bluuebunny/crossref_metadata_2025 huggingface dataset:
Elimination of infused amino acids from plasma of control subjects and of patients with cirrhosis of the liver
Authors: VILSTRUP H. , BUCHER D. , KROG B. , DAMGÅRD S. E.
Published: March 2008

Abstract. In four control subjects and four patients with cirrhosis of the liver a multiple amino acid mixture was infused for 12 h at a constant rate of 68 and 56 μmol α‐amino N/s, respectively. Before infusion the plasma amino N concentration was 2·4 pL 0·2 (mean pL SD) mmol/l in control subjects and 3·5 pL 0·7 mmol/l in patients (P 0·025). The concentration of alanine, proline, arginine, tyrosine, and citrulline was significantly increased in the cirrhosis group. 12 h after the infusion began approximately constant amino N concentrations of 11·4 pL 1·8 mmol/l in controls and 13·7 pL 3·9 mmol/l in patients were attained, and the urea N synthesis rate was 63 pL 17 and 44 pL 8 μmol/s, respectively (P < 0·05). After correction for loss of amino acids in urine this means that on the average 94 per cent of the N load was recovered as urea. The plasma clearance of infused amino acids, calculated as the ratio between infusion rate and steady state concentration, was 6·0 pL 1·2 and 4·1 pL 0·9 ml/s for amino N in the control and cirrhosis group, respectively (P < 0·025). The clearance of individual amino acids ranged between 2·5 and 28 ml/s. The clearance of most amino acids was decreased in the cirrhosis group, and of glycine, proline, lysine, threonine, and arginine significantly so (P < 0·05), reflecting accumulation of amino acids in patients. This indicates that a primary defect in the conversion of amino N in cirrhosis is the reduced urea synthesis.
Reduced pressor effect of angiotensin II and of noradrenaline in normal man following the oral administration of the calcium‐antagonist nifedipine
Authors: VIERHAPPER H. , WALDHÄUSL W.
Published: March 2008

Abstract. The pressor response to both angiotensin II (5, 10 and 20 ng kg‐1min‐1) and to noradrenaline (50, 100 and 200 ng kg‐1 min‐1) was reduced (P < 0·05 to < 0·005) in six healthy male subjects following the administration of the calcium‐antagonist nifedipine (10 mg p.o.). Nifedipine induced a rise in basal plasma noradrenaline concentrations but did not alter the plasma concentrations of adrenaline, dopamine, renin and aldosterone. A slight reduction in the angiotensin II induced rise of plasma aldosterone by nifedipine was observed after the administration of the largest dose of angiotensin II only (P < 0·05). The reduced responsiveness towards pressor agents following oral nifedipine is in keeping with the known antihypertensive effect of calcium‐antagonistic drugs and could provide a concept for the effectiveness of these drugs in hypertensive crisis.
Evaluation of mannitol for use as a probe marker of gastrointestinal permeability in man
Authors: LAKER M. F. , BULL H. J. , MENZIES I. S.
Published: March 2008

Abstract. The absorption, metabolism, space distribution, renal excretion and natural occurrence of mannitol was studied in healthy human volunteers to determine its suitability for use as a probe marker of gastrointestinal permeability. Urinary recovery following oral loading was 8·0–39·6% of the ingested amount. Net absorption during intubation experiments in which a 30 cm segment of small intestine was perfused was 3·6% of perfusate mannitol. The slow rate of removal from the jejunum suggests that mannitol has a very low affinity for facilitated transport systems. Urinary recovery of intravenously injected mannitol approached 100% and renal clearance averaged 131 ml/min. The space distribution, progression of renal excretion and falling plasma concentration simulated that of lactulose rather than 3‐0‐methyl‐D‐glucose suggesting a mainly extracellular distribution. This was supported by measurement of erythrocyte penetration. Stool cultures degraded mannitol to products which included acid and carbon dioxide, when incubated aerobically and anaerobically. Excretion of mannitol, which was found to be naturally present in urine, was reduced but not abolished by fasting. Since mannitol occurs naturally in human urine we conclude that measurement of urinary mannitol following oral administration to assess intestinal permeability may be subject to error.
Polyuria in experimental intrahepatic cholangitis induced by alpha‐naphthyl‐isothiocyanate
Authors: TUR‐KASPA RAN , ADLER RUTH , POPOVTZER MORDECAI M. , ELIAKIM MARCEL
Published: March 2008

Abstract. Alpha‐naphthyl‐isothiocyanate (ANIT)‐induced intrahepatic cholangitis was associated with significant polyuria in rats. The urine output in the experimental rats was about two and a half to four fold higher than that in the controls. The polyuria was accompanied by polydypsia and disappeared when water intake was limited and controlled. The glomerular filtration rate and renal histology remained intact. Dilution and concentration capacities were preserved and the response to exogenous anti‐diuretic hormone was intact. Following water deprivation, the water and electrolyte contents of the renal medulla and papilla were similar in both experimental and control rats. The excretion of a salt‐load in ANIT‐treated rats was delayed. It is concluded that the polyuria in ANIT‐treated rats is secondary to polydypsia. The finding of preserved dilution and concentration capacities in this experimental model contrasts to that in other experimental models of hepatobiliary disease.
Effect of ethanol on blood viscosity and erythrocyte flexibility in healthy men
Authors: HILLBOM M. E. , KASTE M. , TARSSANEN L. , JOHNSSON R.
Published: March 2008

