Observations on aetiology and management of genital fistulas

Methods We evaluated the aetiological factors and outcome of the management of genital fistulas. A review of patients who presented with genital fistulas between January 1998 and June 2002 was performed.Results There were 34 cases of various genital fistulas, including 29 urinary and 5 intestinal fistulas. Among them 14 (41.2%) were attributed to obstetrical causes, 11 (32.3%) to gynaecological surgery, and 9 (26.3%) to other factors like vaginal procedure, coitus, trauma, etc. We had an operation success rate of 85.7% (30 out of 35 repairs). The success rate was 85.71% (24 out of 28) after primary and 83.3% (5 out of 6) after secondary repair (p=1.00). Vaginal repair was done in 28 cases whereas abdominal repair was carried out in 7 cases. The failure rate was 7.14% (2 out of 28) using the vaginal route and 42.8% (3 out of 7) using the abdominal route (p=0.05). The average duration of disease was 11.8±4.9 months vs. 30±10.3 months (p=0.5), the mean size of the fistulas was 1.5±1.0×1.3±0.9 cm vs. 2.4±1.9×2.2±1.8 cm (p=0.02) in successful and failed cases respectively.Conclusion The vaginal repair of fistulas is associated with a higher success rate. Fistulas due to other etiological factors specifically associated with genital malformation, like vaginal procedures and coitus, have the worst prognosis. Larger or longer duration fistulas are associated with poorer prognosis.     

Adipokines and the risk of fracture in older adults

Adiponectin and leptin are adipokines that influence bone metabolism in vitro and in animal models. However, less is known about the longitudinal association of leptin and adiponectin with fracture. We tested the hypothesis that low leptin and high adiponectin levels are each individually associated with fracture risk in a prospective cohort study in Memphis and Pittsburgh among 3075 women and men aged 70 to 79 years from the Health Aging and Body Composition (Health ABC) study. There were 406 incident fractures (334 nonvertebral and 72 vertebral) over a mean of 6.5 ± 1.9 years. Cox regression was used to estimate the hazard ratios for fracture. Sex modified the association between adiponectin and fracture (p = .025 for interaction). Men with the highest adiponectin level (tertile 3) had a 94% higher risk of fracture [hazard ratio (HR) = 1.94; 95% confidence interval (CI) 1.20–3.16] compared with the lowest tertile (tertile 1; p = .007 for trend) after adjusting age, race, body mass index (BMI), education, diabetes, weight change, and hip bone mineral density (BMD). Among women, after adjusting for age and race, this association was no longer significant (p = .369 for trend). Leptin did not predict fracture risk in women (p = .544 for trend) or men (p = .118 for trend) in the multivariate models. Our results suggest that adiponectin, but not leptin, may be a novel risk factor for increased fracture risk independent of body composition and BMD and that these relationships may be influenced by sex. More research is needed to understand the physiologic basis underlying these sex differences. © 2011 American Society for Bone and Mineral Research.     

Abdominal obesity is an independent risk factor for chronic heart failure in older people

OBJECTIVES: To examine whether total and abdominal adiposity are risk factors for the development of chronic heart failure (CHF) in older men and women. DESIGN: Prospective, longitudinal cohort: The Health, Aging and Body Composition study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania, metropolitan areas. PARTICIPANTS: Three thousand seventy-five well-functioning community-dwelling older adults aged 70 to 79. MEASUREMENTS: Body composition using dual energy X-ray absorptiometry, visceral adipose tissue area using computed tomography, adjudicated CHF. RESULTS: Of the remaining (640 participants excluded from original group of 3,075) 2,435 participants (1,081 men, 1,354 women) without coronary heart disease or CHF at baseline, there were 166 confirmed diagnoses of CHF during the median+/-standard deviation (SD) follow-up of 6.1+/-1.4 years. After adjustment for age, race, sex, site, education, smoking, and chronic obstructive pulmonary disorder, all adiposity variables (body mass index (BMI), adipose tissue mass, percentage body fat, waist-to-thigh ratio, waist circumference, and visceral and subcutaneous abdominal adipose tissue) were significant predictors of the development of CHF. In a model that included waist circumference and BMI, waist circumference was associated with incident CHF (hazard ratio (HR)=1.27, 95% confidence interval (CI)=1.04-1.54 per SD increase, P=.02), but BMI was not (HR=1.08, 95% CI=0.86-1.35). When waist circumference and percentage fat were included together, both variables were significant predictors of CHF (waist: HR=1.17, 95% CI=1.00-1.36 per SD increase, P=.05; percentage fat: HR=1.47, 95% CI=1.16-1.87 per SD increase, P=.002). Stepwise adjustment for inflammation, hypertension, insulin resistance, and diabetes mellitus did not decrease the relative risk of a greater waist circumference for the development of CHF (all HR=1.27-1.32, 95% CI=1.02-1.61 per SD increase). CONCLUSION: Abdominal body fat distribution may be a stronger risk factor for CHF than overall obesity.     

