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Biomedical subjects

W M Belknap

Publications and source records attributed to W M Belknap.

8 recordsLinked to original sources
PubMed1995

Transient elevation of sweat chloride concentration in a malnourished girl with the Mauriac syndrome.

Elevated sweat chloride concentration in a patient with Mauriac syndrome has been reported only once. The authors of that report regarded their patient's underlying malnutrition, and not Mauriac syndrome per se, as the cause of the elevated sweat chloride concentration. We describe a second example of transient elevation of sweat chloride concentration, which confirms that the malnutrition intrinsic to Mauriac syndrome, rather than the syndrome itself, was the probable cause of elevated sweat chloride values.

Child↗
PubMed1993

Lactate oxidation for the detection of mitochondrial dysfunction in human skin fibroblasts.

To screen fibroblasts for defects in lactate/pyruvate oxidation, cells were grown to confluence in 25-cm2 flasks, rinsed, and incubated in glucose-free media containing 25 microM L-lactate and 0.1 microCi [D,L-1-14C]lactate. Lactate oxidation was measured as the amount of lactate oxidized in nmol of 14CO2 generated/mg protein/min. Fibroblasts from patients with mitochondrial or peroxisomal disorders had decreased lactate oxidation compared to the control (CON): CON, 1.9 +/- 0.13 nmol/mg/min; neonatal adrenoleukodystrophy (NALD), 0.45 +/- 0.01 (P < 0.001); rhizomelic chondrodysplasia punctata (RCDP), 0.13 +/- 0.002 (P < 0.001); mitochondrial defect of unknown etiology (MIT), 0.77 +/- 0.003 (P < 0.001); pyruvate dehydrogenase (PDH) deficiency, 0.98 +/- 0.02 (P < 0.001). This method is useful for screening fibroblasts for defects in lactate oxidation in patients with mitochondrial or peroxisomal disorders. Confirmation of the site of the defect may then be investigated with specific assays, e.g., PDH, in cellular homogenates: CON, 0.93 +/- 0.02 nmol/mg/min; NALD, 0.55 +/- 0.02; RCDP, 0.44 +/- 0.02; MIT, 0.53 +/- 0.03; PDH deficiency, 0.19 +/- 0.02.

Acidosis, Lactic↗
PubMed1989

Severe pseudomembranous enterocolitis in a child: case report and literature review.

Antibiotic-associated pseudomembranous enterocolitis (PMC), an inflammatory gastrointestinal disease mediated by toxins produced by Clostridium difficile, is increasingly recognized in the pediatric population. We report a case of fulminant PMC in an otherwise normal 2 1/2-year-old child after antibiotic therapy given for a routine childhood illness. The patient had debilitating colitis marked by severe diarrhea, a generalized electrolyte derangement, an extreme protein-losing enteropathy state, rectal prolapse, ascites, pleural effusion, varicella and multiple relapses. The child required specific antimicrobial therapy as well as aggressive supportive care to achieve recovery. A review of the literature for pediatric cases of PMC revealed reported cases in all age groups; the youngest was 5 days old. There were 9 deaths in 43 cases for a mortality rate of about 20%. All but 2 of the cases were associated with antibiotic therapy. The antibiotics most frequently implicated were ampicillin (15), penicillin (11), cephalosporins (7), amoxicillin (6) and clindamycin (5). The onset of symptoms of PMC can begin at any time while the child is taking an antibiotic or up to 21 days after it is discontinued. Children with underlying gastrointestinal motility disorders such as Hirschsprung's disease are predisposed to PMC. Fulminant PMC is a serious but uncommon infectious disease of infancy and childhood, occurring as a complication of routine antibiotic therapy for common childhood illnesses.

Amoxicillin↗
PubMed1988

Sterol synthesis and low density lipoprotein clearance in vivo in the pregnant rat, placenta, and fetus. Sources for tissue cholesterol during fetal development.

