Human cognitive function following binedaline (50 mg and 100 mg) and imipramine (75 mg): Results with a new battery on tests

Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg, IP, for 3 weeks. On abrupt termination of the drug, the animals showed withdrawal hyperactivity which was indicated by increased horizontal locomotion and vertical activity, and diarrhoea. The peak effect was seen 3 days after the withdrawal of diazepam. Effects of various alpha₂ agonists, clonidine, guanfacine and B-HT 920, were studied on the diazepam withdrawal phenomena. Clonidine (100 g/kg, IP) given twice a day at an interval of 12 h prevented both withdrawal-induced hyperactivity and diarrhoea. On the contrary, equimolar doses of guanfacine and B-HT 920 failed to reverse withdrawal-induced hyperactivity but attenuated the effect of diarrhoea. However, higher doses (500 g/kg, IP) of guanfacine and B-HT 920 given twice a day at 12-h intervals were found to be effective. Pretreatment with yohimbine (1.5 mg/kg, IP) reversed the protective effect of clonidine, indicating the involvement of alpha₂ receptors in the action of clonidine.     

Clinical Diagnostic Accuracy in the Management of Primary Stage 1 Cutaneous Malignant Melanoma in a Plastic Surgery Unit

In a retrospective review of 614 primary Stage I cutaneous malignant melanomata and 40 nonmelanoma lesions, the diagnostic accuracy(DA) for malignant melanoma was 86.2%. A positive preoperative clinical diagnosis of malignant melanoma was confirmed histologically in 564/604 (93.3%) of lesions. For 614 histologically proven malignant melanomata a correct pre-operative clinical diagnosis had been made in 564/614 (91.9%).An additional 172 patients were referred for wider excisional surgery within 3 months of a biopsy elsewhere. For the total 786 (614+172) patients, the incidence of biopsy of a clinicially unsuspected (but subsequently histologically proven) malignant melanoma prior to referral to the Plastic Surgery Unit was lowest for lesions of the head and neck (18.3%) and lower limb (19.0%), and highest (almost half of the patients) for lesions of the hands and fingers.Previous reports of the poor level of clinical diagnostic accuracy in cutaneous malignant melanoma have not been confirmed in the present study.

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Normal erythrocyte sedimentation rate in the elderly

Two hundred subjects aged 60-89 were selected for a study aimed at defining a reference range for the erythrocyte sedimentation rate in the elderly. The study extended a previous survey in subjects aged 20-65. The results confirmed that the sedimentation rate increases with age and that women have higher values than men but suggested that over half of elderly patients with disease would have rates within the previously defined "normal" range. It is therefore suggested that an erythrocyte sedimentation rate exceeding 19 mm in the first hour in elderly men and 22 mm in the first hour in elderly women warrants investigation.     

Robotic-Assisted Total Knee Arthroplasty: An Assessment of Content,Quality, and Readability of Available Internet Resources

BackgroundThe use of robotic-assisted total knee arthroplasty (TKA) has significantly increased over the past decade. Internet content is largely unregulated and may contain inaccurate and/or misleading information about robotic TKA. Our goal was to assess the content, quality, and readability of online material regarding robotic-assisted TKA.MethodsWe conducted an internet search for the top 50 web sites from each of the 3 most popular search engines (Google, Yahoo, and Bing) using the search term robotic total knee replacement. Each web site was assessed for content, quality, and readability. Web site quality was assessed utilizing the QUality Evaluation Scoring Tool (QUEST). Readability was assessed utilizing the Simple Measure of Gobbledygook, Flesch-Kincaid Grade Level, and Flesch Reading Ease Formula scores.ResultsGeneral risks of TKA were discussed in 47.2%, while benefits were discussed in 98.6% of all web sites. Inaccurate claims occurred at a significantly higher rate in physician/community hospital sources compared to university/academic web sites (59% vs 28%, P = .045). Web sites from university/academic web sites had the highest QUEST scores, while physician/community hospital sources scored the lowest (16.1 vs 10.6, P = .01). Most web sites were written at a college reading level or higher.ConclusionPatients should be counseled on the largely unregulated nature of online information regarding robotic-assisted TKA. Physicians and hospitals should consider revising the readability of their online information to a more appropriate level in order to provide accurate, evidence-based information to allow the patient to make an informed consent decision.     

