Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar.

OBJECTIVES: With the use of clinical data from a large international cohort, we evaluated and compared affected siblings and isolated cases. STUDY DESIGN: Data from 116 families were collected, and patients conforming to our predetermined diagnostic criteria were analyzed. Phenotypic manifestations of affected siblings and singletons were compared with the use of t tests, Wilcoxon scores, and chi2 analysis. RESULTS: Eighty-eight patients (33 female, 55 male; median age 5.20 years) fulfilled our predetermined diagnostic criteria for Shwachman syndrome; 63 patients were isolated cases, and 25 affected siblings were from 12 multiplex families. Steatorrhea was present in 86% (57 of 66), and 91% (78 of 86) displayed a low serum trypsinogen concentration. Patients older than 4 years more often had pancreatic sufficiency. Neutropenia occurred in 98%, anemia in 42%, and thrombocytopenia in 34%. Myelodysplasia or cytogenetic abnormalities were reported in 7 patients. Short stature with normal nutritional status was a prominent feature. CONCLUSIONS: Clinical features among patients with Shwachman syndrome varied between patients and with age. Similarities in phenotype between isolated cases and affected sibling sets support the hypothesis that Shwachman syndrome is a single disease entity.

Uncertainty in the diagnosis of cystic fibrosis: possible role of in vivo nasal potential difference measurements.

The diagnosis of cystic fibrosis (CF) is not always certain, despite extensive clinical evaluation, multiple sweat chloride tests, and genotype analysis. We hypothesized that nasal transepithelial potential difference measurements have a useful role in this situation. In 11 patients without an established diagnosis of CF, results of simultaneous nasal potential difference (PD) and sweat chloride measurements were compared with those from control subjects, obligate CF heterozygotes, and patients with a confirmed diagnosis of CF. Two patients conformed to the PD profile for CF patients, whereas nine had values corresponding to those of the healthy control subjects. Subsequently the 5-thymidine (IVS8-5T) CF gene variant was identified in the two patients with abnormal PD measurements.

Do infants with cystic fibrosis need a protein hydrolysate formula? A prospective, randomized, comparative study.

OBJECTIVES: We compared the nutritional benefits of a protein hydrolysate and a conventional infant formula in infants newly diagnosed with cystic fibrosis (CF). STUDY DESIGN: Twenty-three infants with CF (<6 months of age) and pancreatic insufficiency were randomized to receive a hydrolysate formula (Alimentum) or a cow's milk-based formula (Similac). Each patient was monitored at 1 month and then every 3 months for 1 year. RESULTS: Eighteen patients (8 Alimentum, 10 Similac) completed the study. At entry, the age distribution and clinical characteristics of each group were comparable. Energy intake with each formula was the same at 1 and 3 months, but at 6 and 12 months the hydrolysate-fed infants had higher age-adjusted energy intake. There were no differences in fecal energy or fecal fat at entry or throughout the study. Although the hydrolysate-fed infants were slightly more malnourished at diagnosis, growth velocity and nutritional status of infants with CF in each group were the same throughout the study. CONCLUSIONS: The results of this randomized study fail to support the use of a hydrolyzed formula for the routine care of infants newly diagnosed with CF.

Lichen striatus: simultaneous occurrence in two nonrelated siblings.

Lichen striatus is an uncommon, self-limited eruption of unknown etiology. What role genetic or environmental influences play in its pathogenesis is unclear. We report two nonrelated, adopted children living in the same household who simultaneously developed lichen striatus.

Use of high-fat formula for premature infants with bronchopulmonary dysplasia: metabolic, pulmonary, and nutritional studies.

