Clinical and Laboratory Features of Metformin Intoxication in Suicidal Patients Attending an Intensive Care Unit.

INTRODUCTION: This study has been performed for the purpose of researching the complications occurred at patients who took metformin overdose in an attempt to suicide. None of the patients has the diagnosis of diabetes mellitus and never used metformin. MATERIALS AND METHODS: This retrospective cross-sectional study was carried out with 21 patients who has neither diagnosed diabetes mellitus nor taken metformin for suicide before. RESULTS: It was observed that there is a moderate, negative (r = -0.63) statistically significant correlation (P < 0.001) between the time of applying to the hospital and arterial blood pH at the arrival and a statistically significant positive mild correlation (P < 0.041) between applying and blood lactate level (r = 0.45), and a moderate positive (r = 0.63) and statistically significant correlation (P < 0.001) between the total metformin dose and blood lactate level at the arrival and a positive, moderate (r = 0.68) significant correlation (P < 0.001) between the creatinine and metformin dose at the arrival. Lactic acidosis has been detected at 8 of 21 patients, 6 patients were hemodialized, 2 patients needed mechanical ventilation, and 2 patients died. It is observed that there is no mortality for early hemodialized patients. CONCLUSION: The most important reason of the mortality in patients who has metformin intoxication is metformin-associated lactic acidosis (MALA). It was considered that hemodialysis therapy could be effective in MALA.

Strict fluid volume control and left ventricular hypertrophy in hypertensive patients on chronic haemodialysis: a cross-sectional study.

Left ventricular hypertrophy (LVH) is very common in haemodialysis patients. We measured left ventricular mass in three groups of haemodialysis patients: group A (n = 40) were normotensive and receiving a strict salt-restricted diet; group B (n = 23) were normotensive and receiving anti-hypertensive drugs; and group C (n = 43) were hypertensive despite anti-hypertensive drug treatment. The interdialytic weight gain in group B and group C was significantly higher than in group A; the mean left atrial index and left ventricular end-systolic and end-diastolic diameter indices were all higher in group B than in group A. The interventricular septum and posterior wall were significantly thicker in group B and group C than group A, resulting in a higher left ventricular mass index. Left ventricular systolic and diastolic function parameters were slightly better in group A than in the other groups. These results show that strict fluid volume control decreases blood pressure, reduces dilated cardiac compartments and corrects LVH more effectively than lowering blood pressure without correcting the volume overload.

By reducing TGF beta 1, octreotide lessens the peritoneal derangements induced by a high glucose solution.

BACKGROUND: Chronic peritoneal dialysis may eventually result in peritoneal fibrosis, which progressively reduces dialytic efficacy. Although the pathogenesis has not been elucidated, it has been proposed that transforming growth factor beta-1 (TGF beta 1) plays a central role in the onset of peritoneal fibrosis. METHODS: Rats were divided into three groups and given saline, hypertonic peritoneal dialysis solution alone, a hypertonic peritoneal dialysis solution plus octreotide intraperitoneally. After four weeks, a one-hour peritoneal equilibration test was done. Dialysate-to-plasma urea ratio, glucose reabsorption, ultrafiltration volume and levels of dialysate protein, TGF beta 1 and cancer antigen 125 (CA 125) were determined. The peritoneal membrane was examined histologically by light microscopy. RESULTS: Compared to the saline group, peritoneal function tests (ultrafiltration volume 6 (5-7) vs 0.0 ml, dialysate-to-plasma urea ratio 0.51 vs 0.76, glucose reabsorption 0.54 vs 0.40 and morphology (thickness 4.5 vs 75.5 microns) were dramatically deranged in hypertonic peritoneal dialysis solution-treated rats, which also had a higher level of TGF beta 1 and undetectable CA 125. In contrast, in hypertonic peritoneal dialysis solution plus octreotide rats' peritoneal function was protected (ultrafiltration volume 3 mL, dialysate-to-plasma urea 0.60, glucose reabsorption 0.51) but peritoneal thickening (37.7 microns) was not so markedly reduced although the production of TGF beta 1 was significantly inhibited. CONCLUSION: These data show that by inhibiting the production of TGF beta 1, octreotide can preserve peritoneal function and remodeling of the mesothelial cell. Although the production of TGF beta 1 was significantly inhibited, peritoneal thickening cannot be completely prevented.

Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%) peritoneal dialysis solution?