Heroin in the United Kingdom: different forms, different origins, and the relationship to different routes of administration

Heroin exists in the United Kingdom in several different forms, which vary not only in their country of origin and purity, but also in their suitability for use by either injecting or by 'chasing the dragon'. The availability of these different forms of heroin has varied considerably over time. A review of the characteristics and availability of these various forms of heroin in recent years is presented, accompanied by consideration of their probable intended use by injection or by 'chasing the dragon'. Samples of black market heroin in the salt form are usually used by injection, whereas the base form is usually taken by 'chasing the dragon'. The heroin yield to the drug user from samples of heroin taken by 'chasing the dragon' varies according to its base or salt format and according to the presence of other drugs in the sample. Heroin samples from different countries of production mostly conform to either base or salt form. Novel approaches at the macro level to prevention and control of heroin-related problems through influence upon this complex heroin market-place should now be considered.     

Acid aspiration prophylaxis in 202 obstetric anaesthetic units in the UK

A postal survey of obstetric anaesthetic units in the UK was conducted by questionnaire to gain information about current acid aspiration prophylaxis. Information regarding the delivery rate and the caesarean section rate under regional techniques was also requested. Replies were received from 202 obstetric anaesthetic units in the UK, a 75% response rate. The results are compared to similar surveys carried out in 1984 and 1988. Sodium citrate and the H(2) antagonist ranitidine remain the drugs most commonly used for acid aspiration prophylaxis. However, the number of departments carrying out routine prophylaxis for patients in active labour has fallen from 75% in 1988 to 57% in the current survey.     

Discriminative-stimulus effects of azaspirodecanedione anxiolytics in baboons trained to discriminate beta-carboline-3-carboxylic acid ethyl ester or pentylenetetrazole

Baboons were trained to discriminate either pentylenetetrazole (PTZ) or beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) from the no-drug condition. Both drugs specifically bind sites in the gamma-aminobutyric acid A (GABA(A)) receptor complex and decrease GABAergic transmission. beta-CCE occasioned drug-lever responding in baboons trained to discriminate PTZ and vice versa. Flumazenil, the benzodiazephine receptor antagonist, blocked beta-CCE, consistent with beta-CCE's receptor binding activity. The azaspirodecanedione anxiolytics buspirone and ipsapirone produced full generalization in all baboons; gepirone and tandospirone yielded full generalization in some baboons and partial in others. These anxiolytics are inactive in the GABA(A) complex and potently bind 5-HT(1A) sites. A specific 5-HT(1A) ligand, 8-hydroxy-2-(di-n-propylamino)tetralin, produced generalization similar to gepirone and tandospirone, which show the most specific 5-HT(1A) binding. The major azaspirodecanedione metabolite, 1-(2-pyrimidinyl)piperazine (an alpha(2)-adrenergic antagonist), occasioned the least drug-appropriate responding. Full generalization to buspirone and ipsapirone may have resulted from dopaminergic or alpha(1)-adrenergic activity combined with 5-HT(1A) activity. The molecular mechanism of the generalization profile for PTZ and beta-CCE shown by the present results is unclear. The data may reflect altered relationships between GABAergic and serotonergic transmission, and altered stimulus effects of the training drugs, in the context of chronically decreased GABAergic transmission.     

Expression of an ovalbumin-specific V{beta}8.2 TCR transgene inhibits collagen arthritis in B10.Q mice

Previous studies have illustrated the importance of T cellsbearing ß TCRs in the induction and development ofcollagen induced arthritis (CIA) in mice. However, the scopeof TCR usage in CIA has yet to be clearly defined. Given theinherent diversity of the TCR repertoire, the relative flexibilityof the arthritogenic TCR repertoire specific for type II collagen(CII) is not clear. Therefore, we chose to examine the influenceof a highly skewed TCR repertoire on CIA. Arthritis susceptibleB10.Q (H-2^q) mice were mated with C57L (H-2^b) animals expressingan ovalbuminspecific V_ß8.2 TCR transgene (Tg) andTg⁺ offspring were further backcrossed to B10.Q. HomozygousH-2^a/q, V_ß8.2 Tg⁺ mice displayed a high level of V_ß8.2⁺T cells in peripheral blood. However, expression of some endogenousV_ß TCR, such as V_ß14, was still detected.Upon immunization with bovine CII in adjuvant, V_ß8.2Tg⁺ mice were highly resistant to CIA when compared with Tg^–littermates. Analysis of sera demonstrated a marked reductionin antibody specific for homologous mouse CII as well as heterologousbovine CII in Tg⁺ animals. Interestingly, V_ß8.2 Tg⁺mice still mounted good antibody responses following immunizationwith human thyroglobulin, indicating that the skewed TCR repertoireaffected anti-CII but not antithyroglobulin responses. Thus,our findings show that constraints placed on the TCR repertoireInhibit pathogenic responses against CII and suggest that inH-2^q mice the arthritogenlc TCR repertoire bears only limitedflexibility.