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Biomedical subjects

V Mavichak

Publications and source records attributed to V Mavichak.

At least 19 recordsLinked to original sources
PubMed2004

The pharmacokinetics of mycophenolate mofetil in Thai kidney transplant recipients.

Mycophenolate mofetil, in addition to cyclosporine and prednisolone significantly reduces the rate of acute rejection. The original recommended dose of MMF is fixed at 2 g/day. However, Thai patients cannot tolerate this dose due to gastrointestinal adverse effects. So the majority of patients are maintained on MMF at doses ranging from 0.5 to 2 g/day, according to their tolerability with an acceptable rate of acute rejection episodes. This study sought to determine the steady state pharmacokinetics of MMF in Thai kidney transplant recipients on stable doses of MMF. Forty-six kidney transplant patients more than 3 months on a stable MMF dose of 0.5, 1, 1.5, and 2 g/day together with cyclosporine and prednisolone underwent a single pharmacokinetic blood sampling for 12 hours following the morning dose of MMF. The analysis of plasma concentrations of mycophenolic acid (MPA), the sole pharmacologically active metabolite of MMF, was performed by using an high performance liquid chromatography method. Sparse efficient sampling strategies were employed to optimize the blood sampling schedule. Hence, blood samples were collected at 0, 0.5, 2, 12 hours after the MMF dose. The sampling time was designed to best estimate AUC(0-tau) at steady state. The initial MPA-Bayesian estimator were used for MPA concentrations that would allow the best estimation of Vc, CLt, and Ka. In this study, there is a high interindividual variability in the AUC. The median MPA AUC was 34.3 ug.h/mL (range 14.1-65.4). Thirty-one of 45 (68.9%) patients had a MPA AUC within 20 to 40 ug.h/mL, which is the most reasonable risk: benefit ratio in terms of preventing acute rejection episodes. Forty-one of 45 (91.1%) patients had MPA AUC within 20 to 60 ug.h/mL, which is the MPA therapeutic range. The highest Pearson correlation coefficient of determination between MPA AUC and a single concentration was observed with MPA 2 hours (r = 0.622) Without a fixed dosing regimen, most Thai kidney transplant recipients who receive MMF as part of a maintenance immunosuppressive regimen have the MPA AUC within the therapeutic window. The single drug concentration that correlates well with the AUC is MPA at 2 hours postdose.

Adult↗
PubMed2004

The role of anti-IL-2 receptor in high-risk kidney transplant patients.

UNLABELLED: Anti-IL-2 receptor has been proved to be effective in reducing the rate of acute rejection in kidney transplantation and also improving both the rate of graft and patient survival. In this study, we retrospectively review the role of anti-IL-2 receptor as induction immunosuppression in immunologically high-risk kidney transplant patient compared with normally low-risk patients. METHODS: From January 1999 to December 2002, we performed 246 kidney transplantations in two transplant centers in Bangkok. These were divided into two groups: group 1, high-risk group containing 50 patients who had one of the following criteria: (1) high panel reactive antibody (>50%); (2) retransplantation; (3) marginal donor (with expectancy of delayed graft function); (4) spouse donor; (5) >4 HLA mismatch. All group 1 patients receive anti-IL-2 receptor as induction immunosuppression (either Basiliximab (n = 27) or Daclizumab (n = 23).) Group 2 consisted of the control group of 196 patients with normal immunological risk. The following data of both groups were collected and analyzed: patient demography, type of donor, acute rejection incidence, severity, and time. RESULTS: In this study, the anti-IL-2 receptors are 27 cases of Basiliximab and 23 cases of Daclizumab. The rates of acute rejection are not significantly different in both groups, namely, 46 of 194 (23.7%) in group 2 compared with 10 of 50 (20%) episodes in group 1 (P = .602). All rejections in both groups responded to pulse steroid treatment. The mortality rate and rate of graft failure were also not significantly different, i.e., 6 of 196 (3.1%) vs 2 of 50 (4.0%) (P = .666) and 7 of 196 (3.6%) vs 3 of 50 (6.0%) (P = .429) in low risk group versus high risk group, respectively. Kaplan-Meier estimates of the probabilities of acute rejection free, patient survival rate, and graft survival rate also showed no difference between groups. CONCLUSIONS: The use of anti-IL-2 receptor antibodies as induction immunosuppression in immunologically high-risk patients results in the same rate of acute rejection, severity of acute rejection, graft survival, and patient survival as recipients with normal immunological risk.

