bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Difference in the Kinetics of Triglyceride Metabolism in Normal and Hypertriglyceridaemic Human Subjects
Authors: Olefsky Jerrold , Farquhar John W. , Reaven Gerald M.
Published: March 2011

Abstract. Several years ago we demonstrated in man that increasing plasma very low density lipoprotein (VLDL) triglyceride (TG) concentrations were associated with increasing VLDL‐TG production rates, and that this relationship described a rectangular hyperbola which could be characterized in terms of enzyme kinetics. Utilizing this approach Nikkilä and Kekki confirmed these observations in a large group of normal subjects. Moreover, after analyzing the Km and Vmax values of their subjects they noted a striking and important sex difference: females were found to have significantly lower Km values than men, whereas the Vmax values for the two groups were the same. This indicates that for a given VLDL‐TG production rate, females will have lower plasma TG concentrations. We have now studied 53 subjects with widely varying plasma TG concentrations, and have been able to detect a similar sex difference in subjects with hypertriglyceridaemia. Furthermore, we have noted a highly significant direct relationship between TG concentration and production in both sexes, and have found no relationship between an individual's Km value and his coexisting plasma TG level. These results allow us to conclude that: 1) the sex difference in TG kinetics which Nikkilä and Kekki originally note in normals can now be extended to include hypertriglyceridaemic subjects, and 2) in general, overproduction, and not underutilization, is the initiating event in most cases of hypertriglyceridaemia.
Relationship between Plasma Concentrations of Angiotensin I, Angiotensin II and Plasma Renin Activity during Cardio‐Pulmonary Bypass in Man*
Authors: Favre L. , Vallotton M. B. , Muller A. F.
Published: March 2011

Abstract. Several reports have demonstrated that the lungs are the most important site of conversion of angiotensin I to angiotensin II. The purpose of the present study was to assess the extent of extra‐pulmonary conversion in man, during cardiopulmonary bypass. Plasma concentrations of angiotensin I and immunoreactive angiotensin II, and plasma renin activity were simultaneously determined, using specific radioimmunoassays, during extra‐corporeal circulation in 13 patients undergoing major cardiac surgery. Generally the renin‐angiotensin system was stimulated during cardiopulmonary bypass with maximum values occurring at different time. A highly significant correlation was found between plasma renin activity and angiotensin I and II concentrations respectively, as well as between these two peptides. Positive correlations were also obtained between arterial and venous samples for plasma renin activity and angiotensin I and II. Thus the presence of angiotensin II in plasma in the absence of pulmonary circulation and its parallel variations with plasma renin activity indicate that converting activity by extra‐pulmonary sources is not negligible.
Glucose‐6‐Phosphate Dehydrogenase (G‐6‐PD) Hamburg, a New Variant with Chronic Nonspherocytic Haemolytic Anaemia
Authors: Gahr Manfred , Schröter Werner
Published: March 2011

Abstract. A new variant of G‐6‐PD with chronic non‐spherocytic haemolytic anaemia and very low activity, named G‐6‐PD Hamburg, was partially purified and biochemically characterized. It was found to have very high lability, an unusually high Km for G‐6‐P (2000 μM), increased utilization rates for 2‐desoxy G‐6‐P (133%) and galactose‐6‐phosphate (87%) and an abnormal pH‐activity curve. The electrophoretic mobility seemed to be normal. The leukocytes also revealed diminished G‐6‐PD activity. No impairment of bactericidal activity of neutrophilic granulocytes, as shown by a normal nitroblue tetrazolium reduction, could be demonstrated.
Bile Salt Metabolism and Bile Formation in the Rat with a Portacaval Shunt
Authors: Herz R. , Paumgartner G. , Preisig R.
Published: March 2011

Abstract. Biliary secretion of bile salts and bile flow were studied in Sprague Dawley rats with liver atrophy resulting from an end‐to‐side portacaval shunt and in sham‐operated controls. Three weeks after the shunt operation the liver to body weight ratio was reduced by 41%. This hepatic atrophy was accompanied by a reduced bile flow, which was 4.9 ± 0.3 (SEM) and 5.9 ± 0.2 (SEM) μ/min per 100 g body wt. in shunted and sham‐operated animals, respectively. By contrast, bile salt pool size and bile salt secretion were not significantly changed by the portacaval shunt. Shunted animals maintained a normal bile salt pool size by increasing bile salt synthesis per unit of liver weight. Thus, cholate synthesis, calculated from cholate pool size and 14C‐cholate turnover rate, was 3.3 ± 0.4 (SEM) and 1.8 ± 0.2 (SEM) μmol/24 h per g liver in shunted and sham‐operated rats, respectively. It is concluded that the atrophic liver in the rat with a portacaval shunt is able to maintain normal bile salt secretion rates and that the observed decrease of bile flow results from a diminution of bile salt independent bile formation.
A Mathematical Model for the Glucose Induced Insulin Release in Man
Authors: Cerasi E. , Fick G. , Rudemo M.
Published: March 2011

