Warfarin or Low-Molecular-Weight Heparin Therapy does not Prolong Pig-To-Primate Cardiac Xenograft Function

Microvascular thrombosis is a prominent feature in cardiac delayed xenograft rejection (DXR). We investigated the impact of warfarin or low-molecular-weight heparin (LMWH) anti-coagulation on xenograft function using a heterotopic pig-to-primate model. Donor hearts were from CD46 transgenic pigs and baboon immunosuppression included tacrolimus, sirolimus, anti-CD20 and TPC, an alpha-galactosyl-polyethylene glycol conjugate. Three groups of animals were studied. Group 1 (n = 9) was treated with warfarin, Group 2 (n = 13) with LMWH and Group 3, received no anti-coagulant drugs. The median duration of xenograft function was 20 days (range 3-62 days), 18 days (range 5-109 days) and 15 days (range 4-53 days) in Groups 1 to 3 respectively. Anti-coagulation achieved the targeted international normalized prothrombin ratio (INR) and anti-factor Xa levels consistent with effective in vivo therapy yet, no significant impact on median xenograft function was observed. At rejection, a similar histology of thrombosis and ischemia was apparent in each group and the levels of fibrin deposition and platelet thrombi in rejected tissue was the same. Anti-coagulation with warfarin or LMWH did not have a significant impact on the onset of DXR and microvascular thrombosis. However, a role for specific anti-coagulant strategies to achieve long-term xenograft function cannot be excluded.     

Norepinephrine modulates glutamatergic transmission in the bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis (BNST) and its adrenergic input are key components in stress-induced reinstatement and maintenance of drug use. Intra-BNST injections of either beta-adrenergic receptor (beta-AR) antagonists or alpha2-adrenergic receptor (alpha2-AR) agonists can inhibit footshock-induced reinstatement and maintenance of cocaine- and morphine-seeking. Using electrophysiological recording methods in an in vitro slice preparation from C57/Bl6j adult male mouse BNST, we have examined the effects of adrenergic receptor activation on excitatory synaptic transmission in the lateral dorsal supracommissural BNST (dBNST) and subcommissural BNST (vBNST). Alpha2-AR activation via UK-14,304 (10 microM) results in a decrease in excitatory transmission in both dBNST and vBNST, an effect predominantly dependent upon the alpha2A-AR subtype. Beta-AR activation via isoproterenol (1 microM) results in an increase in excitatory transmission in dBNST, but not in vBNST. Consistent with the work with receptor subtype specific agonists, application of the endogenous ligand norepinephrine (NE, 100 microM) elicits two distinct effects on glutamatergic transmission. In dBNST, NE elicits an increase in transmission (62% of dBNST NE experiments) or a decrease in transmission (38% of dBNST NE experiments). In vBNST, NE elicits a decrease in transmission in 100% of the experiments. In dBNST, the NE-induced increase in synaptic transmission is blocked by beta1/beta2- and beta2-, but not beta1-specific antagonists. In addition, this increase is also reduced by the alpha2-AR antagonist yohimbine and is absent in the alpha2A-AR knockout mouse. In vBNST, the NE-induced decrease in synaptic transmission is markedly reduced in the alpha2A-AR knockout mouse. Further experiments demonstrate that the actions of NE on glutamatergic transmission can be correlated with beta-AR function.     

Psychological distress among female spouses of male at-risk drinkers.

