Familial dwarfism: case report

Three sisters are described, of consanguinous parents, with multiple trophic hormone deficiencies presenting as short stature. In two of them the size of the sella turcica is large in relation to the skeletal age and height. All three show an acute metabolic response to an administered preparation of human growth hormone.     

Organochlorine detection in the shed skins of snakes

Lizards and snakes eliminate heavy metals in their shed skins. There are no data with regard to reptilian skin as a depuration route for organochlorine (OC) compounds; however, birds deposit OCs in feathers. Corn snakes (Elaphe guttata) were therefore fed thawed mice that had been injected with a mixture of alpha-chlordane, Aroclor 1254 (a polychlorinated biphenyl (PCB) mixture), and lindane (gamma-hexachlorocyclohexane) at 2, 8, and 4 mg/kg, respectively. Feeding of contaminated mice occurred on the first weekly feeding of each month, with remaining weekly feedings consisting of noncontaminated mice, and was continued for 6 months. Shed skins were evaluated in a multiresidue OC scan by gas chromatography. All three chemical contaminants were readily detected in the shed skins: chlordane, 0.155-0.213 ppm; PCB, 3.49-7.01 ppm; lindane: 0.028-0.042 ppm. These data suggest that the shed skin of snakes may serve as an elimination route for OC contaminants and as such may have utility as a noninvasive, nondestructive indicator tissue for assessing environmental contamination.     

Increase in heme oxygenase-1 levels ameliorates renovascular hypertension

BACKGROUND: The heme oxygenase system (HO-1 and HO-2) catalyzes the conversion of heme to free iron, carbon monoxide (CO), a vasodepressor, and biliverdin, which is further converted to bilirubin, an antioxidant. HO-1 induction has been shown to suppress arachidonic acid metabolism by cytochrome P450 (CYP450) monooxygenases and cyclooxygenases (COX), and to decrease blood pressure in spontaneously hypertensive rats (SHR). The Goldblatt 2K1C model is a model of renovascular hypertension in which there is increased expression of COX-2 in the macula densa and increased renin release from the juxtaglomerular apparatus of the clipped kidney. We examined whether HO-1 overexpression, as a prophylactic approach, would attenuate renovascular hypertension and evaluated potential mechanisms that may account for its effect. METHODS: 2K1C rats were treated with cobalt protoporphyrin (CoPP) or tin mesoporphyrin (SnMP) one day before surgery and weekly for three weeks thereafter. We measured systolic blood pressure, HO activity, HO-1, HO-2, COX-1 and COX-2 protein expression, heme content, and nitrotyrosine levels as indices of oxidative stress. Urinary prostaglandin excretion (PGE2), plasma renin activity (PRA), and plasma aldosterone levels were also measured. RESULTS: CoPP administration induced renal HO-1 expression by 20-fold and HO activity by 6-fold. This was associated with a reduction in heme content, nitrotyrosine levels, COX-2 expression and urinary PGE2 excretion, and attenuation of the development of hypertension in the 2K1C rats. There was no decrease in plasma renin activity; however, plasma aldosterone levels were significantly lower. In the 2K1C SnMP-treated rats, blood pressure was significantly higher than that of untreated 2K1C rats throughout the study, and the difference in the size of the smaller left clipped kidney compared to the nonclipped right kidney was significantly increased. CONCLUSION: These findings define an action of prolonged HO-1 induction to interrupt and counteract the influence of the renin-angiotensin-aldosterone system (RAAS) to increase in blood pressure in the 2K1C model of renovascular hypertension. Multiple mechanisms include a decrease in oxidative stress as indicated by the decrease in cellular heme and nitrotyrosine levels, an anti-inflammatory action as evidenced by a decrease in COX-2 and PGE2, interference with the action of angiontensin II (Ang II) as evidenced by an increase in PRA in the face of a decrease in PGE2 and aldosterone, as well as the inhibition of aldosterone synthesis.     