Abstract.The effects of ethanol on blood rheology were studied in twelve healthy male volunteers each serving as his own control. They drank 1.5 g (33 mmol) of ethanol per kg body weight in fruit juice over 2.5 h under controlled laboratory conditions. Blood and plasma viscosity, packed cell volume and erythrocyte flexibility were measured before and 3, 12 and 16 h after ethanol ingestion began, and again during a second session equal volumes of fruit juice were consumed. Packed cell volume varied similarly after ingestion of juice with or without ethanol. Blood viscosity remained almost unchanged after ethanol, while drinking of juice caused an initial decrease followed by a significant (P<0.05) increase from 4.04 (SEM 0.06) to 4.32 (SEM 0.18) mPa.s. The juice also caused more significant fluctuations in erythrocyte rigidity (whole blood) than ethanol, which had parallel but insignificant effects. We conclude that a blood ethanol concentration of 28 mmol 1‐1failed to induce any marked changes in blood rheology.
Analytical subcellular fractionation of normal human skeletal muscle by sucrose density gradient centrifugation
Authors: MARTIN F. C. , LEVI A. J. , SLAVIN G. , PETERS T. J.
Published: March 2008

Abstract. The principle organelle marker enzymes and various adenosine triphosphatase (ATPase) activities were studied in human skeletal muscle. The reproducibility of each assay was established under optimal and linear assay conditions.

Whole homogenates of normal human quadriceps muscle were fractionated by centrifugation on a continuous sucrose density gradient. Gradient fractions were assayed for organelle marker enzymes and frequency‐density histograms were constructed for each enzyme. Good resolution of the principal organelles was obtained.

Adenosine triphosphatase (ATPase) was assayed under conditions of maximal stimulation by Ca2+, or Mg2+ or Na2+, K++ Mg2+. The distribution of these activities was compared with those of the organelle marker enzymes. Both Ca2+‐ATPase and Mg2+‐ATPase were distributed to both the mitochondrial and myofibrillar fractions but could be distinguished by the inhibition of mitochondrial ATPase with sodium azide. The distribution of Na+, K+‐activated, Mg2+‐dependent ATPase (Na+, K+ ATPase) activity suggested a sarcolemmal localization.

The results of electron microscopy of gradient fractions were consistent with the organelle content of the fractions as determined by enzymic analyses. These studies provide reference information for the subsequent investigation of organelle pathology of human muscle disorders.
Comparison of large‐pore membrane haemodialysis and cross‐dialysis in acute hepatic insufficiency in pigs
Authors: GROOT GERRIT H. DE , SCHALM SOLKO W. , SCHICHT IKE , BATAVIER PATRICIA , JONGE MINUS DE , LENS JAAP , TERPSTRA JOHANNES L.
Published: March 2008

Abstract. We studied the duration of survival and the removal of putative toxins in forty pigs with ischaemic hepatic necrosis, undergoing haemodialysis or cross‐dialysis with a large‐pore membrane. Ischaemic hepatic necrosis was induced in conscious animals by tightening a loop around the hepatic artery 3 days after construction of a portocaval shunt. Pigs treated by a dialysis procedure survived significantly longer (45.2 ± 11.9 h) than controls (26.3 ± 5.4 h). There was no difference between haemodialysis and cross‐dialysis.

Blood ammonia initially dropped significantly (P<0.05) more during haemodialysis (560.107±210.51 μmol/1) than during cross‐dialysis (596.131±398.81 μmol/1) but it subsequently increased beyond initial values despite efficient removal during continuous dialysis. Removal of ammonia was greater during cross‐dialysis than during haemodialysis, but haemodialysis was more effective in the removal of the ammonia precursors glutamine and urea.

We conclude that dialysis procedures can prolong survival in pigs with ischaemic hepatic necrosis. The removal of ammonia‐precursors is more effective in the prevention of hyperammonaemia than the removal of ammonia itself. Since dialysis cannot prevent progressive hyperammonaemia, control of excessive toxin production seems mandatory for effective hepatic support.
Plasma aminoacid levels across the brain in patients with respiratory failure
Authors: CANGIANO CARLO , FARBER MARK O. , CARDELLI‐CANGIANO PATRIZIA , ROBERTS LESLIE R. , JAMES J. HOWARD , CASCINO ANTONIA , COCKERILL EDWARD M. , MANFREDI FELICE
Published: March 2008

Abstract. Animal studies and theoretical considerations have suggested that in hypercapnic respiratory failure there is interconversion of glutamic acid to glutamine within the brain, perhaps as part of a local buffering mechanism to minimize hypercapnia‐induced cerebral acidosis. Detection of transcerebral arteriovenous differences, positive for glutamic acid and negative for glutamine, would lend support to this hypothesis. We measured arterial and internal jugular venous levels of twenty‐three aminoacids in four patients with hypercapnic respiratory failure and in four suitable controls. In patients, arterial as well as venous glutamine levels were elevated proportionally, and there was no demonstrable A‐V difference across the brain; arterial and venous glutamic acid levels were the same as controls. All other aminoacid levels, arterial and venous, were normal. These findings confirm the previous observations that in hypercapnic respiratory failure glutamine metabolism is altered, but provide no support for the proposed glutamic acid‐glutamine interconversions within the brain.
Amino acids and lipoproteins in plasma of duodenopancreatectomized patients: effects of glucagon in physiological amounts
Authors: MÜLLER W. A. , CÜPPERS H. J. , ZIMMERMANN‐TELSCHOW H. , MICHELI H. , WYSS T. , RENOLD A. E. , BERGER M.
Published: March 2008

Abstract. Duodenopancreatectomy induces a severe glucagon deficiency and elevated plasma concentrations of alanine, aspartate, glycine, proline, serine, arginine, citrulline, ornithine, phenylalanine and tyrosine. Restoring high physiological plasma glucagon in six such patients by infusing 0.3 mg/24 h of exogenous glucagon reduced significantly (P < 0.01 or 0.001) the mentioned amino acids (except phenylalanine) and further asparagine, glutamine, methionine and threonine. In six normal subjects the same infusion reduced significantly (P < 0.05 to 0.001) plasma alanine, asparagine, glutamate, glutamine, glycine, proline, serine, threonine, arginine, ornithine, lysine and tyrosine. However, the effect was significantly (P < 0.01 or 0.001) less marked for alanine, glutamine, glycine, methionine, serine, threonine and arginine. This particular glucagon sensitivity of duodenopancreatectomized patients suggests that glucagon deficiency is the cause of their hyperaminacidaemia. By co‐trust, lipoprotein concentrations were virtually unaffected by either glucagon deficiency or its replacement.