OBJECTIVE: Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor beta (TGFbeta1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF. METHODS: Twenty-one albino Wistar rats were divided into three groups: (1) the control group (C) received 10 mL isotonic saline intraperitoneally (i.p.), (2) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution i.p., and (3) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution i.p. plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFbeta1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy. RESULTS: Administration of enalapril resulted in preserved UF (-0.2 +/- 0.7 mL vs 1.7 +/- 0.3 mL, p < 0.05), protein loss (2.3 +/- 0.5 g/L vs 1.6 +/- 0.2 g/L, p > 0.05), and peritoneal thickness (77 +/- 7 microns vs 38 +/- 5 microns, p < 0.001). D/P urea increased significantly in the Dx group (p< 0.05). Both higher levels of TGFbeta1 (undetectable vs 298 +/- 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 +/- 0.5 U/L vs 0.11 +/- 0.1 U/L, p > 0.05) were determined in the Dx group. CONCLUSION: These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFbeta1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFbeta1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.

Strict volume control normalizes hypertension in peritoneal dialysis patients.

The aim of this study is to investigate whether normal blood pressure (BP) can be achieved in patients with hypertension on continuous ambulatory peritoneal dialysis (CAPD) therapy by strict volume control without the use of antihypertensive drugs. Of the 78 patients in our center, 47 persons had hypertension and/or were on antihypertensive drug therapy. After discontinuing these drugs, a strong dietary salt restriction was imposed by repeatedly explaining the need for it to patients and families. If this approach did not result in sufficient BP decrease, ultrafiltration (UF) was added by increased use of hypertonic (3.86% glucose) peritoneal dialysis solution. Cardiothoracic index (CTI) on the chest radiograph was also used as a measure of volume control. With salt restriction alone or combined with UF, body weight decreased by a mean of 2.8 +/- 0.5 kg, and BP decreased from a mean of 158.2 +/- 17.0/95.7 +/- 10.3 to 119.7 +/- 16.0/77.9 +/- 9.7 mm Hg in 37 patients, accompanied by a decrease in CTI from 48.0% +/- 5.6% to 42.9% +/- 4.5%. In 19 patients who had residual renal function, 24-hour urine volume decreased to 28% of the pretreatment volume, accompanied by a mean decrease in Kt/V urea from 2.06 +/- 0.5 to 1.85 +/- 0.4. In 7 of the remaining patients who did not respond to the applied treatment, BP decreased from 158.8 +/- 23.2/111.6 +/- 9.8 to 113.5 +/- 14.3/76.4 +/- 6.2 mm Hg after administration of an angiotensin-converting enzyme (ACE) inhibitor. Their CTI was 41.2% +/- 1.3%, indicating the absence of hypervolemia. In 3 patients, the desired results could not be reached because of noncompliance. Our findings show that normal BP can be achieved by severe salt restriction combined with increased UF in the majority of CAPD patients. This is accompanied by a decrease in CTI from upper limits into the normal range, but also by a decrease in residual renal function and Kt/V index. In most of the remaining patients, normal BP can be reached by the use of ACE inhibitors.

How can we standardize peritoneal thickness measurements in experimental studies in rats?

OBJECTIVE: The various methods of measuring peritoneal thickness in experimental studies in rats have yielded conflicting results. Also, no standard method exists to assess histologic findings in peritoneal morphology. We therefore undertook the present study to create a reproducible and standard method for assessing rat peritoneal histology in experimental studies. METHODS: Parietal peritoneal samples from 61 Wistar albino rats were used in the study. Excepting the skin, the whole abdominal wall from each rat was cut two-dimensionally (longitudinally and horizontally), fixed in formalin, and processed routinely for light microscopy. Slides were divided into two groups according to the direction of the inner abdominal muscle fibers in the sections. Longitudinal and horizontal sections of abdominal muscle were evaluated. For every section, one histopathology image was captured from a light microscope to an IBM-compatible computer. Peritoneal thickness (mean of the maximum and the minimum) and submesothelial area (SMA) were drawn on the image. A computer program then automatically performed measurements. Two different measurement methods were compared, based on the same sections. RESULTS: The mean peritoneal thickness was 91 +/- 8 microm in the longitudinal sections and 75 +/- 7 microm in the horizontal sections (p < 0.05). Measurements of the SMA were found to be 47,762 +/- 4,374 microm2 for the longitudinal sections and 40,389 +/- 3,631 microm2 for the horizontal sections (p < 0.05). In both types of sections, a positive correlation (96% for longitudinal and 90% for horizontal) was found between the SMA and the peritoneal thickness (p < 0.01). The SMA measurements correlated significantly with functional properties [ratio of the dialysate concentration of glucose initially and after a 1-hour dwell (D1/D0 glucose), ultrafiltration, and protein loss; p < 0.01]. CONCLUSION: Peritoneal thickness can be measured as a mean of the minimum and maximum values. That measurement strongly correlates with submesothelial area. Both types of sections can be used, but the horizontal and longitudinal sections show systematic differences. All samples in a study should be taken using the same section pattern, either longitudinal or horizontal.

