Describes the findings from the first year of an evaluation of change at a PMS+ site in West Cumbria. The study has used qualitative methods including non-participant observation at the site; face to face interviews with 28 clinical staff; group interviews with administrative and secretarial staff; and the collection of documents. Analysis of the data against a set of "outcome indicators" shows that significant progress has been made towards implementing the model of primary care delivery described in the pilot proposal. Multidisciplinary working is developing in the clinical action groups and the establishment of a primary care emergency unit has changed general practitioner workloads. The new organisation structure is not yet working wholly as anticipated but recently initiated changes are intended to strengthen the role and authority of the management board.

Data Collection↗

PubMed2000

Comparison of 3-D maximum a posteriori and filtered backprojection algorithms for high-resolution animal imaging with microPET.

We have evaluated the performance of two three-dimensional (3-D) reconstruction algorithms with data acquired from microPET, a high resolution tomograph dedicated to small animal imaging. The first was a linear filtered-backprojection algorithm (FBP) with reprojection of the missing data, and the second was a statistical maximum a posteriori probability algorithm (MAP). The two algorithms were evaluated in terms of their resolution performance, both in phantoms and in vivo. Sixty independent realizations of a phantom simulating the brain of a baby monkey were acquired, each containing three million counts. Each of these realizations was reconstructed independently with both algorithms. The ensemble of the 60 reconstructed realizations was used to estimate the standard deviation as a measure of the noise for each reconstruction algorithm. More detail was recovered in the MAP reconstruction without an increase in noise relative to FBP. Studies in a simple cylindrical compartment phantom demonstrated improved recovery of known activity ratios with MAP. Finally, in vivo studies also demonstrated a clear improvement in spatial resolution using the MAP algorithm. The quantitative accuracy of the MAP reconstruction was also evaluated by comparison with autoradiography and direct well counting of tissue samples and was shown to be superior.

Algorithms↗

PubMed2000

Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy.

PURPOSE: The goal of the study was to evaluate the safety and efficacy of a broad oxcarbazepine (OXC) dosage range (600, 1200, and 2400 mg/d) as adjunctive therapy for uncontrolled partial seizures and to determine the relationship between trough plasma 10-monohydroxy derivative concentrations and OXC safety and efficacy. METHODS: This multinational, multicenter, randomized, 28-week, double-blind, placebo-controlled, four-arm, parallel-group trial enrolled 694 patients aged 15-65 years with uncontrolled partial seizures with or without secondarily generalized seizures. The primary efficacy variable was percentage change in seizure frequency per 28 days relative to baseline. RESULTS: The median reduction in seizure frequency was 26%, 40%, 50%, or 8% for patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively (all p < or = 0.0001). Of patients in the 600, 1200, or 2400 mg/d OXC groups, 27%, 42%, and 50% respectively, had more than 50% reduction in seizure frequency compared with 13% for placebo (all p < 0.001). Higher plasma 10-monohydroxy derivative concentrations were associated with larger decreases in seizure frequency (p = 0.0001). During the double-blind treatment phase, 84%, 90%, 98%, and 76% of patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively, reported one or more adverse events. The most common adverse events were related to the nervous and digestive systems. CONCLUSIONS: OXC is safe and effective as adjunctive therapy in patients with uncontrolled partial seizures. OXC 600 mg/d was the minimum effective dosage; effectiveness of OXC increased with dose. The rapid and fixed titration to high doses was associated with an increased risk of adverse events, which could potentially be reduced by adjusting concomitant antiepileptic medication and by using a slower, flexible OXC titration schedule.

Administration, Oral↗

PubMed2000

Molecular characterization of Cryptosporidium isolates obtained from human immunodeficiency virus-infected individuals living in Switzerland, Kenya, and the United States.

A total of 22 Cryptosporidium isolates from human immunodeficiency virus-infected patients from Kenya, Switzerland, and the United States were examined at three genetic loci: the 18S ribosomal DNA, HSP-70, and acetyl coenzyme A synthetase genes. Four distinct Cryptosporidium genotypes were identified: (i) the Cryptosporidium parvum "human" genotype, (ii) the C. parvum "cattle" genotype, (iii) Cryptosporidium felis, and (iv) Cryptosporidium meleagridis. This is the first report of C. meleagridis in a human host. These results and those of others indicate that immunocompromised individuals are susceptible to a wide range of Cryptosporidium species and genotypes. Future studies are required to understand the full public health significance of Cryptosporidium genotypes and species in immunocompromised hosts.

AIDS-Related Opportunistic Infections↗

PubMed2000

Investigation of sudden unexpected deaths in infancy.

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Child↗

PubMed2000

Congenital progressive polymorphic cataract caused by a mutation in the major intrinsic protein of the lens, MIP (AQP0).

