bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal study of bone mineral content in the lumbar spine, the forearm and the lower extremities after spinal cord injury
Authors: BIERING‐SØRENSEN F. , BOHR H. H. , SCHAADT O. P.
Published: March 2008

Abstract. Bone mineral content (BMC) of the lumbar spine, femoral neck and shaft, and proximal tibia was measured by dual photon absorptiometry in six men and two women after traumatic spinal cord injuries. In six of these patients, BMC of the distal forearm was measured as well. The patients were 18–49 years old at injury and had complete motor lesions from C7 to LI. All but one had some spasticity, and they all used a wheelchair. The initial BMC measurements were carried out from 9–167 days (median 43) post‐injury and followed up by 5–13 (median 8) measurements up to 31 ‐53 months (median 41) after the injury. BMC of the lumbar spine and distal forearm remained nearly unchanged in the whole period, and the measurements were within the normal range, except for the lumbar spine when Harrington rods in the scanned area induced high BMC values. In the lower extremities the BMC decreased after injury. New steady‐state levels for BMC were reached at 2 years post‐injury for the proximal tibia and the femoral neck at 40–50% and 60–70% respectively of normal values. For the femoral shaft the decrease in BMC was more slow and it seems that a steady‐state was not reached within our observation period for several of the patients.

This longitudinal study indicates, in agreement with a previous cross‐sectional study, that normal muscle function and load bearing is necessary to prevent bone loss.
Postprandial exocrine pancreatic function during long‐term treatment with the somatostatin analogue SMS 201–995 in acromegalic patients
Authors: LIESSUM P. A. VAN , HOPMAN W. P. M. , PIETERS G. F. F. M. , SMALS A. G. H. , TANGERMAN A. , JANSENJ J. B. M. J. , ROSENBUSCH G. , LAMERS C. B. H. W.
Published: March 2008

Abstract.

Long‐term treatment with the somatostatin analogue SMS 201–995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6‐h urinary excretion of p‐aminobenzoic acid (PABA) and p‐aminosali‐cylic acid (PAS) after s.c. injection of 100 μg SMS or placebo and after ingestion of 2 mmol nBT‐PABA and 2 mmol PAS.

In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P > 0.10) and higher than in healthy volunteers (n= 8, P=0–05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers.

It is concluded that despite a blunted release of the trophic hormone CCK, long‐term treatment with SMS 201–995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.
Detection of autoantibodies to Sm antigen in systemic lupus erythematosus by immunodiffusion, ELISA and immunoblotting: variability of incidence related to assays and ethnic origin of patients
Authors: ABUAF N. , JOHANET C. , CHRETIEN P. , ABSALON B. I. , HOMBERG J. C. , BURI J. F.
Published: March 2008

Abstract. Autoantibodies to small nuclear ribonucleo‐proteins (snRNP) were studied using the techniques of immunodiffusion, ELISA, and immunoblotting in the sera of 150 patients with systemic lupus erythematosus (SLE), and of 29 patients with mixed connective tissue disease; 900 control patients and 100 normal blood donors were examined simultaneously. The incidence of anti‐Sm antibodies in French SLE patients was low compared with the occurrence observed in similar studies in USA (even when highly sensitive assays were used) but was of the same magnitude as European results. Frequency of anti‐Sm antibodies in SLE patients varied moderately when detected by immunodiffusion (12%), or by immunoblotting (17%), however, it seems that the ethnic and/or genetic background of patients induces more significant differences. SLE patients from the French West Indies had anti‐Sm antibodies in 39% of cases when detected by immunodiffusion and in 50% when immunoblotting was used. In these patients the incidence of the antibodies was five times more frequent than that of mainland French patients. Immunization against snRNP does not seem to be a common feature of all SLE patients.
Cellular targets and receptors for interleukin‐6 I. In vivo and in vitro uptake of IL‐6 in liver and hepatocytes
Authors: SONNE O. , DAVIDSEN O. , MØLLER B. K. , PETERSEN C. MUNCK
Published: March 2008

Abstract. Interleukin‐6 (IL‐6) is a potent stimulator of the hepatic synthesis of acute‐phase proteins. 125I‐labelled IL‐6 disappeared from the blood of rats with an overall half‐time of about 1.5 min; 41% of the injected tracer dose was recovered in the liver by 15 min. The clearance was biphasic. The simultaneous injection of tracer and an excess of unlabelled IL‐6 eliminated the initial rapid phase, and reduced the hepatic uptake to 14%. Light microscopic autoradio‐graphy showed 5% of the grains over non‐hepatocytes, and 80% over hepatocytes, accumulating in areas around the bile canaliculi. Thereafter, degradation products accumulated in the bile. At 4d̀C, isolated rat hepatocytes bound IL‐6 with an apparent Kd of 39 pmol 1‐1 to a uniform class of 4500 receptors per cell with an apparent molar mass of 115–120 kg mol‐1. The HepG2 human hepatocellular cell line bound IL‐6 with an apparent Kd of 21 pmol 1‐1 to a uniform class of 1200 receptors per cell with an apparent molar mass of 155–160 kg mol‐1. At 37d̀C, both cell types endocytosed the bound ligand slowly, and degradation products appeared in the medium after a relatively long lag period (40 min in hepatocytes and 1 h in HepG2 cells).,
IgG heavy‐chain subclass restriction of thyrotropin‐binding inhibitory immunoglobulins in Graves' disease
Authors: WEETMAN A. P. , BYFIELD P. G. H. , BLACR C. , REIMER C. B.
Published: March 2008