Abstract. The dynamics of the insulin response to intravenously administered glucose were studied in man. It was shown that (a) insulin response to prolonged stimulation is biphasic; (b) if the glucose stimulus is repeated with short intervals, inhibition of the second response occurs; (c) if longer time‐intervals are used, enhancement of the response is noted at the second stimulation. These findings suggest that when the pancreatic islets are exposed to hyperglycaemia, three kinetically distinct phenomena are initiated. Glucose induces almost instantaneous initiation of insulin release. Shortly thereafter, the pancreas enters a refractory phase. Thirdly, and at a later stage, a state of potentiation is built up in the islets. The effect of glucose on insulin synthesis is not considered here.—Against this background, and based on an earlier model, a mathematical model for the analysis of the glucose‐insulin interplay during glucose infusions was constructed. The model describes the eventual occurrence of glucosuria, changes in the concentration of glucose in its pool, and mimics the effects of regulatory hormones when hypo‐glycaemia appears. Insulin secretion is assumed to be controlled, in a multiplicative manner, by an immediate glucose function, a hypothetical potentiator that is slowly generated by glucose, and a negative factor with a shorter time‐course which corresponds to the refractory phase of the pancreas. A three compartment model is used in the simulation of the metabolism and distribution of insulin after its release. Finally, glucose utilization is described as a multiplicative function, related to the prevailing concentrations of glucose in blood and insulin in the extracellular space.—This model is able to simulate all the experimental situations described in this report, both in normal man and in the diabetic syndrome, in which insulin secretion shows varying degrees of impairment. The results of the simulation of individual experiments are given either as a set of theoretical parameter values, or described as the insulin response of the model to a standard, hypothetical glucose stimulus. The latter alternative is an attractive method for objectively evaluating the insulin response to a standard glucose load in clinical materials.
Rate of in vitro Incorporation of Precursors into Hepatic Lipids and Proteins in Patients with Extrahepatic Cholestasis
Authors: Stakeberg H. , Lundborg H. , Scherstén Tore
Published: March 2011

Abstract. Extrahepatic cholestasis in man is known to be associated with high phosphoglyceride and cholesterol concentrations in serum. Moreover, an abnormal lipoprotein, often referred to as lipoprotein‐X (LP‐X), appears in serum in cases of extrahepatic cholestasis.

The purpose of this study was to determine the rate of incorporation of precursors into hepatic lipids and proteins in vitro and to compare these changes with the lipoproteins in plasma in patients with extrahepatic cholestasis. The rate of incorporation of glycerol into triglycerides and into different classes of phosphoglycerides was determined. The rate of incorporation of leucine into proteins was also determined in liver slices from 15 patients with extrahepatic cholestasis and compared with controls. In cholestatic liver tissue, the rate of incorporation of glycerol into choline phosphoglycerides and into ethanolamine phosphoglycerides was significantly increased. The rate of incorporation of leucine into hepatic proteins was also increased significantly in these patients. The results suggest that the changed metabolism of phospholipids and protein in liver tissue in cholestatic conditions may contribute to the changes in the serum lipoprotein pattern.
The Influence of Body Weight and Cell Size on Lipogenesis and Lipolysis of Isolated Rat Fat Cells*
Authors: Hansen F. Mølgaard , Nielsen J. Høiriis , Gliemann J.
Published: March 2011

Abstract. A method for fractionating isolated fat cells is described. After fixation with osmium tetroxide, the cells are passed through a series of polyamide filters of decreasing mesh width and the number of cells on each filter is counted. — Isolated fat cells from ad libitum fed rats weighing 85–580 g were incubated with [U‐14 C]‐glucose (0.55 mM), fixed with osmium tetroxide and fractionated according to size. When the cells were obtained from one animal the conversion of glucose to neutral lipids per cell increased with increasing cell size just as well in the absence of insulin as in the presence of insulin (10 mU/ml). The following results were obtained from comparisons between animals of different weight: in the absence of insulin, the lipogenesis for cells of the same size remained constant irrespective of the rat weight, whereas in the presence of insulin the lipogenesis for cells of the same size decreased markedly when the rat weight exceeded about 300 g. It is Concluded that factors other than the cell size per se (e.g. age, degree of obesity) determine the responsiveness to insulin. — The hormone‐stimulated lipolysis was studied on unfractionated cell samples from ad libitum fed rats of different weights and the following was found: the glycerol release per 106 cells induced by ACTH and norepinephrine in maximally stimulating concentrations increased with increasing mean cell size or rat weight. In contrast, the glucagon‐induced lipolysis of cells from rats weighing 300–400 g was smaller than that of cells from rats weighing 100–120 g.
Enzyme‐Induced Modifications of Beta Cell Function
Authors: Lambert André E. , Henquin J.‐C. , Orci L. , Renold A. E.
Published: March 2011

Abstract. The effects upon immunoreactive insulin (IRI) release of beta cell membrane modifications induced by pronase, a mixture of proteolytic enzymes extracted from Streptomyces griseus, have been studied in isolated islets of Langerhans. Pretreatment of the islets for 90 min with 4 μg/ml pronase did not modify their IRI content; it slightly increased the basal rate of IRI release and potentiated the secretory response to glucose, leucine and tolbutamide during incubation. In perifused islets, the rapid phase of IRI secretion in response to glucose was more markedly enhanced than the late phase. After preincubation with 4 μg/ml pronase, glucose‐induced IRI release was reversible and abolished in the absence of calcium. Pretreatment for 90 min with 500 μg/ml pronase decreased IRI content of the islets by approximately 25% and provoked a pronounced but transient rise of basal IRI release. This was considered to be a leakage of IRI from damaged beta cells since it persisted in a medium deprived of calcium. The rapid secretory phase in response to glucose was preserved in perifused islets whereas the late phase was markedly reduced. The secretory responses to leucine and tolbutamide were almost completely obliterated. When pretreatment with pronase was carried out in a calcium‐depleted medium, basal IRI release from islets preincubated with 500 μg/ml pronase was only slightly increased whereas IRI secretion induced by glucose was inhibited by 40 and 65%, respectively in islets pretreated with 4 and 500 μg/ml pronase. These results indicate that pronase‐induced modifications of the beta cell membrane influence IRI secretion in a way which depends on the concentration of the enzyme and the presence of extracellular calcium. They are considered to support the hypothesis that membrane systems are involved in IRI releasing mechanisms.
Double Isotope Measurement of Peritoneal Clearance of Iodide and Albumin Loss during Peritoneal Dialysis in Man (Labelled albumin loss in peritoneal dialysis)
Authors: Mariani G. , Bianchi R. , Pilo A. , Palla R. , Toni M.G. , Cazzuola F.
Published: March 2011

Summary. 131I‐labelled Human Serum Albumin and 125I‐sodium iodide were used to measure protein loss from the peritoneum and peritoneal clearance of iodide in a group of 8 uraemic patients, each one being studied after a different number of dialyses.

