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Biomedical subjects

N Case

Publications and source records attributed to N Case.

14 recordsLinked to original sources

Inhibition of experimental acute pulmonary inflammation by pirfenidone.

Pirfenidone, a putative tumor necrosis factor-alpha (TNF-alpha) inhibitor, has recently gained recognition for its therapeutic use in the treatment of idiopathic pulmonary fibrosis. As pulmonary fibrosis may be the result of lung inflammatory processes, we examined the anti-inflammatory potential of pirfenidone in several models of acute pulmonary inflammation. In antigen-induced allergic paradigms, 24 h after antigen challenge, sensitized mice or guinea pigs develop a prominent pulmonary inflammation, reflected by a significant increase in the number of recoverable bronchoalveolar lavage (BAL) total cells and eosinophils. In both species, the pretreatment of animals with pirfenidone (10 and 30 mg/kg) resulted in a dose-dependent inhibition of the antigen-induced pulmonary inflammation, which was reflected by a significant decrease in the BAL eosinophils and total cells by the 30 mg/kg dose. In a non-allergic model of pulmonary inflammation, rats challenged with intratracheal LPS develop a significant increase in BAL neutrophils and total cells, along with significant increases in TNF-alpha and IL-6. Pretreatment with pirfenidone (3 and 30 mg/kg) showed a dose-dependent inhibition of the LPS-induced pulmonary inflammation, reflected by a significant decrease in the number of BAL total and neutrophilic cells at both the 3 and 30 mg/kg dose. However, pirfenidone had no effect on the peak BAL levels of TNF-alpha. In contrast, pirfenidone significantly inhibited BAL levels of IL-6. In summary, we have shown that pirfenidone can inhibit allergic and non-allergic inflammatory cell recruitment and that its pulmonary anti-inflammatory activity is independent of TNF-alpha inhibition.

Animals↗

The dual-diagnosis patient in a psychiatric day treatment program: a treatment failure.

This study was undertaken to determine the effectiveness of treating the dual-diagnosis patient in a standard psychiatric day treatment program. These patients, presenting with psychiatric disorder coexisting with alcohol and/or drug abuse, present a major problem in treatment because of their emotional fragility, their propensity to impulsive acting-out behaviors, and their adaptation to psychiatric symptomatology via self-medication with illicit drugs. Of the 24 dual-diagnosis patients admitted to our Day Treatment Center in 1988, 57% left treatment at or before 8 weeks following admission, as opposed to 21% of a nonsubstance abusing psychiatric control group. Their rate of absenteeism and suspensions for continuing abuse and infraction of the rules was four times that of the controls. In light of these data, it appears that these patients require highly specialized treatment strategies not generally available in a conventional psychiatric day hospital.

Adult↗

Effect of verapamil and other agents on the distribution of anthracyclines and on reversal of drug resistance.

We studied the intracellular distribution of drugs within anthracycline-sensitive and -resistant cells by computer-assisted digitized video fluorescence microscopy. We found that the antitumor antibiotic, daunorubicin, distributes differently in anthracycline-sensitive and -resistant human leukemia cells (HL-60). Verapamil and other agents known to circumvent resistance in pleiotropic drug-resistant cell lines were able to change the pattern of distribution of daunorubicin in the anthracycline-resistant HL-60 cells back to the distribution found in anthracycline-sensitive HL-60 cells. To investigate the biochemical basis for this effect, we studied the distribution of daunorubicin and doxorubicin in a hydrophobic/hydrophilic (membrane/cytoplasmic) environment using the two-compartment cell-free system of Folch. Our results demonstrate that various unrelated drugs known to overcome resistance will also change the distribution of the anthracyclines in the hydrophobic/hydrophilic compartments. Our data allow the hypothesis that various unrelated agents known to circumvent resistance may act by altering the hydrophobic/hydrophilic solubility of anthracyclines in the resistant cell.

Antibiotics, Antineoplastic↗

Acute renal failure in idiopathic nephrotic syndrome.

In 4 adults with idiopathic nephrotic syndrome an acute renal failure with prolonged anuria has been observed. At renal histology 1 patient showed minimal glomerular changes and 3 showed focal glomerulosclerosis. No vascular abnormalities were seen. In all cases severe tubular lesions with casts and cell debris in the lumina were observed. In 2 patients renal function improved after 3 and 6 months, respectively; the remaining 2 died after several months from the onset of acute renal failure being still anuric. Although the pathogenesis of this complication is unknown, tubular obstruction by proteinaceous casts and vasoconstriction may play an important role. The prognosis of this complication is severe, but the possibility of spontaneous recovery even after protracted anuria cannot be ruled out.

Acute Kidney Injury↗

Living alone after myocardial infarction. Impact on prognosis.

OBJECTIVE: To determine if the presence of a disrupted marriage or living alone would be an independent prognostic risk factor for a subsequent major cardiac event following an initial myocardial infarction. DESIGN: Prospective evaluation in the placebo wing of a randomized, double-blind drug trial in patients with an enzyme-documented acute myocardial infarction who were admitted to a coronary care facility. Data for living alone and/or a marital disruption were entered into a Cox proportional hazards model constructed from important physiologic and nonphysiologic factors in the same database. SETTING: Multicenter trial in a mixture of community and academic hospitals in the United States and Canada. PATIENTS: All consenting patients who were 25 to 75 years of age and without other serious diseases were enrolled (placebo, N = 1234) within 3 to 15 days of the index infarction and followed for a period of 1 to 4 years (mean, 2.1 years). Nine hundred sixty-seven patients were followed for 1.1 years and 530 for 2.2 years. PRIMARY OUTCOME MEASURE: Recurrent major cardiac event (either recurrent nonfatal infarction or cardiac death). RESULTS: Living alone was an independent risk factor, with a hazard ratio of 1.54 (95% confidence interval, 1.04 to 2.29; P less than .03). Using the Kaplan-Meier statistical method for calculation, the recurrent cardiac event rate at 6 months was 15.8% in the group living alone vs 8.8% in the group not living alone. Risk remained significant throughout the follow-up period (P = .001). A disrupted marriage was not an independent risk factor. CONCLUSION: Living alone but not a disrupted marriage is an independent risk factor for prognosis after myocardial infarction when compared with all other known risk factors.

Adult↗