/anterior fascile were transected. In 6 of them the pattern of incomplete LBBB was noted. A bipolar intracavitary L-R lead was recorded in 2 of these cases and revealed disappearance of the initial q wave in both. In 7 experiments the left bundle branch was completely transected with consecutive LBBB pattern. In 8 dogs the incision failed to reach the left bundle branch system and the ECG records did not show any form of LBBB pattern. The findings suggest that incomplete LBBB may be a form of left septal fascicular block.


Selective coronary angiography in patients with conduction disturbances of the heart. Selective coronary angiography and left ventriculography was performed in 14 patients with conduction disturbances of the heart or chronic complete heart block. Occlusive coronary arterial diseas was present in 3 patients: 2 of these had had extensive previous myocardial infarction and 1 complained of angina pectoris. The other patients gave no history of coronary artery disease and conduction abnormalities were the consequence of idiopathic fibrosis of the conducting system. The coronary arteries were normal or dilated and were remarkably free of atheroma in this group of older patients. Left ventricular function, as measured by ejection fraction, was normal except in the 2 patients who had had previous myocardial infarction.


Hemodynamic factors associated with the production of pain in angina pectoris. 18 patients with uncomplicated angina pectoris were studied to ascertain the relative significance of individual hemodynamic factors in the production of angina pectoris. Each hemodynamic determinant of myocardial oxygen consumption (heart rate, systemic arterial pressure, LVEDP, and LV dp/dt max) were either altered or controlled as discretely as possible with the use of right atrial pacing, propranolol, phentolamine and ouabain, and the effects of these changes were observed on the onset and total duration of pain. Only heart rate correlated closely with the precipitation of angina. The systemic arterial pressure, LVEDP and LV dp/dt max did not correlate with the production and abolition of angina pectoris. The results indicate that drugs acting only against the effect of sympathetic stimulation of the sinus node would be a major advantage in the treatment of patients with angina pectoris. The unexpected finding that phentolamine did not ameliorate pain in patients with angina pectoris casts doubts as to whether nitroglycerine relieves anginal pain by lowering the systemic arterial pressure.


Myocardial lesions induced by natural catecholamines in vitro. Isolated rat hearts were perfused using a retrograde technique under constant pressure head or constant coronary flow. The addition of 1-epinephrine or 1-norepinephrine (1 microgram/ml) to the perfusion medium for 1 h caused visible and irreversible morphological changes which usually became apparent after 4 h of perfusion in the form of small, pale, opaque spots or streaks gradually enlarging on the surface or on the cross-section area of the myocardium. Light- and electron-microscopic examination showed a disintegration process analogous to that of myocardial infarction but without the infiltration with blood elements. The structural changes were preceded by an increased release of lactate dehydrogenase into the effluent, the most characteristic metabolic change accompanying myocardial injury. Nevertheless, the underlying mechanism of the cardiotoxic action of catecholamines remains to be clarified; several factors under consideration could be eliminated: hyperlipidemia, trombogenic process, acidity due to enhanced production of lactate, reduced total coronary inflow rate and toxicity of oxidation products of catecholamines.


Distribution of 51Cr labeled leukemia cells in mice: comparison with representative normal cells. Cells of two transplantable leukemias of mice, one myeloid and one lymphoid, were labeled with 51Cr in order to follow their distribution in hemopoietic and parenchymatous organs and blood of syngeneic recipients. Distribution of myeloid leukemia cells was compared with that of regenerating bone marrow cells and normal spleen cells. The organ distribution of myeloid leukemia cells was essentially different from that of cells of regenerating bone marrow, and both were different from that of normal spleen cells. Cells of lymphoid leukemia, which are presumably of B-lymphocyte origin, were compared with a B-lymphocyte enriched population, obtained from the lymph nodes of so-called TIR mice (thymectomized, irradiated, and reconstituted with syngeneic bone marrow), and with spleen cells of normal mice. The three patterns of organ distribution were different. It is concluded that the two leukemias studied each have a specific and characteristic distribution.


Studies of the mechanism of polycythemia induced in rats by Ni3S2. Intrarenal injection of 10 mg Ni3S2 elicits polycythemia in rats. This can be attributed either to direct stimulation or to erythropoietin-induced hyperplasia of erythropoietic elements of bone marrow. While studying the mechanism of this experimental model of polycythemia we noted that: (a) extirpation of the injected kidney after the development of the hematologic alterations abolished the polycythemia within 1 month; (b) intravenous, intramuscular or intrahepatic treatment with Ni3S2 was ineffective in producing polycythemia; and (c) there was a modest but statistically significant elevation of plasma erythropoietin levels in rats 2,4 and 8 weeks after injection of Ni3S2, at a time when the hematocrit values were increased. The experiments support the view that Ni3S2 does not directly stimulate erythropoiesis in bone marrow but primarily affects the injected kidney, which in turn (by the continuous liberation of modest amounts of erythropoietin or some hitherto unknown substance) triggers the development of polycythemia.


The isolation of newly formed bone associated cells in vitro: preliminary observations on origin and morphology. Agar-medium suspensions were used to culture guinea-pig femoral bone fragments which had been physically depleted of marrow. A sequential study of the histological events occurring within the regenerating shaft, in the agar wholemount preparations and on the underlying coverglass allowed (1) the localization of the early regenerative cells within the endosteal crevices and their rapid proliferation to fill and 'encapsulate' the explant; (2) the detection of residual marrow granulocytic and mononuclear precursors amidst the regenerative non-hemopoietic cells within the endosteal crevices of bone; (3) a study of the development of the adherent cells on the coverglasses. Cumulative labeling studies indicated that almost all the migrating cells were newly formed cells with a small fraction (less than 5%) within the endosteal crevices observed as unlabeled cells after 5 days of culture. The adherent mononuclear cells were derived directly from the regenerating bone fragment and showed similar morphology and proliferative characteristics (97% cumulative labeling index) to the bone associated cells. A unique feature of these monolayers was the formation of an extensive network of extracellular material between cells. These observations have not been described in monolayers derived from marrow suspensions and appear to be a characteristic of the monolayers derived from regenerating bone fragments.


Effect of hypertransfusion on bone marrow restoration after localized depletion. The reconstitution of marrow in a mechanically depleted medullary cavity was compared in normal and hypertransfused mice. Polycythemia (hematocrit of approximately 70%) prevented the emergence of recognizable erythroid cells but not of erythropoietin-responsive cells as revealed by autoradiographic studies with 55Fe after erythropoietin treatment. The similar regeneration of erythropoietin-responsive cells in normal and hypertransfused mice was shown by comparison of 55Fe labeling in the repopulating relative to the contralateral marrow; in each case, labeling in the repopulating marrow was about 20% of that in the intact contralateral marrow. Polycythemia did not influence the recovery of granulocytic elements in the regenerating marrow even though the myeloblast-metamyelocyte population of the intact contralateral marrow was increased. The findings are intrepreted to support the concept that hematopoietic stem cell commitment to one or another pathway of differentiation is basically a local phenomenon.


Human marrow erythropoiesis in culture: III. Ultrastructural and cytochemical studies of cellular interactions. Human erythroblasts cultured with a methylcellulose clonal assay technique were studied with ultrastructural and cytochemical methods. The intact colonies contained only erythroblasts at a similar stage of maturation, and no macrophages were identified within the colonies. The cultured erythroblasts demonstrated many of the morphologic features described in vivo. Neutral and acid glycoconjugates identified on the plasmalemma stained in a similar way to that seen in vivo with a concanavalin A horseradish peroxidase bridge and dialyzed iron technique. Weak acid phosphatase activity and ferritin-like particles were demonstrated in siderosomes, but these structures lacked peroxidase activity and dialyzed iron reactive acid mucosubstance. Transmission and scanning electron microscopy identified numerous processes which connected early erythroblasts and resembled those described in the marrow of patients with dyserythropoietic disorders. These findings suggest the presence of abnormalities in cultured erythrocytes which should be considered when evaluating pathologic specimens in vitro.


Glutaminase activity in rat skeletal muscle mitochondria. Isolated rat skeletal muscle mitochondria took up about 40-ng-atoms O per mg protein, with glutamine as the only respiratory substrate. The mitochondria incubated in the presence of glutamine and KCN formed both ammonia and glutamate in equivalent amounts. The experiments reported here provide suggestive evidence that rat skeletal muscle mitochondria contain glutaminase (L-glutamine amidohydrolase EC 3.5.1.2.) activity.


