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Biomedical subjects

M E Ament

Publications and source records attributed to M E Ament.

At least 19 recordsLinked to original sources

Excessive chromium intake in children receiving total parenteral nutrition.

Various expert bodies have recommended that the daily parental intake of chromium in children receiving total parenteral nutrition (TPN) should be 0.20 micrograms/kg. To test whether this recommendation is appropriate, we assessed chromium intake, serum chromium concentrations, and renal function in 15 children receiving TPN. The median duration of TPN use was 9.5 (range 1.3-14) years. The children's glomerular filtration rate (GFR), measured by plasma clearance of indium-111-DTPA was lower than that of non-TPN controls (70 [SD 17] vs 110 [10] ml/min per 1.73 m2). The daily chromium intake averaged 0.15 (0.09) micrograms/kg daily but the serum chromium concentration was 20 (4 to 42) times higher than that of the controls (2.1 [1.2] vs 0.10 [0.03] micrograms/l; p less than 0.0001). GFR was significantly inversely correlated with serum chromium concentration (r = -0.60, p less than 0.02), daily chromium intake (r = -0.69, p less than 0.01), cumulative parenteral chromium intake (r = -0.72, p less than 0.01), and TPN duration (r = -0.52, p less than 0.05). We discontinued chromium supplementation of TPN solutions and reassessed the children a year later. Contaminating chromium concentrations were 1.0-1.8 micrograms/l in TPN solutions and 0.9 micrograms/l in fat emulsions. Drinking water contained 4.3-5.7 micrograms/l. Thus, the chromium intake without supplementation was only 0.05 (0.01) micrograms/kg daily. The mean serum chromium concentration fell to 0.50 (0.30) micrograms/l but was still significantly higher than that in the controls (p less than 0.01). The GFR did not change significantly (65 [14] ml/min per 1.73 m2). No patient has shown signs of chromium deficiency. Although our patients were receiving less than the recommended chromium intake during supplementation, their high serum concentrations suggested excessive intake. The recommended parenteral chromium intake for children should be lowered.

Adolescent

Prostaglandin interacts with steroid sex hormones in the regulation of intestinal zinc transport.

1. The effects of prostaglandins (PGs) E1 and E2, testosterone, 17 beta-estradiol and indomethacin on the intestinal zinc transport rates of male and female rats were compared. 2. PGE1 stimulated Jms (the zinc flux rate from mucosa-to-serosa) of jejunal segments from male rats but inhibited Jms of those from female rats in Ussing chamber experiments. 3. 17 beta-Estradiol inhibited Jms of jejunal segments from male rats, while testosterone stimulated it in those from female rats. However, testosterone inhibited Jms of segments isolated from male rats and 17 beta-estradiol that of those from female rats, while in segments from ovariectomized rats, both of these steroid hormones stimulated Jms. 4. When PGE2 was added to an indomethacin containing medium, Jms significantly increased whereas Jsm (the zinc flux rate from serosa-to-mucosa) decreased further.

Alprostadil

Prostaglandin metabolism in relation to the bowel habits of women.

A relationship between the menstrual cycle, changes of bowel habits and concentrations of plasma prostaglandin (PG)E2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (TX)B2 in 3 groups of 8 women with different bowel habit were determined. The concentrations of PGE2, PGF2 alpha and TXB2 were significantly higher in the group who had bowel habits smoother than usual at menses compared to those who had experienced constipation throughout cycle or at menses. However, no differences between at mid-cycle and at menses were observed in the groups who had experienced constipation. These results suggest that constipation of young women is related to the inherited inability of patients to synthesize and secrete PGs in plasma and possibly in small intestine.

Adolescent

Gastric antroplasty for the treatment of delayed gastric emptying and gastroesophageal reflux in children.

Operative correction of symptomatic gastroesophageal reflux (GER) was undertaken in 530 children during a 21-year period. Gastroesophageal fundoplication (GEF) alone was performed in 415 children; 83 had simultaneous GEF and pyloroplasty; 13 had pyloroplasty alone; and 19 had GEF with later pyloroplasty. Of the last 355 children with reflux, 110 (31%) had pyloroplasty. Pyloroplasty was performed for persistent symptoms despite medical therapy when more than 60% of the isotope meal was retained in the stomach at 90 minutes. Children with central nervous system disorders and GER often had delayed gastric emptying (DGE). A modified Heineke-Mikulicz pyloroplasty was used for the first 59 children; the last 56 patients had a more simplified antroplasty with a 2.5- to 3.5-cm vertical incision through the antral muscularis down to the duodenum without mucosal incision; the muscularis was reapproximated in a transverse direction with sutures. With a mean follow-up of 5.8 years, only three patients experienced mild transient dumping. None had pyloroplasty leak or clinical evidence of alkaline reflux. Antroplasty is a helpful, simple adjunct to GEF with low morbidity in children with GER and DGE.

