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Background: Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed bariatric procedure in the United States. Postoperative migration of the stomach into the chest is a rare complicati...

Rigorous research on smartphone apps for individuals pursuing bariatric surgery is limited. A digital health intervention was recently developed using standard behavioral weight loss programs with specific modifications for bariatric surgery. The current study evaluated this intervention for improving diet, exercise, and psychosocial health over 8 weeks prior to surgery in an academic medical center.Fifty patients were randomized to receive either the digital intervention or treatment as usual prior to a surgical procedure. Measures of anxiety, depression, stress, quality of life, physical activity, and diet were administered at baseline and at 8-week follow-up. Statistical power of 80% estimated for N = 50 to detect ES = 0.68 with alpha = 0.05.Results of intent-to-treat (N = 50 baseline, N = 36 follow-up) analyses indicated significant moderate differences in stress and anxiety (ES = - 0.58 to - 0.62) favoring the digital intervention. Effects of the program on total daily calories consumed, body mass index, quality of life, and eating disorder symptoms were small (ES = - 0.24 to 0.33) and not significant. Given small effects for these domains, the sample size of the study likely affected the ability to detect significant differences.The digital health intervention appears to significantly impact several measures of physical activity and emotional functioning in candidates for bariatric surgery, which could augment surgical outcomes.

There has been a recent increased interest in the use of non-steroidal anti-inflammatory drugs (NSAIDs) such as ketorolac for post-operative pain management to minimize opioid use and decrease hospital length of stay (LOS). Although NSAID use has been controversial following bariatric surgery due to anecdotal concerns for increased gastric bleeding, the impact of ketorolac as an adjunct to opioids needs further investigation on LOS and post-operative complications like bleeding. This study aims to evaluate the impact of post-operative ketorolac use on opioid consumption, LOS, and bleeding risk after bariatric surgery. We retrospectively analyzed a prospectively maintained database of all bariatric surgery patients who either underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass surgery (RYGB) at a tertiary center between 2011 and 2015. Patients were stratified into 2 groups based on post-operative pain control regimen as follows: (1) ketorolac and opioids and (2) opioids alone. A total of 1555 patients were identified who underwent either SG (n = 1255) or RYGB (n = 300). The overall LOS was 1.81 ± .059 days for ketorolac-opioid patients vs. 2.09 ± .065 days for opioid-only patients (P

Introduction: The benefit and short-term safety of ketorolac have been established in previous studies however, the risk of bleeding and long-term renal impairment in patients undergoing donor nephrectomy remain unclear. We report our experience at a high-volume transplant center. Method: Between January 1996 and January 2014, 862 consecutive patients underwent laparoscopic donor nephrectomy. Exclusion criteria included nonsteroidal anti-inflammatory drug allergy, asthma, bleeding disorders, long-term opioid use, intraoperative blood loss >700 mL, peptic ulcer disease, bleeding diathesis, and baseline creatinine greater than 1.9 mg/dL. Intravenous ketorolac was administered within 30 minutes following the surgical procedure at a dose of 15 to 30 mg every 6 hours. Patients were categorized into 2 groups according to the administration of ketorolac after surgery. Differences between the groups were analyzed. Primary outcomes were changes in serum creatinine and hemoglobin levels. Poor outcome was defined as postsurgical complications. Results: During this time, 469 (55.3%) received ketorolac. The mean donor age was 39 years, and 360 (42.5%) were male. Left kidneys were procured in 82%. Operative time averaged 210 minutes and warm ischemia time117 seconds. Baseline demographic and operative outcomes were comparable in both groups. No statistically significant differences were found between the ketorolac group and the nonketorolac group in preoperative and postoperative hemoglobin levels and serum creatinine at 1 week, 1 year, and 5 years ( P = .6). Ketorolac use was not associated with increased perioperative morbidity ( P = NS). Conclusion: The use of intravenous ketorolac in patients undergoing donor nephrectomy was not associated with an increased risk of bleeding or renal impairment.

Defective 3β-hydroxysterol-Δ7 -reductase (DHCR7) in the developmental disorder, Smith-Lemli-Opitz syndrome (SLOS), results in a deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). Here, we show that loss of DHCR7 causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis from murine or human cortical neural precursors, and depletion of the cortical precursor pool, both in vitro and in vivo. We found that a major oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), mediates these effects by initiating crosstalk between glucocorticoid receptor (GR) and neurotrophin receptor kinase TrkB. Either loss of DHCR7 or direct exposure to DHCEO causes hyperactivation of GR and TrkB and their downstream MEK-ERK-C/EBP signaling pathway in cortical neural precursors. Moreover, direct inhibition of GR activation with an antagonist or inhibition of DHCEO accumulation with antioxidants rescues the premature neurogenesis phenotype caused by the loss of DHCR7. These results suggest that GR could be a new therapeutic target against the neurological defects observed in SLOS.

Summary Background Sarcoidosis is occasionally seen in association with malignancy, both at the time of cancer diagnosis or during follow up. Aim The purpose of this study is to identify patients with paraneoplastic sarcoid, their associated malignancies and disease characteristics. Methods We identified 289 patients diagnosed histologically with sarcoidosis over a 6-year period in one centre, from 2010 to 2016. Fifty of these patients had a prior or concomitant diagnosis of cancer. Results 17.3% of sarcoid cases had an associated malignancy. The most common malignancies were Gastrointestinal (20%), Haematological (18%), Lung (12%), Gynaecological (12%) and Head and Neck cancer (12%). 74% of sarcoid cases had pulmonary disease with sarcoid diagnostic tissue obtained most frequently via endobronchial ultrasound fine needle aspiration (68%). Most sarcoid cases (66%) were diagnosed within the first year of their malignancy diagnosis. Discussion Careful consideration needs to be given to the possibility that potential cancer recurrences suspected on imaging studies may indeed be sarcoid reactions.

Safety is of utmost importance in live donor nephrectomies. In this study, we describe our initial experience with robot-assisted laparoscopic donor nephrectomy (RDN) in comparison with the standard laparoscopic donor nephrectomy (LDN). We retrospectively reviewed 95 patients who either underwent RDN or LDN performed by a single surgeon from 2011 to 2016 at a tertiary institution. Donor perioperative course and postoperative outcome along with recipient outcomes were compared. Of the 95 cases, 73 were classified as LDN and 22 were classified as RDN. There were no significant differences between the two groups in age, sex, BMI, race, and ASA status. Operative times (p

To enlarge the donor pool, kidney donors with obesity have been considered. We hypothesized that it is safe for patients with obesity to serve as living kidney donors. In this single-center retrospective analysis, we examined the effect of obesity (body mass index (BMI) of 30–35 kg/m2) on glomerular filtration rate (GFR) and creatinine in patients undergoing laparoscopic donor nephrectomy. Other outcomes included intraoperative, 30-, and 90-day complications. We examined the trajectory between patients with obesity versus patients without obesity over time using mixed effects models for the outcomes of creatinine in mg/dL and GFR in mL/min/1.73 m2. Among donors with obesity versus donors without obesity, there were no significant differences in demographics or comorbidities. Baseline creatinine in donors with obesity was significantly greater than that of donors without obesity (p = 0.02). Operative time was significantly longer in donors with obesity versus without obesity (p = 0.03). There was no significant difference in 30-day morbidity between donors with obesity versus without obesity (6.52 vs. 3.57%, respectively; p = 0.38). The rate of graft complications was 8.7% in donors with obesity versus 7.1% in donors without obesity (p = 1.0). 90-day complications were infrequent, and not significant different between the groups. At 6, 12, and 24-month postoperative follow-up, the mean creatinine level in patients with obesity was not significantly different from that of patients without obesity (1.23 vs. 1.31, 1.23 vs. 1.26, and 1.17 vs. 1.19 at 6, 12, and 24 months, respectively). Mean GFR was also not significantly different at 6, 12, and, 24 months. Postoperative creatinine and GFR changes were not significantly different in patients with obesity versus without obesity after laparoscopic donor nephrectomy. These findings suggest that carefully screened living kidney donors with obesity do not experience decreased postoperative renal function.

Laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the two most common bariatric surgeries for treating morbid obesity. The purpose of this study is to determine differences in outcomes from RYGB or SG between patients ages ≥ 60 years and

Obstructive sleep apnea (OSA) is a serious obesity-associated disorder that causes significant short- and long-term medical consequences. The objective of this study is to compare the 6-month and 1-year postoperative symptomatic OSA remission rates of patients undergoing bariatric surgery based on their preoperative body mass index (BMI) stratification, type of bariatric operation—sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB)—and OSA severity. We retrospectively analyzed 297 obese patients with a diagnosis of OSA who had undergone either SG or RYGB between 2011 and 2015. The overall 6-month symptomatic OSA remission rate for patients (n = 255) was 74.5%. At 6 months, patients with a preoperative BMI of 30–34.9 kg/m2 (class I), 35–39.9 kg/m2 (class II), and 40+ kg/m2 (class III) had 100, 70.0, and 75.0% (p = 0.2164) remission rates, respectively. The 6-month remission rates for SG and RYGB were 75.3 and 70.8% (p = 0.5165), respectively. The overall 1-year symptomatic OSA remission rate for patients (n = 162) was 87.1%. At 1 year, class I, II, and III patients had 100, 85.7, and 87.5% (p = 0.5740) remission rates, respectively. The 1-year remission rates for SG and RYGB were 89.2 and 81.2% (p = 0.2189), respectively. A sub-analysis (n = 69) based on preoperative OSA severity levels did not affect the remission outcome at either the 6-month (p = 0.3670) or 1-year (p = 0.3004) follow-up. Most obese patients experience symptomatic remission of their OSA after bariatric surgery, regardless of their preoperative BMI, choice of operation, or OSA severity.

Obesity not only increases the chances of developing diabetes-one of the top causes of death in the United States-but it also results in further medical complications.To compare the 6-month and 1-year postoperative remission rates of type 2 diabetic (T2D) patients after bariatric surgery based on preoperative glycosylated hemoglobin (A1C) stratification and pharmacologic therapy: insulin-dependent diabetic (IDD) versus noninsulin-dependent diabetic (NIDD).Academic hospital, United States.We retrospectively analyzed a prospectively maintained database of 186 obese patients with a diagnosis T2D who had undergone either a sleeve gastrectomy or a Roux-en-Y gastric bypass surgery at our hospital.At 6 months (n = 180), patients who were stratified by preoperative A1C levels (6.5; ≥6.5 to8; ≥8) had 70.5%, 51.7%, and 30.0% remission rates (P.001) and at 1 year (n = 118) patients had 72.0%, 54.0%, and 42.8% remission rates (P = .053), respectively. When patients were substratified by preoperative pharmacologic therapy, IDD and NIDD patients had different remission rates within the same A1C level. At 6-months follow-up within A1C ≥6.5 to8 (IDD versus NIDD), the remission rate was 23.5% versus 64.1% (odds ratio [OR]: .173, confidence interval [CI]: .0471, .6308, P = .0079), and within A1C ≥8 the remission was 24.0% versus 37.5% (OR: .5263, CI: .2115, 1.3096, P = .1676), respectively. At 1-year follow-up within A1C ≥6.5 to8, the remission rate was 30.0% versus 62.9% (OR: .2521, CI: .0529, 1.2019, P = .0838), and within A1C ≥8 the remission was 31.4% versus 61.9% (OR: .2821, CI: .0908, .8762, P = .0286), respectively. Furthermore, when IDD patients were compared between A1C ≥6.5 to8 and A1C ≥8 the remission rates were nearly identical, and for NIDD patients A1C was not significantly associated with remission regardless of the level, except at 6 months.While a difference was observed between overall A1C levels-the lower the A1C level, the higher the remission rate-IDD patients had lower remission rates than NIDD patients irrespective of A1C levels; further, IDD patients performed similarly across A1C levels.

Apheresis technology to collect platelet (PLT) components differs among devices. We evaluated the relationship of the plateletpheresis device with bacterial contamination and reported septic transfusion reactions.Plateletpheresis was performed using Amicus (Fenwal, a Fresenius Kabi Company) or Trima (Trima Accel, TerumoBCT) from 2010 to 2014. All donations used inlet-line sample diversion and were tested by quality control (QC; Day 1) aerobic culture. Rates of bacterial contamination and septic reactions to PLTs were calculated for both devices.During the 5-year study period, plateletpheresis collections using Amicus and Trima devices totaled 1,486,888 and 671,955 donations, respectively. The rate of confirmed-positive bacterial cultures of apheresis PLT donations was significantly higher with Amicus than with Trima (252 vs. 112 per 10Apheresis technology affects bacterial contamination of plateletpheresis collections. The device-specific, higher rate of confirmed-positive bacterial culture results also correlated with a significantly higher rate of reported septic transfusion reactions to apheresis PLTs.

In 2015, thirteen per- and polyfluoroalkyl substances (PFAS), including perfluorohexanesulfonate (PFHxS), perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA) were analyzed in human plasma that were collected from a total of 616 American Red Cross male and female blood donors (ages 20-69) at 6 regional blood collection centers. Plasma samples were analyzed using a validated solvent precipitation-isotope dilution direction-liquid chromatography tandem mass spectrometry method. The data were analyzed in conjunction with prior cross-sectional investigations [2000-2001 (n =645), 2006 (n =600), and 2010 (n =600)] to determine PFAS trends. Age- and sex-adjusted geometric mean serum (2000-2001) and plasma (2006, 2010, 2015) concentrations (ng/mL) were, respectively: PFHxS (2.3, 1.5, 1.3, 0.9); PFOS (35.1, 14.5, 8.4, 4.3); PFOA (4.7, 3.4, 2.4, 1.1); PFNA (0.6, 1.0, 0.8, 0.4); and PFDA (0.2, 0.3, 0.3, 0.1). The percentage decline in these geometric mean concentrations from 2000-2001 to 2015 were: PFHxS (61%); PFOS (88%); PFOA (77%); PFNA (33%); and PFDA (50%). The results indicate a continued decline of PFHxS, PFOS, and PFOA concentrations in American Red Cross blood donors. For the remaining PFAS measured in 2015, including the shorter chain perfluoroalkyls perfluorobutanesulfonate (PFBS) and perfluorohexanoate (PFHxA), the majority of samples were below the lower limit of quantitation.

Transfusion-transmitted West Nile virus (WNV) infection is infrequent as a result of minipool (MP) and individual-donation (ID) nucleic acid testing (NAT) of blood donations. ID-NAT is triggered on the basis of local WNV activity identified by MP-NAT.A 78-year-old male patient who was treated for cardiac disease received 14 blood components from 30 donors in August 2016. He was discharged 7 days after aortic valve replacement and coronary bypass surgery, but was re-admitted on Day 12 with symptoms of viral infection, and eventually was diagnosed with aseptic meningitis. The patent died on Day 51.The patient was positive for WNV-immunoglobulin M (IgM) antibodies in his cerebrospinal fluid on Day 14 and was positive for WNV-IgM (on Days 14 and 16) and WNV-IgG antibodies (on Day 16) in his serum. All associated donations were nonreactive by MP-NAT or ID-NAT. However, one MP-NAT was noted to have an elevated (but negative) signal-to-cutoff ratio, and one donor from that MP was subsequently found positive for WNV-IgM and IgG antibodies; the donor was diagnosed with a WNV-like viral syndrome that had an onset 3 to 5 days postdonation. The donor's plasma was transfused 12 days before the patient's onset of WNV-meningoencephalitis. Conversion to ID-NAT was triggered for the region 7 days after the implicated donation, which was associated with the region's first human WNV case.Despite the possibility of mosquito-borne transmission, this was considered to be a case of transfusion-transmitted WNV infection from an MP-NAT-nonreactive donation collected just before triggering conversion to ID-NAT; a rare event recognized once in 84 million donations.