Anomeric compositions of D-glucose in tissues and blood of rat. The anomeric compositions of D-glucose in the liver, kidney, heart, blood and plasma of rat were determined by our methods for the assay of D-glucose anomers and the percentages of the beta-anomer were found to be 61.8, 61.0, 62.4, 62.7 and 62.9, respectively.


Effect of pentobarbital on the synaptosomal activity of acetylcholinesterase in Mongolian gerbils. The influence of Na pentobarbital anesthesia on the activity of specific and nonspecific cholinesterase was studied in the synaptosomal fraction of Mongolian gerbils' brains. These studies have shown that this barbiturate inhibits the specific activity of acetylcholinesterase only.


Selective inactivation of catalase during protoporphyrin induced photohemolysis of human red blood cells. The level of some enzymatic activities in red blood cells before and after photohemolysis induced by protoporphyrin IX was studied. A 30% decrease in catalase activity was found both in normal erythrocytes and those from patients affected by favism. Other proteins though present in larger amounts inside the erythrocytes are not affected by the photohemolytic process.


Anomalous stability of insulin at very high pressure. Insulin is unaffected by pressures of 48,000 b in the solid state at room temperature, as elucidated both by spectroscopic measurements and bioassay. Its compression curve is reversible. The presence of water does not alter this property. Of a number of other proteins investigated insulin appears to be unique with regard to its pressure stability. The relative rigidity of the molecule combined with its small size may account for some of these properties.


Effect of parathyroidectomy on the fasting-refeeding response in the rat colon. Following fasting and refeeding, the colonic epithelium of the rat exhibits a marked hyperplasia. This response is of a similar magnitude but of a longer duration to that observed in mice. This response is not affected by reducing serum calcium levels to those reported to alter normal tissue proliferation in vivo.


Biotin as a regulator of some haematic parameters and of DNA-content of the liver of old rats. Biotin administration to old rats (28 months) causes in the blood an increase of ATP, glucose, triglycerides, alkaline phosphatase and a decrease of cholesterol and acid phosphatase; in the liver DNA and electrostatic interactions between DNA and histones are increased. Such parameters come within the values shown by adult rats.


The alcohol syndromes: the intrarecombigenic effect of acetaldehyde. Sister chromatid exchange was studied in lymphocyte and fibroblast cultures. Alcohol caused no disturbance under normal conditions but an acetaldehyde level above 40 muM inhibited cell multiplication and elevated SCE considerably. A high acetaldehyde level is thought to elicit the fetal alcohol syndrome, a view supported by clinical and experimental observations.


Distension of the reticulum decreased food but not water intake by sheep. The intakes of pelleted alfalfa by hungry sheep were depressed in a rectilinear manner in relation to the amount of water (0-800 ml) added to a balloon in the reticulum (p less than 0.005). Since the consumption of water by thirsty sheep was not altered by these treatments, the reduction in food intake produced by distending the reticulum was a specific response. The intakes of food were not significantly affected by distending the rumen with 800 ml water in a balloon so it is possible that the amount of fill in the reticulum rather than in the rumen may be important in signalling satiety in sheep.


Correlation between acidic phospholipids and serotonin and between lysolecithin and dopamine in ganglia of the marine mussel, Mytilus edulis. These studies have demonstrated a positive correlation between the acidic phospholipids and the serotonin content and between the lysolecithin and the dopamine content in the cerebral, pedal and visceral ganglia of Mytilus edulis. These relationships were further supported by experiments utilizing 6-hydroxydopamine and 5,6-dihydroxytryptamine.


Effect of electroconvulsive treatment on serum dopamine-beta-hydroxylase activity in man. The activity of dopamine-beta-hydroxylase was measured in the serum before and immediately after electroconvulsive treatments. No significant difference was observed, suggesting that the seizures did not cause an increase in the peripheral sympathetic tone.


Effect of preoperative stress on serum cholesterol level in humans. Effect of preoperative stress on serum cholesterol level in 65 patients of different age groups in a surgical ward, has been studied. In all age groups, statistically significant rise of cholesterol in serum preoperatively was notices as compared with serum cholesterol level at the time of discharge from hospital. The preoperative rise of cholesterol varied from 39 to 56.9% in this series. These findings support previous reports of the effect of mental tension on serum cholesterol level.


An escape phenomenon from water and sodium retention induced by propranolol in rats. Rats given a daily dose of propranolol 45 mg/kg b.wt retain water and sodium for 4 days, escaping during the 5th and 6th days in which their excretions are larger than basal values. Afterwards, in the period studied, they make a new retention and clearing is less accentuated. No relationship could be found between these retentions and plasma renin activity or renal renin content.


Efficacy of ethanol as a discriminative stimulus in ethanol-preferring and ethanol-nonpreferring rats. Rats which exhibited a preference for drinking a 6% w/v solution of ethanol in a free choice situation did not differ in their sensitivity to ethanol from animals exhibiting an aversion for ethanol, as measured by leaning rates in a T-maze task in which ethanol served as a discriminative stimulus.


Effect of desipramine on the contents of some free amino acids of mouse brain. I.p. injections of desipramine-HCl (100 mg/kg) produced decreases in the contents of several amino acids of mouse brain after 1 h. Using a 10-100 mg/kg range of doses, these effects appeared to be dose-dependent for alpha-alanine and aspartate. These changes may be due, in part, to a decrease in cerebral oxidative metabolism (Krebs cycle activity) which occurs secondarily to desipramine-induced hypothermia.


Aflatoxin metabolism and absence of cytochrome P-450 in rat colon tissue during vitamin A malnutrition. Homogenized mucosal linings prepared from vitamin A adequate and deficient male rats were used in metabolic studies of aflatoxin B1 (AFB1). Cytochrome P-420 was identified in both groups which metabolized AFB1 to 4 metabolic products in vitro. The implications of this observation are discussed in relation to colon carcinoma.


Studies on the etiology of the experimental neuropathy from industrial adhesive (glues). Chickens treated by paintbrushing with glue distillate (used in shoe industries), hydrocarbon mixture and TOCP in hexane, developed paralysis (4/5); in these, we have demonstrated a diffuse degeneration of the myelinic sheath of the peripheral and central neurites. Besides TOCP, cyclohexane (because of its higher concentration in the glue distillate and in the hydrocarbon mixture) may be indicated as responsible for occupational neuropathy.


Influence of the thymus on the incidence of secondary and parabiotic disease. The secondary disease in P leads to F1 strain combination depends upon the immune status of both partners. It is most clearly expressed if both donors and recipients are immunologically crippled by thymectomy and irradiation. Conspicuous reduction in the immune potential of parental parabionts induced by thymectomy and irradiation displayed their marked incidence of parabiotic death.


Dexamethasone-induced neutrophilia. Negative correlation with increased plasma adrenaline concentrations. Maximal increments in adrenaline and dexamethasone (DXM) plasma concentrations were observed c15 (T50 40 min) and 30 (T50 210-240 min) minutes after an i.v. DXM dose (6 mg/m2 BSA) in man. There appears, however, to be no direct interaction between these agents in the development of induced neutrophilia, which occurs c240 min postinjection.


Changes in placental permeability to corticosterone and estradiol-17beta toward the end of gestation in the rat. Radioactivity in the fetal plasma 1 h after maternal injection of 14C-4-corticosterone or 14C-4-estradiol-17 beta on day 21 of gestation was markedly higher than that 1 h after injection on day 22. Radioactivity in the maternal plasma was not different on these 2 days. The results suggest that the placental permeability to steroids from the mother to the fetus declines toward the end of gestation in the rat.


Variations au cours de la journée de l'incorporation in vivo de la leucine tritiée dans les protéines du cervelet et du cerveau du jeune rat normal et hypothyroïdien. Daily variations of the in vivo [3H] leucine incorporation into the cerebellar and cerebral proteins of the normal and hypothyroid young rat [(author's transl)]. In the normal and hypothyroid 6-day-old rat, the specific radioactivity (RSA) and the relative RSA (ratio of the RSA to the [3H] lecine concentration of the acido soluble phase) of the cerebral and cerebellar proteins, changes during the day synchronally. They show a maximum at 15.00 h and a minimum at 0.300 h. At all stages studied, these values are significantly lower in the hyothyroid animals than in normal ones.


