Neuropeptide expression following constriction or section of the inferior alveolar nerve in the ferret

Some of the sensory abnormalities that follow peripheral nerve injury may result from the development of ectopic discharge from the damaged axons. Previous studies in our laboratory have shown that, following tight ligation of the inferior alveolar nerve (IAN), there is a close association between the time-course of this neural activity and the accumulation of neuropeptides at the injury site. In this study we investigated whether the type of injury has any effect on the time-course or level of neuropeptide expression. In 36 adult ferrets, the IAN was either loosely constricted or sectioned, and the animals left to recover for 3 days, 3 weeks, or 3 months. The tissue was processed using indirect immunofluorescence and image analysis was used to quantify levels of substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, enkephalin, galanin, and neuropeptide Y. Immunoreactivity to all of the neuropeptides was present within the injured nerve 3 days after both types of injury, and decreased to lower levels by 3 weeks and 3 months. Comparisons between the levels of neuropeptide immunoreactivity in each group revealed that the pattern of accumulation was similar following loose constriction or section, and also similar to that found in our previous study on tight ligation. For each injury the time-course of neuropeptide expression was similar to that of the spontaneous activity we had previously recorded. These data support the suggestion that neuropeptide accumulation may be linked to the development of ectopic neural activity but indicate that the type of injury has little effect on the extent of expression.     

Widespread but regionally specific effects of experimenter- versus self-administered morphine on dendritic spines in the nucleus accumbens,hippocampus, and neocortex of adult rats

We studied the effects of self-administered (SA) vs. experimenter-administered (EA) morphine on dendritic spines in the hippocampal formation (CA1 and dentate), nucleus accumbens shell (NAcc-s), sensory cortex (Par1 and Oc1), medial frontal cortex (Cg3), and orbital frontal cortex (AID) of rats. Animals in the SA group self-administered morphine in 2-h sessions (0.5 mg/kg/infusion, i.v.) for an average of 22 sessions and animals in the EA group were given daily i.v. injections of doses that approximated the total session dose for matched rats in Group SA (average cumulative dose/session of 7.7 mg/kg). Control rats were given daily i.v. infusions of saline. One month after the last treatment the brains were processed for Golgi-Cox staining. In most brain regions (Cg3, Oc1, NAcc-s) morphine decreased the density of dendritic spines, regardless of mode of administration (although to a significantly greater extent in Group SA). However, only SA morphine decreased spine density in the hippocampal formation and only EA morphine decreased spine density in Par1. Interestingly, in the orbital frontal cortex morphine significantly increased spine density in both Groups SA and EA, although to a much greater extent in Group SA. We conclude: 1) Morphine has persistent (at least 1 month) effects on the density of dendritic spines in many brain regions, and on many different types of cells (medium spiny neurons, pyramidal cells, and granule cells); 2) The effect of morphine on spine density (and presumably synaptic organization) varies as a function of both brain region and mode of drug administration; and 3) The ability of morphine to remodel synaptic inputs in a regionally specific manner may account for the many different long-term sequelae associated with opioid use.     

What leads to frequent re-hospitalisation when community care is not well developed?

BACKGROUND: Treatment programmes are largely hospital based in developing countries and yet research on factors predicting frequent re-hospitalisation remains scarce from them. This cross-sectional study of factors predictive of frequent re-hospitalisation explored whether factors reported from developed countries could apply to India. METHODS: Information was collected on four dimensions (socio-demographic, socio-cultural, treatment and illness variables) from 90 patients readmitted to a teaching psychiatric institute in India over a 3 month period. Patients were grouped into Frequently Re-hospitalised (FR) with three or more admissions to hospital in the last 18 months and Less Frequently Re-hospitalised (LFR) with two or fewer admissions in the last 18 months. RESULTS: Support available for treatment, days spent in hospital and cost of treatment had a significant effect on whether the patient was more frequently hospitalised. The place of domicile tended to have an effect on the frequency of hospitalisation. CONCLUSIONS: Factors predictive of frequent re-hospitalisation reported in this study differed from those in developed countries. The above variables identify high users of inpatient beds who may be targeted for specific interventions to reduce re-hospitalisation rates.     

Development of the Cochrane Collaboration's CENTRAL Register of controlled clinical trials

The Cochrane Collaboration has established a centralized database of controlled trials and other studies of health care interventions (called CENTRAL) that serves as the best available resource for all those preparing and maintaining systematic reviews or otherwise searching for trials. CENTRAL is available on The Cochrane Library. This article describes the history and methods of CENTRAL's development and the results of an analysis of the current composition of CENTRAL. As of September 2000, CENTRAL contained almost 300,000 citations to reports of trials, contributed mainly by Cochrane Groups and Centers around the world. Development of CENTRAL has been an ambitious, scholarly undertaking and has resulted in a valuable resource: CENTRAL includes citations to controlled trials that may not be indexed in MEDLINE, EMBASE, or other bibliographic databases; citations published internationally in many languages; and citations that are available only in conference proceedings or other hard-to-access sources.     

