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Biomedical subjects

S C Shah

Publications and source records attributed to S C Shah.

At least 37 records · Page 2Linked to original sources

A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus.

A period of early, intensive insulin treatment is thought to improve subsequent beta-cell function in insulin-dependent diabetes mellitus (IDDM). To study this hypothesis, we randomly assigned adolescents with newly diagnosed IDDM to receive either conventional treatment (n = 14) (NPH insulin, 1 U per kilogram of body weight per day, in two divided doses) or an experimental treatment (n = 12) (a two-week hospitalization with maintenance of blood glucose levels between 3.3 and 4.4 mmol per liter by continuous insulin infusion delivered by an external artificial pancreas [Biostator]). During the two-week intervention, the experimental-therapy group received four times more insulin than the conventionally treated group, and their endogenous insulin secretion was more completely suppressed, as evidenced by a urinary C-peptide excretion rate one seventh that of the conventionally treated group. After the first two weeks, both groups were treated similarly and received similar amounts of insulin. At one year, the mean (+/- SEM) plasma level of C peptide was significantly higher after mixed-meal stimulation in the experimental-therapy group than in the conventionally treated group (0.51 +/- 0.07 vs. 0.27 +/- 0.06; P less than 0.01). The experimental-therapy group also had better metabolic control, as evidenced by lower glycohemoglobin values (7.2 +/- 0.7 vs. 10.8 +/- 1.2 percent; P less than 0.01). We conclude that suppression of endogenous insulin by intensive, continuous insulin treatment during the first two weeks after the diagnosis of IDDM may improve beta-cell function during the subsequent year.

Adolescent↗

Evaluation of endoscopic variceal sclerotherapy in various grades of liver disease.

Forty four patients with portal hypertension of varying etiology, including 25 patients with an acute episode of variceal bleeding and 19 with past history of hematemesis, were followed up for eighteen months following endoscopic variceal sclerotherapy (EVS). Of 11 patients in Child's A group, two died of acute bleed, three were subjected to shunt surgery and the remaining six survived the follow-up period. Ten of 11 cases in Child's C did not survive more than six months in spite of sclerotherapy. We conclude that rebleed and death due to rebleed following EVS occur more commonly in patients with poor hepatic reserve (Child's C) as compared to patients in Child's A and B.

Child↗

Hemoglobin South Florida: a genetic variant with laboratory recognition of only 20% of its product.

Hemoglobin South Florida is a recently identified hemoglobin variant that is not associated with any clinical disorder. The standard electrophoretic procedures routinely utilized to identify hemoglobin variants did not recognize hemoglobin South Florida. The acetylated form of this hemoglobin co-eluted with hemoglobin A1c on a Bio-Rex 70 column. The quantity of this hemoglobin component was consistent with the amount of hemoglobin A1c associated with uncontrolled diabetes mellitus. The affected individuals did not have diabetes. This observation led to the characterization of a hemoglobin variant that otherwise would have gone unrecognized. This is an example of a variant peptide that was unrecognized for two generations in one family. It is likely that this type of unrecognized peptide variation is common in mammals. These silent structural alterations may be responsible for the variable physical responses occurring in humans exposed to the same environmental agents.

Adolescent↗

Hematuria and hypercalciuria in children with diabetes mellitus.

Hematuria of unknown origin occurs in 30% of patients with diabetic nephropathy. In nondiabetic persons, hematuria may be caused by hypercalciuria with or without nephrolithiasis. Eight children with type I diabetes mellitus, hematuria, and hypercalciuria were observed in our clinic during a 1-year period. Two of these also had evidence of renal papillary necrosis. To assess the importance of hypercalciuria in the pathogenesis of hematuria in children with diabetes mellitus, we measured urinary calcium excretion in a large population of such patients. The calcium to creatinine ratio in the urine of diabetic children (0.21 +/- 0.01) was greater than that of nondiabetic children (0.12 +/- 0.01). A calcium to creatinine ratio of 0.28 was established as the upper limit of normal in our nondiabetic population, and 27% of the diabetic children were hypercalciuric on this basis. The diabetic children with hypercalciuria also had hyperphosphaturia and a urinary CaHPO4 X 2H2O molar ion product three times that found in the nondiabetic control population. These data suggest that many children with diabetes are at risk for renal damage due to hypercalciuria. Because hypercalciuria is more common in diabetic than nondiabetic children, it may play a previously unrecognized role in the renal disease associated with diabetes mellitus.

Adolescent↗

Hemoglobin South Florida. New variant with normal electrophoretic pattern mistaken for glycosylated hemoglobin.