Purification of the cytosol oestradiol-receptor complex from foetal guinea-pig uterus using electrofocusing on polyacrylamide plates. The 3H-oestradiol receptor complex obtained from the cytosol fraction of foetal guinea-pig uterus was purified by the following steps: column chromatography in Sephadex G-15 and Ultrogel, and by electrofocusing on polyacrylamide plates. In the final step a concentration of 15-17% of the foetal uterine oestradiol receptor protein was obtained. The isoelectric point (pl) of this receptor was determined to be 6.1-6.2.


Effects of pregnancy and lactation on the serum selenium content of rats. The serum selenium content of rats was measured by means of neutron activation analysis. It was found to drop between the 12th day of pregnancy and term and to return to its original level within 2 days after delivery. Hysterectomy on the 10th day of gestation prevented this decrease. Nursing had no influence on the element level. The findings suggest that placental secretions might be involved in the control of the serum selenium content of rats during pregnancy.


A new method of measuring functional recovery after crushing the peripheral nerves in unanesthetized and unrestrained rats. The distances between the first and fifth digits and between the second and fourth digits of the rat's hind paw were measured after crushing the sciatic nerve. The distances between the digits recovered significantly faster in weak nerve crushing than in strong crushing, and faster in distal nerve crushing than in proximal crushing. These results suggest that this method is available for evaluating the functional recovery after nerve crushing.


[Effect of bonaphthone on embryogenesis in white rats and mice]. Results of testing the embryotropic activity of bonaphthone used in different doses (700; 400; 100; 50 and 2 mg/kg) are reported. With its oral introduction to pregnant rats bonaphthone, given in doses at the level of the therapeutid one (2 mg/kg) and exceeding it by as much as 25 times (50 mg/kg), was found not to produce any damaging effect on the fetus. With its action in doses of 100 and 400 mg/kg a slight embryotoxic effect was noted. In the sublethal dose of 700 mg/kg the preparation displays a moderate embryotoxic action and produces a number of circulatory changes in the fetuses. It is concluded that bonaphthone displays no teratogenic properties.


[Effect of hypoxia and hyperthermia on the processes of lipid peroxidation in the rat liver against a background of the action of gutimine and unsaturated amines]. Following the action of extraordinary stimulants (hypoxic hypoxia, hypoxia+hyperoxia, hypodynamia+hyperthermy) animals demonstrate accumulation of malonic dialdehyde with a simultaneous fall of antiradical activity of the liver tissue. A preliminary introduction to rats of acetylene amines--1,4 bis (3-morpholinopropynyl) benzol 3,4,5-(morpholinopropynyl)-1-methylpyrazol and also of tocopherol antioxidant and gutumine antihypoxant averts activation of the lipids peroxidation processes. The inhibition of peroxidation with the studied agents is attended by stabilization of lyzosomal and mitochondrial membranes. Unsaturated amines prevent destruction of the organelles membranes provoked by the UV-irradiation and incubation at 37 degrees C (pH--4.7).


[Dynamic circulation of toluene in the human body under industrial conditions]. In deep print departments an investigation of dynamic toluene circulation in the organism of individuals occupationally exposed to its effects was carried out. Gas chromatography was employed in studying environmental atmospheric conditions in the departments in determining the proportion of toluene in the expired air, blood and hippuric acid in the urine. Quantitative correlations between the toluene content in the air and its concentration in the blood and in the expired air, as well as between the exposure and excretion of hippuric acid were ascertained. Under a chronic exposure to the effects of toluene a significantly reduced peroxidase activity was recorded.


[Biliary excretion of nitrazepam and its metabolites in rats]. A single intravenous administration of nitrasepam (10 mg/kg) resulted in its excretion as free and conjugated metabolites in the bile of albino rats. The initial compounds, amino- and acetamido derivatives were deteced among free metabolits. Conjugated forms were recovered as N-glucoronides (5-nitro-2-aminobenzophenon and amine) and as O-glucoronides (C3-hydroxylated derivatives of nitrasepam and of acetamide). The presence of a considerable amount of nitrasepam and of its metabolites in the rats' bile is suggestive of their enterohepatic circulation.


[Effect of serotoninergic substances on the brain potentials evoked by stimulation of the dental pulp]. Serotonin like M-serotonin blocking agent morphine and D-serotonin blocking agent diethalamide of lysergic acid is shown by the method of intravenous microinjections to lower and T-serotonin blocking agent tipindol--to increase the amplitude of primary responses from the dental areas of the brain cortex arising in stimulation of the dental pulp. It is suggested that the seroninergic system of the brain can through the intermediary of the M- and D-serotonin-receptors raise the activity of adrenergic and lower the activity of M-cholinergic structures participating in the formation of the functional system of pain reactions. An opposite effect can be accomplished through the medium of the T-serotonin receptors.


[Differences in the inductive effect of small doses of phenobarbital in rats depending on their age and sex]. The induction influence from low doses of phenobarbital introduced for 3 days (10, 10 and 20 mg/kg) on the detoxication rate of hexanal (100 mg/kg) in mongrel rats of different sexes and age was studied. Investigations included measurements of the protein, phospholipids and glycogen content in the liver and the use of continued lateral position time test. A three-day phenobarbital pre-treatment speeded up the hexenal detoxication in rats of all the age groups except the oldest ones (26--32 months). The acceleration as against controls was more spectacular in younger rats and sexually mature female rats (by comparison with sexually mature male rats). As contrasted to controls, a three-day administration of phenobarbital produced in test animals a rise of protein, phospholipids and glycogen content in the liver.


[Mechanism of the pyrazidol potentiation of the hyperglycemic effect of adrenaline]. The effect of pyrazidol, a new tricyclic antidepressant, on the change in the activity of the phosphorylase in homogenates of the liver and heart, produced by epinephrine and cortisol, was studied. Information obtained in intact rats showed pyrazidol capable of potentiating the action of epinephrine, such effect being absent in adrenalectamized animals. The beta-adrenoblocking agent (propranolol) and the alpha-adrenoblocking agent (phentolamine) lower the activation of the phosphorylase called forth both by epinphrine and by the latter together with pyrazidol. In adrenalectomized rats phentolamine exerts against the background of the cortisol and pyrazidol action a more pronounced effect than does propranolol. These data suggest that one of the factors responsible for the potentiation of the antidepressant hyperglycemic action of epinephrine and cortisol is a greater intensity of glycogenolysis, coming as a result of the phosphorylase activation.


[Effect of phenobarbital on the bile-forming function of the liver]. In tests with 178 albino male-rats the effect of phenobarbital in doses of 30--100 mg/kg, administered intraperinoneally singly and multiply, on the biligenic function of the liver was studied. The drug was found to act beneficially on the intensity of biligenesis, the synthesis of primary bile acids and their cojugation with taurine and glycine, as well as on the formation of and cojugation with glucoronic acid and secretion of bilirubin. This action of phenobarbital continues also in the progeny of the female rats receiving phenobarbital at different periods of pregnancy.


[Inhibiting effect of anabasine, anabasamine and lupinine alkaloids on ethanol action in mice]. Anabisis aphylla alcaloids anabasine, anabasamine and lupinine (1/6 and 1/3) DL50, intraperitoneally) lowered the locomotion excitation called forth by aethanol (2 mg/g, by mouth) in mice. Lupinine shortened roughly by a foctor of 3 also the duration of aethanol anesthesia. The reduced excitation was attended by falling a blood aethanol concentration, while shortening of the anesthesia period was not, this suggesting different mechanisms in two disclosed antialcoholic effects of the alcaloids.


[Pharmacological activity of progesterone derivatives]. Tests conducted on rabbits demonstrated that the progesterone derivatives--megestol-acetate, mepregnol-diacetate, melengestrol-acetate, megestro-capronate--display a higher progestagenic action than do progesterone and pregnene. Tests with rats revealed the contraceptive action to be highest with a long-term administration of low doses of mestranol and melengestrol-acetate (ratio of 1:50), or with introduction of mestranol and megpregno-diacetate (ratio of 1:20). When used together with mestranol megestrol-capronate manifests a greater ability of prolonged action and a higher effectiveness in the pre-implantation period as compared to a combination of megestrol-acetate and mestranol.


[Effect of dichlothiazide on the transport of organic substances in the kidneys]. Following a protracted introduction of dichlothiazide to rats (20 mg/kg) and to dogs (5 mg/kg) there occurs a marked increase in the tubular secretion of the cardiotrast and passage of urates with urine. A single and long-term administration of the drug to dogs did not have any substantial effect on the maximal reabsorption of glucose.


