Insulin induces airway smooth muscle contraction.

BACKGROUND AND PURPOSE: Recently, the use of inhaled insulin formulations for the treatment of type I and type II diabetes has been approved in Europe and in the United States. For regular use, it is critical that airway function remains unimpaired in response to insulin exposure. EXPERIMENTAL APPROACH: We investigated the effects of insulin on airway smooth muscle (ASM) contraction and contractile prostaglandin (PG) production, using guinea-pig open-ring tracheal smooth muscle preparations. KEY RESULTS: It was found that insulin (1 nM-1 microM) induced a concentration-dependent contraction that was insensitive to epithelium removal. These sustained contractions were susceptible to inhibitors of cyclooxygenase (indomethacin, 3 microM), Rho-kinase (Y-27632, 1 microM) and p42/44 MAP kinase (PD-98059, 30 microM and U-0126, 3 microM), but not of PI-3-kinase (LY-294002,10 microM). In addition, insulin significantly increased PGF(2alpha)-production which was inhibited by indomethacin, but not Y-27632. Moreover, the FP-receptor antagonist AL-8810 (10 microM) and the EP(1)-receptor antagonist AH-6809 (10 microM) strongly reduced insulin-induced contractions, supporting a pivotal role for contractile prostaglandins. CONCLUSIONS AND IMPLICATIONS: Collectively, the results show that insulin induces guinea-pig ASM contraction presumably through the production of contractile prostaglandins, which in turn are dependent on Rho-kinase for their contractile effects. The data suggest that administration of insulin as an aerosol could result in some acute adverse effects on ASM function.

Herpes zoster as an immune reconstitution disease after initiation of combination antiretroviral therapy in patients with human immunodeficiency virus type-1 infection.

BACKGROUND: Initiation of combination antiretroviral therapy may be followed by inflammatory reactions. We studied the epidemiology of herpes zoster infection among patients with human immunodeficiency virus (HIV) infection who were treated with combination antiretroviral therapy. SUBJECTS AND METHODS: Of 316 patients who initiated combination antiretroviral therapy, 24 (8%) were treated for herpes zoster within 17 weeks of starting therapy. The characteristics of these cases were compared with those of a control group of 96 HIV-1-infected patients, who were matched by age, sex, plasma HIV-1 RNA concentration and CD4 cell counts, and length of follow-up. RESULTS: The incidence of herpes zoster associated with combination antiretroviral therapy was 9 episodes per 100 patient-years. There were no significant differences between cases and controls in age, sex, years of HIV infection, history of herpes zoster, previous acquired immune deficiency syndrome, or baseline mean CD4 and CD8 cell counts before beginning combination antiretroviral therapy. However, patients who developed herpes zoster had a significantly greater mean (+/- SD) increase in the number of CD8 cells than did controls (347 +/- 269 vs. 54 +/- 331 cells/mL, P = 0.0006). In a multivariate analysis, the only factor that was associated with the development of herpes zoster was the increase in CD8 cells from before initiation of combination antiretroviral therapy to 1 month before development of herpes zoster (odds ratio 1.3 per percentage increase; 95% confidence interval: 1.1 to 1.5; P = 0.0002). CONCLUSION: The initiation of combination antiretroviral therapy in HIV-1-infected patients was often associated with the development of herpes zoster, especially in those in whom the number of CD8 cells increased after therapy.

[Cerebral toxoplasmosis in patients with human immunodeficiency virus (HIV) infection. Clinico-radiological and therapeutic aspects in 63 patients]. / Toxoplasmosis encefálica en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). Características clínico-radiológicas y terapéuticas en 63 pacientes.

We have retrospectively reviewed 63 cases of encephalic toxoplasmosis (ET) in HIV-infected patients in order to determine clinical and radiological characteristics, the diagnostic value of serologic determinations, and the response to antioxoplasmic therapy. ET was the AIDS-defining condition in 44% of the patients. Eighty of the patients had a CD4 cell count < 100/microliters when ET was diagnosed. Only 4.8% of the patients had been taking anti-Pneumocytis carinii prophylaxis with cotrimoxazol. The most frequent clinical presentation was focal neurologic signs in 80.9% of the patients, with headache and fever in 53.3% and 42.4%, respectively. The most frequent cerebral CT finding was hipodense lesions (92%) with ring enhancement (68.9%). They were most frequently had a hemisferic location. Seroconversion was detected in two patients (6%), whereas 55 patients had serologic evidence of latent infection by Toxoplasma gondii (87.3%). Ninety eight percent of the patients were treated with sulphadiazine plus pyrimethamine. However, such therapy should be discontinued in 22% of them and switched to clindamycin plus pyrimethamine. The overall mortality rate during the acute phase of the disease was 7.9%, but 41.4% of the survivors exhibited neurologic sequelae. Relapsing ET was detected in 33.3% of the patients, and it was usually due to discontinuation of treatment. The mean survival time after the diagnosis of ET was 11.5 months. ET is the most common opportunistic infection of the central nervous system among our AIDS patients. Primary prophylaxis for toxoplasmic infection seems advisable in our epidemiologic environment, when CD4 cell count is less than 200/microliters and there is serologic evidence of latent infection. Acute ET usually has a good response to therapy, and the acute mortality rate is low. However, most of the survivors will remain with neurologic sequelae. The high frequency of adverse effects to sulphamide therapy with clindamycin make the need of alternative treatment strategies urgent.