Abstract. The IgG subclass composition of antibodies is an important determinant of their function. Thyro‐tropin receptor antibodies cause the hyperthyroidism of Graves' disease but their subclass distribution has been incompletely investigated. We have therefore purified IgG subclasses from Graves' sera by passage over affinity columns designed to deplete all but a single subclass, and then assayed those pure subclass fractions for their ability to displace radiolabelled thyrotropin from its solubilized receptor as a measure of thyrotropin receptor antibody activity. Sufficient activity was recovered for analysis in nine of 10 Graves' patients, in five of whom activity was almost completely (97–100%) restricted to the IgG, subclass; in the remaining four patients the response was predominantly IgG1 and IgG4 with marked under‐representation of the IgG2 subclass. This contrasts with the unrestricted subclass response, in the same fractions, for autoantibodies against thyroglobulin and microsomes. These results suggest that there may be a primary defect at the B‐cell level in Graves' disease.,
Ascorbate‐induced hyperoxalaemia has no significant effect on lactate generation or erythrocyte 2,3, diphosphoglycerate in dialysis patients
Authors: TOMSON C. R. V. , CHANNON S. M. , WARD M. K. , LAKER M. F.
Published: March 2008

Abstract. To examine the possible effects of hyperoxalaemia on anaerobic metabolism and erythrocyte pyruvate kinase activity, we induced a rise in plasma oxalate in 11 dialysis patients by the oral administration of ascorbic acid, 500 mg day‐1 for 3 weeks. Blood samples were taken from the same antecubital vein before and after the supplementation period, without venous stasis, after an overnight fast. This protocol allowed patients to be used as their own controls. Five healthy subjects underwent an identical protocol to exclude any effect of ascorbate per se.

Mean (SEM) plasma oxalate (μmol l‐1) rose from 30.3 (3.5) to 48.4 (6.1) in patients and from 1.4 (0.2) to 6.8 (0.9) in healthy subjects. Whole blood ascorbate (mgl‐1) rose from 70 (0.7) to 26.6 (2.5) in patients and from 9.3 (1.2) to 17.8 (1.8) in healthy subjects (reference range 7.5–20.0 mg l‐1).

No changes were observed in either group in plasma creatinine, bicarbonate, haemoglobin, or erythrocyte 2,3, diphosphoglycerate (2,3 DPG) after the 3 week supplementation period.

Before supplementation lactate generation (area under curve, mmol min l‐1) in the 5 min following a 60 s period of standardized ischaemic forearm exercise was significantly (P= 0.026) greater in patients [69.1 (4.7)] than in healthy subjects [46.9 (6.7)]; no significant change in lactate generation occurred in either group after ascorbate‐induced hyperoxalaemia.

We conclude that changes in plasma oxalate of the order of 20 μmol l‐1 have no significant effect on lactate generation or 2,3, DPG levels in uraemic subjects.,
Gastric microvascular endothelium: a major target for aspirin‐induced injury and arachidonic acid protection. An ultrastructural analysis in the rat
Authors: TARNAWSKI A. , STACHURA J. , GERGELY H. , HOLLANDER D.
Published: March 2008

Abstract. Exposure of the gastric mucosa to aspirin results in exfoliation of the surface epithelium and deep mucosal necrosis. We assessed the changes in the mucosal microvessels during aspirin‐induced injury and arachidonic acid protection of the gastric mucosa using transmission electron microscopy. Male Spra‐gue‐Dawley rats received intragastric pretreatment with either solubilizer (control) or detergent solubi‐lized arachidonic acid (148 mg kg‐1). One hour later 1‐ml suspension of 200 mg kg‐1 body weight acidified aspirin was administered intragastrically. The ultra‐structure of mucosal microvasculature was assessed at 15 min and 4 h after aspirin administration both qualitatively and quantitatively by determining the number of necrotic or damaged capillaries in standardized mucosal sections. In addition, mucosal specimens were immunostained with a specific antiserum against vimentin, an endothelial marker, and fluorescence intensity was measured with a Nikon FX microscopic photometric system. In control rats, aspirin produced significant damage to both superficial and deeper microvessels consisting of: rupture of capillary walls, necrosis of endothelial cells, damage to endothelial organelles, deposition of fibrin and adherence of platelets to damaged endothelium. Vimentin fluorescence was reduced three‐fold. Microvascular injury preceded the development of deep necrotic lesions. Microvascular damage and deep mucosal necrosis were significantly reduced by arachidonic acid pretreatment. We conclude that gastric mucosal microvessels are the major target for aspirin‐induced injury and arachidonic acid protection.,
Effect of a monounsaturated diet vs. a polyunsaturated fatty acid‐enriched diet on blood pressure in normotensive women and men
Authors: MENSINK R. P. , STOLWIJK A. M. , KATAN M. B.
Published: March 2008

Abstract. The effect on blood pressure of monounsaturated and (n‐6)polyunsaturated fatty acids was studied under strict dietary control in normotensive subjects. For 17 days 31 women and 27 men received a control diet providing 19.3% of energy as saturated fat. Then subjects were randomized over two test diets: one diet provided 15.1% of energy from monounsaturated and 7.9% from polyunsaturated fatty acids (‘mono diet’), and the other diet provided 10.8% from monounsaturated and 12.7% from polyunsaturated fatty acids (‘poly diet’). Saturated fat intake was now 12.8% on both diets.