[Effect of cholagogic agents on volumetric natriuresis in rats with experimental dystrophy of the liver]. In experimental dystrophy of the liver in rats provoked by introduction of CCL4 the enlargement of the extracellular space is followed by a diminished excretion of sodium. Administration against this background of cholagogues--dehydrocholic acid (250 mg/kg), flaminum (50 mg/kg) and sodium selenite (30 mg/kg) for a space of 7 days helps restore the volumetric natriuresis. It may be assumed that in experimental dystrophy of the liver the process of formation of the natriuretic factor in the liver is deranged. Introduction of the cholagogues under study helps re-establish its formation. Under these circumstances the sensitivity of the rats' kidneys to the natriuretic factor remains practically unchanged.


[Lysis of fresh experimental thrombi under the action of a secondary adrenaline-heparin-fibrinogen complex]. It is shown that the epinephrine-heparin-fibrinogen complex, as well as a number of other complex compounds of heparin accomplish the prophylaxis of thrombogenesis at the initial stages of the process, the epinephrine-heparin-fibrinogen complex lysing the thrombi in an average of 48 minutes, while the complexes of fibrinogen-heparin and epinephrine-heparin do this in 2--4 hours. The complex heparin compounds exercise a thrombolytic action only on non-stabilized fresh thrombi with less than 15 minutes from the time of their formation.


[Effect of the plan of using antitumor preparations on their efficacy in sarcoma 37]. In tests staged on animals with sarcome 37 the effect of sarcolysine, cyclophosphamide, alexan and cytozine-arabinozine was studied with different scemes of their application. It was found that the degree to which the drugs inhibit the growth of sarcoma 37 depends on the scheme adopted for their administration. In the case of sarcolyzine the highest effect was achieved with a 5-day introduction of the drug (93 per cent of inhibition and resorption of some tumours); cyclophosphamide proved effective with its single administration or an introduction with an interval of 96 hours (78 per cent of inhibition), alexan was active with a 5- and 10-day courses (78 per cent of inhibition and resorption of some tumours). Sarcoma 37 is shown to be a suitable model for studying the activity of drugs depending upon the scheme of their application.


[Comparative study of cystamine conversion in the tissues of white mice and rats]. At different periods following introduction to animals of radioprotector cystamine its unchanged form and oxidation products (hypotaurine and taurine) in tissues were determined. In the tissues of mice and rats the cystamine metabolism is shown to proceed at varying rates, correlating with the level of basal metabolism.


[Differences in the efficacy of gutimine alpha-ketoglutarate in the hypoxic and motor forms of hypoxia]. When used in a dose of 100 mg/kg gutimine alpha-ketogluterate exerts a pronounced antihypoxic action in hypo- and normabaric hpoxic hypoxia ("lifting" albino mice in a pressure chamber to an "altitude" of 10000 m, rarefaction down to 198.7 mm of Hg, PO2--42 mm Hg, the chamber atmosphere containing 5.4 vol % of oxygen with the animals placed in the hermetically sealed chamber containing 5% of oxygen and 95% of nitrogen at 760 mm Hg). The absence of antihypoxic effect of the drug and exygen with the motor form of hypoxia (swimming test with the weight mass of 10 per cent of the body mass) bears evidence to the fact that the pathogenetic mechanisms in these two forms of hypoxia are dissimilar. An inference is drawn to the effect that the protective action of the drug may be associated with correction of the oxygen cycle in the organism.


The value of urinary pregnanediol estimation for monitoring early pregnancies. Urine samples from 76 pregnant women were tested for pregnanediol content during the first 6 weeks of pregnancy. Pregnanediol was measured by gas chromatography in 24-hour urine samples obtained once weekly from 76 randomly selected pregnant women 21, 28, 35, and 42 days after the last menstrual period. Pregnancy was ascertained by a positive hemagglutination inhibition test for human chorionic gonadotropin. In patients in whom the urinary pregnanediol content was less than 3 mg/24 hours the abortion rate was 81.5%, and 18.5% had normal pregnancies and births In patients whose pregnanediol content was greater than 3 mg/24 hours the abortion rate was 8.3%, and 91.7% had normal pregnancies and births. The 24-hour urinary pregnanediol excretion rate reflects corpus luteum function and can be considered as a means of monitoring pregnancy in its initial stage.


Salpingitis isthmica nodosa in female infertility and ectopic tubal pregnancy. Salpingitis isthmica nodosa has been studied in relation to female infertility and tubal ectopic pregnancy. The incidence of this lesion in a control Caucasian population was 0.6%, as compared with incidences of 2.86% in an ectopic group and 50% in a small infertility group undergoing tuboplasty. It is suggested that salpingitis isthmica nodosa should be considered as an etiologic factor in these reproductive disorders. Chronic tubal spasm is suggested as the underlying process.


Evaluation of stricture formation as a complication of vasopuncture and vasography in the guinea pig. Stricture formation at the site of injection for vasography has been observed clinically. An animal model was developed to evaluate this occurrence. Bilateral vasopuncture with a 25-gauge needle was carried out in 25 male guinea pigs. The sites of vas punture were marked with tantalum clips in the perivasal tissue. The left-sided vasa were injected with contrast material and the right sides with normal saline. These 50 vasa were evaluated for radiographic and histologic evidence of inflammation and stenosis 3 months following injection. Ninety-four per cent of the 50 vasa studied showed no significant stenosis. Those vasa exhibiting obstruction were in the first four animals studied, with no correlation as to which material was injected. This finding implicates technical factors as a cause for these results. In the guinea pig, vasopuncture with a fine-gauge needle and meticulous technique does not result in a significant rate of stenosis regardless of the medium injected.


Structural changes in the human vas deferens after tantalum clip occlusion and conventional vasectomy. In 15 human subjects, the vasa deferentia were occluded by applying two tantalum clips on one side and by conventional vasectomy with silk ligatures on the other. After 2 weeks, the occluded segments were recovered for histopathologic examination of serial sections. Obstructing the seminal tract did not, as such, produce any significant change in the vas: the distal and proximal segments appeared to be essentially similar and normal. At the actual site of occlusion, however, tantalum clips produced marked flattening of the tube, complete loss of lining epithelium, distortion of the muscular lamellae, and areas of hemorrhage. The lumen was converted into a narrow slit. Under the ligatures, the damage was largely confined to denudation of the mucosal epithelium. The mucosa of the intersegment left unexcised between two clips showed hyalinization, invasion by macrophages, and degeneration of the epithelium. The changes under the clips suggest that, although clip occlusion may offer several advantages, sterility cannot be reversed merely by removing the clips. The mechanisms of these changes, different in the case of clips and ligatures, are discussed and some possible long-term consequences are considered.


Scanning electrons and light microscopy of the equine seminiferous tubule. Changes within the equine seminiferous tubules during the cycle of the seminiferous epithelium were studied light and scanning electron microscopy (SEM). Once observed with SEM, tubules were sectioned and staged using light microscopy. As viewed by SEM, the weblike, spongy cytoplasm of germ cells or Sertoli cells in stages I and II extended over the entire height of the germinal epithelium. The cytoplasm of the basal portion of the germinal epithelium in stages III to VIII was similar to that in stages I and II. However, the cytoplasm which occupied the luminal third of the epithelium in stages III to VII was smooth appearance. The smooth-surfaced, periluminal cytoplasm diminished in stages VIII. Principal pieces of flagella from spermatids extended into the tubular lumina in all stages whereas the middle pieces extended into the lumen only in stage VIII. Later in stage VIII, the middle pieces, which were thickened with cytoplasm, were connected to the germinal epithelium by stalks. After spermiation, the diameter of the middle pieces was similar to that of ejaculated spermatozoa. Thus, the cytoplasm within the thickened middle pieces contributed to the formation of the cytoplasmic droplets.


The fragmented intrauterine device: an unusual complication of a Lippes loop. Fragmentation on removal of an effective and asymptomatic Lippes Loop is reported. The etiology of this event is hypothesized and the patient's managment is discussed. It is likely that fragmentation occurred as a result of material fatigue secondary to movement about the fixed, embedded tip. Surgical removal was effected.


