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Biomedical subjects

P Malasit

Publications and source records attributed to P Malasit.

29 records · Page 2Linked to original sources

Urinary constituents in an endemic area of stones and renal tubular acidosis in northeastern Thailand.

Nephrolithiasis and endemic renal distal tubular acidosis are common in northeastern Thailand. The etiology is still unknown. It is generally accepted that urine electrolytes influence the capacity of urine to inhibit or promote renal and also bladder stones. The purpose of this study was to analyse the composition of the urine in the indigenous population in the northeast area and compare their values with data obtained from a group of age matched adults, living in Bangkok. Twenty-four hour urine samples from 23 normal adult villagers from six villages within the province of Khon Kaen and 34 normal adults living in Bangkok were collected, and the daily excretion of creatinine, uric acid, calcium and inorganic phosphate, sodium, potassium, chloride, magnesium and oxalate were assayed. Daily urinary sodium, potassium, chloride and phosphate of the villagers were significantly lower than those of Bangkokians. No difference in the urinary excretion of calcium, magnesium, uric acid, oxalate and creatinine was found. The Na/Ca, and Ca/PO4 ratios of villagers were significantly lower than those of the Bangkok subjects. The villagers excreted significantly lower amounts of Na in the face of relatively higher urinary Ca. The above data, combined with our previous study showing the low values of urinary citrate in the villagers in the same areas, strongly indicate that the indigeneous population is at high risk in developing urolithiasis. The causes for these electrolyte abnormalities are still unknown. Low contents of the major electrolytes in their diets might play an important role. Low phosphate output indicates low protein diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular↗

Endemic primary distal renal tubular acidosis in Thailand.

Within a period of 3 years, 103 patients with primary type I distal renal tubular acidosis were reported from two hospitals in the northeast of Thailand, with cases peaking in the summer. The patients' age ranged from 18 to 76 with a mean and mode of 39 and 47 years, respectively. The female to male ratio was 3.3:1. All patients presented with generalized muscle weakness and bone pain and nocturia were frequent manifestations. Hypokalaemia and hyperchloraemic metabolic acidosis were constant findings and were more pronounced in patients with roentgenographic evidence of nephrocalcinosis and osteomalacia. Urinary citrate was extremely low in most of the patients. Nephrocalcinosis and/or renal stones were present in 27.2% of the patients and osteomalacia was found in 23.3%. All patients were Lao-Thai. This is the first report of a large group of patients with distal renal tubular acidosis, endemic within a particular geographical region.

Acidosis, Renal Tubular↗

Severe cases of green pit viper snake venom poisoning.

Two severe cases of green pit viper bites were reported. The clinical manifestations were severe bleeding and diarrhea. The first patient had acute renal failure complicated from severe diarrhea and hypovolemia. Hematological findings showed hypofibrinogenemia and thrombocytopenia. Renal biopsy performed in the first case showed a picture compatible with that of the recovery phase of acute tubular necrosis. Green pit viper antivenine serum together with symptomatic and supportive treatment was given. Both patients recovered uneventfully.

Acute Kidney Injury↗

Relative inefficiency of terminal complement activation.

The efficiency of generation of fluid-phase SC5b-9 and membrane C5b-9(m) complexes relative to cleavage of C3 and C5 was studied. Fluid-phase C activation was induced through addition of purified bacterial Ag to human serum. Sephadex beads were used as particulate activators of the alternative pathway. Rabbit or antibody-coated sheep or human E were used to study formation of cytolytic C5b-9(m) complexes. The molar ratios of C3a:C5a generated in the model systems were found to be in the range of 60 to 200:1 in the case of soluble immune complex activators, and 70 to 150:1 with particulate activators and cells. The efficiency of C5 cleavage relative to C3 cleavage increased on surfaces with the density of antibody and/or C3b-binding sites. With soluble immune complexes, the efficiency of subsequent SC5b-9 generation displayed wide variations dependent on Ag and donor with molar ratios of C5a:SC5b-9 ranging from 30:1 for teichoic acid and sometimes approaching 1:1 for streptolysin-O. In contrast, activation on particles or cells always led to C5a:C5b-9 (calculated as the sum of generated moles SC5b-9 and C5b-9(m] ratios approaching 1:1. Hence, there is an overall inefficiency of terminal sequence activation in the C cascade due first to a dissociation at the level of C5 convertase formation/C5-cleavage and second, to a frequent inefficiency of C5b-utilization in the fluid-phase. The results provide an explanation for the very low levels of SC5b-9 found in plasma of healthy individuals and in patients with C-consuming immune complex disease.

Animals↗

Family study of the major histocompatibility complex in HLA DR3 negative patients with systemic lupus erythematosus.

Susceptibility to systemic lupus erythematosus (SLE) is known to be governed by genes in the HLA region of the 6th chromosome. From previous studies it has not been possible to distinguish between the effects of null genes for the complement component C4 and HLA-DR3, because of the marked linkage disequilibrium between DR3 and a null allele of C4A (C4A QO) in caucasoid populations. We report here an immunogenetic study of 44 cases of SLE, selected because they were DR3 negative. Eighteen of the 30 Caucasoid cases (60%) had extended HLA haplotypes with a C4 null allele, compared with 22 of 60 (37%) of a control panel of 60 DR3 negative normal Caucasoid subjects. This difference is significant (chi 2 = 4.41; 0.05 greater than P greater than 0.01). Of 14 non-caucasoid patients analysed, 10 had a C4 null allele. It is concluded that the null alleles of the C4 A and B genes are themselves directly responsible for conferring susceptibility to SLE.