Both albumin loss and iodide clearance reached a maximum at about the 10th dialytic treatment and then tended towards the initial levels.

Protein loss as determined isotopically was markedly lower than indicated by direct radioimmunoassay measurements performed in three cases. Fitting experimental points by a model which assumes direct passage of protein from plasma to peritoneal cavity suggests the presence of a “delay” pool between plasma and the peritoneal cavity itself (extravascular sites adjacent to peritoneum?).

The shorter retention time of the dialysis solution in the abdomen (4–8 minutes) seemed to us to cause lower protein losses than reported by authors using longer retention times.
Effects of Oral Contraceptive Therapy on the Orcadian Patterns of Cortisol and Thyrotropin (TSH)
Authors: Van Cauter E. , Golstein J. , Vanhaelst L. , Leclercq R.
Published: March 2011

Abstract. The daily variation of serum cortisol and thyrotropin (TSH) has been simultaneously recorded every 30‐min. in 4 women taking the same oral contraceptive containing oestrogens and progestogens and in 4 control women. The circadian rhythm of cortisol persisted under contraceptive therapy with about a 2.5 fold elevation of the mean level and amplitude of the basal rhythm. Theoretical equilibrium calculations of the circadian variations of the free, transcortin‐bound and albumin‐bound cortisol fractions showed that these elevations are explained qualitatively and quantitatively by an oestrogen‐induced increase of the same order of the transcortin cortisol‐binding sites. As a consequence of the already high saturation of transcortin in normal conditions, the magnitude of the variation of free cortisol level resulting from a burst in cortisol secretion varies with the time of day. The role of albumin as a buffer is thereby emphasized. The early morning maximum, characterizing the normal TSH daily pattern, appeared to be considerably enhanced in women under contraceptive therapy. If the circadian variations of TSH are driven by thyrotropir releasing hormone (TRH), these higher morning peaks probably reflect a higher burst of TRH secretion rather than an increased responsiveness of the pituitary to TRH secretion induced by contraceptive therapy. Finall these results do not support the hypothesis of a regulation of TSH circadian variations by an inhibiotry action of cortisol. Contraceptive therapy does not appear to play a role at the level of the central clock or on the resetting mechanism.
Alpha Subunit of Glycoprotein Hormone: Presence in Peripheral Serum after LHRH
Authors: Benveniste R. , Frohman L. A. , Bell J. , Spitz I. , Rabinowitz David
Published: March 2011

Abstract. A method is described for the selective measurement of human luteinizing hormone (hLH) and α subunit. The assays employ highly purified tracers of hLH and of subunit of human chorionic gonadotropin (hCGα) and a “mixed population” of antibody: Population I (directed against determinants on β subunit of hCG) and Population II (directed against determinants on a subunit of hCG). The former is present in greater concentration than the latter. When the mixed antibody is used at high dilution (1:1.2 × 106), Population II is effectively diluted out, and using 125I‐labelled hLH as tracer, the assay recognize hLH, hCG and their β subunits 20–50 times more sensitively than hCGα. When the mixed antibody is used at fivefold higher concentration, Population I is present in relative excess and acts as a “sink” for hCG, hLH and their β subunits. Under these conditions, using 125I‐hCGα as tracer, the assay recognize the α subunit 20 to 50‐fold more sensitively than hLH and hCG. These assays have been employed in the study of sera which have been filtered over Sephadex G‐100. Alpha subunit was detected in serum within minutes after intravenous injection of luteinizing hormone releasing hormone (LHRH) in four subjects tested.
Glucuronidation in Cultures of Human Skin Epithelial Cells
Authors: Rugstad Hans Erik , Dybing E.
Published: March 2011

Abstract. Glucuronidation of p‐aminophenol, p‐nitrophenol and bilirubin has been investigated in cultures of human skin epithelial cells (HE cells) and human skin fibroblasts (FB) and in homogenates from the same cells. HE cells in culture glucoronidated p‐aminophenol and p‐nitrophenol at rates of about 5 and 10 nmol/mg cell protein per h respectively. Bilirubin was not conjugated by HE cells. In homogenates from HE cells supplemented with UDP glucuronic acid (UDPGA) both p‐aminophenol and p‐nitrophenol were glucuronidated at about the same rate as by living cells in culture. Assuming that the transferase activity is the same in the whole cells compared to the homogenates, transferase activity and not UDPGA production may be the limiting factor in glucuronidation of p‐aminophenol and p‐nitrophenol in these cells. The glucuronidation rate of HE cells was not increased by benzpyrene or benzanthrazene. FB did not glucuronidate p‐aminophenol, p‐nitrophenol or bilirubin.
Hepatic Cholesterol Synthesis in Man: Effect of Diazepam and Other Drugs†
Authors: Orlandi F. , Bamonti F. , Dini M. , Koch M. , Jezequel A.M.
Published: March 2011

