Evaluation of the frequency and factors predictive of hernia incarceration following transjugular intrahepatic portosystemic shunt placement.

AIM: To examine the frequency and predictive factors for bowel incarceration following transjugular intrahepatic portosystemic shunts (TIPS) placement to treat refractory cirrhosis-induced ascites. MATERIALS AND METHODS: Ninety-nine patients with known hernias at the time of TIPS placement were identified. Their electronic medical records were reviewed and pertinent pre-procedural, procedural, and outcome variables were recorded. Patients were divided between those that suffered incarceration (study group) and a control group of those with a hernia who did not suffer incarceration. RESULTS: Twelve of the 99 patients (12.1%) suffered hernia incarceration, of which seven (7.1%) suffered incarceration in the first 90 days. One patient who suffered incarceration ultimately died from complications of the incarceration. When comparing all patients who suffered incarceration to controls, incarceration patients were found to have significantly higher albumin levels (mean 3.13 versus 2.73, p=0.02). When just considering those who had incarcerations in the first 90 days to controls, incarceration patients were less likely to have improvement in their ascites (p=0.04). CONCLUSIONS: Incarcerated hernias occur frequently after TIPS placement and can lead to significant morbidity and mortality. Clinicians should be aware of this complication and counsel patients on presenting symptoms prior to placement.

Mutational and biochemical findings in adults with persistent hypophosphatasemia.

A majority of adults with persistently low serum alkaline phosphatase values carry a pathogenic or likely pathogenic variant in the ALPL gene and also have elevated alkaline phosphatase substrate values in serum and urine. These adults may fall within the spectrum of the adult form of hypophosphatasia. INTRODUCTION: The primary objective of this study was to determine what proportion of adults with persistently low serum alkaline phosphatase values (hypophosphatasemia) harbor mutations in the ALPL gene or have elevated alkaline phosphatase (ALP) substrates. Some adults with persistent hypophosphatasemia share clinical and radiographic features with the adult form of hypophosphatasia (HPP). In HPP, ALPL mutations result in persistent hypophosphatasemia and ALP substrate accumulation in plasma (pyridoxal-5-phosphate (PLP)) and urine (phosphoethanolamine (PEA)). METHODS: Biochemical analyses, including serum ALP activity, bone-specific ALP, plasma PLP, and urine PEA, were performed in adults with persistent hypophosphatasemia. Mutational analyses were performed using PCR and Sanger sequencing methods. Gene variants were classified as pathogenic (P), likely pathogenic (LP), variants of uncertain significance (VUS), likely benign (LB), and benign (B). P and LP variants were further grouped as "Positive ALPL variants" and LB and B grouped as "Negative ALPL variants." RESULTS: Fifty subjects completed all mutational and biochemical analyses. Sixteen percent carried only Negative ALPL variants. Of the remaining 42 subjects, 67% were heterozygous for a P variant, 19% for an LP variant, and 14% for a VUS. Biochemical results were highly inter-correlated and consistent with the expected inverse relationship between ALP and its substrates. Subjects harboring Positive ALPL variants showed lower ALP and BSAP and higher PLP and PEA values compared with subjects harboring only Negative ALPL variants. Approximately half of all subjects harboring Positive ALPL variants or ALPL VUS showed elevations in plasma PLP, and three quarters showed elevations in urine PEA. CONCLUSION: Adults with persistent hypophosphatasemia frequently harbor ALPL mutations and have elevated ALP substrates. These adults may fall within the spectrum of the adult form of hypophosphatasia. Clinicians should take note of persistent hypophosphatasemia in their patients and be cautious in prescribing bisphosphonates when present.

Placental findings associated with maternal obesity at early pregnancy.

INTRODUCTION: Obesity during pregnancy is associated with a wide spectrum of maternal, fetal and neonatal complications. This study compared placental pathology in women with obesity and normal weight gravidas. MATERIALS AND METHODS: This is a retrospective case-control study. The sample was randomly selected from a total of 1000 deliveries of largely Caucasian population in a single institution, recruited for the study of sleep disordered breathing, where the placenta is submitted for pathological examination for clinical indications based on national guidelines. Cases (Body mass index - BMI ≥ 30 kg/m(2); n = 47) and controls (BMI < 25 kg/m(2), n = 45) were selected based on BMI obtained from the first prenatal visit. Placental pathology, clinical parameters and limited outcomes were extracted from medical records. Placental weight range was defined as small for gestational age (SGA) if < 10th percentile, large for gestational age (LGA) if > 90th percentile. RESULTS: Mean BMI was 36.2 ± 5.5 in the group with obesity and 21.7 ± 1.9 in the control group (p < 0.01). There was a significantly higher prevalence of diabetes in cases compared to controls (14/47 vs. 3/45, p = 0.006) while preterm birth was significantly higher in the control group (9/47 vs. 19/46, p = 0.02). There were more LGA placentas in cases versus controls (12/47 vs. 2/46, p = 0.007; even after adjusting for diabetes). More histological features of inflammation, marginal insertion of the umbilical cord and intervillous thrombi in the parenchyma were also noted in the case group. CONCLUSIONS: Results from the current study suggest that maternal obesity measured at early pregnancy may have effects on both placental implantation and growth, and further exacerbate the hypercoagulable state in placenta.

