Spontaneous dialytic ultrafiltration with intraperitoneal reinfusion of the concentrate in 15 cirrhotic patients with intractable ascites.

The clinical efficacy and tolerance of dialytic ultrafiltration of ascites through a hemofilter (DUF) with peritoneal reinfusion of the concentrate was evaluated in 15 cirrhotic patients with intractable ascites. All together, 51 DUF procedures were carried out. An average of 8.6 was ultrafiltered during 12 h with no significant change in blood pressure, hemoglobin, coagulation parameters or plasma creatinine. A significant increase in ascitic protein concentration was observed immediately after the procedure and a slight but significant increase in 24 h urinary output. A controlled evaluation of DUF compared to large paracenteses seems to be justified by these preliminary results.     

Human atrial natriuretic factor (hANF) in liver cirrhosis

Mean plasma levels of hANF at admission were significantly higher in liver cirrhosis (LC) patients with ascites (93 +/- 11 ng, n = 20; p less than 0.05) than in LC-patients without ascites (32 +/- 14 ng/l, n = 11) or healthy controls (31 +/- 15 ng/l; range: 5-80 ng/l; n = 106). Diuretic treatment of patients with LC and ascites normalised hANF plasma concentrations (44 +/- 14 ng/l; p less than 0.05). Increase of plasma hANF in LC-patients with ascites after acute volume expansion was lower (relative rise: 159%) than in those without ascites (relative rise: 223%). Volume redistribution into the vascular compartment, induced by peritoneovenous shunt implantation in LC-patients with diuretic treatment-refractory ascites, resulted in a sharp increase of plasma hANF levels (344 +/- 87 ng/l = 420% of preoperative concentration). Normal and slightly increased levels of plasma hANF and the appropriate regulation to volume changes suggest an intact control of the hormone in LC-patients. Neither a lack nor an inappropriate secretion of hANF as a cause for sodium retention as postulated by the overflow theory of ascites accumulation could be found in liver cirrhosis.     

Autoimmunization against beta-endorphin increases food intakes and body weights of obese rats

Opioid peptides in the brain are postulated to mediate the hunger component of the control of food intake and regulation of body weight and concentrations are increased in the pituitaries of genetically obese rodents. However, systemic increases in opioids have been associated with satiety. Thus a chronic decrease in systemic concentrations of the opioid beta-endorphin induced by autoimmunization was predicted to increase food intake and body weight. Zucker obese (n = 20, 568 +/- 13 g) and lean (n = 20, 299 +/- 16 g) rats were autoimmunized against bovine serum albumin (BSA) or BSA conjugated to beta-endorphin (BSA-BE). Eight weeks after immunization serum from BSA-BE rats bound at least 7 times the circulating concentration of beta-endorphin. Food intakes were greater in BSA-BE obese (31.7 vs. 30.4 g/day, p less than 0.001) and lean rats (21.4 vs. 21.0 g/day, p less than 0.007) during weeks 5-8 and only obese rats, weeks 9-12 (31.8 vs. 30.3 g/day, p less than 0.009). Body weight gains were greater for BSA-BE than BSA obese rats during weeks 1-4 (1.34 vs. 0.92 g/day, p less than 0.05) and 9-12 (0.95 vs. 0.43 g/day, p less than 0.01). At 8 weeks the plasma concentrations of "free" beta-endorphin were decreased 78% (34 vs. 154 pmol/l, p less than 0.001) and "total" ("free" plus antibody-bound) beta-endorphin were increased (427 vs. 101 pmol/l, p less than 0.001). These results suggest that systemic concentrations of beta-endorphin may play an important role in the control of food intake and regulation of energy balance.     

