Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial.

Objective: Vitamin E, the most potent naturally occurring lipid soluble antioxidant has been suggested to possess both anti-inflammatory and analgesic activity in humans. This double blind and randomised study used a broad spectrum of clinical and laboratory parameters to investigate whether there was any additional anti-inflammatory or analgesic effects, or both, of orally administered alpha-tocopherol in rheumatoid arthritis patients who were already receiving anti-rheumatic drugs.

Methods: Forty two patients were enrolled and treated with alpha-tocopherol (n = 20) at a dose of 600 mg twice a day (2 x 2 capsules) or with placebo (n = 22) for 12 weeks.

Combination immunotherapy which neutralises the effects of TNF alpha and IL-1 beta attenuates the circulatory failure and multiple organ dysfunction caused by endotoxin in the rat.

Pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF alpha) or interleukin-1 beta (IL-1 beta) are implicated in the pathogenesis of septic shock. Here we investigate the role of endogenous TNF alpha and IL-1 beta on (i) the circulatory failure, (ii) the multiple organ dysfunction syndrome (MODS) and (iii) the induction of the inducible isoform of nitric oxide (NO) synthase (iNOS) caused by endotoxin (LPS) in the anaesthetised rat. Here we demonstrate that (i) a polyclonal antibody against TNF alpha, (ii) a polyclonal antibody against IL-1, (iii) co-administration of polyclonal antibodies against TNF alpha and IL-1 and (iv) neutralisation of the effects of both TNF alpha and IL-1 with one polyclonal antibody directed against both cytokines reduces the circulatory failure, the liver injury/dysfunction, the pancreatic injury (but not the renal dysfunction) caused by endotoxin in the rat.

Effect of first-trimester nuchal translucency on second-trimester maternal serum biochemical screening for Down's syndrome.

We evaluated the effectiveness of 10-14 week nuchal translucency measurement in routine ultrasound screening for Down's syndrome, and its effect on the sensitivity of subsequent maternal serum biochemistry. This was an observational study, in which all women attending for antenatal care at a district general hospital were routinely offered a first-trimester nuchal translucency scan and second-trimester quadruple maternal serum biochemistry as screening tests for Down's syndrome. The main outcome measures were abnormal fetal karyotype and the performance of screening tests.

X-ray microtomography: 3-dimensional imaging of teeth for computer-assisted learning.

X-ray microtomography (XMT), a miniaturised form of computed tomography, has been used to generate 3-dimensional volume data sets of the X-ray absorption of human teeth in vitro, with a resolution of approximately 40 microns (cubic voxel sidelength). Examples are presented of images relevant to dental morphology, cariology, and cavity preparation and restoration. Applications of XMT imaging to dental education are discussed in the context of new approaches to visual learning through computer-assisted methods.

Is Hartmann's the solution?

As Hartmann's solution is commonly used by anaesthetists, we surveyed a group of Part III FRCA candidates to establish their knowledge of its constituents and the purpose and metabolism of the lactate in solution. Of the 82 candidates surveyed only three (4%) accurately recorded the electrolytes and their concentrations in Hartmann's solution. Lactate was stated to be a source of bicarbonate by 52 (63%) and a source of glucose by 17 (21%).

Analysis of primary care staff language about aggression at work using concordancing techniques to identify themes.

Objective: We aimed to describe features of language used during interviews about the extent of aggression and violence at work and their effect on primary care staff.

Method: Forty-four primary health care team members in the West Midlands were interviewed, and interviews were recorded on videotape. The language content of these interviews was analysed using Cobuild concordancing software.

Satisfaction with care of patients attending a dedicated dental clinic: comparisons between 1989 and 1994.

This investigation aimed to audit patient satisfaction with care at a dedicated dental clinic, using previously developed standards and criteria. A self-complete questionnaire was administered to a group of 161 patients assessing the dimensions of care availability, affective behaviour and technical competence. Comparisons with baseline showed a high but slightly decreased level of satisfaction with technical competence, a significantly higher level of satisfaction with the affective behaviour of the clinic staff but a continuing level of dissatisfaction with the availability of care.