Mean blood pressure at the end of the control period was 116/69 mmHg for the mono group and 117/73 mmHg for the poly group. After 5 weeks on the test diet, blood pressure was 115/67 mmHg for the mono group and 117/72 mm Hg for the poly group (difference in changes between the two diet groups was not significant).

These findings suggest that at a high fat intake, linoleic acid, when providing more than 7.9% of energy intake, does not influence blood pressure relative to oleic acid in normotensive women and men.,
Host and tumour factors in cancer metastasis
Authors: FIDLER I. J.
Published: March 2008

Abstract. The process of cancer metastasis is sequential and selective and contains stochastic elements. The growth of metastases represents the endpoint of many lethal events that only few tumour cells survive. Primary tumours contain cells with heterogeneous metastatic properties, and the outcome of metastasis depends on the interplay of tumour cells with various host factors. Collectively, then, our studies and most data reported by others have led us to conclude that metastasis is a highly selective process regulated by a number of mechanisms. This belief is contrary to the once widely accepted notion that neoplastic dissemination is the ultimate expression of cellular anarchy. In fact, suggesting that cancer metastasis is a selective process is a more optimistic view in terms of cancer therapy than the one that contends that tumour dissemination is an entirely random event. A selective biological process is regulated by the interaction of tumour cells with their host, and these complex interactions can be studied and manipulated. A better understanding of the complexity of the processes of tumour evolution, progression, and metastasis should lead to improvements in the treatment of cancer.
Interferon‐γ reverses the stimulation of collagen but not fibronectin gene expression by transforming growth factor‐ β in normal human fibroblasts
Authors: VARGA J. , OLSEN A. , HERHAL J. , CONSTANTINE G. , ROSENBLOOM J. , JIMENEZ S. A.
Published: March 2008

Abstract. It has recently become apparent that several cytokines and growth factors are capable of modulating fibroblast proliferation and biosynthetic activity. To understand the role of these factors in connective tissue regulation, we examined the effects of the simultaneous addition of interferon‐γ (IFN‐γ) and transforming growth factor‐β (TGF‐β) on normal human dermal fibroblast collagen and fibronectin production. In addition, in vitro transcription rates and steady‐state mRNA levels for these molecules were determined by nuclear run‐off assays and Northern and dot‐blot hybridization using specific human cDNA probes. Treatment of cultures with TGF‐β caused stimulation of collagen and fibronectin production. Addition of IFN‐γ to the TGF‐γ‐treated cultures abrogated the stimulatory effects of TGF‐γ on collagen production in a dose‐dependent manner and resulted in a net inhibition of collagen production. In contrast, the increase in fibronectin synthesis induced by TGF‐γ was augmented further by IFN‐γ. These changes in collagen and fibronectin production were accompanied by parallel changes in the steady‐state mRNA levels for these proteins. The effects of TGF‐γ plus IFN‐γ on fibronectin gene expression appeared to be mediated entirely by transcriptional mechanisms, whereas the effects on collagen gene expression resulted from a combination of transcriptional and post‐transcriptional events.
Increased insulin resistance and fat cell lipolysis in obese but not lean women with a high waist/hip ratio
Authors: LANDIN K. , LÖNNROTH P. , KROTKIEWSKI M. , HOLM G. , SMITH U.
Published: March 2008

Abstract. Increased lipolysis in abdominal adipocytes has been suggested to be of importance for the insulin resistance typical for abdominal obesity. In order to differentiate between fat distribution, measured as waist/hip ratio (WHR), and amount of body fat, glucose disposal during a euglycaemic clamp as well as lipolysis in isolated cells from abdominal and gluteo‐femoral regions were studied in 20 obese and 20 lean postmenopausal women with a high (n= 10) and low (n= 10) WHR, respectively.

The lipolytic response was increased in cells from obese women irrespective of region. Furthermore, lipolysis was enhanced in abdominal compared with the gluteo‐femoral cells in obese women with a high WHR. Fasting blood glucose and insulin were increased in both groups of obese women while the degree of insulin resistance was most pronounced in the obese women with a high WHR.

It is concluded that increased body fat is associated with both insulin resistance and increased lipolysis, and that this relationship is stronger in the presence of a high WHR. A high WHR may increase the expression of obesity as a risk for insulin resistance and this may be mediated through an increased lipolytic rate.
Hepatitis B vaccination of haemodialysis patients: randomized controlled trial comparing plasma‐derived vaccine with and without pre‐S2 antigen
Authors: SMIT‐LEIJS M. B. L. , KRAMER P. , HEIJTINK R. A. , HOP W. C. J. , SCHALM S. W.
Published: March 2008

Abstract. The pre‐S2protein of the hepatitis B virus envelope evokes anti‐pre‐S2antibodies and enhances the anti‐HBs response after vaccination in mice. In order to evaluate the immunogenicity of the pre‐S2Ag in man, 102 HBsAg, anti‐HBs, anti‐HBc‐negative haemodialysis patients were vaccinated at random according to one of four vaccination schedules: 5 μg plasma vaccine Pasteur (containing 1 % pre‐S2) or 20 μg plasma vaccine MSD (no pre‐S2) at 0, 1, 2, 4, 6 and 12 months; or 10 μg Pasteur or 40 μg MSD at 0, 1,2 and 6 months. Anti‐HBs levels were measured by RIA and expressed in IU 1‐1; anti‐pre‐S2response was evaluated by both EIA and Western blot analysis.