Abstract. The hepatic synthesis of cholesterol‐measured as incorporation of 14C‐acetate into digitonin‐precipitable sterols‐has been evaluated in needle biopsy material of normal untreated patients and patients under short‐term treatment with Diazepam, Phenobarbital, Chlorpromazine or Diphenylhydantoin. A significant increase of cholesterol synthesis was observed in the first two groups with much higher levels of incorporation in the Diazepam‐treated patients. Moreover in this group the levels were still elevated from 4 to 7 days after drug withdrawal. Ultrastructural and morphometric studies performed on the same biopsy material showed a significant increase of smooth endoplasmic reticulum in hepatocytes of Diazepam‐treated patients; in addition, there seemed to be a positive correlation between the increased cholesterol synthesis and the formation of areas of non vesicular, type 2, smooth endoplasmic reticulum. These findings suggest an early stimulation of the liver cell microsomal system by Diazepam in man; they also point to side effects of some drugs, which are not predictable from studies in Wistar rats.
Deoxyribonucleoside Triphosphates in Human Cells: Changes in Disease and Following Exposure to Drugs
Authors: Tattersall M.H.N. , Lavoie A. , Ganeshaguru K. , Tripp E. , Hoffbrand A.V.
Published: March 2011

Abstract. Deoxyribonucleic acid synthesis requires adequate cellular concentrations of the four deoxyribonucleoside triphosphates. Using a sensitive enzymic assay, we have measured the concentrations (pools) of these compounds in human bone marrow cells and in lymphocytes. The mean concentrations (pmol/106 cells) in normal human bone marrow cells were: deoxyadenosine triphosphate (dATP) 1.5; deoxyguanosine triphosphate (dGTP) 0.4; thymidine triphosphate (dTTP) 1.4 and deoxycytidine triphosphate (dCTP) 0.6; and in normal phytohaemagglutinin (PHA)‐stimulated lymphocytes (72 h cultures); dATP 3.7; dGTP 1.9; dTTP 9.4 and dCTP 2.9. The deoxyribonucleoside triphosphate concentrations were increased approximately threefold in the nucleated marrow cells from patients with leukaemia and myeloproliferative diseases. PHA‐stimulation of lymphocytes caused a marked increase of the deoxyribonucleoside triphosphate concentrations, particularly of dTTP, between 24 and 48 h of culture. In PHA‐stimulated lymphocytes, the antifolate drugs methotrexate, pyrimethamine and trimethoprim, all produced a fall in dTTP and a rise in dATP concentrations within 1 h. These effects could be reversed by folinic acid. 5‐Fluorouracil caused a fall in dTTP and in dCTP but no consistent changes in dATP; hydroxyurea caused a fall in dATP with a rise in dTTP. BCNU caused a significant fall in dATP and dCTP. Dibutyryl cyclic 3′, 5′ adenosine monophosphate and theophylline had no consistent effect on the deoxyribonucleoside triphosphate concentrations. 6‐Mercaptopurine caused a fall in dATP and dGTP, the fall in dATP being marked after 4 h incubation.

It is concluded that measurement of the deoxyribonucleoside triphosphates in human cells provides a new method of studying DNA synthesis in human disease states and of analysing the action of antimetabolite drugs on normal and diseased cells.
Defective Thyroglobulin Endocytosis and Hydrolysis in Thyroid Cold Nodules1
Authors: van den Hove‐Vandenbroucke M.F. , Couvreur‐Eppe M. , De Visscher M.
Published: March 2011

The catabolic phase of thyroid secretion has been studied by incubating thyroid slices with 0.1 % 125 ***I thyroglobulin (Tg) in the following cases: ***11 follicular adenomas (FA), 8 hyerplastic nodules in multinodular glands (NM), 3 carcinomas (follicular or papillary, FC, PC) and normal (N) or micronodular tissue (M). Tg pinocytosis is severely impaired in all cold nodules (25 to 60 % reduction). In the follicular tumours (FA, FC), Tg hydrolysis is more affected than would be expected based only on reduced Tg endocytosis: the hydrolysis products remain in the phagolysosomes instead of being secreted. As far as the acid hydrolases are concerned these enzymatic activities are increased in nearly all nodules, in Particular in follicular adenomas and carcinomas.
The Glucose‐Induced Gastrointestinal Stimulation of Insulin Secretion in Man: Relation to Age and to Gastrin Release
Authors: Rehfeld J.F. , Stadil F.
Published: March 2011

An oral 50 g glucose tolerance test and a simple intravenous glucose infusion test were performed in 20 young (20–32 years), 20 middle‐aged (42–55 years), and 20 old (65–81 years) normal subjects. Blood glucose, serum insulin, and serum gastrin concentrations were measured during all tests, the intravenous glucose infusion duplicated the oral blood glucose curve in young, middle‐aged, and half of the old subjects. In the remaining old subjects the intravenous blood glucose curve was below the oral blood glucose curve. Glucose and insulin concentrations were of similar magnitude in all groups, but maximum concentrations were reached later in the old subjects. Glucose per os induced a rapid rise in serum gastrin concentrations of the order of 10 pmol/l and a subsequent decrease of about 20 pmol/l*** in all groups. The intravenous glucose infusion induced no significant changes in serum gastrin concentrations. The non‐glycaemic (i.e. enteral) stimulation of insulin secretion was expressed as the difference between the integrated incremental areas of the oral and intravenous insulin curves in subjects with identical glucose curves during the two tests. This stimulation was of similar magnitude in all age groups, and it was not correlated to variations in gastrin concentrations. However, in the young subjects the enteral stimulation was greater during the first 30 minutes and smaller during the two last hours when compared to the old subjects.