Adolescent

Carnitine status of children receiving long-term total parenteral nutrition: a longitudinal prospective study.

Nine children receiving carnitine-free total parenteral nutrition for 7.2 +/- 2.6 years since birth were prospectively studied for 3 years. Plasma values of total and free carnitine were 50% lower than those of age-matched healthy control subjects (p less than 0.02) but did not decrease further during the 3-year period. No significant abnormalities in free fatty acids, triglycerides, or cholesterol were found. The mean levels of alanine and aspartate aminotransferases and of alkaline phosphatase were slightly increased (p less than 0.02) at the initiation of the study but remained in the same range 3 years later. The low plasma carnitine values appeared to be without clinical consequence after 10 years of carnitine-free total parenteral nutrition.

Carnitine

Iodine supplementation in children receiving long-term parenteral nutrition.

In 18 children receiving long-term total parenteral nutrition (TPN) without iodide supplements, thyroid function test results were normal but serum iodide levels were greater than in control subjects (p less than 0.01). Iodine contamination of TPN solutions and fat emulsions accounted for only half of the recommended parenteral intake. Skin absorption of topical iodinated disinfectant may explain the adequate, if not excessive, iodine intake. We conclude that iodine is an unnecessary supplement in TPN solutions.

Adolescent

Central venous catheter sepsis caused by unusual Gordona (Rhodococcus species: identification with a digoxigenin-labeled rDNA probe.

We describe central line sepsis caused by Gordona (Rhodococcus) species in two patients, which complicated receipt of long-term total parenteral nutrition at home. Species identification was attempted by conventional biochemical analysis and analysis of polymorphisms in the ribosomal RNA genes with use of a digoxigenin-labeled rDNA probe. Using these techniques, we identified our first patient's isolate as Gordona terrae. The isolate from our second patient was biochemically atypical and could not be reliably matched to any of the recognized Gordona (Rhodococcus) species. To our knowledge, these patients are the first to have been reported with systemic infection caused by Gordona (Rhodococcus) species. The first patient's infection resolved after 6 weeks of intravenous therapy with vancomycin with the catheter left in situ; however, infection in the second patient required catheter removal for cure. These cases show that immunocompetent patients receiving long-term parenteral nutrition may develop central line infections with these unusual species of microorganisms.

Actinomycetales Infections

OKT3 treatment of steroid-resistant rejection in pediatric liver transplant recipients.

Of a total of 187 consecutive liver grafts in 149 pediatric recipients, 59 episodes of steroid-resistant, biopsy-proven rejection (32% of grafts) were treated with OKT3 monoclonal antibody. After 59 OKT3-treated episodes, liver function at the end of treatment was normal in 40%, improved in 35%, and unchanged in 24%. Of 21 partial responses, 12 episodes eventually resolved to yield an overall complete response rate of 59%. CD3-positive T-cells greater than 5% occurred during 61% of OKT3-treated rejection episodes and was associated with impaired efficacy of OKT3 (30% complete response rate). Six grafts were re-treated with OKT3 for rejection and in all CD3-positive T-cells could not be maintained less than 5%. Of the six grafts requiring repeat OKT3, five failed-retreatment and required retransplantation. OKT3 antibodies of low titer were found prior to a second use of OKT3 in 65% of episodes. Patients treated with OKT3 after failing more than two preceding steroid courses had a significantly increased chance of graft loss (57%; p = 0.01). We conclude that this group of pediatric patients appeared less responsive to OKT3 compared to other series combining pediatric and adult recipients, possibly due to a more vigorous immune response in the child.

Antibodies

Serum lipid abnormalities in pediatric liver transplant patients.

UNLABELLED: Little is known about serum lipid abnormalities in pediatric liver transplant recipients. We performed a longitudinal cohort review of 102 outpatient pediatric liver recipients surviving greater than 6 months and immunosuppressed with cyclosporine and prednisone (+/- azathioprine). The median age was 6 years, median months posttransplant 25, and male-to-female ratio 1:1.5. The average cholesterol (mean of individual means) was 177 +/- 45 mg/dl and average triglyceride level 158 +/- 71 mg/dl. The mean percent of cholesterol levels greater than 170 mg/dl and triglyceride levels greater than 140 mg/dl was 47% and 50%, respectively. Age, obesity, sex, and family history of risk factors had no significant effect on cholesterol or triglyceride levels. Bivariate regression analysis showed no meaningful association between cholesterol or triglyceride levels and cyclosporine levels, cyclosporine dose, prednisone dose, or diastolic blood pressure. Triglyceride and cholesterol neither increased nor decreased with time posttransplant. The rate of change of triglyceride or cholesterol could not be predicted by the rate of change of cyclosporine levels (or dose), or prednisone dose. We found no evidence that rises or falls in cholesterol or triglyceride levels coincided with rises or falls in either cyclosporine level or prednisone dose. Cholestasis was significantly associated with increased cholesterol and triglyceride levels (P = 0.05). A multivariate analysis was unable to predict cholesterol or triglyceride levels from three predictors: cyclosporine level, prednisone dose, and liver function. The mean dietary intake of fat and cholesterol was above RDA and exercise patterns were suboptimal in school-aged children. CONCLUSIONS: 50% of children had a mean cholesterol greater than 75th percentile (170 mg/dl); 20% were above the 95th percentile; 56% had a mean triglyceride level greater than 140 mg/dl. By these criteria the majority of pediatric liver transplant patients have lipid abnormalities that may predispose them to atherosclerosis in later life.