Clinical efficacy of peritoneovenous shunting for the treatment of severe ovarian hyperstimulation syndrome

We investigated prospectively the clinical efficacy of a newly developed continuous autotransfusion system of ascites (CATSA) without protein supplement in patients with severe ovarian hyperstimulation syndrome (OHSS). Peritoneovenous shunting was used to recirculate ascites. The CATSA was performed for 5 h at a rate of 100-200 ml/h once a day. Eighteen patients were treated with the CATSA (CATSA group) and 36 were treated with an intravenous 37.5 g/day of albumin supplement (albumin group). Hospital stay was significantly shorter in the CATSA group than in the albumin group (10.0 +/- 5.7 versus 13.9 +/- 6.2 days, P < 0.01). Haematocrit value reached <40% significantly earlier in the CATSA group (on hospital days 3.9 +/- 3.2 versus 5.9 +/- 2.5, P < 0.01). Using a single procedure, haemoconcentration, urinary output and pulse pressure were markedly improved in the CATSA group compared with the albumin group. Discomfort due to massive ascites diminished promptly and did not recur in nine of 18 CATSA group patients, whereas it persisted in all 36 patients in the albumin group. The serum concentration of protein was maintained in the CATSA group, whereas it did not increase in the albumin group despite daily supplementation with 37. 5 g of albumin. Apparent adverse effects of each procedure were not observed in either group. The mean values of several parameters in the serum pertinent to the coagulation-fibrinolysis system did not change significantly in either group after the procedure. It was concluded that the CATSA procedure expanded circulating plasma volume without exogenous albumin and appeared to lead to a prompt recovery from severe conditions of OHSS.     

Preservation of renal structure and function in the rat remnant kidney model of chronic renal failure by enalapril treatment

The remnant kidney model of chronic renal failure was established in rats subject to subtotal (1 7/8) nephrectomy and the evolution of renal injury studied over a period of 6 wk. One wk after subtotal nephrectomy, rats had a mean conscious systolic blood pressure of 158 +/- 5 mm Hg and serum creatinine of 128 +/- 9 mumol/l. Both systolic blood pressure and serum creatinine rose over the next 5 wk in concert with progressive glomerulosclerosis and proteinuria. Enalapril, an angiotensin converting enzyme inhibitor, was administered (5 mg/kg/day) to rats (n = 11) from 1 wk after subtotal nephrectomy. Enalapril lowered systolic blood pressure over the treatment period. Systolic blood pressure was 122 +/- 5 mm Hg compared with 176 +/- 7 mm Hg in untreated rats (p less than 0.001) at 6 wk. Serum creatinine 6 wk after subtotal nephrectomy was 110 +/- 9 mumol/l with enalapril treatment, compared with 159 +/- 21 mumol/l (p less than 0.025) in control animals. Enalapril treated rats had lower urinary protein excretion than controls (15 +/- 3 mg/24 hr vs 85 +/- 22 mg/24 hr, p less than 0.0001) at 6 weeks. Glomerulosclerosis, assessed by blinded histological score, was also reduced in the enalapril treated group (1.79 +/- 0.08 vs 2.36 +/- 0.16, p less than 0.01). Enalapril treatment was associated with a reduction in filtration fraction (51Cr-EDTA/125I-hippurate clearance). At 6 wk, filtration fraction was 0.30 +/- 0.03 in enalapril treated and 0.48 +/- 0.03 in control rats (p less than 0.001). Enalapril treatment in the subtotal nephrectomy model of renal failure preserved renal structure and function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of the aminoterminal peptide of procollagen type III and laminin P1 in serum of patients with chronic liver disease

Serum concentration of the aminoterminal peptide of procollagen type III (P III P) and that of the high-molecular-weight glycoprotein laminin P1 (LP1) were determined by a specific radioimmunoassay (RIA) in patients with different chronic liver diseases. Besides the routine laboratory tests, histological verification of the liver samples obtained by needle biopsy and a complex hepatitis B virus marker analysis by RIA (Biomedica-Sorin), or ELISA (Behringwerke, Marburg, FRG) kits were carried out in order to set up the correct clinical diagnosis. In normal controls, the P III P and LP1 concentrations were 7.8 +/- 1.1 ng/ml (n = 10) and 0.08 +/- 0.1 units/ml (n = 7), respectively. Patients with fatty liver (n = 25) showed a significant elevation in P III P concentration (18.6 +/- 2.7 ng/ml). Such an elevation was not unequivocally demonstrated before. In this group of patients LP1 level was also increased (1.4 +/- 0.2 units/ml, n = 10). In liver cirrhosis (n = 51) both P III P and LP1 concentrations were found to be consistently elevated.     