In the light of the marked hypoaminacidaemia in glucagonoma patients these results attribute to glucagon a major role as a regulator of protein metabolism.
Digitoxin intoxication with severe thrombocytopenia: reversal by digoxin‐specific antibodies
Authors: HESS T. , RIESEN W. , SCHOLTYSIK G. , STUCKI P.
Published: March 2008

Abstract. As a result of overdosage a 77‐year‐old patient with heart disease developed digitoxin intoxication, associated with arrhythmias, extracardiac symptoms of intoxication and severe thrombocytopenia. Treatment with digoxin‐specific antibody fragments relieved the signs and symptoms of intoxication within a few hours. The rise in platelet count from the pretreatment value of 26 000/mm3 to 47 000 within 12 h and to over 60 000/mm3 within 16 h of starting the antibody infusion may also be attributed to the treatment with antibodies. Such a rapid recovery from digitoxin‐induced thrombocytopenia has not hitherto been described.

Digoxin‐specific antibodies, obtained by immunization of sheep with a digoxin‐albumin conjugate, were used to treat intoxication with digitoxin, since cross‐reaction had been demonstrated in vitro and in animal experiments. The present paper briefly discusses the mode of action and the general problems relating to the antibody therapy of digitalis poisoning.
The effects of an opiate agonist and antagonist on the human upper gastrointestinal tract
Authors: REES W. D. W. , SHARPE G. R. , CHRISTOFIDES N. D. , BLOOM S. R. , TURNBERG L. A.
Published: March 2008

Abstract. Endogenous opiates may play a role in regulating intestinal function and we have investigated this possibility in the human upper gastrointestinal tract using loperamide as a locally‐acting opiate agonist and naloxone as antagonist. Loperamide (4 mg) had no effect on the fasting pattern of motor activity in the antrum, duodenum and proximal jejunum. However, naloxone (40 μg kg‐1 h‐1 i.v.) abolished interdigestive motor activity in five of ten subjects and reduced antroduodenal motility index per cycle in all subjects (antrum: 1230 ± 120 to 130 ± 140 mm2; duodenum: 1120 ± 150 to 225 ± 160 mm2; P < 0.005). These effects were not significantly affected by loperamide. Plasma motilin exhibited cyclic variation with significantly higher concentrations during antroduodenal phase 3 than during phases 1 and 2 of the interdigestive cycle. Plasma motilin was not altered by naloxone or loperamide, and neither drug had any effect on basal gastric acid secretion, duodenal output of amylase and bile salt or duodenogastric reflux. The results suggest that endogenous opiates regulate fasting motor activity in the human gastrointestinal tract but do not influence basal secretory function of the stomach, pancreas or biliary tree.
Rabbit lung lipids in experimental fibrosis and emphysema: lipolytic activity and content and distribution of lipids
Authors: ROSARIO E. , GONZALEZ‐SANTOS P.
Published: March 2008

Abstract. An in vitro study of lung lipolytic activity in rabbits was performed using tissue homogenates and perfusion methods.

Thirty‐two animals were divided into three groups: (a) control; (b) lung fibrosis induced by talc‐powder and (c) lung emphysema group, induced by elastase.

In minced lung tissue, incubated with lipid substrate, the release of free fatty acids (FFA) was, in the control group, 5.65 ± 1.12 μmol g wet tissue‐1 h‐1 and in the emphysema group 2.57 ± 0.56 μmol g wet tissue‐1 h‐1, (P < 0.02).

Perfusion with lipid substrate did not reveal any significant differences between the three groups with respect to the total quantities of FFA released. It did, however, show that, in the emphysema group, the rate at which FFA were released during the perfusion was slower than in the control group.

Moreover, in the emphysema group there was a significant decrease in phospholipid content (control 29.8 ± 1.48 mg/g wet tissue, emphysema 26.1 + 1.14 mg/g wet tissue; P < 0.05), and consequently in total lipids (control 47.1 ± 2.64 mg/g wet tissue, emphysema 38.6 ± 0.24 mg/g wet tissue; P < 0.05) in relation to the control group. The decrease in phospholipids is a consequence of the significant decrease in the lecithin (control 53.7 ± 2.02%, emphysema 43.7 ± 2.40%; P < 0.01) and lysolecithin fractions (control 10.5 ± 1±52%; emphysema 56 + 1.26%; P < 0.05).

There were no differences between the control and the fibrotic groups. The lower rate of lung lipolytic activity in the emphysema group may be connected with a decrease in lung lipoprotein lipase (LPL).