Adolescent

Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients.

Plasma-free choline levels have previously been found below normal in patients receiving long term parenteral nutrition (TPN). In a group of 15 patients receiving home TPN who had low plasma free choline levels (6.3 +/- 0.8 mmol/L), we found 50% had hepatic steatosis. These patients were given oral lecithin or placebo in a double-blind randomized trial for 6 weeks. Lecithin supplementation led to an increase in plasma free choline of 53.4% +/- 15.4% at 2 weeks (P = 0.04), which continued at 6 weeks. The placebo group had no change in plasma-free choline at 2 weeks, but a significant decrease of 25.4% +/- 7.1% (P = 0.01) at 6 weeks. A significant and progressive decrease in hepatic fat was indicated by increased liver-spleen CT Hounsfield units at 2 and 6 weeks (7.5 +/- 1.7 units, P = 0.02; 13.8 +/- 3.5 units, P = 0.03) in the lecithin supplemental group. Nonsignificant changes were seen in the placebo group. It was concluded that hepatic steatosis in many patients receiving long term TPN is caused by plasma-free choline deficiency and may be reversed with lecithin supplementation. Choline is a conditionally essential nutrient in this population.

Aged

OKT3 prophylaxis in liver transplantation.

In a randomized prospective study of liver transplant recipients, we compared prophylaxis with OKT3, steroids, and azathioprine to cyclosporine, steroids, and azathioprine. Seventy-two percent of patients receiving OKT3 prophylaxis were rejection free in the first 14 days compared to 41% in the cyclosporine group (P = 0.02). However, after 14 days through a mean of 6.3 months, the overall incidence of rejection did not differ between the two groups (74% for the cyclosporine group and 48% for the OKT3 group). There was no increase in the rate of infectious complications noted in the OKT3-treated group. Thirty-nine percent of the OKT3-treated patients developed anti-OKT3 antibodies. Eight patients in the OKT3 group required reuse of OKT3 for rejection. Six of these continued to have greater than 10% CD3-positive cells with retreatment. Five were rescued successfully. With a mean survival of greater than 674 +/- 209 days in the OKT3-treated group and 626 +/- 242 days in the cyclosporine-treated group, no overall differences in graft and patient survival, liver function, renal function, late rejection incidence, or infectious complications were evident between the two groups. We conclude that OKT3 offers no long-term benefit compared to cyclosporine prophylaxis and should be reserved for treatment of rejection in patients in whom cyclosporine may be contraindicated.

Adult

Failure of duplex sonography to diagnose hepatic artery thrombosis in a high-risk group of pediatric liver transplant recipients.

Excellent correlation between angiographic findings and duplex sonography has been previously reported in the diagnosis of hepatic artery thrombosis (HAT), the most common technical complication of pediatric orthotopic liver transplantation (OLT). We now report a significant incidence of false-negative sonograms, ie, hepatic artery reported as patent but thrombosed on subsequent angiography. HAT was diagnosed in 10 of 57 pediatric OLT recipients evaluated prospectively by duplex sonography. In 5 patients HAT was diagnosed only by angiography even though arterial wave forms were observed on duplex sonography. Selective angiography demonstrated extensive collateral vessel formation arising from the superior mesenteric artery, the celiac axis, or both. The 5 patients shared very similar clinical courses marked by relapsing bacteremias with multiple enteric organisms, associated with focal infarctions of the liver. Four of the grafts had difficult arterial reconstructions and 3 of 5 had segmental bile duct dilation. We conclude that duplex sonography has proven to be a valuable screening tool in evaluating hepatic artery patency but must be correlated with angiography studies in a high-risk group of pediatric transplant patients characterized clinically by relapsing bacteremia and radiographically by false-negative duplex examinations.

Child

Renal function of children receiving long-term parenteral nutrition.

