Biomedical subjects

Shahid Husain

Publications and source records attributed to Shahid Husain.

43 records · Page 3Linked to original sources

PubMed2002

The impact of novel immunosuppressive agents on infections in organ transplant recipients and the interactions of these agents with antimicrobials.

Several of the new immunosuppressive agents that are used to treat transplant recipients possess in vitro activity against specific pathogens, enhance the activity of antimicrobial agents, or have unique drug interactions with antimicrobial agents. Mycophenolate mofetil may have a protective effect against Pneumocystis carinii; it also enhances the activity of ganciclovir and has strong antiviral activity against human immunodeficiency virus type 1. High doses of mycophenolate mofetil have been associated with a higher frequency of tissue-invasive cytomegalovirus disease but not with asymptomatic cytomegalovirus infection. Rapamycin exhibits potent in vitro fungicidal activity against Cryptococcus neoformans and several pathogenic fungi in transplant recipients; however, it is not known whether its immunosuppressive effect in organ transplant recipients outweighs its antifungal activity. Recognition of the unique characteristics of these agents and the evolving spectrum of opportunistic infections has implications for the differential diagnosis, management, and prophylaxis of infections in organ transplant recipients in the modern immunosuppressive era.

Anti-Infective Agents↗

PubMed2002

Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial.

BACKGROUND: The value of azithromycin for treatment of acute bronchitis is unknown, even though this drug is commonly prescribed. We have investigated this question in a randomised, double-blind, controlled trial. METHODS: Adults diagnosed with acute bronchitis, without evidence of underlying lung disease, were randomly assigned azithromycin (n=112) or vitamin C (n=108) for 5 days (total dose for each 1.5 g). All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer. The primary outcome was improvement in health-related quality of life at 7 days; an important difference was defined as 0.5 or greater. Analysis was by intention to treat. FINDINGS: The study was stopped by the data-monitoring and safety committee when 220 patients had been recruited. On day 7, the adjusted difference in health-related quality of life was small and not significant (difference 0.03 [95% CI -0.20 to 0.26], p=0.8). 86 (89%) of 97 patients in the azithromycin group and 82 (89%) of 92 in the vitamin C group had returned to their usual activities by day 7 (difference 0.5% [-10% to 9%], p>0.9). There were no differences in the frequency of adverse effects; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects, compared with none in the azithromycin group. Most patients (81%) reported benefit from the albuterol inhaler. INTERPRETATION: Azithromycin is no better than low-dose vitamin C for acute bronchitis. Further studies are needed to identify the best treatment for this disorder.

Acute Disease↗

PubMed2002

Nocardia infection in lung transplant recipients.

BACKGROUND: Nocardia is responsible for infection in both normal and immunocompromised hosts. Organ transplant recipients are increasingly recognized as a sub-group of immunocompromised patients in whom nocardia is an important pathogen. The frequency of nocardia in organ transplant recipients varies between 0.7% and 3%. Nocardia infection has largely been reported in heart, kidney and liver transplant recipients. Presentations of nocardia in lung transplant recipients have been restricted primarily to case reports. The present study reviews the clinical and epidemiologic characteristics of nocardia infection in lung transplant recipients at our institution. METHODS: A retrospective cohort study of 473 lung transplant recipients from January 1991 to November 2000 was done at a university hospital. Patient demographics, immunosuppressive regimen at the time of isolation of nocardia species, use of trimethoprim-sulfamethoxazole for Pneumocystis carinii prophylaxis, rejection episodes in the preceding 6 months, concurrent pathogens, site of infection, radiologic findings and treatment and outcome were recorded. RESULTS: Nocardia infection was found in 2.1% (10 of 473) of our lung transplant recipients. Median time of onset was 34.1 months after transplantation. Nocardia species included N farcinica in 30% (3 of 10), N nova in 30% (3 of 10), N asteroides complex in 30% (3 of 10) and N brasiliensis in 10% (1 of 10) of patients. Post-transplant diabetes was present in 50% (5 of 10) of patients. The primary indication for lung transplantation was emphysema in 40% (4 of 10). Native lung involvement was noted in 75% (3 of 4) of patients with single lung transplant. Breakthrough nocardia infection were noted in 6 patients who were receiving trimethoprim-sulfamethoxazole prophylaxis for P carinii pneumonia; all breakthrough isolates remained susceptible to trimethoprim-sulfamethoxazole. Overall mortality was 40% (4 of 10). All patients (3 of 3) with infection due to N farcinica, except 1 (1 of 7) with infection due to other nocardia species, died. Seventy-five percent (3 of 4) of deaths were attributable to nocardia infection. CONCLUSIONS: Nocardia infection tended to involve the native lung in single lung transplant recipients. Trimethoprim-sulfamethoxazole for P carinii prophylaxis at the doses given was not protective against nocardiosis in these patients. Infection with N farcinica was associated with poor outcome. Thus, species identification and extended courses of antibiotics based on antimicrobial susceptibility testing are important in management of these patients.

