Loss of the gastric acid barrier may lead to recurrent enteric infections, small intestinal bacterial overgrowth, persistent diarrhoea, and thus malnutrition. To investigate this possibility, a new, non-invasive test of gastric acid secretion was developed ideal for field use in the developing world, where chronic diarrhoea and undernutrition are common. The test relies on the capacity of the kidney to retain H+ during gastric acid secretion, leading to a post-prandial urine 9alkaline tide9. Gastric intubation studies of seven healthy adult volunteers showed a direct relation between changes in gastric acid secretion and changes in urine acid output (measured as the H+/creatinine molar ratio in spot urine samples). Subjects who secreted gastric acid in response to stimulation with a sham feed showed a fall in urine acid output > 0.5 mmol H+/mmol creatinine (range -7.4 to -1.52 mean -1.12). The most reproducible decrease in urine acid output in response to normal food was observed around the time breakfast was usually eaten and was abolished by 36 hours of treatment with ranitidine. Breakfast time reductions in postprandial urine acid output in 22 healthy English children were comparable with those in healthy adults, and significantly different from values in achlorhydric adults. They were much more variable, however, in 106 Gambian children in whom values spanned both normochlorhydric and achlorhydric ranges (-12.7 to +1.8). Measuring changes in urine acid output at breakfast time provides a reliable indirect measure of gastric acid secretion that can be used in field conditions, enabling the relation between gastric acid output and the development of diarrhoeal diseases to be investigated.
through the decade (x2=577, df=9, p<.<0001), mainly owing to the high incidences in 1978 and particularly 1979.I analysed the 31 cases occurring in 1979 in more detail to see whether the expected associations had been distorted.The male to female ratio was 27:4 (6 8:1).Firstborn children constituted 42% of cases (13/31) compared with 31 °0 of live-born children.The number of affected infants born each
Sera from 100 children (ages, 6 to 16 years) presenting with upper gastrointestinal symptoms were examined for antibodies to Helicobacter pylori by enzyme-linked immunosorbent assay (ELISA) based on crude, loosely cell-associated antigens and a partially purified urease antigen preparation. All children underwent endoscopy, and 20 children were shown to have H. pylori infection by histology or direct culture. Serum anti-H. pylori immunoglobulin G (IgG) levels (crude antigen) were clearly raised in the infected group, particularly after preabsorption of sera against a Campylobacter jejuni antigen preparation, while IgM and IgA ELISA determinations did not discriminate between infected and H. pylori-negative patients. Only 14 children in the infected group had raised anti-urease IgG levels. Two patients in whom the organism was not demonstrated or cultured had raised specific IgG levels against both crude and urease antigens and pathological features consistent with H. pylori disease. Immunoblotting studies did not reveal any single protein antigen or simple combination of antigens that could be considered as a candidate for a more defined serodiagnostic reagent. Anti-H. pylori antibody determinations (crude antigen) performed on posttreatment samples from children in whom the organism could no longer be demonstrated suggested that sustained IgG levels may not be a reliable index of treatment failure. An IgG ELISA based on crude, loosely cell-associated antigens of H. pylori can be used for the serodiagnosis of H. pylori infection in childhood.
2073 Background: CT-2106 is a novel camptothecin (CPT) conjugate in which CPT is bound to a biodegradable water soluble poly-L-glutamic acid-glycine polymer. Conjugation of CPT to the polymer allows for greater stability in circulation, increased potential for exclusion from normal tissue, and enhanced permeability and retention in tumor tissue. CT-2106 has demonstrated significant anti-tumor activity in multiple human tumor cell lines in vivo, including lung and colon cancers. This study was designed to determine the pharmacokinetics of CT-2106 in patients with advanced malignancies. Methods: Patients were treated with CT-2106 as a 10 minute intravenous infusion every 21 days. Blood and urine samples were collected during treatment cycles 1 and 2. Samples were analyzed for conjugated and unconjugated CPT with validated HPLC/FD methods. Noncompartmental PK analysis of plasma concentration-time data was made by WinNonLin (Ver. 4.01). Results: Twenty-four patients have been treated. Conjugated CPT doses were 12 mg/m2 (3 patients), 25 mg/m2 (7), 50 mg/m2 (3), 75 mg/m2 (8), and 105 mg/m2 (3). Data is currently available from blood and urine samples from 17 patients (mean age 62.8, range 46–77). Plasma Cmax and AUC values for conjugated and unconjugated CPT indicate CT-2106 PK linearity from 12 to 75 mg/m2. The apparent termination t1/2 of unconjugated CPT is quite long -approximately 40 hours. Five days after the first administration (cycle 1), the excretion in urine of CT-2106 and unconjugated CPT accounted for 27.9% and 5.1% of the administered dose, respectively. The excretion pattern did not change during cycle 2. A major CPT conjugated species found in urine was glu-gly-CPT. Dose-limiting toxicities include: grade 3/4 neutropenia with concomitant grade 3 thrombocytopenia in 3 patients (105 mg/m2); grade 2 hematuria in 1 patient (25 mg/m2). Most adverse events have been mild or moderate. Conclusions: CT-2106 generates prolonged systemic exposures to unconjugated CPT in plasma; also, urine excretion levels of conjugated camptothecin are substantial. This study is ongoing to determine the MTD and collect further pharmacokinetc data. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics, Inc.
This paper describes 110 cases of childhood duodenal ulcer, which were diagnosed over 26 years: 63 were diagnosed by barium meal examination; 47 by upper gastrointestinal endoscopy. The mean age at diagnosis was 11.2 years, with symptoms reported in 46% before 10 years and in 15% before 6 years of age. There was often a considerable delay in diagnosis, particularly in the younger age group. Nocturnal pain (61%) and a close family history of duodenal ulcer disease (62%) were the most valuable pointers to the diagnosis. Fifteen children had required surgery for persistent symptoms. Thirty four had received treatment with an H2 receptor antagonist, and all but four had had a satisfactory initial response. Seventy per cent relapsed within six months of discontinuing treatment, and long term maintenance treatment may therefore be necessary.
We add five cases of 20p deletion to the 10 cases already published. Four had craniofacial, vertebral, ocular, and cardiovascular features of Alagille syndrome, which adds weight to the assignment of this disorder to the short arm of chromosome 20. Included in our series is the first report of familial transmission of a 20p deletion.
Abstract. Beesley, J., Eastham, E. J., Jackson, R. H. and Nelson, R. (Department of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, England). Clindamycin associated pseudomembranous colitis. Acta Paediatr Scand, 70:129, 1981.–Pseudomembranous colitis is rare in children. We describe a case associated with clindamycin in which Clostridium difficile and its enterotoxin were isolated from the stool. Treatment with oral vancomycin brought about a prompt and complete recovery.
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