The influence of hyperinsulinaemia on calcium-phosphate metabolism in renal failure

Background. Patients with renal failure are characterized by impaired insulin-mediated glucose uptake. Insulin plays a major role in the maintenance of phosphate homeostasis but it remains to be determined whether in uraemia insulin-dependent renal and extrarenal phosphate disposal is also affected. Methods. The effects of hyperinsulinaemia on serum concentrations of phosphate, ionized calcium and intact PTH as well as renal excretion of calcium and phosphate was studied under euglycaemic conditions (glucose clamp technique) in patients with advanced renal failure and in healthy subjects. Fifteen patients with renal failure (mean serum creatinine 917 &mgr;mol/l) and 12 control subjects were included. All subjects underwent a 3-h euglycaemic clamp with constant infusion of insulin (50 mU/m²/min) following a priming bolus. The urine was collected for 3 h before and throughout the clamp. Results. The tissue insulin sensitivity (M/I) was lower in patients with renal failure than in control subjects (5.3±2.4 vs 6.7±1.8 mg/kg/min per mU/ml, P=0.001) but the phosphate lowering action of insulin was larger in patients with renal failure than in control subjects. Urinary calcium excretion increased (P<0.05) and phosphate excretion did not change during the clamp in both groups. Despite a decrease of serum ionized calcium in the group of patients with renal failure and no change in the control group, plasma PTH fell significantly in both groups but this effect was still significant after 180 min only in the renal failure group. A significant correlation was observed between changes in serum phosphate and PTH induced by hyperinsulinaemia (r=0.48, P<0.01). Conclusions. Phosphate-lowering effect of insulin is well preserved in severe renal failure despite the resistance to insulin-stimulated glucose uptake. The decrease of serum PTH observed during hyperinsulinaemia appears to be independent of serum ionized calcium.     

Treatment with a cyclin-dependent kinase inhibitor, seliciclib, is effective in reducing glomerular macrophage numbers and the severity of established experimental glomerulonephritis

Aim: The cyclin‐dependent kinase inhibitor, seliciclib (R‐roscovitine, CYC202), has anti‐proliferative activity through its inhibition of cyclin‐dependent kinase 2. We hypothesized that treatment with seliciclib would reduce glomerular macrophage numbers and glomerular crescent formation in experimental crescentic glomerulonephritis even when treatment is started after onset of disease. Method: Nephrotoxic nephritis (NTN) was induced in Wistar Kyoto rats. In experiment 1, seliciclib (150 mg/kg per day) was given by oral gavage from 1 h before induction of NTN and continued to day 14. In experiment 2, treatment was started on day 4 of NTN and continued to day 14 in order to examine the effect of seliciclib in established glomerulonephritis. Results: In experiment 1, seliciclib reduced proteinuria (119.5 ± 13.9 vs 191.4 ± 18.8 mg/day, P < 0.01), serum creatinine (54.0 ± 3.0 vs 81.0 ± 2.5 µmol/L, P < 0.005) and glomerular crescent score (23.9 ± 2.1 vs 44.6 ± 2.2, P < 0.005) in comparison with controls. In experiment 2, seliciclib ameliorated established glomerulonephritis, with reduction in proteinuria (58 ± 16 vs 165 ± 13 mg/day, P < 0.005), serum creatinine (39 ± 3 vs 62 ± 5 µmol/L, P < 0.05), glomerular macrophage numbers (6.8 ± 2.5 vs 18.5 ± 1.2 ED1+ cells per glomerular cross section, P < 0.05), glomerular cell proliferation (1.2 ± 0.37 vs 4.2 ± 0.80 bromodeoxyuridine (BrdU)+ cells per glomerular section, P < 0.05) and crescent score (10.8 ± 1.6 vs 43.9 ± 1.4, P < 0.05), in comparison with the controls. Conclusion: Seliciclib is effective in both prevention and treatment of established crescentic glomerulonephritis in Wistar Kyoto rats, in association with a reduction in the number of glomerular macrophages. We suggest that seliciclib, or other cyclin‐dependent kinase inhibitors, may represent a novel therapeutic approach for patients with proliferative glomerulonephritis.     

Effect of Carbohydrate Restriction in Patients with Hyperinsulinemic Hypoglycemia after Roux-en-Y Gastric Bypass

Background

Hyperinsulinemic hypoglycemia is a rare complication of Roux-en-Y gastric bypass (RYGB) surgery. Meals with a high carbohydrate (carb) content and high glycemic index (GI) may provoke these hypoglycemic attacks. The aim of this study is to assess the effects of reducing meal carb content and GI on glycemic responses in patients with post-RYGB hypoglycemia.