BACKGROUND: Congenital cataract, when inherited as an isolated abnormality, is phenotypically and genetically heterogeneous. Although there is no agreed nomenclature for the patterns of cataract observed, a recent study identified eight readily identifiable phenotypes. METHODS: The Moorfields Eye Hospital genetic eye clinic database was used to identify a four generation family with isolated autosomal dominant congenital cataracts. All individuals (affected and unaffected) underwent a full ophthalmic assessment. RESULTS: The results of the molecular linkage study identifying a missense mutation in the gene encoding the major intrinsic protein of the lens (MIP) have been published elsewhere. Affected individuals had bilateral discrete progressive punctate lens opacities limited to mid and peripheral lamellae with additional asymmetric polar opacification. One young female had predominantly cortical cataract and another had serpiginous nuclear opacities. CONCLUSIONS: This phenotype has not been recorded in human families before and has been termed polymorphic. The pattern of opacification appears to reflect the distribution of MIP in the lens. Furthermore, this is the first clear evidence of allelic heterogeneity in this condition following the identification of a family with lamellar cataracts who have a different mutation within the MIP gene.

Adolescent↗

PubMed2000

Tumoral distribution of long-circulating dextran-coated iron oxide nanoparticles in a rodent model.

PURPOSE: To investigate the accumulation and cellular uptake of long-circulating dextran-coated iron oxide (LCDIO) particles in malignant neoplasms in vivo. MATERIALS AND METHODS: A gliosarcoma rodent model was established to determine the distribution of a model LCDIO preparation in tumors. LCDIO accumulation in tissue sections was evaluated with multichannel fluorescence microscopy with rhodaminated LCDIO, green fluorescent protein as a tumor marker, and Hoechst 33258 dye as an intravital endothelial stain. Uptake into tumor cells was corroborated with results of immunohistochemical and cell culture uptake experiments. The effect of intratumoral LCDIO uptake on magnetic resonance (MR) imaging signal intensity was evaluated with a 1.5-T superconducting magnet. RESULTS: Tumoral accumulation of LCDIO was 0.11% +/- 0.06 of the injected dose per gram of tissue in brain tumors and was sufficient for detection at MR imaging. In tumor sections, LCDIO was preferentially localized in tumor cells (49.0% +/- 4.6) but was also taken up by macrophages in tumors (21.0% +/- 3.1) and by endothelial cells in the areas of active angiogenesis (6.5% +/- 1.4). In cell culture, LCDIO uptake was strongly correlated with growth rate of tumor cell lines. CONCLUSION: Tumoral LCDIO accumulation was not negligible and helped explain MR imaging signal intensity changes observed in clinical trials. Microscopically, LCDIO accumulated predominantly in tumor cells and tumor-associated macrophages. Uptake into tumor cells appeared to be directly proportional to cellular proliferation rates.

Animals↗

PubMed2000

The histologic classification of 602 cases of feline lymphoproliferative disease using the National Cancer Institute working formulation.

Case information and histologic slides for 688 admissions of feline tissues from 12 veterinary institutions were assembled and reviewed to determine tissues obtained by biopsy or necropsy, age and sex of cat, tumor topography, feline leukemia viral antigen status, histologic frequency of mitoses, diagnosis, presence of necrosis, and presence and degree of sclerosis. Histologic sections were examined to place the lesions in one of the diagnostic categories of the National Cancer Institute working formulation (NCI WF) for lymphomas or lymphoid leukemia. Correlations between the various factors determined were tested using contingency tables and chi-square analysis to provide a statistical comparison between the levels of observations determined by case examination with the numbers expected from chance alone. Significant correlations (P < or = 0.05) were found between diagnosis and tumor topography, the frequency of mitoses, necrosis, sclerosis, and age, between mitoses and necrosis, topography, age, and feline leukemia viral infection status, between topography and necrosis and age, and between leukemia viral status and age. Significant correlations between diagnosis and tumor topography included a greater than expected number of cases of acute and chronic lymphoid leukemia and multicentric distribution of tumor. Small cell lymphomas were more frequent than expected in enteric and cutaneous areas and less frequent than expected in mediastinal, renal, and multicentric areas. In contrast, the high-grade small noncleaved type of lymphomas was found significantly more frequently than expected in the mediastinum and less frequently than expected in enteric tissues. In comparing diagnosis and frequency of mitoses, the lymphomas classified as low grade by the NCI WF were significantly more frequent than expected in the lower categories (0-2/100x) of mitoses, and those classified as high-grade lymphomas were more frequent than expected in the higher categories (4-8/1OOx) of mitoses. In comparing diagnosis and sclerosis, diffuse sclerosis was more frequent than expected for the intermediate grade lymphomas of mixed cell type and for the high-grade lymphomas of the immunoblastic polymorphous type. In comparing diagnosis and locally extensive necrosis, this feature was more frequently observed than expected for cases of intermediate grade lymphoma of the small-cleaved cell category and for the high-grade lymphoma of the immunoblastic cell type. In comparing mitoses and necrosis, the lower grade lymphomas were, in general, characterized by a lower frequency of mitoses and a lower incidence of necrosis then would be expected from chance alone. In contrast, the higher grade lymphomas were characterized by more frequent mitoses and a higher incidence of necrosis. In tests comparing mitoses and tumor topography, lymphomas of the alimentary tract were more frequently observed than expected in the category with the lowest level of mitoses (0-1/100x), whereas lymphomas of the mediastinum and kidney were more frequently observed than expected in the categories with a higher level (4-20/ 100x) of mitoses.

