Biomedical subjects
Publications and source records attributed to P Miralles.
Crohn's disease is a chronic granulomatous disorder, which may involve any segment of the gastrointestinal tract from the mouth to the anus. Although extraintestinal manifestations are frequent, involvement of skin distant to the gastrointestinal tract is uncommon. We report a case of Crohn's disease affecting penile and scrotal skin.
Three patients with progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) worsened clinically and radiologically. At the time of deterioration all three had reduced HIV viraemia and increased CD4 cell counts. Brain biopsy in all three disclosed PML and marked perivascular lymphoplasmacytic infiltration. We reviewed the slides of 28 brain biopsies diagnostic of PML. Inflammatory changes were observed in four out of nine patients on HAART and in one out of 19 patients not on HAART.
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A 40-year-old human immunodeficiency virus (HIV)-positive man had three relapses of visceral leishmaniasis (VL). In the third he developed nodular skin lesions of three types, some reminiscent of Kaposi's sarcoma. Biopsy of each type disclosed abundant dermal macrophages with a huge number of intracellular and extracellular Leishman-Donovan bodies. Rapid improvement of lesions was achieved after antiparasitic treatment. AIDS leads to atypical forms of leishmaniasis. Leishmania has been detected both in normal and pathological skin of these patients due to dissemination during VL. It is suspected that a considerable proportion of the population may be infected in endemic areas, Leishmania being opportunistic in immunosuppressed individuals. It is important to recognize the range of lesions that may occur in patients with HIV and VL, many of which are non-specific and may cause diagnostic difficulty.
JC polyomavirus (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a central nervous system infection that mainly affects AIDS patients. The extensive application of highly active antiretroviral therapy (HAART) is leading to the appearance of "long-term" survival PML patients. A reliable and feasible qualitative-quantitative test for both the detection of JCV and follow-up of its viral burden in this emerging group of patients is clearly required. With this aim, a dual qualitative-quantitative nested PCR is presented in this study for the analysis of JCV DNA in cerebrospinal fluid (CSF). Two newly designed internal controls, one competitive and the other noncompetitive, have been constructed to adapt this PCR to either measure the JCV burden or to allow a highly confident determination of JCV presence or clearance. The analytical sensitivity of the technique allows the detection of 0.01 fg (three genomes) of JCV DNA. Its qualitative application has been evaluated by analyzing single CSF samples from a group of 17 patients with PML and a control group of 20 patients with diverse neurological conditions other than PML, yielding sensitivity and specificity values of 100 and 90%, respectively. The quantitative application has been evaluated in vitro in blind tests with samples including serial dilutions of JCV, and in all cases the samples were successfully ordered considering the JCV titer. The dual quantitative-qualitative application offered by this nested PCR may provide an answer to the new requirements for evaluating and finely monitoring PML in AIDS patients receiving HAART.
OBJECTIVES: To evaluate the efficacy of highly active antiretroviral therapy (HAART) in 12 patients with AIDS-associated progressive multifocal leukoencephalopathy (PML). PATIENTS AND METHODS: The diagnosis of PML was established by brain biopsy in six patients and by neuroimaging findings and PCR detection of JC virus in cerebrospinal fluid (CSF) in six patients. We also studied 13 consecutive AIDS patients with biopsy-proven PML cared for in the same institution before HAART was available. Eleven patients of the HAART group and eight patients of the control group received intravenous arabinoside cytosine cycles. RESULTS: With HAART, the median decrease in the HIV viral load was 3.58 log10 copies/ml and the median increase in the CD4 cell count was 74x10(6)/l. The median survival time after PML diagnosis was 545 days in the HAART group and 60 days in the control group (P<0.001, log-rank test). In the HAART group, the neurological deficits improved substantially in six patients and stabilized in six patients. Eleven patients underwent follow-up cranial computed tomography or magnetic resonance scan that showed improvement of PML lesions in 10 patients and stabilization in one patient. Follow-up CSF analysis showed clearance of JC virus in six out of seven patients who had an initial positive result. CONCLUSIONS: This study shows that HAART may increase the survival, clinical status and radiological features of AIDS patients with PML. Clearance of JC virus from CSF has been found, suggesting that immune reconstitution can interrupt the JC virus lytic cycle.
