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Biomedical subjects

J Verdejo

Publications and source records attributed to J Verdejo.

At least 19 recordsLinked to original sources

[Expression of different HIV-1 phenotypic subpopulations through the natural history of the infection].

BACKGROUND: Multiple viral subpopulations coexist in an HIV infected patient with dynamics of selection established between them. In order to get insight on the phenotype of these subpoblations, and its relation with disease progression, we have studied the biological variability of HIV-1 in 113 patients. Variability was related with CD4+ T lymphocyte counts, clinical status, way of viral transmission and antiretroviral treatment. PATIENTS AND METHODS: 113 patients (80 adults and 33 children) were studied for HIV-1 isolation in cocultures of infected and non infected lymphocytes. Viral replication was evaluated as rapid (R)/slow (S) or high (H)/low (L). Syncytia formation was estimated in MT2 cell line (SI/NSI). The tropism toward lymphocytes and monocytes (LM) was studied on H9 and U937 cell lines. RESULTS: Up to 86.7% of viral isolates were R, 56.6% were H and 49.6% were SI. These percentages increased with disease progression. Eight viral strains were R/H/NSI cocultivated in MT2 cells and SI in cocultured lymphocytes (NSI/SI), which may be considered as a new phenotype. All the SI isolates and all the R/H (SI and NSI) isolates were LM. Three categories were established: R/H/SI/LM, R/H/NSI/LM and S/L/NSI/NLM. The first two categories corresponded to patients with CD4+ T lymphocytes <200 x 10(6)/I (56%, 50%). The third category corresponded to patients with > 500 x 10(6)/I (53.3%). CONCLUSIONS: Viral replication and SI phenotype, independently, are useful markers for severity of HIV infection. The biological differences among NSI of the 3 viral phenotype categories, including the new subgroup NSI/SI, may indicate the existence of more pathogenic NSI subpopulations.

Adolescent↗

Visceral leishmaniasis in patients infected with the human immunodeficiency virus.

The experience with 52 episodes of visceral leishmaniasis diagnosed in 43 patients is reported. The most common symptoms were fever (81%), splenomegaly (65%), hepatomegaly (63%), and pancytopenia (73%). In 79% of the patients, CD4+ cell counts were < 100 cells/mm3. Prior or simultaneous diagnosis of AIDS was made in 29 (67%) patients. Diagnosis was considered fortuitous in 19% of the episodes. In 27% of the episodes, the diagnosis was made on the basis of demonstration of parasites outside the reticuloendothelial system, chiefly blood (7 cases) and gastrointestinal mucosa (5 cases). Parasites were frequently observed or cultured from blood (22/37 episodes) or the digestive tract (8/9 episodes). High antimony doses were more effective than low doses in achieving clinical or parasitological cure (rate of cure, 80% vs. 40%, p = 0.11). Severe toxicity was observed in six (11.7%) of the 51 treated episodes. Severe AIDS-related diseases [odds ratio (OR) 10, p < 0.05] and CD4+ counts (OR 12, p < 0.05) were independent factors for early death. Prophylaxis with monthly pentamidine was not useful in reducing relapses of visceral leishmaniasis.

AIDS-Related Opportunistic Infections↗

Failure of adjusted doses of subcutaneous heparin to prevent thromboembolic phenomena in pregnant patients with mechanical cardiac valve prostheses.

OBJECTIVES: This report describes our experience with the use of an anticoagulant regimen of adjusted doses of subcutaneous heparin during pregnancy in women with cardiac valve prostheses. BACKGROUND: Gravid patients with prosthetic heart valves require long-term anticoagulant therapy. To avoid the increased incidence of fetal morbidity and mortality associated with the use of coumarin agents in such patients during pregnancy, anticoagulation with subcutaneous heparin has been suggested. Controversy exists concerning the appropriate treatment of these patients. METHODS: Forty pregnancies in 37 women with prosthetic heart valves were prospectively followed up. Subcutaneous heparin was administered from the 6th until the end of the 12th week and in the last 2 weeks of gestation. Heparin was given every 8 h in the first 36 cases and every 6 h in the last 4 cases, and the dose adjusted to maintain the activated partial thromboplastin time at 1.5 to 2.5 times the control level. Acenocoumarol was used at other times. RESULTS: The incidence rate of spontaneous abortions was 37.5%; there was one neonatal death (2.5%) due to cerebral hemorrhage. No signs of coumarin-induced embryopathy were found in any of the 16 live-born infants studied by the geneticist. One mother died of gastrointestinal bleeding while receiving oral anticoagulant agents. There were two cases of fatal massive thrombosis of a mitral tilting-disk prosthesis during heparin therapy. The study was interrupted after the last of these two cases. CONCLUSIONS: The regimen of adjusted doses of subcutaneous heparin used in this study is not effective to prevent thrombosis of mechanical valve prostheses during pregnancy. The use of heparin from the 6th to the 12th week of gestation does not decrease the high incidence of fetal wastage associated with anticoagulant therapy. Coumarin agents provide adequate protection against thromboembolism during pregnancy in patients with mechanical valve prostheses.

