Low dose desensitisation does not reduce the toxicity of sulphasalazine in rheumatoid arthritis

To investigate the apoptosis-inducing effect of glucocorticoid on gastric epithelial cell expressing different p53 genes, a human gastric epithelial cell line-GES-1 was transfected with either wild type or mutant p53 cDNA in vitro. The cells were treated with hydrocortisone in a concentration range of 0.2-0.8 g/L. Apoptotic cells were found in those transfectants. The apoptotic response of the wild-type p53-transfected GES-1 cells was much more marked than that of the mutant p53 transfected ones. It can be inferred that the glucocorticoid secreted not only suppress the immunological response during inflammation, but induce gastric epithelial cell apoptosis as well. If the gastric epithelial cell contains mutant p53 genes, the glucocorticoid confer a selective growth advantage which advance the malignant process.     

Hypoxia enhances [3H]noradrenaline release evoked by nicotinic receptor activation from the human neuroblastoma SH-SY5Y

We have used the human sympathetic neuronal line SH-SY5Y to investigate the effects of hypoxia on noradrenaline (NA) release evoked by either raised [K+]o (100 mM) or the nicotinic acetylcholine receptor (nAChR) agonist dimethylphenylpiperazinium iodide (DMPP). NA release was monitored by loading cells with [3H]NA and collecting effluent fractions from perfused cells kept in a sealed perifusion chamber. Cells were challenged twice with either stimulus and release was expressed as that evoked by the second challenge as a fraction of that evoked by the first. K+-evoked release was unaffected by hypoxia (PO2 approximately 30-38 mm Hg), but release evoked by DMPP was significantly increased. For both stimuli, replacement of Ca2+o with 1 mM EGTA abolished NA release. K+-evoked release was also dramatically reduced in the presence of 200 microM Cd2+ to block voltage-gated Ca2+ channels, but DMPP-evoked release was less affected. In hypoxia, DMPP-evoked Cd2+-resistant NA release was dramatically increased. Our findings indicate that hypoxia increases NA release evoked from SH-SY5Y cells in response to nAChR activation by increasing Ca2+ influx through the nAChR pore, or by activating an unidentified Cd2+-resistant Ca2+-influx pathway. As acetylcholine is the endogenous transmitter at sympathetic ganglia, these findings may have important implications for sympathetic activity under hypoxic conditions.     

Relative value of computed tomography scanning and venous sampling in establishing the cause of primary hyperaldosteronism

The purpose of this study was to evaluate the relative merits of the postural stimulation test, adrenal computed tomography (CT) and venous sampling in the differential diagnosis of patients presenting with primary hyperaldosteronism. The records of 20 patients presenting with primary hyperaldosteronism were reviewed retrospectively. There were 15 patients with a unilateral aldosterone-producing adenoma (APA), four patients with idiopathic hyperaldosteronism (IHA) and one patient with primary adrenal hyperplasia (PAH). The postural stimulation test was based on measurements of plasma aldosterone and renin activity at 08.00 h and at noon after 4 h of ambulation. The CT scans of the adrenals were reviewed by a single radiologist. Bilateral venous sampling of adrenal veins was attempted in all patients and blood collected for aldosterone and cortisol assay. Plasma aldosterone concentration increased after 4 h of standing in all cases of hyperplasia but was also demonstrated in 10/15 patients with a surgically-proven APA. If one defines a significant postural rise as being greater than 30%, then 8/15 patients with APA can be considered as being posturally responsive. Computed tomography scanning correctly identified all 15 cases of APA and also classified correctly the remaining five cases of hyperplasia (four cases of IHA and one case of PAH). Venous sampling failed technically in 4/15 cases of APA and in one case of IHA: a total of 5/20 (25%,). A correct diagnosis of APA or IHA was established in all the remaining cases. However, the one case of PAH was treated successfully by adrenalectomy following venous sampling, which suggested a unilateral adrenal lesion: this one result was the only instance where venous sampling altered clinical decision-making. Computed tomography scanning may be used alone to confirm the cause of hyperaldosteronism where postural studies suggest an adrenal adenoma, and such patients may be considered for early surgery. Venous catheterization studies are not necessary routinely. but may still be useful in selected patients, particularly when CT scanning shows no clear lesion.     

Vitamin E modifies neither fructosamine nor HbA1c levels in poorly controlled diabetes

OBJECTIVE: To examine the effects of vitamin E on total serum protein glycation (fructosamine), hemoglobin glycation (HbA1c), and serum levels of glucose, total cholesterol, triglycerides, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B. MATERIAL AND METHODS: Sixty poorly controlled diabetic patients were randomly assigned to receive either 1200 mg/day of vitamin E or identical placebo capsules during a two month period following a double blind cross-over design with a four week wash-out period between regimens. RESULTS: Seven patients were excluded from the study because of reasons not related to the medication. In the remaining 53 patients, the levels of serum glucose, fructosamine, HbA1c, total cholesterol, HDL-C, LDL-C, Apo A1 and Apo B did not vary significantly with vitamin E as compared with placebo. CONCLUSIONS: No significant effects of vitamin E on any of the parameters evaluated were observed in poorly controlled diabetic patients.     