Eighty‐four per cent (95% confidence interval: 75–93) of the patients exhibited an anti‐HBs response of 2 IU l‐1or more and 71% (95% confidence interval: 61–81) reached an anti‐HBs level of at least 10 IU l‐1 within 13 months of the start of vaccination. Anti‐HBs response correlated with age (the response rate decreased with increasing age) but not with either the type of vaccine or dosage. An anti‐pre‐S2response was observed in 16% (EIA) and 46% (Western blot) of the patients immunized with the Pasteur vaccine and none (EIA, Western blot) of the MSD group. The level of anti‐pre‐S2antibodies correlated with high anti‐HBs titres; an anti‐pre‐S2response occurred in only one anti‐HBs‐negative patient.

The addition of 1% pre‐S2to the HBsAg plasma hepatitis B vaccine had no significant effect on the anti‐HBs response in haemodialysis patients and did not markedly broaden protective immunity. Further studies of recombinant vaccines with a higher pre‐S2content are needed to document the possibility of enhanced immunogenicity of pre‐S2Ag‐containing hepatitis B vaccines in man.
Iodide‐induced hypothyroidism in patients after thyroid resection
Authors: CLARK O. H. , CAVALIERI R. R. , MOSER C. , INGBAR S. H.
Published: March 2008

Abstract. The purpose of this investigation was to determine whether an intrinsic defect in thyroid hormone production is required for the development of iodide‐induced hypothyroidism or does it also develop in TSH‐stimulated normal thyroid tissue. To answer this question, we studied the response to iodine administration (180 mg iodide daily for 3–4 months) in eight euthyroid patients who had had partial thyroidectomies 2 months to 10 years previously for benign thyroid nodules, and in three euthyroid control subjects. In all 11 euthyroid patients, basal serum TSH concentrations increased during iodide administration. In six of the eight patients who had previous thyroid operations and in two of the three control patients, basal serum TSH concentrations increased into the abnormal range (greater than 6 U ml‐1). Increased serum TSH concentrations were noted as early as 1 week after potassium iodide had been started and the increased levels persisted during the period of iodide administration. Although basal values for serum TSH concentration were initially within the normal range, those patients with highest basal serum TSH values developed the greatest increase in TSH in response to potassium iodine. Among the eight patients treated by partial thyroidectomy, serum T4 concentrations decreased in five, serum T3 concentration decreased in three and all five developed mild symptoms of hypothyroidism while receiving iodide. Serum T4 concentrations also decreased slightly in two of the three control patients. Serum total iodine levels increased from 70pM 0.5 to 315.7 pM 108.6 g dl‐1 (mean‐pM standard error) during potassium iodide administration, but there was no correlation between the level of serum iodide concentration achieved and inhibition of thyroid function. When iodide was discontinued, symptoms disappeared and thyroid function tests returned to baseline levels within 1 month in all patients, It thus appears that a restricted thyroid mass and/or a mild increase in TSH stimulation is all that is required for the development of hypothyroidism in man when exposed to excessive iodide.
Arterial wall hypoxia following hyperfusion through the vasa vasorum is an initial lesion in atherosclerosis
Authors: MARTIN J. F. , BOOTH R. F. G. , MONCADA S.
Published: March 2008

Abstract. Pressure on the outside of arteries can cause physical and biochemical changes in the vessel wall of rabbits which are characteristic of atherosclerosis. It is hypothesized that occlusion of the vasa vasorum causes ischaemia of the arterial media which results in smooth muscle cell proliferation and cellular accumulation of cholesteryl esters. Hypoxia increases mRNA for platelet‐derived growth factor in arterial wall cells and increases the activity of acyl CoA: cholesterol acyltransferase (ACAT). Such a mechanism may explain many of the anatomical, actuarial and environmental risk factors for atherosclerosis. Hyperfusion of the vasa vasorum may follow thrombosis.
Increased thromboxane formation in patients with antiphospholipid syndrome
Authors: ÅRFORS L. , VESTERQVIST O. , JOHNSSON H. , GRÉEN K.
Published: March 2008

Abstract. Thirty‐one patients with IgG antibodies to cardiolipin (ACLA) were studied to determine their in vivo formation of the platelet aggregating and vasoconstricting substance thromboxane A2 (TxA2) and the platelet inhibiting and vasodilating substance prostacyclin (PGI2). This was done by measurements in urine of their enzymatically formed metabolites 2,3‐dinor‐TxB2 and 2,3‐dinor‐6‐keto‐PGF1x, respectively, using gas chromatography mass spectrometry. It is demonstrated that patients with IgG ACLA have a highly significant increase in the biosynthesis of TxA2 compared with age‐matched healthy controls (807 pM 163 [SEM] vs. 230 pM 15 pg mg‐1 creatinine, P= 0.0000005). A significant increment of the formation of PGI2 was also found (189 pM 23 (SEM) vs. 125 pM 11 pg mg‐1 creatinine, P= 0.03), although this was much less pronounced than that for TxA2. We conclude that the highly increased formation of TxA2, reflecting platelet activation, in patients with IgG ACLA is of pathophysiologic relevance for their tendency to arterial and venous thrombosis and hence that they should be considered for prophylactic treatment with inhibitors of TxA2 formation, like aspirin.
Atrial natriuretic factor, cyclic 3‘,5’‐guanosine monophosphate and prostaglandin E2 in liver cirrhosis: relation to blood volume and changes in blood volume after furosemide
Authors: JESPERSEN B. , JENSEN L. , SØRENSEN S. S. , PEDERSEN E. B.
Published: March 2008