The low content of lung phospholipids in the cited group may be a result of damaged lung lipolytic activity.
Hormonal regulation of lipogenesis in human diploid fibroblasts from normal subjects and from patients with familial hypertriglyceridaemia
Authors: LEMMEN C. , WOLFRAM G. , BARTH C. A. , ZÖLLNER N.
Published: March 2008

Abstract. Lipogenesis has been investigated in diploid fibroblasts derived from patients with familial hypertriglyceridaemia (FHT) and compared with cells from healthy persons. There was no difference in acetyl‐CoA carboxylase activity in both cell types. Incorporation of [2‐14C]‐acetate into triglyceride fatty acids was slightly increased (34%) by the FHT lines. Addition of triiodothyronine caused a marked rise in [2‐14C]‐acetate incorporation by the FHT lines whereas the normal lines exhibited only control values. Maximal rise in [2‐14C]‐acetate incorporation was obtained with 5 μg/ml for 72 h. Under these conditions, acetate incorporation by the FHT lines was 220% of the controls, compared with 94% by the normal lines. Measurements of acetyl‐CoA carboxylase specific activity supported the results obtained with measurements of acetate incorporation into triglyceride fatty acids. Individual FHT lines differ much in their quantitative answer to thyroid hormones, although the described effects were obtained with all eight lines under study. Insulin increased acetyl‐CoA carboxylase activity and incorporation of [2‐14C]‐acetate in lipids in both cell types, but with no difference between normal and FHT lines. The results seem to reflect a higher lipogenic capacity of the hypertrigly‐ceridaemic fibroblasts compared with normal cells.
Sympathetic nervous activity, renin‐angiotensin system and renal excretion of prostaglandin E2 in cirrhosis. Relationship to functional renal failure and sodium and water excretion
Authors: ARROYO VICENTE , PLANAS RAMÓN , GAYA JOAN , DEULOFEU RAMÓN , RIMOLA ANTONIO , PÉREZ‐AYUSO OSA M. , RIVERA FRANCISCA , RODES JOAN
Published: March 2008

Abstract. To investigate if functional renal failure in cirrhosis could be related to disturbances of vasoactive systems, plasma renin activity, plasma catecholamines and urinary prostaglandin E2 (PGE2) were determined in twenty‐two normal subjects and sixty‐five cirrhotics. Furthermore, in thirty‐three of these subjects, the effect of lysine‐acetylsalicylate (450 mg i.v.) on renal function was studied.

Patients with ascites without renal failure showed higher renin, noradrenalin and urinary PGE2 than normal subjects (5.9±0.8 v. 1.1±0.1 ng ml‐1 h‐1, P < 0.001; 512 ± 39 v. 224±17 pg/ml, P < 0.001; and 603 ± 71 v. 377±36 ng/day, P < 005, respectively). Patients with functional renal failure showed higher (P < 0001) renin (13.5±1.9) and noradrenalin (1114±134) and lower (P < 005) urinary PGE2 (199 ± 36) than normal subjects and cirrhotics without renal failure. On the whole, patients glomerular filtration rate correlated (P < 0001) with urinary PGE2 (r= 0.55), renin (r=‐0.52) and noradrenalin (r=‐0.52).

Lysine‐acetylsalicylate did not alter renal function in normal subjects and cirrhotics without ascites. However, it reduced water diuresis (8.8 ± 0.9–2.7 ± 0.5 ml/min) and sodium excretion (from 57.1 ± 13.9 to 3.9 ± 11 μmol/min) in all the nineteen cirrhotics with ascites studied and the glomerular filtration rate (95.4 ± 11.8–46.7 ± 9.5 ml/min) in eleven of these patients. Urinary PGE2 decreased in all patients (3.13 ± 0.65–0.54 ± 0.11 ng/min).

The study suggests that: (a) functional renal failure in cirrhosis with ascites may be a consequence of an imbalance between vasoactive systems, (b) renal prostaglandins are involved in the tubular handling of sodium and water in these patients.
Changes in plasma renin activity and haemodynamics during vasodilator therapy in conscious dogs with myocardial infarction or chronic volume overload
Authors: POULEUR H. , ENGLER R. L. , LINK J. , PRINTZ M. P. , COVELL J. W.
Published: March 2008

Abstract. The aim of the study was to compare the changes in plasma renin activity induced by a vasodilator in normal dogs and in dogs with an impaired cardiac reserve. In normal conscious dogs, a 60‐min nitroprusside infusion increased plasma renin activity from 1.05 ± 0.26 to 8.35 ± 1.20 ng, angiotensin I ml‐1 h‐1 (P < 0002) and heart rate from 83 + 6 to 149±15 beats/min (P < 0.002). In five dogs in which a aortocaval fistula had been created 4 weeks earlier, the same infusion still increased plasma renin activity but significantly less than in normal dogs (0.90 ± 0.29 to 4.44 ± 0.64 ng ml‐1 h‐1; P < 0.01) and the heart rate was unchanged (134 ± 4 to 139 ± 7 beats/min; NS). Similarly, in five dogs with a previous myocardial infarction, the heart rate response to nitroprusside was blunted (108 to 107 beats/min;NS) and plasma renin activity increased less than in normal dogs. Plasma renin activity also increased acutely after hydralazine administration in dogs which myocardial infarction (1.05 ± 0.26 to 8.99 ± 0.79 ng ml‐1 h‐1; P < 0.05); after 1 week of hydralazine, plasma volume had increased from 54.9 ± 0.9 ml kg‐1 to 74.5 ± 4.9 ml kg‐1 (P < 0.05) and plasma renin activity remained higher than control (4.66 ± 0.66 ng ml‐1 h‐1; P± 0.01). In conclusion, vasodilator therapy rapidly activates vasoconstrictor forces and fluid retention even in dogs with limited cardiac reserve. Although the regulation of plasma renin secretion appears altered in these models of heart disease, the renin response remains sufficient to seriously limit the beneficial effects of vasodilator therapy.
The measurement of superoxide anion production by granulocytes in whole blood. A clinical test for the evaluation of phagocyte function and serum opsonic capacity
Authors: VITE P. BELLA , DRI P. , BIANCA V. DELLA , SERRA M. C.
Published: March 2008

