Reboxetine may be helpful in the treatment of amphetamine withdrawal.
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Adrenergic Uptake Inhibitors↗
Biomedical subjects
A McBride
Publications and source records attributed to A McBride.
Anxiety and feelings of medical students conducting their first gynecological examination.
We examined the anxiety of medical students when they conduct their first gynecological examination. The students (226) from two universities completed anonymous questionnaires providing measures of state and trait anxiety and anxiety and confidence feelings, before and after conducting their first bimanual and speculum examination. This took place during a structured, self-directed learning session and involved examination of a professional patient. Students state anxiety was significantly elevated immediately before and fell to below baseline levels after the examination (p < 0.001). Students' reported feelings of increased confidence during the examination (p < 0.001). Students who had personally had a Pap smear test were most anxious before (p < 0.003) but during the examination, students who had experienced a gynecological exam felt less anxious (p < 0.002). The students experiencing the greatest decreases (before to after) in state anxiety were those who had never experienced sexual intercourse (p < 0.005). Most students (96%), particularly those who were more anxious during the examination (p < 0.001) and who experienced a greater decrease in anxiety from before to after the examination (p < 0.008) would recommend this method of learning to other students. In summary, medical students are anxious when they conduct their first gynecological examination, appear to be influenced by their personal experiences and appreciate methods of learning that reduce their anxiety.
Adult↗
An abundance of bacterial ADP-ribosyltransferases--implications for the origin of exotoxins and their human homologues.
ADP-ribosylation is a post-translational modification that can be seen in many contexts, including as the primary mechanism of action of many important bacterial exotoxins. By data-mining complete and incomplete bacterial genome sequences, we have discovered >20 novel putative ADP-ribosyltransferases, including several new potential toxins.
ADP Ribose Transferases↗
Immunohistochemical expression of the alpha5 integrin subunit in the normal adult rat central nervous system.
We investigated the distribution of the alpha5 integrin subunit in the normal adult rat CNS using immunohistochemical methods. Results indicated that the alpha5 integrin subunit was expressed on the vast majority of neurons throughout the brain and spinal cord. In general, neurons showed diffuse cytoplasmic labelling, although many cortical neurons in layers 4 and 5 did show punctate labelling on the cell surface. In addition, axons within the white matter of the brainstem and caudal CNS areas were labelled, with the most intense labelling seen within the white matter of the spinal cord. In addition, labelling of astrocytes was seen throughout white matter, with particularly heavy astrocyte labelling in the spinal cord. The widespread distribution of the alpha5 subunit suggests a general function for the alpha5beta1 integrin receptor (the only integrin receptor that includes the alpha5 subunit) in the adult CNS. The increased expression of fibronectin, the only known ligand for the alpha5beta1 integrin receptor, known to occur around the site of a CNS lesion suggests a possible role for the alpha5beta1 receptor in the response of neurons in the vicinity of a CNS injury.
Animals↗
Needle fixing is not a myth: comments on Al-Adwani's "The myth of needle fixation".
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Humans↗
Joint heavy use of alcohol, cigarettes and coffee and the risk of suicide.
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Alcohol Drinking↗
Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.
