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J M Molina

Publications and source records attributed to J M Molina.

At least 55 records · Page 3Linked to original sources

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation.

Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.

Acyclovir↗

Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients.

The safety and efficacy of a once-daily regimen that combines emtricitabine, didanosine, and efavirenz was studied among 40 previously untreated human immunodeficiency virus (HIV)-infected patients. The median plasma HIV RNA level was 4.77 log(10) copies/mL at baseline and decreased by a median of 3.5 log(10) copies/mL at 24 weeks, with 98% and 93% of patients achieving plasma HIV RNA levels <400 and <50 copies/mL, respectively. The median CD4 cell count was 373 cells/microL at baseline and increased by a median of 159 cells/microL at week 24. The most common treatment-related adverse events were mild to moderate central nervous system symptoms (73% of patients), diarrhea (33%), rashes (10%), and biochemical abnormalities. Adverse reactions led to permanent drug discontinuation in only 1 patient. The once-daily combination therapy of emtricitabine, didanosine, and efavirenz was safe and demonstrated strong antiviral and immunologic effects that lasted for the 24-week period of the study.

Adult↗

Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA.

OBJECTIVE: Intestinal microsporidiosis caused by Enterocytozoon bieneusi is a cause of chronic diarrhoea in patients with HIV infection for which there is no current therapy. This study was designed to assess the safety and efficacy of oral fumagillin in this infection. DESIGN: A dose-escalation trial. METHODS: Twenty-nine HIV-infected patients with E. bieneusi infection were consecutively enrolled in the trial. Oral doses of fumagillin were given to four groups of patients for 14 days: 10 mg/day (group 1), 20 mg/day (group 2), 40 mg/day (group 3), and 60 mg/day (group 4). Patients were seen at weeks 1, 2, 4 and 6 to assess safety and efficacy. Efficacy was assessed primarily by the clearance of microsporidia from stools and follow-up duodenal biopsies. RESULTS: Thirteen patients complained of abdominal cramps, vomiting or diarrhoea during the study, and three patients had fumagillin withdrawn because of adverse events. Thrombocytopenia, neutropenia and hyperlipasaemia were the most frequent biological adverse events. Twenty-one out of 29 patients transiently cleared microsporidia from their stools during the study. By week 6, however, all patients in groups 1, 2 and 3 had parasitic relapse. Interestingly, eight out of 11 (72%) patients treated with 60 mg/day (group 4) apparently cleared microsporidia from their gastrointestinal tract and gained weight. No parasitic relapse was documented in these eight patients during a mean follow-up of 11.5 months. CONCLUSION: Treatment with fumagillin at 60 mg/day for 14 days has promise as an effective oral treatment for E. bieneusi infections.

AIDS-Related Opportunistic Infections↗

Multiple bonding in four-coordinated titanium(IV) compounds.

Theoretical description (MP2/6-311G* and B3LYP/6-311G*) is presented for hypovalent titanium alkoxide model compounds showing linear angleTi-O-C angles. This feature is explained by the existence of a polarized triple Ti-O bond. In contrast, a series of 18 electron germanium derivatives displaying bent angleGe-O-C angles contain polarized single Ge-O bonds. The nature of the Ti-O and Ge-O bonds is established by means of natural bond order, atoms-in-molecules theory, and electron localization function analyses.

Journal Article↗

Disseminated infection due to Encephalitozoon cuniculi in a patient with AIDS: case report and review.

OBJECTIVE AND METHODS: Infections due to microsporidia are increasingly recognized as opportunistic infections in patients with AIDS. We describe here a case of disseminated infection due to Encephalitozoon cuniculi and review the literature on this microsporidial infection. RESULTS: All 12 patients reported in the literature had AIDS and nine presented with disseminated infection involving the kidneys, sinuses, lungs, brain and conjunctiva. Asymptomatic infection was seen in three patients. Microsporidia were detected by light microscopy examination of urine samples in all the cases. Species identification was performed by various genotypic methods or transmission electron microscopy. Eight of 12 patients who received albendazole therapy experienced clinical improvement with documented clearance of spores in five of these eight patients. Two patients relapsed. CONCLUSIONS: E. cuniculi infection should be considered in severely immunocompromised HIV-infected patients with multi-organ involvement and fever, especially when renal failure is present. Microsporidial spores are usually seen in urine samples and in the involved organ. Albendazole therapy seems to be effective.