Abstract. The paper reports a simple, sensitive and time‐saving procedure for the assay of the function of the phagocytes on microsamples of whole blood. The method consists in the evaluation of the stimulation of superoxide anion (O2‐) production (as superoxide dismutase‐sensitive cytochrome c reduction) by leukocytes in whole blood challenged with (a) phagocytosable particles (opsonized zymosan); (b) particles that become phagocytosable by virtue of the opsonizing capacity of the plasma of blood samples (zymosan); and (c) a soluble agent such as phorbol myristate acetate. Preliminary studies indicate that this procedure can be used as a routine test because it enables information to be obtained about the respiratory responsiveness of phagocytes and about cellular and humoral defects of phagocytosis.
Diabetes mellitus, glucose tolerance and insulin response to glucose in patients with primary hyperparathyroidism before and after parathyroidectomy
Authors: LJUNGHALL S. , PALMÉR M. , ÅKERSTRÖM G. , WIDE L.
Published: March 2008

Abstract. In a retrospectively analyzed series of 441 patients operated for primary hyperparathyroidism (HPT), the prevalence of diabetes mellitus was 8.2%, which was three times higher than in the unselected age‐matched population. Following parathyroid surgery, the need for antidiabetic treatment was unchanged. The insulin response to an intravenous glucose load was enhanced preoperatively [95 mU/l ± 41 (SD)] in twenty‐six prospectively studied patients compared to postoperative (65 ± 41 mU/l) investigations (P < 0.01). This response was inversely correlated (r= 2, P < 0.01) to the serum phosphate concentrations but not related to calcium or parathyroid hormone levels.

Postoperatively, most HPT patients experienced a deterioration of their glucose tolerance (t for i.v. glucose 54 ± 12 and 64 ± 21 min, respectively, P < 0.05), and one‐third of them had pathological values at follow‐up. Despite this, neither the fasting blood glucose levels nor the values for haemoglobin A1c were significantly affected.
Free cholesterol distribution during in vitro lipolysis of rat plasma very low density lipoprotein: lack of a role for blood and heart cells
Authors: PERRET BERTRAND‐PIERRE , EISENBERG SHLOMO , CHAJEK‐SHAUL TOVA , DECKELBAUM RICHARD , OLIVECRONA THOMAS
Published: March 2008

Abstract. In the present study, an attempt was made to quantify free cholesterol transfer from lipolyzed VLDL to HDL, blood cells and heart cells. The experiments were carried out in vitro or in the isolated perfused rat heart with rat plasma VLDL labelled biosynthetically with [14C]‐palmitic acid and [3H]cholesterol, and with bovine milk lipoprotein lipase, human blood cells (erythrocytes, leucocytes and platelets) or rat plasma HDL. Exchange and transfer of free cholesterol was followed by radioactivity and specific activity determinations. The study demonstrated an exchange of free cholesterol between VLDL and blood cells (6–10 h) and VLDL and HDL (120 min). However, none of the blood cells tested served as acceptor for lipolysis‐generated free cholesterol, whereas HDL did. In the isolated perfused rat heart, a maximum of 25% of the free cholesterol radioactivity lost from VLDL was found in the tissue. Since exchange must have contributed to this process, the transfer of free cholesterol molecules to the heart is necessarily lower. The study thus demonstrated minimal or possibly no net transport of free cholesterol from VLDL to cells and cell membranes.
Duodenal bulb pH in normal subjects
Authors: HANNIBAL STEEN , RUNE SIMON J.
Published: March 2008

Abstract. Four pH electrodes strapped together at 1·5 cm intervals were positioned in the pyloric region. Electrodes situated in the stomach record steady acid pH while electrodes distal to the pylorus show fluctuating pH, thereby enabling the electrodes to be localized from the pH pattern. Digital pH values were sampled and stored at a rate of 2/s from each electrode. For each 10‐min period, the mean hydrogen ion activity, the percentage of time that the pH was at < 3·0 and number of pH spikes were computed. Fourteen healthy subjects were studied in the fasting state and for 3 h after 300 ml chocolate milk. Log mean hydrogen ion activity in the proximal part of the duodenal bulb was (median and interquartile range): fasting pH 2·40 (2·23–3·00); 0–60 min after meal: pH 5·7 (4·92–5·95); 60–120 min: pH 2·31 (1·95–3·20) 120–180 min: pH 2·20 (1·99–2·44). Repeated studies in twelve subjects showed a linear correlation between 1st and 2nd study, r=0·87. A significant linear correlation was found between peak acid output to pentagastrin and postprandial bulb acidity.
Investigation of human skeletal muscle structure and composition by X‐ray computerised tomography
Authors: GRINDROD SUE , TOFTS PAUL , EDWARDS RICHARD
Published: March 2008

Abstract. In muscular dystrophy and metabolic myopathy there is wasting and replacement of the muscle bulk with fat and fibrous tissue. A method for estimating the fat content of muscle and the cross‐sectional area from computerised tomography (CT) scans is presented. Data from the quadriceps muscle of fifty patients show the effect of fat replacement on muscle strength. The CT scans have shown that the pattern of wasting in individual muscle groups is characteristic of the type of myopathy. In Duchenne muscular dystrophy, hypertrophic and pseudohypertrophic muscle have hitherto been indistinguishable, but this method allows a clear distinction to be made. Quantitative CT offers a new approach to the investigation of muscle diseases and can also be of considerable value in selecting sites for needle biopsy of muscle.
Defective neutrophil motility in patients with primary ciliary dyskinesia
Authors: VALERIUS NIELS HENRIK , KNUDSEN BODIL BYGUM , PEDERSEN MOGENS
Published: March 2008

Abstract. Microtubules are important in the regulation of the motile functions of a variety of cells, including leukocytes, ciliated cells and spermatozoa. Polymorphonuclear leukocyte function was studied in ten patients with primary ciliary dyskinesia, an inherited disorder of microtubules in sperm tails and cilia.