Antibodies, Monoclonal↗
PubMed1997

Crossmatching technique facilitating kidney transplantation.

Accelerated acute cellular rejection (AR) continues to be a serious problem in kidney transplantation (KT), suggesting that undetected presensitization may be encountered. The purpose of this study was to determine the most sensitive crossmatching (XM) technique to detect the preformed antibody (Ab) which may cause AR. One hundred and twenty two sera from 98 patients, on the waiting list for KT at Ramathibodi Hospital were XMed with 23 cadaveric splenic lymphocytes including 2 living related KT (LR-KT). The XM was performed by 3 different techniques namely, standard microlymphocytotoxicity test (standard NIH), antihuman globulin microlymphocytotoxicity test (AHG) and flow cytometric XM (FCXM). The XM results revealed that 8 out of 75 (10.7%) tests were negative by standard NIH, i.e., 5 tests were positive by AHG only and 1 test was positive by FCXM only and 2 tests were positive by both AHG and FCXM. In addition, the patients who had the AHG technique were not done, 5 out of 47 (10.7%) tests were also negative by standard NIH but were positive by FCXM. The sensitivity of the techniques was done by titrations of anti HLA-A2. It was found that FCXM was the most sensitive technique, followed by AHG and standard NIH, consecutively. In the retrospective study of LR-KT, case #1, the standard NIH for XM using pre-KT blood sample was negative while AHG and FCXM were strongly positive. The patient had AR at day 2 post-KT which confirmed by needle biopsy. The serum at day 11 and day 116 post-KT were tested again and were positive by the 3 techniques. Case #2, pre-KT blood sample showed negative T-XM by the 3 techniques while auto-B and B-XM were positive by standard NIH and AHG but negative by FCXM. This patient had rejection at day 16 after KT. The post-KT blood sample at day 30 showed positive auto T/B and T/B-XM by standard NIH and AHG whereas it was still negative by FCXM. It was also noted that Ab to donor B cell was better detected by standard NIH and AHG than FCXM. In conclusion, FCXM is more sensitive than standard NIH and AHG, however this technique is limited in detecting IgM T and B cell Ab. AHG technique can detect both IgG and IgM antidonor T and B cell Abs. In addition, AHG technique is more sensitive than standard NIH and does not require sophisticated equipment. AHG technique should be appropriate for routine XM, especially, in LR-KT and sensitized patients.

Cadaver↗
PubMed1992

Bartter's syndrome: evidence suggesting a distal tubular defect in a hypocalciuric variant of the syndrome.

Renal tubular function was examined in 5 adult patients aged 18-30 years with Bartter's syndrome associated with renal magnesium wasting and hypocalciuria. In the 3 patients studied during hypotonic saline diuresis, distal tubular fractional chloride reabsorption was lower than that reported in normal subjects. In response to a single intravenous dose of furosemide (40 mg), the increment in the excretion of sodium, chloride, and magnesium was equal to or greater than in normal subjects, while in 2 patients, in response to intravenous chlorothiazide (500 mg), the increment in sodium excretion was less than in normal subjects. Magnesium chloride infusion was undertaken in 2 patients in order to compare magnesium and calcium excretions at similar plasma magnesium levels in patients and in normal subjects. The patients exhibited magnesium wasting only at normal or low plasma magnesium levels, while calcium excretion was reduced in the patients at normal and elevated plasma magnesium levels. We conclude that in these patients the enhancement of renal magnesium reabsorption by hypomagnesemia is defective, and the hypomagnesemia is not the cause of the hypocalciuria. The tubule defect responsible for these abnormalities of magnesium and calcium excretion may be located beyond the side of action of furosemide, in the thiazide-sensitive segment of the distal convoluted tubule.