AIDS-Related Opportunistic Infections↗

Genetic homology among thirteen Encephalitozoon intestinalis isolates obtained from human immunodeficiency virus-infected patients with intestinal microsporidiosis.

The ribosomal DNA internal transcribed spacer sequences of 13 unrelated Encephalitozoon intestinalis isolates obtained from human immunodeficiency virus (HIV)-infected patients with intestinal microsporidiosis were analyzed by gene amplification and DNA sequencing. Among these isolates, we found only one genetic lineage which suggests that E. intestinalis may have a clonal distribution in HIV-infected patients.

Animals↗

[Comparative analysis of viral load by bDNA HCV RNA-2.0 and amplicor HCV monitor in patients with hepatitis C infection].

BACKGROUND: Two standardized techniques, Quantiplex (bDNA-2.0) and Amplicor Monitor have been evaluated for the quantification of virus load of HCV with these objectives: a) determinate the relationship between virus load and genotype, and b) evaluate the virus load in serial serum samples and in patients with normal or slightly increased liver enzymes in an area with a high prevalence of genotype 1. RESULTS: A significant correlation of 0.7 (p < 0.0001) in virus load has been observed by both methods, but the virus load is smaller by Monitor than by Quantiplex and does not depend on genotype. The relationship Monitor/Quantiplex is smaller in patients with non-1 genotype than in patients with genotype 1a (p = 0.01) and 1b (p = 0.005). Virus characteristics are similar in patients with normal or slightly increased enzymes than in patients with high enzymes. Virus load by both methods is not related to the age, sex, know duration of the infection, transmission manner of the infection neither to the histologic activity index. CONCLUSION: The virus load not depends on genotype. The determination of virus load in a single serum sample adequately reflects the virus load are in several serum samples in patients with chronic HCV infection. The genotype and the virus load are similar in patients with normal enzymes than in patients with high enzymes.

Adult↗

[ROC curve analysis of factors predictive of non-response to interferon treatment in patients with chronic hepatitis C, genotype 1].

The objectives of this study included: 1) to identify pretreatment variables predictive of absence of response in 107 patients with chronic hepatitis C, genotype 1, treated with interferon-a (IFN-a) at a dose of 3 MU three times weekly for 3-12 months and classified into two groups: group A, nonresponders vs. patients with a complete response, and group B, nonresponding and relapsing patients vs. patients with a sustained response; and 2) to establish a prognostic index using ROC curve analysis. The rate of sustained response was 6. 5% at the 24-month follow-up. The pretreatment characteristics with predictive value using ROC curves were as follows: in group A, age, GGT, serum ferritin, viral load, and grade and stage of the histological lesion; and in group B, known duration of infection, GPT, GGT, serum ferritin, viral load, and grade and stage of the histological lesion. In both group A and group B the positive predictive value (the probability of predicting an absence of response when the variable is present) was greater than the negative predictive value (mean: 84.3% vs. 41.1%, 99% vs. 16.5%, respectively). In group A, based on the prognostic index, the positive predictive value when three variables were present was 96% and the sensitivity was 63.5%, with the test being unequivocal in 6.5%, whereas when four or five variables were present, the positive predictive value was 97% and 100% and the sensitivity was 40.5% and 18%, respectively. In group B, the positive predictive value when two variables were present was 100% and the sensitivity was 87%, whereas when three, four, five and six variables were present the sensitivity was between 73% and 28%. In group A, age, GGT and ferritin were the predictive variables independently associated with an absence of response, with a relative risk of 6.5, 4.8 and 3.1, respectively, whereas in group B we did not find variables independently associated with an absence of response. It was concluded that in patients with genotype 1, it is possible to predict the absence of response to IFN therapy with a high degree of reliability.

