Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims.

BACKGROUND: The serotonin deficiency hypothesis of suicide has been important heuristically. Few studies have directly examined the brainstem dorsal raphe nucleus (DRN) serotonin neurons. We determined the number and morphometry of DRN serotonergic neurons in suicide victims (n = 7) compared to controls (n = 6). METHODS: Brainstems were collected at autopsy, fixed and cryoprotected. Tissue was sectioned, stained for Nissl and processed with an antiserum that cross-reacts with tryptophan hydroxylase. All DRN neurons were identified, counted and analyzed every 1000 microns. Neuron morphometry was characterized by soma area (micron 2), sphericity, perimeter, length and density (neurons per mm3). RESULTS: Neuron number and density was higher in suicide victims (1,780 +/- 127 neurons/mm3) than controls (1,349 +/- 68). The DRN volume did not differ between groups (66 +/- 9 mm3 for controls vs. 67 +/- 5 mm3 for suicides). Mean neuronal area and sphericity did not differ between suicides and controls. The total number and the density of DRN neurons did not correlate with age. CONCLUSIONS: The finding of an increased number of neurons indicates that impaired serotonergic transmission found in association with serious suicide attempts is not due to fewer neurons.     

Intra-articular tenoxicam improves postoperative analgesia in knee arthroscopy

PURPOSE: Non Steroidal Anti-inflammatory drugs have a well documented benefit in the relief of postoperative pain. This study was designed to compare the analgesic effect of intra-articular tenoxicam 20 mg with intravenous tenoxicam on postoperative pain in 88 patients undergoing day case knee arthroscopy. METHODS: A prospective, double blind, randomized trial was performed. All patients received a standard general anesthetic. Patients in group A received 20 mg tenoxicam made up to 40 ml with normal saline intra-articularly (ia) and 2 ml normal saline i.v. Patients in group B received 40 ml normal saline intra-articularly and 2 ml, 20 mg of tenoxicam, i.v. RESULTS: Both groups of patients were similar with respect to age, weight, sex and tourniquet inflation time. Patients receiving ia tenoxicam had lower pain scores (at rest and upon movement) at 30, 60, 120 and 180 min postoperatively (0.8+/-0.2 vs. 2.5+/-0.2 at rest and 1.24+/-0.2 vs. 3.4+/-0.2 at movement at 60 min; P< 0.0001). Fewer patients required additional analgesia in the first four hours postoperatively (33% vs. 84%; P<0.00001) and the time to first analgesia (23.7+/-11.2 vs. 9.4+/-0.6; P<0.02) was longer in those receiving ia tenoxicam. CONCLUSION: Intra-articular tenoxicam provides superior postoperative analgesia and reduces postoperative analgesic requirements compared with i.v. tenoxicam in patients undergoing day case knee arthroscopy.     

Patients' perspectives on services for epilepsy: a survey of patient satisfaction, preferences and information provision in 2394 people with epilepsy.

The objectives of this study were to provide a comprehensive survey of satisfaction with care, care preferences and information provision for patients with epilepsy, and to formulate recommendations for the development of epilepsy services based on the findings. A questionnaire was distributed to 4620 patients who were currently receiving antiepileptic drugs for epilepsy, regardless of aetiology, duration or severity. Two different samples of patients with epilepsy were questioned: the first an unselected sample drawn from primary care, and the second consisting of consecutive patients drawn from hospital clinics. There were 2394 responses to the questionnaire. Satisfaction with primary and hospital care was high, both overall and for specific aspects. However, two major shortcomings were identified. First, few respondents felt that their care was shared between hospital and GP. Secondly, provision of information about epilepsy was perceived to be poor, particularly by the elderly. Younger patients and patients with severe epilepsy had a higher satisfaction with and preference for hospital care, whereas older age groups were more satisfied with and preferred primary care. Patients' main reasons for preferring primary care were that it was more personal and the GP was more familiar with them, and secondary care was preferred because the hospital doctor knew more about epilepsy. In conclusion, we have conducted the largest representative UK survey of patients' perceptions and views of the care available for epilepsy. Although patient satisfaction was high, information provision is poor and the shared care model is not operating effectively. We recommend that an emphasis be placed on methods for improving the interface between primary and secondary care. The setting up of hospital epilepsy centres, as recommended by the recently published Clinical Standards Advisory Group report on epilepsy, would provide a focus for these efforts and for information provision.     

NHS services for epilepsy from the patient’s perspective: a survey of primary, secondary and tertiary care access throughout the UK

