[The hospital service in the field of domiciliary care of the aged].
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Biomedical subjects
Publications and source records attributed to M Perez.
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The effectiveness of chemiluminescence (ChL) in vitro to measure free radicals generated as a result of metabolic disorganization caused by radiation sickness is evaluated. The results are correlated with those obtained by measuring superoxide dismutase (SOD) activity and lipid peroxide as levels of thiobarbituric acid reacting substances (TBARS). To this aim, livers from irradiated Wistar rats were removed immediately (day 0) after irradiation and also 7 and 14 d later. ChL results, expressed in arbitrary units (AU)/min/mg protein, were analyzed for irradiated samples and controls, for different doses at different times. Increased levels of ChL emission were observed not only on day 0, but also on days 7 and 14. On the other hand, SOD activity showed a decrease on the 7th d, and significantly higher lipid peroxide levels were observed in the assays performed on the 14th d, at all exposure doses. The correlation between temporal changes in the SOD activity, ChL emission, and higher TBARS levels a week later were evident from the data. These results indicate that the ChL technique proved to be useful in combination with other techniques currently used for evaluating radiation oxidative injury.
Osteoclast activity is inhibited by elevated [Ca2+]o; however, the underlying molecular mechanism is unknown. We used the human osteoclast-like cells GCT23 to elucidate their cation-sensing properties. Cells responded to elevated [Ca2+]o with rapid concentration-dependent [Ca2+]i transients (EC50 = 7.8 mm, time to peak 44 +/- 4 sec) that were due to release from intracellular stores, followed by Ca2+ influx across the plasma membrane. Ca2+ store depletion by thapsigargin, endothelin-1, or bradykinin activated calcium entry pathways. Cells responded similarly to Ni2+ and Cd2+ with albeit slower kinetics (EC50 <10 microm and <100 microm, times to peak 140 +/- 25 sec and 150 +/- 24 sec, respectively). The three cations stimulated inositol phosphate production (two-fold, p <.02) similar to bradykinin (2.5-fold, p <. 002), which activates a phospholipase C (PLC)-coupled receptor in GCT23 cells. The cells did not respond to 0.1-1 mM Gd3+ or neomycin B, indicating that the parathyroid calcium receptor (PCaR) is not functionally expressed. In confirmation, PCaR could not be detected by reverse transcriptase polymerase chain reaction in GCT23 cells and in mouse osteoclasts, and the calcimimetic compound NPS R-568 failed to produce the left shift of the concentration-response curve characteristic for PCaR. Our data demonstrate for the first time that cation sensing by osteoclast-like GCT23 cells is mediated by a PLC-coupled receptor that is not identical to PCaR.
OBJECTIVE: To determine the effects on symptoms, pulmonary function, sleep, and other clinical variables of treating kyphoscoliosis-associated chronic alveolar hypoventilation with nocturnal nasal ventilation. DESIGN: Sixteen patients with kyphoscoliosis were treated with nocturnal nasal ventilation delivered by volume-cycled (seven patients) and pressure-cycled (nine patients) ventilators. Dyspnea, morning headaches, fatigue, hypersomnolence, and perceived sleep quality were assessed. RESULTS: All pretreatment symptoms improved significantly with nasal ventilation. Likewise, PaO2 (mm Hg), PaO2/FlO2, PaCO2 (mm Hg), pH, and forced vital capacity (in milliliters and as a percentage of predicted normal) significantly improved with treatment. Maximum inspiratory pressures and maximum expiratory pressures also significantly increased. Tidal volumes increased significantly and breathing frequency decreased (not significant). Although perceived sleep quality improved, as well as sleep oxyhemoglobin saturation, there was no significant change in sleep architecture. Hospitalization days for respiratory difficulties also decreased from 10.9 +/- 13.3 days in the 6 mo before intermittent positive-pressure ventilation to 0 days during the first 6 mo of treatment. CONCLUSIONS: Although not apparently affecting sleep architecture, nocturnal nasal ventilation can significantly improve nocturnal and daytime blood gases, pulmonary function, and symptoms of hypoventilation for patients with severe kyphoscoliosis.
In vivo immunization and secondary culture techniques were used to generate cytotoxic T lymphocytes against a tumour cell clone obtained from a methylcholantrene-induced fibrosarcoma. Our CTLs differed from classical CTLs (Ly2+ and MHC restricted) in that our lymphocytes exhibited a non-MHC restricted cytotoxic activity directed to the original tumour and to other MCA-induced tumours, but have failed to demonstrate any killing activity against a wide range of tumour cell lines of diverse origin (including NK sensitive targets). Depletion and phenotypic studies demonstrated that these cells bear the Thyl.2 antigen but are negative for both Ly2 and L3T4 antigens. These CTLs may belong to a double negative subset (CD4-, CD8-) involved in the anti-tumour response.