Neutrophil chemotaxis in Boyden chambers was slightly reduced, but only one patient showed a migration below normal values. In vivo mobilization of polymorphonuclear leukocytes into skin windows was also slightly decreased. In contrast, neutrophil polarization and orientation was normal. The bactericidal activity of neutrophils from patients with primary ciliary dyskinesia was normal, while the ingestion of bacteria was decreased.

The abnormalities of neutrophil function in patients with primary ciliary dyskinesia are related to motility. It is suggested that the microtubule defect responsible for the abnormal pattern of ciliary beating is a general abnormality also responsible for the depression of polymorphonuclear leukocyte motility.
The renin‐angiotensin system during converting enzyme inhibition with captopril in patients with severe treatment‐resistant hypertension
Authors: RASMUSSEN STEN , NIELSEN META DAMKJÆR , IBSEN HANS , LETH ARNE , GIESE JØRN
Published: March 2008

Abstract. The effect of captopril on blood pressure (BP) and various components of the renin‐angiotensin system was assessed in ten severely hypertensive patients. Captopril acutely reduced the BP with a maximum decrease of 23% at 90–120 min.

Maintenance treatment with captopril alone could not control the BP in any of the patients. Addition of hydrochlorothiazide markedly reduced the BP, while supplementation with propranolol caused no consistent changes.

Three patients attained a supine diastolic blood pressure (SDBP) ≤90 mmHg. Only two patients had a fall in SDBP less than 10 mmHg. One patient stopped because of taste disturbances.

Monitoring the renin‐angiotensin system showed suppressed plasma concentrations of angiotensin II and increased levels of angiotensin I and renin, indicating the inhibition of converting enzyme activity. Plasma concentration of renin substrate decreased significantly. This observation has important implications for the methodology of renin assays.

Captropril is an effective alternative in the treatment of hypertensive patients not readily controlled with conventional therapy.
Immune complex‐like material in the serum and plasma exchange in patients with metastatic cancer
Authors: KRIEGER G. , BEYER J.‐H. , KEHL A. , KNEBA M. , KABOTH U. , NAGEL G. A.
Published: March 2008

Abstract. Clinical significance of immune complex‐like material in the serum was investigated in tumour patients undergoing plasma exchange with albuminsaline solution and subsequent chemotherapy. Immune complexes were detected by the C1q binding assay or the Raji cell radioimmunoassay in nine out of forty‐five patients before this therapy.

Levels of immune complexes were decreased to 10–30% of the initial value by plasma exchange depending on exchanged plasma volume. In contrast to other serumproteins like α1‐antitrypsin and α2‐macroglobulin, which showed protein specific increase during follow up after plasma exchange in all patients, recovery rates of immune complexes and IgG were highly individual but parallel in each patient.

Clinical response to this protocol did not correlate with immune complex status, suggesting that removal of the measured immune complex like material had little clinical significance or was not longlasting enough to provide therapeutic benefit.
Simultaneous assay of noradrenaline and its deaminated metabolite, dihydroxyphenylglycol, in plasma: a simplified approach to the exclusion of phaeochromocytoma in patients with borderline elevation of plasma noradrenaline concentration
Authors: BROWN M. J.
Published: March 2008

Abstract. The fate of noradrenaline released from sympathetic endings differs from that of noradrenaline secreted directly into the bloodstream. This has been used to establish a single sample test for the exclusion of phaeochromocytoma in patients with borderline elevation of plasma noradrenaline concentration. This test is based on the measurement of the ratio in plasma of noradrenaline to its deaminated metabolite, dihydroxyphenylglycol (DHPG). The latter was shown to reflect mainly nervous release of noradrenaline and its plasma concentration was not increased during intravenous noradrenaline infusion. In seventeen phaeochromocytoma patients the ratio in plasma of noradrenaline to DHPG was greater than 2 (range 2·05–3·57); in nineteen non‐phaeochromocytoma patients the reverse was found, the ratio of DHPG to noradrenaline being greater than 2 (range 2·08–2·74). Since DHPG can be measured simultaneously with noradrenaline, measurement of the plasma ratio of these two catechols may prove a simple method of differentiating phaeochromocytoma from non‐phaeochromocytoma patients.
Effect of ciprofibrate treatment on biliary lipids in patients with hyperlipoproteinaemia
Authors: ANGELIN BO , EINARSSON KURT , LEIJD BARBRO
Published: March 2008

Abstract. Treatment with hypolipidaemic drugs such as clofibrate increases secretion of biliary cholesterol and induces supersaturation of bile, leading to an increased risk of gallstone formation. Ciprofibrate is a phenoxyisobutyrate derivative with lipid‐lowering effects in hyperlipoproteinaemia. We analysed serum lipid levels and biliary lipid composition and cholesterol saturation of gallbladder bile in nineteen hyperli‐poproteinaemic patients before and after 6 weeks treatment with ciprofibrate, 100 mg daily. In addition, hepatic secretion rates of biliary lipids were determined in eight of the patients. Ten of the patients were also studied after 1 year of treatment.

Short‐term treatment reduced the serum cholesterol levels by about 20% (P < 0·001) and the serum triglycerides by about 40% (P < 0·001). The relative cholesterol concentration and cholesterol saturation of bile were not significantly increased for the group as a whole, nor in patients with familial hypercholesterolaemia (n= 9), or with other types of hyperlipidaemia (n= 10). During treatment, however, fourteen patients had saturated bile compared with nine before treatment. An increase in cholesterol saturation was the consequence of an increased hepatic secretion of cholesterol whereas the secretion rates of bile acids and phospholipids were unaffected.

After 1 year of treatment the serum lipid concentrations were reduced to about the same level as after 6 weeks, whereas biliary lipid composition and cholesterol saturation had returned to pre‐treatment values.

