Long-Term Consequences of Hepatitis C Viral Clearance on the CD4 (+) T Cell Lymphocyte Course in HIV/HCV Coinfected Patients.

The long-term impact of pegylated-interferon plus ribavirin treatment outcome on CD4 T cell course in patients coinfected with human immunodeficiency virus and hepatitis C virus is largely unclear in the literature. The aim of this study was to investigate the impact of HCV-RNA clearance by standard anti-HCV therapy on long-term CD4 cells recovery in HIV/HCV patients on successful combined antiretroviral therapy. We retrospectively enrolled HIV/HCV-coinfected patients on HIV medications and treated for hepatitis C. CD4 + T cell counts were registered at baseline and after hepatitis C therapy. Multiple linear regression analysis was performed to identify independent predictors of CD4 + T cell change following the anti-HCV treatment outcome. Of the 116 patients enrolled, 54 (46.6%) reached a sustained virological response. During a follow-up of 24 months, the SVR group showed a mean annual increase in CD4 + T cell from baseline of 84 cells/ll at 1 year and of a further 38 cells/ll within the second year (P = 0.01, 0.001, resp.). An insignificant mean increase of 77 cells/ll occurred in the non-SVR group within month 24 (P = 0.06). Variables associated with greater CD4 gains were higher nadir, lower preinterferon CD4 counts, and lower body mass index (BMI).

Epidemiologic aspects of abnormal ankle brachial index in the HIV infected population.

AIM: HIV infection is strongly associated with accelerated vascular atherosclerosis and increased cardiovascular events. The prevalence of peripheral arterial disease (PAD) in HIV infected patients is not clearly defined and the results of different reports are contradicting. OBJECTIVE: To determine the prevalence of abnormal Ankle Brachial Index (ABI) and associated risk factors in HIV infected population. METHODS: The ABI was measured manually using 5.0 MHz handheld Doppler probe in 173 HIV infected patients. The cohort was categorized according to the ABI measurements as; normal group (ABI 0.9 to 1.3), peripheral arterial disease (PAD) group (ABI<0.9), and High ABI group (ABI>1.3). Several demographic, atherosclerosis risk factors and HIV infection parameters have been evaluated as potential risk factors. RESULTS: Median age of the cohort was 49 years (inter-quartile ranges [IQR]: 42.5 to 54); 63.4% were males. Abnormal ABI was found in 47(27.2%) patients; twenty four (13.9%) had PAD and 23(13.3%) had high ABI. Among the risk factors evaluated, we observed that PAD group is associated with diabetes (Relative risk [RR]: 4.19; 95% confidence interval [CL]: 2.13 to 8.27; P=0.0002) and age above 49 (Relative risk [RR]: 3.96; 95% confidence interval [CL]: 1.56 to 10.0; P=0.002). However, the High ABI group was significantly associated with male gender (RR: 3.94; 95% CI: 1.23 to 12.70; P=0.009). CONCLUSION: HIV infection is associated with increased prevalence of abnormal resting ABI.

The role of postexercise measurements in the diagnosis of peripheral arterial disease in HIV-infected patients.

Peripheral arterial disease (PAD) is a marker of atherosclerosis, which is not well studied in the population with human immunodeficiency virus (HIV). We prospectively enrolled HIV-infected patients who had normal resting ankle-brachial index (rABI) readings. All participants performed either a treadmill walking test (TT) or pedal plantar flexion test (PFT). Patients were divided into 2 groups according to postexercise changes; PAD and No-PAD group. The 2 groups were compared with regard to established cardiovascular disease risk factors and other HIV infection parameters. Peripheral arterial disease was present in 30 (26.5%) of 113 consecutive HIV-infected patients included in the study. Mean age was 47 ± 10 years. The risk factors studied did not differ significantly among the 2 groups except for male gender, which was significantly associated with PAD (RR: 4.15; CI: 1.6 to 11.1: P < .0008). The prevalence of PAD, diagnosed by significant drop in postexercise ABI and ankle pressure in patients with HIV is high.

Evaluation of the use of UPLC-TOFMS with simultaneous [14C]-radioflow detection for drug metabolite profiling: application to propranolol metabolites in rat urine.

The non-selective beta-adrenergic receptor antagonist propranolol [1-(isopropylamino)-3-(1-naphthoxy)-2-propanol] is metabolised extensively in vivo. Enumerating and identifying the many metabolites that result from multiple biotransformations provides a considerable analytical challenge, greatly aided by efficient chromatography coupled to sensitive mass spectrometric detection. Here the use of the newly introduced high-resolution technique of "ultra performance liquid chromatography" (UPLC) linked to quadrupole time-of-flight mass spectrometry (TOFMS) with simultaneous [(14)C]-radioflow detection was applied to rapid metabolite profiling. [14C]-propranolol, dosed intraperitoneally to rat at 25 mg kg(-1) and 200 microCi kg(-1) was used as a model compound for this evaluation. Some 14 metabolites were detected in the urine by this technique including a number of conjugated metabolites such as sulphates, several isobaric glucuronides and two novel di-glucuronides.

Percutaneous microdecompressive endoscopic cervical discectomy with laser thermodiskoplasty.

OBJECTIVE: To study the surgical outcome of outpatient percutaneous microdecompressive endoscopic cervical discectomy with lower energy laser for shrinkage of disc material (thermodiskoplasty). METHOD: Since 1994, 200 patients with herniated cervical discs have presented at the authors' clinic, with unilateral radicular pain. The diagnosis was confirmed by MRI or CT, and EMG. RESULTS: At an average follow-up of 25 months, 94.5% of the cases had good-to-excellent results. Eleven patients (5.5%) remained symptomatic, with persistent neck and upper extremity pain associated with paresthesias. There were no significant postoperative complications. Average time before returning to work was 10 days. CONCLUSIONS: Percutaneous microdecompressive endoscopic cervical discectomy with laser thermodiskoplasty has proven to be a safe and efficacious minimally invasive procedure.