We investigated the relationship between the activation of the c-myc and c-K-ras proto-oncogenes and the acquisition of metastatic potential in a methylcholanthrene-induced BALB/c fibrosarcoma. The murine fibrosarcoma GR9 was originally induced in BALB/c mice following exposure to the carcinogenic chemical 3-methylcholanthrene. To induce spontaneous metastasis, we used two tumor cell clones (B9 and G2) known to differ in their metastatic potential, local tumor growth, H-2 class I expression and sensitivity to natural killer (NK) cells. The metastatic nodes were obtained from the lung, liver and kidney. The results showed: (1) amplification of the c-myc proto-oncogene in original tumor clones as well as in all metastatic nodes; (2) mRNA overexpression without amplification of the K-ras proto-oncogene in the metastatic cells, regardless of their anatomical location; (3) no c-K-ras point mutations at codons 12 and 61, and (4) in general, a statistically significantly reduced in vitro sensitivity of metastatic tumor cells to NK cells as compared with the tumor clones used to induce them (p<0.05). These results therefore suggest that overexpressed c-K-ras mRNA is important during tumor progression, perhaps rendering metastatic tumor cells more resistant to lysis by NK cells.
A pair matched case/control study was conducted from January 1991 to 30 June 1992 in order to define clinical and laboratory findings associated with DMAC infection in AIDS patients. Since DMAC infection is usually associated with advanced immunodeficiency, and therefore also with other opportunistic illnesses, in addition to the number of CD4+ lymphocytes, cases and controls were matched using the following criteria: date of AIDS diagnosis and antiretroviral therapy, number and severity of associated opportunistic infections and, whenever possible, type of Pneumocystis carinii prophylaxis, age and gender, in this order of relevance. Cases (defined as patients presenting at least one positive culture for MAC at a normally sterile site) and controls presented CD4+ lymphocyte counts below 50 cel/mm3. A significantly higher prevalence of general, digestive and respiratory signs, increased LDH levels, low hemoglobin levels and CD4+ cell counts were recorded for cases when compared to controls. Increases in gammaGT and alkaline phosphatase levels seen in cases were also recorded for controls. In conclusion, the strategy we used for selecting controls allowed us to detect laboratory findings associated to DMAC infection not found in other advanced immunosupressed AIDS patients without DMAC.
Forty one cases of pemphigus vulgaris and thirty cases of pemphigus foliaceus were investigated at Hospital Universitário Clementino Fraga Filho from 1978 to 1999. They were divided into two treatment groups: one group received up to 100 mg of oral prednisone daily and the other group received >120 mg daily. The dose up to 100 mg provided good initial control of pemphigus vulgaris and pemphigus foliaceus and did not increase the mortality rate associated to disease. The dose >120 mg induced higher morbidity. These data allowed us to establish a regimen of oral prednisone (1-2 mg/kg/daily) with maximum of 120 mg daily in the treatment of pemphigus vulgaris and pemphigus foliaceus.
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In the present study we show the capacity of an extract of the fern Polypodium leucotomos (PLE) to partially inhibit the production of cytokines showing a Th1 pattern (IL-2, IFN-gamma and TNF-alpha) in human PHA-stimulated peripheral blood mononuclear cells. The percentage of inhibition was 24% for IL-2, 72% for INF-gamma and 53% for TNF-alpha. With regard to Th2 cytokines, the addition of PLE resulted in a significant increase (33%) in IL-10 production. Surprisingly, the production of the inflammatory cytokine IL-6 was completely abolished (100% inhibition) by PLE at all doses tested. In a second experiment in vivo we show that, the topical application of PLE to the skin of hairless albino mice (Skh-1) significantly diminished the mast cell infiltrate as well as the number of blood vessels triggered by chronic ultraviolet B (UVB) irradiation. These data show that PLE moderately inhibits the immunological Th1 responses, thus explaining the immunosuppressive as well as the anti-inflammatory and antioxidant activities reported in other studies carried out with PLE. The clear inhibitory effect on TFN-alpha and IL-6 production strongly suggest that this may be the mechanism by which PLE: (a) inhibits angiogenesis in vivo in the mouse model described here, and (b) prevents Langerhans' cells depletion caused by solar irradiation in humans. Taken together, these data suggest that PLE works through the induction of suppressive/anti-inflammatory cytokines such as IL-10 and/or TGF-beta which in turn appear to allow the partial deactivation of macrophages or other accessory cells. These features suggest that PLE could be useful in the treatment of autoaggressive/inflammatory conditions due to an exacerbation of Th1 responses.
BACKGROUND. A 35-year-old parturient developed a unilateral facial nerve palsy after an epidural blood patch for treatment of subarachnoid-cutaneous fistula. CONCLUSIONS. Idiopathic facial paralysis and other pathogenic mechanisms are discussed. The course of the events support the suggestion that changes in subarachnoid and epidural pressures after an epidural blood patch could precipitate an injury to the 7th nerve.