Low-dose cortisone for male infertility. Thirty-eight males with idiopathic infertility were randomly treated with low-dose thyroid and low-dose cortisone. Pregnancy followed treatment with cortisone in 7 of 33 courses and followed treatment with thyroid in 4 of 30 courses (P = 0.5, not significant [NS]). The mean pretreatment count in all patients was 12.3 million/ml. The mean post-treatment count with thyroid was 11.2 million/ml as compared with 13 million/ml for cortisone treatment (P = 0.4, NS). Pretreatment motility was 45% as compared with 44% following thyroid treatment and 43% following cortisone treatment (P = 0.7, NS). The pregnancy rate seemed to correlate with pretreatment counts rather than with the type of treatment. The efficacy of low-dose cortisone for idiopathic fertility would seem to be in question.


Alterations of the clinically noninvolved skin in patients with malignant melanoma. An electron microscopic study before and after repeated application of BCG. Clinically noninvolved skin of 5 patients with metastasizing malignant melanoma (MM) has been investigated under the electron microscope before and 4 weeks after repeated BCG inoculations (4 X). Increased melanin content, giant and unusual melanosomes, signs of cellular activity and some degenerative changes of the melanocytes were observed both in nontreated and in treated patients. Langerhans cells were markedly stimulated containing melanosome complexes and membrane-bound inclusions of different size and shape. Presence of amyloid, macrophage and plasma cells were also observed prior to and after repeated BCG inoculation, however, cellular infiltration was increased after this treatment and several dermal Langerhans cells appeared. These observations suggest that alterations of the melanocytes occur in MM, which are not confined to the tumor area. Moreover, BCG treatment seems to stimulate the tissue reaction against the tumor, including the activity of Langerhans cells.


Untreated acrodermatitis enteropathica in adults. In the literature six cases of acrodermatitis enteropathica (AE1 are described in which the patients survived to adult age. In a few of these cases the symptoms diappeared at the onset of puberty, while in the rest the disease had a fluctuating course with long symptom-free intervals and an uncharacteristic symptomatology. Two cases are reported. In case 1 there remained only characteristic skin changes on the feet at adult age, in case 2 both skin and intestinal symptoms diappeared at adult age. For long periods this patient was invalidated through depressions, a symptom which is characteristic of children suffering from an active AE. The same patient developed parkinsonism at a relatively young age. In both cases a very low serum zinc level essentially supported the diagnosis. It is possible that AE in adults is underdiagnosed because of an uncharacteristic symptomatology.


HL-A antigens in Behçet's disease. A family study. Histocompatibility antigens (HL-A) were studied in a family with Behçet's disease (BD). All who had symptoms or signs of BD had either HL-A B5 or BW35, or both. The increased number of families with BD recently reported supports the suggestion that positive family history may assist the diagnosis of BD.


Ultrastructural and biochemical studies on a case of elastosis perforans serpiginosa. Ultrastructural and biochemical studies on the collagen and elastin fibres of the dermis from a patient with Elastosis perforans serpiginosa are described. Qualitative and quantitative alterations on collagen and elastin are shown, which give some evidence for considering the disease as a connective tissue defect.


Immunologic abnormalities in psoriasis: the inhibition of leucocyte migration by stratum corneum antigens. The migration inhibition of peripheral blood leucocytes by stratum corneum (SC) antigens extracted from psoriatic scales and normal skin was studied in 25 patients with psoriasis and 12 normal controls. In 44% of patients, the radius of the area of spontaneous migration in the absence of antigen was significantly reduced. 9 out of 25 psoriatic cases showed inhibition of leucocyte migration after the addition of both SC antigens. Migration inhibition with SC antigens was observed only in patients in whom the radius of spontaneous migration area appeared to be normal. The data did not confirm the evidence of delayed hypersensitivity to epidermal SC antigens in patients with psoriasis. The decrease of spontaneous leucocyte migration in psoriasis might be dependent on the influence of antibodies against stratum corneum and/or immune complexes coated on lymphocyte or leucocyte surface membrane.


The effect of coal tar distillate, cadmium sulfide, ichthyol sodium and omadine MDS on the epidermis of the guinea pig. In 20 guinea pigs 4 test areas were treated with a standard surfactant vehicle twice weekly for 3 weeks. In another 20 animals the same treatment was carried out with the addition of 1% cadmium sulfide on one area, of 10% coal tar distillate on another, 2% ichthyol sodium on the 3rd and 1% Omadine MDS on the 4th. At the end of the test in both animal collectives the number of mitoses in the basal cells of the epidermis (Colcemid method) and the thickness of the epidermis (microscopically) were determined in each of the 4 test areals. All 4 agents lead to a significant inhibition of mitoses compared with the surfactant vehicle. Coal rat also produces an acanthosis. The mitosis inhibition supports the opinion that these agents are suitable for the treatment of dandruff.


Cutaneous manifestations associated with aminoaciduria. Report of two cases. This is a report of 2 cases revealing photosensitivity in association with aminoaciduria. The first is a patient with psoriasis and the second, a patient with Ehlers-Danlos syndrome, mitis type. The display of the above combinations seems peculiar. The psoriatic lesions become confined mainly to the exposed surface and intermingled with those of photodermatitis forming lesions which are a mixture of the two processes. In the case with Ehlers-Danlos, the disease presented rupioid plaque-like erythematous oozing lesions which seem somewhat different from those of the photodermatosis yet known.


[Perforating osteoma--regional acquired osteomatosis (author's transl)]. Three osteomas had spontaneously appeared on the lateral side of the arm in a 44-year-old woman; one of them showed a slight depression in its center and proved histologically to be an osteoma perforans.


Effects of somatostatin and verapamil on growth hormone release and 45Ca fluxes. Increasing the extracellular K+ concentration to 71 mM causes a phasic release of growth hormone and efflux of 45Ca from perifused bovine pituitary cells. Verapamil (20 micron) partially inhibits the initial phase of growth hormone release and 45Ca efflux and completely inhibits the second phase. Somatostatin (1 microgram/ml) partially inhibits both phases of growth hormone release but does not modify 5+-induced 45Ca efflux. Incubation of pituitary cells in 71 mM K+ increases 45Ca incorporation; verapamil (20 micron) completely prevents, and somatostatin (1 microgram/ml) partially inhibits, the K+-induced increase in 45Ca incorporation. The results suggest that 71 mM K+ increases both calcium entry into the cells and calcium redistribution within them, and that verapamil only inhibits the K+-induced calcium entry. Somatostatin may inhibit calcium entry into tissue stores.


A high-performance liquid chromatography method for hemoglobin A1c. Hemoglobin A1c (HbA1c) is a glycosylated derivative of hemoglobin and is one of a family of derivatives whose concentrations are elevated in patients with diabetes mellitus. Published methods for the measurement of HbA1c are relatively tedious and require modest amounts of blood. A high-performance liquid chromatographic (HPLC) method for the determination of HbA1c is presented. The method is rapid (20 minutes), precise (coefficient of variation of 5-10 per cent), uses small amounts of sample (3 microliter.), can be automated. A sample preparation technique using filtration was developed that shortened and simplified preparation of venous blood and allowed use of capillary samples. HbA1c was measured by this method in three age-stratified groups of controls and a group of insulin-requiring juvenile diabetics. There was clear separation of HbA1c values between all normals (5.9 +/- 1.3, 5.6 +/- 0.7, 7.1 +/- 0.9 per cent) and the diabetics (12.1 +/- 2.4 per cent). Use of this method can facilitate large-scale clinical investigations and permit biochemical investigations of the metabolism and formation of hemoglobin A1c where small sample sizes are necessary.