Intermittent androgen deprivation after PSA-complete response as a strategy to reduce induction of hormone-resistant prostate cancer.

Objectives: The increasing interest in exploring the use of intermittent androgen deprivation in prostate cancer has prompted a retrospective review of patients who elected to stop treatment.

Methods: Case records were reviewed.

Results: Twenty patients after 3 to 48 months (median 12) of endocrine therapy elected to stop therapy.

Ascorbate promotes low density lipoprotein oxidation in the presence of ferritin.

Whilst catalytic iron has been implicated in the development of atherosclerosis by initiating low density lipoprotein (LDL) oxidation, the source of such iron remains uncertain. Here, we show that LDL oxidation in the presence of ferritin was stimulated by ascorbate (15-60 microM), whilst this effect was inhibited by the iron chelator desferrioxamine. Ascorbate also showed an antioxidant activity at high concentrations (125-250 microM).

Persistent increase in the rates of apoptosis and dicentric chromosomes in surviving V79 cells after X-irradiation.

In parallel to delayed reproductive death and delayed micronuclei in surviving V79 cells that have been reported, the frequency of apoptosis and dicentrics was investigated in the same cell line, 1-2 weeks after X-ray doses between 1 and 12 Gy. Apoptosis was assessed by morphological criteria after staining with Giemsa and using the Apoptag method in parallel. The frequency of apoptosis peaked 48 h after irradiation at about 35% as a function of dose and then decreased to about 10% on day 3.

The electrically stimulated gracilis neosphincter incorporated as part of total anorectal reconstruction after abdominoperineal excision of the rectum.

Objective: The authors investigated the feasibility and effectiveness of combining electrically stimulated gracilis neoanal (ESGN) sphincter and a coloperineal anastomosis in selected patients after abdominoperineal excision of the rectum (APER).

Summary Background Data: The ESGN is effective in the treatment of idiopathic fecal incontinence.

Methods: Between March 1989 and September 1993, 12 patients (9 men, 3 women) with a median age of 59.

Airway response of asthmatic subjects to inhaled allergen after exposure to pollutants.

Background: Recent studies have suggested that air pollutants resulting from vehicle exhaust emissions and burning of fossil fuels, either in combination or individually, may enhance the airway response of asthmatic subjects to inhaled allergen. It was hypothesised that the airway response to inhaled allergen after exposure to a combination of 400 ppb nitrogen dioxide (NO2) and 200 ppb sulphur dioxide (SO2) is increased 24-48 hours after exposure.

Methods: Thirteen mild atopic asthmatic volunteers were exposed for six hours to a single exposure of air and three exposures of the combination of 400 ppb NO2 + 200 ppb SO2 in randomised order, and then challenged with increasing concentrations of Dermatophagoides pteronyssinus allergen either immediately after exposure to air, or immediately, 24 hours or 48 hours after exposure to the combination of the two pollutants, until a 20% fall in forced expiratory volume in one second (FEV1) was recorded.

Oct-1 interacts with conserved motifs in the human thyroid transcription factor 1 gene minimal promoter.

The homeodomain containing thyroid transcription factor 1 (TTF-1) is a lung- and thyroid-enriched protein implicated in the regulation of a number of pulmonary specific genes. Within the lung TTF-1 is expressed within the epithelial cells. Although the molecular mechanisms that govern this tight cell-type-specific distribution are unclear, transient transfection studies have suggested that tissue specificity is conferred in part by regions of the proximal promoter.

Adriamycin stimulates proliferation of human lymphoblastic leukaemic cells via a mechanism of hydrogen peroxide (H2O2) production.