Renal function was assessed in 13 children at a mean (+/- SD) age of 9 +/- 4.9 years who had been receiving total parenteral nutrition for 7.9 +/- 4.1 years. All children had normal blood pressure, urinary sediment, and serum creatinine concentrations (58.3 +/- 1.0 mumol/L). Glomerular filtration rate was measured by plasma clearance of diethylenetriaminepentaacetic acid labeled with indium 111. All 13 children had decreased glomerular filtration rate (65.5 +/- 11.9 ml/min per 1.73 m2; range 49.5 to 83.7). Creatinine clearance was 69.1 +/- 10.9 ml/min per 1.73 m2. No tubular damage, as assessed by beta 2-microglobulinuria, was detectable. Renal ultrasonography showed normal architecture with no evidence of nephrocalcinosis in all subjects. The kidney size was normal in seven children; six had reduced (less than -1 SD) size. No relationship was seen between the true glomerular filtration rate and diagnosis, number of episodes of infections, or antibiotics used. The duration of total parenteral nutrition was inversely correlated with the true glomerular filtration rate (r = -0.66, p less than 0.01). The decrease in glomerular filtration rate was not related to the underlying disease or to the nephrotoxic drugs used; the mechanism was not identified. We conclude that long-term total parenteral nutrition is associated with a decrease in glomerular filtration rate.

Blood Chemical Analysis

The long-term outcome of OKT3 compared with cyclosporine prophylaxis after liver transplantation.

We report the long-term follow-up (greater than 1 year) of 46 patients (12 pediatric) randomized to receive OKT3 for the first 14 days after OLT with low-dose steroids compared with 39 patients (8 pediatric) who received cyclosporine, steroids, and azathioprine. The mean period of follow-up for survivors was 648 +/- 261 days for the OKT3 group and 682 +/- 216 days for the cyclosporine group. Of the OKT3 patients, 46% were rejection-free in the first month compared with 31% of CsA-treated patients (P = NS). Rejection occurred after 1 month in 21% of the OKT3 group patients compared with 19% of the CsA group patients. One patient in each group developed vanishing bile duct syndrome. Eight patients in the OKT3 group and 13 in the CsA group experienced steroid-resistant rejection and required OKT3 rescue. In the 8 patients in whom OKT3 was reused, 4 had a positive ELISA after prophylaxis, and in 6, CD3-positive cells were greater than 10% during OKT3 reuse. Five patients resolved the episode. Of patients receiving OKT3 prophylaxis, 39% developed anti-OKT3 antibodies. In the OKT3 group 83% of patients and in the CsA group 75% currently have normal liver function. There was no difference in serum creatinine for either adult or pediatric recipients at 12 months in the two groups. Eight episodes (2 CMV) of severe infection occurred after 1 month in the OKT3 group compared to 11 (4 CMV) in the CsA group. Graft survival, 63% for the OKT3 group and 73% for the CsA group, and patient survival, 67% for the OKT3 group and 84% for the CsA group, were not significantly different in the two groups. We recommend reserving the use of OKT3 for resistant rejection or when cyclosporine is contraindicated, as we can show no long-term benefit from its routine prophylactic use.

Antibodies, Monoclonal

Development of squamous cell carcinoma in chronic perineal sinus and wounds in Crohn's disease.

Two patients with Crohn's disease who developed squamous cell carcinoma in chronic sinus tracts are reported. Because nonhealing perineal sinus tracts or fistulas are relatively common in patients with Crohn's disease, the diagnosis of carcinoma may not be considered until the malignancy is advanced. Because of the potential for a surgical and oncologic "cure," early diagnosis may improve the prognosis. Malignancy should be considered in patients with nonhealing perineal sinuses who develop severe continuous perianal pain. Diagnosis is best made by needle aspiration cytology and sinus tract biopsy. Treatment should include wide excision of the sinus tract, surrounding soft tissue, and lymph nodes, followed by chemotherapy and radiotherapy in selected cases.

Adult

Effect of intravenous taurine supplementation on plasma, blood cell, and urine taurine concentrations in adults undergoing long-term parenteral nutrition.

Thirty-four adults undergoing long-term parenteral nutrition (TPN) were treated either with or without intravenous taurine for less than or equal to 24 mo. Statistical comparisons were carried out in eight patients randomly assigned to receive intravenous taurine, usually 10 mg.kg-1.d-1, and 10 patients not receiving taurine. Compared with normal adults, baseline plasma taurine and urine taurine-creatinine ratios were decreased in both groups and platelet taurine was reduced in the taurine-treated group. During taurine treatment the mean of the mean values for taurine became normal in plasma and platelets and remained normal in erythrocytes, granulocytes, and lymphocytes; urine taurine-creatinine ratios rose to approximately five times normal. During follow-up, patients not given taurine had plasma, erythrocyte, and granulocyte taurine and urine taurine-creatinine ratios below normal values and the concentrations of taurine-treated patients. Their platelet taurine was also subnormal. Thus, 10 mg taurine.kg-1.d-1 intravenously normalizes plasma and blood cell taurine concentrations in long-term TPN patients.

Adult