In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection

Human natural killer (NK) cells form a circulating population in a state of dynamic homeostasis. We investigated NK cell homeostasis by labelling dividing cells in vivo using deuterium-enriched glucose in young and elderly healthy subjects and patients with viral infection. Following a 24-hr intravenous infusion of 6,6-D(2)-glucose, CD3(-) CD16(+) NK cells sorted from peripheral blood mononuclear cells (PBMC) by fluorescence-activated cell sorter (FACS) were analysed for DNA deuterium content by gas chromatography mass spectrometry to yield minimum estimates for proliferation rate (p). In healthy young adults (n=5), deuterium enrichment was maximal approximately 10 days after labelling, consistent with postmitotic maturation preceding circulation. The mean (+/- standard deviation) proliferation rate was 4 x 3 +/- 2 x 4%/day (equivalent to a doubling time of 16 days) and the total production rate was 15 +/- (7 x 6) x 10(6) cells/l/day. Labelled cells disappeared from the circulation at a similar rate [6 x 9 +/- 4 x 0%/day; half-life (T((1/2))) < 10 days]. Healthy elderly subjects (n=8) had lower proliferation and production rates (P=2 x 5 +/- 1 x 0%/day and 7 x 3 +/- (3 x 7) x 10(6) cells/l/day, respectively; P=0 x 04). Similar rates were seen in patients chronically infected with human T-cell lymphotropic virus type I (HTLV-I) (P=3 x 2 +/- 1 x 9%/day). In acute infectious mononucleosis (n=5), NK cell numbers were increased but kinetics were unaffected (P=2 x 8 +/- 1 x 0%/day) a mean of 12 days after symptom onset. Human NK cells have a turnover time in blood of about 2 weeks. Proliferation rates appear to fall with ageing, remain unperturbed by chronic HTLV-I infection and normalize rapidly following acute Epstein-Barr virus infection.     

Transient growth hormone therapy to rats with low protein-inflicted intrauterine growth restriction does not prevent elevated blood pressure in later life

Intrauterine growth restriction (IUGR) is a risk factor for the development of hypertension in later life. Insulin-like growth factor I and growth hormone (GH) have the potential to improve metabolic syndrome after IUGR in adult animals. The objective of the present study was to examine whether transient GH treatment of pups after weaning can prevent the development of arterial hypertension in adult rats. IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams and litter size was reduced to six male neonates after birth. Recombinant human GH was applied by daily subcutaneous injections at a dose of 3 microg/g body weight between days 24 and 60 of life. Control animals received vehicle treatment (VEH) only. Birth weight was significantly lower in low protein (LP) animals than in normal protein (NP) animals (5.1 +/- 0.3 g vs. 5.9 +/- 0.7 g, p < 0.05). Until weaning at day 23, LP animals reached similar body length, but had reduced body weight compared to NP animals. Intraarterially measured mean arterial blood pressure at day 120 was elevated in LP-VEH compared to NP-VEH animals (113 +/- 6 mmHg vs. 101 +/- 6 mmHg, p < 0.01). However, transient GH-treatment did not prevent arterial hypertension in LP animals (112 +/- 5 mmHg). Our data suggest that GH treatment between days 24 and 60 of life does not or at least not permanently reprogram blood pressure elevation after IUGR.     