The consequences of alcoholism on the mental health of spouses of lifetime at-risk drinkers are only known from studies on alcoholics already in treatment. A retrospective analysis was conducted using data from a Quebec community health survey. The purpose of this study was twofold. First, our goal was to ascertain the mental health of female spouses living with a male lifetime at-risk drinker. Secondly, we wanted to examine the relationship between male lifetime at-risk drinkers (aged 30-54 years) and the psychological distress of their nondrinking female spouses. Lifetime at-risk drinking, for the purposes of this study, was defined as having at least two positive answers to the CAGE questionnaire. Couples wherein both spouses were deemed not at-risk for problem drinking by the CAGE instrument (0 or 1 positive answer) formed the control group. Psychological distress was measured using the Indice de Détresse Psychologique de l'Enquête Santé Québec (Préville, M., Boyer, R., Potvin, L., Perreault, C., & Légaré, G. (1992). La détresse psychologique: détermination de la fiabilité et de la validité de la mesure utilisée dans l'enquête Santé Québec. Cahier de recherches #7, Montréal, Santé Québec.). It measures symptoms of anxiety, depression, aggressivity, and cognitive impairments. Scores of >or=22 (out of 100) were indicative of a high level of psychological distress. This study confirmed higher levels of psychological distress in female spouses of male lifetime at-risk drinkers in the general population. An exploratory study examined the association between the psychological distress of female spouses and each of the following nine independent variables: male partner lifetime at-risk drinker, stressful life events, job situation, socioeconomic status, perceived health status, presence of children less than 15 years, length of the marital relationship, presence of a confidant, and availability of social support. Lifetime at-risk drinking is a risk factor for the spouse's psychological distress. An examination of the demographic characteristics related to alcohol intake in male lifetime at-risk drinkers is also described in this study.     

Prospective comparative study of cefotetan with piperacillin for prophylaxis against infection in elective colorectal surgery

This study compared one dose of cefotetan with three doses of piperacillin as prophylaxis against wound infection in 153 patients undergoing elective colorectal surgery. The patients were randomized into two groups: the first received 2 g cefotetan intravenously with induction of anaesthesia (n = 75), and the second received three doses of 2 g piperacillin (n = 78). Wound infection was defined as the presence of an abscess or discharging pus from the wound. In the cefotetan group there were 14 (19%) wound infections and 13 (17%) in the piperacillin group. There were three septic deaths, one in the cefotetan group and two in the piperacillin group. Both groups were comparable with regard to age, sex, nature of pathology and pre- and perioperative risk factors. No significant haematological or biochemical abnormalities were detected. The only adverse reaction was one patient who had an allergic reaction (rash) to piperacillin. These data suggest that single-dose cefotetan is as effective as triple-dose piperacillin in prophylaxis against infection in elective colorectal surgery.     

Social services for deaf and hearing-impaired clients: a review of the literature

Emphasis on the social service needs of the deaf and hearing impaired has increased in the past decade. The literature that resulted from this attention is fragmented, however, and does not always offer the structure and direction that is needed. This review of the literature identifies issues related to effective service delivery with the objective of enhancing practitioners' understanding and awareness of the social service needs of the deaf community. A second objective is to stimulate interest and action in service delivery, program development, and direct service for the deaf.     

Differential antagonism of the behavioral depressant and hypothermic effects of 5'-(N-ethylcarboxamide) adenosine by theobromine

The methylxanthine, theobromine (3,7-dimethylxanthine), was tested in mice, to determine whether theobromine could function in vivo as an adenosine receptor antagonist, in keeping with its reported in vitro effects as a blocker of agonist binding to the adenosine A-1 receptor. Theobromine doses, which themselves had no direct effects on spontaneous locomotor activity, completely blocked N6-cyclohexyladenosine-induced suppression of locomotor activity but were without effect on 5'-N-ethylcarboxamide adenosine (NECA)-induced decreases in motor activity. In contrast to the specific antagonism, theobromine blocked the hypothermia induced by both of these adenosine analogs. These results demonstrate that theobromine is an active in vivo adenosine receptor antagonist and that the antagonism of N6-cyclohexyladenosine sensitive systems occurs even though theobromine does not stimulate spontaneous locomotor activity. Thus, the behavioral stimulant effects of methylxanthines may be more related to effects on NECA-sensitive systems, which are not blocked by theobromine. The use of in vivo differences in the effects xanthine may provide a useful tool in the development of compounds to probe the mechanisms of caffeine induced CNS effects.     

WONCA Online电子病例介绍——小肠梗阻

·病例简介:患者,女,52岁。腹部绞痛,伴呕吐、腹胀,2d以来无排气。无发热、头晕、晕厥等,无腹部手术史。·既往史:高血压。·体格检查:体温37·2℃,心率110次/min,血压138/92mm Hg(1mm Hg=0·133kPa)。腹部膨隆,全腹触痛,上腹部有局限性压痛点,无反跳痛,肠鸣音弱,Murphy′s征阴