Anal fistula plug: a prospective evaluation of success, continence and quality of life in the treatment of complex fistulae.

AIM: Curing complex anal fistula without compromising continence can be extremely challenging. This study investigated the healing rate, continence and quality of life of patients after treatment of complex anal fistula of cryptoglandular origin with a bioprosthetic plug. METHOD: Consecutive patients were prospectively followed in four referral centres. Following seton conditioning, a bioprosthetic plug was inserted into the fistula and sutured to the anal sphincter. Clinical evaluation was performed at 10 days, 6 weeks and 6 months after surgery, and was completed by telephone interviews. Anal continence and quality of life were evaluated using the Fecal Incontinence Score Index and the Short Form-36 Health Survey, version 2 (SF-36 v2) questionnaire. RESULTS: Forty-six patients presenting with a complex anal fistula and a median of three previous fistula surgeries were included. The 6-month recurrence rate was 30.7% (95% CI: 15.9-42.8%), increasing to 48.0% (95% CI: 30.6-61.1%) after 2 years. Follow up was continued for a median of 68.1 months, and 26 (56.5%) recurrences were identified. Anal continence improved from a median of 19 points to 12 points at 6 months of follow up (P = 0.008). Quality of life markedly improved in all scales. The physical summary score increased from 47.2 to 56.2 (P < 0.001), and the mental summary score increased from 48.5 to 55.3 (P = 0.013). CONCLUSION: The bioprosthetic fistula plug demonstrated a healing rate close to 50% in complex cryptoglandular fistula. Also, it markedly improved anal continence and quality of life. These data support the use of a bioprosthetic plug as first-line therapy for complex fistula instead of more aggressive and potentially debilitating surgical options.

Quantification of Rare Earth Elements in the Parts Per Million Range: A Novel Approach in the Application of Laser-Induced Breakdown Spectroscopy.

This work extends a previous percentage level concentration study of the optical emission spectra for six rare earth elements, europium (Eu), gadolinium (Gd), lanthanum (La), praseodymium (Pr), neodymium (Nd), and samarium (Sm), along with the transition metal, yttrium (Y) using laser-induced breakdown spectroscopy (LIBS). The concentration of these six rare earth elements and yttrium has been attempted for the first time systematically down to parts per million (ppm) concentration levels ranging from 30 to 300 ppm. The authors have developed multivariate models for each element capable of predicting concentration with acceptable to excellent levels of accuracy. Additionally, partial least squares regression coefficients were used to identify key spectral features able to be used in this lower concentration regime. This study has demonstrated that it is conceivable to quantify the six rare earth elements along with yttrium at low concentrations in the parts per million levels.

Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND & AIMS: Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. METHODS: Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n=138) or 20 mg omeprazole twice daily (n=70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. RESULTS: Histologic assessment of 33,658 biopsies showed no significant difference (P> .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. CONCLUSIONS: No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.

Phylogenetic analysis of Hepatozoon species (Apicomplexa: Adeleorina) infecting frogs of Nova Scotia, Canada, determined by ITS-1 sequences.

Species of Hepatozoon are apicomplexan parasites infecting tetrapod vertebrates and hematophagous arthropods. Two species, Hepatozoon catesbianae and Hepatozoon clamatae, have been described inhabiting the erythrocytes of bullfrogs and green frogs. A number of characteristics typically used to distinguish between members of this genus are shared between these 2 species, prompting speculation as to whether or not these organisms are in fact distinct species. To test the species distinction, bullfrogs and green frogs were captured at various sites across Nova Scotia, blood samples were collected, and DNA was extracted from samples containing parasites. The internal transcribed spacer 1 (ITS-1) from geographically diverse samples of both species was amplified by PCR, sequenced, and analyzed. ITS-1 sequences from the 2 species revealed single-nucleotide polymorphisms at 6 sites. Phylogenetic analysis of these molecular data and cytopathological features place isolates of each species in separate monophyletic groups. Comparison of the ITS-1 sequences between isolates from Nova Scotia and Ontario revealed that ITS-1 sequences of H. catesbianae from a previous study were mischaracterized as being those of H. clamatae. Phylogenetic data based on molecular variation and cytopathological features from this study provide the strongest evidence to date supporting the distinction between these 2 species.

Honey bee-collected pollen in agro-ecosystems reveals diet diversity, diet quality, and pesticide exposure.

