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Biomedical subjects

J M Molina

Publications and source records attributed to J M Molina.

At least 73 records · Page 4Linked to original sources

[Early prediction of lack of response to treatment with interferon and interferon plus ribavirin using biochemical and virological criteria in patients with chronic hepatitis C].

The objectives of this study were the following: 1) to evaluate the predictive value of the detection of RNA-HVC compared to GPT in the third month of treatment in patients with chronic hepatitis C treated with IFN, and at the first and third month in patients treated with IFN and ribavirin for 6 and 12 months. The study included: A) 80/132 patients treated with IFN (3 MU/3 times a week for 6-12 months), and B) 70/110 patients who had previously not responded to IFN, and who were treated with combination therapy (IFN: standard dose, ribavirin: 1200 mg/day) for 6 months (n = 40) and 12 months (n = 30). In group A, the positive predictive value (the probability of predicting the lack of response if the RNA-HVC was positive or if the GPT was elevated at the third month) was greater for RNA-HVC than for GPT (97.9% vs. 94.4%), although the response was not unequivocal (2.3% vs. 10.5%). The negative predictive value was 48.6% vs. 36.2%, respectively. The prediction level (odds ratio) of RNA-HVC and of GPT was 39.7 vs. 8.78 (p <0.000001 vs. p <0.002). The positive predictive value was 97.6% in patients with genotype 1, 4 and 5, and 100% in those with genotype 2 and 3. In group B, the positive predictive value was also greater for RNA-HVC than for GPT at the first month (100% vs. 94.4%) following six months of therapy, the odds ratio being infinite vs. 7.6. The positive predictive value was greater for RNA-HVC at the third month than at the first (100% vs. 91%), whereas it was similar for GPT (100%) with 12 months of therapy, the odds ratio being greater for GPT than for RNA-HVC at the first month (infinite and 7.27). The following was concluded: 1) detection of RNA-HVC at the third month of treatment with IFN predicts in advance a lack of response in patients, with a minimum risk of error; 2) in patients with six months of combined therapy, the detection of RNA-HVC at the first month is extremely reliable in the prediction of a lack of response, whereas after 12 months of combined therapy, elevated GPT values at the first month and the detection of RNA-HVC at the third are highly predictive of a lack of response.

Adolescent↗

Results of the ALBI trial: a randomized comparison of stavudine/didanosine, zidovudine/lamivudine and alternating treatment in antiretroviral-naive patients.

In the ALBI trial, 151 antiretroviral-naive patients with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 10,000 to 100,000 copies/ml and CD4 cell counts > or = 200 cells/mm3 received 24 weeks of treatment with stavudine/didanosine (n=51), zidovudine/lamivudine (n=51) or stavudine/didanosine for 12 weeks followed by zidovudine/lamivudine (n=49). Baseline plasma HIV-1 RNA and CD4 cell counts were comparable in the treatment groups. The mean decrease in plasma HIV-1 RNA at 24 weeks in the stavudine/didanosine group (2.26 log10) was significantly greater than that in either the zidovudine/lamivudine group (1.26 log10) or the alternating treatment group (1.58 log10) (P<0.0001 for both). Proportions of patients with plasma HIV-1 RNA level <500 copies/ml (91% vs 42% and 60%) and <50 copies/ml (47% versus 4% and 9%) were significantly greater in the stavudine/didanosine group (P<0.001 for pairwise comparisons). Stavudine/didanosine was associated with a mean increase in CD4 cell count (124 cells/mm3) significantly greater than that in the zidovudine/lamivudine group (62 cells/mm3, P<0.01) and comparable to that in the alternating group (118 cells/mm3). All study regimens were well tolerated. These findings, indicating superiority of stavudine/didanosine over zidovudine/lamivudine in virological and immunological response over 24 weeks, suggest that the combination should be considered as a basis for highly active antiretroviral therapy.

Anti-HIV Agents↗

Stavudine, didanosine and nevirapine in antiretroviral-naive HIV-1-infected patients.