Alleles↗

Complement and dengue haemorrhagic fever/shock syndrome.

The complement system is activated in DHF/DSS. The peak of activation and the presence of C3a and C5a anaphylatoxins coincided with the onset of shock and leakage. The levels of C3a correlated well with disease severity. This indicated an important role of the complement system in the pathogenesis of shock. Circulating immune complexes as assayed by two standard techniques were not detected in the majority of patients, and if detected were found in small amount. The role of circulating immune complexes in the activation of complement in DHF/DSS needs to be reinvestigated, and other possible mechanisms leading to complement activation should be sought.

Antigen-Antibody Complex↗

Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites.

Victims of snake bites are often subjected to cutaneous or conjunctival hypersensitivity testing before being given antivenom. None of 12 early (anaphylactic) reactions was predicted by these tests in 25 Nigerian and Thai patients. The incidence and severity of early reactions was the same whether antivenom was given by intravenous injection over 10 minutes or diluted and given as an intravenous infusion over 30 minutes. Although antivenom activated complement in vitro, there was no evidence of complement activation or formation of immune complexes in patients bitten by snakes who were treated with antivenom, whether or not they developed early reactions. Higher doses of antivenom might induce the complement activation and formation of immune complexes (aggregates) that have been observed during the clinically more severe reactions associated with homologous immunoglobulin treatment.

Anaphylaxis↗

Lupus nephritis: clinicopathological study of 162 cases in Thailand.

One hundred and sixty two cases of lupus nephritis biopsied over three years in Thailand were studied. A pattern of clinical and histological renal disease very similar to that seen in the United States or Europe emerged. The predominant histological type was World Health Organisation class IV (diffuse proliferative; 58.6%). Patients with renal insufficiency (creatinine greater than or equal to 2 mg/100 ml) or hypertension at the time of biopsy had a considerably worse three year survival. Certain features such as sclerotic glomeruli, tubular atrophy, and an interstitial mononuclear cell infiltrate were significantly associated with a worse outcome (0.05 greater than p greater than 0.01), and patients who died with poor renal function had significantly higher chronicity scores than those in other groups (p less than 0.05). These findings emphasise the importance of chronic renal damage in the morbidity and mortality of patients with lupus nephritis.

Adolescent↗

Molecular composition of complement-solubilized complexes and their fate in vivo.

Radiolabelled bovine serum albumin (BSA)-rabbit anti-BSA complexes formed at equivalence were solubilized by fresh human sera as a source of complement and analysed in 10-50% w/w sucrose density gradients. The solubilized complexes were heterogeneous, having sizes ranging from 9 to 25 S. The profiles of antigen and antibody in the complexes matched each other, indicating that solubilization is not due to dissociation of antigen-antibody bonds. The complexes could be precipitated from solution by specific antisera to C3 or C3c, but not to C1q, C4 or rabbit Fc. Although insoluble precipitates could be solubilized via the alternative pathway alone, the process was more rapid when the classical pathway was also available. Unlike the complexes which had not been solubilized by complement, a small fraction of the latter could not be dissociated at low pH(2.8) or by cationic detergent, and appeared to be covalently held together. Large aggregates of heated IgG could also be solubilized. In this case the process depended largely or solely on the classical pathway. The fate of labelled solubilized complexes was studied after i.v. injection into C3H/He mice. Clearance from the blood was slower and uptake by liver and lung was diminished compared with insoluble complexes. Solubilized complexes were preferentially taken up and retained in germinal centres of the spleen. This may be important for the generation of B-memory cells.

Animals↗

Hereditary angio-oedema with mesangiocapillary glomerulonephritis.

A patient with hereditary angio-oedema (HAO) developed mesangiocapillary glomerulonephritis (MCGN) under observation. HAO is characterized by an inherited defect of complement-deficiency of C1 esterase. MCGN is often associated with another complement abnormality which leads to depression of serum C3 and there is some evidence that the complement abnormality precedes the nephritis. The coincidence of these two rare diseases in the present patient, and in one previously described, suggests that other complement abnormalities may predispose to the development of MCGN.

Angioedema↗

Idiopathic membranous nephropathy.

The clinical and histopathological features of 37 patients with idiopathic membranous nephropathy are presented. Males were four times as commonly affected as females and the age at presentation ranged from nine to 70 years. The period of observation varied from three months to 23 years. Twenty-eight patients (76 percent) presented with the nephrotic syndrome and nine patients (24 per cent) presented with non-nephrotic proteinuria. At the end of the study, of the patients presenting with the nephrotic syndrome, seven (25 per cent) were in remission, seven (25 per cent) remained nephrotic, nine (32 per cent) showed only proteinuria and five (18 per cent) were dead or on dialysis. Altogether eight patients (28 per cent) developed renal failure. The nine patients who presented with non-nephrotic proteinuria appeared to do better, and none developed renal failure. The occurrence of spontaneous remission makes assessment of benefit from immunosuppressive therapy difficult. However, analysis of our data and a review of the literature suggest that in this condition oral prednisone, cyclophosphamide and azathioprine have no significant therapeutic properties. Histological assessment confirmed the occurrence of mild (Grade 1) changes in patients biopsied soon after presentation, and tubular atrophy increased with the duration of illness. Immunofluorescence confirmed deposition of mainly IgG and complement. Repeat biopsies in 14 patients showed no histological improvement and remission was not accompanied by resolution of histological abnormalities.

Adolescent↗