Glucose-induced alterations of the metabolism of an isolated capillary preparation. A preparation of blood capillaries was isolated from the rete mirabile of the eel swin bladder. The capillaries, incubated for two hours at 37 degrees C. in Krebs-Ringer bicarbonate buffer with 5 mM glucose, contained 29.3 +/- 4.6 nmoles of sorbitol per gram and released in the medium 725 +/- 60 nmoles of fructose per gram. When glucose in the medium was raised from 5 to 30 mM, capillary sorbitol and medium fructose rose by approximately 100 per cent. There were no accompanying changes in capillary water content as determined by the ratio of wet weight to dry weight and by the difference between water-3H space and inulin-14C space. Respiration of capillary tissue was lower at 30 mM glucose than at 5 mM glucose. The addition of 30 mM mannitol to a medium containing 30 mM glucose did not restore the oxygen uptake by capillary tissue to values obtained with a medium containing 5 mM glucose alone. It is concluded that the polyol pathway is operative in vertebrate blood capillaries. At high medium glucose concentration, the activity of the pathway is enhanced, respiration is depressed, and water content is unchanged


Loss of insulin response to ingested amino acids after jejunoileal bypass surgery for morbid obesity. Amino acid tolerance tests were performed before and after jejunoileal bypass surgery for morbid obesity to determine whether an enteric factor(s) originating in the bypassed jejunum and/or ileum potentiates the insulin response to oral nitrogen loading. Preoperatively a 30-gm. mixture of amino acids given orally evoked a larger peak insulin than an intravenous load yielding comparable plasma amino acid elevations (82 +/- 17 muU./ml versus 38 +/- 8 muU./ml., p less than 0.05). Four months after operation, basal insulin concentrations were 46 per cent (p less than 0.001) of preoperative values. After surgery the response to intravenous amino acids was preserved when expressed as percentage increase above basal. In contrast, the peak increment and the percentage increase in insulin secretion after 30-gm. oral amino acid loading was significantly blunted (p less than 0.005). A smaller amino acid load (16.5 gm.) was given preoperatively to duplicate the plasma amino acid elevations seen postoperatively with the 30-gm. mixture given by mouth. The insulin response postoperatively was still significantly lower (167 +/- 33 per cent versus 98 +/- 16 per cent, p less than 0.05). After various explanations for the diminished postoperative insulin release following oral amino acid ingestion are considered, the results are best explained by the loss of an enteric insulinotrophic factor(s) normally released by the bypassed portions of jejunum or ileum in response to ingested protein.


Quantitative vitreous fluorophotometry. A sensitive technique for measuring early breakdown of the blood-retinal barrier in young diabetic patients. Vitreous and aqueous humor fluorescein concentrations were measured one hour after graded intravenous fluorescein was given to 20 juvenile diabetics, ages 20 to 40, with and without retinopathy, and to 12 controls of similar age. Vitreous fluorescein concentrations were significantly higher in diabetics, indicating breakdown of the blood-retinal barrier. Mean vitreous fluorescein values were 10.66 +/- 0.65 for the diabetics and 4.28 +/- 0.37 ng./ml. for the controls. Breakdown of the blood-retinal barrier was also confirmed in diabetics under the age of 20 without retinopathy. The blood-aqueous barrier was similarly altered in diabetics. Vitreous fluorophotometry quantitatively measures breakdown of the blood-retinal barrier, possibly the earliest detectable ocular vascular abnormality in juvenile diabetic patients.


Decline of pulmonary function.

Decline of pulmonary function. Pulmonary function declines with normal aging, but environmental pollutants such as cigarette smoke undoubtedly hasten the process--probably by triggering inherent deficiencies or irritating endogenous changes.


Using computerized tomography to identify neurologic problems. Computerized tomography (CT) scanning accurately identifies neurologic abnormalities in many elderly patients, often making it possible to differentiate symptomatic neurologic changes of normal aging from treatable pathologic states such as occult masses and cerebral infarction producing much the same symptoms. The scan also singles out patients in whom further diagnostic measures are necessary. The advantages of CT--low morbidity, noninvasiveness, and high sensitivity--far outweigh its limitations. Concomitant cerebral atrophy and metabolic imbalance do not significantly affect diagnostic accuracy. Risks are minimal, related chiefly to contrast allergy, and occasionally to anesthetics for patients who cannot remain motionless during the procedure.


Considering "social nutrition" in assessing geriatric nutrition. "Social nutrition" is of great importance to the well-being of elderly people, who often are socially isolated and hungry for interaction with others. The physician should be sensitive to this need and explore the geriatric patient's social situation. The physician's suggestions have significant impact on elderly patients, and a social prescription often enhances a medical regimen. It is important to suggest to these patients attainable goals, such as social contacts at mealtimes. Even the Meals on Wheels program may help meet their social needs.


Diagnosing and treating myxedema and myxedema coma. Every patient with myxedema has hypothyroidism, but not every hypothyroid patient has myxedema. It often is possible to diagnose myxedema on clinical grounds alone. Characteristic symptoms are weakness, cold intolerance, mental and physical slowness, dry skin, typical facies, and hoarse voice. Results of the total serum thyroxine and free thyroxine index tests usually will confirm the diagnosis. L-thyroxine is the treatment of choice for myxedema, but it must be given to elderly patients with extreme caution. The transition from the hypothyroid to the euthyroid state brings about changes that put an added burden on the heart. The patient's clinical status and results of thyroid function tests determine the proper maintenance dose. Myxedema coma is rare but often fatal. It occurs most often in elderly women and may be mistaken for one of the chronic debilitating diseases common to this age group. Primary treatment is prompt administration of adequate doses of thyroid hormone--either l-throxine given intravenously of L-triiodothyronine given by nasogastric tube. It also is essential to identify and treat the condition precipitating the coma.


Defining and treating urinary infections. Urinary infections increase not only with age but also with progressive disability and dependence. The reasons are not clear, but the rising incidence may be due to loss of bactericidal prostatic secretion in men; an increase in residual urine with ischemia of the bladder wall in both sexes; and recumbency, poor nutrition, and perhaps decreased defficiency of the autoimmune system in elderly patients with chronic diseases. Laboratory diagnosis of infections depends on the demonstration of 100,000 or more organisms of a single type in the urine. Fewer than this, or the presence of two or more types of organisms, indicates contamination. Careful collection and handling of urine specimens are necessary to avoid false-positive results. Pyelonephritis and acute cystitis are symptomatic infections and require antibiotic treatment. Chronic bacteriuria, however, usually does not produce symptoms, and since there is no clear evidence that it causes changes in renal function, antibiotic therapy usually is unnecessary.


Is low-renin hypertension an overdiagnosed syndrome? The controversy surrounding low-renin hypertension ranges from the concept that it carries a favorable prognosis to the therory that it a form of nephrosclerosis. At least a part of the debate may result from the use of different methods of classifying patients with this condition. The study presented here clearly shows that age and sex have an important influence on plasma renin activity. Women had lower values than age-matched men, and studies in normal volunteers showed that plasma renin activity decreases with age. Other factors also affect renin profiling. Diabetes is associated with renin suppression, and blacks have lower values of plasma renin activity than whites. In addition, use of anti-inflammatory drugs such as aspirin significantly lowers renin levels. Since some of these variables have not been considered in published studies to date, it would seem that the true incidence of low-renin hypertension among hypertensives is lower than the accepted figure of 25%.


Geriatric gynecologic problems increasing. Over a 3-year period, the percentage of geriatric patients with gynecologic problems treated in one Canadian hospital almost doubled. Pelvic pain, uterine bleeding, and voiding problems were the most common symptoms. Concomitant diseases existed in 60% of the patients, with cardiac and pulmonary problems the most frequent. Uterine fibroids and genital cancer were the most common pathologic diagnoses. Hysterectomy was part of the operative procedure in 37 of 50 patients, and these operations required more time and longer postoperative hospitalization than others. Complications developed in 24% of the patients, with cellulitis, phlebitis, and fever seen most often.


Spontaneous variations in level of arousal among aged individuals. Correlations with functional abilities and mental performances. The aim of this study was to assess whether spontaneous interindividual variations in arousal level appreciated by telemetric recordings of physiological variables were related to mental performance and functional ability in institutionalized aged subjects. The sample studied was made up of 18 subjects (16 women and 2 men) aged 82-97, living in an old age home in Paris. Telemetric recordings of EEG, EKG, EMG and EOG were obtained over 8-hour periods, during the subjects' normal daily activity schedule. The Stockton Geriatric Rating Scale (SGRS), Benton's Visual Retention Test (VRT) and the Trail Making Test (TMT) were independently used to assess behaviour and mental performance of these aged persons. All correlations between telemetric data and psychological evaluations (the psychometric tests as well as the rating scale) were highly significant, even once the influence of the cultural level was controlled.


Aortic lathyrism and atheroma in the rat by prolonged hyperlipidic diet. Constant, deep, extensive aortic atheroma can be induced in rats that are athero-resistant. Two main factors are involved in this experimentation: (1) Parietal alteration following chronic experimentation with beta-aminopropionitrile (BAPN, 8 weeks) and a metabolic factor with hyperlipid diet. Electronmicroscopic examination has shown progressive lesions in the elastic framework and modifications of cells in the media with dedifferentiation into fibromyocytes and also multiply. The changes are responsible for hyperplasia of the intima as well as its thickening and collagenization. They support observations made in man during aortic aging. (2) A metabolic factor with hyperlipidic diet. This diet given at various times during intoxication causes lip deposition in the intima and substantial penetration into the media when the lesions are developing.


