精神分裂症患者血浆高香草酸浓度与临床症状、性别和药物治疗的关系

目的：通过分析精神分裂症患者中枢多巴胺代谢产物－血浆高香草酸浓度（ｐＨＶＡ）与临床指征的关系,进一步探讨多巴胺神经递质及其药物治疗在精神分裂症的作用。方法在４６例长期药物治疗、５８例未治疗精神分裂症患者中,采用高液相色谱连接电化学分析仪测定ＰＨＶＡ;测前评定阳性症状量表（ＳＡＰＳ）和阴性症状量表（ＳＡＮＳ）。结果（１）与６２例健康对照组比,治疗组ＰＨ－ＶＡ显著减低,未治疗组显著增高,以阴性症状组为     

Developing best practice for fungal specimen submission - fungal audit of general practice

The objective of this study was to investigate the management of suspected fungal nail infections by general practitioners (GPs) and determine whether guidance is sought when submitting specimens for investigation or treating cases. Questionnaires were sent to all GPs (n = 2420) served by five Health Protection Agency (HPA) collaborating laboratories in the South West of England. A total of 769 GPs responded – topical and oral antifungals were never used by 29% and 16% of GPs respectively. When antifungals were prescribed, topicals were normally given because of the severity of infection (32%); Amorolofine (53%) was the preferred choice. Oral antifungals were most often prescribed after receipt of a laboratory report (77%); Terbinafine was the preferred choice (86%). Seventy percent of GPs would only treat a suspected nail infection with oral antifungals after sending a sample for investigation, yet 27% never waited for a microscopy report before prescribing oral antifungal treatment. GPs routinely send specimens from suspected fungal nail infections for microbiological investigation, yet treatment is often prescribed before a result is received. With clinical signs of fungal infections often non‐specific, GPs should rely on laboratory results before prescribing expensive and lengthy antifungal treatments. Laboratories could further reduce antifungal use by including guidance on microscopy and culture reports.     

O6-methylguanine-DNA methyltransferase depletion and DNA damage in patients with melanoma treated with temozolomide alone or with lomeguatrib

We evaluated the pharmacodynamic effects of the O⁶-methylguanine-DNA methyltransferase (MGMT) inactivator lomeguatrib (LM) on patients with melanoma in two clinical trials. Patients received temozolomide (TMZ) for 5 days either alone or with LM for 5, 10 or 14 days. Peripheral blood mononuclear cells (PBMCs) were isolated before treatment and during cycle 1. Where available, tumour biopsies were obtained after the last drug dose in cycle 1. Samples were assayed for MGMT activity, total MGMT protein, and O⁶-methylguanine (O⁶-meG) and N7-methylguanine levels in DNA. MGMT was completely inactivated in PBMC from patients receiving LM, but detectable in those on TMZ alone. Tumours biopsied on the last day of treatment showed complete inactivation of MGMT but there was recovery of activity in tumours sampled later. Significantly more O⁶-meG was present in the PBMC DNA of LM/TMZ patients than those on TMZ alone. LM/TMZ leads to greater MGMT inactivation, and higher levels of O⁶-meG than TMZ alone. Early recovery of MGMT activity in tumours suggested that more protracted dosing with LM is required. Extended dosing of LM completely inactivated PBMC MGMT, and resulted in persistent levels of O⁶-meG in PBMC DNA during treatment.     

Revisiting Ocular Allergy: Evaluating Symptoms,Benzalkonium Chloride and Efficacy of Topical Ketotifen 0.025%

ABSTRACT

This interesting study raises a scientific issue for revisiting three important elements on diagnosis, use of preservatives and selection of the appropriate topical treatment. Itchy feeling can be encountered in other ophthalmic conditions misdiagnosed as allergy, benzalkonium chloride is responsible for surface toxicity resulting in reduced efficacy and tolerability of topical allergy medications and it should be avoided on the management of ocular allergy. Unpreserved ketotifen 0,025% has been shown to be the least toxic formulation being the optimum option for efficacy and tolerability on the management of ocular allergy.     

Balloon-dilatable arterial banding prosthesis: experimental study

Two arterial banding prostheses were developed that could be dilated by an intraluminal balloon dilator. One prosthesis consisted of radiopaque umbilical tape with a pleat secured by four 8-0 silk sutures thinly coated with silicone type A medical adhesive. This design was used to band the main pulmonary artery in five dogs, the subclavian artery in five, and the aorta in one. The second prosthesis, a stainless steel fatigued helix encased in a siliconized shield, was used to band the main pulmonary artery in two dogs and the descending aorta in two. After a mean duration of 89 days the bands were dilated with an intraluminal balloon dilator at 6 atm (608 kPa) of pressure for 30 seconds. In all 15 experiments the bands dilated and the gradient at the band was reduced. The stainless steel helix was more successful and has technical advantages for clinical application.     

Relationships among cell survival, O6-alkylguanine-DNA alkyltransferase activity, and reactivation of methylated adenovirus 5 and herpes simplex virus type 1 in human melanoma cell lines

O6-Alkylguanine-DNA alkyltransferase (ATase) activity and host cell reactivation (HCR) of 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MTIC)-methylated viruses were compared in human melanoma cell lines that were sensitive or resistant to killing by the antitumor DNA-methylating agent MTIC. Enhanced HCR of adenovirus 5 (defined as the Mer+ phenotype) generally showed a semiquantitative correlation with the natural or induced resistance of the host cells to the toxic effects of MTIC and to the level of ATase activity. However, one MTIC-resistant cell line was found (MM170) which had a low level of ATase and intermediate HCR of adenovirus. The HCR of herpes simplex virus type 1 (HSV-1) was enhanced in the Mer+ cells that had natural resistance to MTIC compared with Mer- cells. On the other hand, HCR of HSV-1 in Mer+ cells with induced resistance to MTIC was similar to that in Mer- cells. Neither adenovirus 5 nor HSV-1 infection induced ATase activity in Mer- cells. This indicates that resistance to the toxic effects of methylating agents is not invariably associated with high levels of ATase activity in human melanoma cells. Furthermore, while induction of the Mer+ phenotype from Mer- cells was usually accompanied by the recovery of ATase activity, induced Mer+ cells had less proficient repair than natural Mer+ cells, as judged quantitatively by slightly lower cellular resistance and qualitatively by deficient HCR response for HSV-1. These results suggest that the Mer- and induced Mer+ cells lack an ATase-independent DNA repair mechanism. No differences in MTIC-induced DNA repair synthesis or strand breaks were found between the Mer-, natural Mer+, and induced Mer+ phenotypes. However, UV-induced DNA repair synthesis was higher in the natural Mer+ than in the Mer- or induced Mer+ cells, both of which had increased cellular sensitivity to the antimetabolites methotrexate and hydroxyurea. These differences may be related to the effects observed with MTIC. A wide range of ATase activities was found in human melanoma biopsy material.