European honey bees Apis mellifera are important commercial pollinators that have suffered greater than normal overwintering losses since 2007 in North America and Europe. Contributing factors likely include a combination of parasites, pesticides, and poor nutrition. We examined diet diversity, diet nutritional quality, and pesticides in honey bee-collected pollen from commercial colonies in the Canadian Maritime Provinces in spring and summer 2011. We sampled pollen collected by honey bees at colonies in four site types: apple orchards, blueberry fields, cranberry bogs, and fallow fields. Proportion of honey bee-collected pollen from crop versus noncrop flowers was high in apple, very low in blueberry, and low in cranberry sites. Pollen nutritional value tended to be relatively good from apple and cranberry sites and poor from blueberry and fallow sites. Floral surveys ranked, from highest to lowest in diversity, fallow, cranberry, apple, and blueberry sites. Pesticide diversity in honey bee-collected pollen was high from apple and blueberry sites and low from cranberry and fallow sites. Four different neonicotinoid pesticides were detected, but neither these nor any other pesticides were at or above LD50 levels. Pollen hazard quotients were highest in apple and blueberry sites and lowest in fallow sites. Pollen hazard quotients were also negatively correlated with the number of flower taxa detected in surveys. Results reveal differences among site types in diet diversity, diet quality, and pesticide exposure that are informative for improving honey bee and land agro-ecosystem management.

Accuracy of thin section magnetic resonance using phased-array pelvic coil in predicting the T-staging of rectal cancer.

Magnetic resonance (MR) imaging may contribute to staging rectal cancer and inform the decision regarding administration of pre-operative radiotherapy. The accuracy of MR has been debated. The aim of the present study was to determine the accuracy of thin section T2-weighted MR images in rectal cancer patients. MR results were compared with histological assessment of resection specimens. Over a 2-year period, 42 patients were studied. Histological staging was pT2 n = 13, pT3 n = 25 and pT4 n = 4. MR diagnostic accuracy was 74%. MR sensitivity and specificity was 62% and 79% for pT2 lesions, 84% and 59% for pT3 lesions and 50% and 76% for pT4 lesions. Estimation of tumour penetration by thin section MR imaging of rectal cancers using pelvic phased-array coil has moderate diagnostic accuracy. The limitations of MR should be acknowledged when selecting rectal cancer patients for pre-operative radiotherapy.

Considerations About Pollen Used for the Production of Allergen Extracts.

Pollen is a biological product obtained to manufacture tree, weed, and grass allergen extracts, used to diagnose and treat allergies. Genetic and environmental factors affect the composition of pollen, e.g., the plant varieties from which pollen are obtained, weather, and levels of air pollution during plant growth. Therefore, appropriate guidelines and training of personnel to perform the activities associated with pollen are essential to produce appropriate allergen extracts. Various regulatory institutions, which vary in different countries, including the Food and Drug Administration (FDA) in the USA, control how such products should be produced. For example, the FDA regulates the manufacturing of pollen extracts but not the quality of the pollen used to prepare them, relying on each manufacturer to set its own standards to do so. To the contrary, European regulatory agencies, including the European Medicines Agency, control both the quality of the pollen and the manufacturing process to produce pollen extracts. Regulatory agencies, allergen manufacturers, scientific institutions, and pollen collection entities should collaborate to develop and implement guidelines appropriate for worldwide use for both the collection and processing of pollen raw materials. This article provides an overview of the subject of pollen for use in allergen extracts.

Protective effect of flunarizine and nifedipine alone and in combination with anticonvulsant drugs against PTZ-induced seizures in mice.

The anticonvulsant effect of flunarizine has been compared to that of nifedipine in the pentylenetetrazole (PTZ)-induced seizure incidence/latency test and the PTZ seizure threshold test in mice. Nifedipine was found to have anticonvulsant activity in both models but flunarizine only had an anticonvulsant effect in the PTZ seizure incidence/latency test. Interactions with commonly used anti-epileptic drugs were also examined. In both models, the anticonvulsant effects of small doses or carbamazepine and phenytoin were enhanced by flunarizine and the effects of small doses of ethosuximide were enhanced by nifedipine. The effects of large doses of the anti-epileptic drugs were not further enhanced by either flunarizine or nifedipine. It is possible that these findings in mice are relevant to the variability of the responses to calcium antagonists as add-on therapy for epilepsy in man.

Silver(I) carboxylates: versatile inorganic analogs of carboxylic acids for supramolecular network formation.

Dimeric motifs formed by silver(I) carboxylates, illustrated here by the unit Ag2(CF3CO2)2, resemble the well known dimerization of carboxylic acids, i.e. 'H2(RCO2)2', but exhibit greater flexibility, while permitting further elaboration into neutral coordination networks through linkage of the silver centres via ditopic ligands.

A complete proton and carbon-13 NMR analysis of fluocinonide, a fluorinated corticosteroid.