The results suggest that: 1. A simple intravenous glucose infusion test can be used to copy the oral blood glucose curve. 2. The size of the enteral stimulation of insulin secretion during the whole test is independent of age. 3. The action of the glucose‐induced enteral stimulation is delayed with age, and closely linked to the dynamics of the glycaemic stimulus. 4. The glucose‐induced gastrin release is probably too small to affect insulin secretion significantly.
Is Phlorizin or Its Aglycon the Inhibitor of Intestinal Glucose Transport?
Authors: Blum A.L. , Haemmerli U.P. , Lorenz‐Meyer H.
Published: March 2011

Inhibition of glucose transport by phlorizin was examined in man by perfusion of an isolated small bowel segment. Inhibition was similar in normal and lactase deficient subjects. Since the small bowel of lactase deficient subjects contains only very small amounts of phlorizin hydrolase, phlorizin and not a product of enzymatic cleavage is the inhibitor of the small intestinal glucose carrier.
Immune Complex Deposits in Systemic Lupus Erythematosus Kidney without Histological or Functional Alterations†
Authors: Cruchaud A. , Chenais F. , Fournié G.J. , Humair L. , Lambert P.H. , Mulli J.C. , Chatelanat F.
Published: March 2011

This study demonstrates that in systemic lupus erythematosus (SLE), the presence of immune complexes on the glomerular basement membrane (GBM) does not invariably result in histological and/or functional lesions of the kidney. Among a group of 29 lupus patients, six subjects were selected for thorough investigation, because their renal function was normal or only slightly altered though they had suffered from SLE for 20 months to 18 years. All patients had antinuclear factor, anti‐native‐DNA antibody and a low level of complement; 3 had anti‐denatured‐DNA antibody, 2 had denatured DNA‐anti‐denatured‐DNA circulating complexes and 3 had anti‐RNA‐protein antibody. Kidney biopsies disclosed either no histological lesion or minimal changes in five of them and diffuse proliferative glomerulonephritis in one. By contrast, using the immunofluorescent technique, granular deposits containing the third component of complement (C3) were found on the GBM of all patients; IgG was present in 5 cases, IgM in 3, fibrinogen in 2 and IgA in one. Granular deposits were also found in the mesangium of all cases, in the vessel wall of two cases and around the tubules of one. Electron microscopy confirmed the presence of subendothelial and mesangial deposits. Our results also showed a good correlation between the importance of deposits and the presence of denatured DNA‐anti‐denatured‐DNA circulating complexes. From the data obtained in these 6 cases as well as in the 23 other patients of the group, 3 categories of lupus patients could be distinguished with regard to kidney involvement: 1) patients with insignificant histological lesions, no immune deposits and essentially normal function; 2) patients with definite histological lesions, immune deposits and renal insufficiency and 3) patients with few if any histological lesions and little functional impairment contrasting with important immune deposits. The resistance of some patients to the nephrotoxic effects of immune deposits shows that lupus nephritis depends on intricate pathogenic mechanisms and suggests that these are possibly antagonized by “protective” factors.
Decreased Haem Synthetase Activity in Blood Cells of Patients with Erythropoietic Protoporphyria
Authors: De Goeij A.F.P.M. , Christianse K. , van Steveninck J.
Published: March 2011

Abstract. A constant finding in erythropoietic protoporphyria (E.P.P.) is a raised protoporphyrin content of the erythrocytes. It has been shown before that the biosynthesis of this protoporphyrin takes place in the erythroid cell. In circulating blood cells of patients with E.P.P. the haem synthetase activity is significantly decreased. This observation and the increased protoporphyrin concentration in the cells can be explained by assuming a decreased stability of haem synthetase in the red blood cells of E.P.P. patients.
Insulin Metabolism, Insulin Sensitivity and Hormonal Responses to Insulin Infusion in Patients Taking Oral Contraceptive Steroids
Authors: Srivastava M.C. , Oakley N.W. , Tompkins C.V. , Sönksen P.H. , Wynn V.
Published: March 2011

Abstract. The metabolism of unlabelled human monocomponent insulin was studied in a group of six patients being treated with combined oestrogen‐progestogen oral contraceptives (OC) and compared with a group of ten normal subjects. The parameters of insulin metabolism were determined by a priming dose ‐ continuous infusion technique which enabled measurements of metabolic clearance rate (MCR) of insulin to be made at four separate steady state hormone concentrations spanning the physiological range. In normal subjects MCR was greatest at low insulin concentrations, falling from 24.7 ml/kg/min. at 16 μU/ml to 11.4 ml/kg/min. at a mean concentration of 280 μU/ml. In the OC group, MCR averaged 20.5 ml/kg/min. and did not change with increasing plasma insulin concentration. The plasma half‐disappearance time (T 1/2) was longer than normal in the OC group (5·6 vs. 4·4 min., p < 0·05) despite a higher MCR. The prolonged T 1/2 indicated that the apparent distribution space was increased in those on OC (166·6 vs. 82·7 ml/kg., p < 0·0025). The results are interpreted as indicating increased capillary permeability to insulin and increased peripheral degradation. The fact that MCR did not fall in the OC group with increasing plasma insulin concentrations whereas it did in normal subjects, suggested that OC leads to the loss of saturable component of insulin degradation that is present in normal subjects. Insulin sensitivity (as judged by induced hypoglycaemia) was reduced in the OC group while growth hormone responses were within the normal range. Plasma cortisol was increased in those taking OC but the response to insulin induced hyperglycaemia was less marked than normal. The results indicate a significant alteration in insulin metabolism in these subjects, which may contribute to the impairment of carbohydrate tolerance seen in some women taking combined OC.
The Response of Thyrotropin and Triiodothyronine to Various Doses of Thyrotropin Releasing Hormone in Normal Man
Authors: Weeke J.
Published: March 2011