BACKGROUND: Serotonergic medications with various mechanisms of action are used to treat psychiatric disorders and are being investigated as treatments for drug dependence. The occurrence of fenfluramine-associated valvular heart disease (VHD) has raised concerns that other serotonergic medications might also increase the risk of developing VHD. We hypothesized that fenfluramine or its metabolite norfenfluramine and other medications known to produce VHD have preferentially high affinities for a particular serotonin receptor subtype capable of stimulating mitogenesis. METHODS AND RESULTS: Medications known or suspected to cause VHD (positive controls) and medications not associated with VHD (negative controls) were screened for activity at 11 cloned serotonin receptor subtypes by use of ligand-binding methods and functional assays. The positive control drugs were (+/-)-fenfluramine; (+)-fenfluramine; (-)-fenfluramine; its metabolites (+/-)-norfenfluramine, (+)-norfenfluramine, and (-)-norfenfluramine; ergotamine; and methysergide and its metabolite methylergonovine. The negative control drugs were phentermine, fluoxetine, its metabolite norfluoxetine, and trazodone and its active metabolite m-chlorophenylpiperazine. (+/-)-, (+)-, and (-)-Norfenfluramine, ergotamine, and methylergonovine all had preferentially high affinities for the cloned human serotonin 5-HT(2B) receptor and were partial to full agonists at the 5-HT(2B) receptor. CONCLUSIONS: Our data imply that activation of 5-HT(2B) receptors is necessary to produce VHD and that serotonergic medications that do not activate 5-HT(2B) receptors are unlikely to produce VHD. We suggest that all clinically available medications with serotonergic activity and their active metabolites be screened for agonist activity at 5-HT(2B) receptors and that clinicians should consider suspending their use of medications with significant activity at 5-HT(2B) receptors.
Dose-Response Relationship, Drug↗
2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors.
Several 2-alkyl-5-methoxytryptamine analogues were designed and prepared as potential 5-HT(6) serotonin agonists. It was found that 5-HT(6) receptors accommodate small alkyl substituents at the indole 2-position and that the resulting compounds can bind with affinities comparable to that of serotonin. In particular, 2-ethyl-5-methoxy-N, N-dimethyltryptamine (8) binds with high affinity at human 5-HT(6) receptors (K(i) = 16 nM) relative to 5-HT (K(i) = 75 nM) and was a full agonist, at least as potent (8: K(act) = 3.6 nM) as serotonin (K(act) = 5.0 nM), in activating adenylate cyclase. Compound 8 displays modest affinity for several other populations of 5-HT receptors, notably h5-HT(1A) (K(i) = 170 nM), h5-HT(1D) (K(i) = 290 nM), and h5-HT(7) (K(i) = 300 nM) receptors, but is otherwise quite selective. Compound 8 represents the first and most selective 5-HT(6) agonist reported to date. Replacing the 2-ethyl substituent with a phenyl group results in a compound that retains 5-HT(6) receptor affinity (i.e., 10: K(i) = 20 nM) but lacks agonist character. 2-Substituted tryptamines, then, might allow entry to a novel class of 5-HT(6) agonists and antagonists.
Adenylyl Cyclases↗
Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications.
OBJECTIVE: To assess the effectiveness, safety and cost implications of leflunomide treatment for rheumatoid arthritis. DESIGN: Systematic review. SETTING: Four trials retrieved from Medline, Embase, the Cochrane Library, Econlit, HMIC (Dhdata), HMIC (Helmis), HMIC (King's Fund Database) and Best Evidence3. MAIN OUTCOME MEASURES: Efficacy measures (including tender joint counts, swollen joint counts, assessment of functioning, Health Assessment Questionnaire, Modified Health Assessment Questionnaire, pain (visual analogue scale), Erythrocyte Sedimentation Rate, C-reactive Protein), radiological progression and treatment adverse events. RESULTS: Leflunomide therapy was demonstrated to be significantly superior to placebo in relation to the efficacy outcome measures and it slowed the radiological progression of patients' disease in three studies. Treatment success and duration of sustained response were also significantly superior than on placebo, as were quality of life measures. Leflunomide treatment was comparable to sulphasalazine and methotrexate with respect to efficacy, radiological progression and quality of life measures. The most common adverse effects leading to withdrawal from leflunomide treatment were gastrointestinal symptoms (diarrhoea and nausea), allergic reactions (rash and pruritus), alopecia, dyspepsia, hypertension and elevated transaminase levels. Weight loss and dizziness have also been reported for leflunomide therapy. Leflunomide is more expensive than most DMARDs, costing about pound400 a year more than sulphasalazine. CONCLUSION: Despite the small number of published articles relating to leflunomide treatment, the evidence suggests that leflunomide is similar in efficacy to both sulphasalazine and methotrexate, although with a differential pattern of side-effects. There is a need for further research to assess the long-term outcomes of leflunomide treatment.