High body mass index and short- and long-term renal allograft survival in adults

BACKGROUND: The effect of recipient obesity on kidney allograft survival remains enigmatic. The purpose of this study was to evaluate the effect of donor and recipient body mass index on graft survival. METHODS: Retrospective study of 193 consecutive, adult renal transplants, with at least six months follow-up (mean 24+/-14.1 months). Patients were divided into two groups based upon body mass index (BMI), [weight (kg)/height (m)]: normal (<30.0, n=137) and obese (> or =30.0, n=56). Endpoints were graft loss, defined as either total loss of graft function (return to dialysis) or patient death with a functional graft. Unadjusted and adjusted multivariate analysis techniques, including Kaplan-Meier and Cox proportional hazards regression were used. RESULTS.: Individuals with a BMI > or =30 were not more likely to experience graft loss (O.R. 0.93, 95% C.I. 0.50, 1.72). Rates of acute rejection were not increased in obese recipients. While mortality was not increased in the BMI > 30 group, morbidity, especially surgical, had an increased incidence. The ratio of recipient to donor BMI did not influence graft survival. CONCLUSION: Obese recipients (BMI > or =30.0) were not at increased risk for graft failure. Additionally, matching donor and recipient BMI's would not appear to substantially improve transplant outcome. Obese recipients do have increased posttransplant morbidity and risk all the known health consequences associated with obesity. Careful evaluation and clinical management of obese patients allows for successful kidney transplantation with results equivalent to normal BMI patients.     

Outcome of lung transplantation for patients requiring concomitant cardiac surgery

BACKGROUND: The clinical results of lung transplantation and concomitant cardiac surgery are unclear. The effect of cardiopulmonary bypass on the pulmonary allograft is controversial, and the effect of cardiac arrest and cardiac surgery in this setting is unknown. Our aim was to review the operative results and long-term survival in this group of patients. METHODS: A retrospective review of all lung transplantations between 1988 and 2003 was performed. Patients who had concomitant cardiac surgery during lung transplantation were compared with those who underwent lung transplantation alone. The variables analyzed included allograft ischemic times, use of cardiopulmonary bypass, early graft dysfunction, postoperative morbidity, survival, length of mechanical ventilation, length of stay in the intensive care unit, and overall hospital stay. RESULTS: During this period, 35 of 700 lung transplant recipients (15 single and 20 bilateral transplantations) underwent concomitant cardiac surgery. The cardiac procedures were for patent foramen ovale (n = 18), atrial septal defect (n = 9), ventricular septal defect (n = 2), coronary bypass (n = 4), and "other" (n = 2). Allograft ischemic time, use of extracorporeal membrane oxygenation, length of hospital stay, operative mortality, and survival were not significantly different between the 2 groups. Ventilator time and intensive care unit stay were longer in the cardiac surgery group. CONCLUSIONS: Cardiac surgery at the time of lung transplantation can be performed with acceptable morbidity and mortality. The immediate and long-term survival in these patients is similar to that of other lung transplant recipients. Lung transplantation should continue to be offered to patients with normal ventricular function who require concomitant limited cardiac surgery.     

Acculturation, parent-child acculturation differential, and chronic disease risk factors in a Mexican-American population

Acculturation is typically defined in terms of individual responses to a dominant culture. In the present study, we examined the effects of different levels of acculturation among family members. Specifically, we looked at the health and risk behavior in Mexican-American children as related to a variety of psychosocial predictors, especially the differences in orientation toward Mexican- and Anglo-American cultures between them and their parents. Mother and child pairs (n = 106) noted their orientation toward both Anglo and Mexican cultures. Childrens dietary and sedentary behaviors, tobacco and alcohol use (and susceptibility to use), and depressive symptoms were also measured. Males were more likely to be sedentary and consume higher levels of total fat and saturated fat, whereas girls reported higher levels of depression. Anglo-oriented youth consumed lower levels of calories from fat but also more alcohol than did their Mexican-oriented counterparts. The latter was particularly the case among those children who were relatively more Anglo oriented than were their parents. Parent–child acculturation differential in terms of the differences in Mexican orientation, in comparison, predicted susceptibility to tobacco use. However, the sum of the absolute values of these two differences predicted only lifetime alcohol use, and in a counter-intuitive direction. This familial measure of acculturation shows some promise, but additional formative research is needed to operationalize this construct.     