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In this paper we present a prospective evaluation of 100 patients with Group A Streptococcal (GAS) bacteremia evaluated in our hospital over a 10-year period. Sixty-two patients were intravenous drug users (IVDU); all but 1 of these had an obvious cutaneous portal of entry related to the injection of illicit drugs. Twenty-seven patients had infectious metastasis, and the presence of septic pulmonary embolism was associated with suppurative phlebitis. Four of these patients had endocarditis. In the non-IVDU group, 24 patients had an underlying disease, and 12 were immunosuppressed. In 14 cases the infection was of hospital acquisition; in 35% infection was related to medical manipulations. Comparing the IVDU and non-IVDU groups, GAS bacteremia in IVDU patients is associated with a more benign outcome, a longer time of evolution before diagnosis, and a lower frequency of septic shock and mortality than in non-IVDU patients. Although in the univariate analysis GAS bacteremia was associated with several variables, in the multivariate analysis only the presence of shock and nosocomial acquisition of the infection were independently associated with a fatal outcome. Fifty-two patients were infected with human immunodeficiency virus (HIV); 5 of these were in the non-IVDU group. During the last 5 years of study, GAS bacteremia in our hospital was 39 times more frequent in HIV-infected patients than in patients without HIV. Nine patients presented clinical criteria corresponding to Streptococcal toxic shock syndrome (STSS), although its incidence was lower in the IVDU group. In the non-IVDU group, STSS was more frequent in patients with a necrotizing portal of entry, an age between 20 and 40 years, women, and when the origin of the infection was the skin or soft tissue. Six patients with STSS died, and death was associated with the presence of necrotizing lesions and lower counts of white cells, platelets, or hemoglobin.
Since the emergence of AIDS, disseminated Mycobacterium avium complex (MAC) infection has become a growing cause of morbidity and mortality in this group of patients. Our objective was to study the incidence and the clinical and microbiological features of MAC infection in HIV-positive patients as well as the response to a therapy regimen combining clarithromycin and ethambutol. At our hospital, the first patient with disseminated MAC infection was diagnosed in 1988. Since then, 54 HIV-positive patients with MAC infection have been diagnosed (30/1,000 HIV-positive patients). MAC represented 12% of recovered mycobacteria in HIV-positive patients and this percentage has increased from 3.9% in 1988 to 16.4% in 1994. All episodes of MAC infection occurred in patients with advanced HIV diseases (mean CD4: 73/microliter). MAC infection was the disease diagnosing AIDS in 23.4% of cases. The most common clinical manifestations included fever (85.7%), weight loss (55%), and pulmonary involvement (50%). A total of 55 specimens were processed for mycobacterial culture from 54 patients (mean of 10.2 specimens per patient). A total of 122 were positive (21.9%: 2.25 positive specimens per patient). The specimens with the greater percentage of positive results were bone marrow aspirates (65.3%) and blood cultures (47.7%), followed by respiratory (16.5%) and urine specimens (5.3%). Regarding therapy, sixteen of the 54 investigated patients did not receive specific drugs for MAC infection, 7 were treated with different combinations of active drugs against MAC (rifampin, clofazimine, amikacin, ethambutol, and isoniazid) and 31 received a combination of clarythromicin (1 g/12 hourly) and ethambutol (400 mg/12 hourly). Seventy-four percent of patients treated with clarythromicin and ethambutol improved clinically, and the mean survival time in these patients (253 days) was significantly longer than that in not treated patients (p < 0.05). No significant differences were noted in survival time between the group of patients treated with clarythromicin and ethambutol and that with other drug combinations. The incidence of disseminated MAC infection in our environment is increasing in patients with advanced HIV disease. The combination of clarythromicin plus ethambutol was well tolerated and efficient for the treatment of disseminated MAC infection.
The case of a 30-year-old, female, HIV-positive intravenous drug user who suffered from isolated cerebral mucormycosis is reported. Treatment with amphotericin B at an accumulative dose of 5.5 grams led to significant recovery, and there was no recurrence of disease over a follow-up period of six months. Patients with isolated cerebral mucormycosis in whom surgery would be a high-risk or impossible procedure could be managed medically with prolonged courses of intravenous amphotericin B.