Eleven perfluorinated alkyl acids (PFAAs) were analyzed in plasma from a total of 600 American Red Cross adult blood donors from six locations in 2010. The samples were extracted by protein precipitation and quantified by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). The anions of the three perfluorosulfonic acids measured were perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS). The anions of the eight perfluorocarboxylic acids were perfluoropentanoate (PFPeA), perfluorohexanoate (PFHxA), perfluoroheptanoate (PFHpA), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA). Findings were compared to results from different donor samples analyzed at the same locations collected in 2000-2001 (N = 645 serum samples) and 2006 (N = 600 plasma samples). Most measurements in 2010 were less than the lower limit of quantitation for PFBS, PFPeA, PFHxA, and PFDoA. For the remaining analytes, the geometric mean concentrations (ng/mL) in 2000-2001, 2006, and 2010 were, respectively, PFHxS: (2.25, 1.52, 1.34); PFOS (34.9, 14.5, 8.3); PFHpA (0.13, 0.09, 0.05); PFOA (4.70, 3.44, 2.44); PFNA (0.57, 0.97, 0.83); PFDA (0.16, 0.34, 0.27), and PFUnA (0.10, 0.18, 0.14). The percentage decline (parentheses) in geometric mean concentrations from 2000-2001 to 2010 were PFHxS (40%), PFOS (76%), and PFOA (48%). The decline in PFOS suggested a population halving time of 4.3 years. This estimate is comparable to the geometric mean serum elimination half-life of 4.8 years reported in individuals. This similarity supports the conclusion that the dominant PFOS-related exposures to humans in the United States were greatly mitigated during the phase-out period.

Item does not contain fulltext CONTEXT: Illicit drug use is associated with risky sexual behaviors in adolescents and young adults. However, few studies have examined these associations among drug users of all reproductive ages, using a control group of nonusers. METHODS: Associations between marijuana and cocaine use, and outcomes related to sexual behaviors and reproductive health, were assessed using data from the 2002 National Survey of Family Growth. Overall, 4,928 men and 7,643 women aged 15-44 were interviewed. Chi-square tests, t tests and multivariable logistic regression analyses were used; in supplementary analyses, men and women were stratified by age-group (25 or younger, and older than 25), to capture the understudied older adults who use drugs. RESULTS: Twenty-seven percent of men and 16% of women reported use of marijuana or cocaine in the last year. Drug users were younger than nonusers at first vaginal sex (mean, 15.2-16.1 vs. 17.3-17.5 years) and were more likely to have engaged in risky sexual behaviors in the last year, including having had sex with a nonmonogamous partner (odds ratios, 3.3-5.2 for men and 2.9-6.5 for women), while high on alcohol or drugs (10.1-18.0 and 8.1-24.2), or in exchange for money or drugs (2.7-2.8 and 2.3-9.2). They also were more likely to have undergone STD testing or treatment. Drug use was associated with risky sexual behaviors in both age-groups. CONCLUSION: Programs aimed at reducing sexual risks among drug users should address the behaviors of men and women of all reproductive ages.

The purpose of this study was to determine the concentration trends of a nine-target-analyte homologous series of perfluorocarboxylates from six American Red Cross adult blood donor centers. A total of 645 serum and 600 plasma samples were obtained in 2000-2001 and 2006, respectively, with samples stratified for each 10-year (20-69) age- and sex-group per each location. Samples were extracted by protein precipitation and quantified by using tandem mass spectrometry. The nine perfluorocarboxylates were perfluorobutanoate (PFBA, C(3)F(7)CO(2)(-)), perfluoropentanoate (PFPeA, C(4)F(9)CO(2)(-)), perfluorohexanoate (PFHxA, C(5)F(11)CO(2)(-)), perfluoroheptanoate (PFHpA, C(6)F(13)CO(2)(-)), perfluorooctanoate (PFOA, C(7)F(15)CO(2)(-)), perfluorononanoate (PFNA, C(8)F(17)CO(2)(-)), perfluorodecanoate (PFDA, C(9)F(19)CO(2)(-)), perfluoroundecanoate (PFUnA,C(10)F(21)CO(2)(-)), and perfluorododecanoate (PFDoA, C(11)F(23)CO(2)(-)). The majority of measurements were less than the lower limit of quantitation for PFPeA, PFHxA, and PFDoA. For the remaining targeted analytes, the geometric mean serum and plasma concentrations (ng/mL) for 2000-2001 and 2006 were, respectively, as follows: PFBA 2.61 vs 0.33, PFHpA 0.13 vs 0.09, PFOA 4.70 vs 3.44, PFNA 0.57 vs 0.97, PFDA 0.16 vs 0.34, and PFUnA 0.10 vs 0.18. Estimates of the 95th percent tolerance limits (ng/mL) were as follows: PFBA 5.3 vs 1.4, PFHpA 0.4 vs 0.4, PFOA 12.3 vs 7.7, PFNA 1.4 vs 2.2, PFDA 0.4 vs 0.8, and PFUnA 0.3 vs 0.5. Important observations were the decline in PFBA and increase in PFNA, PFDA, and PFUnA concentrations between 2000-2001 and 2006. The longer chain length perfluorocarboxylates were also highly correlated with each other.

Because bariatric surgery is becoming increasingly common, gastroenterologists need to be familiar with the surgical and endoscopic anatomy of the operations in use today. This review focuses on the 4 most commonly performed bariatric operations in the United States: Roux-en-Y gastric bypass, adjustable gastric band, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch. The anatomy and mechanism of action of each procedure is discussed and illustrated. Emphasis is placed on the endoscopic anatomy, with review of the commonly encountered complications. Emerging techniques and devices are reviewed.

We describe a family with a novel, inherited AXIN2 mutation (c.1989G>A) segregating in an autosomal dominant pattern with oligodontia and variable other findings including colonic polyposis, gastric polyps, a mild ectodermal dysplasia phenotype with sparse hair and eyebrows, and early onset colorectal and breast cancers. This novel mutation predicts p.Tyr663X, which is a truncated protein that is missing the last three exons, including the DIX (Disheveled and AXIN interacting) domain. This nonsense mutation is predicted to destroy the inhibitory action of AXIN2 on WNT signaling. Previous authors have described an unrelated family with autosomal dominant oligodontia and a variable colorectal phenotype segregating with a nonsense mutation of AXIN2, as well as a frameshift AXIN2 mutation in an unrelated individual with oligodontia. Our report provides additional evidence supporting an autosomal dominant AXIN2-associated ectodermal dysplasia and neoplastic syndrome.

Background Pulmonary embolism (PE) is an uncommon, life-threatening complication after living donor nephrectomy (LDN), and is considered among the most common causes for donor mortality. Most cases of postoperative PEs are thought to originate in deep venous thrombosis (DVT) of the lower extremities. Case Report A 56-year-old, healthy woman underwent laparoscopic left LDN. Her postoperative course was complicated by PE, presenting at postoperative day 7. Doppler ultrasonography of her lower extremities did not demonstrate DVT. Both transthoracic echocardiogram and contrast-enhanced computed tomography demonstrated a floating thrombus within the inferior vena cava (IVC) originating from a thrombus in the left renal vein stump. Symptoms resolved with systemic anticoagulation. Repeat transesophageal echocardiography demonstrated resolution of the IVC thrombus. Conclusions Thrombus originating in left renal vein stump should be considered in patients who develop PE after LDN, especially when lower extremity DVT is not demonstrated.