Transient elevation of interleukin-16 levels at the initial stage of meningitis in children

IL-16 is an immunomodulatory cytokine that is characterized by chemotactic activity and stimulation of proinflammatory cytokine expression in monocytic cells. We studied IL-16 using ELISA in children with meningitis. When meningeal symptoms existed, IL-16 levels were high in the cerebrospinal fluid (CSF) of both bacterial (939 +/- 877 ng/l, n = 20) and aseptic (341 +/- 371 ng/l, n = 23) meningitis. The values in the CSF were significantly higher than those in non-meningitis controls (29 +/- 8 ng/l, n = 22, P < 0.0001). After meningeal symptoms disappeared, IL-16 levels in bacterial (191 +/- 149 ng/l, n = 10, P = 0.0042) and aseptic (159 +/- 188 ng/l, n = 13, P = 0.0118) meningitis were lower than those during the symptomatic stage. IL-16 levels were the highest before day 5 of the illness and then gradually fell. Significant correlations were found between IL-16 levels and both G-CSF levels (r = 0.783, n = 11, p = 0.0029) and IL-6 levels (r = 0.818, n = 12, P = 0.0005) in the CSF of bacterial and aseptic meningitis. IL-16 levels in all CSF samples from non-meningitis controls were lower than those in serum. In contrast, IL-16 levels in the CSF in six of 16 samples from bacterial meningitis and two of 18 samples from aseptic meningitis were higher than those in serum. Serum levels of IL-16 did not fluctuate throughout the course of meningitis. These data indicate that IL-16 levels rise transiently in CSF at the initial stage of meningitis. We speculate that IL-16 may promote inflammatory responses during meningitis in concert with other proinflammatory cytokines.     

The effect of iodine restriction on thyroid function in patients with hypothyroidism due to Hashimoto's thyroiditis

Lifelong thyroid hormone replacement is indicated in patients with hypothyroidism as a result of Hashimoto's thyroiditis. However, previous reports have shown that excess iodine induces hypothyroidism in Hashimoto's thyroiditis. This study investigated the effects of iodine restriction on the thyroid function and the predictable factors for recovery in patients with hypothyroidism due to Hashimoto's thyroiditis. The subject group consisted of 45 patients who had initially been diagnosed with hypothyroidism due to Hashimoto's thyroiditis. The subjects were divided randomly into two groups. One group was an iodine intake restriction group (group 1) (iodine intake: less than 100 micro g/day) and the other group was an iodine intake non-restriction group (group 2). The thyroid-related hormones and the urinary excretion of iodine were measured at the baseline state and after 3 months. After 3 months, a recovery to the euthyroid state was found in 78.3 % of group 1 (18 out of 23 patients), which is higher than the 45.5% from group 2 (10 out of 22 patients). In group 1, mean serum fT4 level (0.80 +/- 0.27 ng/dL at the baseline, 0.98 +/- 0.21 ng/dL after 3 months) and the TSH level (37.95 +/- 81.76 micro IU/mL at the baseline, 25.66 +/- 70.79 micro IU/mL after 3 months) changed significantly during this period (p < 0.05). In group 2, the mean serum fT4 level decreased (0.98 +/- 0.17 ng/dL at baseline, 0.92 +/- 0.28 ng/dL after 3 months, p < 0.05). In the iodine restriction group, the urinary iodine excretion values were higher in the recovered patients than in non-recovered patients (3.51 +/- 1.62 mg/L vs. 1.21 +/- 0.39 mg/ L, p=0.006) and the initial serum TSH values were lower in the recovered patients than in the non-recovered patients (14.28 +/- 12.63 micro IU/mL vs. 123.14 +/- 156.51 micro IU/mL, p=0.005). In conclusion, 78.3% of patients with hypothyroidism due to Hashimoto's thyroiditis regained an euthyroid state iodine restriction alone. Both a low initial serum TSH and a high initial urinary iodine concentration can be predictable factors for a recovery from hypothyroidism due to Hashimoto's thyroiditis after restricting their iodine intake.     