In an ongoing, open-label, non-comparative study, the safety and efficacy of nevirapine/stavudine/didanosine were evaluated in 100 antiretroviral-naive adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV-1 RNA (pVL) > or = 5000 copies/ml. Sixty patients received nevirapine twice daily (VIRGO I) and 40 received nevirapine once daily (VIRGO II); all patients received didanosine once a day. After median follow-ups of 44 weeks in VIRGO I and 30 weeks in VIRGO II, the following virological results were observed (ongoing study): an intent-to-treat, non-completer equals failure analysis at week 24 showed the proportions of patients with pVL <500 copies/ml were 78% in VIRGO I (60% <50 copies/ml) and 75% in VIRGO II. An on-treatment analysis at week 52 showed 80% of patients with a pVL <500 copies/ml and 59% with <50 copies/ml in VIRGO I. The mean CD4 cell count increase was +171 cells/mm3 at week 24 and +218 cells/mm3 at week 52 in VIRGO I and +158 cells/mm3 at week 24 in VIRGO II. Cutaneous rash (grades 1 to 3) occurred in 24% of patients leading to nevirapine discontinuation in eight of 24 patients. Five other patients discontinued therapy during the first 24 weeks because of hepatic cytolysis, peripheral neuropathy or biological pancreatitis. The nevirapine/stavudine/didanosine combination is a convenient and safe regimen, with rapid and potent immunological and antiviral effects sustained over 12 months.

Anti-HIV Agents↗

The prevalence of Dirofilaria immitis in Gran Canaria, Canary Islands, Spain (1994-1996).

Blood samples from 2034 dogs were tested to detect Dirofilaria immitis antigen during three consecutive years (from 1994 to 1996) in Gran Canaria Island, Canary Islands, Spain. The prevalence of heartworm infection was 67.02% in 1994, 58.92% in 1995 and 52.18% in 1996, with a mean prevalence of 58.89%. Heartworm infection was more common in males (56.19%) than in females (43.81 %), in dogs aged between 3 and 6 years old. The distribution of the disease in the different climatic zones was studied. Chronological changes in the dog's prevalence for heartworm infection in the three consecutive years and the role of the epidemiological factors in the changes of the positive rates were evaluated.

Age Distribution↗

Use of the cytomegalovirus (CMV) antigenemia assay for the rapid diagnosis of primary CMV infection in hospitalized adults.

We assessed the value of the cytomegalovirus (CMV) antigenemia assay for diagnosing primary CMV infection in adults. The CMV antigenemia assay was performed for 40 patients admitted to our unit over a 2-year period with unexplained fever and suspected primary CMV infection. Nine of the 10 patients with primary CMV infection had positive CMV antigenemia assays, and the results were available within 5 hours. All 10 patients had a mononucleosis-like syndrome. All but one of the 30 other patients had negative CMV antigenemia assays. A false-positive result was obtained for a patient with systemic lupus erythematosus. Overall, the CMV antigenemia assay was 90% sensitive and 96% specific for the diagnosis of primary CMV infection. Therefore, the CMV antigenemia assay appears to be a simple, rapid, inexpensive test for the diagnosis of primary CMV infection in hospitalized adults.

Adult↗

Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial.

A double-blind placebo-controlled trial was conducted to assess the efficacy and safety of albendazole (400 mg twice daily for 3 weeks) for the treatment of Encephalitozoon intestinalis infection in patients with AIDS. Clearance of microsporidia from the intestinal tract was obtained in 4 of 4 patients in the albendazole group versus 0 of 4 in the control group (P = .01, one-sided Fisher's exact test) and was associated with significant clinical benefit. All 4 controls subsequently cleared microsporidia following open-labeled albendazole treatment. To investigate the effect of albendazole in preventing relapse, these 8 patients were then randomly assigned to receive either albendazole (400 mg twice daily) or no treatment for the next 12 months. Albendazole significantly delayed the occurrence of relapse (P = .04, one-sided log-rank test). In human immunodeficiency virus-infected patients with E. intestinalis infection, albendazole has parasitologic and clinical efficacy and reduces the risk of relapse.

AIDS-Related Opportunistic Infections↗

Risk factors for intestinal microsporidiosis in patients with human immunodeficiency virus infection: a case-control study.