Methods

Fourteen patients with post-RYGB hypoglycemia underwent two meal tests: a mixed meal test (MMT) with a carb content of 30 g and a meal test with the low GI supplement, Glucerna SR 1.5® (Glucerna meal test (GMT)). Plasma glucose and serum insulin levels were measured for a period of 6 h.

Results

Peak glucose levels were reached at T ₃₀ during GMT and at T ₆₀ during MMT, and they were 1.5?±?0.3 mmol/L lower during GMT than during MMT (7.5?±?0.4 vs 9.0?±?0.4 mmol/L, P?T ₃₀ plasma, insulin was 30.7?±?8.5 mU/L higher during GMT than during MMT (P?Conclusion A 30-g carb-restricted meal may help to prevent post-prandial hypoglycemia in patients with post-RYGB hypoglycemia. The use of a liquid, low GI, supplement offers no additional advantage.     

Modulators of growth in primary culture of rat proximal tubular cells II

Summary: The present studies assessed the effects of manipulating extracellular sodium (Na) concentration and Na transport on cellular hypertrophy and hyperplasia in primary culture of rat proximal tubular cells. A concentration-dependent effect on thymidine incorporation and protein content was observed with cell culture media Na concentration of 130, 140 and 150 mmol/L. This effect was independent of osmolality (matched with mannitol) and no stimulatory effect occurred if choline was substituted for Na. Cells derived from sham-operated (Sx) animals exposed to a higher media concentration of Na (150 vs 140 mmol/L) had both stimulated thymidine incorporation to 186.8 ± 35.41% (P<0.05) and enhanced cell protein content to 134.7 ± 135% (P<0.05). This effect was more pronounced in cell cultures derived from unilaterally nephrectomized (Nx) animals, being 212.8 ± 31.5% (P<0.01) for thymidine incorporation (P<0.05 vs cells from sham-operated animals grown in high Na media) and 114.4 ± 3.2% (P<0.001) for protein content (P=0.11 vs sham-operated cells grown in similar conditions). the addition of 10^?4 mmol/L ethylisopropyl amiloride hydrochloride (EIPA) to Nx cells in a normal or high Na concentration media resulted in a decrease in cellular protein content to 82.6 ± 6.8% (P<0.05) and 85.5 ± 0.2% (P<0.0001) compared to respective controls. 10^?4 mol/L EIPA in media supplemented with insulin-like growth factor (IGF-1) blocked the proliferative response normally seen in response to this growth factor from 156.6 ± 13.7 to 27.5 ± 3.1% (P<0.0001) compared to control. However, the presence of EIPA did not abrogate the hypertrophic response elicited by IGF-1 (cell protein content 128.1 ± 13.1% of control with IGF-1 vs 124.9 ± 12.5 with IGF-1 and EIPA; P= n.s.). Addition of 10^?4 mol/L EIPA to 10% serum derived from either Sx or Nx animals blocked the growth response to the sera, limiting the cellular protein content to 76.6 ± 5.5% (P<0.0001) and 89.7 ± 4.4% (P<0.0001) and thymidine incorporation to quiescent levels of 0.2 ± 0.1% (P<0.0001) and 0.4 ± 0.1% (P<0.0001) compared to respective controls. In summary, rat renal proximal tubular cell growth is influenced by Na concentrations in the cell culture environment and inhibited in the presence of EIPA. This supports a role for altered epithelial transport in the cellular growth response to a number of stimuli.     

Dyslipidaemia in patients with lupus nephritis

Aim: There is little data on the prevalence and severity of dyslipidaemia in Asian patients with lupus nephritis (LN). Whether the dyslipidaemia in LN patients differs from subjects with comparable levels of renal impairment also remains undefined. Methods: Lipid profiles of 100 Chinese patients with quiescent LN (age 46.3 ± 9.3 years, 83% female, maintenance prednisolone dose 5.80 ± 2.43 mg/day) were studied and compared with 100 controls who had non‐lupus non‐diabetic chronic kidney diseases (CKD), matched for sex, age and renal function. Results: LN patients and CKD controls had similar renal function and proteinuria, while blood pressure was higher in controls. Twenty‐five percent of LN patients and 17% of controls were receiving statin treatment. Despite this, 59% of LN patients and 46% CKD controls showed abnormal lipid parameters (P = 0.066). LN patients showed higher levels of total cholesterol (TC) and triglycerides (TG) than controls (5.28 ± 0.12 vs 4.86 ± 0.08 mmol/L, P = 0.004; and 1.62 ± 0.12 vs 1.20 ± 0.07 mmol/L, P = 0.002, respectively). More LN patients had abnormal TC, TG or low‐density lipoprotein cholesterol (LDL‐C) (54%, 16% and 38%; P = 0.016, = 0.005 and = 0.021, respectively). Hydroxychloroquine (HCQ) treatment was associated with lower TC, LDL‐C and HDL‐cholesterol. Conclusion: Dyslipidaemia is prevalent in LN patients and is more severe than controls with a similar degree of CKD despite disease quiescence, low steroid dose and low level of proteinuria. Concomitant corticosteroid and renal impairment are likely contributing factors. HCQ treatment is associated with reduced severity of dyslipidaemia in LN patients.     