Serum adiponectin and coronary heart disease risk in older Black and White Americans

CONTEXT: Adiponectin may influence the risk of coronary heart disease (CHD) independently of traditional cardiovascular risk factors. OBJECTIVE: Because body composition and adiponectin levels vary by race, we examined the relationship of adiponectin with prevalent and incident CHD in a cohort of older Black and White adults. DESIGN AND SETTING: We conducted a cross-sectional and prospective cohort study at two U.S. clinical centers. PARTICIPANTS: Participants included 3075 well-functioning adults between ages 70 and 79 yr enrolled in the Health, Aging, and Body Composition study. MAIN OUTCOME MEASURES: Prevalent CHD was defined as history of myocardial infarction, coronary artery bypass graft, percutaneous coronary transluminal angioplasty, angina, or major electrocardiogram abnormalities. After excluding those with prevalent CHD, incident CHD was defined as hospitalized myocardial infarction or CHD death. RESULTS: At baseline, 602 participants (19.6%) had CHD. During 6 yr of follow-up, 262 (10.6%) incident CHD events occurred. Whites had higher median adiponectin than Blacks (12 vs. 8 microg/ml, P < 0.001). Race modified the effect of adiponectin (P for interaction was 0.002 for prevalent CHD, and P = 0.02 for incident CHD). Among Whites, an inverse association of adiponectin with CHD was explained by high-density lipoprotein and glucose. Among Blacks, a doubling of adiponectin was associated with a 40% higher risk of both prevalent CHD (odds ratio, 1.41; 95% confidence interval, 1.11-1.78) and incident CHD (hazards ratio, 1.37; 95% confidence interval, 1.01-1.87) after adjusting for explanatory variables. CONCLUSION: High circulating concentrations of adiponectin were associated with higher risk of CHD in older Blacks, even accounting for traditional CHD risk factors.     

The role of mutant UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 in regulating serum intact fibroblast growth factor 23 and matrix extracellular phosphoglycoprotein in heritable tumoral calcinosis

CONTEXT: Familial tumoral calcinosis (TC) results from disruptions in phosphate metabolism and is characterized by high serum phosphate with normal or elevated 1,25 dihydroxyvitamin vitamin D concentrations and ectopic and vascular calcifications. Recessive loss-of-function mutations in UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) and fibroblast growth factor-23 (FGF23) result in TC. OBJECTIVE: The objective of the study was to determine the relationship between GALNT3 and FGF23 in familial TC. DESIGN, SETTING, AND PATIENTS: We assessed the major biochemical defects and potential genes involved in patients with TC. Intervention: Combination therapy consisted of the phosphate binder Sevelamer and the carbonic anhydrase inhibitor acetazolamide. RESULTS: We report a patient homozygous for a GALNT3 exon 1 deletion, which is predicted to truncate the encoded protein. This patient had high serum FGF23 concentrations when assessed with a C-terminal FGF23 ELISA but low-normal FGF23 levels when tested with an ELISA for intact FGF23 concentrations. Matrix extracellular phosphoglycoprotein has been identified as a possible regulator of phosphate homeostasis. Serum matrix extracellular phosphoglycoprotein levels, however, were normal in the family with GALNT3-TC and a kindred with TC carrying the FGF23 S71G mutation. The tumoral masses of the patient with GALNT3-TC completely resolved after combination therapy. CONCLUSIONS: Our findings demonstrate that GALNT3 inactivation in patients with TC leads to inadequate production of biologically active FGF23 as the most likely cause of the hyperphosphatemic phenotype. Furthermore, combination therapy may be effective for reducing the tumoral burden associated with familial TC.