The aims of this study were to estimate the proportion of patients with epilepsy who made primary care and/or hospital outpatient medical consultations within 1 year; to formulate a model of the explanatory variables that influence whether patients consult or not; and to estimate the frequency of referral to, and waiting time for, hospital outpatient clinics in patients with new-onset seizures. Suggestions are offered for improvement of epilepsy services based on the findings. A questionnaire was distributed to 3455 unselected patients identified at population level from primary care practices in all NHS regions of the UK. There were 1652 respondents with epilepsy of all types, irrespective of aetiology, duration or severity. Fifty-two per cent of the whole sample made at least one medical consultation of any type specifically for epilepsy (42.0% primary care, 30.5% hospital, 20.4% both). Most patients with controlled epilepsy (74.5%) had no consultations. Of patients with severe epilepsy, 27.5% made no primary care consultations, 43.4% no hospital consultations and 14.1% no consultations of either type. Gender did not influence the likelihood of either GP or hospital consultations in patients with either controlled or active epilepsy. Increasing seizure frequency was associated with a greater likelihood of one or more hospital consultations for epilepsy, whereas increasing duration of epilepsy was associated with a decreased likelihood of either type of consultation. Age affected consultation rates: of those patients over the age of 65 years, only 29.9% made a medical consultation for epilepsy, compared to 53.8% of young adults. Patients under the age of 17 years were less likely to have consulted a GP and more likely to have consulted a hospital doctor. Ninety percent of new-onset patients had been referred to a hospital doctor, and the mean wait was 6.5 weeks. In conclusion, many patients with epilepsy, including severe epilepsy, are not receiving specialist input, and a significant proportion are receiving no medical supervision. The elderly are over-represented in this group. Care tends to be polarized between hospital or primary care, falling short of the ideal of shared care. It will be important to address the influences on consultation seeking in epilepsy, particularly for those patients currently under no medical supervision.     

Rehospitalization of Psychiatric Patients in a Managed Care Environment

This study examined predictors of readmission to a general hospital psychiatric unit that provided acute inpatient care. Participants were 370 patients admitted to the inpatient unit over a 15-month period. During this period, 105 (28%) patients were readmitted to the unit. Readmitted patients were compared to patients who were not readmitted on (a) symptom improvement during hospitalization, (b) psychosocial and clinical variables, and (c) length of hospitalization. The readmitted patients presented with levels of psychological symptoms similar to those of patients who were not readmitted. Moreover, readmitted patients and patients who were not readmitted reported comparable relief in symptom severity during hospitalization. Readmitted patients were more likely to have at least one previous psychiatric hospitalization, be unemployed, be participating in day treatment, and receiving medicare and social security disability insurance. Rehospitalization is a significant problem and the patients' self-reported symptomatology is not a major determinant of readmission for inpatient treatment.     

Characterization of microwell cultures of dissociated brain tissue for studies of cell-cell interactions

Microwell cultures of dissociated tissue from prenatal rat hippocampus and cerebral cortex as well as from early postnatal cerebellum were used for quantification of neuronal aggregation, process extension, and fasciculation. It was shown that the cells in culture from these different brain regions developed differently with regard to both architecture and rate of differentiation. The effect of a polyclonal antibody against the neural cell adhesion molecule (NCAM), the excitatory amino acid receptor agonist N-methyl-D-aspartate (NMDA), and the neurotoxin acrylamide on aggregation and fiber formation was investigated. Exposure to the NCAM antibody led to formation of fewer but larger aggregates and stimulated the morphological development of the cultures. Acrylamide affected aggregate formation, leading to smaller but more numerous aggregates, and it inhibited process extension and fasciculation. Treatment with NMDA affected process formation and led to formation of more numerous but smaller aggregates. Some of these effects were strongly tissue-dependent. Thus, large differences were seen regarding the effect of the NCAM antibody on aggregation and process extension in cultures from the different brain areas. The culture systems appear to represent convenient and reliable screening tools to study the influence of putative morphoregulatory substances on cell-cell interactions during early neuronal development. J. Neurosci. Res. 47:163–172, 1997. © 1997 Wiley-Liss, Inc.     

Epidermal growth factor receptor activation: how exon 19 and 21 mutations changed our understanding of the pathway.

The discovery of epidermal growth factor receptor (EGFR) mutations in never-smokers has been the most relevant finding ever in non-small cell lung cancer. When patients whose tumors bear the sensitizing mutations are treated with the tyrosine kinase inhibitors gefitinib or erlotinib, we witness response rates and durations never before reported, including complete responses. At the same time, the presence of EGFR mutations has raised numerous new questions, tantalizing data, and new challenges for treatment. This is particularly true as we try to generalize the findings in lung cancer to other malignancies. The indiscriminate use of gefitinib or erlotinib in the general lung cancer population results in meager survival benefit for patients. Similarly, the tyrosine kinase inhibitors have limited activity in a variety of tumor types with EGFR overexpression. This has led to the question of whether EGFR remains a viable target in patients other than those whose tumors contain mutations, and whether the modest activity of cetuximab in colorectal cancer and head and neck cancer represents all that we can expect from inhibition of this pathway in the absence of mutation. Mechanisms of pathway activation other than mutation have been discovered in recent years, and include overexpression mediated by gene amplification or by amplification of a dinucleotide repeat in the EGFR promoter, mutation of an extracellular region on EGFR generating a mutant protein termed EGFRvIII, and enhanced signaling due to heterodimerization with other members of the EGFR family, particularly overexpression of HER2/HER3. The extent to which these paths to EGFR activation will confer sensitivity to the tyrosine kinase inhibitors or to EGFR monoclonal antibodies is being explored. Thus far, published clinical data suggest that there is little room for the administration of gefitinib or erlotinib in the absence of EGFR mutations. The five articles in this edition of CCR Focus will address the various mechanisms of EGFR pathway activation and provide insight into the potential for translation into clinical relevance.