Adolescent↗

Receiver operating characteristics curve analysis of factors predictive of nonresponse to interferon therapy in patients with chronic hepatitis C.

OBJECTIVES: 1) to identify pretreatment variables predictive of nonresponse to interferon-alpha (IFN-alpha) in patients with chronic hepatitis C, and 2) to establish a prognostic index in these groups using receiver operating characteristics curve analysis. METHODS: 132 patients were treated with IFN-alpha at a dose of 3 megaunits three times a week for 3-12 months. The response was compared in patients with a complete response vs nonresponders, and patients with a sustained response vs nonresponders plus relapsers. Factors predictive of response were identified by analyzing clinical, biochemical, virological and histological variables. RESULTS: The sustained response rate was 12.8% at 24 months of follow-up. The pretreatment characteristics with a predictive value (PV) according to area under the ROC curve and 95% confidence interval > 0.5 were age, known duration of infection, history of transfusion, GGT, serum ferritin levels, viral load, genotype, and grade and stage of the histological lesion. The positive PV (the probability of predicting absence of response when the variable is present) was notably greater than the negative PV (mean: 94.9% vs 24.8%, respectively). In addition, when 4 and 6 variables were present, the positive PV was 100% and sensitivity was 60.2% and 22.1%, respectively. The predictive variables independently associated with an absence of response were genotypes 1, 4 and 5, GGT > 24 IU/l and grade of the histological lesion > 6. CONCLUSIONS: It was possible to predict the absence of both primary and posttreatment response with an acceptable degree of reliability.

Adult↗

The VIRGO study: nevirapine, didanosine and stavudine combination therapy in antiretroviral-naive HIV-1-infected adults.

The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.

Adult↗

Seroprevalence of Trypanosoma evansi in dromedaries (Camelus dromedarius) from the Canary Islands (Spain) using an antibody Ab-ELISA.

After the description in Grand Canary Island of a case of dromedary trypanosomosis caused by Trypanosoma evansi in 1998, an indirect enzyme immunoassay for the detection of specific anti-T. evansi IgG (Ab-ELISA) was used to assess the seroprevalence of this disease on the Canary Islands. Seroprevalence was 9.0% in the four studied islands (Gran Canaria, Tenerife, Lanzarote and Fuerteventura), varying from 10.0 to 7.5% by island (not significantly different). Prevalence using Ab-ELISA was higher than that observed when a parasitological method (microscopic observation of blood smears) was used (1.3%).

Animals↗

[Cytomegalovirus enteritis in AIDS. 2 cases].

BACKGROUND: It is uncommon for manifestations of cytomegalovirus infection to be limited to the small bowel in AIDS patients. CASE REPORTS: Two HIV-positive patients developed cytomegalovirus infection involving the small bowel with no other visceral localization. Recurrences were frequent despite medical therapy. DISCUSSION: The clinical manifestations, diarrhea, fever, vomiting and abdominal pain, suggest the diagnosis of cytomegalovirus enteritis in AIDS patients. Confirmation is obtained from the small bowel study and pathology examination of biopsy specimens. Treatment is generally based on medical and surgical management using intravenous anti-cytomegalovirus drugs and partial resection. Prognosis often remains less than satisfactory in this condition which is often diagnosed late.

AIDS-Related Opportunistic Infections↗

The ALBI trial: a randomized controlled trial comparing stavudine plus didanosine with zidovudine plus lamivudine and a regimen alternating both combinations in previously untreated patients infected with human immunodeficiency virus.