In contrast to clofibrate ciprofibrate exerts hypolipidaemic effects without consistently increasing the relative cholesterol concentration in bile. In some patients it leads to a transient rise in cholesterol saturation of gallbladder bile. This effect is due to an enhanced secretion of cholesterol probably because of a mobilization of tissue cholesterol.
Direct and indirect measurement of urinary kallikrein excretion in patients with essential hypertension and normotensives: relation to age and plasma renin and aldosterone levels
Authors: KOOLEN M. I. , DAHA M. R. , FRÖLICH M. , ES L. A. VAN , BRUMMELEN P. VAN
Published: March 2008

Abstract. The relevance of age and activity of the renin‐angiotensin‐aldosterone system to the excretion of urinary kallikrein (Ukal) was studied in twenty‐five patients with essential hypertension and forty normotensive controls. The age range for both study groups was 20–60 years. Ukal was measured by radioimmunoassay and by an amidolytic assay. Results of both assays correlated closely (r= 0·93, n= 65, P < 0·001). For all hypertensives Ukal excretion was not significantly different from that of controls. However, older hypertensives (> 40 years, n= 13) had a significantly lower Ukal excretion than normotensives of the same age (n= 20) (radioimmunoassay 67·2 (SEM 7·2) v. 105·1 (SEM 8·4) μg (24 h)‐1; and amidolytic method 0·84 (SEM 0·10) v. 1·13 (SEM 0·08) U (24 h)‐1). No correlation was found between Ukal excretion and plasma renin or aldosterone. In fact, the aldosterone level was highest in older hypertensives.

In conclusion, the lower Ukal excretion in hypertensives over 40 is likely to be secondary to the long‐standing high blood pressure. Under basal conditions, Ukal excretion seems little influenced by the activity of the renin‐angiotensin‐aldosterone system.
Biochemical changes in parenchymal lung tissue associated with posttraumatic respiratory failure
Authors: NERLICH ANDREAS G. , NERLICH MICHAEL L. , JOACHIM HANS , MÜLLER PETER K.
Published: March 2008

Abstract. We analysed the composition of parenchymal lung tissue from eleven multiply injured patients who died of protracted respiratory failure after an accident and six normal lungs. Lung wet and dry weights, protein, DNA, RNA and collagen amounts were determined in the lungs.

Concentrations per dry weight of all parameters revealed only minor changes. Since there was a marked, time‐dependent increase in both wet and dry weight, total lung contents of all components showed highly significant increases with survival time. Protein and RNA contents were elevated linearly in all patients, whereas DNA and collagen increased only in patients surviving more than 2 weeks. No correlation existed between biochemical data and a morphological fibrosis score, while morphometrically estimated cellularity and DNA concentration agreed well.

Our results provide evidence that the reparative process for lung injury associated with traumatic shock is a tissue remodelling involving all tissue components in the long run.
Size and strength of the quadriceps muscles of old and young women*
Authors: YOUNG A. , STOKES M. , CROWE M.
Published: March 2008

Abstract. Muscle weakness and wasting may be evaluated objectively by dynamometry and compound ultrasound imaging. We have measured the voluntary isometric strength of the quadriceps muscles of healthy women in their 70s (n= 25) and in their 20s (n= 25) and have compared it with the mid‐thigh cross‐sectional area of the same muscles.

The two groups of women showed similar variability when strength was measured on consecutive days (coefficients of variation: 8%). The older women were 35% weaker than the young women (P < 0·001) and their quadriceps cross‐sectional area was 33% less (P < 0·001). Quadriceps strength and cross‐sectional area were correlated (r= 0·66, P < 0·001, elderly; r= 0·53, P < 0·01, young) and the principal axis of the relationship was closely similar for the two groups of women. There is therefore no difference in the intrinsic strength of the quadriceps muscles of healthy women in their third and eighth decades.

This report also provides normative data for the objective evaluation of quadriceps weakness and/or wasting in female patients. The techniques involved are straightforward, the dynamometer is easily made, and compound ultrasound imaging is widely available.
Tlymphocyte subsets in homosexual men from Copenhagen
Authors: GERSTOFT JAN , PETERSEN CARSTEN S. , KROON SUSANNE , ULLMAN SUSANNE , BENTSEN KIRSTEN , DICKMEISS EBBE , NIELSEN JENS OLE , MOGENS HANS , ANDERSEN KERZEL , LORENZEN IB
Published: March 2008

Abstract. Screening of sixty‐six asymptomatic homosexual men from Copenhagen revealed significantly lower Leu‐3a/Leu‐2a ratios as compared to controls. Ten (15%) of the homosexuals had a ratio ≤ 1·0. The low Leu‐3a/Leu‐2a ratios were the result of an increase in the absolute number of Leu‐2a cells. Homosexuals with many partners and those who had been sexual partners of patients with the acquired immuno‐deficiency syndrome (AIDS) had significantly lower ratios than those without these features. Cytomegalovirus was isolated from urine and/or sputum of 15% and this was associated with a Leu‐3a/Leu‐2a ratio ≤ 1·0. The observed immunological abnormalities could either represent latent infection with the putative AIDS agent or alternatively be caused by repeated infections and/or exposure to allogenic spermatocytes or lymphocytes.
A glucose transfer from membrane glycoconjugates to haemoglobin in isolated young red blood cells: another biosynthetic way for glycosylated haemoglobins
Authors: GILLERY PHILIPPE , MAQUART FRANÇOIS‐XAVIER , CORCY JEAN‐MARC , RANDOUX ALAIN , BOREL JACQUES PAUL
Published: March 2008

Abstract. Human red blood cells (RBC) are separated by centrifugation into young and old ones, as demonstrated by lower enzymatic activities and lower potassium content of the older ones. The young RBC fraction represents 5% of total RBC. After incubation for 24 h in a neutral buffer, the young RBC HbA1c content increases significantly from 4·2 to 5·2% of total Hb. No increase is found in the case of old RBC. When young RBC have been extracted for 1 h by a neutral buffer prior to incubation, there is no more increase of HbA1c.