Adult↗

PubMed2002

Impact of human herpesvirus-6 on the frequency and severity of recurrent hepatitis C virus hepatitis in liver transplant recipients.

A role of tumor necrosis factor-alpha (TNF-alpha) In the immunopathogenesis of hepatitis C virus (HCV) infection has been proposed. The novel herpes virus, human herpes virus-6 (HHV-6), is amongst the most potent inducers of cytokines, including TNF-alpha. The impact of HHV-6 viremia on the progression of recurrent HCV hepatitis was assessed in 51 HCV-positive liver transplant recipients. The frequency of recurrent HCV hepatitis did not differ between patients with HCV viremia (47.6%, 10/21) as compared with those without HCV viremia (46.7%, 14/30, p = 0.9). However, the patients with HHV-6 viremia had a significantly higher fibrosis score upon HCV recurrence than those without HHV-6 viremia (mean 1.5 vs. 0.3, p = 0.01). An association between cytomegalovirus (CMV) viremia and HCV recurrence was not documented; 50% (15/30) of the patients with CMV viremia and 42.8% (9/21) of those without CMV viremia had recurrent HCV hepatitis (p > 0.5). Receipt of ganciclovir (administered upon the detection of CMV viremia) was associated with lower total Knodell score (mean 5.2 vs. 6.9, p = 0.05) and a trend towards lower fibrosis score (mean 0.44 vs. 1.00, p = 0.12) in patients with recurrent HCV hepatitis. Thus, HHV-6 viremia in HCV-positive liver transplant recipients identified a subgroup of patients at increased risk for early fibrosis upon HCV recurrence.

Cytomegalovirus↗

PubMed2002

Bronchiolitis obliterans and lung transplantation: evidence for an infectious etiology.

Bronchiolitis obliterans (OB) or bronchiolitis obliterans syndrome (BOS) remains a major hurdle in the long-term survival of lung transplant recipients. The pathogenesis of OB or BOS remains to be fully discerned, but it is hypothesized that allogenic or nonallogenic insults result in the release of chemokines and T lymphocytes propagating the injury and ultimately recruiting fibroblasts culminating in intraluminal proliferation. Infectious agents, with or without other exogenous factors, have been proposed to have a contributory role in the development of OB or BOS. Cytomegalovirus (CMV) is an immunomodulating virus that may lead to persistent stimulation of T cells with the release of chemokines that may promote OB. Animal studies have correlated the development of OB with CMV infection. However, assessment of CMV as a risk factor for the development of OB or BOS in clinical studies has yielded conflicting results. CMV infection was noted to have a hazard ratio of 1.62 in one study, whereas CMV pneumonitis was associated with relative risk of 2.3. Additional studies did not find a higher risk for developing OB or BOS with CMV. Other viruses including respiratory syncytial virus and parainfluenza viruses can promote epithelial damage and act synergistically with chronic rejection in the development of OB. A higher (47%) incidence of BOS has been noted during the respiratory virus season. The evidence of Pneumocystis carinii pneumonia or other infectious episodes causing OB is lacking. Thus, although the role of infectious agents in the development of OB or BOS is biologically plausible, an incontrovertible association between infection and OB or BOS has not been documented. This is a US government work. There are no restrictions on its use.

Bronchiolitis Obliterans↗

PubMed2002

Burkholderia cepacia infection and lung transplantation.