Type 2 diabetes mellitus affects more than 170 million people worldwide. Because this disease is strongly linked to obesity, the term "diabesity" has been coined to describe the confluence of the 2 disease processes. Bariatric surgery has been performed for many years to achieve sustained weight loss in the morbidly obese population. As a secondary effect, a remarkable improvement in glycemic control is commonly achieved postoperatively. This has led to substantial interest in the use of bariatric procedures to treat type 2 diabetes mellitus. Surgical procedures in common use include the adjustable gastric band, the Roux-en-Y gastric bypass, the biliopancreatic diversion with duodenal switch, and the sleeve gastrectomy. Additionally, several investigational procedures including the ileal interposition and duodenal-jejunal bypass have been proposed as primary interventions for type 2 diabetes mellitus. These operations achieve their metabolic effects through a combination of volume restriction, intestinal bypass, and hormonal changes. As more data become available on the positive effect of bariatric procedures on type 2 diabetes mellitus, the use of such operations may grow. Bariatric surgery may ultimately become a major tool in the long-term treatment of type 2 diabetes mellitus. This manuscript presents an extensive review of the literature supporting these concepts.

Natural orifice transluminal endoscopic surgery (NOTES) is an experimental surgical approach. Several intra-abdominal procedures have been successfully performed in animals and humans although the long-term safety is still unknown. Potential advantages are reduction of wound-related complications, reduced postoperative pain, improved cosmesis, and short recovery time. This study aimed to measure the overall perception among health care workers and medical students. Materials: A brief 9-item survey was created to measure the perception among health care workers and medical students. A total of 120 surveys were completed. Results: Overall, 15% had a favorable perception, 29% had an unfavorable perception, and 55% were undecided. A total of 40% considered the possibility of avoiding wound-related complications the most appealing advantage, whereas 54% cited unknown safety as the most concerning possible disadvantage. Current occupation, previous knowledge, and affiliation to the surgical department influenced the overall perception. Conclusion: Most health care workers and medical students in our sample were undecided in their perception of NOTES.

Gastrojejunal anastomotic stricture is the most commonly occurring short-term complication after Roux-en-Y gastric bypass. Endoscopic balloon dilation is the first-line treatment for stricture. However, an optimal dilation protocol has not been identified. This study aimed to document routine management of stricture after laparoscopic gastric bypass and its impact on postoperative weight loss.Charts of patients who underwent gastric bypass from 2000 to 2006 were reviewed using a standardized abstraction form. Patients with stricture were matched with control subjects based on age +/-5 years, gender, and preoperative body mass index (BMI +/- 5). Patients with at least 6 months of follow-up assessment were included in the study.Of the 113 patients included in the study, 20% were male, 26% black, 19% Hispanic, and 51% white. Their mean age was 42 +/- 10 years (range, 22-66 years). The mean preoperative BMI was 47.0 +/- 5.4 kg/m(2) for the case group and 46.6 +/- 5.5 kg/m(2) for the control group (p = 0.3). After adjustment for patient characteristics, using a larger balloon was associated with reduced odds of stricture recurrence (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12-0.85; p = 0.02). All the patients were without signs or symptoms of stricture at the last follow-up visit (20 +/- 17 months). Weight loss was similar between the two groups. The percentage of estimated weight loss (%EWL) at 12 months postoperatively was 66% for the study participants and 67% for the control subjects (p = 0.5). Baseline alcohol use and higher preoperative BMI were associated with a higher BMI 6 months postoperatively (p = 0.004 and p0.001, respectively).Initial dilation with a larger balloon is safe and may prevent stricture recurrence. Further study of modifiable risk factors for reduced weight loss after surgery, such as alcohol use, may improve patient outcomes.

Identification of microsatellite unstable (MSI-H) colorectal cancers (CRCs) is important not only for the identification of hereditary nonpolyposis colorectal cancer syndrome but also because MSI-H CRCs have a better prognosis and may respond differently to 5-fluorouracil-based chemotherapy. We present 2 nearly equivalent logistic regression models for clinical use that predict microsatellite instability based on the review of 1649 CRCs from patients of all ages collected in a population-based case control study in northern Israel. One hundred ninety-eight of these 1649 tumors demonstrated a high degree of microsatellite instability (12%). Multivariate analysis found that2 tumor-infiltrating lymphocyte (TIL) cells per high-powered field, the lack of dirty necrosis, the presence of a Crohn-like reaction, right-sided location, any mucinous differentiation (mucinous or focally mucinous) and well or poor differentiation, and age less than 50 were all independent predictors of MSI-H. We developed 2 logistic regression models that differ only by the statistical approach used to analyze the number of TIL cells per high-powered field, where the slightly more accurate (and complex) model uses the log of the total number of TIL cells. The simpler clinical model uses a cut-off of 2TIL cells per high-powered field. The accuracy of both models is high, with an 85.4% versus 85.0% probability of correctly classifying tumors as MSI-H. By employing the simpler model, pathologists can predict the likelihood of microsatellite instability by compiling the MSI probability score (Table 4 and Fig. 1) from simple histologic and clinical data available during sign-out. Our model shows that approximately 43% of CRCs have a MSI probability score of 1 or less and hence have little likelihood (3%) of being MSI-H. Although this model is not perfect in predicting microsatellite instability, its use could improve the efficiency of expensive diagnostic testing.

Substance abuse poses significant health risks to childbearing-aged women in the United States and, for those who become pregnant, to their children. Alcohol is the most prevalent substance consumed by childbearing-aged women, followed by tobacco, and a variety of illicit drugs. Substance use in the preconception period predicts substance use during the prenatal period. Evidence-based methods for screening and intervening on harmful consumption patterns of these substances have been developed and are recommended for use in primary care settings for women who are pregnant, planning a pregnancy, or at risk for becoming pregnant. This report describes the scope of substance abuse in the target population and provides recommendations from the Clinical Working Group of the Select Panel on Preconception Care, Centers for Disease Control and Prevention, for addressing alcohol, tobacco, and illicit drug use among childbearing-aged women.

Background Similar to gastric bypass patients, a regimen of ursodeoxycholic acid in the immediate postoperative period might obviate the need for routine cholecystectomy. Routine cholecystectomy has been recommended for patients who undergo biliopancreatic diversion (BPD), because of the high prevalence of gallstones in the obese patient and presumed development of gallstones postoperatively. We have considered elective cholecystectomy only if gallbladder disease were present. The aim of this study was to assess the need for cholecystectomy in the postoperative period in such patients. Methods In this retrospective study, the data from 219 patients who had undergone BPD with duodenal switch (BPD/DS), from January 1999 to January 2003, were analyzed. We performed a 150-cm alimentary limb and 100-cm common channel BPD/DS. The patients received 600 mg ursodeoxycholic acid orally daily for 6 months. The following data were recorded: demographics, medical history, medication, weight loss, diagnostic evaluation, and operative and pathologic data. Results Of the 219 patients who underwent surgery, 59 were men (26.9%) and 160 women were (73.1%) (mean age 41.7 years, mean body mass index 55.7 kg/m 2 ). The mean follow-up was 30 months (range 12–48). Of the 219 patients, 57 (19.6%) underwent cholecystectomy: 28 (12.7%) preoperatively, 10 (4.5%) simultaneously, and 19 (8.7%) postoperatively. Simultaneous cholecystectomy was performed when the patient had a history of colic episodes with gallbladder disease (disclosed by preoperative ultrasonography). The postoperative cholecystectomy pathology reports showed cholecystitis in only 7 patients. Conclusion The results of our study have shown that the incidence of postoperative cholecystectomy in BPD/DS patients is low, and cholecystitis is rare. Routine cholecystectomy in BPD/DS patients is no longer recommended.

Pulmonary embolism is the leading cause of death after bariatric surgery and represents one of the many potential life-threatening conditions after bariatric surgery. The Advanced Bariatric Life Support (ABLS) initiative was developed to teach practising bariatric surgeons, emergency physicians, and allied health professionals the need for accurate and timely diagnosis and management of life-threatening bariatric surgery complications. This case study was derived from the ABLS file and discusses the difficulty in differentiating between two major complications after gastric bypass — pulmonary embolism vs leak. Accurate diagnosis and expeditious treatment are of utmost importance to prevent death associated with these serious bariatric surgical complications.