Prorenin and active renin concentrations in plasma and ascites during severe ovarian hyperstimulation syndrome

The pathophysiology of ovarian hyperstimulation syndrome (OHSS) remains unclear. Several lines of evidence indicate that OHSS is associated with a stimulation of the renin-angiotensin system (RAS), but its functional significance as well as its role in the pathogenesis of the syndrome are not yet determined. OHSS is associated with high plasma and ascitic concentrations of total renin, renin activity (RA) and angiotensin II (Ang II). Their ovarian or renal origin is, however, still a matter of debate. To clarify these issues further, total renin, active renin, prorenin, RA and aldosterone were measured in plasma and ascites of nine patients who developed severe OHSS after in-vitro fertilization. Blood and ascites were sampled simultaneously during therapeutic paracentesis. Total renin and prorenin concentrations were significantly higher in the ascites (mean concentration +/- SE respectively of 5920 +/- 1430 mIU/l and 5250 +/- 1350 mIU/l) than in the plasma (respectively 3060 +/- 740 mIU/l and 2000 +/- 460 mIU/l) (P = 0.020 and 0.017 respectively). Conversely, active renin and RA concentrations tended to be lower, although not statistically significantly so in the ascites (respectively 670 +/- 190 mIU/l and 47 +/- 11 ng Ang I/ml/h) than in the plasma (respectively 1060 +/- 370 mIU/l and 75 +/- 21 ng Ang I/ml/h). Aldosterone concentrations were significantly higher in the serum (2609 +/- 374 pg/ml) than in the ascites (2025 +/- 347 pg/ml) (P = 0.015). The concentration gradient between plasma and ascites for total renin and prorenin supports the hypothesis of their ovarian origin in ascites and, to a large extent, in plasma, while it is likely that the high plasma active renin and RA concentrations reflect a peripheral activation of the RAS. In conclusion, the present findings are consistent with a marked stimulation of both ovarian and renal RAS during OHSS.      

Determination of free thyroxine by adsorption on Sephadex gel

The authors describe a simplified method for the measurement of free thyroxine based on the affinity of Sephadex gel for thyroxine. Radiolabeled thyroxine added to diluted serum is adsorbed by the gel proportionally to the free thyroxine concentration of the sample. The concentration of binding proteins present in the sample does not affect the adsorption of free thyroxine on the gel. The adsorbed thyroxine is separated by centrifugation and filtration using a rigid filter. Calibration is made against the equilibrium dialysis method. The intra (CV of 4.9 p. cent, 6.1 p. cent, 10.2 p. cent for concentrations of free thyroxine of 14.1, 27.1 and 67.6 pmol/l respectively) and interassay (CV of 5.3 p. cent, 8.2 p. cent, 9.2 p. cent at 9.4, 23.0 and 83.1 pmol/l respectively) imprecisions are comparable to equilibrium dialysis. The results obtained with this method show a good correlation with those of a two-step radioimmunoassay for patients without non-thyroidal diseases or pregnancy (r2 = 0.85, n = 50). The reference range (mean +/- two standard deviations) determined in 108 euthyroid adults is 10.3 to 21.9 pmol/l. Results obtained for hypothyroid patients (7.7 +/- 2.3 pmol/l, mean +/- one standard deviation, n = 26), hyperthyroid patients (47.4 +/- 22.9 pmol/l, n = 32), patients with non-thyroidal illnesses (18.7 +/- 4.9 pmol/l, n = 35) and pregnant women (10.8 +/- 1.7 pmol/l, n = 20) are in good agreement with those reported using equilibrium dialysis or ultrafiltration. Our method offers an alternative to more tedious techniques of free thyroxine determination in the hospitalized population for which the use of analog methods has been criticized.     

Sequence of structural changes and elastin peptide release during vascular remodelling in sheep with chronic pulmonary hypertension induced by air embolization.