The use of dietary fat in preference to carbohydrate offers the theoretic advantage of diminishing carbon dioxide production and thus the respiratory quotient, which may be beneficial for babies with chronic lung disease. Ten premature infants (birth weight (mean +/- SEM), 1.13 +/- 0.12 kg; postnatal age, 9 +/- 1 weeks) with bronchopulmonary dysplasia were alternately fed a high-fat and a high-carbohydrate formula each for 1 week, in randomized order. Lower rates of carbon dioxide production (6.6 +/- 0.3 versus 7.4 +/- 0.4 ml/kg per minute; p < 0.05), and consequently lower respiratory quotients (0.80 +/- 0.02 versus 0.94 +/- 0.01 ml/kg per minute; p < 0.005), were observed during the administration of the high-fat formula. There were no significant differences in results of pulmonary function tests with the use of either formula. Both formulas were equally well tolerated and able to promote adequate growth and normal biochemical profiles. However, weight gain was significantly greater with the administration of the high-carbohydrate formula, possibly because of an increase in the accretion of body fat. We conclude that the short-term use of high-fat formula for infants with bronchopulmonary dysplasia decreases carbon dioxide production while maintaining adequate growth and nutritional status.

Bentiromide test using liquid-chromatographic measurement of p-aminobenzoic acid and its metabolites for diagnosing pancreatic insufficiency in childhood.

We assessed the diagnostic capability of the bentiromide test using a high-pressure liquid-chromatography method to analyze p-aminobenzoic acid and its metabolites in plasma as an indirect measure of exocrine pancreatic function. Mean total amine concentration in pancreatic-insufficient subjects was significantly lower than in control subjects. There were 3 of 15 false-negative results and no false-positive results. We conclude that this chromatographic method is an effective means of analyzing p-aminobenzoic acid and its metabolites after ingestion of bentiromide.

Correlation of intestinal lactulose permeability with exocrine pancreatic dysfunction.

Increased intestinal permeability to lactulose has been reported in patients with cystic fibrosis (CF). To determine whether this finding is unique to CF or whether it is related to accompanying exocrine pancreatic dysfunction, we evaluated 31 patients with CF and 10 with Shwachman syndrome who had variable degrees of pancreatic dysfunction, together with 17 healthy control subjects. There was no significant difference in the mean urinary lactulose excretion, expressed as the percentage of dose recovered, between CF and non-CF patients with pancreatic insufficiency (2.1% +/- 1.2% and 1.9% +/- 0.8, respectively) or between CF and non-CF patients with pancreatic sufficiency (0.6% +/- 0.5% and 0.6% +/- 0.3%, respectively). However, there was a significant difference in mean lactulose excretion between the pancreatic-insufficient and the pancreatic-sufficient patients (both CF and non-CF groups; p less than 0.001 and p less than 0.013, respectively). We further analyzed the results from 26 of the 41 patients (16 patients with CF and 10 non-CF patients) with pancreatic dysfunction who had previously undergone quantitative pancreatic function testing. A nonlinear, inverse relationship was found between urinary lactulose excretion and exocrine pancreatic function determined by duodenal trypsin output. These data confirm a direct relationship between intestinal lactulose permeability and the degree of exocrine pancreatic dysfunction, unrelated to the cause of the pancreatic disease.

The establishment of an academic health sciences library in a developing country: a case study.

The development of a Faculty of Medical Sciences (FMS) and an academic health sciences library for the University of the West Indies (UWI) has proven to be a polemical and political issue due to the depressed economy of the country. Although FMS is still shrouded in politics and controversy after its inaugural year, the Medical Sciences Library (MSL) has expanded its dimensions and is actively developing a biomedical information network within the country. This will result in better dissemination and control of biomedical information. The library now participates in joint projects with other health sciences libraries in the country with the goal of joint automated listings of holdings and shared cataloging projects. This paper examines the development of the library and explains the difficulties experienced in its developmental stages due to politics, the delay in appointment of a medical sciences librarian, and the financial decline in the local economy.

Effects of cisapride in patients with cystic fibrosis and distal intestinal obstruction syndrome.