Temporal changes in glucose and insulin homeostasis after biliopancreatic diversion and laparoscopic adjustable gastric banding

BackgroundObesity surgery is associated with improvement in type 2 diabetes mellitus. Our aim was to examine the effects of biliopancreatic diversion (BPD) and laparoscopic adjustable gastric banding (LAGB) on the body mass index, fasting insulin level, glucose level, and insulin resistance in morbidly obese subjects with type 2 diabetes mellitus. The setting was the Department of Surgery, Morriston Hospital (Swansea, Wales, United Kingdom).MethodsA total of 13 morbidly obese patients (7 BPD, 6 LAGB) underwent serial measurements of fasting glucose and insulin at baseline, immediately after surgery (days 1–7), and 1, 6, and 12 months postoperatively. The homeostasis model of assessment–insulin resistance was calculated.ResultsIn the BPD group, the glucose levels had normalized by day 3 (5.6 ± 1 mmol/L) and the difference was statistically significant at 6 and 12 months postoperatively (5 ± .7 and 4.4 ± .5 mmol/L, respectively). The insulin levels had improved from day 1, and the difference was statistically significant at days 2, 5, 6, and 7 (19 ± 9, 14.2 ± 7, 15.2 ± 8, and 17.4 ± 8 mU/L, respectively). All diabetes medications were stopped on the fourth postoperative day. In the LAGB group, no statistically significant changes were seen in the glucose levels. Statistically significant changes in insulin were seen on days 1 and 2 (19 ± 13 and 13 ± 6.5 mU/L, respectively). The homeostatic model of assessment–insulin resistance had improved in both groups (BPD, 1.6 ± 1.2, P < .01; and LAGB, 4.3 ± 1.4, P < .05).ConclusionBPD causes immediate remission of type 2 diabetes mellitus. Leptin might play an important role in the early improvement of insulin resistance in fasting states after BPD. In the LAGB group, glucose homeostasis improved, but the patients still required diabetes medications, although the dosages were reduced.     

INSULIN AND MINERALOCORTICOIDS INFLUENCE ON EXTRARENAL POTASSIUM METABOLISM IN CHRONIC HEMODIALYSIS PATIENTS

Insulin-mineral corticoids effects on extrarenal K⁺ metabolism in dialysis patients. During the inter-dialytic interval in dialyzed patients, hydrogen and potassium ions are regulated by extrarenal mechanisms. We studied the hormonal and acidotic effects on the extrarenal potassium metabolism, in selected, anuric and stable, hemodialysis patients. Fifteen patients, were grouped according to the mean mid-week pre-dialysis K⁺ over the past 12 months: > 6.0 mEq/L (G1, n = 5), = 5.1–6.0 mEq/L (G2, n = 5), ≤5.0 mEq/L (G3, n = 5). After a mid-week hemodialysis session and 12 h fasting, they received 1 g/Kg glucose p.os (A). Insulin, aldosterone, renin, pH, HCO₃^?, glucose, body weight, blood pressure and heart rate were measured before and 60′ after the meal. We recorded the same parameters, except insulin, in 15 patients, similarly grouped, before hemodialysis (T0) and on 3 consecutive off dialysis days (T1–T3); G1 received fluorohydrocortisone (FHC) 0.1 mg–0.3 mg/day, according to body weight and G3 spironolactone (SLT) 200 mg per day. G2 were controls (B). (A) A significant rise in glycemia (81 ± 23 to 157 ± 52 mg/dL, P < 0.001) and insulin (11.8 ± 6.2 to 46.8 ± 19.5 μU/mL, P<0.001), with a drop in K⁺ (5.1 ± 0.6 to 4.8 ± 0.7 mEq/L, P= 0.001) and aldosterone (453 ± 373 to 383 ± 364 pg/mL, P<0.01), were noted at T60 vs. T0, in all groups. Insulin levels correlated negatively (r = ?0.54, P<0.04) to serum K⁺ at T60, in all patients. (B) No major pH, HCO₃ and aldosterone changes were observed in the 3 groups. Despite that, K⁺ dropped in G1 by FHC (6.7 ± 0.9 to 5.9 ± 0.6 mEq/L, P<0.05), rose in G3 by SLT (4.4 ± 0.4 to 5.4 ± 0.3 mEq/L, P<0.05) and remained unchanged in controls (5.8 ± 0.2 to 5.8 ± 0.6 mEq/L), (T0 vs T3 pre-dialysis values). Glucose significantly lowered K^? by promoting adequate insulin secretion. Drugs affecting aldosterone action significantly influenced potassium metabolism. Acid-base balance was not important in K⁺ handling in steady state anuric dialysis patients.     