The progression of structural changes in the pulmonary arterial bed were followed in a model of chronic pulmonary hypertension. Chronically instrumented awake sheep received continuous air embolization for 0 (controls), 1, 4, 8, or 12 days (n = 5-6/group). After the period of embolization, the lungs were removed, the pulmonary arteries were distended with barium-gelatin, and the lungs were fixed via the airways with formal-saline. Quantitative techniques were applied to sections from random blocks from the lungs of each animal. One day of embolization resulted in granulocyte sequestration in the lung interstitium and in small vessels; additionally, intraalveolar and perivascular edema was present. By 4 days, increased medial thickness, appearance of muscle in smaller arteries than normal (e.g., muscular arteries at alveolar duct level: control = 1.2 +/- 1.2%; day 4 = 22.7 +/- 7.7) and reduction in number of barium-filled intraacinar arteries was found. The arterial changes progressed in severity to day 8 and were similar at day 12. Since arterial remodelling involves increased elastin deposition, the concentration of elastin peptides was measured in lung lymph. Increased flux of elastin peptides was apparent from day 2 of embolization and continued to increase to a level 20 x baseline by day 12 (baseline 351 +/- 86 micrograms/15 min; day 12 = 6338 +/- 2999). Comparison of the onset of the structural changes with previous findings shows that the arterial remodelling parallels the onset of sustained pulmonary hypertension. The increase in lung-lymph elastin peptides by day 2 provides evidence that vascular remodelling is initiated before day 4 of embolization. The early sequestration of granulocytes and appearance of edema suggest that these may be part of the trigger to the development of the structural changes.     

Additive antiproteinuric effect of combination therapy with ACE inhibitor and angiotensin II receptor antagonist: differential short-term response between IgA nephropathy and diabetic nephropathy

In previous studies, the synergistic antiproteinuric effect of the combination therapy of ACE inhibitors and angiotensin II receptor antagonists (ATRAs) has been inconsistent in relation to underlying renal diseases. The influence from the blood pressure (BP) - reducing effect in some studies might also contribute to this inconclusiveness. To examine the possibility of the benefit being different according to underlying renal diseases, we undertook a crossover therapeutic trial of the combination therapy in two selected homogenous groups of patients with diabetic and non-diabetic renal diseases. The BP-reducing effect was excluded during the study. Nineteen biopsy-proven IgA nephropathy, as examples of non-diabetic renal diseases, and 24 type 2 diabetic nephropathy patients were selected as the study subjects. The subjects had to meet the follow criteria: a creatinine clearance (Ccr) between 25 - 90 ml/min/1.73 m2, 24-hr urinary protein excretion rate over 1.0 g/day and a BP maintained at less than 130/80 mmHg, with more than six-month therapy of ramipril, (5.7 +/- 0.4 mg/day, 13 +/- 2 month). The baseline data between the two groups showed no significantly differences. After a 12-week stabilization period (control period), 4 mg, once daily, dose of candesartan (combination period) followed by a placebo (placebo period), or vice versa, were administered in addition to the ramipril, for 12 weeks. The combination, with candesartan, did not change the Ccr, BP, serum and urinary electrolytes or the urea. The 24 hour urinary protein excretion rate was significantly reduced by the combination therapy in the patients with IgA nephropathy (3.1 +/- 0.3 g/day in combination, 4.2 +/- 0.3 in control, and 4.3 +/- 0.2 in placebo; p < 0.05). However, the patients with diabetic nephropathy showed no reduction in their proteinuria with the combination therapy (3.8 +/- 0.2 g/day in combination, 3.9 +/- 0.3 in control, and 4.1 +/- 0.3 in placebo; p=NS). The changes in proteinuria showed no relationship with the changes in the BP in IgA nephropathy. In conclusions, the benefit of combination therapy of its antiproteinuric effect was different between IgA and diabetic nephropathy over the 12-week trial. The difference in the pathophysiological role, and the importance of the renin- angiotensin system, between the two diseases might contribute to the discrepancy in the result. We suggest the discrimination of the underlying renal diseases in the study subjects is an important prerequisite for future studies on this issue.     

