FPL 62064, a topically active 5-lipoxygenase/cyclooxygenase inhibitor

FLP 62064 [N-(4-methoxyphenyl)-1-phenyl-1H-pyrazole-3-amine] is a dual inhibitor of prostaglandin synthetase and 5-lipoxygenase. The compound had anti-inflammatory activity in vivo in a number of models. It inhibited peritoneal inflammation induced by immune-complex when given locally. When applied to the skin, FPL 62064 inhibited UV irradiation-induced erythema and PGE2 formation in the guinea pig and also oedema formation and eicosanoid production in the mouse ear produced by arachidonic acid. Co-injected with arachidonic acid in rabbit skin, FPL 62064 inhibited oedema and eicosanoid formation.     

Self-administration in baboons and the discriminative stimulus effects in rats of bupropion,nomifensine, diclofensine and imipramine

The behavioral effects of the antidepressants nomifensine, diclofensine, bupropion, and imipramine were examined using a cocaine substitution drug self-administration procedure in baboons and a cocaine drug discrimination procedure in rats. Intravenous self-administration of the antidepressants was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a fixed-ratio 80-response or 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time-out allowing a maximum of eight injections per day. The antidepressants or their vehicles were substituted for cocaine for a period of 15 days, followed by a return to the cocaine baseline. Nomifensine, diclofensine, and bupropion all maintained self-administration behavior at levels above those maintained by their respective vehicles. Some doses of nomifensine, diclofensine, and bupropion maintained levels of behavior similar to those maintained under baseline cocaine conditions. High doses of imipramine maintained levels of behavior above those maintained by its vehicle, but the amount of behavior maintained under these conditions was extremely small. In a second experiment rats were trained to discriminate 32 µmol/kg cocaine (IP 10 min presession) from no drug in a two-lever food reinforced drug discrimination procedure in which responding on one lever was reinforced following ten consecutive responses when the session was preceded by cocaine administration, while responding on the other lever was similarly reinforced in the absence of cocaine pretreatment. Cocaine, nomifensine, diclofensine, and bupropion all dose-dependently occasioned cocaine-appropriate responding. Imipramine did not occasion cocaine-appropriate responding over a range of behaviorally active doses.     

Granulomatous Pneumocystis carinii pneumonia in a patient with the acquired immunodeficiency syndrome.

A patient with an unusual granulomatous response to infection with Pneumocystis carinii is described. The diagnosis was made by open lung biopsy after two negative bronchoalveolar lavages.     

Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis.

Despite recent advances in understanding the immunopathogenesis of oral lichen planus (LP), the initial triggers of lesion formation and the essential pathogenic pathways are unknown. It is therefore not surprising that the clinical management of oral LP poses considerable difficulties to the dermatologist and the oral physician. A consensus meeting was held in France in March 2003 to discuss the most controversial aspects of oral LP. Part 1 of the meeting report focuses on (1) the relationship between oral LP and viral infection with special emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular the immune mechanisms resulting in lymphocyte infiltration and keratinocyte apoptosis. Part 2 focuses on patient management and therapeutic approaches and includes discussion on malignant transformation of oral LP.     

Conchotome and needle percutaneous biopsy of skeletal muscle.

Percutaneous muscle biopsy is an important and acceptable technique in the study of conditions involving human skeletal muscle. A review of 436 conchotome and needle muscle biopsies obtained over 18 months in this centre is presented.     

Demonstration of human papillomavirus types 6 and 11 in juvenile laryngeal papillomatosis by in-situ DNA hybridization

A study is reported in which an in situ hybridization technique for the demonstration of human papillomavirus (HPV) employing a biotin--streptavidin polyalkaline phosphatase complex has been successfully applied to formalin-fixed paraffin-processed tissue obtained from ten patients with juvenile laryngeal papillomatosis. In all cases, positive results were obtained for either HPV type 6 or 11. Normal vocal cord epithelium was negative.     

Impact of a region-wide approach to improving systems for heart attack care: the West Midlands thrombolysis project.

OBJECTIVE: To describe changes in delay to administration of thrombolytic therapy associated with a region-wide audit. DESIGN: Observational study of patients admitted with suspected myocardial infarction (MI) based on continuous audit. SUBJECTS: 18877 patients admitted to 23 hospitals with suspected MI between April 1995 and March 1998. RESULTS: Of 11232 patients with a discharge diagnosis of definite MI, 8802 (46.6%) received thrombolytic therapy during hospitalisation, with 5155 patients eligible for treatment on admission to hospital on the basis of established indications. Call-to-needle time for those eligible for treatment on admission fell from median 105 min in the first year of the project to 85 min in year 3 (P<0.001), and door-to-needle time fell from 45 to 35 min (P<0.001). Forty percent of eligible patients were treated within the then current national standard of 90 min from time of call for help, with nearly 49% in the final year and 20% being treated within the new national standard of 60 min, by the third year. CONCLUSION: The proportion of eligible patients receiving thrombolysis within 1 h of the call for help doubled during the 3-year project but the majority of patients still wait longer than 60-min 'call-to-needle'. New systems to reduce delays to administration of thrombolysis to within 60 min of call for help are required, including consideration of pre-hospital treatment.