The interactive role of mucosal T lymphocytes in intestinal growth, development and enteropathy

Abstract Over the past 15–20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten-sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function.     

PERCEPTIONS OF DRINKERS AND ABSTAINERS IN A SAMPLE OF SCOTTISH ADULTS

Following Davies and Stacey's investigation (1972, Teenagersand Alcohol, HMSO, London) into perceptions of drinking andabstaining among Scottish teenagers, this study extended theirgeneral method to an investigation of the perceptions of 239Scottish adults. Results showed that the stereotypes of theheavy drinker as ‘tough and rebellious’ and theabstainer as ‘weak and cissy’ persist into adulthood.Heavy drinkers were seen as low on ‘sociability’and ‘sexual attractiveness’ and abstainers wereseen as less ‘sociable’ than moderate drinkers.There was also some evidence of a ‘double standard’in perceptions of male and female drinking roles. Other findingsconcerning the effects on perceptions of subjects sex and drinkingbehaviour are compared to those reported in the earlier studyand implications for the treatment of alcohol problems are discussed.It is concluded that the dimensions described by Davies andStacey represent a relatively stable structure within futureresearch where fresh initiatives in alcohol education may belocated.     

A trial of relapse prevention with severely dependent male problem drinkers

Over the last two decades, relapse prevention has emerged as a major focus of the treatment of drug problems. Few studies have demonstrated any impact on generally high relapse rates. In this paper the outcome of a controlled trial of a relapse prevention programme with male problem drinkers (n=60) attending an Alcohol Treatment Unit is reported. Subjects who met the inclusion criteria were allocated to a relapse prevention (n=20) procedure or a discussion (n=20) or no-additional treatment (n=20) control procedure. Subjects were followed-up at 6 and 12 months by the first author. The relapse prevention programme was associated with significantly greater increases in pre- and post-treatment self-efficacy compared to the discussion control group and significantly greater probability of total abstinence than all controls over the first 6-month follow up. In addition, the relapse prevention programme was associated with significantly longer survival time to an initial lapse and relapse than the controls. At 12-month follow-up, treatment effects had been eroded. It was concluded that the relapse prevention programme was an effective treatment in the short term and that longer-term impact may require greater focus on maintenance factors, such as the individual's environment.     

Implantation of Active Can Implantable Defibrillators in the right Pectoral Region

Routinely the active can ICD is placed in the left side pectoral position, which theoretically gives optimal conditions for a low defibrillation threshold. Some patients, bowever, demand a right pectoral position, which possibly could result in a bigger defibrillation threshold. A right pectoral position was used in 3 of 85 active can ICDs implanted in our institution from 1994. the DFT was 12 J in two and 18 f in one patient. Thus, right pectoral implantation is feasible and offers an alternative approach in selected patients.     

A functional and clinical reinterpretation of human perineal neuromuscular anatomy: Application to sexual function and continence

Modern anatomical and surgical references illustrate perineal muscles all innervated by branches of the pudendal nerve but still organized into anatomically distinct urogenital and anal triangles with muscles inserting onto a central perineal body. However, these conflict with the anatomy commonly encountered during dissection. We used dissections of 43 human cadavers to characterize the anatomical organization of the human perineum and compare our findings to standard references. We found bulbospongiosus and the superficial portion of the external anal sphincter (EAS) were continuous anatomically with a common innervation in 92.3% of specimens. The superficial transverse perineal muscle inserted anterior and lateral to the midline, interdigitating with bulbospongiosus. The three EAS subdivisions were anatomically discontinuous. Additionally, in 89.2% of our sample the inferior rectal nerve emerged as a branch of S3 and S4 distinct from the pudendal nerve and innervated only the subcutaneous EAS. Branches of the perineal nerve innervated bulbospongiosus and the superficial EAS and nerve to levator ani innervated the deep EAS. In conclusion, we empirically demonstrate important and clinically relevant differences with perineal anatomy commonly described in standard texts. First, independent innervation to the three portions of EAS suggests the potential for functional independence. Second, neuromuscular continuity between bulbospongiosus and superficial EAS suggests the possibility of shared or overlapping function of the urogenital and anal triangles. Clin. Anat. 29:1053–1058, 2016. © 2016 Wiley Periodicals, Inc.     