Changes in serum prolactin, sex hormones and thyroid function with alternate nightly nocturnal home haemodialysis

Aim: Uraemia is associated with hyperprolactinaemia, low total (TT) and free (FT) serum testosterone, high luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) and, in women, anovulatory cycles and premature menopause. We hypothesize that extended hours haemodialysis may improve these derangements. Methods: This is an observational cohort study of 30 men (age 54 ± 13 years, body mass index (BMI) 28.1 ± 5.8 kg/m²) and seven women (age 41 ± 11 years, BMI 32.2 ± 11.2 kg/m²) established on chronic home haemodialysis (3–5 h, 3.5–5 sessions weekly) who were converted to nocturnal home haemodialysis (6–9 h, 3.5–5 sessions weekly). Serum was collected at baseline and 6 months for measurement of TT, sex hormone binding globulin (SHBG), LH, FSH, prolactin, thyroid‐stimulating hormone and thyroxine. Results: In the male patients (n = 25), serum prolactin significantly fell (281 (209.5–520) vs 243 (187–359) mU/L, P = 0.001) and TT (12.6 ± 5.8 vs 15.2 ± 8.1 nmol/L, P = 0.06) and FT (281 ± 118 vs 359 ± 221 pmol/L, P = 0.01) increased. SHBG, LH and FSH were unchanged. At 6 months, two of the three women under 40 years of age had return of regular menses after being amenorrhoeic or having prolonged and irregular menses at baseline. There were insufficient women in this study to further analyse changes in sex hormone levels. Thyroid function tests remained stable. Conclusion: Alternate nightly nocturnal haemodialysis significantly improves hyperprolactinaemia and hypotestosteronaemia in men. Menstrual cycling may be re‐established in young women. The effect of these changes on fertility has not been established. Patients should be counselled about the possibility of increased fertility before conversion to extended hours haemodialysis regimens.     

Impact of rHuEPO therapy initiation on soluble adhesion molecule levels in haemodialysis patients

Background: Increased levels of soluble adhesion molecules have been reported in haemodialysis (HD) patients. Recent studies have shown that recombinant human erythropoietin (rHuEPO) elicits proliferation and migration of endothelial cells and modifies endothelial function. The present study was design to explore the effects of rHuEPO on serum levels of soluble adhesion molecules in HD patients. Methods: Soluble serum levels of E‐selectin (sE‐selectin), intracellular adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1) were measured by ELISA in 29 rHuEPO naïve HD patients (20 males, 9 females) and 10 control subjects at baseline and second month. The HD patients with a haemoglobin level lower than 10.0 mg/dL (n = 19) were administered rHuEPO therapy and other HD patients (n = 10) were followed as a placebo group. Results: Serum levels of soluble adhesion molecules were significantly higher in HD patients compared with the control group. A significant rise from the baseline in sE‐selectin levels (77 ± 70 vs 100 ± 86 ng/mL, P < 0.05) was observed 2 months after rHuEPO initiation, while sICAM‐1 and sVCAM‐1 levels decreased (271 ± 261 vs 197 ± 89 and 1043 ± 243 vs 990 ± 236 ng/mL, respectively, P < 0.05). Conclusions: The present data indicate that rHuEPO could have an important action on serum levels of soluble adhesion molecules in HD patients. rHuEPO might modify the expression of adhesion molecules from endothelial cells either. However, the exact mechanism responsible for the serum elevation of these molecules in HD patients is yet to be fully elucidated.     