Abstract. The relationship between serum thyrotropin (TSH) and serum triiodothyronine (T3) before and after injection of different doses of thyrotropin releasing hormone (TRH), given as single injections or as multiple injections with short intervals, was investigated in normal men. A positive correlation between prestimulated serum TSH and serum T3 levels and between the increase in the serum TSH and the serum T3 levels after TRH was found when repeated tests were performed in the same individual. There was a dose dependent TSH and T3 response to TRH. The smallest dose that produced a maximal response of both TSH and T3 was only 30 μg TRH. After six injections of 30 μg TRH with an interval of 30 minutes the increase in TSH was two times and the increase in T3 was three times as high as the maximal increase after single injections of TRH. This test with multiple injections of TRH may prove to be of clinical value in the measurement of both pituitary and thyroid function in selected patients. The close positive correlation between the serum TSH and serum T3 levels in basal conditions, demonstrated in four normal subjects in this study, probably reflects the steady state level determined by the hypothalamus from which the feedback control of TSH secretion operates.
Endothelial Injury Induced by Bacterial Endotoxin: Effect of Complement Depletion
Authors: Evensen S.A. , Pickering R.J. , Batbouta J. , Shepro D.
Published: March 2011

Abstract. The role of complement activation in the pathogenesis of endothelial injury caused by bacterial endotoxin was investigated in the rat. DNA synthesis in aortic endothelium was compared 48 hours after an intravenous injection of endotoxin (50 ‐ 500 μg) in normal rats and in rats depleted of haemolytic complement by purified cobra venom factor. At the time of endotoxin administration the rats treated with cobra venom factor had less than 3 ***% of the normal haemolytic complement level, their fibrinogen level was increased and clot retraction was impaired. Endotoxin stimulated endothelial DNA synthesis to the same degree in normal and in complement‐depleted rats. Cobra venom factor alone did not stimulate endothelial DNA synthesis. The complement‐depleted rats given 500 μg endotoxin were less thrombocytopenic than normal rats at the time of sacrifice, but the difference was not statistically significant. We conclude that the injurious effect endotoxin has on endothelium is not mediated by activation of late components of complement.
Ischaemic Heart Disease and Associated Risk Factors in 40 Year Old Men in Edinburgh and Stockholm
Authors: Oliver M.F. , Nimmo I.A. , Cooke Margaret , Carlson L.A. , Olsson A.G.
Published: March 2011

Abstract. The incidence of ischaemic heart disease in men in their early forties is approximately three times greater in Edinburgh than in Stockholm. To gain more information about some of the possible reasons for this striking difference,*** random sample of apparently healthy men aged 40 was selected from each city. Identical clinical and biochemical measurements were made and interlaboratory variations were eliminated by making each analysis in the same laboratory. Serum triglycerides were higher in Edinburgh men than in Stockholm men, and the shapes of the distribution curves were significantly different. Serum cholesterol concentrations were similar in the two cities. Fasting plasma glucose concentrations were the same in the two cities. After a standardised glucose load, the mean plasma glucose decreased in men in both cities and significantly more in Edinburgh. There were significantly more men in Edinburgh with high insulin values. There were significantly more cigarette smokers in Edinburgh. This is possibly the most clear‐cut difference between the cities. Edinburgh men were shorter than Stockholm men. Analysis of the distributions of high risk characteristics showed that Edinburgh had more putative high risk individuals for ischaemic heart disease. This study is exploratory in nature and the differences found cannot by themselves explain the greater incidence of ischaemic heart disease in Edinburgh compared with Stockholm. Nor are they likely to be independent of such influences as diet, physical activity and ethnic origin. The fact that such marked differences can be found emphasises the potential value of studying in this way populations with dissimilar incidence of disease.
Effect of Lipids on Insulin, Growth Hormone and Exocrine Pancreatic Secretion in Man*
Authors: Raptis S. , Dollinger H.C. , von Berger L. , Kissing J. , Schröder K.E. , Klör U. , Pfeiffer E.F.
Published: March 2011

Abstract. Influences of fat on release of insulin, growth hormone and pancreatic enzyme secretion were studied in 35 metabolically healthy subjects. A fat solution containing 40 g of soy bean oil was administered, I.V., orally and intraduodenally. In all cases there was a similar increase of insulin but the rise in serum insulin after oral or intraduodenal fat administration was not related to the changes in plasma free fatty acids, free glycerol and triglyceride levels. Blood sugar responded according to insulin secretion. The route of fat administration may possibly influence growth hormone secretion. Following intraduodenal fat administration volume and bicarbonate contents of the duodenal juice rose slightly whereas trypsin and bilirubin content increased considerably. These results suggest that insulin secretion after oral or intraduodenal administration of fat is influenced by intestinal factors. Cholecystokinin‐pancreozymin and gastric inhibitory polypeptide are qualified to serve as such factors.
Transport ATPases of Cardiac Sarcolemma in 20,25‐Diazacholesterol Induced Myopathy
Authors: Fiehn W. , Seller D. , Kuhn E. , Bartels D.
Published: March 2011

Abstract. 20,25‐Diazacholesterol, known to induce myotonia in skeletal muscle, also affects cardiac muscle as can be concluded from the development of cardiomegaly. At the same time (Na+, K+) ATPase of cardiac sarcolemmal membranes of the 20,25‐diazacholesterol treated rats showed an increased activity as compared with control animals (91% and 46% stimulation respectively). The Ca++ stimulated ATPase showed the same tendency (96% and 64% stimulation).

