Men's issues: gender role conflict and substance abuse

The present paper aims to explore issues related to men within the context of seeking help for substance abuse. The male gender role is in conflict with help-seeking behaviour and with the fundamental principles of therapy, i.e. introspection, emotional expressivity and acknowledgement of difficulties. This creates a paradox for the male seeking psychological treatment and, it will be argued, particularly for the male substance abuser. It is argued that interventions which address the gender role and challenge men's perceptions of themselves are critical variables in the outcome of therapy, i.e. enabling them to make the necessary changes in order to promote psychological well-being. An examination of the male gender role in relation to intrapsychic issues and family systems will be followed by a brief discussion of therapeutic interventions. Some of the difficulties and issues confronted by workers who work with male substance abusers will be explored.     

Early postnatal maturation of GABAA-mediated inhibition in the brainstem respiratory rhythm-generating network of the mouse

It is well established that GABA_A‐mediated postsynaptic potentials are excitatory in many brain regions during embryonic and early postnatal life. The pre‐Bötzinger complex (PBC) in the brainstem is an essential component of the respiratory rhythm‐generating network, where GABA_A‐mediated inhibition plays a critical role in generating a stable respiratory rhythm in adult animals. In the present study, using the perforated patch technique, we investigated the maturation of GABA_A receptor‐mediated effects on rhythmically active PBC neurons and on the motor output in slice preparations from P0–15 neonatal mice. The reversal potential of GABA_A receptor‐mediated current (E_GABA‐A) switched from depolarizing to hyperpolarizing within the first postnatal week. E_GABA‐A was ?13.7 ± 9.8 mV at P0, then it changed to ?44.8 ± 7.0 mV at P2 and ?71.5 ± 6.8 mV at P4. Perfusion of bicarbonate‐free saline has no detectable influence on E_GABA‐A, indicating that a lack of Cl^– extrusion during P0–3 is mainly responsible for early GABA_A‐ergic excitation. At the network level, blockade of GABA_A receptors with bicuculline did not significantly change the frequency of rhythmic bursts recorded from hypoglossal nerve roots before P3, whereas it increased the coefficient of variation. After P3, bicuculline increased burst frequency with little effect on the coefficient of variation. Thus, chloride‐mediated inhibition, which appears in PBC neurons after P3, coincides with the appearance of GABA_A‐mediated modulation of the respiratory rhythm. GABA_A receptor‐activated inhibition may therefore be necessary for frequency modulation in the respiratory network beginning on the fourth postnatal day in the mouse brainstem.     

Long-term survival of the T-28 versus the TR-28 cemented total hip arthroplasties

Between 1974 and 1980, 550 total hip arthroplasties (THAs) (479 patients) were performed using T-28 and TR-28 cemented prostheses (TR-28 is shot-blast chrome and T-28 is polished stainless steel). There were 379 cemented THAs in 321 patients in the T-28 group and 171 cemented THAs in 158 patients in the TR-28 group. Average follow-up of the patients still alive at the end of the study was 20.96 years in the T-28 group and 17.54 years in the TR-28 group. When considering failure as revision of the hip for aseptic acetabular loosening, there were 36 (9.5%) failures in the T-28 group and 12 (7%) failures in the TR-28 group. This difference was statistically significant (P = .0132). When considering failure as radiographic acetabular loosening with or without radiographic femoral loosening, there were 52 failed acetabula (13.7%) in the T-28 group and 18 failed acetabula (10.5%) in the TR-28 group. These differences were not statistically significant. When considering failure as revision for aseptic femoral loosening with or without acetabular component loosening, there were 42 failures (11.1%) in the T-28 group and 22 failures (12.8%) in the TR-28 group. This difference was not statistically significant. When considering failure as radiographic femoral loosening with or without acetabular component loosening, there were 42 failures (11.1%) in the T-28 group and 27 failures (15.8%) in the TR-28 group. This difference was statistically significant for log-rank test (P = .0318) and Wilcoxon's test (P = .0083). Surface finish may be an important contributor to the survival of cemented femoral stems.     

Evidence for cytotoxic T lymphocyte response against human lung cancer: reconstitution of antigenic epitope with peptide eluted from lung adenocarcinoma MHC class I