Partner violence intervention in the busy primary care environment

BACKGROUND: Few studies of intimate partner violence (IPV) interventions have been conducted in primary care settings. Based on recommendations, we implemented a multifaceted IPV intervention that included a sticker placed in medical charts listing screening questions, routine IPV screening by nursing staff, clinician follow-up for women screening positive, and referral to on-site services. METHODS: A prospective cohort study compared multiple measures collected at the intervention site and a center providing usual care. Measures included self-reported IPV, documented IPV screening and IPV experiences, and quantity of IPV materials taken from the centers. RESULTS: Of 746 charts reviewed in a random chart review conducted at the intervention site, 36.6% were tagged for IPV screening, and of those tagged, 86.1% had documentation of screening. Approximately 5% (11 of 235) of women screened positive for IPV; about half had documented clinician follow-up and referral to on-site services. Comparison of survey responses and medical record reviews (intervention site) indicated that the screening protocol primarily identified severely abused women (sensitivity 80%, specificity 98%), but rarely identified women experiencing low to moderate levels of abuse. IPV brochures were taken from the intervention site at a rate of 51 per 1000 visits versus 29 per 1000 visits taken from the control site. CONCLUSIONS: Utilizing screening as the only gateway to on-site services limited access for many IPV victims. The removal of IPV brochures from examination rooms suggests that providing contact information for self-referral to on-site services may improve access.     

The contribution of transfusion to HCV infection in England

The English HCV lookback programme has identified some individuals with transfusion-transmitted HCV infection. The path from the collection of donations from HCV-infected donors to the identification of infected recipients was constructed. The probability of different outcomes at each branch was derived from data collected during this programme. This path of probabilities was then used to produce a complete estimate of the number of recipients infected by blood transfusions (dead and alive at the end of 1995) by re-entry of blood components that fell out of the lookback at various steps prior to recipient testing, and entry of components from HCV-infected donations that were never identified for lookback. Less than 14,000 recipients were estimated to have been infected with HCV during the decade prior to the start of donation testing. Over 60% of these were expected to have died by the end of 1995. Transfusion has infected a large group of individuals. However, this group constitutes a very small, and declining, proportion of all HCV infections in the population.     

Bed-blocking. Discharge of the late brigade

Delayed discharges are seen as a litmus test for how the whole health and social care system is working. The problem has been exacerbated by delays in developing intermediate care schemes. There has been less use of the private nursing homes for intermediate care than envisaged a year ago, possibly because of NHS concerns about standards. More support should be given to people with chronic conditions to keep them out of hospital.     

Enhanced uptake of ifosfamide into GH3 prolactinomas with hypercapnic hyperoxic gases monitored in vivo by (31)P MRS

Previously, ³¹P magnetic resonance spectroscopy (MRS) has been used to detect ifosfamide (IF) in vivo and to show that breathing carbogen (5% CO₂/95% O₂) enhances the uptake and increases the efficacy of IF in rat GH3 prolactinomas [Rodrigues LM, Maxwell RJ, McSheehy PMJ, Pinkerton CR, Robinson SP, Stubbs M, and Griffiths JR (1997). In vivo detection of ifosfamide by ³¹P MRS in rat tumours; increased uptake and cytotoxicity induced by carbogen breathing in GH3 prolactinomas. Br J Cancer 75, 62–68]. We now show that other hypercapnic and/or hyperoxic (5% CO₂ in air, 2.5% CO₂ in O₂) gas mixtures also increase the uptake of IF into tumors, measured by ³¹P MRS. All gases caused an increased uptake (C_max) of IF compared to air breathing, with carbogen inducing the largest increase (85% (P<.02) compared to 46% with 2.5% CO₂ in O₂ (P<.004) and 48% with 5% CO₂ in air (P<.004)). The T_max (time of maximum concentration in tumor posintravenous injection of IF) was significantly (P<.04) later in the cohort that breathed 5% CO₂ in air. The increased uptake of IF with carbogen breathing was selective to tumor tissue and there were no significant increases in any of the normal tissues studied, suggesting that any host tissue toxicity would be minimal. Carbogen breathing by patients causes breathlessness. There was no significant difference in IF uptake between breathing carbogen and 2.5% CO₂ in O₂ and, therefore, the ability of 2.5% CO₂ in O₂ to also increase IF uptake may be clinically useful as it causes less patient discomfort.     

New approaches for mesothelioma: biologics, vaccines, gene therapy, and other novel agents

Although malignant mesothelioma is not a classically immunogenic cancer, there is abundant evidence for immune recognition. The relative ease of obtaining tumor tissue makes mesothelioma ideal for studying surrogate biomarkers such as lymphocytic infiltration or expression of transduced genes. There is evidence that malignant mesothelioma patients as well as asbestos-exposed persons without mesothelioma have impaired immune responsiveness. Substantial progress has been made in animal models using several biological and immunological techniques, but clinical application has been problematic. Systems studied have included lysis by interleukin-2 (IL-2)-activated lymphokine-activated killer (LAK) cells, tumor necrosis factor-alpha (TNF-alpha), a p16-expressing adenovirus vector, suicide gene therapy using the herpes simplex virus-tyrosine kinase (HSV-tk) followed by ganciclovir, and immunomodulatory gene therapy with IL-2, IL-4, interferon-gamma (IFN-gamma), IFN-alpha, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and IL-1beta transfected into tumors. Vaccinia virus has been studied as a vector for cytokine gene transfer. Suicide gene therapy has been combined with a tumor vaccine. The University of Western Australia is initiating a pilot study of autologous vaccination in malignant mesothelioma. Novel agents under study include the angiogenesis inhibitors SU5416, bevacizumab, and thalidomide. ZD1839, an orally administered, highly selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, is being tested in a phase II trial. Since platelet-derived growth factor (PDGF) is thought to be an autocrine growth factor for mesothelioma STI-571 (Gleevec; Novartis, Basel, Switzerland), a highly selective inhibitor of the PDGF receptor tyrosine kinase, is being tested in a phase II trial. The development of more active cytotoxic combinations in this disease should facilitate further studies of chemoimmunotherapy. It seems likely that no single treatment modality will be effective by itself.