The Retrogastric Transventricular Approach for Drainage of the "Supragastric" Pancreatic Pseudocyst

The majority of pancreatic pseudocysts develop in a retrogastric situation and are amenable to transgastric cystogastrostomy through the anterior gastric wall. We have encountered two pseudocysts in an unusual situation, in which adherence of the anterior gastric wall to the anterior parietal peritoneum precluded this approach. A retrogastric exposure through the lesser sac allowed for the creation of a cystogastrostomy through the superior aspects of the anterior and posterior gastric walls, adjacent to the lesser curvature of the stomach. This type of drainage is successful despite the theoretical failure to satisfy the dictum of dependent drainage.     

Malignancy: Granulocyte Colony Stimulating Factor Increases the Efficacy of Conventional Amphotericin in the Treatment of Presumed Deep-Seated Fungal Infection in Neutropenic Patients following Intensive Chemotherapy or Bone Marrow Transplantation for Haematological Malignancies

A prospective, comparative study of empiric amphotericin B with, or without, granulocyte colony stimulating factor was carried out to assess whether the addition of granulocyte colony stimulating factor to empiric amphotericin B improves the clinical response in neutropenic patients with suspected or proven fungal infection. Fifty nine neutropenic adults with haematological malignancy and antibiotic-refractory fever or clinical evidence of deep-seated fungal infection were studied. Patients received intravenous colloidal amphotericin B (1 milligram per kilogram body weight) with or without subcutaneous granulocyte colony stimulating factor (three to five micrograms per kilogram body weight). Thirty patients received amphotericin alone and 29 amphotericin plus granulocyte colony stimulating factor. Nearly twice as many patients responded to amphotericin B with concomitant administration of granulocyte colony stimulating factor (62%) as responded to amphotericin alone (33%; difference in proportions 0.29, 95%CI 0.03-0.54). Clinical response in patients receiving granulocyte colony stimulating factor coincided with neutrophil recovery in most cases. Addition of granulocyte colony stimulating factor to empiric amphotericin B significantly reduced the number of patients requiring salvage therapy with lipid-associated or liposomal formulations of amphotericin B addition of granulocyte colony stimulating factor to empiric intravenous amphotericin B improves the response rate and thereby reduces the number of patients requiring salvage therapy with liposomal or lipid-associated preparations of amphotericin B.     

Circumvention of P-glycoprotein-mediated drug resistance in human leukaemic cells by non-immunosuppressive cyclosporin D analogue, SDZ PSC 833

Summary. Cyclosporin A (CSA) exhibits greater multidrug resistance (MDR) modulating activity in vitro than other MDR modulators such as verapamil and quinidine. However, the immunosuppressive and nephrotoxic effects of CSA may limit its clinical use. PSC 833, a new cyclosporin D derivative, exerts a higher MDR reversal activity but lacks toxic or immunosuppressive effects. The drug-resistant sublines K/DAV₁₀.,, K/DAU₂₀₀. K/DAU₃₀o. K/DAU₄₀o, K/ DAU500 and K/DAU₆₀o have been derived from the drug-sensitive parental cell line, K562 cl.6 and CEM/VLB₁₀₀ is a drug-resistant derivative of CCRF-CEM. We report a comparison of the effects of PSC 833 and CSA on daunorubicin (DAU) transport kinetics and chemosensitivity in these cell lines. Both CEM/VBL₁₀₀ and KS62 cl.6 DAU-resistant cells displayed high levels of P-glycoprotein (PGP), decreased DAU accumulation and increased DAU efflux when compared to their parental cells. PSC 833 was 1-6-, 3-4-, 4-9- and 4-6-fold more effective than CSA in reversing DAU resistance in higher resistance CEM/VLB₁₀o, K/DAU₄₀o, K/DAU500 and K/DAU₆₀o cells respectively. DAU transport kinetics showed that PSC 833 was more effective than CSA in increasing cellular DAU accumulation and decreasing DAU efflux in higher resistant leukaemia subclones. PSC 833 could restore DAU retention at lower doses and was more active than CSA in all the resistant cells. A 89-100% restoration of intracellular DAU retention were gained by PSC 833 at 1-0ftM in K562 cl.6 DAU-resistant sublines, whereas a 73-100% restoration of DAU retention was obtained by CSA only at 30-0 β, M in the same resistant sublines. PSC 833 at 3-0/XM is sufficient to restore full DAU retention in all resistant cells. CSA, however, even at 30-0 pM, cannot confer full restoration of DAU retention in higher resistance K562 cl.6/DAU sublines. By measuring MDR modulator-mediated short-term inhibition of PGP function, PSC 833 was found to be at least 10-30 times more active than CSA. As no effect on DAU retention and sensitivity has been found in sensitive parental cells with PSC 833, it is suggested that PSC 833 may act by blocking the effluxing function of PGP in the resistant leukaemia cells.