BACKGROUND: Cancer-associated, major histocompatibility complex (MHC)-restricted peptide antigens have been elucidated in human melanomas and ovarian, breast, and renal carcinomas; but relatively little is known about lung cancer antigens. METHODS: To work toward delineation of lung cancer-associated antigens, we developed tumor infiltrating lymphocytes (TILs), peripheral blood mononuclear cell-derived cytolytic T cell lines (CTL), autologous lung cancer cell lines, and normal lung cell lines from 17 patients undergoing lung cancer resections. The TILs and CTL lines were subsequently evaluated for markers of activation and specific lysis of autologous or allogeneic lung cancer cell lines or both. RESULTS: Freshly isolated TILs contained a more activated T cell population compared with the patients' peripheral blood T cells as evidenced by an increased expression of HLA-DR, CD25, and CD45RO. TILs isolated from 15 patients lysed allogeneic lung cancer lines. TILs lysed autologous lung cancer but not autologous normal lung or Epstein-Barr virus transformed B cell lines (B-LCL) in 4 of 8 cases tested, suggesting tumor specificity. A CTL line (RHPBL57.1) was generated from peripheral blood mononuclear cells of an HLA-A24(+) patient by stimulation against an established HLA-A24(+) allogeneic lung cancer cell line. RHPBL57.1 lysed the lung cancer cell line in an HLA-A24-restricted manner. Moreover, RHPBL57.1 specifically lysed autologous B-LCL pulsed with peptides, eluted from MHC class I and isolated from the HLA-A24(+) lung cancer cell line. CONCLUSIONS: TILs isolated from patients with lung cancer are predominantly an activated population of T cells with evidence of tumor and MHC class I-restricted lysis. Furthermore, we provide evidence for a lung cancer-associated, MHC class I-bound peptide antigen(s) that reconstitutes the epitope recognized by a lung cancer specific CD8(+) T cell line derived from a patient with lung cancer.     

Treatment of restenosis

Carotid restenosis after endarterectomy is observed in up to 24.1% of patients with long-term follow up. Indication for reintervention in asymptomatic patients however should be reserved for greater than 80% stenosis. Treatment options include repeat surgical reconstruction as well as intraoperative or percutaneous balloon angioplasty +/- stenting. We compared our past experience with 66 operative reconstructions in 64 patients with a recent series of 60 patients who underwent intraoperative balloon-dilatation and stenting. After conventional surgery 2 patients (3.1%) suffered a permanent neurological deficit, one patient developed a TIA (1.5%). After intraoperative dilation and stenting 8 patients (13.3%) suffered a stroke; 2 patients died after surgery (one stroke, one myocardial infarction) (mortality 3.3%). When compared to conventional operative repair intraoperative carotid balloon angioplasty and stenting of restenosis is complicated by a substantial increase in morbidity and mortality and cannot be recommended as routine therapy.     

"Not unaffected by northern winds"? Swiss psychiatry and eugenics in the period between world warms

On the basis of the publications and meeting reports of the Swiss Society of Psychiatry this essay examines the relationship of Swiss psychiatry and eugenics during the time between the wars. In a democratic country Swiss psychiatry, on the one hand held a leading position in the justification of eugenic measures, on the other hand a majority of Swiss psychiatrists refused coercive measures, and in World War II disassociated from the racialist eugenics and healthpolicy that were established in NS-Germany. Thus, in difference to NS-Germany the practice of eugenic sterilizations in Switzerland wasn't regulated by any specific national law.     

An investigation of human and rat liver microsomal mycophenolic acid glucuronidation: evidence for a principal role of UGT1A enzymes and species differences in UGT1A specificity.

Mycophenolic acid (MPA; 1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzylfuranyl)-4-methyl-4-hexenoate), the active metabolite of the immunosuppressant prodrug, mycophenolate mofetil, undergoes glucuronidation to its 7-O-glucuronide as a primary route of metabolism. Because differences in glucuronidation may influence the efficacy and/or toxicity of MPA, we investigated the MPA UDP-glucuronosyltransferase (UGT) activities of human liver microsomes (HLMs) and rat liver microsomes with the goal of identifying UGTs responsible for MPA catalysis. HLMs (n = 23) exhibited higher average MPA glucuronidation rates (14.7 versus 6.0 nmol/mg/min, respectively, p < 0.001) and higher apparent affinity for MPA (K(m) = 0.082 mM versus 0.20 mM, p < 0.001) compared with rat liver microsomes. MPA UGT activities were reduced >80% in liver microsomes from Gunn rats. To identify the active enzymes, human and rat UGT1A enzymes were screened for MPA-glucuronidating activity. UGT1A9 was the only human liver-expressed UGT1A enzyme with significant activity and exhibited both high affinity (K(m) = 0.077 mM) and high activity (V(max) = 28 nmol x min(-1) x mg(-1)). Spearman correlation analyses revealed a stronger relationship between HLM MPA UGT activities and 1A9-like content (r(2) = 0.79) relative to 1A1 (r(2) = 0.20), 1A4-like (r(2) = 0.22), and 1A6 (r(2) = 0.41) protein. A different profile was observed for rat with three active liver-expressed UGT1A enzymes: 1A1 (medium affinity/capacity), 1A6 (low affinity/medium capacity), and 1A7 (high affinity/capacity). Our data suggest that UGT1A enzymes are the major contributors to hepatic MPA metabolism in both species, but 1A9 is dominant in human, whereas 1A1 and 1A7 are likely the principal mediators in control rat liver. This information should be useful for interpretation of MPA pharmacokinetic and toxicity data in clinical and animal studies.