BACKGROUND: American Red Cross surveillance data on transfusion-related acute lung injury (TRALI) fatalities were analyzed to evaluate the association with components from donors with white blood cell (WBC) antibodies and to examine the potential impact of the selective transfusion of plasma from male donors. STUDY DESIGN AND METHODS: Suspected TRALI reports in 2003 through 2005 were identified and all fatalities were reviewed and classified by three physicians as “probable TRALI” or of “unrelated etiology,” with independent review of the associated serologic investigation. Hospital investigational and reporting biases could not be fully controlled in this retrospective study. RESULTS: A total of 550 reports of suspected TRALI, including 72 fatalities, were investigated. The number of reports increased each year and the rate varied by geographic region. Retrospective review of fatalities revealed 38 cases of probable TRALI, the majority (24 of 38 [63%]) after plasma transfusion. A female, WBC antibody–positive donor was involved in 71 percent (27 of 38) of cases and in 75 percent (18 of 24) of cases involving plasma transfusion. Female antibody-positive donors were more likely to be associated with probable TRALI than with unrelated cases (p = 0.0001; odds ratio [OR], 9.5; 95% confidence interval [CI], 2.9-31.1]. The rate of probable TRALI among recipient fatalities was higher for plasma components (1:202,673; OR, 12.5; 95% CI, 5.4-28.9) and apheresis platelets (PLTs; 1:320,572; OR, 7.9; 95% CI, 2.5-24.8) compared to red cells (1:2,527,437). Male donors contributed 64.5 and 52.0 percent of distributed apheresis PLTs and plasma components, respectively, in 2005. CONCLUSION: Plasma components linked to female donors with WBC antibodies were responsible for the majority of probable TRALI fatalities. Prudent measures to limit transfusion of WBC antibody–containing plasma components may prevent as many as six fatalities per year in the Red Cross system.

Several large series of laparoscopic donor nephrectomy (LDN) have been published, largely focusing on immediate results and short-term complications. The aim of this study was to examine the results of LDN and collect medium-term and long-term donor followup. We examined the results of two surgeons who performed 500 consecutive LDNs from 1996 to 2005. Prospective databases were reviewed for both donors and recipients to record demographics, medical history, intraoperative events, and complications. Patients were followed between 1 month and 9 years after surgery to assess for delayed complications, especially hypertension, renal insufficiency, incisional hernia, bowel obstruction, and chronic pain. Left kidneys were procured in 86.2% of cases. Mean operative time was 3.5 h, and warm ischemia time averaged 3.4 min. Hand-assistance was used in 13.8%, and conversion rate was 1.8%. Intraoperative complication rate was 5.8% and was predominantly bleeding (93.1%). Most (86.2%) of the operative complications occurred during the initial 150 cases of a surgeon, compared with 10.3% in the subsequent 150 cases (p = 0.003). Operative time decreased by 87 min after the initial 150 cases (p < 0.001). Immediate graft survival was 97.5%. Delayed graft function occurred in 3.0% of recipients, and acute tubular necrosis occurred in 7.0%. Thirty-day donor complication rate was 9.8%. Mean donor creatinine was 1.24 on the first postoperative day, 1.27 at 2 weeks, and 1.24 at 1 year. At a mean followup of 32.8 months, long-term donor complications consisted of 11 cases of hypertension, 9 cases of prolonged pain or paresthesia, 2 incisional hernias, 1 small bowel obstruction requiring laparoscopic lysis of adhesions, and 1 hydrocele requiring repair. LDN can be performed with acceptable immediate morbidity and excellent graft function. Operative time and complications decreased significantly after a surgeon performed 150 cases. Long-term complications were uncommon but included a likely underestimated incidence of hypertension.

Background Previous reports have questioned the safety of bariatric surgery in older patients. The aim of this study was to quantify the perioperative morbidity and mortality of older patients undergoing laparoscopic bariatric procedures at our institution. Methods A retrospective chart review of all laparoscopic bariatric procedures performed from February 1999 to September 2005 was performed to identify patients at Mount Sinai Medical Center who were older than 60 years at surgery. Results We identified 55 patients (36 women and 19 men). The mean age was 61.5 years (range 60–70), and the mean body mass index was 46.2 kg/m2 (range 38.1–61.0). Of the 55 patients, 33 (60%) had undergone laparoscopic Roux-en- Y gastric bypass, 9 (16%) laparoscopic gastric banding, 7 (13%) laparoscopic biliopancreatic diversion with duodenal switch, 3 (5.5%) laparoscopic revisional surgery, and 3 (5.5%) laparoscopic sleeve gastrectomy. The mean operative time was 2.3 hours (range 1.1–5.5). No patients required conversion to open surgery, and no perioperative mortality occurred within 30 days. The morbidity rate was 7.3% (n = 4). One patient developed an anastomotic bleed that was treated conservatively, and another patient developed an empyema that was successfully drained with a chest tube. That patient also developed a urinary tract infection, and another patient had a wound infection. The mean length of stay was 2.8 days (range 1–14). Conclusions In a carefully selected patient population in a medical center with appropriate experience, laparoscopic bariatric surgery can be performed safely with low morbidity and mortality in the elderly population.

Reports on the accuracy of magnetic resonance angiography (MRA) and magnetic resonance venography (MRV) in evaluating living donor renovasculature employ few patients or omit the consequences of inaccurate scans. We retrospectively compared intraoperative findings to MRA/MRV scans in 146 donor-recipient pairs. For detecting accessory arteries and early branching, MRA sensitivity was 57.6%, specificity 96.5%, false positive rate 3.5%, false negative rate 42.4%, positive predictive value 82.6%, negative predictive value 88.6% and overall accuracy 87.7%. By excluding clinically inconsequential accessory arteries, MRA sensitivity rose to 73.1%, specificity to 96.7% and overall accuracy to 92.5%. For MRVs, sensitivity was 56.2%, specificity 99%, false positive rate 1%, false negative rate 43.8%, positive predictive value 90%, negative predictive value 94.8% and accuracy 94.5%. Inaccurate scans were associated with prolonged donor and recipient operations and more frequently reconstructed arteries, but did not affect clinical outcomes. Because most missed accessory arteries are inconsequential, MRA is a useful, less invasive method for defining donor renovascular anatomy.

Previous investigators have suggested that laparoscopic splenectomy should be the procedure of choice for the treatment of benign hematologic disorders unresponsive to medical therapy. To evaluate the safety and utility of laparoscopic splenectomy for a variety of splenic disorders, we reviewed our collective experience at 2 institutions. We studied our 8-year experience by retrospective chart review. Patient demographic data, splenic pathology, intraoperative events, concomitant procedures, and all adverse perioperative events were recorded. A total of 131 patients had laparoscopic splenectomy, and there were 8 conversions to open surgery. Pathology included 63 with idiopathic thrombocytopenic purpura (ITP), 23 malignancies, 12 thrombotic thrombocytopenic purpura (TTP), 10 autoimmune hemolytic anemia (AIHA), and 23 others. Accessory spleens were noted in 21 patients (16%). Concomitant surgical procedures included 12 hepatic biopsies, 4 distal pancreatectomies, 4 cholecystectomies, and 7 others. Mean operative time was 170 minutes. There were 16 major complications in 16 patients and 2 deaths. Median postoperative length of stay was 3 days. Conversions, due mostly to bleeding, are related to splenic pathology and medical comorbidity and are not temporally related to surgical experience (learning curve). The morbidity, mortality, and conversion rates were low. Laparoscopic splenectomy permits an appropriate abdominal exploration and is associated with a short hospital stay. It is the procedure of choice for most indications for splenectomy.

