Biomedical subjects
Publications and source records attributed to R Ford.
The publication of the national service framework for mental health provides a good opportunity to review acute psychiatric services, which are unpopular with patients and understaffed. The framework recommends a balance of hospital beds, community provision and home care. Planning should usually cover one or more primary care groups.
BACKGROUND: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is related to Helicobacter pylori infection and may depend on this infection for growth. OBJECTIVE: To determine the response of gastric MALT lymphoma to antibiotic treatment. DESIGN: Prospective, uncontrolled treatment trial. SETTING: University hospital referral center and three collaborating university and community hospitals. PATIENTS: 34 patients with stage I or stage II N1 gastric MALT lymphoma. INTERVENTION: Two of three oral antibiotic regimens--1) amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2)tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily--were administered sequentially (usually in the order written) for 21 days at baseline and at 8 weeks, along with a proton-pump inhibitor (lansoprazole or omeprazole) and bismuth subsalicylate. MEASUREMENTS: Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsy. Partial remission was defined as a reduction in endoscopic tumor stage or 50% reduction in the size of large tumors. RESULTS: 34 patients were followed for a mean (+/-SD) of 41 +/- 16 months (range, 18 to 70 months) after antibiotic treatment. Of 28 H. pylori-positive patients, 14 (50% [95% CI, 31% to 69%]) achieved complete remission, 8 (29%) achieved partial remission (treatment eventually failed in 4 of the 8), and 10 (36% [CI, 19% to 56%]) did not respond to treatment. Treatment failed in all 6 (100% [CI, 54% to 100%]) H. pylori-negative patients. Patients with endoscopic appearance of gastritis (stage I T1 disease) were most likely to achieve complete remission within 18 months. Tumors in the distal stomach were associated with more favorable response than tumors in the proximal stomach. CONCLUSIONS: A subset of H. pylori-positive gastric MALT lymphomas, including infiltrative tumors, may respond to antibiotics. The likelihood of early complete remission seems to be greatest for superficial and distal tumors.
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Most human lymphomas remain heterogeneous biologic entities in spite of recent advances in the description of their clinical presentation, cellular morphology, immunophenotype, and genotype. Elucidation of genetic alterations causing malignant transformation may explain pathogenesis, refine differential diagnosis, clarify prognosis, and provide rational basis for new therapy. During the last year the expression of anaplastic lymphoma kinase clarified presentation and provided clues toward the outcome of anaplastic large cell lymphoma; the breakpoints of t(2;5) were mapped; constitutive activation of anaplastic lymphoma kinase by a chromosomal inversion was described; transformation was shown to be independent of nuclear localization of anaplastic lymphoma kinase; and phospholipase C-gamma was identified as a molecular target for the kinase activity of anaplastic lymphoma kinase. Molecular characterization of recurrent chromosome abnormalities has identified new candidate oncogenes: bcl-9, bcl-10, PAX-5, MMSET, and c-maf. Their precise role in malignant transformation, and the frequency of their alteration in lymphoma and myeloma, is not yet defined. The expression of the antiapoptotic protein bcl-2 on aggressive lymphomas was shown to be associated with inferior disease-free survival by several investigators. This may be a target of pharmacologic reduction of bcl-2 levels. Can these advances in molecular pathogenesis improve cure rates for lymphoma? The spectacularly successful molecular modeling of inhibitors for HIV protease suggests that this may be an attainable objective.
A series of novel 6-substituted 5,6-dihydro-5-hydroxy-alpha-pyrone esters, 1 approximately 3, isolated from fermentations of a Phomopsis sp. (Xenova culture collection no. X22502) have been identified as inhibitors of lipopolysaccharide (LPS)-induced cytokine production. These include the (6S)-4,6-dimethyldodecadien-2E,4E-dienoyl ester of phomalactone, 1, and two analogues bearing a prop-2E-enoic acid moiety at the 6-position of the alpha-pyrone ring. (6S)-4,6-Dimethyl-2E,4E-dienoic acid, 4, and a hydroxylated analogue, 5, were also isolated and characterised. The most potent cytokine production inhibitor was 1, which inhibited LPS-induced tumour necrosis factor alpha (TNFalpha) production by U937 cells and LPS-induced interleukin 1beta (IL-1beta) production by peripheral blood mononuclear cells (PBMC) with IC50 values of 80 nM and 190 nM respectively. The effect of 1 in PBMC was selective for IL-1beta relative to TNFalpha. The inhibition of IL-1beta production by 1 involved a post-translational mechanism of action at the level of IL-1beta secretion as demonstrated by the lack of an effect on cell-associated IL-1beta production. 1 showed no effect on the activity of caspase 1 in cytosolic extracts from the THP1 monocytic cell line.