Effect of Sairei-to on irreversible glomerular sclerotic lesions in rats

The effects of Sairei-to and its active components on a model of irreversible mesangial proliferative glomerulonephritis induced by injecting monoclonal antibody (MoAb) 1-22-3 into uninephrectomized rats were examined. The significant suppressive effects of Sairei-to and its active components on proteinuria were demonstrated on days 7, 14, 21 after MoAb 1-22-3 injection compared with phosphate-buffered saline (PBS)-treated controls. On day 21, light microscopy revealed that the drugs reduced mesangial cell proliferation, mesangial matrix expansion (matrix score: 84.5±41.6 for Sairei-to, 76.1±31.9 for Syo-saiko-to, 66.7±46.3 for its three components vs 162.4±26.1 for PBS, P<0.005) and crescent formation (mean percentage: 2.25% for Sairei-to, 1.71% for Syo-saiko-to, 1.43% for its three components vs 18.86% for PBS, P<0.005). The kidney weights of the groups given the drugs were significantly lower than the PBS group value (1.03±0.08 g with Sairei-to, 1.11±0.12 g with Syo-saiko-to, 1.06±0.12 g with its three components vs 1.39±0.20 g with PBS, P<0.01 or P<0.05). Immunofluorescence analysis revealed that the drugs suppressed the expression of transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and collagen type I in the glomeruli, and reduced the numbers of ED1-positive cells in the glomeruli and OX8-positive cells in the glomeruli and in the tubular interstitium. The blood biochemistry results revealed significant differences between the total cholesterol levels (70.0±5.9 mg/dL with Sairei-to, 66.0±6.4 mg/dL with Syo-saiko-to, 76.6±8.4 mg/dL with its three components vs 104.3±26.6 mg/dL with PBS, P<0.05). We conclude that Sairei-to and its active components have suppressive effects on proteinuria and mesangial matrix expansion in rats with irreversible renal sclerosis. Transforming growth factor-β, collagen type I and α-SMA expression and infiltration by ED1- and OX8-positive cells were also suppressed by these drug preparations.     

Increased coated-platelet levels in chronic haemodialysis patients

Aim: To determine if levels of coated‐platelets, which are potentially pro‐thrombotic, are increased in end‐stage renal disease patients on haemodialysis, a condition associated with high cardiovascular disease risk. Methods: In a cross‐sectional observational study, coated‐platelet levels were measured by flow cytometry in 25 end‐stage renal failure haemodialysis patients and 25 controls without renal disease. Associations between coated‐platelet levels and clinical and biochemical factors relevant to renal and cardiovascular disease were evaluated. Results: Mean ± SD coated‐platelet levels were higher in the dialysis group than in the control group (39.3 ± 14.3% vs 30.9 ± 10.3%, P = 0.02). The number of subjects with high coated‐platelet levels (>40%) was larger in the dialysis than in the control group (13/25 vs 4/25, χ² test, P = 0.007). On univariate analysis, coated‐platelet levels correlated with serum C‐reactive protein levels in renal failure (r = 0.47, P = 0.02) and inversely with white cell count in the control group (r = ?0.60, P = 0.001). Coated‐platelet levels were higher in dialysis patients reporting alcohol abstinence than among those reporting ‘social’ drinking (44.3 ± 12.6 vs 28.8 ± 13.5%, P = 0.01). Age, gender, body weight, smoking, diabetes, lipid levels and lipid‐lowering drugs were not associated with coated‐platelet levels (all P > 0.05). Conclusion: Coated‐platelet levels are increased in haemodialysis patients relative to subjects with normal renal function, and are related to inflammation and alcohol abstinence. Other vascular risk factors, such as smoking, lipids and diabetes, were not related to coated‐platelet levels. Coated‐platelets may be implicated in the increased thrombosis and vascular risk in end‐stage renal disease.     

Abnormal cell calcium concentrations in cultured bone cells obtained from femurs of obese and noninsulin-dependent diabetic rats

