Anti-tissue transglutaminase antibodies in the follow-up of adult coeliac disease

Background  The detection of auto antibodies directed against tissue transglutaminase (anti-tTG antibodies) has a well-established role in the diagnosis of coeliac disease, but the value of these antibodies in long-term follow-up is controversial.
Aims  To determine if serial anti-tTG antibody measurements could confirm adherence to a gluten-free diet (GFD) and identify patients at risk of disease complications.
Methods  In a 54-month cohort follow-up study, 182 adult patients were assessed. Data recorded included self-assessment of GFD adherence; anti-tTG antibody concentration and serum ferritin, vitamin B12 and folate. Where available, bone mineral density (BMD) and duodenal histology data were retrieved.
Results  Persistently elevated anti-tTG antibody levels were significantly associated with abnormal duodenal histology ( P  < 0.001), low ferritin ( P  < 0.01) and poor adherence to the GFD ( P  < 0.001). The specificity was >85% while the sensitivity was 39–60%. Anti-tTG antibody concentrations fell rapidly following successful initiation of a GFD, and maintenance of normalization identified those who continued to be adherent to the diet.
Conclusions  This study supports a strategy of using anti-tTG antibody concentrations to monitor newly diagnosed and established patients with coeliac disease, and to target dietetic intervention to reduce the risk of complication.     

From the brain to bad behaviour and back again: Neurocognitive and psychobiological mechanisms of driving while impaired by alcohol

Issues. Driving while impaired by alcohol (DWI) is responsible for substantial mortality and injury. Significant gaps in our understanding of DWI re‐offending, or recidivism, reduce our ability to practically assess recidivism probability and to match interventions to individual risk profiles. These shortcomings reflect the baffling heterogeneity in the DWI population and the limited focus of much existing DWI recidivism research to psychosocial, psychological and substance use correlates. Approach. This narrative review summarises the evidence for the contribution of neurocognitive and psychobiological mechanisms to DWI behaviour and recidivism. Given the nascent nature of this literature, insight into the putative contribution of these mechanisms to DWI is also drawn from other experimental literatures, particularly those on alcohol use disorders and cognitive and behavioural neuroscience. Key Findings. Alcohol‐related neurotoxicity and dysregulation of hypothalamic–pituitary–adrenal axis and serotonergic systems may underlie certain offender characteristics consistently correlated with heightened DWI risk, persistence and intervention resistance. Their markers are less vulnerable to sources of bias than subjective psychosocial indices and are more far‐reaching than alcohol abuse in explaining DWI behaviour and recidivism. Implications. The investigation of neurocognitive and psychobiological mechanisms in DWI research is a promising avenue for discerning clinically meaningful subgroups within the DWI population. This can lead to research and development in alternative assessment and more targeted intervention technologies. Conclusion. Multidimensional research in DWI and recidivism offers novel avenues for increasing road safety.[Brown TG, Ouimet MC, Nadeau L, Gianoulakis C, Lepage M, Tremblay J, Dongier M. From the brain to bad behaviour and back again: Neurocognitive and psychobiological mechanisms of driving while impaired by alcohol. Drug Alcohol Rev 2009;28:406–418]     

Methadone levels and neonatal withdrawal

The purpose of this study was to observe the effects of methadone exposure in utero, with special reference to maternal and neonatal methadone concentrations and neonatal withdrawal. Two groups of mother-infant pairs were studied. In the first group, serum methadone concentrations were determined in infants at 1, 6 and 24 h after delivery. In the second group, blood was obtained at 24, 48, 72 and 96 h after birth. There was no correlation between neonatal serum levels and the intensity of withdrawal symptoms. There was no relationship between maternal methadone dose at delivery or maternal serum levels and neonatal methadone levels. The results of this study may be complicated by the prenatal exposure of the neonates to other drugs of abuse apart from methadone.     