Absorption↗
PubMed1988

Renal magnesium wasting and hypocalciuria in chronic cis-platinum nephropathy in man.

1. The renal handling of calcium and magnesium was studied in six patients with persistent hypomagnesaemia after cis-platinum treatment for testicular tumours. 2. In comparison with normal subjects, the patients showed hypomagnesaemia (mean 0.54 mmol/l), which was associated with a normal urinary magnesium excretion (mean 4.83 mmol/24 h). Urinary calcium excretion was significantly lower in the patients than in the normal subjects (mean 2.05 vs 5.15 mmol/24 h, respectively; P less than 0.01), despite slightly higher total serum calcium levels (2.53 vs 2.38 mmol/l, respectively; P less than 0.05). During magnesium chloride infusion, when serum magnesium levels were comparable in patients and controls, urinary calcium excretion remained lower in the patients, indicating that hypomagnesaemia was not the cause of the hypocalciuria. 3. Dietary magnesium supplementation resulted in a significant increase in the serum magnesium levels in the patients, while dietary magnesium deprivation resulted in a comparable decrease in urinary magnesium excretion in patients and controls (to 1.46 and 2.00 mmol/day, respectively), although the serum magnesium level fell further (to 0.46 mmol/l) in the patients. 4. The dissociation of renal calcium and magnesium excretion appears to be part of the intrinsic tubular defect caused by cis-platinum. This dissociation of urinary calcium and magnesium excretion, which resembles that seen in Bartter's syndrome, may result from a lesion in the distal convoluted tubule.

Administration, Oral↗
PubMed1988

Sodium thiosulfate prevents cisplatin-induced hypomagnesemia.

Clearance studies were performed in four groups of male Wistar rats to assess the protective effect of sodium thiosulfate on cisplatin-induced hypomagnesemia. In group I, sodium thiosulfate (400 mg/kg) was injected intraperitoneally once weekly for 3 consecutive weeks. In group II, only cisplatin (2.5 mg/kg) was administered. In group III, both cisplatin (2.5 mg/kg) and sodium thiosulfate (400 mg/kg) were injected via the intraperitoneal route. When both drugs were administered together, they were injected into different parts of the peritoneal cavity. In group IV cisplatin was administered intraperitoneally and sodium thiosulfate intravenously. Sodium thiosulfate prevented a rise in plasma creatinine. The overall glomerular filtration rates of groups III and IV were the same as in group I. Hypomagnesemia was noted in group II, whereas in groups I, III, and IV the plasma magnesium level remained unchanged. The fractional excretion of magnesium was also higher in group II than in groups I, III, and IV. These differences persisted for the duration of the study. These results suggest that concurrent injections of sodium thiosulfate intraperitoneally or intravenously prevented the hypomagnesemic and the nephrotoxic effects of cisplatin and can be of clinical significance.

Animals↗
PubMed1988

Continuous peritoneal dialysis in acute renal failure from severe falciparum malaria.

Severe falciparum malaria complicated by acute renal failure resulted in very high mortality. Ten patients with acute renal failure from falciparum malaria (infected rbc up to 80%) were continuously dialysed using Tenckhoff peritoneal catheter. Five were oliguric and BUN was maintained between 60 to 80 mg/dl (21.4 to 28.6 mmol/l) by hourly 1 to 1.5 liter dialysate exchange during the acute phase. The peritoneal urea clearance (mean +/- SD) was 12.1 +/- 1.2 ml/min with urea nitrogen removal of 13.4 +/- 2.3 g/day. In nonoliguric cases dialysis was also needed for additional removal of waste products since the remaining renal function could not cope with the hypercatabolic state. Peritoneal glucose absorption (135 to 565 g/day) gave considerable caloric supply without volume load and also contributed to the prevention of hypoglycemia. Varying degree of acute respiratory failure developed in all patients with 5 cases (2 oliguric and 3 nonoliguric) progressing to pulmonary edema. Swan-Ganz catheterization and hemodynamic study suggested the role of increased capillary permeability and volume overload from endogenous water formation in the development of pulmonary complication. Continuous removal of fluid and waste products minimized these problems and may prevent the progression of respiratory failure. One patient died of severe sepsis and the other nine survived. This study showed the beneficial contribution of continuous peritoneal dialysis in the management of acute renal failure from severe falciparum malaria.