Whereas the greatest relative increase in body mass occurs during the third trimester of fetal life, the source of the cholesterol that supports this growth is uncertain. These studies used [3H]water and 125I-cellobiose-labeled low density lipoproteins to quantitate absolute rates of cholesterol acquisition in vivo by the fetus of the rat. Preliminary studies demonstrated that [3H]water administered intravenously to the mother rapidly equilibrated with the body pool of water in the fetus and that 22-microgram atoms of H from the water pool were incorporated into each micromole of newly synthesized cholesterol. After administration of [3H]water to pregnant rats, the rates of sterol synthesis per 100 g of whole body weight were severalfold higher in the fetus than in the dams. Individual organs of the dam such as the liver, however, had much higher synthetic rates than those in the fetus. When maternal hepatic cholesterol synthesis was suppressed by cholesterol feeding, newly synthesized cholesterol disappeared from the maternal blood yet there was essentially no change in the rate of appearance of newly synthesized sterol in the fetus, placenta, and fetal membranes. The placenta did take up low density lipoproteins at rates equal to about one-third of that seen in the maternal liver, but none of the apolipoprotein or cholesterol was transferred to the fetus. These studies indicate that the rat fetus receives little or no cholesterol from the mother but, rather, satisfies its need for cholesterol during fetal development through local synthesis. Furthermore, the fetal membranes appear to be an important site for sterol synthesis in the fetal compartment.

Animals↗
PubMed1988

Bile acid efflux from suckling rat hepatocytes.

To further assess bile acid transport by the developing rat liver, we compared the rate of efflux of taurocholate from hepatocytes isolated from suckling and mature rat livers. Cell content of taurocholate (nmol/mg cell protein), after preloading with [14C]-radiolabeled plus cold bile acid (5-100 microM) was similar in both groups. Total taurocholate efflux, estimated by the decrease in cell taurocholate content, was unexpectedly greater from suckling rat hepatocytes. There was a higher bile acid efflux rate over time and a lower final cell content. Efflux from suckling rat hepatocytes was increased after preloading in incubation concentrations of taurocholate which were above the physiologic range of portal blood concentrations. Inasmuch as the bile acid binding protein content is known to be reduced in the cytoplasm of developing rat liver, intracellular taurocholate may exist largely as free ligand and thus be more readily diffusable. We speculate that the in vivo correlation of enhanced efflux is back diffusion of bile acid from the cell into the sinusoid. The effect could, in part, account for the known absence of a lobular gradient for bile acid uptake in suckling rats and, therefore, contribute to the inefficient hepatic transport of bile acid observed in developing rat liver.

Age Factors↗
PubMedDate not supplied

Physiologic cholestasis II: serum bile acid levels reflect the development of the enterohepatic circulation in rats.

We have shown that serum bile acid concentrations are elevated in human infants reflecting physiologic immaturity of the enterohepatic circulation. To define further the ontogeny of bile acid metabolism in mammals, we examined maturational changes in the serum concentration of total cholate conjugates by radioimmunoassay in fetal, neonatal, suckling, and mature Sprague-Dawley rats. Fetal (21st day) levels were low (1.4 +/- 0.23 microM; X +/- S.E.), possibly due to minimal enterohepatic cycling in utero. The concentrations in samples obtained minutes after birth, prior to suckling were significantly elevated (12.6 +/- 2.37; p less than 0.001 vs. fetal); these high values persisted after feeding was initiated (6 hr = 13.5 +/- 0.99), but fell at 12 hr (5.2 +/- 0.81) and remained unchanged for the duration of the first day. Serum values fluctuated briefly, being 9.6 +/- 0.73 on Day 4, and the rose progressively through the suckling period (Day 10 = 7.2 +/- 9.57; Day 14 = 10.4 +/- 1.70; Day 21 = 16.8 +/- 1.93); there was a dramatic peak after weaning (Day 28 = 21.8 +/- 1.53). The serum concentration of cholate conjugates then fell (5.6 +/- 0.68 on Day 42) to achieve adult levels by 56 days (4.0 +/- 0.55), a value substantially different from that of all developing animals (p less than 0.025). These data corroborate studies which suggest that a period of physiologic cholestasis occurs in the developing rat. Serum cholate conjugate concentrations likely reflect interrelated morphologic alterations (bile canalicular structure and portal blood flow) and physiologic changes (bile acid synthesis, pool size, and transport) occurring in the enterohepatic circulation during early life.

Age Factors↗