Decrease in anogenital distance among male infants with prenatal phthalate exposure

Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2-36 months of age. AGD was significantly correlated with penile volume (R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent (R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples (n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p-values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score (p-value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.     

Effect of feeding-tube properties on residual volume measurements in tube-fed patients

BACKGROUND: The effect of feeding tube size and port configuration on the ability to measure gastric residual volume (GRV) is poorly understood. In addition, there is confusion about the need to measure GRVs during feedings into the small bowel. This study sought to (1) compare the volume of gastric contents obtained from small-diameter feeding tubes and large-diameter sump tubes concurrently positioned in the stomach and (2) describe the distribution of GRVs during small-bowel feedings. METHODS: For the first objective, GRV measurements were made from 10-Fr tubes (n = 645) and 14-Fr or 18-Fr sump tubes (n = 645) concurrently present in 62 critically ill patients. Sixty-milliliter syringes were used to measure GRVs from the 10-Fr tubes; the fluid was returned to the stomach and measurements were repeated from the large-diameter sump tubes. To address the second research objective, 890 GRV measurements were made from 14-Fr or 18-Fr gastric sump tubes (not connected to suction) in 75 critically ill patients who were receiving small-bowel feedings. RESULTS: When GRVs were >50 mL, a linear regression equation indicated that volumes obtained from the large-diameter sump tubes were about 1.5 times greater than those obtained from the small-diameter tubes concurrently present in the stomach, p < .001. Gastric volumes > or =100 mL were found in 11.6% of the 890 measurements made in patients receiving small-bowel feedings; volumes > or =150 mL were found in 5.4% of the measurements. CONCLUSIONS: The findings suggest that GRVs obtained from large-diameter sump tubes are about 1.5 times greater than those obtained from 10-Fr tubes. Large GRVs occur in at least 5% of patients receiving postpyloric feedings.     

Trauma surgery malpractice risk: perception versus reality

OBJECTIVE: We set out to compare the malpractice lawsuit risk and incidence in trauma surgery, emergency surgery, and elective surgery at a single academic medical center. SUMMARY AND BACKGROUND DATA: The perceived increased malpractice risk attributed to trauma patients discourages participation in trauma call panels and may influence career choice of surgeons. When questioned, surgeons cite malpractice risk as a rationale for not providing trauma care. Little data substantiate or refute the perceived high trauma malpractice risk. We hypothesized that the malpractice risk was equivalent between an elective surgical practice and a trauma/emergency practice. METHODS: Three prospectively maintained institutional databases were used to calculate and characterize malpractice incidence and risk: a surgical operation database, a trauma registry, and a risk management/malpractice database. Risk groups were divided into elective general surgery (ELECTIVE), urgent/emergent, nontrauma general surgery (URGENT), and trauma surgery (TRAUMA). Malpractice claims incidence was calculated by dividing the total number of filed lawsuits by the total number of operative procedures over a 12-year period. RESULTS: Over the study period, 62,350 operations were performed. A total of 21 lawsuits were served. Seven were dismissed. Three were granted summary judgments to the defendants. Ten were settled with payments to the plaintiffs. One went to trial and resulted in a jury verdict in favor of the defendants. Total paid liability was 4.7 million dollars(391,667 dollars/year). Total legal defense costs were 1.3 million dollars(108,333 dollars/year). The ratio of lawsuits filed/operations performed and incidence in the 3 groups is as follows: ELECTIVE 14/39,080 (3.0 lawsuits/100,000 procedures/year), URGENT 5/17,958, (2.3 lawsuits/100,000 procedures/year), and TRAUMA 2/5312 (3.1/100,000 procedures/year). During the study period, there were an estimated 49,435 trauma patients evaluated. The incidence of malpractice lawsuits using this denominator is 0.34 lawsuits/100,000 patients/year. CONCLUSIONS: These data demonstrate no increased risk of lawsuit when caring for trauma patients, and the actual risk of a malpractice lawsuit was low.     

Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension

BACKGROUND: Prenatal environment has been shown to modify adult blood pressure profile, but the underlying mechanisms are not well understood. The role of renal immune cell infiltration, oxidative stress, and nitric oxide bioavailability in the pathogenesis was investigated. METHODS: Adult hypertension in rat offspring was induced by maternal low protein diet. Oxidative stress was determined by quantitative immunoblotting for nitrotyrosine, and T-cell and macrophage content by immunostaining, in offspring kidneys before and after the onset of hypertension. Nitric oxide metabolites (NOx) were measured in 24-hour urines. A group of offspring was treated with the immunosuppressive drug mycophenolate mofetil (MMF) to reduce inflammation, or with the superoxide dismutase mimetic Tempol to reduce oxidative stress, for a 3-week period before the onset of hypertension. RESULTS: During the prehypertensive stage, at 4 weeks of age, the low protein diet pups exhibited an increase in kidney nitrotyrosine content and in number of immune cells, both of which persisted in untreated animals after hypertension was established, at 8 weeks of age. Urine NOx was increased at 4 weeks and unchanged at 8 weeks of age. Both MMF and Tempol treatment prevented the immune cell infiltration, the increase in kidney nitrotyrosine abundance, and the development of hypertension. The effect on blood pressure persisted throughout the 4- to 10-week observation period after discontinuation of the treatments. CONCLUSION: Renal oxidative stress and infiltrating immune cells may play a pathogenetic role in prenatally programmed hypertension. Nitric oxide bioavailability does not appear impaired.     

Psychosocial distress of Tibetans in exile: integrating western interventions with traditional beliefs and practice

A psychosocial care project for Tibetan torture survivor's and other Tibetan refugees suffering from psychological distress was opened in Dharamsala, North India in 1995 by a western non-government organisation (NGO) in collaboration with the Tibetan government-in-exile. The clinic explicitly sought to integrate western and local traditional approaches to healing. The aim of the present study was to examine the views of key stakeholders of the project in the context of broader cultural and social issues faced by exiled Tibetans. Twenty individual interviews were conducted with 'officials' (members of the Tibetan government-in-exile, religious leaders, other community leaders, and senior medical staff), the staff of the project (Tibetan and western) and the clients themselves. The interviews were taped, transcribed, and analysed using a grounded theory approach. All interviewees considered that mental health was an important issue and that awareness of psychological health in the community had improved since the initiation of the project. Clients and staff of the project, and some of the 'officials', believed that it provided a much-needed service and that it effectively and sensitively combined western psychological approaches with local cultural and religious beliefs and practices. However, a majority of the 'officials' felt that mental health issues were not a top priority in the competing health needs of the community, and that other ways of dealing with such problems (using traditional approaches or local health services) were adequate. Given these and other factors, the longer-term sustainability of the project appears to be a major challenge. According to the users and providers interviewed, the current project has developed an important and beneficial psychosocial support service. However, the continuing debate amongst community leaders regarding the place and future of the project suggests the importance of accommodating the views and priorities of all local stakeholders--and focusing on sustainability and capacity building of relevant community members--from the outset of such projects. This includes acknowledging the perceived threat to traditional beliefs and coping strategies--particularly in the context of wider socio-cultural disruption--posed by initiatives seeking to integrate western intervention approaches with local healing resources.     

A biochemical prognostic model of outcome in paracetamol-induced acute liver injury

BACKGROUND: The aim of this study was to develop a prognostic model of outcome for patients with paracetamol induced acute liver injury based on admission parameters METHODS: We used a cohort of 97 patients admitted to the Scottish Liver Transplant Unit between 1997 and 1998 to identify biochemical prognostic markers of outcome and thus create a prognostic model. Blood samples were taken on admission for analysis. The model was subsequently validated by testing it on a second cohort of 86 patients admitted between 1999 and 2000. RESULTS: The following were identified as independent variables of poor prognosis (death/ transplant); phenylalanine, pyruvate, alanine, acetate, calcium, haemoglobin and lactate. A prognostic model was then constructed by stepwise forward logistic regression analysis: (400xPyruvate mmols/L)+(50xPhenylalanine (mmols/L)-(4 x Hemoglobin (g/dL). A value of <16 had an accuracy of 93% in predicting death correctly. When applied to the validation cohort this model had a positive predictive value of 91%, a negative predictive value of 94%, a sensitivity of 91%, and a specificity of 94%. On the same population overall, the positive and negative predictive value of the King's criteria were 94% and 93% respectively, whereas their sensitivity and specificity were 88% and 96% respectively. CONCLUSIONS: Using admission characteristics our model is able to identify patients who die from paracetamol overdose fulminant hepatic failure as accurately as King's College criteria, but at a much earlier stage in their condition.     