Cholestatic pregnancy is associated with reduced placental 11ßHSD2 expression.

INTRODUCTION: Intrahepatic Cholestasis of Pregnancy (ICP) is associated with an increased risk of fetal morbidity and mortality and is characterised by elevated bile acids in the maternal and fetal compartments. Bile acids have been shown to attenuate renal 11ßHSD2 expression and, given the protective role of placental 11ßHSD2 in preventing fetal exposure to excessive maternal cortisol, we aimed to establish whether raised serum bile acids in ICP influence placental 11ßHSD2 expression. METHODS: Placental tissue from human and murine cholestatic pregnancy was evaluated for changes in 11ßHSD2 mRNA expression compared to uncomplicated pregnancy using quantitative PCR. Parallel in vitro studies were performed using BeWo choriocarcinoma cells to assess the effect of different bile acid species on 11ßHSD2 gene expression and whether concurrent UDCA administration can reverse any bile acid induced changes. RESULTS: Placental 11ßHSD2 mRNA expression was reduced in human and murine cholestatic pregnancy. In BeWo cells, treatment with the primary bile acid CDCA resulted in reduced 11ßHSD2 gene expression, while treatment with other primary bile acids had no significant effect. Furthermore, the tertiary bile acid UDCA, used in the treatment of ICP did not significantly affect 11ßHSD2 mRNA levels either alone, or when co-administered with CDCA. DISCUSSION: Under cholestatic conditions placental 11ßHSD2 mRNA is reduced. Studies in BeWo choriocarcinoma cells demonstrated that CDCA is likely to be the specific bile acid that mediates this effect. UDCA, the main bile acid used to treat cholestasis, did not reduce placental 11ßHSD2 expression, further supporting its use in the management of ICP.

Clinical manifestations of obstructive sleep apnoea in pregnancy: more than snoring and witnessed apnoeas.

Sleep disordered breathing and its symptoms have been associated with a multitude of fetal and maternal complications including gestational hypertensive disorders, gestational diabetes and possibly pre-term labour and other markers of alterations in fetal wellbeing. The disease remains underdiagnosed in the general population but likely also in pregnancy, mostly because providers do not appropriately screen for the disorder. Sleep disordered breathing may manifest differently in women, since women report more fatigue and less snoring than men do. This paper discusses typical presentations of sleep disordered breathing but also reports some less obvious presentations to help providers recognise those manifestations and screen for the disorder when warranted. Our case series describes patients with diagnoses such as chronic hypertension, pre-eclampsia, pulmonary hypertension, nocturnal asthma and panic attacks, who were diagnosed with sleep disordered breathing and offered treatment with CPAP during pregnancy.

Age and long-term protective immunity in dogs and cats.

Vaccination can provide an immune response that is similar in duration to that following a natural infection. In general, adaptive immunity to viruses develops earliest and is highly effective. Such anti-viral immune responses often result in the development of sterile immunity and the duration of immunity (DOI) is often lifelong. In contrast, adaptive immunity to bacteria, fungi or parasites develops more slowly and the DOI is generally short compared with most systemic viral infections. Sterile immunity to these infectious agents is less commonly engendered. Old dogs and cats rarely die from vaccine-preventable infectious disease, especially when they have been vaccinated and immunized as young adults (i.e. between 16 weeks and 1 year of age). However, young animals do die, often because vaccines were either not given or not given at an appropriate age (e.g. too early in life in the presence of maternally derived antibody [MDA]). More animals need to be vaccinated to increase herd (population) immunity. The present study examines the DOI for core viral vaccines in dogs that had not been revaccinated for as long as 9 years. These animals had serum antibody to canine distemper virus (CDV), canine parvovirus type 2 (CPV-2) and canine adenovirus type-1 (CAV-1) at levels considered protective and when challenged with these viruses, the dogs resisted infection and/or disease. Thus, even a single dose of modified live virus (MLV) canine core vaccines (against CDV, cav-2 and cpv-2) or MLV feline core vaccines (against feline parvovirus [FPV], feline calicivirus [FCV] and feline herpesvirus [FHV]), when administered at 16 weeks or older, could provide long-term immunity in a very high percentage of animals, while also increasing herd immunity.