This paper presents a complete analysis of the proton and carbon-13 NMR spectra of 21-acetoxy-6 alpha,9-difluoro-11 beta-hydroxy-16 alpha,17-(1-methylethylidene) bis-(oxy) pregna-1,4-diene-3,20-dione, a potent anti-inflammatory fluorosteroid. The 300 MHz proton spectrum was analyzed using a combination of the two-dimensional homonuclear chemical shift correlation (COSY) technique and one-dimensional NOE difference spectra. Exact coupling constants and chemical shifts were obtained by spectral simulation and iteration. The carbon-13 spectrum was assigned from the proton spectrum via a two-dimensional heteronuclear chemical shift experiment, and long-range fluorine-proton couplings were confirmed by a fully coupled heteronuclear COSY-type experiment.

Isolation and structure elucidation of two new calpain inhibitors from Streptomyces griseus.

Two new peptides, a diketopiperazine of N-methyltyrosine (1) and a tetrapeptide containing N-methyltyrosine (2), were isolated from an actinomycete strain Streptomyces griseus. These compounds inhibit the enzyme calpain in the micromolar range and were characterized on the basis of spectroscopic analysis, amino acid analysis and sequencing. The structure of the tetrapeptide N-methyltyrosyl-N-methyltyrosyl-leucyl-alanine (2), was also confirmed by total synthesis.

Frequent deliberate self-harm: repetition, suicide and cost after three or more years.

This is a follow-up study of 44 patients who were admitted to the Royal Infirmary of Edinburgh after frequent deliberate self-harm (defined as three or more episodes of deliberate self-harm within one week) at least once between 1982 and 1987. Forty-two patients (95%) were traced after a minimum of three years (range 3yr 1 mo 8yr 9mo). Thirty eight patients were known to have repeated self-harm an average of 13 times during the follow-up. Only two patients had died, one of these by probable suicide. The average cost solely attributable to the in-patient accommodation and psychiatric assessment of this group during follow-up was 34,036.60 pounds (1986-87 prices).

Missing driver in the Sun-Earth connection from energetic electron precipitation impacts mesospheric ozone.

Energetic electron precipitation (EEP) from the Earth's outer radiation belt continuously affects the chemical composition of the polar mesosphere. EEP can contribute to catalytic ozone loss in the mesosphere through ionization and enhanced production of odd hydrogen. However, the long-term mesospheric ozone variability caused by EEP has not been quantified or confirmed to date. Here we show, using observations from three different satellite instruments, that EEP events strongly affect ozone at 60-80 km, leading to extremely large (up to 90%) short-term ozone depletion. This impact is comparable to that of large, but much less frequent, solar proton events. On solar cycle timescales, we find that EEP causes ozone variations of up to 34% at 70-80 km. With such a magnitude, it is reasonable to suspect that EEP could be an important part of solar influence on the atmosphere and climate system.

Electrocardiographic abnormalities and uremic cardiomyopathy.

BACKGROUND: Progressive renal disease is associated with an increased risk of cardiovascular death, specifically sudden death. We investigated the link between uremic cardiomyopathy, QT interval and dispersal, and arrhythmias (by ambulatory ECG monitoring) in patients at different stages of progressive renal disease. METHODS: In a cross-sectional study we investigated 296 patients with nondiabetic renal disease (53 transplant recipients, 55 hemodialysis patients, and 188 throughout the range of chronic renal failure). Patients underwent echocardiography, ECG, and ambulatory blood pressure and ECG monitoring. RESULTS: Left ventricular mass was increased from the earliest stages of renal disease (near-normal renal function), the predominant pattern being eccentric left ventricular hypertrophy (LVH). There was a progressive increase in LVH with loss of renal function, so that more than 80% of patients on renal replacement therapy have LVH, the dominant pattern being concentric LVH. The prevalence of diastolic dysfunction increased in parallel with changes in left ventricular mass but systolic dysfunction and ventricular dilatation did not. Increased QT interval and QT dispersal were associated with poor renal function (maximal in dialysis patients), and were linked to LVH and other echocardiographic abnormalities. Arrhythmias were uncommon on ambulatory recording but were more common with poor renal function, in the presence of uremic cardiomyopathy, and increased QT interval and dispersal. CONCLUSION: LVH is present from the earliest stages of progressive renal disease. This, and other forms of uremic cardiomyopathy, is linked to increased QT interval and dispersal, and with minor rhythm abnormalities, providing a link with the high risk of sudden death in this population.

Is there a delay in the onset of the antidepressant effect of electroconvulsive therapy?

The severity of depression in 11 drug-free unipolar patients diagnosed with definite major depressive disorder was assessed using the Hamilton Rating Scale for Depression during a course (5-10 treatments) of bilateral electroconvulsive therapy (ECT). The degree of improvement after three treatments of ECT was six times greater than the improvement that occurred over the remainder of the course. Although depressed patients who recover with ECT require repeated treatments, the treatments early in a course of ECT can have marked antidepressant effect.