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Biomedical subjects

F Laguna

Publications and source records attributed to F Laguna.

At least 19 recordsLinked to original sources

[Ankle-brachial index in patients with diabetes mellitus: prevalence and risk factors].

INTRODUCTION: Diabetic patients have a high cardiovascular morbidity and mortality rate. Ankle brachial index (ABI) is an available, straightforward and reproducible method for the detection of peripheral vascular disease and for improving risk stratification in this population. The objective of our study was to evaluate the prevalence of a low and a pathological ABI in type 2 diabetics older than 60 years and to study the risk factors associated with its development. PATIENTS AND METHODS: 1,360 subjects between 60 and 79 years, 213 of them diabetics, without symptoms of intermittent claudication and who gave their consent to have an ABI measurement in their primary care center were included in the study. Cardiovascular risk factors were evaluated in all participants. An ABI < 0.9 was considered low and a value < 0.9, >or= 1.4 or non-compressible was considered pathological. RESULTS: Prevalence of a low ABI in subjects with or without diabetes was 11.3% and 4.3% and prevalence of a pathological ABI was 18.8% and 7%, respectively. Factor associated with a low or pathological ABI were gender, age, duration of diabetes, the type of antidiabetic treatment and the presence of vascular disease in another vascular bed. After multivariate adjustment, only age (OR: 1.15; 95% CI: 1.04-1.27) and duration of diabetes (OR: 1.05; 95% CI: 1.01-1.10) continue being significant. The prevalence of a pathological ABI did not differ between diabetics without vascular disease and non-diabetics with previous cardiovascular disease. CONCLUSION: The prevalence of a low or pathological ABI is elevated in diabetic subjects and relates with age, duration of diabetes and the presence of vascular disease in another vascular bed.

Aged↗

Visceral leishmaniasis in those infected with HIV: clinical aspects and other opportunistic infections.

Cases of visceral leishmaniasis (VL) in HIV-positive individuals have been reported from most areas of the world where the geographical distributions of the two infections overlap. The majority of the co-infected cases that have been recorded, however, live around the Mediterranean basin. In these subjects, the length of the incubation period of VL is presumably very short, particularly in those who have severe immunodepression. At diagnosis, almost all cases of VL/HIV co-infection have been found to have fewer than 200 CD4+ cells/microl blood, and about 50% meet the AIDS-defining criteria during their first episode of VL. The clinical manifestations of VL in HIV-infected individuals may be similar to those seen in HIV-negative cases; fever, pancytopenia and hepato-splenomegaly, for example, are found in 75% of all the HIV-positive cases. Following the dissemination of the parasites, however, the HIV-positive cases may develop unusual, multi-organ pathology. Almost all the cases of co-infection are very prone to VL relapses, even after carefully managed antileishmanial treatment. The opportunistic infections that are often seen in HIV-positives frequently develop during VL episodes, the signs and symptoms of the leishmaniasis then confusingly overlapping with those of the other infections.

AIDS-Related Opportunistic Infections↗

Treatment of leishmaniasis in HIV-positive patients.

Although, in southern Europe, there has been considerable experience in the treatment of visceral leishmaniasis (VL) in HIV-positive patients, the optimal therapy has yet to be established. Pentavalent antimony salts, free amphotericin B deoxycholate (ABD) and lipidic formulations of amphotericin B are the drugs most commonly used. Treatment with pentavalent antimonials requires daily injections for 28 days, is not well tolerated and leads to initial clinical cure in only 66% of the co-infected cases. Free ABD has to be given, intravenously, for just as long, has significant toxicity and leads to initial clinical cure in even fewer cases (62%). In a prospective, comparative trial, treatment of co-infected cases with a pentavalent antimonial was found to have similar efficacy and toxicity to treatment with free ABD. The duration of treatment and the associated toxicity may both be reduced by the use of lipidic formulations of amphotericin B. Anecdotal evidence and the results of non-randomized trials indicate that treatment with liposomal amphotericin B is highly effective. In a comparative trial, amphotericin B lipid complex was found to be not only as effective as a pentavalent antimonial but also better tolerated. At the moment, however, such lipidic formulations have only been tested against VL/HIV cases in Europe, not elsewhere in the world, and they remain very expensive. However successful the treatment in terms of initial clinical cure, almost all VL/HIV cases develop VL relapses. Although the data available on secondary prophylaxis are limited and often inconclusive, it appears that regular treatment with a pentavalent antimonial drug, liposomal amphothericin B or amphotericin B lipid complex can reduce the incidence of leishmanial relapses in HIV-positive patients with VL. The development of new regimens, use of new oral drugs (such as miltefosine) and the development of new antileishmanial drugs could all improve the treatment of HIV-related VL in the future.