Lethal murine graft-versus-host disease induced by donor gamma/delta expressing T cells with specificity for host nonclassical major histocompatibility complex class Ib antigens

Although T-cell receptor (TCR) alpha/beta expressing cells have a well-known role in graft-versus-host disease (GVHD) generation, the role of TCR gamma/delta expressing cells in this process has remained unclear. To elucidate the potential function of TCR gamma/delta cells in GVHD, we have used transgenic (Tg) H-2d mice (termed G8) that express gamma/delta heterodimers on a high proportion of peripheral T cells. In vitro, G8 Tg gamma/delta T cells proliferate to and kill C57BL/6 (B6) (H-2b) which express gene products (T10b and T22b) from the nonclassical major histocompatibility complex (MHC) class Ib H-2T region. The infusion of G8 Tg (H-2Td) TCR gamma/delta cells into lethally irradiated [900 cGy total body irradiation (TBI)] B6 (H-2b) mice resulted in the generation of lethal GVHD characterized histologically by destruction of the spleen, liver, lung, and colon. Lethal GVHD was prevented by the injection of anti-TCR gamma/delta monoclonal antibodies. Immunohistochemical analysis of B6 recipients post-bone marrow transplantation (BMT) confirmed that G8 Tg TCR gamma/delta cells infiltrated GVHD target tissues (skin, liver, colon, and lung) and were absent in recipients treated with anti-TCR gamma/delta monoclonal antibodies (MoAbs) but not anti-CD4 plus anti-CD8 MoAbs. In contrast, injection of TCR gamma/delta+ cells into irradiated (900 cGy TBI) B6.A-TIaa BoyEg mice that do not express either T10b or T22b did not induce lethal GVHD. Similarly, in a different GVHD system in which sublethal irradiation without bone marrow (BM) rescue was used, B6 but not B6.A-TIaa/BoyEg mice were found to be susceptible to TCR gamma delta+ cell mediated GVHD-induced lethality characterized by an aplasia syndrome. These results demonstrate that TCR gamma/delta cells have the capacity to cause acute lethal GVHD in mice and suggest that nonclassical MHC class Ib gene products expressed on GVHD target organs are responsible for G8 Tg TCR gamma/delta+ cell mediated lethality.     

Aspiration pneumonia following surgically placed feeding tubes

BACKGROUND: The enteral route is preferred in surgical patients requiring nutritional support; however, controversy surrounds the choice of location of feeding tube placement. Although jejunostomy has been commonly accepted as superior to gastrostomy for long-term nutritional support because of an assumed lower risk of aspiration pneumonia, recent studies suggest that reevaluation of common practices of surgical tube placement is warranted. PATIENTS AND METHODS: We conducted a retrospective chart review of gastrostomy and jejunostomy procedures from 1986 to 1993. Demographic information and complications related to the procedure were reviewed. Aspiration pneumonia was defined as respiratory symptoms, leukocytosis, and infiltrate on chest radiograph. RESULTS: Sixty-nine gastrostomies and 86 jejunostomies were performed during the study period. Six patients were diagnosed with aspiration pneumonia; 2 cases of which occurred with jejunostomy and 4 cases occurred with gastrostomy (P = not significant). CONCLUSIONS: There was no difference in rates of pulmonary aspiration or other complications between gastrostomy and jejunostomy. We suggest that when a surgically placed feeding tube is required, the determination of appropriate procedure be based on clinical factors such as the technical difficulty of the operation or long-term feeding goals.     

Pollutant transport during a regional O3-episode in the mid-Atlantic states

Ozone (O3) concentrations in the Baltimore-Washington (B-W) metropolitan area frequently exceed the National Ambient Air Quality Standard (NAAQS) in the summer months. The most extreme O3 events occur in multi-day high O3 episodes. These events can be regional in scale, with O3 concentrations exceeding the NAAQS at numerous locations along the eastern U.S. seaboard, and are typically associated with slow-moving or stagnant high pressure systems. In the B-W region, the most extreme events typically occur with surface high pressure overhead or just west of the region and an upper air high-pressure area (ridge) to the west or northwest. Besides providing conditions conductive to local O3 production (subsidence and strong low-level inversions, weak horizontal winds, little cloud cover), this weather pattern may also result in transport of O3 and its precursors from heavily industrialized areas west and north of the B-W region. In this paper, observations and back trajectories made during the severe regional O3 event of July 12-15, 1995, are used to confirm the hypothesis that significant regional-scale transport of O3 and its precursors occur during extreme O3 events of the standard type in the B-W area.