Summary Cytoplasmic free calcium concentration [Ca²⁺]i was quantified in cultured bone cells with osteoblastic characteristics. The cells were obtained from femurs of obese (fa/fa) Wistar-Kyoto rats, from nonobese, noninsulin-dependent diabetic (NIDD) Sprague Dawley rats, and from their appropriate controls. [Ca²⁺]i was also determined in bone cells obtained fromin vivo insulin-treated NIDD rats. Obese (Wistar Kyoto) rats had increased body weight (313±13 vs. 249±4 g;P<0.01), decreased femur weights (0.68±0.05 vs. 0.89±0.05 g;P<0.05), similar glucose levels (148±5 vs. 139±3 mg/dl), and higher plasma insulin levels (6.0±0.5 vs. 0.7±0.1 ng/ml;P<0.01) when compared with their nonobese [(fa/+); (+/+)] littermates. Nonobese, NIDD rats, compared with their appropriate controls (nondiabetic Sprague Dawley rats) had higher plasma glucose levels (235±32 vs. 145±3 mg/dl;P<0.01) but their plasma insulins, body weights, and femur weights were similar to controls (0.7±0.1 vs 0.6±0.1 ng/ml; 302±4 vs. 318±14 g; 0.97±0.4 vs. 0.98±0.04 g, respectively). Long-term (4 weeks) daily insulin treatment (2 u/100 g) of the NIDD rats increased their plasma insulin (1.9 ng/ml;P<0.05) and body weight (369±13 g;P<0.05) but did not change their plasma glucose levels (225±5 mg/dl), or femur weights (0.98±0.4 g). [Ca²⁺]i in bone cells derived from the femurs of obese animals was higher than in cells derived from their nonobese littermates (156±22 vs. 71±13 nM;P<0.01). In bone cells from NIDD rats, [Ca²⁺]i was lower compared with controls (146±22 vs. 229±19 nM;P<0.001). Insulin treatment of the diabetic animals augmented the decrease in [Ca²⁺]i in their bone cells (68±11 nM;P<0.005 compared with nontreated rats). These data reveal that [Ca²⁺]i in cultured bone cells from obese nondiabetic and nonobese NIDD rats differs from that of their controls. Compared with their controls, the changes in [Ca²⁺]i in bone cells from the NIDD and obese animals were in opposite directions. Whether the underlying mechanisms for the changes in cell [Ca²⁺]i in nondiabetic obese and nonobese NIDD animals differ, and whether the changes in [Ca²⁺]i observed in the cultured cells reflect thein vivo condition in bone cells of these animals are questions that await further investigations.     

多囊卵巢综合征患者血纤溶能力的研究

目的了解多囊卵巢综合征(PCOS)患者的血纤溶能力及服用二甲双胍后血纤溶能力的变化。方法(1)对照组20例、PCOS患者30例,分别取血检测组织纤溶酶原激活物(t-PA)、纤溶酶原激活抑制物(PAI-1)的活性;(2)PCOS高胰岛素血症者10例,分别给予二甲双胍750~1 500 mg/d治疗,比较治疗前、后t-PA、PAI-1活性。结果PCOS组的血胰岛素(INS)、游离睾酮(F-T)t、-PA、PAI-1分别为(24.42±12.30)mU/L(、2.70±1.50)ng/L、(0.17±0.06)KU/L(、0.88±0.05)AU/ml,对照组分别为(10.04±6.12)mU/L(、1.70±1.00)ng/L(、0.28±0.04)KU/L、(0.70±0.09)AU/ml。10例PCOS患者经二甲双胍治疗后INS、F-Tt、-PA、PAI-1分别为(12.20±7.78)mU/L、(1.70±1.00)ng/L、(0.26±0.08)KU/L、(0.70±0.35)AU/ml。结论PCOS患者的血纤溶能力低于正常者,而服用二甲双胍后血纤溶能力明显改善。     

Metabolic effects of erythropoietin in patients on peritoneal dialysis

Insulin and lipid metabolism were studied in seven patients (19±1 years) with end-stage renal disease on continuous cycling peritoneal dialsysis (CCPD) before and after 6 months of therapy with human recombinant erythropoietin (EPO) to correct anemia. Hematocrit increased from 22.2±1.8% to 34.8±1.8% (P<0.001) following EPO treatment. Serum ferritin (P<0.05) and serum iron (P<0.01) decreased significantly after anemia correction. There were no significant differences in the height, weight, anthropometric measures, or intakes of protein and total calories in the patients before and after the 6 months of EPO therapy. There were no differences in serum biochemical parameters, including 1,25-dihydroxyvitamin D₃ and parathyroid hormone in these patients before and after 6 months of EPO therapy. Residual renal function and Kt/V_urea were also not different before and after 6 months of EPO therapy. The hyperinsulinemic euglycemic clamp technique was used to measure insulin sensitivity. Before EPO, insulin sensitivity was low in patients on CCPD (238±19 mg/m² per min) compared with controls (320±30; P<0.01). After 6 months of EPO therapy, insulin sensitivity increased by 28% (305±26, P<0.01 vs. pre-EPO values), so that these values were no longer different from control values. The hyperglycemic clamp technique was used to measure insulin secretion. Before EPO, both early- and late-phase insulin secretion were elevated in patients on CCPD compared with controls (P<0.01 in both cases). These indices of insulin secretion decreased significantly (P<0.01) following 6 months of EPO. Before EPO, plasma triglycerides, total cholesterol, low-density lipoprotein, cholesterol, and apolipoprotein B were elevated in patients compared with controls. These lipid concentrations decreased significantly following 6 months of EPO. Thus, treatment of anemia by EPO is associated with improvements in insulin and lipid abnormalities in uremic patients on CCPD. Received September 23, 1997; received in revised form January 20, 1998; accepted January 22, 1998     