AIDS-Related Opportunistic Infections↗

A nested polymerase chain reaction (Ln-PCR) for diagnosing and monitoring Leishmania infantum infection in patients co-infected with human immunodeficiency virus.

We investigated a Leishmania-specific nested polymerase chain reaction (Ln-PCR) for the diagnosis and treatment monitoring of L. infantum infections in patients co-infected with human immunodeficiency virus (HIV). Peripheral blood and bone marrow samples from 89 HIV patients in Spain suspected of having leishmaniasis were examined by different diagnostic techniques (Ln-PCR, microscopy, NNN culture and indirect fluorescent antibody test). The sensitivity of Ln-PCR compared with microscopy and culture of bone marrow was 95.45% using blood and 100% when using bone marrow. 38 of these patients with confirmed leishmaniasis were entered in a chemotherapy trial (reported elsewhere), and samples from them were collected before treatment, one month after treatment ended and during follow-up (1-20 months), and examined similarly. Ln-PCR was shown to be a good method for testing efficacy of treatment and for predicting relapses after treatment (relapses were predicted on average 5 months earlier than when using classical diagnostic techniques). We suggest that Ln-PCR (especially using peripheral blood) should be the technique of choice for diagnosis, monitoring the success of treatment, and predicting relapses in patients with HIV and suspected or confirmed L. infantum infection.

AIDS-Related Opportunistic Infections↗

Diagnostic utility of a multiplex herpesvirus PCR assay performed with cerebrospinal fluid from human immunodeficiency virus-infected patients with neurological disorders.

We used a multiplex nested-PCR assay for the simultaneous detection in cerebrospinal fluid (CSF) of five human herpesviruses (HVs) (cytomegalovirus [CMV], Epstein-Barr virus [EBV], varicella-zoster virus [VZV], herpes simplex virus [HSV], and human herpesvirus 6 [HHV-6]) in a clinical evaluation of human immunodeficiency virus (HIV)-infected patients with neurological disorders. This method, which has the advantages of being rapid and economical, would be of particular interest for the diagnosis of neurological syndromes caused by more than one HV. We studied 251 CSF samples from 219 patients. HV DNA was demonstrated in 93 (37%) of the CSF samples (34% of the patients). CMV was the HV most frequently detected in our patients (25%), while EBV, VZV, HSV, and HHV-6 DNAs were present in significantly fewer cases (7, 4, 3, and 1%, respectively). When results were compared with the final etiological diagnoses of the patients, the multiplex HV PCR showed high specificity for the diagnosis of CMV and VZV neurological diseases and for cerebral lymphoma (0.95, 0.97, and 0.99, respectively). The sensitivity of the assay was high for CMV disease (0.87), was low for cerebral lymphoma (0.33), and was not evaluable for VZV disease due to the small number of patients with this diagnosis. Nevertheless, detection of VZV DNA had possible diagnostic value in four of the nine cases, and EBV DNA amplification always predicted the diagnosis of cerebral lymphoma in patients with cerebral masses. Detection of HSV DNA was frequently associated with CMV amplification and fatal encephalitis. HHV-6 was not considered to have a pathogenetic role in the three cases in which it was detected. This multiplex HV PCR assay is a specific and clinically useful method for the evaluation of HIV-infected patients with neurological disorders related to HV.