Three-year duration of immunity in dogs vaccinated with a canarypox-vectored recombinant canine distemper virus vaccine.

Two studies evaluated the duration of serologic response to the recombinant, canarypox-vectored canine distemper virus vaccine (Recombitek, Merial). Serologic duration of immunity was shown to be at least 36 months. Thus, Recombitek provides protection when administered less frequently than the manufacturer's label. After the initial vaccination protocol of two or more doses administered approximately 4 weeks apart, with the last dose given at 12 to 16 weeks of age or older, and re-vaccination at 1 year of age, Recombitek can confidently be readministered every 3 years with assurance of protection in immunocompetent dogs. This allows the vaccine to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force and others.

Three-year serologic immunity against canine parvovirus type 2 and canine adenovirus type 2 in dogs vaccinated with a canine combination vaccine.

A group of client-owned dogs and a group of dogs at a commercial kennel were evaluated for duration of antibody responses against canine parvovirus type 2 (CPV-2) and canine adenovirus type 1 (CAV-1) after receiving a combination vaccine containing recombinant canarypox-vectored canine distemper virus (CDV) and modified-live CPV-2, CAV-2, and canine parainfluenza virus, with (C6) or without (C4) two serovars of Leptospira (Recombitek C4 or C6, Merial). Duration of antibody, which correlates with protective immunity, was found to be at least 36 months in both groups. Recombitek combination vaccines can confidently be given every 3 years with assurance of protection in immunocompetent dogs against CPV-2 and CAV-1 as well as CDV. This allows this combination vaccine, like other, similar modified- live virus combination products containing CDV, CAV-2, and CPV-2, to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force.

Surfactant effects on alpha factors in full-scale wastewater aeration systems.

Aeration is an essential process in the majority of wastewater treatment processes, and accounts for the largest fraction of plant energy costs. Aeration systems can achieve wastewater oxygenation by shearing the surface (surface aerators) or releasing bubbles at the bottom of the tank (coarse- or fine-bubble aerators). Surfactants accumulate on gas-liquid interfaces and reduce mass transfer rates. This reduction in general is larger for fine-bubble aerators. This study was conducted to evaluate mass transfer effects on the characterization and specification of aeration systems in clean and process water conditions. Tests at different interfacial turbulence regimes were analysed, showing higher gas transfer depression for lower turbulence regimes. Higher turbulence regimes can offset contamination effects, at the expense of operating efficiency. This phenomenon is characteristic of surface aerators and coarse bubble diffusers and is here discussed. The results explain the variability of alpha factors measured at small scale, due to uncontrolled energy density. Results are also reported in dimensionless empirical correlations that describe mass transfer as a function of physiochemical and geometrical characteristics of the aeration process.

Effect of recombinant canine distemper vaccine on antibody titers in previously vaccinated dogs.

Two canine distemper virus (CDV) vaccine types are currently commercially available: modified-live virus (MLV) vaccines and a canarypox recombinant CDV (rCDV) vaccine (Recombitek, Merial). This study compared the ability of the rCDV vaccine and MLV vaccines to significantly enhance (boost) the antibody response of previously immunized adult and juvenile dogs. A significant (fourfold or greater) increase in titer occurred in significantly more dogs revaccinated with Recombitek C-4 or Recombitek C-6 than with the MLV-CDV vaccines. This study demonstrates that Recombitek, the only vaccine for dogs containing rCDV, is more likely to significantly boost the CDV antibody response in previously vaccinated dogs than are the MLV-CDV vaccines. Because rCDV vaccine can boost the antibody titer of dogs previously vaccinated with an MLV vaccine, it can and should be used when core vaccines are readministered.

Effect of vaccination with recombinant canine distemper virus vaccine immediately before exposure under shelter-like conditions.