Follicle growth patterns and endocrinological abnormalities in infertile women with minor degrees of endometriosis

Summary. Eighteen patients whose only demonstrable cause of infertility was a minor degree of endometriosis and whose partners were normal, were investigated prospectively for one menstrual cycle using ultrasonography and endocrine profiles. Twelve cycles appeared to be normal. A luteinized unruptured follicle (LUF) occurred in two cycles and one patient had a follicular cyst. In a further two patients there was inadequate or abnormal folliculogenesis whilst in the last patient the follicle ruptured prematurely. This study describes the variety of endocrinological abnormalities found in women with mild endometriosis, and concludes that, in this series at least, there is a low frequency of LUF.     

Endocrine effects of 17 alpha-hydroxyprogesterone caproate during early pregnancy: a double-blind clinical trial

Summary. The clinical and endocrine effects of progestogen therapy in early pregnancy were investigated using a double-blind randomized trial in 64 patients who had a viable fetus at 6 weeks gestation and had an increased risk of miscarriage. The patients were randomly allocated to receive either 17 alpha-hydroxyprogesterone caproate or a placebo between 7 and 12 weeks gestation. Four fetal ultrasonographic variables and 17 maternal endocrine variables were studied in each woman. Only four maternal serum variables (17 alpha-hydroxyprogesterone, prolactin, thyroxin and thyroxin binding globulin) rose significantly. The serum progesterone levels in the hormone supplemented group were on average 20% higher than in the placebo group but the difference was not statistically significant. However, the relation between the progesterone levels and the fetal outcome was not clear. Therefore it is not advisable to prescribe 17-OHP-C during early pregnancy to prevent a miscarriage.     

The clinicopathological features, treatment and survival of gastric adenocarcinoma in Omani Arab patients

Background: Gastric carcinoma (GC) is the second most frequent cancer worldwide and the most common cancer in the Sultanate of Oman. The surgical and medical management of GC varies worldwide, and variable ethnic differences in clinicopathological features and survival have been observed. The aim of this work was to study clinicopathological features, management and survival trends of GC in Oman and to assess the impact of aggressive management trends on survival. Methods: A retrospective study of gastric adenocarcinoma cases, treated at three main hospitals in Oman over a 12‐year period, was undertaken. The study was divided into period I (1993–1998) and period II (1999–2004), based on the evolution of cancer services. Results: A population of 339 patients was included in the study (M : F ratio 1.9 : 1). GC was mainly a disease of elderly males with mean ages of 60.3 and 59.3 years for periods I and II, respectively. The most prevalent types of GC observed during periods I and II were distal (60.7% vs. 57.7%), ulcerating (64.3% vs. 63.7%) and intestinal (80.9% vs. 78.4%), with no significant differences between them. The main histopathology was adenocarcinoma with an increase in the signet cell variant (4% to 12.1%, P, 0.03) during period II. Advanced stages III and IV constituted 71.1% and 76.5% of all patients in periods I and II, respectively (P, 0.9). More D2 lymph node dissections and increased use of adjuvant chemo‐radiotherapy and palliative chemotherapy were noted during period II. Median survival time for the entire cohort was 12.3 months (95% CI 9.7–14.4) with a 5‐year overall survival rate of 16.5%. The 5‐year overall survival for periods I and II was 14% and 19% (P, 0.27), respectively. Conclusion: GC in Oman is seen predominantly in elderly males who display predominately distal, ulcerative lesions with an intestinal‐type histology. GC continues to present in advanced stages, with poor prognosis. This fact underscores the need for early diagnosis to achieve a better outcome. There is a need to employ early detection policies of gastric cancer in developing countires as aggressive treatment does not alter the outcome of advanced presentaion.     

Upper GI Bleeding in an Emergency Hospital: Etiology,Prognosis and Improved Survival by Endoscopic Hemostasis