The aim of this study was to describe the occurrence and clinical characteristics of symptomatic internal hernias (IH) after laparoscopic bariatric procedures. We conducted a retrospective review of cases of IH after 1,064 laparoscopic gastric bypasses (LGB) and biliopancreatic diversions with duodenal switch (LBPD-DS) performed from September 1998 to August 2002. We documented 35 cases of IH (overall incidence of 3.3%). The IH occurred in 6.0% of patients with retrocolic procedures and 3.3% of patients with antecolic procedures. Most were in the Petersen defect (55.9%) and at the enteroenterostomy site (35.3%). A bimodal presentation was observed, with 22.9% of patients with IH diagnosed in the early postoperative period (2–58 days) and 77.1% in a delayed fashion (187–1,109 days). A laparoscopic approach to the repair of IH was possible in 60.0% of patients. Complications occurred in 18.8% of patients, including one death (2.9%). Complete closure of all mesenteric defects is strongly recommended during laparoscopic bariatric procedures to avoid IH and their associated complications.

The authors assessed the potential for a pharmacokinetic/pharmacodynamic interaction between desloratadine and fluoxetine. This randomized, placebo-controlled, open-label study was conducted in 54 healthy volunteers. Subjects received 1 of 3 treatments: desloratadine 5 mg plus fluoxetine 20 mg, desloratadine 5 mg plus placebo, or fluoxetine 20 mg plus placebo. Serial electrocardiograms (ECGs) were performed at baseline and day 35. Treatment effects on C(max) and AUC were assessed. During coadministration of desloratadine with fluoxetine, the ratio of the mean log-transformed C(max) and AUC values for desloratadine following concomitant fluoxetine therapy revealed a small increase in C(max) values of 15% (90% confidence interval [CI], 95%-139%) but no increase for AUC values (90% CI, 82%-123%). Corresponding values for 3-OH desloratadine demonstrated small increases in mean log-transformed C(max) and AUC ratios: 17% (90% CI, 100%-136%) and 13% (90% CI, 96%-132%), respectively. Statistical evaluation of the ratio of the mean C(max) and AUC values for fluoxetine following concomitant desloratadine therapy revealed small decreases of 9% (90% CI, 72%-115%) and 11% (90% CI, 69%-113%), respectively. Corresponding values for norfluoxetine demonstrated modest increases in mean log-transformed C(max) and AUC ratios: 22% (90% CI, 100%-139%) and 18% (90% CI, 101%-136%), respectively. Coadministration of desloratadine with a potent inhibitor of CYP2D6 did not result in clinically relevant changes in its pharmacokinetic parameters. Desloratadine administration was not associated with clinically important changes in the pharmacokinetics of fluoxetine, a drug metabolized by CYP2D6. The most common adverse event in all groups was headache (65%). Desloratadine plus fluoxetine caused no significant changes in ECGs or ventricular rate.

Perfluorooctanesulfonyl fluoride-based products have included surfactants, paper and packaging treatments, and surface protectants (e.g., for carpet, upholstery, textile). Depending on the specific functional derivatization or degree of polymerization, such products may degrade or metabolize, to an undetermined degree, to perfluorooctanesulfonate (PFOS), a stable and persistent end product that has the potential to bioaccumulate. In this investigation, a total of 645 adult donor serum samples from six American Red Cross blood collection centers were analyzed for PFOS and six other fluorochemicals using HPLC-electrospray tandem mass spectrometry. PFOS concentrations ranged from the lower limit of quantitation of 4.1 ppb to 1656.0 ppb with a geometric mean of 34.9 ppb [95% confidence interval (CI), 33.3-36.5]. The geometric mean was higher among males (37.8 ppb; 95% CI, 35.5-40.3) than among females (31.3 ppb; 95% CI, 30.0-34.3). No substantial difference was observed with age. The estimate of the 95% tolerance limit of PFOS was 88.5 ppb (upper limit of 95% CI, 100.0 ppb). The measures of central tendency for the other fluorochemicals (N-ethyl perfluorooctanesulfonamidoacetate, N-methyl perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamide, perfluorooctanoate, and perfluorohexanesulfonate) were approximately an order of magnitude lower than PFOS. Because serum PFOS concentrations correlate with cumulative human exposure, this information can be useful for risk characterization.

Biliopancreatic diversion with duodenal switch (BPD-DS) is a well-known emerging open procedure that appears to be as effective as other bariatric operations and has been shown to provide excellent long-term weight loss. Therefore we looked at the safety and efficacy of the laparoscopic BPD-DS procedure compared to open BPD-DS in superobese patients (body mass index >60). A retrospective study of 54 superobese patients (body mass index >60) was carried out from July 1999 to June 2001: laparoscopic BPD-DS in 26 patients and open BPD-DS in 28 patients. Median preoperative body weight was 189.8 kg (range 155.1 to 271.2 kg) in the laparoscopic BPD-DS group and 196.5 kg (range 160.3 to 298.9 kg) in the open BPD-DS group. Median body mass index was 66.9 kg/m(2) in the laparoscopic group and 68.9 kg/m(2) in the open group. The two groups were compared by means of the unpaired t test, which yielded the following results: Major morbidity occurred in six patients (23%) in the laparoscopic BPD-DS group and in five patients (17%) in the open BPD-DS group (P = 0.63). There were two deaths in the laparoscopic BPD-DS group (7.6% mortality) and one death (3.5% mortality) in the open BPD-DS group (P = 0.51). Preoperative comorbidity was improved in eight patients in the laparoscopic BPD-DS group and two patients in the open BPD-DS group (P < 0.02). Laparoscopic BPD-DS is a technically feasible procedure that results in effective weight loss similar to the open procedure. However, both open and laparoscopic BPD-DS procedures are associated with appreciable morbidity and mortality in the superobese population. Additional studies are needed to determine the best surgical treatment for superobesity.

BACKGROUND: Trypanosoma cruzi, the agent of Chagas' disease, continues to be a concern for blood safety, as demonstrated by recent transfusion-transmitted cases in the United States and Canada. The chronic nature of Chagas', coupled with increasing numbers of immigrants from T. cruzi-endemic countries, suggests that Chagas' is a long-term public health problem. Herein, we report on a multiyear epidemiologic study of T. cruzi in Los Angeles and Miami blood donors. STUDY DESIGN AND METHODS: From May 1994 to September 1998, blood donors in Los Angeles and Miami were queried regarding birth or time spent in an endemic country. Donations of “yes” respondents were tested by EIA, confirmed by radioimmunoprecipitation assay, and if confirmed as seropositive, enrolled in look-back investigations. RESULTS: A total of 1,104,030 Los Angeles and 181,139 Miami donors were queried regarding risk; 7.3 and 14.3 percent, respectively, responded yes. Seropositive rates were 1 in 7,500 Los Angeles and 1 in 9,000 Miami donors. In Los Angeles, seroprevalence rates increased significantly from 1996 to 1998 and were significantly higher for directed donors than nondirected donors. Look back identified 18 recipients, all of whom were seronegative for T. cruzi. CONCLUSION: Significant numbers of T. cruzi-seropositive donors contribute to the U.S. blood supply. The incidence of seropositivity is enhanced by minority recruitment efforts necessitated by donor demographic shifts. Similarly, high rates among directed donations in Los Angeles are attributable to a disproportionate number of at-risk directed donors. Current look-back data likely underestimate the frequency of transfusion- transmitted T. cruzi. These results indicate that con- tinued evaluation of transfusion as a mode of T. cruzi transmission in the United States is needed.