Abstract. Plasma concentrations of atrial natriuretic factor (ANF) and cyclic 3′,5‐guanosine monophosphate (cGMP) were measured in 11 cirrhotic patients with ascites, 11 cirrhotic patients without ascites and 15 control subjects. The following were determined in 15 of the cirrhotic patients and in all the control subjects: blood volume (BV) and furosemide‐induced changes in BV, plasma values of ANF, cGMP, angiotensin II (AII), aldosterone (Aldo), arginine vasopressin (AVP) and urinary excretion rates of cGMP, prostaglandin E2 (PGE2), water and sodium. Basal plasma levels of ANF and cGMP were higher in patients with cirrhosis than in controls, but were the same in both groups of cirrhotics (ANF: cirrhosis with ascites 12.7, without ascites 13.4, and in controls 5.8 pmol l‐1 (medians); cGMP: 7.7, 7.4 and 4.3 nmol l‐1, respectively). BV was less reduced after furosemide in the cirrhotic patients (6.0%) than in the healthy subjects (10.1%), but basal BV did not differ. Urinary sodium excretion rates after furosemide were significantly lower in the cirrhotic patients than in the controls. PGEl excretion rate increased after furosemide in the cirrhotic patients (0.29 to 0.66 pmol minl‐1; P < 0.01) but not in the controls (0.31 to 0.38 pmol minl‐1). After furosemide ANF and cGMP decreased slightly in both groups whereas AII and Aldo increased; AVP increased in the controls, but not in the cirrhotic patients.

In conclusion, plasma values of ANF and cGMP are increased in liver cirrhosis both with and without ascites. This and the elevated PGEl2 excretion after furosemide may be compensatory phenomena in order to facilitate renal sodium excretion.
Arachidonic acid absorption in human jejunum in organ culture: effects of ethanol
Authors: BARROS H. , CHEN Q. , FLORÉN C.‐H. , NILSSON Å.
Published: March 2008

Abstract. Human jejunal tissue obtained by peroral biopsy was cultured in control medium and in medium containing 100 mmol 1‐1 ethanol. Subsequently, the incorporation and metabolism of [3H]‐arachidonic and [14C]‐linoleic acid were evaluated. Of the two fatty acids a significantly higher amount of [3]‐arachidonic acid was incorporated into phospholipids and more [14.C]‐linoleic acid was incorporated into triacylglycer‐ols. This preferential distribution of the labelled fatty acids was not affected by ethanol, but when ethanol was present in the tissue culture medium, there was a significant decrease in the incorporation of both fatty acids into tissue phospholipids. The study thus shows that ethanol in moderate concentrations can affect human jejunal absorption and metabolism of poly‐enoic fatty acids, contributing to a decrease in the amount of eicosanoid precursors available in jejunal tissue.
Acute effects of antacids on gastric juice components in duodenal ulcer patients
Authors: WEBERG R. , BERSTAD K. , BERSTAD A.
Published: March 2008

Abstract. In 10 duodenal ulcer patients gastric juice was aspirated every 10 min for 20 min before and 200 min after sham feeding. One antacid tablet or placebo was given 80 min after the sham feeding. Analyses of the aspirates showed that antacids reduced mean hydrogen ion activity and pepsin concentration significantly for 40 and 60 min, respectively, and increased phospholipid concentration for 30 min, compared with placebo. Highest mean pH was 2.52. The percentage of pH readings at or above pH levels of 2, 3, and 4 during the 2 h period following antacid administration was 29, 10, and 2%, respectively. No significant differences between antacid and placebo were found regarding intragastric concentrations of bile acids and prostaglandin E2. When one antacid tablet was administered 80 min after a real meal, the effect on intragastric pH was similarly weak, but lasted slightly longer.

Acid neutralization alone can hardly explain the ulcer‐healing effect of low‐dose antacids. Antacid‐induced increase in intragastric concentration of phos‐pholipids is a new and potentially important observation.
Hyperoxaluria or hypercalciuria in nephrolithiasis: the importance of renal tubular functions
Authors: LINDSJÖ M. , FELLSTRÖM B. , DANIELSON B. G. , KASIDAS G. P. , ROSE G. A. , LJUNGHALL S.
Published: March 2008

Abstract. The role of the kidney in states of hyperoxaluria and hypercalciuria was investigated in seven patients with hyperoxaluria after jejunoileal bypass (JIB) and six patients with idiopathic hypercalciuria (IHC). Eight apparently healthy persons formed a control group.

Besides hyperoxaluria, the patients with JIB displayed an elevated plasma concentration of oxalate and the oxalate clearance was increased and higher than creatinine clearance, indicating a net tubular secretion of oxalate. The JIB patients had lower 24‐h urinary excretions of calcium, phosphate, magnesium and citrate and higher serum parathyroid hormone (PTH) than controls, indicating increased secretion of PTH to compensate for calcium malabsorption.

IHC patients exhibited increased fasting urinary calcium even though their serum values were similar to those in the controls. These results indicate a reduced tubular calcium reabsorption, which was most pronounced in patients with highest PTH values.