Abnormalities, Drug-Induced↗

Switching from zidovudine to didanosine in patients with symptomatic HIV infection and disease progression. ddI Iberian Study Group.

This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n=133), 500 mg/d of didanosine (n=131), or 200 mg/d of didanosine (n=136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3 or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of > or = 2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).

AIDS-Related Complex↗

[Colony-stimulating factors and HIV-related neoplasms].

OBJECTIVE: it is analyzed a group of patients with HIV related malignancy treated with myelosuppressive therapy with granulocyte colony stimulating factor (G-CSF) to study the efficacy of hematopoietic growth factors in these subjects. PATIENTS AND METHODS: it was studied the clinical and hematological evolution of 20 patients with HIV related malignancy treated with standard dose of chemotherapy and 5 micrograms/Kg/day of G-CSF starting 24 hours after the completion of chemotherapy administration. It was done an epidemiological study and was determined haemoglobin level, and the number of leukocytes, monocytes, neutrophils, lymphocytes, CD4+ lymphocytes and platelets before and after the chemotherapy administration. RESULTS: all of the patients were men with mean age of 37 +/- 2 years. The mean of lymphocyte CD4+ count was 17 x 10(6)/l and the tumor was the first aids manifestation in 50% of the subjects. The mean days of hospitalization was 14 +/- 3 days. As the result of the G-CSF administration, the leucocyte and the neutrophil count was statistically elevated (p < 0.01) and the platelets, the lymphocytes and the monocytes were not statistically elevated. Only one patient had a severe adverse reaction. Seventeen patients (85%) are dead, but only in 3 the cause was an infectious disease. CONCLUSION: the use of G-CSF prophylactically can elevate the neutrophil count and avoid the apparition of febrile neutropenia in patients with HIV related malignancies.

Adult↗

[Diagnosis of 4 cases of intestinal microsporidiosis in AIDS patients].

BACKGROUND: Most of the latest clinical and epidemiologic studies indicate that microsporidiosis and above all Enterocytozoon bieneusi cause approximately 7-50% of otherwise unexplained diarrhea in HIV-infected patients. Four cases of intestinal microsporidiosis in AIDS-patients are reported. METHODS: Detection of spores of microsporidiosis in stool samples from HIV-infected patients was performed by the following techniques: 1) light microscopy, using Kokoskin's modification of the Weber trichrome stain; 2) electron microscopy, for confirmation (only available in one case), and 3) indirect immunofluorescence assay (IIF), performed on all positive samples. Rabbit polyclonal antibodies anti-Encephalitozoon cuniculi, anti-E. hellem and anti-E. (Septata) intestinalis were used to eliminate the possibilities of presence of microsporidiosis other than E. bieneusi. RESULTS: Detection of spores of microsporidiosis by trichrome stain was positive in all samples from the 4 patients. By elimination, IIF confirmed the presence of Enterocytozoon bieneusi in all 4 cases. E. bieneusi was identified by electron microscopy in the only case available. Three patients had CD4+ lymphocyte counts < 100 x 10(6)/l and one < 500 x 10(6)/l. All had AIDS and three of them were homosexual. Two patients remained positive for microsporidiosis for almost 5 months. CONCLUSIONS: Despite the very few cases described in Spain, these preliminary data lead us to believe that intestinal microsporidiosis should be considered as an possible cause of diarrhea in our country also, and mainly in acute immunodeficiency patients.

Acquired Immunodeficiency Syndrome↗

Twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent recurrent toxoplasmic encephalitis in patients with AIDS. Spanish Toxoplasmosis Study Group.