Mycobacterium fortuitum keratitis. Clinicopathologic correlates and corticosteroid effects in an animal model.

Mycobacterium fortuitum keratitis is an indolent infection of traumatized corneas in humans. To study this disorder in an animal model, 10(4) M fortuitum organisms (10 microliters) were inoculated into the stroma of both corneas of 16 New Zealand albino rabbits. Eight of the rabbits were also given bilateral subconjunctival injections of methylprednisolone acetate (20 mg in 0.5 ml) at the time of inoculation. Two corticosteroid-treated and two untreated rabbits were selected each week after inoculation for histopathological examination and quantitative cultures. Corneal lesions in corticosteroid-treated eyes were characterized clinically by indolent ulcerations and satellite lesions that slowly enlarged; on histopathologic examination at each week, acute inflammation and microorganisms were consistently present. Corneal lesions in untreated eyes were characterized clinically by small infiltrates that progressed little over time; at weeks 1 and 2, light microscopic examination showed intrastromal granulomatous and/or mixed acute and chronic inflammation with focal intrastromal necrosis, but at weeks 3 and 4 there was no evidence of active disease. Organisms could not be identified microscopically in corneas of any untreated rabbits. Mean values for quantitative cultures of corneas were higher in corticosteroid-treated rabbits after week 1, although standard deviations were large. These results suggest that M fortuitum keratitis in rabbits is made worse by corticosteroid use. Clinical and histopathologic changes were compared with human disease and found to be similar in corticosteroid-treated rabbits.

Cytomegalovirus retinopathy as the initial manifestation of the acquired immunodeficiency syndrome.

Of 100 consecutive patients with human immunodeficiency virus infection and cytomegalovirus retinopathy, 15 did not have a previous diagnosis of the acquired immunodeficiency syndrome before the ocular infection. All had other HIV-related disorders that would place them in Group IV of the Centers for Disease Control hierarchical classification system for HIV infections. In nine patients, cytomegalovirus retinopathy was the only disorder that fulfilled the Centers for Disease Control criteria for diagnosis of AIDS. In the other six, examination disclosed additional preexistent or concurrent nonocular disorders that were also diagnostic of AIDS. No demographic, medical, or ophthalmic characteristics distinguished the nine patients for whom cytomegalovirus retinopathy was initially the only manifestation of AIDS. On the basis of published figures for the prevalence of cytomegalovirus retinopathy in patients with AIDS, and the incidence with which HIV-infected persons develop AIDS, it is estimated that approximately 1.8% of patients with AIDS have cytomegalovirus retinopathy as the first manifestation and that less than 1% of HIV-infected persons will develop cytomegalovirus retinopathy as the initial manifestation of AIDS during the first seven years after infection with HIV.

Survival of patients with the acquired immune deficiency syndrome after development of cytomegalovirus retinopathy. UCLA CMV Retinopathy Study Group.

To study the survival of patients with acquired immune deficiency syndrome (AIDS) who develop cytomegalovirus (CMV) retinopathy, the medical records of 100 consecutive patients with AIDS and CMV retinopathy were reviewed Data of AIDS diagnosis, CMV retinopathy diagnosis, and death were determined for each patient. The median interval from CMV retinopathy diagnosis to death for patients whose infection was diagnosed between May 1984 and September 1987 was 5 months. The interval had increased significantly since 1981. The interval from AIDS diagnosis to CMV retinopathy diagnosis (median, 9 months) did not increase. Based on extent and location of retinal lesions at the time patients were first examined, increased survival could not be attributed to earlier diagnosis of CMV retinopathy. Patients treated with ganciclovir lived longer after diagnosis of CMV retinopathy (median, 7 months) than untreated patients (median, 2 months; P less than 0.001). Although this finding suggests that ganciclovir may prolong survival, the effect of treatment cannot be established conclusively because patients were not randomly assigned to treatment or no treatment groups. The location of retinal lesions had no apparent prognostic significance for survival. Survival after diagnosis of AIDS was significantly shorter if CMV retinopathy was the initial manifestation of the syndrome.

Pulmonary disease associated with pleural "asbestos" plaques.

The diagnosis of asbestos-related pulmonary disease is frequently based in part on the identification of pleural plaques; however, postmortem observations have suggested that pleural plaques may occur without associated pulmonary disease. To examine this issue, we compared the pulmonary parenchymal pathology in 93 patients with pleural plaques to 93 control patients matched for age, race, and sex, all autopsied at The Johns Hopkins Hospital between Jan 1, 1981 and March 31, 1986. Pulmonary sections were graded without knowledge of the patient's group for peribronchiolar fibrosis, other types of fibrosis, emphysema, and pleural changes. Correlations were found between the presence of pleural plaques and peribronchiolar fibrosis (p less than 0.001), alveolar fibrosis (p less than 0.05), large scars (p less than 0.02), scar-related emphysema (p less than 0.02), and pleural thickening (p less than 0.005). A history of smoking was also associated with pleural plaques (p less than 0.05). Interstitial fibrosis was not significantly different between the two groups. Peribronchiolar fibrosis was neither universally nor exclusively present in patients with pleural plaques, being found in 49 (53 percent) of 93 subjects with and 36 (39 percent) of 93 subjects without plaques. The results suggest that caution must be exercised in extrapolating from the identification of pleural plaques to a diagnosis of asbestos-related pulmonary disease.