We conclude that hyperoxaluria in JIB patients is associated both with intestinal hyperabsorption and with enhanced tubular secretion of oxalate, and that in some patients with IHC hypercalciuria is due to reduced tubular reabsorption of calcium.
Effect of human recombinant erythropoietin on anaemia and dialysis efficiency in patients undergoing continuous ambulatory peritoneal dialysis
Authors: STEINHAUER H.B. , LUBRICH‐BIRKNER I. , DREYLING K.W. , SCHOLLMEYER P.
Published: March 2008

Abstract. The effect of long‐term treatment with human recombinant erythropoietin (rHuEPO) has been studied in nine end‐stage renal disease patients on continuous ambulatory peritoneal dialysis (CAPD).RHuEPO was administered subcutaneously twice weekly in rising doses starting with 50 Ukg–1 body weight. After 3 months of rHuEPO haemoglobin increased from 77±7 ± 3±2 to 112±7 ± 5±6 g l–1 (P < 0±03), haematocrit rose from 22±8 ± 1±2 to 30±3 ± 1±7% (P < 0±01). A consistent decrease in ferritin concentration was observed during this time (P < 0±05). After 12 months of rHuEPO treatment and increased oral iron supplementation the rises of haemoglobin and haematocrit remained stable without other significant haematological changes.

The rHuEPO‐induced rise in haematocrit was associated with an increased peritoneal ultrafiltration (UF) without change in diuresis and body weight. UF improved from 128 ± 28 ml 4 h–1 dwell time to 273 ± 45 ml 4 h–1 (P < 0±03) within 3 months of rHuEPO treatment, and remained stable during the following study period (month 12: 253 ± 43 ml 4h–1, P < 0±05).

The rise in UF resulted in improved peritoneal clearances of creatinine, urea, potassium, and phosphate (P < 0±05, month 3). No change was observed in serum urea, creatinine, calcium, and potassium. Serum phosphate increased throughout the first 6 months of rHuEPO (P < 0±05). No severe adverse effects of rHuEPO treatment could be observed.

The present results demonstrate that long‐term subcutaneous administration of rHuEPO is effective in correcting renal anaemia in CAPD patients and may improve dialysis efficiency by increased peritoneal ultrafiltration.
Thyroid function tests in patients with acquired immune deficiency syndrome and healthy HIV1‐positive out‐patients
Authors: FELDT‐RASMUSSEN U. , SESTOFT L. , BERG H.
Published: March 2008

Abstract. The thyroid function tests as well as evidence of thyroiditis were studied in 18 male patients with acquired immune deficiency syndrome (AIDS) and 12 healthy HIV1‐positive persons compared with an age‐matched control group. Serum total thyroxine was not significantly different between the groups, but both serum total triiodothyronine, triiodothyronine uptake test, and free thyroid hormone indices showed significantly decreasing values from HIV1‐positive healthy persons to AIDS patients compared with controls (P value from < 0.05 to < 0.001). Serum TBG was elevated in HIV1‐positive subjects and in patients with AIDS, with a significant inverse correlation with the T3‐uptake test (Spearman's.= 0.657, P < 0.01). There was no correlation between thyroxine binding globulin and the other measured variables. The serum level of thyrotropine was not significantly different in the groups, whereas serum thyroglobulin was significantly lowered in the AIDS group. There was no correlation between thyroid function variables and survival time, hepatic function and ratio of T‐helper to T‐suppressor cells. No evidence of thyroiditis was observed. In conclusion thyroid tests showed an atypical outcome in HIV1‐positive patients with or without AIDS compared with the pattern normally seen in non‐thyroid illness, and should, therefore, caution the interpretation of the biochemical changes when diagnosing abnormal thyroid function in these patients.
Doppler echocardiographic analysis of cardiac flow during the Mueller manoeuver
Authors: ANDREAS S. , WERNER G.S. , SOLD G. , WIEGAND V. , KREUZER H.
Published: March 2008

Abstract. The inspiration against a closed airway, the Mueller manoeuver, leads to a negative intrathoracic pressure. It is controversially discussed whether this is causing an augmentation of right heart murmurs. There is only limited knowledge on the temporal relationship of the negative intrathoracic pressure with right and left ventricular filling and stroke volume. To investigate this relationship, the flow through the mitral, aortic, tricuspid and pulmonary valves was studied continuously by Doppler echocardiography during a standardized Mueller manoeuver in 15 healthy subjects (age 45 ± 10 years). Five heart beats after the initiation of the manoeuver, flow through the mitral and aortic valve decreased 12.2 ± 7.2% (P < 0.001) and 10.1 ± 6.6% (P < 0.001), respectively. A transient increase of 15.1 ± 9.2% (P < 0.001) in tricuspid flow was followed by a 14.3 ± 9.8% (P < 0.005) increase of flow through the pulmonary artery. Ten heart beats after the initiation of the Mueller manoeuver, flow through the pulmonary artery again reached baseline, while tricuspid flow remained below baseline values. In contrast to previous studies, our results indicate that the Mueller manoeuver causes a small and transient increase in right ventricular stroke volume which is unlikely to cause a marked augmentation in right heart murmurs.
Hyperaluminaemia in critically ill patients: role of antacid therapy and impaired renal function
Authors: ITTEL T.H. , GLADZIWA U. , MÜCK W. , SIEBERTH H.G.
Published: March 2008