A prospective unmatched case-control study was conducted to determine risk factors for intestinal microsporidiosis in persons infected with human immunodeficiency virus (HIV) who had < or = 200 CD4 cells/mm3. In multivariate analysis, case-patients (n = 30) were more likely than were control-subjects (n = 56) to have < or = 100 CD4 cells/mm3 (odds ratio [OR], 6.5; 95% confidence interval [CI], 1-42), to report male homosexual preference (OR, 7.6; 95% CI, 1-59.5), and to report swimming in a pool in the previous 12 months (OR, 9.2; 95% CI, 2.1-38.9). In summary, intestinal microsporidiosis in persons with HIV infection and < or = 200/mm3 CD4 cells is associated with male homosexuality and swimming in pools, suggesting fecal-oral transmission, including sexual and waterborne routes.

AIDS-Related Opportunistic Infections↗

Blinded, externally controlled multicenter evaluation of light microscopy and PCR for detection of microsporidia in stool specimens. The Diagnostic Multicenter Study Group on Microsporidia.

The quality parameters for the detection of microsporidia in identical sets of 50 stool samples were determined for six laboratories where technicians used light microscopy and for six laboratories where technicians used PCR. The average overall sensitivities were 67% (89% for patient samples only) for the PCR laboratories and 54% (80% for patient samples only) for the light microscopy laboratories. Specificities were 98 and 95%, respectively. Differences in results were most apparent between the individual laboratories rather than between the two major methods used.

Animals↗

Determination of types of Enterocytozoon bieneusi strains isolated from patients with intestinal microsporidiosis.

To determine the types of Enterocytozoon bieneusi strains associated with intestinal microsporidiosis, we developed a rapid and efficient approach for typing parasites obtained from stool specimens by PCR-restriction fragment length polymorphism (PCR-RFLP). Typing was based on DNA polymorphism of the ribosomal DNA internal transcribed spacer (ITS) region of E. bieneusi. RFLPs generated with two restriction enzymes (NlaIII and Fnu4HI) in PCR-amplified ITS products were used to classify strains into different lineages. This approach was successfully used to differentiate 78 strains that had been obtained from the stools of 65 patients with intestinal microsporidiosis. Among the 78 strains, we found four genetically unrelated lineages, showing the genetic diversity of E. bieneusi. Type I strains of E. bieneusi were found in a majority of the samples, accounting for 51 (78%) of the 65 microsporidiosis cases. In contrast, type II, III, and IV strains were found in only 8 (12%), 3 (5%), and 3 (5%) cases, respectively. All strains of E. bieneusi we have tested so far fall into one of four different lineages, and this study shows that human intestinal microsporidiosis is most often associated with type I strains. PCR-RFLP analysis of the ITS region of E. bieneusi should be useful for epidemiological studies.

AIDS-Related Opportunistic Infections↗

[Human immunodeficiency virus and resistance].

It has been demonstrated that following prolonged treatment with reverse transcriptase inhibitors, especially with nucleoside analogs, resistant viral strains appear that show mutations in the nucleotides of the gene that codifies reverse transcriptase. These mutations cause changes in amino acids, which gradually increases resistance. In this study we evaluated the applicability af the LiPA HIV-1 RT test in determining the presence of mutations in this gene that can lead to resistance to antiretroviral treatments.Twenty-one samples were studied without previous knowledge of the antiviral treatments that the patients had received. No mutations in the HIV-1 stains from untreated patients were found. In the other patients who had undergone various treatment regimens, the results obtained With the LiPA HIV-1 RT made in possible to retrospectively identify the different nucleoside analogs they had been treated with. The most frequently found mutations were those that lead to a certain degree of resistance to AZT, followed by those related to resistance to ddl, which in effect in this order were the drugs used in the treatment of the patients. However, the LiPA HIV-1 RT test has certain limitations. It can only detect mutations that can be recognized by its sequences. As such, including sequences that would make it possible to study the possible genotypic variations in the gene that codifies the protease of HIV-1 would be helpful, given the importance of the protease inhibitors in clinical practice. In any case, direct sequencing continues to be standard method as it allows us to obtain full information on the genes that need to be studied.