Islet Hyperplasia in Adults: Challenge to Preoperatively Diagnose Non-Insulinoma Pancreatogenic Hypoglycemia Syndrome

Background Pancreatic hyperfunctional islet hyperplasia in adults has been more and more frequently described in the literature. Postprandial neuroglycopenia, a negative normal fasting test, negative pancreatic imaging results, and positive intra-arterial calcium stimulation of serum insulin are characteristic. In affected patients the term non-insulinoma pancreatogenic hypoglycemia syndrome (NIPHS) was proposed. Materials and Methods/Patients We also encountered fasting hypoglycemia in such patients and therefore evaluated clinical and biochemical data in patients with NIPHS (n = 11), patients with insulinoma (n = 70), and patients in whom hypoglycemia was ruled out (n = 70). Results Patients with NIPHS were younger (median age: 41 years; range: 18–66) and mostly non-obese (median body mass index/BMI: 22.2 kg/m²; range: 19–39) compared with patients with an insulinoma (median age: 50 years; median: BMI 26.1 kg/m²). During an oral glucose tolerance test (OGTT) followed by a standard fasting test, neuroglycopenia was observed postprandially with a mean minimal blood glucose level of 36 ± 9 mg/dl in 7 out of 11 patients. Spontaneous hypoglycemia during the fast was 38 ± 5 mg/dl in 8 out of 11 patients. The corresponding insulin levels were 9.2 ± 9.8 mU/l (OGTT) and 6.8 ± 5.4 mU/l (fasting), significantly lower than in patients with insulinoma (P < 0.001), but not different from patients without hypoglycemia (P = 0.05). After pancreatic resection 8 patients (73%) were cured with enduring euglycemia. Pathohistological islet abnormalities with hyperplasia, hypertrophy, and microadenomatosis were confirmed in all patients. Conclusion In patients with postprandial and/or fasting neuroglycopenia NIPHS may be suspected when insulin levels are low but inadequately suppressed and localization studies failed to show a distinct pancreatic tumor.     

Does a reduction in dialysate sodium improve blood pressure control in haemodialysis patients?

Introduction: There has been debate as to the value of lower sodium dialysates to control blood pressure in haemodialysis patients, as sodium is predominantly removed by ultrafiltration. Methods: Re‐audit of clinical practice following reduction in dialysate sodium concentration. Results: Overall dialysate sodium concentration decreased from 138.9 ± 1.7 to 137.8 ± 1.7 mmol/L (mean ± standard deviation), resulting in a reduction in pre‐ and post‐dialysis mean arterial pressure (MAP) of 4 mmHg (from 100.6 ± 15.6 to 97.1 ± 15.6, P < 0.01 and from 91.7 ± 15.6 to 87.1 ± 14.6, P < 0.001 respectively), yet fewer patients were prescribed antihypertensives (49.6 vs 60.6%), and less antihypertensive medications/patient (mean 0.86 vs 1.05), ultrafiltration requirements (2.8% vs 3.2% body weight, P < 0.001), and symptomatic intradialytic hypotension (0.19 vs 0.28 episodes per week, P < 0.001). A multivariable model showed that for a dialysate sodium of 136 mmol/L, younger patients had higher MAP than older patients (0.35 mmHg lower MAP/year older; but with a dialysate sodium of 140 mmol/L, there was minimal association of MAP with age (0.07 mmHg higher MAP/year older). Conclusion: Change in clinical practice, amounting to a modest reduction in dialysate sodium was associated with a reduction not only in pre‐ and post‐dialysis blood pressures, but also ultrafiltration requirements and symptomatic intradialytic hypotension. However, this effect on blood pressure was most marked for older patients and women, within minimal effects for younger patients, and lesser effects for men, suggesting that dialysate sodium reduction alone may help improve blood pressure control, but requires additional factors such as dietary sodium restriction to be effective in younger male patients.     