Abstract. A significant rise in serum concentrations of aluminium was demonstrated in 23 patients prophylactically treated with the antacid magaldrate, whereas no increase in serum aluminium was observed in another 26 critically ill patients, in whom the use of antacids was avoided. In parallel, urinary excretion rates of aluminium rose to values close to maximum 72 h after antacid therapy had been started. Hyperaluminaemia was most marked in patients with acute renal failure undergoing continuous haemofiltration, but a significant increment in serum aluminium was also noted in patients with impaired renal function in the predialytic state. In the latter group and in patients with normal renal function there was a significant negative correlation between urinary excretion rates of aluminium and creatinine clearance after 48 h of treatment suggesting an enhancement of gastrointestinal absorption of aluminium in the presence of chronic renal failure. Maximum serum concentrations of aluminium did attain critical values in some patients with acute renal failure, but no overt signs of aluminium toxicity were noted. However, in light of both, possible subtle toxicity and enhanced absorption of aluminium in critically ill patients with renal failure, the prophylactic use of antacids in this setting should be reevaluated cautiously.
Identification of patients at high risk for colorectal carcinoma from biopsy studies of the apparently normal colorectal mucosa.A multivariate analysis
Authors: SANDFORTH F. , WITZEL L. , BALZER T. , GUTSCHMIDT S. , JANICKE I. , RIECKEN E.O.
Published: March 2008

Abstract. A number of phenotypic abnormalities of the colorectal mucosa which appears normal have been described to be biomarkers of cancer development. To improve their sensitivity and specificity, we simultaneously determined 10 morphological and histochemical parameters in biopsies from the colonoscopically normal mucosa of the descending colon, sigmoid, and rectum. The results were analysed by multivariate statistical methods. We tested the discriminating power of proliferative, morphometric, enzyme and mucin histochemical parameters from 80 patients either at average risk (controls), with an increased risk for colorectal carcinoma (high‐risk), or with a manifest carcinoma. The following parameters were investigated: number of mitotic figures per crypt, crypt length, apical, medial and basal crypt diameter, crypt surface, activity of succinate dehydrogenase (EC 1.3.99.1), activity of acid β‐galactosidase (EC 3.2.1.23), sulpho‐ and sialomucin contents. Univariate statistical analyses revealed that crypt length, crypt diameter and crypt surface were significantly increased in the high‐risk group, the carcinoma carriers having intermediate values between average‐risk and high‐risk patients. In a two‐group discriminant analysis, high‐risk or carcinoma patients could be separated from average‐risk patients with a sensitivity of 92.9% and a specificity of 100%. When the analysis was repeated for three groups (carcinoma carriers separated from high‐risk patients), sensitivity and specificity were 100% for each group. We conclude that identification of patients at risk for colorectal carcinoma is possible from the normal‐appearing left colonic and rectal mucosa by morphometric and cytochemical analysis of biopsies.
Involvement of heparin cofactor II in chymotrypsin neutralization and in the pancreatic proteinase—antiproteinase interaction during acute pancreatitis in man
Authors: TOULON P. , CHADEUF G. , BOUILLOT J.L. , AMIRAL J. , CAMBILLAUH M. , SULTAN Y. , AIACH M.
Published: March 2008

Abstract. Heparin cofactor II is a proteinase inhibitor which inhibits both chymotrypsin and thrombin, and displays great similarities with antithrombin III, the main inhibitor of thrombin in human plasma. Since acute pancreatitis is known to be associated with modification of the proteinase‐antiproteinase equilibrium, we studied heparin cofactor II and antithrombin III as well as other biochemical and haematological parameters in 10 patients experiencing attacks of acute pancreatitis. Heparin cofactor II activity decreased during the first week of illness, while its antigen concentration remained subnormal. This discrepancy between antigen concentration and activity which persisted during the first week of illness was due both to complex formation of heparin cofactor II with its target proteinases and to partial proteolysis of the inhibitor. Heparin cofactor II was shown to form a complex with chymotrypsin in the plasma of such patients. Antithrombin III levels remained unchanged throughout the study, with no discrepancy between its activity and antigen concentration. No modification of haemostasts was shown either, except for a rise in the fibrinogen level during the first days of illness. It is concluded that, unlike antithrombin III, heparin cofactor II is involved in the proteinase‐inhibitor equilibrium in patients with acute pancreatitis, and that heparin cofactor II might react as an inhibitor of pancreatic proteinases rather than an inhibitor of thrombin.
Evaluation of urinary hydroxypyridinium crosslink measurements as resorption markers in metabolic bone diseases
Authors: ROBINS S.P. , BLACK D. , PATERSON C.R. , REID D.M. , DUNCAN A. , SEIBEL M.J.
Published: March 2008

Abstract. Analyses of the urinary concentration relative to creatinine of the collagen crosslinks, pyridino‐line (Pyd) and deoxy‐pyridinoline (Dpd) were made in 47 patients with metabolic bone diseases to assess the validity of these assays as indicators of bone resorption. The mean values for patients with Paget's disease of bone, primary hyperparathyroidism and osteomalacia were significantly higher (P < 0.001) than those for age‐matched healthy individuals. During treatment of Paget's disease with bisphosphonates, there was a steady decline in the urinary concentration of the crosslinks to the normal range; this change occurred earlier than for serum alkaline phosphatase. There were significant correlations (P < 0.01) between the concentrations of both crosslinks and the corresponding values for hydroxyproline. At lower crosslink concentrations, however, these relationships were less marked due to large variations in hydroxyproline values. The results show that measurements of urinary Pyd and Dpd provide clinically applicable indices of bone resorption that are more specific than other markers.
Glutathione metabolism in activated human neutrophils: stimulation of glutathione synthesis and consumption of glutathione by reactive oxygen species
Authors: BILZER M. , LAUTERBURG B.H.
Published: March 2008