Aged↗
Contraception: a new practical learning package.
BACKGROUND: A new self-directed learning package was developed to assist medical students learn the counselling and practical skills to enable them to communicate with men and women about contraception and related matters. OBJECTIVES: This paper describes the package and the way it was facilitated, the students' ratings of the package and their feedback about the session on the first time it was presented at four teaching hospitals. RESULTS: The students rated the contraception package as average. The reasons given were: no introduction to the contraception session, lack of a trained person to conduct and facilitate the contraception learning session, poor organization at one of the hospitals and too little emphasis on self-assessment. The assumption that the students had a basic hormonal knowledge prior to the contraception sessions was incorrect. DISCUSSION: The results suggest the contraception learning package needs a person with contraceptive knowledge, patient-doctor skills and experience with self-directed learning to be present throughout the 3-hour session and for tools to be available that emphasize self-assessment during the session. OUTCOME: The modifications to be made to the learning package include pairing male and female students, a reduction in duration of the learning stations, an additional learning station relating to hormonal contraception, and inclusion of pregnancy and ovulation testing. These modifications were suggested by the participating students.
Adult↗
Functional renal perfusion imaging with colour mapping: is it a useful adjunct to spiral CT of in the assessment of abdominal aortic aneurysm (AAA)?
AIM: To ensure optimal timing with pre-operative spiral CT for abdominal aortic aneurysms (AAA), an initial 'timing' single level CT is commonly performed with a small bolus of contrast. This can be exploited to obtain adjunct functional information on renal perfusion. We have investigated the potential of this to measure renal perfusion, to produce colour renal perfusion maps and to predict surgical outcome in infrarenal aortic aneurysm assessment. METHODS: We studied 21 patients being assessed for repair of infrarenal AAA. Prior to the spiral CT, a single level through the renal hili and aorta was scanned after the intravenous injection of 25 ml of contrast given at 10 ml/s. Ten 1 s duration scans were performed from 8 to 30 s after injection. Optimal timing for CT angiography can then be determined. Time-density curves were then drawn for both kidneys and aorta using regions of interest (ROIs) or pixel-by-pixel analysis. Renal cortical perfusion was measured using both ROI analysis and pseudocolour perfusion images. Following previous work, perfusion was calculated as the peak upslope of the tissue time density curve divided by peak aortic enhancement. RESULTS: Cortical mean perfusion averaged 2.48 ml/min per ml (range 0.8-3.7 ml/min per ml n = 34) and the values obtained agreed with literature expectations. Follow up in the 10 patients proceeding to AAA repair suggest low mean perfusion values and predict a raised postoperative creatinine (P < 0.05) CONCLUSIONS: Additional functional data and imaging can be obtained from the initial timing scan of a CT study, without requiring a dedicated study.
Aged↗
Stimulation of transposition of the Mycobacterium tuberculosis insertion sequence IS6110 by exposure to a microaerobic environment.
The Mycobacterium tuberculosis-specific insertion sequence IS6110/986 has been widely used as a probe because of the multiple polymorphism observed among different strains. To investigate transposition of IS6110, a series of artificially constructed composite transposons containing IS6110 and a kanamycin resistance marker were constructed. The composite transposons were inserted into a conditionally replicating, thermosensitive, Escherichia coli-mycobacterial shuttle vector and introduced into M. smegmatis mc2155. Lawns of transformants were grown at the permissive temperature on kanamycin-supplemented agar and subsequently prevented from further growth by shifting to the non-permissive temperature. Under normal atmospheric conditions, kanamycin-resistant papillae appeared after only about 5-6 weeks of incubation. However, these events were not associated with transposon mobilization. In contrast, lawns that were exposed to a 48 h microaerobic shock generated kanamycin-resistant papillae after only 6-14 days. These events were generated by conservative transposition of the IS6110 composite transposon into the M. smegmatis chromosome, with loss of the shuttle vector. In common with other IS3 family elements, transposition of IS6110 is thought to be controlled by translational frameshifting. However, we were unable to detect any significant frameshifting within the putative frameshifting site of IS6110, and the level of frameshifting was not affected by microaerobic incubation. The finding that transposition of IS6110 is stimulated by incubation at reduced oxygen tensions may be relevant to transposition of IS6110 in M. tuberculosis harboured within TB lesions.