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Whole pelvic osteomyelitis: unusual finding in staphylococcal sepsis.

We describe an infrequent case of combined infection of bone, articulation and lung by Staphylococcus aureus, with affectation of all pelvic bones. Studies with 99m Tc pyrophosphate were repeatedly negative, becoming positive following the appearance of radiological signs.

Disseminated cytomegalovirus infection in an immunocompetent adult successfully treated with ganciclovir.

We report the case of a previously healthy man who suffered a disseminated cytomegalovirus infection. He presented with prolonged fever, weight loss of 8 kg, anicteric hepatitis, upper digestive tract bleeding from gastric ulcers, acute polyneuritis and bilateral retinitis. Immunodeficiency was not detected either during admission or during a 3-year follow-up period. The patient was treated with ganciclovir (5 mg/kg BID) during 4 weeks with a favourable clinical outcome. To our knowledge, this is the first reported case with such characteristics.

Pseudomonas aeruginosa bronchopulmonary infection in patients with AIDS, with emphasis on relapsing infection.

The aim of this study was to delineate the clinical and therapeutic characteristics of Pseudomonas aeruginosa bronchopulmonary infection in acquired immunodeficiency syndrome (AIDS) patients. Eighteen AIDS patients had 39 episodes of P. aeruginosa bronchopulmonary infection. Their mean CD4 cell count was 0.012+/-0.011 cells x 10(9) x L(-1) and two episodes (5.1%) occurred in neutropenic patients. Ten patients (55.5%) had 21 outbreaks of pseudomonal infection. Relapses were more frequent in patients with chronic bronchitis (80 versus 0%, p=0.03) and in those who received initial oral antibiotic therapy (100 versus 55.6%, p=0.25). Three patients died, but death was directly related to pseudomonal infection in only one patient. In a case-control study, patients with bronchopulmonary P. aeruginosa infection had a survival comparable to patients in the control group. Immunoglobulin prophylaxis was administered to three patients with relapses, without success. The two patients who had P. aeruginosa eradicated were those who began triple antiretroviral therapy and had a CD4 cell increase >0.150 cells x 10(9) x L(-1). Relapsing Pseudomonas aeruginosa bronchopulmonary infection affects patients with advanced human immunodeficiency virus infection, prior underlying lung disease, chronic bronchitis and initial oral antibiotic therapy. Immune reconstitution through triple antiretroviral therapy succeeded in eradicating Pseudomonas aeruginosa respiratory infection in two patients.

Tuberculous pulmonary gangrene: report of a case and review.

Pulmonary gangrene is an uncommon but life-threatening complication of bacterial pneumonia. Only four cases of pulmonary gangrene due to Mycobacterium tuberculosis have been described to date; another case of pulmonary gangrene was attributed to unidentified mycobacteria. We report a fetal case of tuberculous pulmonary gangrene (TPG) and review the literature on this infection. To our knowledge this is the first case of TPG documented by thoracic computed tomographic scanning. Radiological features of pulmonary gangrene are distinctive, and identification of pulmonary parenchyma in the mass on computed tomography may be considered as pathognomonic. Analysis of the six cases revealed that most of the patients were aged, and one-half of them were alcohol abusers. Right-upper-lobe involvement predominated. When performed, sputum smears disclosed acid-fast bacilli. M. tuberculosis was cultured from sputum or pathologic material in five of the six cases. Four patients (66.7%) died. Four of six patients with TPG received antituberculous therapy, and two of them survived; no patient underwent surgical intervention. Although surgical management has been successfully employed in cases of bacterial pulmonary gangrene, TPG has always been treated with medical therapy alone. In spite of administration of antituberculous therapy, mortality is high.