Objective: This study was performed to assess the electrocardiographic safety and pharmacokinetics of desloratadine in combination with the CYP3A4 inhibitor ketoconazole. Design: A randomised, placebo-controlled, third-party—blind, 2-way crossover study. Participants: 24 healthy volunteers (12 men, 12 women; age 19 to 50 years). Interventions: 7.5mg of desloratadine orally per day in combination with placebo or with 200mg of ketoconazole every 12 hours for 10 days. After a minimum 7-day washout period, participants received the alternative treatment. Main outcome measures: ECG parameters. Results: Comparable maximum corrected QT (QTc) intervals were observed after coadministration of desloratadine and placebo or ketoconazole (431 and 435 msec, respectively). The desloratadine/ketoconazole combination did not induce any statistically significant or clinically relevant changes in QTc, QT, PR or QRS intervals compared with desloratadine alone; ventricular rate was slightly slower when desloratadine was given with ketoconazole. At steady state, coadministration of ketoconazole resulted in no significant change in area under the desloratadine concentration-time curve (AUC) from 0 to 24 hours compared with desloratadine/placebo. Coadministration of desloratadine and ketoconazole resulted in a 1.3-fold increase in desloratadine maximum concentration (Cmax) that was not clinically relevant. The most common adverse event was headache, reported in 42 and 38% of individuals, respectively, after coadministration of desloratadine/placebo and desloratadine/ketoconazole. There were no reports of dizziness or syncope. Conclusion: Coadministration of desloratadine and ketoconazole was well tolerated and was associated with minimal increase in AUC and Cmax. The combination did not induce any clinically relevant electrocardiographic changes.

Recent studies have demonstrated a decline in the use of osteopathic manipulative treatment (OMT) by osteopathic physicians, reflecting a trend that may begin in medical school. The authors used a questionnaire to examine the teaching and use of OMT in five rotations and the perceptions of 86 graduating osteopathic medical students of their experiences following their core manipulative medicine rotation. Most students indicated that they applied osteopathic principles sometimes (39.5%) or often (29.1%) during rotations. Forty-three percent of students rated their ability to apply osteopathic principles as average. The number of students who indicated that they rarely used OMT during their rotations was 31 (36.0%) for internal medicine, 21 (24.4%) for surgery, 23 (26.7%) for pediatrics, and 24 (27.9%) for obstetrics/gynecology. When asked why OMT was not used during a rotation, 47.2% of respondents cited time constraints, and 21.7% stated that their attending physicians discouraged the use of OMT. These results demonstrate a distinction between students' perceived level of osteopathic principles and skills and their application during clinical rotations.

Calcium-sensitive potassium (KCa) channels play a critical role in mediating perinatal pulmonary vasodilation. Because infants with persistent pulmonary hypertension of the newborn (PPHN) have blunted vasodilator responses to birth-related stimuli, we hypothesized that lung KCachannel gene expression is decreased in PPHN. To test this hypothesis, we measured KCa channel gene expression in distal lung homogenates from both fetal lambs with severe pulmonary hypertension caused by prolonged compression of the ductus arteriosus and age-matched, sham-operated animals (controls). After at least 9 days of compression of the ductus arteriosus, fetal lambs were killed. To determine lung KCa channel mRNA levels, primers were designed against the known sequence of the KCa channel and used in semiquantitative RT-PCR, with lung 18S rRNA content as an internal control. Compared to that in control lambs, lung KCa channel mRNA content in the PPHN group was reduced by 26 ± 6% ( P < 0.02), whereas lung voltage-gated K+ 2.1 mRNA content was unchanged. We conclude that lung KCa channel mRNA expression is decreased in an ovine model of PPHN. Decreased KCa channel gene expression may contribute to the abnormal pulmonary vascular reactivity associated with PPHN.

Objective We assessed the pharmacokinetics and tolerability of 5 mg loratadine syrup (1 mg/mL) in children aged 2 to 5 years. Methods Two studies were undertaken. A single-dose, open-label bioavailability study was performed to characterize the pharmacokinetic profiles of loratadine and its metabolite desloratadine. Plasma concentrations of loratadine and desloratadine were determined at 0, 1, 2, 4, 8, 12, 24, 48, and 72 hours after a single administration of 5 mg loratadine syrup to 18 healthy children (11 male, 7 female; 12 black, 5 white, 1 other; mean age ±SD, 3.8 ± 1.1 years; mean weight ± SD, 17.4 ± 4.4 kg) In addition, a randomized, doubleblind, placebo-controlled, parallel-group study was performed to assess the tolerability of 5 mg loratadine syrup after multiple doses. Loratadine (n = 60) or placebo (n = 61) was given once daily for 15 days to children with a history of allergic rhinitis or chronic idiopathic urticaria. In the loratadine group, 27 boys and 33 girls (52 white, 8 black) were enrolled, with a mean age ± SD of 3.67 ±1.13 years and a mean weight ± SD of 17.2 ±3.8 kg. In the placebo group, 27 boys and 34 girls (53 white, 7 black, 1 Asian) were enrolled, with a mean age ± SD of 3.52 ± 1.12 years and a mean weight ± SD of 17.3 ± 2.9 kg. Tolerability was assessed based on electrocardiographic results, occurrence of adverse events, changes in vital signs, and results of laboratory tests and physical examinations. Results: The peak plasma concentrations of loratadine and desloratadine were 7.78 and 5.09 ng/mL, respectively, observed 1.17 and 2.33 hours after administration of loratadine; the areas under the plasma concentration-time curve to the last quantifiable time point for loratadine and desloratadine were 16.7 and 87.2 ng·h/mL, respectively. Single and multiple doses were well tolerated, with no adverse events occurring with greater frequency after multiple doses of loratadine than after placebo. Electrocardiographic parameters were not altered by loratadine compared with placebo. There were no clinically meaningful changes in other tolerabihty assessments. Conclusion Loratadine was well tolerated in this small, selected group of children aged 2 to 5 years at a dose providing exposure similar to that with the adult dose (ie, 10 mg once daily).

To examine the combined effects of image resolution and display luminance on observer performance for detection of abnormalities depicted on posteroanterior chest radiographs.A total of 529 radiographs were displayed on a specially constructed view box at three luminance levels (770, 260, and 85 cd/m(2)) and three resolutions (100-microm, 200-microm, and 400-microm pixels). Each image was reviewed nine times by six radiologists who participated in this study. The abnormalities included nodule, pneumothorax, interstitial disease, alveolar infiltrates, and rib fracture. Negative (normal) radiographs were also included.Receiver operating characteristic curves indicated that the effect of image luminance was greater than that of resolution. The detection of pneumothorax, interstitial disease, and rib fracture showed statistically significant differences (P. 05) due to luminance. The detection of pneumothorax was the only abnormality with a statistically significant difference due to resolution. There was no evidence that luminance was related to image resolution for any of the abnormalities.At a resolution of 400-microm pixels or higher across the field of view and a luminance of 260 cd/m(2) or more, primary diagnosis with posteroanterior chest radiographs is not likely to be affected by the quality of display.

Background: Persistent postoperative dysphagia occurs in up to 24% of patients who undergo a laparoscopic Nissen fundoplication for reflux disease [7]. We hypothesized that patient history, pH testing, and esophageal manometry could be used to preoperatively identify patients at risk for this complication. Methods: Of 156 laparoscopic Nissen fundoplications performed over a 27-month period, we identified 19 patients (12%) who suffered from postoperative dysphagia longer than 3 months. The presenting complaint of preoperative swallowing difficulty was noted as was the presence of a known esophageal stricture. Preoperative pH testing and esophageal manometry were performed for all subjects. We compared the following parameters to an age and gender-matched control group: history of esophageal stricture, presence of preoperative dysphagia, DeMeester reflux score, upper esophageal sphincter pressure and relaxation, esophageal body motility, location of respiratory inversion point, and lower esophageal sphincter length, resting pressure, and relaxation. Data were compared via t-test and Fisher's exact test. Results: Patients who presented before surgery with complaints of difficulty swallowing were more likely to suffer from postoperative dysphagia (p= 0.029). Incidence of stricture, DeMeester score, and manometric measurements did not differ between the dysphagia and control groups (p > 0.05 for all parameters). Conclusions: Although preoperative studies are not helpful in identifying patients at risk for persistent dysphagia after laparoscopic Nissen fundoplication, patients presenting with the preoperative complaint of difficulty swallowing are at increased risk for this complication.