The effect of L-carnitine on insulin resistance in hemodialysed patients with chronic renal failure.

We investigated the effect of L-carnitine in seven patients, four female and three male (mean age 44.4 +/- 6.0 years) with chronic renal failure. Six patients, four female and two male (mean age 49.3 +/- 2.2 years) with chronic renal failure were given a placebo (0.9% sodium chloride) as control. After the basal data were obtained, patients received a single intravenous dose of L-carnitine (1 g) or placebo and two hours later insulin sensitivity was studied by the intravenous insulin tolerance test. No change was observed in biochemical data and K(itt) values in the placebo group. K(itt) increased significantly with carnitine (from 2.99 +/- 0.3 to 3.54 +/- 0.2%/min, p < 0.03) compared to the control group (p < 0.02). This result suggests that L-carnitine may improve the insulin resistance common among uremic patients.

Intravenous alfacalcidol improves insulin resistance in hemodialysis patients.

We have examined the effect of a four-week intravenous treatment with 1 alpha-hydroxyvitamin D3 on insulin sensitivity in 14 patients on chronic hemodialysis compared with 10 healthy control subjects by the insulin tolerance test. Compared to controls, the uremic patients have featured increased levels of parathyroid hormone (1085.0 +/- 822.1 vs 74.2 +/- 8.7 pg/ml, p < 0.001), insulin resistance (the rate constant for plasma glucose disappearance, K(in): 3.1 +/- 0.5 vs 4.5 +/- 0.4%/dk, p < 0.002), increased levels of insulin (30.5 +/- 7.3 vs 20.4 +/- 2.8 microIU/ml, p < 0.04) and increased levels of C-peptide (6.0 +/- 2.1 vs 3.9 +/- 12, ng/ml, p < 0.001). Following treatment with 1 alpha-hydroxyvitamin D3, levels of parathyroid hormone decreased from 1085.0 +/- 822.1 to 772.1 +/- 620.1 pg/ml (p < 0.004), the K(in) values increased significantly (from 3.1 +/- 0.5 to 4.1 +/- 0.4%/dk, p < 0.004) and reached the level near to that of controls, the insulin concentrations decreased from 30.5 +/- 7.3 to 28.7 +/- 9.2 microIU/ml (p > 0.05) and C-peptide concentrations increased from 6.0 +/- 2.1 to 7.5 +/- 2.5 ng/ml (p < 0.02). In summary, uremic patients with secondary hyperparathyroidism developed insulin resistance and hyperinsulinemia. Intravenous 1 alpha-hydroxyvitamin D3 treatment has improved insulin sensitivity directly or by reducing secondary hyperparathyroidism in uremic patients on chronic hemodialysis.

Short term reduction of left ventricular mass in primary hypertrophic cardiomyopathy by octreotide injections.

Growth factors have been shown to be associated with primary hypertrophic cardiomyopathy. Octreotide, a long acting somatostatin analogue, can prevent the stimulating effect of growth factors and decrease the left ventricular mass in patients with acromegaly. In the light of these results, three patients with primary hypertrophic cardiomyopathy were treated with subcutaneous octreotide (50 micrograms three times a day during the first week and 100 micrograms twice a day for the following three weeks). Initially, two patients were in New York Heart Association class II in and one was in class III. At the end of a four week treatment session all were in class I. There were significant decreases in left ventricular posterior wall thickness, interventricular septum thickness, and left ventricular mass in all three patients. Both left ventricular end diastolic and end systolic diameters had increased in all of the patients at the end of the fourth week. Two of three patients showed improved diastolic filling: their hyperdynamic systolic performance returned to normal. No side effects were observed during octreotide treatment. The considerable improvement obtained with the short term octreotide treatment in patients with primary hypertrophic cardiomyopathy seems promising.