Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infancy. We have previously shown that the TPN solution is directly toxic to the liver, and that this toxicity appears to be mediated by one or more amino acids. Elevated serum methionine levels, without corresponding increases in its metabolites, suggest that accumulation of this toxic amino acid may cause TPN cholestasis. Nine-week-old rabbits (n = 28) were divided into three groups. The FED group was fed standard rabbit chow ad libitum. The TPN group was not fed and received only i.v. TPN (including methionine 121 mg.kg-1.d-1), and lipids. The EXP group was fed chow ad libitum and received i.v. methionine (121 mg.kg-1.d-1). After 14 d, we evaluated bile flow, bromosulfophthalein excretion, serum liver enzymes, liver histology, and serum amino acid levels. Bile flow was significantly depressed in the TPN and EXP groups compared with FED controls (32.9 +/- 9.4 and 45.7 +/- 14.4 versus 82.9 +/- 13.8). Excretion of the bilirubin analog bromosulfophthalein tended to be delayed by methionine infusion (p = 0.15). Serum liver enzymes (aspartate transaminase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase) were normal in all groups. Histologic liver injury in the EXP group was similar to that caused by TPN. Balloon degeneration, and portal inflammation were seen in both groups. Homocysteine, an early metabolite of methionine, was elevated in the TPN and EXP groups compared with FED controls. Intravenous methionine is hepatotoxic. Despite full oral feeding, it produces a depression of bile flow and histologic liver injury similar to that seen with TPN. Elevated homocysteine levels suggests an enzymatic block early in the pathway of methionine metabolism. We believe that methionine may be an important factor in the pathogenesis of TPN cholestasis.

In a previous study of rachitic children in Jos, Nigeria we concluded that inadequate dietary intake of calcium was the primary contributing factor to the development of their rickets. The objective of the present study was to determine the effect of calcium supplementation in 10 children with radiographically and biochemically proven rickets from the same geographical area. Rachitic children were provided with calcium supplements of 1000 mg/day for a period of 3 months. Serum and urine samples were obtained at baseline and at 24 hours, 1 week, 4 weeks, and 12 weeks after initiation of supplementation. Serum calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were measured at each time point. Dietary recalls obtained at two separate times were used to estimate usual daily intakes of calcium and phosphorus. Ten non-rachitic age-matched controls from the same geographical area were recruited for comparison. Nine of 10 rachitic subjects had radiographic evidence of healing after 3 months of calcium therapy. Although serum calcium concentrations returned to control levels, other biochemical data indicated that the rickets of these subjects may have been multifactorial in aetiology, pointing to a possible defect in the synthesis of 25-hydroxyvitamin D.

The Fulani are semi-nomadic pastoralists of the western Sahel whose culture and economy are centered on cattle. We have shown previously that Fulani children and adolescents (5-18 years old) are stunted and underweight. Nutritional status and lung function were studied in Fulani children and adolescents (n = 70), aged 6-18, and compared with a non-Fulani, rural Nigerian control group (n = 153) of the same age. Participants were restricted to healthy individuals with no prior history of respiratory disease and no symptoms of an upper respiratory tract infection within the past 6 weeks. Significant deficits in forced vital capacity (FVC; Fulani males, 1.51 l; non-Fulani males, 1.86 l, p = 0.009; Fulani females, 1.36 l; non-Fulani females, 1.79 l, p < 0.001), forced expiratory volume in one second (FEV1; Fulani males, 1.44 l; non-Fulani males, 1.76 l, p = 0.02; Fulani females, 1.24 l; non-Fulani females, 1.69 l, p < 0.001), and peak expiratory flow rate (PEFR; Fulani males, 2.69 l/s; non-Fulani males, 3.48 l/s, p = 0.002; Fulani females, 2.29 l/s; non-Fulani females, 3.35 l/s, p < 0.001) were found in both the Fulani boys and girls compared with the non-Fulani controls. The diminished lung function in the Fulani group could be attributed to respiratory muscle weakness or an overall deficit in energy.

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