Animals↗

PubMed2000

Determination of size in invasive breast carcinoma: pathologic considerations and clinical implications.

The widespread use of mammography has made the detection of increasingly small, often impalpable, invasive breast carcinomas possible. An enhanced understanding of morphological factors, among the foremost of which is size of invasive component of carcinoma, is changing the management of breast cancer To the uninitiated, the determination of size of invasive component is seemingly simple but in practical terms is complicated by a number of ambiguous issues. Practical guidelines for the assessment of size of invasive carcinoma are proposed.

Adult↗

PubMed2000

Compliance and psychological reactance in schizophrenia.

OBJECTIVES: Non-compliance with neuroleptic medication in schizophrenia is a major cause of relapse. A number of sociodemographic variables, and illness, attitudinal and treatment variables, have been demonstrated to be associated with non-compliance. The present study examined a range of these variables and their predictive value in determining past and current compliance. METHODS: Thirty-nine patients suffering from schizophrenia and three patients suffering from schizoaffective disorder completed a series of questionnaires assessing psychological reactance, insight, subjective response to medication, perceived threat to freedom of choice, and degree of current and past compliance. Logistic regression analyses were performed to determine which factors best predicted past and current compliance. RESULTS: Psychological reactance and age were found to be the best predictors of past compliance, with an interaction between reactance and perceived threat to freedom of choice posed by treatment provision also making a significant contribution. Past compliance behaviour and subjective response to medication predicted current compliance most significantly. CONCLUSIONS: Reactance is an important predictor of compliance history especially when patients perceive treatment to be a threat to freedom of choice. Subjective response to neuroleptics is most important in predicting current compliance. Implications for intervention are discussed.

Adult↗

PubMed2000

Hydrocephalus: comparison of clipping and embolization in aneurysm treatment.

OBJECT: In this retrospective study conducted at Atkinson Morley's Hospital and Middlesbrough General Hospital, the authors analyzed 100 matched patients who had suffered subarachnoid hemorrhage (SAH) to determine whether the technical procedure by which aneurysms are treated affects the development of chronic hydrocephalus. METHODS: Four hundred seventy-five patients presented with SAH between 1995 and 1998. Exclusion criteria included posterior circulation aneurysms, multiple aneurysms, electively clipped or embolized aneurysms, angiographically undetected SAH, patients who died within 1 month of neurosurgical intervention, and patients with the same aneurysm location but a different Fisher grade. The authors matched 50 patients who underwent embolization of their aneurysms with another 50 who had similar Fisher grades and aneurysm types and underwent clipping of their aneurysms. The maximum incidence of ruptured aneurysms occurred in patients who were between 41 and 60 years of age, with women preponderant in both study groups. In each group, 27 patients had anterior communicating artery aneurysm, 13 had posterior communicating artery aneurysm, seven had middle cerebral artery aneurysm, and three had internal carotid artery aneurysm. The lesions in three patients in each group were Fisher Grade I, in 23 patients they were Fisher Grade II, in 14 they were Fisher Grade III, and 10 patients had Fisher Grade IV SAH. Nine patients among those with clipped aneurysms and eight of the patients who underwent embolization had hydrocephalus for which they needed intervention. These interventions included lumbar puncture, ventricular drainage, and ventriculoperitoneal (VP) shunt placement; three patients in each group needed VP shunt placement. CONCLUSIONS: The technical procedure used to treat aneurysms, whether clipping or embolization, does not significantly affect the development of chronic hydrocephalus. However, a larger sample of patients is needed for accurate comparisons and stronger conclusions.

Adolescent↗

PubMed2000

Preliminary results from the Canadian Veterinary Urolith Centre.

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Animals↗

PubMed2000

Leukocytosis is proportional to HELLP syndrome severity: evidence for an inflammatory form of preeclampsia.

BACKGROUND: We investigated the possibility that HELLP syndrome is in part a systemic inflammatory response. METHODS: We evaluated total white blood cell (WBC) counts of all patients with severe preeclampsia with and without HELLP syndrome admitted to our hospital between 1995 and 1997. Patients were grouped by diagnosis and timing of platelet nadir. Analysis of variance and regression analysis were used for data analysis. RESULTS: Of 177 patients, 91 had HELLP syndrome, and 86 had severe preeclampsia alone. The WBC counts were significantly higher in patients with HELLP syndrome (12.5 +/- .442 x 10(9)/L) than in patients with severe preeclampsia (10.3 +/- .288 x 10(9)/L). Regression analysis showed that platelet counts varied inversely with WBC counts. Also, patients with class I HELLP syndrome had significantly higher WBC counts than patients with other classes of HELLP syndrome. CONCLUSION: The finding of an association between increasing leukocytosis and worsening thrombocytopenia early in the course of HELLP syndrome supports the hypothesis that it may represent an inflammatory process.

Analysis of Variance↗

PubMed2000

Primary care groups. Back to basics.

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General Practice↗