Quality assurance in bariatric surgery

Quality assurance is a function that exists in manufacturing,engineering, and the service industry. Bariatric surgery is an undertaking with a special form of consumer product and service.In this day of limited resources and significant value exchanges among stakeholders (ie, patients, surgeons, third-party payers),the goal of the bariatric community is to deliver quality outcomes with safety, efficacy, and efficiency. The American Society for Bariatric Surgery and the Surgical Review Corporation, in conjunction with the bariatric community, will use quality assurance methods to produce quality outcomes that will satisfy the value exchanges of all stakeholders.     

Hereditary hyperuricemia and renal disease

Hyperuricemia and gout have long been known to run in families. As well as an apparently multifactorial genetic component to classic gout itself, 2 rather unusual sex-linked single-gene disorders of purine biosynthesis or recycling have been defined: deficiency of the enzyme hypoxanthine-guaninephosphoribosyl transferase (HPRT), and overactivity of PPriboseP synthase. Both result in overproduction of urate, hyperuricemia, and secondary overexcretion that may lead to acute or chronic renal damage. Familial juvenile hyperuricemic nephropathy (FJHN) and autosomal-dominant medullary cystic kidney disease (ADMCKD) are more common but less well-defined hyperuricemic conditions resulting from a decrease in the fractional excretion of filtered urate, with normal urate production. Although having features in common, ADMCKD is distinguished in particular by the presence of medullary cysts. One major group of both disorders is associated with mutations in the gene for uromodulin, but this accounts for only about one third of cases, and genetic heterogeneity is present. Whether the genes involved in these latter disorders contribute to the polygenic hyperuricemia and urate underexcretion of classic gout remains unexplored.     

Ductal carcinoma in situ of the breast and heparanase-1 expression: a molecular explanation for more aggressive subtypes

BACKGROUND: Ductal carcinoma in situ of the breast (DCIS) forms a heterogeneous group of lesions with varying invasive potential. This study tested whether heparanase-1 (HPR1), an endoglycosidase that specifically degrades the heparan sulfate (HS) proteoglycans in the breast extracellular matrix, was associated with the most aggressive DCIS subtypes. STUDY DESIGN: Fifty-seven DCIS specimens and 10 normal breast specimens were examined for HPR1 expression using immunohistochemical staining. Twenty-seven arbitrarily selected specimens were also examined for HS deposition by immunofluorescence staining, confirming HPR1 activity. Patient medical records were obtained to explore a possible association between biologic potential using Van Nuys Prognostic Index (VNPI) and HPR1 expression. RESULTS: Twenty-one (75%) of 28 comedo and microinvasive DCIS specimens stained HPR1 positive; 4 (14%) of 29 other subtypes (papillary, cribriform, and solid subtypes) stained HPR1 positive on immunohistochemistry (p = 0.003). Among 27 DCIS stained for HS, we found that 8 (67%) of 12 HPR1-negative DCIS had intact HS deposition in the extracellular basement membrane; none of the 15 HPR1-positive DCIS stained HS positive. Six (86%) of seven DCIS with VNPI scores 8 to 9 and 14 (50%) of 28 DCIS with VNPI scores 5 to 7 were HPR1 positive; only 3 (17%) of 18 DCIS with VNPI scores 3 to 4 were HPR1 positive. Median VNPI score in patients with HPR1-positive DCIS was 7 (range 3 to 9), compared with 4.5 (range 3 to 7) in patients with HPR1-negative DCIS (p < 0.001). CONCLUSIONS: HPR1 was expressed at a significantly higher frequency in the invasive comedo and DCIS with microinvasion subtypes than in the noninvasive subtypes. HPR1 expression was inversely associated with HS deposition in the extracellular basement membrane of the DCIS. HPR1 expression was associated with a higher VNPI score. These observations suggest that HPR1 expression in DCIS can play an important role in development of DCIS into an invasive breast cancer.