Vaccination with modified-live virus (MLV) canine distemper virus (CDV) vaccine has historically been recommended for animals in high-risk environments because of the rapid onset of immunity following vaccination. Recombinant CDV (rCDV) vaccine was deemed a suitable alternative to MLV-CDV vaccination in pet dogs, but insufficient data precluded its use where CDV was a serious threat to puppies, such as in shelters, kennels, and pet stores. In this study, dogs experimentally challenged hours after a single dose of rCDV or MLV vaccine became sick but recovered, whereas unvaccinated dogs became sick and died. Dogs vaccinated with a single dose of rCDV or MLV vaccine 1 week before being experimentally challenged remained healthy and showed no clinical signs. Dogs given one dose of rCDV vaccine hours before being placed in a CDV-contaminated environment did not become sick. These findings support the hypothesis that rCDV vaccine has a similar time-to-immunity as MLV-CDV vaccines and can likewise protect dogs in high-risk environments after one dose.

Creating the patient safety mindset.

Two health care systems--Intermountain Health Care in Salt Lake City and Baptist Memorial Health Care in Memphis--have made patient safety an organization-wide priority, which has given both systems comprehensive cultures of safety.

Low molecular weight heparin versus unfractionated heparin in the colonoscopy peri-procedure period: a cost modeling study.

OBJECTIVE: The aim of this study was to compare the economic outcomes of peri-procedure anticoagulation approaches for elective colonoscopy. METHODS: Decision analysis was used to model the economic outcomes of five peri-procedure anticoagulation options: outpatient low molecular weight heparin (LMWH), inpatient unfractionated heparin infusion (UFHi), continuous warfarin (with probability of a repeat procedure using LMWH or UFHi), and discontinuation of anticoagulation therapy. The model's base-case scenario assumed drug therapy options for high-risk patients were equally effective in preventing a thromboembolic event (0.1% risk), with a higher probability for the no anticoagulation strategy (0.4%); event costs were based on published data and adjusted to 1997 dollars. Drug costs reflected 1997 average wholesale price. Medical costs for other variables were estimated based on local hospital charges. Indirect costs were not considered. Risk probabilities and LMWH drug cost were tested in sensitivity analysis. RESULTS: In the base-case scenario, costs for the options evaluated were $1436/patient, $1792/patient, $1848/patient, $2629/patient, and $5196/patient for no anticoagulation, continuous warfarin/repeat LMWH, LMWH as outpatient, continuous warfarin/repeat UFHi, and UFHi as inpatient respectively ($1997). Discontinuing anticoagulation was the least costly approach but involved the greatest thromboembolic risk. The cost of continued warfarin anticoagulation/repeat LMWH was minimally less than the LMWH option, but assumes 25% of patients would require a second procedure. The traditional approach (UFHi) requires an extended hospitalization and is the most costly option. Varying risk category or LMWH cost in sensitivity analysis had a negligible impact on overall costs. CONCLUSION: Within the model's assumptions, LMWH offers a novel, convenient, and economical solution to the problem of peri-procedure anticoagulation for elective colonoscopy.

Recent advances in the chemistry of spinosyns.

The spinosyns are a new class of fermentation-derived insect control agents that are effective against a variety of chewing insect pests. The successful introduction of spinosad into the agricultural marketplace represents an important milestone in the use of natural products for commercial pest control. The development of a natural product presents additional limitations relative to a synthetic material. While the latter affords some degree of control in building appropriate physical attributes such as photostability, a natural product, designed to function in a different environment, is often less suited for traditional spray applications. Despite its intrinsic photolability, spinosad is stable enough to perform under field conditions. In an effort to generate analogs with improved physical characteristics, we have developed a variety of conditions for selectively modifying different portions of the molecule, and we have discovered analogs with greater activity against a broader spectrum of pests. The inability to translate improved greenhouse activity to actual field conditions resulted in a detailed study of the effects of formulations and crystallinity on biological activity. Through this effort, measurably improved field performance of synthetic spinosyn analogs relative to the natural product have now been observed.

Your CEO. Are you short-staffed or short-sighted?

Hiring the right CEO is the board's most important job. You may want to look outside of the usual hierarchy for your next chief exec--but be sure you know what you want. And don't leave succession planning until you are left leaderless.

Natural selection.

Complementary and alternative medicine (CAM) is a consumer-driven mode of care whose time has come. As one expert puts it: "Your biggest risk is not getting involved, not finding out what patients are doing." Learn how to integrate CAM into your other services and how to get your physicians' support.

The humanity of palliative care.

Contrary to popular belief, palliative care is not just for dying patients. It's a comprehensive, compassionate system of caring for patients with painful, chronic conditions. A national program, the Center to Advance Palliative Care, maintains that this treatment option belongs in all U.S. hospitals.