Anti-HIV Agents↗

[Primary cerebral lymphoma in AIDS. Retrospective study of 20 patients].

OBJECTIVES: Analyze the epidemiological pattern of primary central nervous system lymphoma in AIDS patients together with the clinical expression and course under treatment. METHODS: We retrospectively reviewed 20 patients with AIDS-associated primary central nervous system lymphoma hospitalized in our unit between April 1992 and July 1996. Diagnosis was considered probable when an expansive intracranial process was associated with CT-scan enhancement and antitoxoplasma therapy failure in patients with extraneurological localization. Diagnosis was considered to be certain after histological confirmation. RESULTS: Most-patients were male (19/20), with a median CD4 cell count of 9/mm3 (range 0-138). Ninety percent had AIDS before diagnosis. The presenting symptoms were mental status changes (70%), neurologic deficits (55%), fever without another cause (30%), increased intracranial pressure (25%) or seizures (25%). Opportunistic diseases were usually associated (60%). CT-scan (18/20) showed spontaneous iso or hyperdense lesions, most often solitary (67%), with nodular contrast enhancement (72%). When performed (7/20), magnetic resonance imaging showed hypointense lesions on T1-weighted images with marked contrast enhancement. Diagnosis of primary central nervous system lymphoma was suspected in 19 patients because of the failure of antitoxoplasma treatment; 4 patients had stereotactic biopsy which confirmed the diagnosis. Patients were treated with either total brain radiation therapy (10%), corticosteroids (30%), or both (60%). The median survival time after onset of symptoms was better with combined therapy or radiation therapy alone than with steroids alone (6 vs. 2 months). Interestingly, most of the patients died from neurological complications of lymphoma (85%). DISCUSSION: The frequency of lymphoma-related death is probably due to better management of opportunistic infections and the effect of antiretroviral therapy. Further studies combining antiretroviral therapy, radiation and chemotherapy in patients with good performance status should be considered to improve the poor prognosis of AIDS-associated primary central nervous system lymphoma.

AIDS-Related Opportunistic Infections↗

Sternal abscess due to Bartonella (Rochalimaea) henselae in a renal transplant patient.

Bartonella henselae, previously called Rochalimaea henselae, is the causative agent of cat scratch disease (CSD) in immunocompetent subjects and bacillary angiomatosis in immunocompromised ones. Bone lesions are common in bacillary angiomatosis, but not in CSD. We present the case of a patient with a renal transplant treated by immunosuppressive therapy who developed a sternal abscess with a histological pattern of CSD. The CT pattern was that of a lytic bone lesion with adjacent fluid collection. The diagnosis was made on the basis of a polymerase chain reaction amplification performed on bone material. Bartonella henselae is a newly described bacteria that causes CSD in a normal host and bacillary angiomatosis in immunocompromised patients. We report a case of an osteolytic lesions of the sternum with adjacent fluid collection related to CSD, which occurred in a patient with a renal transplant.

Abscess↗

IgG concentration in mammary secretions of goats throughout lactation in healthy and coagulase-negative staphylococci infected udders.

Radial immunodiffusion was used to determine immunoglobulin (Ig)-G concentrations in 16 mammary secretions from uninfected udder halves and in 10-14 secretions from halves subclinically infected with coagulase-negative staphylococci in goats throughout lactation. IgG concentrations in samples from uninfected halves decreased rapidly during the first week after parturition (P < 0.001 ), henceforth falling slowly up to 30 d post-partum (P < 0.001). From 30 d post-partum to 180 d of lactation, IgG concentration showed a continuous decline to the end of the experiment but these changes were not statistically significant until 150 d after kidding (P < 0.01). IgG concentrations in lacteal secretions of halves harbouring coagulase-negative staphylococci showed a similar pattern, from the first month of lactation, to that observed in healthy udder halves, but concentrations were always lower. These differences were significant from 2 months after parturition (P < 0.001). IgG concentrations were compared with somatic cell counts obtained using an automatic counter (Fossomatic).

Animals↗