It is becoming clear that adriamycin cytotoxicity may be mediated by semiquinone-free radicals derived from the drug itself and reactive oxygen species (ROS). Recent evidence supports the concept that low concentrations of ROS are able to stimulate cell proliferation, and, based on the observation that subtoxic concentrations of adriamycin can also induce cell proliferation, we hypothesize that low concentrations of adriamycin stimulate cell proliferation by a ROS generation mechanism. We have employed spin-trapping and electron spin resonance (ESR) spectroscopy to investigate the nature of the adriamycin-generated ROS.

Obesity genes.

This review highlights the considerable advances in the understanding of the inheritance of fatness and the possible genetic mechanisms. The investigation of animal models confirms the fundamental importance of genes in determining fatness and demonstrates a genetic link between adipocyte function, derangements of steroid metabolism, insulin secretion and hypothalamic regulation. The heterogeneous nature of human obesity makes it unwise to extrapolate directly from the findings in animals but these findings do provide important clues to the situation in man.

Validation of a particle enhanced immunoturbidimetric assay for serum beta 2-microglobulin on the Dade aca.

We describe the development and validation of a fully automated homogeneous immunoassay for serum beta 2-microglobulin on the Dade aca clinical analyzer. The assay employs latex enhanced immunoturbidimetry, with an affinity purified polyclonal antibody covalently coupled to a 40 nm latex particle. The assay working range is < 0.

Effect of different storage temperatures, sample collection procedures and immunoassay methods on osteocalcin measurement.

The apparent instability of measured osteocalcin has been reported as method-dependent and related to preanalytical variables such as storage temperature, and the use of anticoagulants and protease inhibitors. The aim of this study was to determine a sample collection procedure which minimised osteocalcin degradation. Blood samples from five normal individuals were collected with or without anticoagulants and protease inhibitors (heparin, EDTA, or heparin and aprotinin) and stored at 4 degrees C, -20 degrees C or -70 degrees C for up to 7 days, 28 days and 90 days respectively.

Proliferative verrucous leukoplakia: a report of ten cases.

A particularly aggressive form of oral leukoplakia that commences with a hyperkeratosis, spreads to become multifocal and verruciform in appearance, and later becomes malignant has been termed proliferative verrucous leukoplakia. Ten patients with persistent multifocal verruciform white patches were investigated. Lesions were often bilateral and affected predominantly mandibular alveolar and buccal mucosa.

Acidic fibroblast growth factor enhances neurite outgrowth and stimulates expression of GAP-43 and T alpha 1 alpha-tubulin in cultured neurones from adult rat dorsal root ganglia.

The affects of acidic fibroblast growth factor (FGF-1) on neurite outgrowth were investigated and related to the levels of mRNA encoding the growth associated protein genes GAP-43 and the neuron specific alpha-tubulin, T alpha 1, in primary cultures of dorsal root ganglia (DRG) neurones from adult rats. In response to FGF-1, sensory neurones produced a high level of neurite outgrowth which was highest (2.70 +/- 0.

Testis conservation studies in germ cell cancer justified by improved primary chemotherapy response and reduced delay, 1978-1994.

Objective: To investigate the need for the continued encouragement of early diagnosis of germ cell cancer of the testis, in view of the prevailing cure rate of 95%.

Patients And Methods: The study comprised a retrospective review of 453 unselected and previously untreated patients referred to one centre between 1978 and 1984, comparing the delay from first symptoms with the histological diagnosis.

Results: With a delay of < 30 days, 20% of patients had overt metastases at presentation and if the delay was > 4 months.

Molecular cloning of the forkhead transcription factor HNF-3 alpha from a human pulmonary adenocarcinoma cell line.

We have cloned the human homologue of HNF-3 alpha from the pulmonary adenocarcinoma cell line NCI-H441. Full-length HNF-3 alpha which was found to be 2872 bp encoded a protein of 473 amino acids. The human protein is highly related to the rat and mouse homologues and the forkhead DNA binding domain is highly conserved between all species yet identified.