An 8.75-yr-old Caucasian boy was discovered to have a markedly elevated (14.8%) hemoglobin A1c (HbA1c) as estimated by ion-exchange chromatography (Bio Rex 70). Glycohemoglobin (GHb) measured by a colorimetric method with thiobarbituric acid (TBA) was normal (equivalent to a 6.4% HbA1c). Nondiabetic quantities of GHb were found with affinity chromatography, and the glucose tolerance test was normal. Intensive efforts to identify an abnormal variant hemoglobin by several electrophoretic methods were unsuccessful. A family survey identified a similar abnormality in 11 other individuals, revealing an autosomal-dominant pattern. None of the affected individuals had any other hematologic abnormality. Structural analysis in one family member revealed a new hemoglobin variant (approximately 45% of the total hemoglobin) with the substitution of methionine for valine at the beta-NH2-terminal. In addition, the initiator methionine residue was preserved. Approximately 20% of the variant hemoglobin was modified by acetylation of the NH2-terminal methionine. The modified variant coeluted with HbA1c. We suggest that patients who do not have an explanation for their elevated HbA1c should have GHb measured by the TBA method or affinity chromatography because hemoglobin electrophoresis does not identify this confounding artifact.

Adolescent↗

Hypercalciuria, hyperphosphaturia, and growth retardation in children with diabetes mellitus.

The role of hypercalciuria and hyperphosphaturia in the growth retardation of children with diabetes mellitus was investigated in 157 children with diabetes whose mean height was less than that of 37 nondiabetic siblings of similar age (P less than .025). Hyperglycemia, hypercalciuria, and hyperphosphaturia were assessed coincident with the height measurement of each child in a cross-sectional survey. The distribution of height percentiles of the children with diabetes was skewed to the left with 61% at or below the 50th percentile. Eleven percent of the insulin-dependent children with diabetes mellitus were shorter than would be anticipated by a normal distribution of the 157 children. The duration of diabetes (hyperglycemia) had the greatest influence upon the children's height. Children with diabetes were shorter than the nondiabetic subjects by the fourth year of hyperglycemia, and this difference in height became statistically significant after 7 years or more of diabetes. The degree of hypercalciuria and hyperphosphaturia was more closely associated with reduced height in children with diabetes than was the degree of hyperglycemia, although the renal wastage of calcium and phosphorus seemed to be the result of glucosuria. Because hypercalciuria and hyperphosphaturia impair growth in nondiabetic children, they may also play an important role in the poor growth of children with diabetes mellitus.

Adolescent↗

Glycosylated hemoglobin: colorimetric vs chromatographic measurement.

Glycosylated hemoglobin (GHb) was measured by a chromatographic method using HPLC (HbA1c) as well as a colorimetric method using thiobarbituric acid (TBA) on samples collected from 40 diabetic subjects. GHb measured by HPLC correlated well with the colorimetric method (r = 0.7). Freezing the samples caused an immediate increase of the HbA1a+b but not the HbA1c results. 4 weeks storage of the red cells at room temperature, 4 degrees C or -20 degrees C altered the results of GHb measured by HPLC but not the TBA reaction. Half of the total ketoamine linked hexoses detected by the TBA reaction was found in the HbA0 fraction as measured by ion exchange chromatography. The colorimetric method (r = 0.53) had better correlation than the HPLC method (r = 0.27) with mean blood glucose values during the 4 weeks preceding sample collection. GHb measured by the TBA reaction more accurately represents the ketoamine linked sugar in hemoglobin, is less subject to handling artifacts and more accurately reflects the blood glucose values during the preceding 4 weeks.

Blood Preservation↗

Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N alpha-acetylation.

The hemoglobin variant South Florida has been shown by protein sequencing and fast-atom-bombardment mass spectroscopy to have a substitution of methionine for the NH2-terminal valine of the beta-globin chain. In addition, there was complete retention of the initiator methionine on the mutant polypeptide. Approximately 20% of the protein was acetylated at the NH2 terminus of the beta chain. A search of a comprehensive data bank of protein and gene sequences revealed 84 unrelated vertebrate proteins that have not undergone cleavage of leader sequences. A highly nonrandom distribution of residues at the NH2 termini of these proteins predicts removal of the initiator methionine as well as NH2-terminal acetylation. Proteins that undergo removal commonly have serine, alanine, glycine, or valine, as the NH2-terminal residues. The first three residues favor N alpha-acetylation. Proteins that retain the initiator methionine commonly have a charged residue or methionine at the second position. Information on Hb South Florida and other hemoglobins coupled with this survey of primary sequence provides insights into the NH2-terminal processing of proteins.

Acetylation↗