Characterization of Tamm-Horsfall protein in a rat nephrolithiasis model

PURPOSE: The role of Tamm-Horsfall protein in calcium oxalate stone formation is controversial. It is unclear whether Tamm-Horsfall protein has a role in crystallization. If it does, does it act as an inhibitor or promoter of crystallization? To elucidate the nature of its involvement we characterized Tamm-Horsfall protein in a rat model of calcium oxalate nephrolithiasis by in vivo and in vitro techniques. MATERIALS AND METHODS: Calcium oxalate nephrolithiasis was induced in male Sprague-Dawley rats. The amino acid and carbohydrate composition of Tamm-Horsfall protein from normal rats and those with nephrolithiasis was determined. The Tamm-Horsfall protein gene and protein expression in the kidneys were examined by in situ hybridization and immunohistochemistry. Furthermore, the interaction of Tamm-Horsfall protein and calcium oxalate crystals was assessed by an in vitro crystal aggregation assay. RESULTS: Tamm-Horsfall protein from rats with nephrolithiasis was biochemically similar to that from normal rats. Although Tamm-Horsfall protein was associated with crystal deposits in the renal papillae of rats with nephrolithiasis, Tamm-Horsfall protein messenger RNA expression in the kidneys remained unchanged. In each group Tamm-Horsfall protein inhibited calcium oxalate crystal aggregation by 47%, indicating no change in functional capabilities. CONCLUSIONS: The results of this study indicate that urinary excretion, and the biochemical nature and functional capabilities of Tamm-Horsfall protein remain unchanged during experimental calcium oxalate nephrolithiasis. Although staining for Tamm-Horsfall protein was evident in the papillae of rats with nephrolithiasis, the site of Tamm-Horsfall protein synthesis remained cells of the thick ascending limbs of the loop of Henle.     

Retrospective case series analysis of patients with inflammatory bowel disease on azathioprine. A district general hospital experience

OBJECTIVES: The aim of this study was to look at our practice of using azathioprine and to compare our results with those in published trials both from the point of view of response and also the side-effect profile. DESIGN: A retrospective case series analysis was done on patients with inflammatory bowel disease (IBD) who were on azathioprine at Leicester General Hospital. METHODS: 111 patients (47 males, 64 females, mean age 35.3 years) were included from gastroenterology outpatients records between November 1997 and August 1998. Clinical and demographic details were collected. Response in Crohn's disease was determined using the Harvey-Bradshaw index. In case of ulcerative colitis the following parameters were used: stool frequency; rectal bleeding, weight gain, and general well-being. Logistic regression was performed to look at the influence of age, sex and diagnosis in relation to the response/relapse rate. RESULTS: The average duration of treatment with azathioprine was 28.6 months. The starting dose of 1.53 mg/kg was similar to the maintenance dose (1.51 mg/kg). 58 patients had Crohn's disease and 53 patients were diagnosed with ulcerative colitis. 85 patients were steroid-dependent, 9 steroid-resistant, and 17 patients were started on azathioprine on the basis of extensive disease either seen at the time of endoscopy or radiologically. Improvement in clinical features at 3, 6 and 12 months was 69.5, 77 and 84.1%, respectively. 74% patients showed an improvement in relapse rates during the first year on azathioprine compared to 1 year prior to treatment. 68% patients who had shown improvement at 1 year were no longer taking steroids (p = 0.002). Logistic regression did not show any statistically significant influence of age, sex or diagnosis on response. 4.5% patients had leukopenia requiring dose reductions. Severe leukopenia (leukocyte count <2.5 x 10(9)/l) occurred in 3.6% patients. CONCLUSIONS: Response rates in our IBD patients on azathioprine are comparable with those of the published data despite using a relatively smaller dose.     

Secular trends in height among children during 2 decades: The Bogalusa Heart Study

OBJECTIVE: To examine trends in height among 5- to 17-year-old children between 1973 and 1992. DESIGN: A panel design consisting of 7 cross-sectional surveys. PARTICIPANTS: All schoolchildren residing in Bogalusa, La, were eligible. A total of 24 070 examinations were performed. RESULTS: During the study period, the mean height of schoolchildren increased by 0.70 cm per decade independently of race, sex, and age. Trends were most pronounced among preadolescents, blacks, and boys, with 9- to 12-year-old black boys showing a height increase of 1.8 cm per decade. We observed a decrease in the number of relatively short children (<10th percentile of height) and an increase in the number of tall children (>90th percentile of height). Because a secular trend was not seen among the 15- to 17-year-old children, our findings likely reflect an acceleration of maturation. CONCLUSIONS: It has generally been assumed that secular increases in height among schoolchildren in the United States ceased by the mid-1900s. Our findings, which may be due to various environmental factors, demonstrate that care must be taken when using nonconcurrent reference data to assess the growth of children. Additional study is needed to determine if these secular trends are continuing and to examine possible explanations and consequences of these trends.     