Adaptation, Physiological↗
Perceived sensitivity of mammographic screening: women's views on test accuracy and financial compensation for missed cancers.
OBJECTIVES: To estimate women's expectations of the accuracy of screening mammography and to explore attitudes towards compensation for missed cancers. DESIGN: Cross sectional survey (by telephone). SETTING: Australia; population-based survey conducted in April 1996. PARTICIPANTS: Random sample of women aged 30-69 years. A total of 2935 women completed the Breast Health Survey (adjusted response rate 65%). A random sample of 115 completed this sub-survey on perceived sensitivity of mammographic screening and compensation for missed cancers. RESULTS: About one third of women (32.2%, 95% CI 23.7, 40.7) had an unrealistically high expectation of the sensitivity of screening mammography, reporting it to be 95% or higher. Approximately 40% of the women (43.5%, 95% CI 34.4, 52.6) thought that screening mammography should pick up all cancers (should have a sensitivity of 100%). Just under half the women (45.2%, 95% CI 36.1, 54.3) said financial compensation should be awarded for a cancer missed by screening mammography even if the cancer was missed as a consequence of the small failure rate of the test. Younger women living in metropolitan areas and women who had realistic expectations of the accuracy of the tests were more likely to favour financial compensation. CONCLUSION: Unrealistically high expectations of the sensitivity of screening mammography were common in this group of women. Many women favoured financial compensation for missed cancers even if the cancer was missed solely because of the failure rate of the test. Public education is required to inform women of the limited sensitivity of breast cancer tests but this may not reduce claims for financial compensation when cancers are missed.
Adult↗
Psychosocial care needs of parents of children with new-onset seizures. 3.
The Parent Report of Psychosocial Care was developed to address the concerns, needs for care and satisfaction with care received of parents of children with new-onset seizures. Parents were interviewed three months and six months after their child's first seizures using the instrument. Mothers especially identified continued needs for information and support and were worried about unlikely events such as brain tumors and death. The results from this study indicate that parents' needs for information and support need to be assessed at every encounter with the health care system during the first 6 months after the child's first seizure.
Adaptation, Psychological↗
Benzodiazepines: time for reassessment.
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Anxiety Disorders↗
Rumination and psychological distress among bereaved partners.
Recently bereaved men who evidenced more negative ruminative thoughts in free-response interviews showed greater psychological distress on several outcome measures both 1 month and 12 months after their loss and less increase in positive morale over this 12-month period. Men who engaged in more analysis of themselves and the meaning of their loss reported greater positive morale 1 month after their loss but showed more persistent depression and absence of positive states of mind over the 12 months following their loss. Finally, men who reported more social friction also evidenced more enduring depressive symptoms over the year than did men who reported less social friction. These results are generally consistent with other studies that have shown that self-reflective, ruminative coping with negative emotions and social friction are associated with longer and more severe periods of depressed mood following stressful events.
Acquired Immunodeficiency Syndrome↗
Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene.
The tissue amyloid deposits that characterize systemic amyloidosis, Alzheimer's disease and the transmissible spongiform encephalopathies always contain serum amyloid P component (SAP) bound to the amyloid fibrils. We have previously proposed that this normal plasma protein may contribute to amyloidogenesis by stabilizing the deposits. Here we show that the induction of reactive amyloidosis is retarded in mice with targeted deletion of the SAP gene. This first demonstration of the participation of SAP in pathogenesis of amyloidosis in vivo confirms that inhibition of SAP binding to amyloid fibrils is an attractive therapeutic target in a range of serious human diseases.
Amyloid↗