A total of 151 previously untreated patients infected with human immunodeficiency virus type 1 (HIV-1) with CD4 cell counts >/=200/microL and plasma HIV-1 RNA levels of 10,000-100,000 copies/mL were randomly assigned to 24 weeks of open-labeled stavudine plus didanosine (group 1), zidovudine plus lamivudine (group 2), or stavudine plus didanosine followed by zidovudine plus lamivudine (group 3). The mean decrease in HIV-1 RNA level was greater in group 1 (2.26 log10 copies/mL) than in groups 2 (1.26 log10 copies/mL) or 3 (1.58 log10 copies/mL; P<.0001). The mean increase in CD4 cell counts was greater in groups 1 (124 cells/microL) and 3 (118 cells/microL) than in group 2 (62 cells/microL; P=.02). All regimens were generally well tolerated. The combination of stavudine plus didanosine reduced plasma HIV-1 RNA concentrations and increased CD4 cell counts more effectively than did the combination of zidovudine plus lamivudine or the regimen alternating both combinations.

Adult↗

Usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death in patients with AIDS.

A cohort study of 214 human immunodeficiency virus (HIV)-infected patients was performed to assess the usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death. Multivariate analysis revealed that only positive baseline CMV antigenemia assays (relative risk [RR], 7.2; 95% confidence interval [CI], 3.7-14.2; P = .0001) and CD4 cell counts (RR, 0.98; 95% CI, 0.97-0.99; P = .009) were associated with CMV disease. A positive baseline CMV antigenemia assay was also associated with death by multivariate analysis (RR, 2.2; 95% CI, 1.5-3.4; P = .0003). Increasing levels of CMV antigenemia during follow-up were associated with increased risks of CMV disease and death. A positive CMV antigenemia assay that showed > 10 cells per 2 x 10(5) polymorphonuclear leukocytes during follow-up was 91% sensitive and 84% specific for predicting a diagnosis of CMV disease; the negative predictive value for this positive test was high (97%). Therefore, the CMV antigenemia assay appears to be a simple, rapid, and inexpensive test for predicting the occurrence of CMV disease and death in patients with advanced HIV infection.

AIDS-Related Opportunistic Infections↗

[The effect of iron depletion on the response to interferon treatment in patients with chronic hepatitis C. Pilot study].

UNLABELLED: It has been reported that increase in serum ferritin levels and/or in hepatic iron content is associated with a poor response to interferon treatment in patients with chronic hepatitis C (CH-C). AIM: To determinate whether iron depletion by phlebotomy (PB) increases the response to interferon therapy in chronic hepatitis C. PATIENTS AND METHODS: We have evaluated 12 patients with CH-C (genotype 1b = 11, 1a = 1), increased ALT levels, positive serum VHC-RNA and increased serum ferritin levels (> 220 ng/ml), including 8 previously non responders to interferon therapy and 4 naive subjects. Phlebotomies were performed weekly (mean number per patient: 6, range: 5-12) until serum ferritin levels were < 100 ng/ml, followed by interferon treatment (3MU thrice weekly for 3-12 months depending on the response). RESULTS: Multiple regression analysis showed that serum ferritin levels were not related to serum ALT levels (p = 0.18) or viral load (p = 0.06). Serum ALT levels decreased significantly post-PB (58 U/l, range: 35-141 U/l) as compared to pretreatment levels (164 U/l, range: 51-216 U/l, p < 0.006) and normalized in two subjects. HCV-RNA was positive in one of the latter and negative in the other. Eleven of the twelve patients did not respond to interferon after three months of therapy (increased serum ALT levels in 10 subjects and positive HCV RNA in 11). One additional patient, who had not been treated previously with interferon and had low pretreatment viral load, had a sustained response after 12 months of interferon therapy. Viral load did not decreased either with PB or following interferon treatment. By contrast, serum ferritin levels did not increase with interferon treatment or during the 6 month follow-up period. CONCLUSIONS: Decreasing serum ferritin levels by phlebotomies does not increase HCV erradication rate after interferon treatment. Sustained response to interferon therapy is an infrequent event and is more dependent on viral factors (viral load and genotype).

Adult↗