The extract contains a glycoconjugate that is both soluble in neutral buffers and in chloroform. A glycolipid extractable from the young RBC membrane contributes to HbA1c formation but disappears from old RBC, in which glycosylation by free glucose occurs. These processes are stereospecific.
Control of the acute‐phase serum amyloid A and C‐reactive protein response: comparison of total replacement of the hip and knee
Authors: MAURY C. P. J. , TEPPO A.‐M. , RAUNIO P.
Published: March 2008

Abstract. The acute‐phase serum protein response induced by arthroplasty of the knee was compared with that induced by arthroplasty of the hip in patients with rheumatoid arthritis (RA). Total replacement of the knee (n= 13) caused a markedly greater serum amyloid A protein (SAA) (P<0·001) and C‐reactive protein (CRP) (P<0·001) elevation that did total replacement of the hip (n=13). This effect was not merely due to the use of tourniquet in the knee arthroplasties, since synovectomy of the knee, matched for the duration of the use of tourniquet, induced an SAA response that was significantly lower (P<0·001) than that caused by replacement of the knee; the SAA response after knee synovectomy was similar to that after hip arthroplasty. The kinetics and magnitude of the SAA response in patients with reactive amyloidosis were similar to those found in RA patients without amyloidosis.

The results show that replacement of the knee is a stronger stimulator of SAA and CRP elevation than replacement of the hip. Thus, total replacement of the knee, possibly due to the performance of the arthroplasty under ischaemic conditions, appears to be more traumatic to the organism than total replacement of the hip.
Platelets during alimentary hyperlipaemia induced by cream and cod liver oil
Authors: NORDØY A. , LAGARDE M. , RENAUD S.
Published: March 2008

Abstract. Healthy male subjects were given 100 g lipids as cream or cod liver oil. They were examined before and during alimentary hyperlipaemia. Cream increased platelet coagulant activity in plasma and reduced it in washed platelets. Both meals increased platelet sensitivity to thrombin and collagen. Cod liver oil reduced the uptake of arachidonic acid (AA) in platelets. Washed platelets prelabelled with [14C]‐AA increased radioactivity 10‐fold in free fatty acids (FFA) by exposure to thrombin [2 U (109 platelets)‐1] for 20 s. This increase was augmented by cod liver oil. Phosphatidylethanolamine and phosphatidylcholine were the most significant donors of AA during thrombin stimulation. By exposure of prelabelled washed platelets to thrombin [0·3 U (109 platelets)‐1] for 4 min the percentage distribution of [14C]‐AA increased after cod liver oil in FFA plus the products of AA metabolism formed by the cyclooxygenase and lipoxygenase pathways.

This study indicates that intake of a meal rich in lipids induces acute disturbances in platelets that may favour thrombosis. These effects were observed after intake of both saturated and polyunsaturated fatty acids.
Acute effect of smoking on fibrinolysis: increase in the activity level of circulating extrinsic (tissue‐type) plasminogen activator*
Authors: ALLEN R. A. , KLUFT C. , BROMMER E. J. P.
Published: March 2008

Abstract. The acute effect of cigarette smoking on the fibrinolytic enzyme system in blood was studied. It was found imperative to have an initial 30 min rest period, after venipuncture, to obtain a stable baseline in the fibrinolytic studies.

The average heart rate, in inhaling smokers, increased from 64 to a peak of 79 beats min‐1 5–10 min after commencement of smoking. A peak in fibrinolytic activity was found to occur later, at 22·5 min. Analysis of the increase in fibrinolytic activity revealed no demonstrable activation of intrinsic systems via factor XII, nor changes in plasminogen, prekallikrein and C1‐inactivator. No plasmin‐α2‐antiplasmin complexes were detectable. The increase (P<0·01) was found to be due to extrinsic (tissue‐type) plasminogen activator, revealed as C1‐inactivator‐resistant plasminogen activator activity, and further identified by quenching with anti‐tissue plasminogen activator IgG.

Thus, smoking appears to elicit a significant increase in the level of activity of circulating extrinsic plasminogen activator.
Enhanced fibrinolytic activity during cardiopulmonary bypass in open‐heart surgery in man is caused by extrinsic (tissue‐type) plasminogen activator
Authors: STIBBE JEANNE , KLUFT CORNELIUS , BROMMER EMILE J. P. , GOMES MARIA , JONG DICK S. DE , NAUTA JAN
Published: March 2008

Abstract. The nature of the enhanced blood fibrinolytic activity which is known to occur during cardiopulmonary bypass is not understood. We show here that the cause is an increase in extrinsic (tissue‐type) plasminogen activator.

In six patients, the nature of the enhanced blood fibrinolytic activity that evolved during cardiopulmonary bypass was characterized by differential inhibition using the fibrin plate method and was shown to be C1‐inactivator‐resistant (extrinsic‐activator activity). The C1‐inactivator‐resistant‐activator activity was completely quenched by an antibody against extrinsic (tissue‐type) plasminogen activator but not by antiurokinase, proving that the activity was due to the presence of extrinsic (tissue‐type) plasminogen activator. The concentration of extrinsic (tissue‐type) plasminogen activator increased during cardiopulmonary bypass and disappeared rapidly thereafter. Fibrinogen, plasminogen and α2‐antiplasmin were not consumed during cardiopulmonary bypass, while no increase or occasionally a moderate one in fibrinogen degradation products occurred. This is in accord with the property of extrinsic (tissue‐type) plasminogen activator which activates plasminogen predominantly at sites where fibrin is present and not in the free circulation.