AIDS-Related Opportunistic Infections↗

[The recommendations of GESIDA/SEFH/PNS for improving adherence to antiretroviral treatment. AIDS Study Group of the Spanish Society of Hospital Pharmacy and the National Plan on AIDS of the Minister of Health and Consumers].

The main objective of HAART is to achieve a complete suppression of the viral replication for long time. However, when the therapeutic drug levels are low, HIV can replicate and it can develop resistances. This fact can be the reason of treatment failure, HIV transmission of resistant strains and therefore an inappropriate use of the economical resources. In order to get the adequate therapeutic drug levels it is necessary to have a good adherence to the treatment. We review the factors that influence the adherence, the evaluation methods and we recommend the possible intervention strategies which should be given by a multidisciplinary team, integrated by physicians, pharmacists, nurses, psychologists and other personal support. To start HAART is not an emergency. For this reason is very important to prepare to the patient and to identify the non-adherence factors in order to correct it. Once the HAART is indicated it is very important to offer information during the medical prescription and when the drugs are dispensed. During the therapy is necessary to follow actively all patients on HAART. In order to make therapeutical decisions we need to know the patient drug adherence rate. We recommend to use several methods to calculate the drug adherence rate, being the most commonly used the patient interview, the patient questionnaire, the refill count, the pharmacy visits rate together with the viral load evolution of the patient. In order to get all this information it is necessary to have a very good communication between all the people involved in HIV infected patients care. If non-adherence is detected it is necessary to start the intervention strategies to correct it and if they fail it might be necessary in some cases to stop HAART. The potential benefits of the adherence programs can justify the economical spend in human and hospital facilities resources.

Anti-HIV Agents↗

[Recommendations of GESIDA (Grupo de Estudio de SIDA)/National Plan on AIDS with respect to the anti-retroviral treatment in adult patients infected with the human immunodeficiency virus in the year 2000 (II)].

OBJECTIVE: To update the recommendations for antiretroviral therapy (ART) in adult HIV-infected persons according to the new scientific advances and the existence of new antiretroviral drugs in the last two years. METHODS: The ART recommendations have been condensed by a panel of experts from the Spanish AIDS Study Group (Grupo de Estudio de Sida-GESIDA) of the Spanish Infectious Diseases and Clinical Microbiology Society (SEIMC) and from the Clinical Advisory Panel (CAP) of the Secretariat of the Spanish National Plan on AIDS (SPNS) of the Ministry of Health. Three levels of evidence have been established depending if the data came from randomized and controlled studies, from cohort or case-control studies or from descriptive studies and expert opinions, for that purpose we have reviewed the advanced in HIV pathophysiology and results of efficacy (clinical, virologic and immunologic) and security (toxicity) from clinical trials involving ART lasting at least 12 months, from cohort studies and pharmacokinetic and security data of antoiretrovírico drugs, presented in international conferences or published in biomedical journals in the last two years. In each situation we have established either to recommend or to consider or not recommend ART. RESULTS: Nowadays, ART consistent of at least three drugs constitutes the election therapy for chronic HIV infection, since it delays clinical progression, increases significantly the survival and diminishes hospital admissions and associated costs. The decision to start ART must be based upon three elements: presence or absence of symptoms, plasma vírica load and CD4+ cells counts. Thus, in asymptomatic cases with a high CD4+ cells count (> 500/microliter) and low vírica load (< 10,000 copies/ml by branched DNA bDNA or < 20,000 copies/ml by reverse-transcription polymerase chain reaction [RT-PCR] or nucleic acid sequence based amplification [NASBA]) we recommend to delay ART. In symptomatic patients we recommend to start it, and in asymptomatic patients, we could recommend or consider ART initiation depending on the risk of progression, established by the vírica load and the CD4+ cells count. In any case, if therapy is started, the objective must be to reach an indetectable vírica load (< 50 copies/ml). The adherence to ART plays a key role for its initial moment and for the duration of the antiviral response. ART can achieve a restoration of cellular immunity inb the advanced patients. There are few therapeutic options in failing patients due to cross-resistance. Resistance studies can be useful in this setting. The toxicity (lypodistrophy) is a new and limiting factor of ART which requires to look for new therapeutic options. ART criteria for acute infection, pregnancy, post-exposure prophylaxis and when to use resistance testing are discussed. CONCLUSIONS: In this moment, there is a more conservative attitude towards starting ART than in previous recommendations in which a virus eradication was considered. On the other hand, the high number of disposable drugs, the more sensitive monitorization methods (plasma vírica load) and the possibility of performing resistance studies make therapeutic strategies more dynamic and individualized for each patient and situation. In any case, it is mandatory to ensure a perfect adherence to ART from the patients.