Association between dietary factors and plasma adiponectin concentrations in men

BACKGROUND: Adiponectin, an adipocyte-derived peptide, improves insulin sensitivity, has antiinflammatory and antiatherogenic effects, and is associated with a lower risk of ischemic heart disease (IHD) and type 2 diabetes. However, little is known about dietary predictors of plasma adiponectin concentrations in humans. OBJECTIVE: Our objective was to examine cross-sectionally the association between dietary factors and plasma adiponectin in men. DESIGN: Our study included 532 male participants of the Health Professionals Follow-Up Study who were selected as control subjects for an investigation of biological predictors of IHD. Diet, lifestyle, and anthropometric data were assessed by questionnaires. RESULTS: After multivariable adjustment, adiponectin was significantly inversely related to glycemic load (-1.3 mg/L per 1-SD increase; P = 0.02) and tended to be positively associated with total fat intake (0.7 mg/L per 0.5% of energy from fat instead of carbohydrates; P = 0.06). We also found a significant nonlinear association between plasma adiponectin concentrations and alcohol intake (P for quadratic trend = 0.01). Thus, whereas nondrinkers had mean plasma adiponectin concentrations of 16.48 mg/L, those who consumed 0.1-4.9, 5.0-14.9, 15.0-29.9, or >/=30 g alcohol/d had mean concentrations of 16.79 (P = 0.77 compared with nondrinkers), 18.97 (P = 0.02), 19.11 (P = 0.01), and 18.39 (P = 0.10) mg/L, respectively. CONCLUSIONS: Moderate alcohol intake is associated with higher adiponectin concentrations, whereas a carbohydrate-rich diet with a high glycemic load is associated with lower adiponectin concentrations in men with no history of cardiovascular disease. Although the strength of these associations was modest, our observations highlight the hypothesis that dietary factors may modulate plasma adiponectin concentrations-a potential mediator related to a reduced IHD risk.     

Adiponectin and future coronary heart disease events among men with type 2 diabetes

Adiponectin, predominantly synthesized in the adipose tissue, seems to have substantial anti-inflammatory properties and to be a major modulator of insulin resistance and dyslipidemia, mechanisms that are associated with an increased atherosclerotic risk in diabetic patients. However, it is unknown whether higher levels of adiponectin are associated with a reduced risk for coronary heart disease (CHD) among diabetic individuals. We investigated the association between plasma adiponectin levels and incidence of CHD among 745 men with confirmed type 2 diabetes in the Health Professionals Follow-up Study. Participants were aged 46-81 years and were free of diagnosed cardiovascular disease at the time of blood draw in 1993/1994. During an average of 5 years of follow-up (3,980 person-years), we identified 89 incident cases of CHD (19 myocardial infarction and 70 coronary artery bypass surgery), confirmed by medical records. Levels of adiponectin were inversely associated with BMI and directly associated with age, alcohol intake, and duration of diabetes (P < 0.05). After adjustment for age, BMI, smoking, alcohol consumption, duration of diabetes, and other lifestyle factors, adiponectin was associated with a decreased risk for CHD events. The multivariate relative risk for CHD for a doubling of adiponectin was 0.71 (95% CI 0.53-0.95). Further adjustment for HDL cholesterol attenuated this association (0.78 [0.57-1.06]). The inverse association between adiponectin and CHD was consistent across strata of aspirin use, family history of myocardial infarction, alcohol consumption, insulin use, duration of diabetes, and levels of HbA(1c), triglycerides, C-reactive protein, and HDL cholesterol. Our study suggests that increased adiponectin levels are associated with a moderately decreased CHD risk in diabetic men. This association seems to be mediated in part by effects of adiponectin on HDL cholesterol levels.