Acute upper gastrointestinal bleeding (UGIB) is a frequent diagnosis prompting hospital admission or complicating another preexisting condition. This report examines the experience of an urban medical center in the utilization of endoscopy and endoscopic hemostasis in the diagnosis and management of UGIB over a four-year period. The first portion of this study examines 562 admissions to a single institution with UGIB. The most common causes of bleeding were acute gastric mucosal lesions (AGML), 24%; esophageal varices (EV), 22%; gastric ulcers, 19%; duodenal ulcers, 14%; Mallory-Weiss tears, 11%; and esophagitis, 3%. Nonoperative treatment was sufficient in the majority of patients (89.5%). Endoscopic therapy was utilized in 144 patients (26%), of whom 12 required a subsequent operation. Fifty-eight patients (10.5%) underwent surgery; however, emergent operations were required in only 2.5% of the patients. Factors correlating with mortality included shock at the time of admission (SBP < 80), transfusion requirements of > 5 U PRBC, and presence of EV (each p < 0.001). The second part of this study examines the effect of thrombogenic sclerotherapy on both short and long-term survival in 101 patients referred with bleeding esophageal varices. Alcoholic cirrhosis was responsible for the majority (88%) of EV, and most patient were Child's C classification (84%). In long-term follow-up, rebleeding was significantly reduced (p = 0.03) in patients compliant with follow-up sclerotherapy. A trend toward decreased mortality was noted in patients compliant with sclerotherapy and in those who avoided further alcohol usage.     

Incidence of ICD Lead Related Complications During Long-Term Follow-Up: Comparison of Epicardial and Endocardial Electrode Systems

The aim of this study was to evaluate the longterm stability of epicardial and endocardial lead systems for third-generation cardioverter defibrillators (ICDs) and to assess the usefulness of diagnostic tools. One hundred forty patients with 61 epicardial (43.6%) and 79 nonthoracotomy systems (56.4%) were followed for 2 5 ± 19 months. A total of 18 (12.9%) lead related complications were documented. Complications of epicardial systems were detected in 10 patients (16.4%) during a follow-up time of 36 ± 8 months: crinkling of patch electrodes in 6 patients (9.8%), insulation breakage of sensing electrodes in 2 patients (3.3%), and adapter defect in 2 patients (3.3%). Eight of the patients (10.1%) with transvenous-subcutaneous systems had lead related complications during a 13 ± 6 months follow-up: fracture of the subcutaneous patch lead in 2 patients (2.5%), dislodgment of the right ventricular lead in 2 patients (2.5%), dislodgment of the superior vena cava lead in 2 patients (2.5%), insulation breakage of sensing electrodes in 1 patient (1.3%), and connector defect in 1 patient (1.3%). There was no significant difference in the incidence of lead related complications between epicardial and endocardial systems (P > 0.05). Fractures, dislodgments, and crinklings were documented within the first 8 ± 5 months by regular chest X ray. Defects of insulation, adapter, or connector were detected 22 ± 10 months after implantation and were associated with delivery of multiple inappropriate ICD therapies. An operative lead revision was indicated for 4 epicardial (6.6%) and 6 endocardial (7.6%) lead systems. Conclusions: Endocardial lead systems offer a similar long-term stability as compared to epicardial had systems. Chest X ray is the most useful tool to detect lead fracture, dislodgment. and patch crinkling. Marker recordings or real-time electrograms have not been helpful in this series to identify patients with suspected lead defects prior to the experience of inappropriate ICD discharges.     

Increased human erythrocyte sodium-Iithium countertransport in hyperlipidaemic patients may indicate increased membrane lipid fluidity

Abstract. Erythrocyte sodium-lithium countertransport (SLC) activity, membrane fluidity, plasma trigly-ceride and cholesterol were measured in hyperlipidaemic patients and normal subjects. Fluidity was assessed by the fluorescence anisotropy (inversely related to fluidity) of the probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,4-trimethylammonium-3,5-hexatriene (TMA-DPH). In a second group of patients the maximum velocity (Vmax) and external sodium affinity constant (k_m) of SLC was also measured.
In the first group of patients, SLC activity was increased compared with the controls (0.279 ± 0.019 vs. 0.213 ± 0.013, P = 0.006) as was membrane fluidity in the deep hydrophobic regions (DPH anisotropy 0.211 ± 0.0007 vs. 0.215 ± 0.0011, P = 0.007). There was a strong correlation between SLC and DPH anisotropy (Rs= -0.72, P= < 0.001) which was due to the correlation between Vmax and DPH anisotropy (Rs=-0.90, P= < 0.001).
Increases in Vmax of SLC in hyperlipidaemic patients may be due to differences in lipid organisation in the deep hydrophobic regions of the membrane which may affect the turnover rate of the transporter.