Acquired Immunodeficiency Syndrome↗

Treatment of visceral leishmaniasis in HIV-infected patients: a randomized trial comparing meglumine antimoniate with amphotericin B. Spanish HIV-Leishmania Study Group.

BACKGROUND: Visceral leishmaniasis is common in patients with HIV infection living in endemic areas, but the most effective and safe treatment remains unknown. OBJECTIVE: To compare the efficacy and safety of meglumine antimoniate versus amphotericin B in HIV-infected patients with first episodes of visceral leishmaniasis (VL). DESIGN: An open, multicentre, prospective and randomized trial. SETTING: Twelve tertiary hospitals. PATIENTS: Eighty-nine consecutive HIV-infected patients diagnosed with VL. Patients were randomly assigned to treatment with either meglumine antimoniate (20 mg pentavalent antimony per kilogram of body weight per day) or amphotericin B (0.7 mg/kg per day) both for 28 days. Treatment was considered successful if a bone marrow aspirate performed 1 month after the end of therapy did not detect parasites. Relapse was defined as the reappearance of parasites after an initial cure. RESULTS: An initial cure was attained in 29 of 44 patients (65.9%) randomly assigned to treatment with meglumine antimoniate and 28 of 45 (62.2%) randomly assigned to treatment with amphotericin B. The incidence of moderate to severe adverse events was similar in both groups. The patients treated with meglumine antimoniate had higher incidences of cardiotoxicity (14 versus 0%, P = 0.02) and chemical pancreatitis (30 versus 0%, P < 0.01). However, in the amphotericin B group, nephrotoxicity was more frequent (36 versus 5%, P < 0.01). There was no difference in survival or relapse-free interval according to the allocated group of therapy. CONCLUSION: Treatment of VL with meglumine antimoniate or amphotericin B was shown to have similar efficacy and toxicity rates in Spanish HIV-infected patients. The differences in the toxicity patterns could be useful in choosing one of these agents as first-line treatment.

AIDS-Related Opportunistic Infections↗

Molecular characterization by PCR-fingerprinting of Candida dubliniensis strains isolated from two HIV-positive patients in Spain.

Six Candida dubliniensis isolates were recovered from two HIV-infected individuals in the course of a prospective study of recurrent oral candidosis among HIV-positive patients in Spain. Candida albicans strains as well as non-albicans strains were also obtained from these two patients. C. dubliniensis strains were germ-tube-positive and produced abundant chlamydospores. Fingerprinting the genomic DNAs of these six C. dubliniensis with the C. albicans-specific probe 27A as well as karyotyping was performed to confirm the identification of these isolates. Further analysis of their genomic DNAs was performed by PCR-fingerprinting with the core sequence of phage M13, and they exhibited species-specific multilocus band patterns, clearly distinct from those of C. albicans isolates analyzed in this study and in a previous one (Diaz-Guerra 1997). Intraspecies variation was also seen among PCR patterns yielded by C. dubliniensis isolates from different patients. Although few strains have been analyzed, the use of this PCR-fingerprinting procedure is a promising tool for further epidemiologic studies with C. dubliniensis. The isolation of C. dubliniensis from Spanish HIV-infected patients contributes to the idea of widespread geographic distribution of this species.