In the plasma of the treated rats creatine phosphokinase activity was found to be elevated whereas the amount of protein‐bound iodine was decreased, a finding that is common in myotonic dystrophy.
IgG subclass distribution and relative functional affinity of thyroid microsomal antibodies in postpartum thyroiditis
Authors: WEETMAN A. P. , FUNG H. Y. M. , RICHARDS C. J. , McGREGOR A. M.
Published: March 2011

An association between the development of postpartum hypothyroidism and high levels of IgG1 subclass microsomal (M) antibodies has been reported. Using an assay designed to detect reasonable levels of all the four IgG subclasses, we found no differences in the proportion of each IgG subclass in M antibodies of patients with postpartum hyperthyroidism or hypothyroidism compared with control postpartum patients with M antibodies but no thyroid dysfunction. However the total amount of M antibody of each IgG subclass was elevated above the controls in the patients with thyroid dysfunction. The relative functional affinity of M antibodies did not differ between controls and patients with hypothyroidism but declined 5 and 10–12 months after delivery compared to values at 2 months. These results do not support the suggestion that the amount of IgG1 subclass M antibodies particularly determines the course of postpartum thyroiditis. Rather, the total M antibody level, in all four subclasses, is associated with clinical outcome. Resolution of the disease, despite persisting M antibodies, may occur in part because the relative functional affinity of these antibodies declines after delivery.
Pituitary‐gonadal hormones and adrenal androgens in non‐cirrhotic female alcoholics after cessation of alcohol intake
Authors: VÄLIMÄKI M. , PELKONEN R. , HÄRKÖNEN M. , TUOMALA P. , KOISTINEN P. , ROINE R. , YLIKAHRI R.
Published: March 2011

To investigate the sex‐hormone profiles associated with chronic alcoholism in women we examined 16 non‐cirrhotic alcohol abusers (aged 18–46 years). They were admitted for the treatment of alcoholism (duration of 2–16 yrs) to a social hospital for 6 weeks. Their mean daily alcohol consumption was 170 g. Blood samples for serum LH, FSH, prolactin (PRL), oestrone (E1), oestradiol (E2), progesterone (P), 17‐α‐hydroxyprogesterone (17‐OHP), androstenedione (A) and dehydroepiandrosterone (DHEA) were drawn three times a week during the hospital stay. Similar blood samples were taken from 10 control women during one menstrual cycle. The cycles were anovulatory in two patients and in none of controls. Serum LH and FSH levels were similar in alcoholic and control women but serum concentrations of PRL were increased 2–4‐fold in alcoholic women. In the patients serum, concentrations of E1 and E2 tended to be lower during the follicular and midcycle phases, as did those of P and 17‐OHP during the luteal phase. Compared with the controls, serum levels of A were increased 2–3‐fold in the patients. A parallel difference between the two groups was seen in serum DHEA concentrations. We conclude that until liver injury, even heavy alcohol drinking has only minor effects on the secretion of gonadotrophins and ovarian steroids. Hypersecretion of PRL and adrenal androgens may well be an initiating mechanism for sexual dysfunction of female alcoholics.
Long‐term effects of acetazolamide and sodium chloride loading on cisplatin nephrotoxicity in the rat
Authors: HEIDEMANN H. Th. , HOFFMANN K. , INSELMANN G.
Published: March 2011

The protective effect of acetazolamide or sodium chloride loading on cisplatin nephrotoxicity was investigated in rats. After a single dose of cisplatin (5 mg kg−1 i.p.) kidney function was studied after 5, 28 and 84 days. Acetazolamide (75 mg kg−1 i.p.) was administered as a single dose prior (30 min) to the cisplatin injection. By the time of cisplatin administration, the rats were sodium depleted except the sodium‐loaded group. Five days after the cisplatin administration all rats received a regular rat chow for the rest of the experiment. Cisplatin alone caused renal failure that could be observed for up to 12 weeks (ClCr 0·32 ± 0·13 vs. 0·62 ± 0·06 ml min−1 × 100 g BW−1) with polyuria (UVol 41·2 ± 4·5 vs. 18·4 ± 4·6 ml 24 h−1). Pretreatment with acetazolamide was the most protective manoeuvre tested. Five days after cisplatin, kidney function was significantly better than in rats treated with cisplatin alone (ClCr 0·21 ± 0·06 vs. 0·03 ± 0·01 ml min−1 × 100 g BW−1), after 28 days the only sign of nephrotoxicity was polyuria (UVol 28·9 ± 3·7 vs. 19·0 ± 2·6 ml 24 h−1) after 84 days no differences could be observed at all. Sodium chloride loading was less protective on cisplatin nephrotoxicity. Impaired renal function could still be observed after 12 weeks (ClCr 0·41 ± 0·05 vs. 0·62 ± 0·06 ml min−1 × 100 g BW−1) with no difference in comparison with the rats treated with cisplatin alone. However, since 12 rats died in the group having received cisplatin alone and only one rat in the high‐salt group, sodium chloride loading is regarded as being advantageous over sodium depletion on cisplatin nephrotoxicity.
Salivary gland mucoepidermoid carcinoma is a clinically, morphologically and genetically heterogeneous entity: a clinicopathological study of 40 cases with emphasis on grading, histological variants and presence of the t(11;19) translocation
Authors: Schwarz Stephan , Stiegler Clemens , Müller Maximilian , Ettl Tobias , Brockhoff Gero , Zenk Johannes , Agaimy Abbas
Published: March 2011

Schwarz S, Stiegler C, Müller M, Ettl T, Brockhoff G, Zenk J & Agaimy A (2011) Histopathology 58, 557–570 Salivary gland mucoepidermoid carcinoma is a clinically, morphologically and genetically heterogeneous entity: a clinicopathological study of 40 cases with emphasis on grading, histological variants and presence of the t(11;19) translocation

Aims:  To correlate World Health Organization (WHO) grade, patient’s outcome and presence of t(11;19) to histological tumour variants in 40 well‐characterized mucoepidermoid carcinomas (MECs).