Burkholderia cepacia has emerged as an important pathogen in patients with cystic fibrosis (CF) undergoing lung transplantation. Taxonomic analyses have divided B. cepacia into 7 closely related species called genomovars. The prevalence of B. cepacia infection ranges from 2% to 13% in CF patients with genomovar III being most prevalent. Risk factors for the acquisition of B. cepacia include greater severity of underlying CF, increasing age, having a sibling colonized with B. cepacia, and previous hospitalizations. One-year survival in patients with CF undergoing lung transplantation usually have been reported to be less than 70%. The antimicrobial resistance pattern of B. cepacia has correlated with inconsistent effect on survival. Presence of genomovar III also has been linked with survival of B. cepacia-infected patients; the survival rates were inferior for genomovar III as compared with non-genomovar III patients. Standard infection control techniques including isolation of both colonized and noncolonized individuals with frequent sputum culture have been recommended to prevent CF patients from acquiring B. cepacia infection. B. cepacia is inherently resistant to antipseudomonal antibiotics, colistin, and polymyxin. The combination of 2 or more antibiotics usually is recommended for the treatment of B. cepacia infections. Studies delineating the epidemiology and influence of B. cepacia infection on lung transplantation are warranted. This is a US government work. There are no restrictions on its use.

Burkholderia Infections↗

PubMed2002

Alterations in arachidonic acid release and phospholipase C-beta(1) expression in glaucomatous human ciliary muscle cells.

PURPOSE: Prostaglandin (PG) F(2alpha) and other Ca(2+)-mobilizing agonists, such as carbachol (CCh) and endothelin (ET)-1, induce an increase in uveoscleral outflow, in part through receptor-mediated mechanisms in the ciliary muscle. Because changes in uveoscleral outflow across the ciliary muscle could cause elevation of intraocular pressure (IOP) in patients with glaucoma, the present study was conducted to investigate the possibility that basal and agonist-induced second-messenger formation may be altered in glaucomatous human ciliary muscle (g-HCM) cells compared with normal (n)-HCM cells. METHODS: Normal and glaucomatous HCM cells were cultured from donor eyes, the cells were identified based on their positive immunostaining with smooth muscle-specific anti-alpha-actin (SM), anti-SM-myosin, and anti-desmin antibodies. Activation of phospholipase A(2) (PLA(2)) was measured by the release of [(3)H] arachidonic acid (AA) into the medium, accumulation of PGE(2) was measured by radioimmunoassay, [(3)H]myo-inositol phosphate production was measured by ion-exchange chromatography, and phospholipase C (PLC)-beta(1) expression was determined by immunoblot analysis with polyclonal antibodies specific for PLC-beta(1). RESULTS: Homogenous primary cell cultures from normal and glaucomatous human ciliary muscle were established and characterized. The data obtained can be summarized as follows: Both n- and g-HCM cells exhibited similar morphologic characteristics and immunoreactivities. The effects of the agonists on AA release in both n- and g-HCM cells were in the following order: PGF(2alpha) > ET-1 > CCh; their effects on PGE(2) release were in the following order: PGF(2alpha) > CCh > ET-1; and their effects on inositol phosphate production were in the following order: CCh > ET-1 > PGF(2alpha). Both the basal- and stimulated release of AA were significantly higher in the g-HCM cells than in the n-HCM cells (for PGF(2alpha), 60% vs. 151%). The basal release of PGE(2) in g-HCM cells was two- to fivefold higher than that of n-HCM cells, and there are alterations in the effects of the agonists on PGE(2) release. Agonist-induced inositol phosphate production in g-HCM cells was considerably lower than that of n-HCM cells (CCh, 58% vs. 421%), and the amount of PLC-beta(1) expressed in g-HCM cells, compared with that in n-HCM cells, was markedly reduced (by 44%). CONCLUSIONS: These data are the first to show that basal and agonist-induced AA release and inositol phosphate production as well as expression of PLC-beta(1) are altered in g-HCM cells compared with that of n-HCM cells. The molecular mechanisms underlying these alterations in g-HCM cells could include changes in sensitivity and number of receptors, overexpression of PLA(2) and the cyclooxygenases, and underexpression of PLC-beta(1). Alterations in these signaling pathways in g-HCM cells could contribute to changes in the uveoscleral outflow pathway, which may lead to an increase in IOP in patients with glaucoma. Comparative studies on the signaling pathways in g- and n-HCM cells can provide important information about the regulation of uveoscleral outflow and the pathologic course of glaucoma.

Actins↗