In a double-blind, placebo-controlled, crossover trial, we investigated the effects of the prokinetic drug cisapride in patients with cystic fibrosis and chronic recurrent distal intestinal obstruction syndrome (DIOS). After a baseline period, 17 patients (12.9 to 34.9 years; 12 boys) received, in random order, cisapride (7.5 to 10 mg) and placebo three times daily by mouth, each for 6 months. Gastrointestinal symptoms (flatulence, abdominal pain, fullness, abdominal distension, nausea, anorexia, heartburn, diarrhea, vomiting and regurgitation) were scored three times monthly and physical examinations assessed. At baseline and at each 6-month period, assessment included food intake for 7 days, 3-day stool collection, pulmonary function tests, and abdominal radiographs. During cisapride therapy compared with placebo, there were significant reductions in flatulence (p less than 0.005), fullness, and nausea (p less than 0.05). Patients with the worst symptom scores benefited most from cisapride. With cisapride, 12 patients felt better and three worse (p less than 0.05); physicians judged 11 patients improved and two worse (p less than 0.05). No side effects were noted. There were no significant differences between cisapride and placebo periods in nutritional status, x-ray scores, pulmonary function, food intake (fat, protein, calories), stool size and consistency, and fecal losses of fat, bile acids, chymotrypsin, and calories. For acute episodes of DIOS, intestinal lavage was needed 6 times in 4 patients during treatment with cisapride, and 11 times in 6 patients receiving placebo. In comparison with unselected patients with cystic fibrosis and pancreatic insufficiency who were receiving enzyme supplements and who had no distal intestinal obstruction, fecal fat losses (percentage of intake) were almost twice as high in the study group with DIOS (31.2 +/- 20.6% vs 16.2 +/- 17.6%; p less than 0.01). We conclude that in the dosage used, long-term treatment with cisapride appears to improve chronic abdominal symptoms in patients with cystic fibrosis and DIOS, but fails to abolish the need for intestinal lavage. Cisapride treatment had no effect on digestion and nutritional status of cystic fibrosis patients with pancreatic insufficiency.

Evaluation of the injury profile of personnel in a busy urban EMS system.

The occupational injury profile of emergency medical technicians (EMTs) and paramedics is not well described. We retrospectively studied 254 injuries over a 3.5-year period in a busy urban EMS system. Low back strain was the most common injury (93/254, 36%), with EMTs suffering a significantly higher injury rate than paramedics (0.33 v 0.17 injuries/person-years at risk, P = .03). Lifting caused 58/93 (62.4%) of back injuries, and most occurred at the scene to which personnel were dispatched (58/93, 62.4%). The back injuries were recurrent in 31% of personnel. The data showed trends toward higher overall injury rates among EMTs compared with paramedics (0.83 v 0.55, P = 0.057) and women compared with men (0.86 v 0.50, P = 0.11). There was a significantly higher injury rate among personnel less than 30 years of age compared with those 30 years or older (0.65 v 0.39, P = 0.01). Over 25% of the personnel injured had more than one injury per year. There was no correlation between injury rates and job experience. Approximately 96 injuries accounted for 481 compensation days with low back strain the cause of 375 days (78%). Our findings suggest a high incidence of occupational injury in EMS personnel with EMTs and persons under 30 years of age at higher risk. Guidelines for prevention programs are suggested.

Elevated serum immunoreactive pancreatic cationic trypsinogen in acute malnutrition: evidence of pancreatic damage.

We used a sensitive probe of pancreatic dysfunction, serum immunoreactive cationic trypsinogen, to study 50 infants and children with varying degrees of malnutrition. Patients were classified into subgroups according to the severity of malnutrition. Mean serum trypsinogen concentration was significantly elevated in 25 patients with "severe" malnutrition (77.4 +/- 42.0 ng/ml, P less than 0.001) and in 23 with "moderate" malnutrition (55.2 +/- 16.1 ng/ml, P less than 0.02) compared with the mean value (32.5 +/- 10.4 ng/ml) for well-nourished controls. The level of circulating trypsinogen tended to rise with increasing severity of malnutrition. There was no relationship between serum trypsinogen and other variables such as age, specific diagnosis, or mode of feeling. Elevated serum trypsinogen levels could not be attributed to renal disease or cystic fibrosis. In patients who showed an improvement in nutritional status, serum trypsinogen tended to revert toward normal. Elevated serum trypsinogen values in acutely malnourished infants and children may result from pancreatic acinar cell damage or regurgitation of enzymes from obstructed pancreatic ducts.