Unusual presentations in myositis ossificans progressiva. A case report

Myositis ossificans progressiva is a rare connective tissue disorder. We present here a case of myositis ossificans progressiva with some unusual presentations and associated congenital skeletal anomalies that are reported very infrequently in the literature. The case report highlights the importance of early diagnosis in a case of rapidly progressive myositis ossificans progressiva.     

Bisphosphonate therapy in fibrous dysplasia

Fibrous dysplasia is proliferation of fibrous tissue within the bone marrow causing osteolytic lesions and pathologic fractures. Recently, second generation bisphosphonates have shown promise in the treatment of patients with fibrous dysplasia. In the current study, six patients with fibrous dysplasia were treated with either oral alone or oral and intravenous bisphosphonates. The participants were observed for changes in N-telopeptide, pain score, and radiographic changes. In the current study, the combination bisphosphonate therapy diminished pain, prevented fractures, lowered N-telopeptide values, and led to partial resolution of fibrous dysplasia lesions.     

Overexpression of connexin 43 in skeletal myoblasts: Relevance to cell transplantation to the heart

OBJECTIVE: Skeletal myoblast transplantation is a promising strategy for treating end-stage heart failure. One potential problem in the development of functional, synchronously contracting grafts is the degree of intercellular communication between grafted myoblasts and host cardiomyocytes. Thus it is expected that enhancement of intercellular gap junction formation would result in improved efficiency of skeletal myoblast transplantation. In this study we investigated whether myoblasts overexpressing connexin 43, a major cardiac gap junction protein, would enhance this intercellular communication. METHODS AND RESULTS: L6 rat skeletal myoblast cell lines overexpressing connexin 43 were generated by means of gene transfection and clonal selection. Connexin 43 overexpression of these myoblasts, which continued both in undifferentiated and differentiated states (up to 17-fold greater protein level in comparison with control-transfected myoblasts, as measured with Western blotting), was observed on cell surfaces where gap junctions should exist. Both dye microinjection and scrape loading with fluorescent dyes showed enhancement in intercellular dye transfer between connexin 43-transfected myoblasts compared with that found in control-transfected cells. Morphologically, these myoblasts fused and differentiated into multinucleated myotubes more rapidly, demonstrating a higher level of cellular creatine kinase activity as a marker of myogenic differentiation throughout the culture period compared with that of control-transfected myoblasts. CONCLUSIONS: We have generated connexin 43-overexpressing skeletal myoblast cell lines that resulted in improved formation of functional intercellular gap junctions, which could be relevant to synchronous contraction of grafted myoblasts in the heart. In addition, these cells demonstrated more rapid differentiation, which would also be advantageous in a graft for transplantation to the heart.     

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.