Abstract. Since glutathione (GSH) is involved in the modulation of the function of polymorphonuclear leucocytes (PMN) such as phagocytosis and production of reactive oxygen species, the metabolism of GSH was studied in human PMN. The concentration of GSH in resting PMN amounted to 13.3 nmol 10‐7PMN and remained stable over 100 min of incubation. Upon activation of PMN with phorbol myristate acetate intracellular GSH decreased to 50% of the resting concentration within 80 min. In the presence of buthionine sulfoximine, which inhibits the synthesis of GSH, the depletion of intracellular GSH was dramatically accelerated, indicating that activation of PMN is associated with a marked stimulation of GSH synthesis. Since a similar depletion of GSH was seen in the presence of propargylglycine, an inhibitor of the cystathionine pathway, most of the cysteine required for the resynthesis of GSH must originate from methionine and not from cysteine generated by the catabolism of GSH. Further studies showed that GSH is sequentially oxidized by O2‐and HOCl, first to GSSG and then to an unidentified compound, most likely a chloramine. In the presence of an adequate supply of GSH and NADPH which is required for the reduction of GSSG ‐by glutathione reductase this further oxidation of GSSG was prevented. Thus, the highly toxic HOCl generated by PMN can be detoxified by the glutathione reductase system. The capacity of PMN to re‐synthesize GSH may be an important determinant of PMN function.
Probucol increases cholesteryl ester transfer protein activity in hypercholesterolaemic patients
Authors: FRANCESCHINI G. , CHIESA G. , SIRTORI C. R.
Published: March 2008

Abstract. Probucol, a widely used lipid lowering drug, reduces both low‐ and high‐density (LDL and HDL) lipoprotein levels and can induce a regression of tissue lipid deposits in both animals and man. The suggested mechanism(s) involve the prevention of LDL oxidative modifications and, possibly, an improvement in the reverse cholesteryl ester transport system. Probucol administration to 10 hypercholesterolaemic patients increased the activity of the cholesteryl ester transfer protein (CETP) by 50%. The rise of CETP activity was significantly related with the plasma steady‐state drug levels (r= 0·51, P < 0·005), thus suggesting that probucol may directly stimulate CETP synthesis and/or release. Furthermore, CETP activity was inversely related with HDL‐cholesterol levels, both in the whole series of 10 patients (r= ‐0·56, P < 0·001) and, more so, in the single individuals (r between ‐0·77 and ‐ 0·97), thus suggesting that the reduction of plasma HDL‐cholesterol levels is a direct consequence of CETP stimulation. These findings support the hypothesis that an improvement in the reverse cholesteryl ester transport is a major mechanism of probucol and that this may explain the drug induced plasma lipoprotein changes.
Familial defective apo B‐100, characterization of an Italian family
Authors: CORSINI A. , McCARTHY B. J. , GRANATA A. , SORIA L. F. , BERNINI S. FANTAPPIÈ , ROMANO C. , ROMANO L. , FUMAGALLI R. , CATAPANO A. L.
Published: March 2008

Abstract. Familial defective apolipoprotein (apo) B‐100 is a genetic disorder presenting with hypercholes‐terolaemia and abnormal low‐density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B‐100 gene. In the present study thirteen members of a family with moderate hypercholesterolaemia (250–350 mg dl‐1) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolaemia (FH, receptor deficiency). We then studied the interaction between LDL and their receptors by an in vitro cell binding assay. LDL from nine affected members displayed a reduced affinity (2·5‐fold) for the receptor, and were less effective than LDL from control and unaffected members in suppressing LDL receptor expression and in stimulating cholesterol esterification. LDL from the affected members had normal electrophoretic mobility, size and chemical composition. Partial delipidation did not modify the LDL binding defect. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolaemics. Analysis of DNA from family members showed a point mutation leading to an Arg to Gln substitution at amino acid 3500 of the mature protein that segregated with hypercholesterolaemia and LDL defective binding. We conclude that this family is affected by familial defective apolipoprotein B‐100 (FDB).
Regional variation in adipose tissue lipoprotein lipase activity: association with plasma high density lipoprotein levels
Authors: POULIOT M.‐C. , DESPRÉS J.‐P. , MOORJANI S. , LUPIEN P. J. , TREMBLAY A. , NADEAU A. , BOUCHARD C.
Published: March 2008

Abstract. The associations of adipose tissue lipoprotien lipase (AT‐LPL) activity with body fatness and plasma lipoprotein levels were studied in the light of the recently described regional differences in AT‐LPL activity. In this regard, heparin‐releasable LPL activity was measured in abdominal and femoral adipose tissues of 29 pre‐menopausal women. Body fatness variables were all positively correlated with abdominal and femoral AT‐LPL activities expressed per 106 cells. However, abdominal and femoral AT‐LPL activities expressed per unit of cell surface displayed divergent association patterns with body fatness and plasma lipoprotein levels. Indeed, only abdominal AT‐LPL activity remained significantly correlated with body fatness variables after adjustment for fat cell surface. Furthermore, whereas abdominal AT‐LPL activity tended to be negatively correlated with plasma HDL‐cholesterol levels, femoral AT‐LPL activity was positively correlated with plasma HDL2‐cholesterol (r= 0·40, P < 0·05) concentration and with the HDL2‐cholesterol/HDL2‐cholesterol ratio (r=0·49, P<0·01). These results demonstrate the importance of taking into account the regional variation in metabolic activity of adipose tissue when studying its associations with body fatness, and with plasma lipoprotein levels. The lack of association between abdominal AT‐LPL activity and plasma HDL2‐cholesterol levels lead us to suggest that AT‐LPL activity may not be causally related with plasma HDL levels.