Methods and results:  MECs were classified as ‘classical’ based on the presence of equal proportions of the three cell types or the dominance (≥50%) of mucous cells together with at least one other cell type, and as ‘variant’ if composed of ≥80% of a single non‐mucous cell type. Classical MECs were more common (n = 23). Variant MECs had predominant squamoid (n = 9), eosinophilic (n = 5) or clear cell (n = 3) morphology. Twenty‐seven tumours were WHO grade 1, three grade 2 and ten grade 3. The t(11;19) was detected in 82%, 35% and 0% of classical MEC, variant MEC and non‐MEC, respectively. Classical MECs were associated significantly with age ≤60 years (P < 0.001), grade 1 (P < 0.001) and t(11;19) (P = 0.003). Short overall survival was associated significantly with age >60 years (P = 0.001) and Union for International Cancer Control (UICC) stage >I (P = 0.031), residual tumour (P < 0.001), tumour grade >1 (P = 0.001) and squamoid variant (P = 0.002) in Kaplan–Meier analysis.

Conclusions:  The results underscore the great histological diversity of MEC, the reproducibility of the WHO grading criteria and the value of histological subtypes as an additional prognostic factor.
Impact of a multi‐faceted training intervention on the improvement of hand hygiene and gloving practices in four healthcare settings including nursing homes, acute‐care geriatric wards and physical rehabilitation units
Authors: Eveillard Matthieu , Raymond Françoise , Guilloteau Véronique , Pradelle Marie‐Thérèse , Kempf Marie , Zilli‐Dewaele Marina , Joly‐Guillou Marie‐Laure , Brunel Patrick
Published: March 2011

Aims.  To assess the impact of a multi‐faceted training program on the compliance with hand hygiene and gloving practices.

Background.  Hand hygiene is considered as the cornerstone of the prevention of hospital‐acquired infections. Several studies have enhanced the poor effectiveness of training programs in improving hand hygiene compliance.

Design.  A before–after evaluation study.

Methods.  The study was conducted in four healthcare settings before and after an intervention program which included the performance feedback of the first evaluation phase, three six‐h training sessions, the assessment of hand hygiene performance with teaching boxes and the organisation of one full‐day session devoted to institutional communication around hand hygiene in each setting. Hand hygiene compliance and quality of hand rubbing were evaluated. Hand hygiene opportunities were differentiated into extra‐series opportunities (before or after a single contact and before the first contact or after the last contact of a series of consecutive contacts) and intra‐series opportunities (from the opportunity following the first contact to the opportunity preceding the last in the same series).

Results.  Overall, 969 contacts corresponding to 1,470 hand hygiene opportunities (760 during the first phase and 710 during the second) were observed. A significant improvement of observed practices was recorded for the hand hygiene compliance in intra‐series opportunities (39·0% vs. 19·0%; p < 10−5), the proportion of gloves worn if indicated (71·4% vs. 52·0%; p < 0·001) and the quality of hand rubbing (85·0% vs. 71·9%; p < 10−5).

Conclusions.  Some of the performances measured for both hand hygiene and gloving practices were improved. We plan to extend this investigation by performing a qualitative study with experts in behavioural sciences to try improving practices for which adherence was still weak after the training program such as hand hygiene in intra‐series opportunities.

Relevance to clinical practice.  This study underscored the usefulness of implementing contextualised training programs, while more traditional courses have shown little impact.
Family quality of life of Chinese families of children with intellectual disabilities
Authors: Hu X. , Wang M. , Fei X.
Published: March 2011

Background  The concepts of quality of life and family quality of life (FQOL) are increasingly being studied in the field of intellectual disabilities (ID) in China as important frameworks for: (1) assessing families' need for supports and services; (2) guiding organisational and service delivery system changes; and (3) evaluating quality family outcomes. The present study focused on exploring the perceptions of Chinese families who have a child with an ID regarding FQOL as well as examining the factor structure of FQOL concept from Chinese families.

Methods  The Chinese version of the Family Quality of Life Scale was used to survey Chinese families living in the urban and suburban areas of Beijing who have a child with ID. A total of 442 families participated in this study. Confirmatory factor analysis was used to test the factor structure of FQOL. Multivariate analysis was also used to examine group differences among families in terms of family demographic variables.

Results  A five‐factor structure of the FQOL construct was found in the Chinese sample, suggesting a similar factor structure found from US families in the literature. Different living conditions (e.g. housing and transportation) tended to affect significantly families' satisfaction ratings of their FQOL. It is also found that family income and severity of disability of the child are predictors of families' satisfaction ratings of FQOL.

Conclusion  The preliminary findings of this study suggest a cross‐cultural factor structure comparability of FQOL between samples in the USA and China. Results call for further examination of the family‐centred service and support as a mediator on the interactive relationship between family characteristics, family needs and FQOL outcomes.