OBJECTIVE: To evaluate the efficacy of twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent toxoplasmic encephalitis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized, open, multicenter trial. Patients were randomly assigned to receive sulfadiazine (500 mg) four times per day plus pyrimethamine (25 mg) plus folinic acid (15 mg) either daily (n = 60) or twice weekly (n = 45). SETTING: 8 university teaching hospitals. PATIENTS: Between February 1990 and June 1993, 105 patients with HIV infection were enrolled after each had had resolution of an acute episode of toxoplasmic encephalitis treated with sulfadiazine (1 g four times per day) plus pyrimethamine (50 mg/d) plus folinic acid (15 mg/d) for 4 to 8 weeks. MEASUREMENTS: Clinical and biological evaluations done every 30 to 60 days. End points were toxoplasmic encephalitis relapse, death, and interruption of therapy due to adverse reactions. RESULTS: After a median follow-up period of 11 months (range, 1 to 39 months), patients receiving the twice-weekly regimen had a higher rate of relapse then patients receiving the daily regimen (19.5 compared with 4.4 per 100 patient-years; incidence rate ratio, 4.36 [95% CI, 1.05 to 25.5]; P = 0.024). The estimated cumulative percentages of relapse at 12 months were 30% and 6%, respectively (P = 0.029), with an adjusted risk ratio (adjusted for age, sex, risk behavior, previous diagnosis of AIDS, Pneumocystis carinii pneumonia prophylaxis before initial episode of toxoplasmosis, CD4 cell count, baseline number of brain lesions, radiologic sequelae, and antiretroviral therapy during follow-up) of 5.6 (CI, 1.2 to 25.6; P = 0.028). Patients receiving the twice-weekly regimen had 1.6 times (CI, 0.9 to 2.9 times; P = 0.11) the adjusted risk for death of patients receiving the daily regimen. No statistical differences were found in the patients who stopped receiving the regimens due to adverse effects. No patient developed P. carinii pneumonia during the study period, even though 17 patients (10 receiving the daily regimen and 7 receiving the twice-weekly regimen) had had an episode of P. carinii pneumonia before study entry. CONCLUSIONS: At the given doses, a combination of sulfadiazine, pyrimethamine, and folinic acid was less effective when administered twice weekly than when administered daily, although the twice-weekly regimen was much more effective than historic controls.

AIDS-Related Opportunistic Infections↗

[Non-Hodgkin's lymphomas associated with the acquired immunodeficiency syndrome. A multicenter clinical study of 77 cases].

BACKGROUND: The aim of the present was to study the prevalence of non Hodgkin's lymphoma (NHL) in AIDS patients as well as the clinicopathologic characteristics, response to treatment and survival. METHODS: From January 1984 to January 1991, 77 patients with NHL associated with AIDS diagnosed in 9 hospitals in Madrid were retrospectively studied. RESULTS: Ninety-two per cent of the patients were men (mean age 30 years: range: 9-66 years), 62% were intravenous drug abusers and 20 (26%) homosexuals. Pathologic study determined that 62 (80%) patients had high grade NHL (44% small noncleaved), 17% immunoblastic and 20% unclassifiable, and 15 (20%) had intermediate grade (16% diffuse large cell) being all the cases of the B immunophenotype. Sixty-five per cent were in advanced stages and 69% had B symptoms. Extranodal localizations were present in 88%, bone marrow in 29% and CNS in 29%. Six cases had primary CNS lymphomas. 50% of the patients had less than 200 x 10(6)/l CD4 lymphocytes. Forty-seven patients were evaluable for response to chemotherapy: 12 (26%) showed a complete response 27 (57%) a partial response and 8 (17%) did not respond. Opportunistic infections developed in 18%. The estimated survival at 3 years was 14% (median 6 months). On univariate analysis the parameters related to the worst survival were: primary CNS lymphoma, liver involvement, lack of treatment response, LDH > or = 300 UI/l, alkaline phosphatase > or = 500 UI/l and ESR > or = 70 mm. CONCLUSIONS: Non Hodgkin's lymphomas associated with AIDS usually behave in an "aggressive" way with a high frequency of advanced stages, B symptoms, high grade histologic subtypes and extranodal involvement. Response to treatment is poor, bone marrow toxicity frequent and survival short.

Adolescent↗

A prospective study of the risk of tuberculosis among HIV-infected patients.

OBJECTIVE: To evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients. METHODS: Prospective longitudinal follow-up of 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration > or = 5 mm). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. RESULTS: Active TB developed in 23 out of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +/- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test but a positive Multitest developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and nine who converted during follow-up). Active TB developed in seven out of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in four out of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +/- 103 x 10(6)/l (range, 1-400 x 10(6)/l). CONCLUSIONS: Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 10(6)/l, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.

AIDS-Related Opportunistic Infections↗