Rumination syndrome in adolescents

OBJECTIVES: To evaluate the clinical presentation and to assess the usefulness of antroduodenal manometry (ADM) and the results of multidisciplinary team management in 12 neurologically normal adolescents (9 girls) with rumination.Study design: All patients had extensive investigations that ruled out other causes of their chronic symptoms. We performed ADM in all patients. A multidisciplinary approach was used for the nutritional and behavioral rehabilitation of these patients. RESULTS: The median age at presentation was 14 years (range, 9-19 years), and the average duration of symptoms was 17 months. All patients complained of postprandial, effortless regurgitation, and the majority had weight loss and abdominal pain. Results of fasting ADM were normal in all. The postprandial ADM showed brief, simultaneous pressure increases at all recording sites, associated with regurgitation in 8 patients. No emesis was observed in the other 4 children during the study. Treatment included nutritional support in combination with antidepressants and anxiolytics (n = 6), cognitive therapy with biofeedback or relaxation techniques (n = 7), and pain management (n = 2). Resolution or improvement of symptoms was seen in 10 of the 12 patients, and successful transition to oral feedings was achieved in all during the follow-up period, which ranged from 5 to 36 months. CONCLUSIONS: Rumination is a distinct functional gastrointestinal disorder of otherwise healthy children and adolescents, which can be diagnosed on the basis of clinical features. The ADM shows a characteristic pattern and rules out motility disorders that are often confused with rumination. A multidisciplinary team approach is associated with satisfactory recovery in most patients.     

A novel S-nitrosothiol (RIG200) causes prolonged relaxation in dorsal hand veins with damaged endothelium

BACKGROUND: Reduced nitric oxide bioavailability caused by endothelial dysfunction or damage is a contributory factor in the initiation and progression of a number of cardiovascular diseases. Delivery of exogenous nitric oxide is an attractive therapeutic option, but current agents lack selectivity for areas of endothelial damage. We tested the hypothesis that a novel nitric oxide donor drug, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6-tetra-O-acet yl-P-glucopyranose [RIG200], which has selective effects in endothelium-denuded isolated arteries in vitro, would exert similar effects in dorsal hand veins with experimentally damaged endothelium in vivo. METHODS: Venodilator responses to sodium nitroprusside and RIG200 were compared in two groups of healthy volunteers (age range, 18 to 63 years; n = 7 for each group) in norepinephrine 70% maximum effective concentration (EC70) preconstricted hand veins with use of the Aellig technique. In this doubleblind study, subjects were randomly assigned to receive either sodium nitroprusside or RIG200 (infusions of 0.06 and 6 nmol/min into the hand vein) before and 2 days after 15 minutes of local venous irription with distilled water. Endothelial function was assessed in all subjects on both visits with use of the endothelium-dependent vasodilator acetylcholine (1 nmol/min). RESULTS: Irrigation of hand veins with distilled water abolished endothelium-dependent dilatation in response to acetylcholine in both study groups (n = 14) but did not affect the amplitude or duration of responses to the conventional nitric oxide donor sodium nitroprusside (P = .87; n = 7). However, responses to RIG200 were significantly prolonged during the washout phase (30 minutes) in veins after water irrigation (P = .02; n = 7). CONCLUSION: These studies confirm that RIG200 has prolonged effects in veins with damaged endothelium, a characteristic that might be exploited therapeutically to target nitric oxide delivery to damaged blood vessels.     

I-Cell Disease (Mucolipidosis II) Presenting as Neonatal Fractures: A Case for Continued Monitoring of Serum Parathyroid Hormone Levels

A severe form of I-cell disease (mucolipidosis II) can present in the newborn period as multiple fractures. The bone disease in these patients is believed to be due to hyperparathyroidism. We report a case where bone disease was present at birth but the parathyroid hormone levels were initially normal and did not increase until 37 d of age. Supplemention with vitamin D was needed to normalize the parathyroid hormone levels despite adequate intake of vitamin D, calcium and phosphorus. We suggest that in patients with I-cell disease, continued evaluation for hyperparathyroidism may be necessary despite initial normal parathyroid hormone levels.     

Asymptomatic Paget’s disease of bone presenting with complete atrioventricular block

Paget＇s disease of bone is a deforming bone disease （osteitis deformans） characterized by increased bone remodeling, bone hypertrophy, and abnormal bone structure, leading to bone expansion, deformities, easy fractures, and occasionally, neoplastic transformation. It is the second most common bone disorder after osteoporosis. The disease is relatively rare in Asia but is common in Europe and North America, affecting approximately 2% of the population over 50 years,     

Risk factors predicting complications in blood culture-proven typhoid fever in adults

To create a prognostic model for complications of blood culture-proven typhoid fever in adults (> or = 15 y old), a retrospective cohort was assembled though review of the medical records of the hospitalized patients treated for typhoid fever over a 3-y period ending January 1995. Of the 59 patients included, 21 (35.6%) developed various complications of typhoid fever. No patient included died. Four baseline variables (abdominal pain, systolic blood pressure < 100 mmHg, hypoalbuminaemia < 32 g/l and laboratory evidence of disseminated intravascular coagulation) were independently associated with complications and were used to create a prognostic model. The prediction accuracy of the model was determined using the concordance index (c-index). The results (c-index, 0.915 [95%, CI, 89.0-93.0]) showed that the model predicted complications significantly better than chance. The model stratified patients into 3 prognostic stages: low risk for complications (0%; stage I), intermediate risk (42.9%; stage II) and high risk (92.3%; stage III) (p = 0.001). If validated in other settings, it will help clinicians in predicting complications in patients with blood culture-proven typhoid fever on admission.