Influence of aldosterone synthase gene C-344T polymorphism on focal segmental glomerulosclerosis

Aim: We evaluated the influence of C‐344T polymorphism of the aldosterone synthase gene, associated with aldosterone levels and the development of arterial hypertension, on focal segmental glomerulosclerosis (FSGS). Methods: We studied 81 patients with primary FSGS followed up for 8.0 ± 12 years. Patients were classified according to their slope of reciprocal serum creatinine into group A (slow progressors, n = 57) and B (fast progressors, n = 24). One hundred healthy volunteers were analysed as controls. The biopsies of n = 50 patients were reviewed and analysed by the same pathologist. C‐344T polymorphism was determined by polymerase chain reaction. Results: The allele frequencies differed significantly between patients (C‐allele: 0.55, T‐allele: 0.45) and controls (C‐allele: 0.45, T‐allele: 0.55; P < 0.05). Patients carrying the C‐allele tended to have a higher percentage of sclerosed glomeruli (41.8 ± 30% vs 31. 2 ± 19% in TT genotype, ns) and tubulointerstitial fibrosis (22.8 ± 18% vs 16.0 ± 5%, ns). The rate of deterioration of renal function was higher in the CC/CT genotypes (?0.216 ± 0.449 dL/mg per year) compared to the TT genotype (?0.030 ± 0.041 dL/mg per year, P = 0.002). Furthermore, 36.4% of the C‐allele carriers and none of the patients with the TT genotype belonged to group B (P = 0.005). C‐allele carriers also had a worse kidney survival in the Kaplan–Meier analysis (P = 0.027). Conclusion: Our results indicate that aldosterone synthase gene C‐344T polymorphism not only acts as a risk factor for the development of FSGS, but also may influence its pathologic appearance and could serve as a marker of disease progression.     

Changes in fatigability of the striated anal canal after childbirth

Aim Anal manometry is an established assessment tool for patients with faecal incontinence. Fatigue rate index (FRI) has been shown to discriminate between symptomatic patients and controls. The aim of this study was to compare manometry and fatigability of the anal canal in nulliparous women before and after childbirth. Method An air‐filled manometry device was used to record maximum resting and squeeze pressures, fatigue rate (recorded over 20 s) and FRI. Recordings were made before and after vaginal delivery. Results Nineteen women were studied. Resting anal canal pressure was not significantly different before and after delivery (57.1 ± 13.6 vs 51.1 ± 11.9 cmH₂O, P = 0.1). Squeeze pressure was significantly lower postpartum (106.5 ± 43.6 vs 75.5 ± 45.6 cmH₂O, P < 0.001). Fatigue rate was significantly reduced postpartum (?129.5 ± 74.7 vs?76.1 ± 54.8 cmH₂O/min, P = 0.001), but FRI was not significantly altered (1.23 ± 1.49 vs 1.41 ± 1.27 min, P = 0.09). Conclusion Maximal squeeze pressure and fatigue rate of the anal canal are significantly reduced after childbirth. Resting anal canal pressure and FRI are not significantly different.     

CELLULAR POTASSIUM DEPLETION PREDISPOSES TO HYPOKALAEMIA AFTER ORAL SODIUM PHOSPHATE

Background : Oral sodium phosphate has become an attractive alternative to polyethylene glycol for colonic cleansing preparatory to elective colorectal surgery. Its use, however, has been associated with hypokalaemia. The authors of the present study tested the hypothesis that patients with cellular depletion of potassium are at significant risk for hypokalaemia with oral sodium phosphate bowel preparation. Methods : In 23 patients, total body potassium was measured by whole-body counting and intracellular water volume was measured by bioimpedance analysis before oral sodium phosphate bowel preparation. Patients were divided into those whose serum potassium fell to 3.5 mmol/L or lower (Group 1) and those whose did not after sodium phosphate treatment (Group 2). Results : The fall in serum potassium concentration over the period of oral sodium phosphate administration was significantly negatively correlated with intracellular potassium concentration measured prior to administration (r=-0.65, P= 0.0009). In Group 1, serum potassium concentration fell from 4.1 ± 0.1 (standard error of the mean (SEM)) mmol/L to 3.2 ± 0.1 mmol/L (P± 0.0001) while in Group 2 there was no significant change in this concentration (4.0 ± 0.1 vs 3.9 ± 0.1 mmol/L) as a result of sodium phosphate treatment. Intracellular potassium concentration prior to administration of sodium phosphate was significantly lower in Group 1 (117 ± 9 mmol/L vs 143 ± 7 mmol/L, P < 0.05). Conclusions : Caution should be exercised when treating patients with oral sodium phosphate who are considered to be cellularly depleted of potassium. These patients are at risk of hypokalaemia after this treatment.