OBJECTIVES: To provide (via the Mental Health Act Commission's "national visit") empirical evidence on ward occupancy levels, use of the Mental Health Act 1983, nurse staffing, and care of female patients on acute adult psychiatric wards. DESIGN: One day survey of a stratified random sample. SETTINGS: 119/250 (47%) acute adult psychiatric inpatient units in England and Wales. SUBJECTS: End sample of 263 acute psychiatric inpatient wards. MAIN OUTCOME MEASURES: Ward occupancy rates; number of patients detained under the Mental Health Act and proportion "absent without leave"; nurse staffing levels, skill mix, and vacancies;proportion of women with self contained, women-only facilities. RESULTS: Mean ward occupancy was 99% (95% confidence interval 97% to 102%). A ward mean of 30% (28% to 32%) of patients were detained under the Mental Health Act; of all detained patients, 1% (1% to 2%) were absent without leave. A ward mean of 0.3 (0.29 to 0.31) nurses were on duty per patient at the time of the visit. An estimated ward mean of 31% (30% to 32%) of nurse staffing may have been through casual contracts--higher in inner (48% (43% to 53%)) and outer London (45% (41% to 48%)). On 26% (21% to 32%) of wards, there were no nurses interacting with patients. A ward mean of 36% (30% to 41%) of female patients had self contained, women-only facilities. CONCLUSIONS: Attention should focus on improving the quality of acute inpatient psychiatric care as well as of community care.
A 24-hour home care team for people with severe mental illness has led to a reduction in inpatient stays and reduced service costs, according to a controlled evaluation. The 24-hour availability was popular with users. Home treatment should not be seen as an exclusive alternative to inpatient care. Admission is essential in some cases.
The Rel family of transcriptional activators form a large diverse group of proteins that are involved in the activation of genes involved in immunity, development, apoptosis and cancer. So far, none of the rel genes cloned in mammals appear to be required for embryonic development. We have cloned and characterized a cDNA from an embryonic cDNA library that encodes a novel Xenopus Rel protein, called Xrel3. Xrel3 is a member of the cRel subfamily and is most closely related to but distinct from other Xenopus Rel members. The expression of Xrel3 mRNA was investigated using Northern analysis, RNase protection assay, reverse transcriptase-linked polymerase chain reaction and in situ hybridization. Messages are present maternally and are slightly enriched in the equatorial region of the blastula stage embryo. At gastrulation, the accumulation of Xrel3 messages declines to undetectable levels but then increases after neurulation. In situ RNA hybridization was used to determine the spatial location of Xrel3 messenger RNA in embryos. Messages are localized to the developing forebrain, dorsal mid-hindbrain region, the inner ear primordium, or otocyst, and in the notochord. Overexpression by microinjection of Xrel3 RNA induced tumors in the developing embryo that appeared after gastrulation. The location of the tumors depended on the location of the injection site. These results suggest that Xrel3 might have a generalized role in regulation of cell differentiation in the embryo.
Human colorectal carcinoma (CRC) cell survival for the first 24 h after implantation in the hepatic sinusoid determines its potential to colonize the liver. Nearly 10-fold more highly metastatic CX-1 cells survive within the livers of nude mice 24 h after intrasplenic injection than weakly metastatic clone A cells. Because CRCs contact sinusoidal endothelial cells (SECs) during implantation, we sought to determine whether SECs were more toxic to clone A than to CX-1 cells. When 2 x 10(4) vital dye-labeled CRC cells were added to murine SEC monolayers, more than 30% of clone A cells lost calcein AM fluorescence compared to fewer than 5% of CX-1 cells after 24 h of coculture with SECs. Kupffer cells did not mediate this effect, because neither enriched Kupffer cells nor SECs treated with a Kupffer cell inhibitor altered the SEC-mediated toxic effect to clone A cells. Pretreatment with a nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine, superoxide dismutase, or dexamethasone, blocked SEC-mediated toxicity to clone A cells, whereas calcium chelation and catalase did not. In addition, clone A cells were more sensitive to a superoxide donor, 3-morpholinosydnonimine N-ethylcarbamide, than were CX-1 cells, and neither cell line was sensitive to sodium nitroprusside, a nitric oxide donor. Thus, unstimulated murine SECs produce reactive oxygen species that are selectively toxic to weakly metastatic clone A cells. This may be a mechanism by which host liver cells eliminate weakly metastatic neoplastic cells.
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All NHS services are expected to make in-patient wards single-sex. However, as LESLEY WARNER and RICHARD FORD report, women in psychiatric hospitals still have to share sleeping accommodation with men, and still experience sexual harassment, violence, threat and abuse. Some units are unable even to guarantee 24-hour access to a female member of staff.
A pathways study looking at the process of acute care found the most vulnerable people admitted to hospital appeared to be the least likely to have received effective community care. Community services must be more systematically focused on those most in need. Day hospitals need to function as acute alternatives to inpatient care. Accommodation for newer service users must be considered.
Interviews conducted by other users can be a successful means of capturing mental health users' views on services. In this study, more than a third of those with severe mental health problems considered themselves over-medicated, and many wanted more 'talking therapies'. More than three-quarters were satisfied with their community psychiatric nurse but under half were satisfied with their consultant. A fifth did not know how to get help in a crisis.
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