Spontaneous ascitic infection in cirrhotic Africans. Descriptive study apropos of 12 cases

BACKGROUND: Spontaneous ascitic infection (SAI) is a frequent and serious complication of cirrhosis. OBJECTIVE: In a retrospective study, the authors report clinical and biological data associated with SAI for cirrhotic patients in an African medical centre. METHODS: Twenty-two cirrhotic patients with ascites were included in a one-year study (November 1996 to October 1997). Clinical and biological data were obtained through medical files. FINDINGS: The mean age of the 22 cirrhotic patients with ascites (12 men, 10 women) was 48.9 years. Twelve cases of SAI were found. In a univariate analysis, the more frequent data in patients with SAI when compared to patients without SAI were: fever or hypothermia (91.7% versus 10%, p = 0.002), abdominal pain (83.3% versus 40%, p = 0.046), cloudy ascitic fluid (66.7% versus 10%, p = 0.003), medium albuminemia (18.2 g/l versus 23 g/l, p = 0.02), medium prothrombin rate (42.8% versus 58.3%; p = 0.04) and ascitic fluid protein level < or = 10 g/l (91.7% versus 30%, p = 0.01). The protein level in ascitic fluid cirrhotic patients was significantly lower in SAI than in patients without SAI (7.6 g/l versus 11 g/l; p = 0.005). In a multivariate analysis, protein levels in ascitic fluid were the only factor associated with SAI (p = 0.024).     

Use of recombinant erythropoietin on secondary anemia in patients in the terminal phase of renal insufficiency on hemodialysis

A group of 6 patients with a history of end-stage renal insufficiency on hemodialysis was receiving erythropoietin (EPO) in a dosage of 50 IU/kg body weight i. v. The hemogram values were followed regularly every week and the patients underwent other laboratory evaluations every month. At the beginning of the study, the number of erythrocytes amounted to 2.2 +/- 0.3 x 10(12)/l. After 4 weeks it was 2.3 +/- 0.4 (NS) (p = 0.001), after 8 weeks 2.8 +/- 0.4 (p = 0.007), and after 12 weeks 3.2 +/- 0.3. At the beginning, hemoglobin was 70 +/- 8 g/l, after 4 weeks 76.3 +/- 13.7 (NS), after 8 weeks 95.7 +/- 14.3 (p = 0.008), and after 12 weeks 102.2 +/- 12 (p = 0.001). The hematocrit value rose from 21.4 +/- 3.4 at the beginning of the study to 32.1 +/- 3.6 (p = 0.001) after 12 weeks. The trial showed no significant effect of EPO on serum potassium which amounted to 5.3 +/- 0.4 mmol/l at the beginning of the trial and 5.6 +/- 0.8 (NS) after 12 weeks; the rate of the rise of platelets from 132.8 +/- 2.4 x 10(9)/l to 155.2 +/- 42.2 was not significant either. The results demonstrate a marked improvement in the red blood cells of patients receiving EPO in the end-stage of renal insufficiency and its influence on their general condition. One female patient was excluded from the study participation because of a severe bone pain.     

Does cadmium contribute to the development of renal parenchymal hypertension?

In our study we investigated 36 out-patients with renal disease, 22 of whom were hypertensive. In all patients proteinuria was present (4.30 +/- 5.05 g protein/day) and kidney diseases were verified by renal biopsy. Blood cadmium in non-smokers was significantly (p less than 0.05) lower than in smokers. We found a positive correlation between cadmium-concentration of blood and urine (p less than 0.01, R = 0.44) and between cadmium-concentration of blood and blood uric acid (p less than 0.01, R = 0.44). Proteinuria was weakly correlated with cadmium concentration of urine (p less than 0.05, R = 0.35). Patients with renal hypertension showed a significantly higher (p less than 0.05) urine cadmium excretion per day (1.60 +/- 1.12 micrograms/day) compared to normotensives with a disease of the kidney (1.14 +/- 1.47 micrograms/day). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.     

Atorvastatin improves peritoneal sclerosis induced by hypertonic PD solution in rats