Age differences in short-term memory and cell loss in the cortex of the rat. Studies with human and animal subjects have indicated age declines in short-term memory and cell loss in the cortex. Cell loss has been estamated by descriptive nonautomated methods. Declines in short-term memory may be related to reduced learning, movtivation, motor capacity, or some combination of these factors. Passive-avoidance tests of memory minimize these factors. Direct correlational studies on learning and memory in relation to cell loss in the same subject are not feasible in man and they have not been reported previously in animals. The aims of this study were to examine age differences in learning and short-term passive-avoidance memory in relation to cell packing density in the visual cortex of the Fisher 344 rat. Cell counts were made with a computer-guided, automated, image-analyzing system (TAS, Leitz). The following observations were made: (1) significant age differences in 2- and 6-hour short-term passive-avoidance retention or memory between mature and senescent rats were related to nonsignificant age differences in original learning inferred from starting latencies, running time and running distance and (2) sd compared to mature rats were associated with significant differences in neuron but not glia-vascular cell density in area 17 in the presence of nonsignificant age differences in cortical depth and brain weight. Aims of further studies are to establish the role of cell loss from the hippocampus in loss of short-term spatial memory with age and to develop criteria for differential counting of small neurons, glia, endothelial cells and pericytes.


Tissue specificity and age changes for the pattern of the H1 group of histones in chromatin from mouse tissues. Polyacrylamide gel electrophoresis of the H1 group of histones extracted from different rat and mouse tissues shows a different pattern of fraction (H1, H1 degrees, H1 degrees met) when the two species are compared. Different tissues of each species also have a different pattern of H1 histone fraction and subfraction. However, the age-associated changes of mouse H1 histones from liver and spleen chromatin show the same type of alteration of fraction ratios which had been demonstrated in our earlier research with rat tissues. In both species there is a relative increase of the F1 degree and F1 degree met fractions in tissues from old animals. The presence of the F1 degree fraction in only non-dividing cells suggests that there may be an age-specific type of chromatin condensation.


Psychiatric illness in the elderly. A comparison of GP records and survey findings. The GP records of 200 elderly people living at home were scrutinized and estimation made of physical and psychiatric disability. These estimations were compared with those made independently by a psychiatrist interviewing the subjects at home. There was a reasonable agreement between the two assessments of functional disorder and between the two assessments of physical disabilities. Whereas the survey psychiatrist's diagnoses of mental disorder correlated positively with the presence of physical illness, this did not hold for those considered to have evidence of psychiatric illness using GP records alone. The duration of a positive psychiatric history obtained from GP records was consistent with a discrimination between late onset (recent) and chronic neurosis.


The decrease in noradrenaline concentration in the posterior tibial artery with age. The concentrations of noradrenaline and adrenaline were studied in specimens of the posterior tibial artery obtained from 18 subjects at postmortem examination. The mean noradrenaline concentration was 167 ng/g artery (range 17-449 ng/g) and the mean adrenaline concentration was 5 ng/g (range 0--21 ng/g). There was no difference in noradrenaline and adrenaline concentrations expressed in ng/g between male and female subjects. Expressed in ng/cm artery the arterial noradrenaline concentration was insignificantly lower in the females than in the males. The arterial noradrenaline concentration decreased considerably with age and to the same extent in both sexes.


Comparison of "early gastric cancer" in Britain and Japan. Before the introduction of endoscopy, four out of 720 cases of gastric cancer were diagnosed before the cancer had breached the muscularis propia, an incidence of 0.5%. Using endoscopy and endoscopic biopsy, 10 out of 101 cases of gastric cancer were diagnosed at this "early" stage, an incidence of 10%. Their clinical, morphological, and histological characteristics are compared with those of Japanese "early gastric cancers" and reveal a remarkable similarity. The results of this study suggest that a higher proportion of British gastric cancers could be diagnosed at an "early" stage by more intensive investigation of dyspeptic patients using up to date radiological techniques, fibreoptic endoscopy, and endoscopic biopsy.


Effect of glucocorticoids on gastrin secretion in man. In order to investigate the effect of glucocorticoids on gastrin secretion, plasma gastrin levels were measured by radioimmunoassay in patients with Cushing's syndrome and those treated with glucocorticoids. Fasting plasma gastrin levels were significantly higher in these patients than in normal subjects, with exaggerated response to food. Conversely, short-term treatment or intravenous infusion of glucocorticoids had no significant influence on gastrin secretion in normal subjects. The possible mechanism by which glucocorticoids cause hypergastrinaemia are discussed.


Effect of secretogogues on mucosal blood flow in the antrum and corpus of the stomach. Gastric mucosal blood flow in the rat was determined by the indicator fractionation technique of Sapirstein using Rb86Cl. Antral and corpus flow rates were determined in response to increasing doses of pentagastrin and histamine and the effect of vagotomy was determined. With progressive stimulation the antral:corpus flow ratio increased with both stimulants; however, vagotomy and noradrenaline reduced blood flow in both areas of mucosa. It is concluded that the antrum, as well as the corpus, actively responds to secretory stimulants by an increase in mucosal blood flow and support is provided for the theory that the antrum plays an active role in the control of parietal cell blood flow and secretion.


Clinical presentation of patients with "dyspepsia". Detailed symptomatic study of 360 patients. This paper describes the clinical presentation of 360 patients suffering from "dyspepsia" at the time of their initial visit to two hospitals in Yorkshire. Disease categories studied were cholecystitis, duodenal ulcer, gastric ulcer, gastric cancer, and "functional" dyspepsia, with at least 50 patients in each category. The findings of this series are contrasted with "textbook" descriptions of these conditions. Some contrasts are quite surprising-for example, most of the 360 patients claimed that their pain was not aggravated by food. It is suggested that one reason for diagnostic error in this area of medicine is that clinicians have a faulty mental "database" of information with regard to the presentation of the various diseases concerned.


Inhibitory effect of cimetidine on gastric acid secretion vagally activated by physiological means in duodenal ulcer patients. Vagal activation of gastric acid secretion by modified sham feeding in six patients with duodenal ulcer produced a peak acid response amounting to 52% of the peak acid output after pentagastrin stimulation (PAOpg). Cholinergic reflex stimulation of gastric acid secretion by fundic distension in another six patients with duodenal ulcer produced a peak acid response of 45% of PAOpg. Intravenous infusion of cimetidine in a dose of 100 mg/h markedly inhibited the acid sham feeding response by 90-100% and almost abolished the acid response to fundic distension. The results suggest that gastric acid secretion evoked by physiological vagal activation in man is profoundly inhibited by H2-receptor blocking agents.


Physiological factors influencing serum bile acid levels. This study defines the effects of fasting (prolongation of an overnight fast for a further four hours), feeding (the response to eating the three main ;solid' meals of the day), and cholecystokinin-induced gallbladder contraction (75-100 units of CCK given as a bolus intravenous injection) on serum individual bile acids in five to eight healthy control subjects. The serum conjugates of the two primary bile acids, cholic and chenodeoxycholic, were measured using sensitive specific radio-immunoassays. During fasting, there was no significant change in the levels of the serum individual bile acids (conjugates of cholate, 1.28 +/- 0.19; conjugates of chenodeoxycholate, 1.17 +/- 0.17 mumol/l). After breakfast, the serum conjugates of cholate and chenodeoxycholate increased significantly but thereafter the mean values remained high with less consistent responses to lunch and dinner, some subjects showing a peak and trough response to all three meals, while others showed a plateau response throughout the day. After breakfast, the serum chenodeoxycholate conjugates increased more rapidly (peak at 60 minutes when the concentration reached 2.07 +/- 0.30 mumol/l) and to a greater extent than the conjugates of cholate (peak at 90 minutes; 1.50 +/- 0.24 mumol/l). A similar pattern of results was seen after intravenous CCK, suggesting either preferential jejunal absorption of chenodeoxycholate conjugates and/or preferential hepatic clearance of cholate conjugates. These results provide essential background data for future studies of serum individual bile acids in intestinal and hepatic disease.