The dose proportionality of lubeluzole, a drug in clinical development for the treatment of acute ischemic stroke, was evaluated in a Phase I, single-center, open-label, randomized-dosing-sequence, three-way crossover clinical trial in 12 healthy adults. An equal number of male and female volunteers were enrolled in the trial, with a mean weight (+/- SD) of 73.2 +/- 11.9 kg, mean height (+/- SD) of 66.8 +/- 4.6 inches, and a mean age of 36.1 +/- 5.2 years. Subjects received intravenous infusions of 5 (A), 10 (B), and 15 mg (C) of lubeluzole over 1 hour on three separate occasions, with a minimum washout period of 2 weeks. The treatment sequences were A-B-C; A-C-B; B-A-C; B-C-A; C-A-B; and C-B-A. One male and one female were assigned to each sequence. After the 5-, 10-, and 15-mg doses, maximum concentration (Cmax) was 58.1, 113, and 138 microg/L, respectively, and the area under the curve from 0 to (AUC(0-infinity)) was 771, 1384, and 2025 microg x h/L. There were no statistically significant differences among the groups in mean terminal half-life, steady-state volume of distribution, total plasma clearance, or dose-normalized AUC(0-infinity). Dose-normalized values of Cmax differed significantly between the groups. No serious adverse events were reported, and no changes were observed in cardiac function, as judged by the QT(c) interval. The pharmacokinetics of lubeluzole appear to be linear at intravenous infusion doses of 5, 10, and 15 mg, and these doses are well tolerated by healthy adults.

Sensitive and reproducible assessments of hypothalamic-pituitary-adrenal (HPA) axis function were used to assess the systemic exposure and tolerability of mometasone furoate aqueous nasal spray (MFNS) in 96 children aged 3 to 12 years with allergic rhinitis. In the first phase of the study, older children (aged 6 to 12 years) received MFNS at 50, 100, or 200 micrograms or placebo once daily for 7 days, and plasma cortisol concentrations were measured by radioimmunoassay before and after treatment. Plasma cortisol concentrations were not statistically significantly different from baseline values on day 7 or day 8 (1 day after treatment was stopped). Also, the mean plasma cortisol and 24-hour urinary free-cortisol concentrations of the MFNS-treated and placebo groups were not statistically significantly different. Additionally, mometasone furoate was undetectable in almost all plasma samples collected at 0.5, 1, and 2 hours after dosing on days 1 and 7. Because these findings indicated that MFNS could be safely administered to patients aged 6 to 12 years, a more rigorous assessment was conducted in younger patients (aged 3 to 5 years). The younger patients also received MFNS at 50, 100, or 200 micrograms or placebo once daily, but for a longer duration (14 days). HPA axis function was determined by the response to cosyntropin stimulation on the final day of treatment. The younger patients demonstrated a normal cortisol response to cosyntropin stimulation on day 14; that is, all the patients had an increase in plasma cortisol concentration of at least 7 micrograms/dL to at least 18 micrograms/dL. Mean plasma cortisol concentrations for the MFNS-treated groups were not statistically significantly different from the mean concentration for the placebo group, either before or after cosyntropin stimulation. MFNS was also found to be well tolerated by both the younger and older children, with headache the most frequently reported adverse event in both the placebo- and MFNS-treated groups. No clinically relevant changes in the results of physical examinations, clinical laboratory determinations, or electrocardiography were noted. These results indicate that the intranasal administration of up to 200 micrograms of MFNS once daily for up to 14 days in children aged 3 to 12 years who have allergic rhinitis is well tolerated and does not result in clinically relevant systemic exposure.

Background: Bloodwarmers, mandatory for use in trauma resuscitation, are currently limited to a maximum temperature of 42°C by the American Association of Blood Banks. Using newly available inline microwave bloodwarming technology, we sought to identify the maximal temperature to which blood may be safely heated. Methods: Using an inline microwave bloodwarmer, we warmed refrigerated packed red blood cells to settings ranging from Off to 60°C. We evaluated heated blood for changes in red cell structure and function by measuring hemoglobin/hematocrit, potassium, lactate dehydrogenase, plasma hemoglobin, blood smear, osmotic fragility, Po 2 giving 50% O 2 saturation, and hemoglobin electrophoresis. Results: Measures of hemolysis showed no increase above control until temperatures of 51 to 53°C were achieved (p < 0.05). Red cell size remained unaffected until temperatures of 53°C were achieved (p < 0.05). Osmotic fragility was not elevated until 60°C (p < 0.05). PO 2 giving 50% O 2 saturation was low for all samples. Hemoglobin electrophoresis remained unchanged at all temperature settings. Conclusion: An inline microwave bloodwarmer may be used to heat blood safely to 49°C. Blood warmed to this temperature may significantly increase the amount of heat returned to the hypothermic trauma patient.

HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes.Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates.Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥ 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms.This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.

Background Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking. Methods The HIV Prevention Trials Network 057 protocol was a phase 1, open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate (TDF) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no infant dosing; no maternal dosing/infant 4 mg/kg doses on days 0, 3, and 5; maternal 900 mg doses/infant 6 mg/kg doses on days 0, 3, and 5; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses. Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants. Plasma, amniotic fluid, and breast milk tenofovir concentrations were determined by liquid chromatographic-tandem mass spectrometric assay. The pharmacokinetic target was for infant tenofovir concentration throughout the first week of life to exceed 50 ng/mL, the median trough tenofovir concentration in adults receiving standard chronic TDF dosing. Results One hundred twenty-two mother-infant pairs from Malawi and Brazil were studied. Tenofovir exposure in mothers receiving 600 and 900 mg exceeded that in nonpregnant adults receiving standard 300 mg doses. Tenofovir elimination in the infants was equivalent to that in older children and adults, and trough tenofovir plasma concentrations exceeded 50 ng/mL in 74%-97% of infants receiving daily dosing. Conclusions A TDF dosing regimen of 600 mg during labor and daily infant doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL throughout the first week of life and should be used in the studies of TDF efficacy for HIV prevention of mother-to-child transmission and early infant treatment.

Patients with cystic fibrosis (CF) of the same age differ significantly in their degree of pulmonary disease. Based on preliminary observations, we postulated that the activity of my-eloperoxidase would be significantly increased in patients with greater structural lung damage than in those with less lung damage. Acid extracts of weighed sputum samples were assayed for lactoferrin concentrations by ELISA. Activities of peroxidase, cathepsin G, and elastase (with and without proteinase 3) were determined by kinetic analysis using chromogenic substrates. The patients were divided into quartiles based on their Brasfield chest-radiograph score. Patients in the first quartile (least amount of structural lung abnormality) were compared to those in the fourth quartile. The concentration of lactoferrin, a specific (secondary) granule protein of neutrophils, did not differ between the two patient groups. However, the activities of the neutrophil primary granule proteins, peroxidase, elastase, and elastase plus proteinase 3, were significantly elevated in the group with the most structural lung abnormality. Sputum albumin concentration was used to estimate leakages of plasma proteins into the airways. Peroxidase activity, but not the activity of cathepsin G, of elastase, or of elastase plus proteinase 3, correlated significantly with albuminig sputum in both quartile groups. To confirm the association of sputum peroxidase activity with differences in lung structure and to test its correlation with lung function, spirometry was performed in a second group of patients during the week prior to the time of sputum sampling. In this second group, increased sputum peroxidase activity was associated with worse Brasfield scores and with decreased percent-predicted forced expiratory volume in 1 sec. Lactoferrin concentration again did not differ between the groups. Bacterial factors also did not differ. The results indicate that the degree of lung damage in patients with CF was more closely related to sputum peroxidase activity than to age, gender, CFTR genotype, or sputum bacterial parameters. Further study is required to determine whether or not peroxidase activity in the airway causes this lung damage. © 1995 Wiley-Liss, Inc.