Acute Kidney Injury↗
PubMed1986

Regional migratory osteoporosis of the lower extremities with vertebral osteoporosis.

Regional migratory osteoporosis is a disorder of unknown etiology, characterized by successive episodes of joint pain, accompanied by localized osteoporosis. The disorder affects the lower limbs, usually the region of the foot, knee, or hip, and each episode usually lasts several months and is followed by spontaneous recovery. This disorder has not previously been reported to cause episodes of vertebral osteoporosis. We describe three patients in whom regional osteoporosis, involving the lower limbs, was associated with simultaneous vertebral osteoporosis indistinguishable from idiopathic osteoporosis. These cases suggest that this disorder might be responsible for some cases of apparent idiopathic spinal osteoporosis.

Adult↗
PubMed1986

Long-term morphological and biochemical observations in cisplatin-induced hypomagnesemia in rats.

A model of cisplatin (cis-diamminedichloroplatinum II) induced hypomagnesemia with renal magnesium wasting was developed in rats. Following three weekly intraperitoneal injections of cisplatin (2.5 mg/kg body weight) hypomagnesemia was evident after the second injection of cisplatin and persisted for at least 24 weeks after the last injection. The plasma magnesium concentration was 0.69 +/- 0.01 mM in cisplatin-treated rats and 0.79 +/- 0.01 mM in control rats 24 h after the second injection (less than 0.01). Despite a lower plasma magnesium concentration in cisplatin-treated rats, the fractional urinary excretion of magnesium was similar in both groups, indicating inappropriate renal magnesium excretion in cisplatin-treated rats. Rat kidneys fixed in situ by arterial infusion were examined by light and electron microscopy at the following times: 24 h after the first and second injections and 48 h and 1, 4, 8, 16, and 24 weeks after the third injection. Focal necrosis of the proximal tubule cells in the outer stripe of the medulla (S3 segment) was noted 24 h after the second injection. Following this, there was dilatation of the S3 segment proximal tubules which were lined by variably flattened epithelial cells devoid of brush borders. Many of these cells had enlarged, hyperchromatic nuclei, and few mitoses were observed. These changes were most extensive at 4 weeks, diminished after this, but were still present focally at 24 weeks. In this model the cisplatin-induced hypomagnesemia persists long after discontinuation of therapy as in humans, and the S3 segment is the prime target of the cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Studies on the pathogenesis of cisplatin-induced hypomagnesemia in rats.

After three weekly intraperitoneal injections of cisplatin (2.5 mg/kg body wt), male Wistar rats developed chronic hypomagnesemia, which was evident from the second week and persisted throughout the 8-week experiments. Plasma magnesium concentration was 0.69 +/- 0.01 mM in cisplatin-treated rats compared to 0.80 +/- 0.02 mM in pair-fed control rats (P less than 0.01) in the eighth week of experimentation. Despite a similar dietary magnesium intake, urinary excretion of magnesium in cisplatin-treated rats was inappropriately high, relative to the lower plasma magnesium concentration, indicating the presence of renal magnesium wasting induced by cisplatin. During the 3 weeks of cisplatin injections, metabolic balance studies indicated abnormal renal excretion and a reduction in the fractional intestinal absorption of magnesium. A compensatory period of significantly greater retention of magnesium then occurred in cisplatin-treated rats beginning in the fourth week. Clearance and recollection micropuncture studies in a separate group of rats revealed normal magnesium and calcium transport in the superficial proximal and distal nephron. Following acute MgCl2 infusion, the urinary excretion of magnesium and calcium were significantly higher in cisplatin-treated rats than in control rats; however, micropuncture studies of superficial nephrons failed to demonstrate abnormal transport of these divalent cations. It is possible, therefore, that 7 weeks of cisplatin treatment led to tubular adaptation that might have obscured the defect in magnesium reabsorption. Morphological examination indicated that pathological changes were confined to the S3 segment of proximal corticomedullary nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