BACKGROUND: Peritoneal sclerosis is a complication of peritoneal dialysis and results in ultrafiltration failure. It is related to chronic peritoneal injury due to dialysis solution content and recurrent peritonitis. Statins have anti-inflammatory properties which may be of value in modulating responses to injury. We evaluated the capacity of atorvastatin to modify peritoneal alterations secondary to hypertonic glucose. METHODS: Thirty-two non-uremic rats were divided into three groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n=10) and group III received hypertonic PD solution (10 ml/day) plus 80 mg/L atorvastatin in drinking water (n=11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D 1 /D 0 glucose), ultrafiltration volume (UF), dialysate protein, TGF-beta 1 and VEGF levels were determined. RESULTS: Administration of atorvastatin resulted in preserved UF (4.9+/-0.8 vs 7.5+/-0.6 mL, p <0.01), protein loss (2.2+/-0.2 vs 2.1+/-0.1 g/L, p >0.05), and peritoneal thickness (53+/-3 vs 26+/-4 microm, p <0.01). D 1 /D 0 glucose was significantly reduced in the dextrose group (0.70+/-0.02 vs 0.56+/-0.04, p <0.01). Both higher levels of TGF-ss 1 (206+/-40 vs 474+/-120 pg/mL, p<0.05), and VEGF in dialysate effluent (4+/-0.4 vs 7.9+/-3 pg/mL, p>0.05), was determined in the dextrose group. CONCLUSION: Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of atorvastatin led to prevention of these alterations. We suggest that the anti-inflammatory properties of statins are useful in providing protection of the peritoneal membrane from the effects of hypertonic glucose.     

Effect of oral administration of Terminalia chebula on gastric emptying: an experimental study

Terminalia chebula is a commonly advocated agent in Ayurveda for improving gastrointestinal motility. Charles Foster rats (150-200 gms of either sex) were divided into four groups as follows--Group 1 (n = 15) normal animals; Group II (n = 6) rats administered metoclopramide (1.35 mg/kg); Group III (n = 8) rats given atropine (0.45 mg/kg). These agents were injected intramuscularly, 30 mins before the experiment. Rats from Group IV (n = 8) were administered Terminalia chebula (100 mg/kg/day for 15 days orally). Metoclopramide and atropine have established prokinetic and antikinetic activities respectively and are therefore included for comparison. All rats were then given a test meal of methyl cellulose (1.5%) mixed with phenol red (50 mg/100 ml) orally and gastric emptying was measured 20 mins later. Gastric emptying of normal rats (Group I) was found to be 51.6 +/- 7.79%. Metoclopramide significantly increased the gastric emptying (76.33 +/- 12.37%; p < 0.01) and atropine inhibited the motility (% gastric emptying being 7.26 +/- 19.76%; p < 0.01). Terminalia chebula was found to increase the percent gastric emptying (86.57 +/- 6.65%; p < 0.01). Thus from this study it appears that Terminalia chebula can serve as an useful alternative to prokinetic drugs available today.     

Vascular endothelial growth factor is bound in amniotic fluid and maternal serum.

To study vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) concentrations and their possible binders, serum from 22 non-pregnant and 55 pregnant women (15 at weeks 10-13; 40 at term), umbilical vein (n = 24) and artery (n = 13) and amniotic fluid (a pool of 50 at weeks 15-17; 11 at term) were assessed for VEGF and PlGF by an enzyme-linked immunosorbent assay. In amniotic fluid and maternal serum VEGF concentrations were <16 ng/ml and added VEGF was not recovered. VEGF was detected in serum from mothers post-partum (137 +/- 142 ng/l, mean +/- SD), umbilical artery (421 +/- 288 ng/l) and vein (502 +/- 339 ng/l) and non-pregnant controls (182 +/- 147 ng/l), and added VEGF was fully recovered. PlGF was detected in pregnancy serum (52 +/- 23 ng/l early pregnancy; 439 +/- 217 ng/l term pregnancy) and in amniotic fluid (early pregnancy 56 ng/l; term pregnancy 30 +/- 18 ng/l). PlGF was fully recovered in all samples. Gel filtration and isoelectric focusing revealed that in maternal serum and amniotic fluid [125I]VEGF was bound to a protein with an Mr of 400-700 kDa and an isoelectric point of approximately 8. This protein was not identical with alpha-2-macroglobulin (by an immunofluorometric assay), pregnancy zone protein or pregnancy associated plasma protein-A (by immunodiffusion). In conclusion, VEGF-binding activity is present in amniotic fluid and maternal blood. It disappears after delivery and is not detectable in fetal or non-pregnant serum.