Candida↗

Infection of sand flies by humans coinfected with Leishmania infantum and human immunodeficiency virus.

To determine the role that Leishmania infantum/human immunodeficiency virus (HIV) coinfected patients could play in the epidemiology of visceral leishmaniasis (VL), we applied direct xenodiagnosis of VL in this study to test the infectivity of six coinfected patients to colonized Phlebotomus perniciosus. All patients proved to be infective for the sand flies. The infectivity of patients who had still not received specific treatment for VL was inversely proportional to their absolute CD4+ T lymphocyte cell count. It has been proven that P. perniciosus can acquire and allow the development of L. infantum by feeding on L. infantum/HIV coinfected patients. Since this sand fly is an important vector of VL in southern Europe, a new natural anthroponotic cycle could be considered in the epidemiology of L. infantum/HIV coinfection. The design of leishmaniasis control programs and the management of coinfected individuals should take these findings into account.

Adult↗

Change in fluconazole susceptibility patterns and genetic relationship among oral Candida albicans isolates.

OBJECTIVE: To assess the genetic homogeneity or heterogeneity within each set of Candida albicans isolates colonizing/infecting the oral cavities of HIV-infected patients undergoing azole therapy when changes in susceptibility to fluconazole were detected. DESIGN: Fourteen HIV-positive patients suffering recurrent episodes of oral candidosis were prospectively followed from the first episode to the isolation of strains with decreased susceptibility to fluconazole. The strains of C. albicans isolated either from episodes or controls throughout the prospective study were analysed. METHODS: Electrophoretic karyotyping and hybridization with the repeated sequence probe 27A were used to delineate sequential isolates. In vitro susceptibility tests to fluconazole and ketoconazole were also performed. The results obtained by DNA fingerprinting with the probe combined with computer-assisted analysis were used to assess the genetic relationships amongst the strains. In addition, comparison with the genetic relatedness of a group of geographically unrelated strains was made. RESULTS: Isogenic populations of sequential isolates were observed only in two patients; 12 patients harboured heterogenic populations over time, although in 11 patients there was a predominant strain that was isolated more than once, and only one of these patients carried strains with a similarity index less than 80%. With the exception of two patients, each patient carried a major strain that became less susceptible to fluconazole. The similarity index for the unrelated strains was 59%. CONCLUSIONS: HIV-infected patients may carry a mixed population of strains, but the strains tend to be related to each other. The strains were maintained throughout the course of infection and at least one developed secondary resistance to fluconazole.

AIDS-Related Opportunistic Infections↗

[Gallium-67 (Ga-67) scintigraphy in tuberculosis and Mycobacterium avium-M. intracellulare infections in patients with HIV infections].

BACKGROUND: Diagnosis of mycobacterioses in HIV infected patients is sometimes difficult because of atypical findings. The aim of this study was to assess the utility of gallium scintigraphy in diagnosis of AIDS related mycobacterioses in patients with fever of unknown origin. PATIENTS AND METHODS: We retrospectively reviewed the scans of 220 HIV(+) patients with fever (176 males [80%] and 44 females) who were evaluated with conventional diagnostic procedures at least of a week before. RESULTS: Gallium scintigraphy was positive in 114 patients (51%) and negative in 106 (49%). Mycobacteria were isolated in 83 patients (38%), 75 of these patients (90%) had a positive scintigraphy (sensitivity 90%; specificity 71%). Positive predictive value was 66% and negative predictive value was 92%. Mycobacterium avium-M. intracellulare (MAI) and M. tuberculosis were diagnosed in 22 (29%) and 53 (71%) HIV(+) patients, respectively. Seventy one (94%) of 75 patients with mycobacterioses had gallium uptake in at least two localizations. CONCLUSIONS: 67Ga scintigraphy is very useful in HIV(+) patients with fever of unknown origin. A negative gallium scintigraphy makes unlikely the diagnosis of mycobacterioses.

AIDS-Related Opportunistic Infections↗