Assessment of the (14C) aminopyrine breath test in liver disease. Different methods of performing the (14C) aminopyrine breath test have been assessed. A tracer dose of 2 muCi without a loading dose and with a single breath collection at two hours was the method selected, since it gave the best discrimination between patients with hepatocellular diseases and normal subjects (5.2 +/- 0.2%, mean +/- SEM). Reduced values occurred in patients with chronic active hepatitis (with and without cirrhosis) (1.5 +/- 0.2%), alcoholic cirrhosis (1.7 +/- 0.4%) and hepatitis (2.5 +/- 0.3%), and late primary biliary cirrhosis suggesting defective microsomal function with respect to demethylation. Normal results were common in early primary biliary cirrhosis. Two weeks of prednisolone therapy caused some improvement in the breath test in nine of 10 patients with chronic active hepatitis. It is concluded that the (14C) aminopyrine breath test is a simple test for detecting hepatocellular dysfunction, but has no obvious diagnostic advantage over the determination of serum aspartate transaminase and two hour post-prandial bile-acids.


Jejunal monosaccharide, water, and electrolyte transport in patients with chronic pancreatitis. Jejunal perfusion studies were performed to assess water, electrolyte, d-xylose, and d-glucose transport in 16 patients with chronic calcific pancreatitis (eight with and eight without steatorrhoea) and in 10 control subjects. The patients with steatorrhoea demonstrated significantly less xylose, water, and electrolyte absorption than patients without steatorrhoea and control subjects, when an isosmotic slaine-xylose solution was perfused. On the other hand, when an isosmotic saline-glucose solution was perfused, the patients with steatorrhoea absorbed significantly more glucose, water, and electrolytes than control subjects. Significant correlation was demonstrated between the absorption of xylose as measured by the segmental perfusion technique and the peak serum xylose level during perfusion as well as the five-hour urinary xylose excretion after a 25 g oral dose of xylose. The xylose absorption measured by small bowel perfusion also correlated significantly with pancreatic juice amylase and trypsin concentrations obtained during a standard pancreatic function test.


Hyposplenism in inflammatory bowel disease. Splenic function was assessed in 35 patients with ulcerative colitis and 20 patients with Crohn's disease. Hyposplenism was diagnosed if there were Howell-Jolly bodies in the peripheral blood film or if there was prolongation of clearance from the peripheral blood of injected 51-Cr-labelled heat-damaged red blood cells. Thirteen of the patients with ulcerative colitis had hyposplenism as compared with only one patient with Crohn's disease. Conversely, heat-damaged red cell clearance values faster than the normal range were found in six out of the 20 patients with Crohn's disease. Four patients with hyposplenism and ulcerative colitis developed life-threatening septicaemia in the early postcolectomy period, two of these being further complicated by disseminated intravascular coagulation.


Relationship between splenic size and splenic function. The rate of clearance of 51Cr labelled heat-damaged red cells from the circulation has been compared with the dimensions of the posterior scan of the spleen in 79 cases including nine controls. A strong negative correlation was found between the clearance half-time and the parameters of the scan but, as there was a large variation about the regression line, in the assessment of hyposplenism determination of the rate of clearance of heat-damaged red cells cannot be replaced by the easier determination of spleen size by scanning.


Effect of bran particle size on stool weight. The increase in stool weight after feeding 20 g (dry weight) of bran daily was measured when this was of large particle size and after milling to small particle size. Twenty-eight investigations were carried out in 21 normal subjects. With coarse bran, stool weight was significantly greater than with the fine bran (mean 219.4 g/d coarse bran, 199-0 g/d fine bran: difference 20.4 g SE +/-6.4, P less than 00.1). The coarse bran also had a greater water-holding capacity (7.3 g water/g coarse bran, 3.9 water/g fine bran). Coarse bran was 2 1/2 times the volume of fine gran for a given weight and more fine bran will, therefore, be taken when bran is prescribed by the spoonful.


Cellulose-decomposing fungi of salt marshes in Egypt. Seventy-five species and three varieties which belong to thirty-four genera were identified from 74 soil samples collected from salt marshes in Egypt. The most frequent fungi were Aspergillus fumigatus, Aspergillus niger, Cladosporium herbarum and Alternatia alternata, followed by Aspergillus terreus, Curvularia spicifera and Penicillium notatum. Six genera were of moderate occurrence: Penicillium, Fusarium, Curvularia, Rhizopus, Stachybotrys, and Chaetomium. Five genera were of low occurrence: Paecilomyces, Cephalosporium, Epicoccum, Mucor and Myrothecium.


Effect of various inhibitors on the multiplication of BLE bacteriophage in Bacillus licheniformis. A total of 40 substances were tested for their inhibitory effect on the multiplication of a bacteriophage in a growing culture of Bacillus licheniformis and their influence on bacitracin production. Acriflavine was the only substance which, at a concentration of 3 microgram ml-1, completely suppressed phage multiplication while having no effect on the growth of Bacillus licheniformis and on the production of the antibiotic.


Cellulolytic activity of some soil fungi. The cellulolytic activity of some soil fungi isolated from soil and decomposing pieces of plant material was observed to depend upon the genera of fungi, the nature of substrate and the temperature. The cellulase produced in the presence of cellulose powder was active against CMC and vice versa.


Development of activity of lymphocytes estimated from nucleolar morphology in infants. Changes in nucleolar morphology of the lymphocytes were studied in peripheral blood smears of infants from birth up to one year of life. A marked proportional increase of lymphocytes with active nucleoli was found during the first month.


Calculation of biomass production in algal suspension layer illuminated from two sides. Equations were derived for biomass production in optically dense algal suspension under the limit conditions of low- and very high-intensity stirring. A formula was obtained for the concentration of algae which gives maximum production at a given intake of radiation energy.


H-Y antigen: localization of the H-Y gene. Testicular development in a patient with deletion of the distal (fluorescent) segment of the Y chromosome is described. The presence of a normal dose of H-Y antigen was demonstrated by Goldberg's cytotoxicity test. It is concluded that the distal fluorescent segment of the Y chromosome is void of genes regulating H-Y antigen activity.


The lipid composition of human testis in testicular feminization syndrome. Testicular tissues obtained from 12 cases of testicular feminization syndrome were subjected to lipid analyses. The total lipids formed 2.75% of the total wet weight of the testicular tissue. Total cholesterol represented 30%, glycerides 33% and phospholipids 37% of the total lipids, respectively. Fractionation studies revealed that free cholesterol formed 66.7% and esterified cholesterol 33.3% of the total cholesterol. Triglycerides represented 89.89% and monoglycerides 10.11% of the total glycerides. Separation of phospholipids showed that phosphatidly choline (46.54%) and phosphatidly ethanolamine (24.89%) to be the major phosphoipid classes.


Pentobarbital anesthesia: interference in the effects of other pharmacological agents and of electrical stimulation on prolactin secretion. In adult male rats, a pretreatment regimen of serial injections of dexamethasone (1 mg/kg), morphine (20 mg/kg) and pentobarbital (40 mg/kg) was evaluated for use in conjunction with studies on the effects of hypothalamic electrical stimulation on prolactin secretion. Serum prolactin levels were measured before and 15 min after electrical and sham stimulation of the hypothalamic arcuate nucleus in rats subjected to either the pharmacological regimen or to pentobarbital anesthesia alone. Pentobarbital alone caused a transient rise in serum prolactin levels, which obscured any effect of electrical or sham stimulation; this interference was not overcome by the addition of dexamethasone and morphine treatment. Thus, the result indicate that the acute stimulatory affect of pentobarbital anesthesia on prolactin release may interfere with further manipulation of prolactin-controlling mechanisms, by either pharmacological or surgical means. Furthermore, the dexamethasone-morphine-pentobarbital pretreated rat does not provide an adequate preparation for studing the effects of electrical stimulation on prolactin secretion.


Hospital-sponsored groups offer viable malpractice insurance. Hospital - sponsored insurance organizations can offer their members many advantages, especially reasonable and stable malpractice insurance coverage and premium rates. To do so, they must ensure their financial stability through the support of the insured and through adequate reinsurance, compete effectively with commercial insurance companies, comply  with federal regulations regarding reimbursement to hospitals for premiums, and develop effective internal management.


Management structure review results in program consolidation. Outside pressures create a need for reappraisal of this hospital's management structure and decision-making process relative to resource allocation. To meet this challenge, a California medical center planned the consolidation of existing management programs, with additional emphasis on management planning.


A little knowledge is a useful thing.

A little knowledge is a useful thing. In any organization, particularly a large one, individuals and departments become isolated, thus making the overall effort of the organization less effective. At Lawrence (MA) General Hospital, a special two-year program was implemented to correct this fault and to make all hospital employees aware of the entire operation.