To evaluate the efficacy and safety of intravenous cytarabine in the treatment of AIDS-associated progressive multifocal leukoencephalopathy (PML), we reviewed the charts of all human immunodeficiency virus-infected patients with PML who were seen during a 28-month period at our institution. Patients with biopsy-proven PML were offered therapy with intravenous cytarabine (2 mg/[kg.d] for 5 days every 4 weeks). The diagnosis of PML was histologically confirmed for 13 patients. The median CD4 cell count was 91 x 10(6)/L. A median of three courses of cytarabine was administered to eight patients. Two patients developed mild drug-related toxicities. Clinical and/or radiological signs of improvement were observed for three patients treated with cytarabine; no signs of improvement were noted for the untreated patients. Median survival time after the diagnosis of PML was 102 days (range, 46-220 days) for patients who received cytarabine and 60 days (range, 28-72 days) for untreated patients matched for Karnofsky scores (P = .06, logrank test). Although cytarabine is well tolerated by patients with AIDS and PML, only modest short-term clinical improvement in the conditions of patients treated with the drug has been observed, with no significant impact on survival.
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To assess the frequency and etiology of fever of uncertain origin (FUO) in patients infected with the human immunodeficiency virus (HIV) and to evaluate the yield of diagnostic procedures used in their evaluation, we reviewed the clinical charts of all patients admitted to an AIDS unit during a 15-month period. FUO was defined by the endurance of a fever (temperature, > 38.2 degrees C) for at least 4 weeks before admission and the uncertainty of diagnosis after 3 days, despite appropriate investigation. Of 580 patients evaluated, 50 (8.2%) had FUO. Patients with FUO were at advanced stages of HIV infection (median CD4+ cell count, 71/mm3), and a vast majority (84%) had previously diagnosed AIDS. A cause of the fever was identified for 44 patients (88%), and infections accounted for 82% of all cases. Tuberculosis (42%), visceral leishmaniasis (14%), and disseminated Mycobacterium avium complex infection (14%) were the most frequent diagnoses. Examination of lymph node aspirates, bone marrow biopsy, and culture of clinical specimens for mycobacteria were the procedures with the highest diagnostic yield. Among 6 patients with fever of no identified etiology, 4 died while febrile, and fever was self-limited in the other 2 patients. FUO is common among patients with advanced HIV infection. Since a cause, usually infection, can be identified in most patients, long-lasting fever should not be attributed to HIV itself.
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OBJECTIVE: To assess the risk for development of tuberculosis among anergic patients infected with the human immunodeficiency virus (HIV). DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: All HIV-infected patients who had a baseline positive protein purified derivative test (PPD) and delayed-type hypersensitivity skin tests. MEASUREMENTS: Development of active tuberculosis. RESULTS: Of 374 patients, 108 (29%) had positive results of PPD tests, 154 (41%) had negative results of PPD tests but no skin anergy, and 112 (30%) were anergic. Conversion of the PPD to positive was observed in 10 of 67 (15%) patients with previously negative results of PPD tests and no anergy and in 3 of 36 (8%) anergic patients who were retested during the follow-up period (mean, 26 months). The risk for active tuberculosis to develop in patients not receiving isoniazid chemoprophylaxis was similar in patients with a positive PPD test result (10.4 cases per 100 person-years) and in anergic patients (12.4 cases per 100 person-years) and higher in both groups than in nonanergic patients with a negative PPD test result (5.4 cases per 100 person-years). Tuberculosis was more frequent among intravenous drug abusers with no previous isoniazid treatment (63 of 290, 22%) than among homosexual men (0 of 29) or patients in other HIV transmission categories (0 of 31). Preventive therapy with isoniazid reduced tuberculosis development (4% as compared with 31%; P = 0.008). Among 15 anergic patients who had CD4 counts measured within 3 months of tuberculosis development, only 1 (7%) had more than 500 CD4 cells/mm3. CONCLUSIONS: Anergic HIV-infected patients are at high risk for development of tuberculosis. Anergic HIV-infected patients, in addition to HIV-infected patients with positive results of PPD tests, should be offered preventive therapy if they live in areas with a high prevalence of tuberculosis, at least when the CD4 count decreases to less than 500 CD4 cells/mm3.
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