Adequacy and prognostic impact of treatment for severe exacerbation of chronic obstructive pulmonary disease. / Adecuación e impacto pronóstico del tratamiento de las exacerbaciones graves de la enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To define the clinical characteristics of patients hospitalised in pneumology and internal medicine departments for chronic obstructive pulmonary disease (COPD) exacerbation, to assess the compliance with the recommendations of the clinical practice guidelines and to determine the impact on the patients' prognosis. METHODOLOGY: We conducted a retrospective longitudinal study that randomly included patients hospitalised for COPD exacerbation in a tertiary hospital. We collected demographic and clinical variables (degree of dyspnoea and obstruction, previous exacerbations, comorbidities), readmission and mortality data and criteria for compliance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and the Spanish COPD guidelines (GesEPOC). We performed a univariate, multivariate and survival analysis. RESULTS: The study included 108 patients, and the mean age was 71.48±11.65 years. The readmission rate was 26.4% at 3 months and 43.4% at 1 year. The hospital mortality rate was 3.9%, the mortality rate at 3 months was 21.9%, and the mortality rate at 1 year was 27.4%. The patients hospitalised in the internal medicine department had higher mortality during hospitalisation (p=.043), at 3 months (p=.028) and at 1 year (p=.007) compared with the rates for the pneumology department. Overall compliance with the clinical guidelines was 63% for the clinical evaluation (less for the patients in internal medicine: 56.1% vs. 73.8%, p=.063). For the treatment, the compliance was 26.9% for GOLD and 28.7% for GesEPOC. Compliance with the GOLD guidelines in the use of corticosteroids was associated with a lower rate of long-term readmissions (p=.041) and hospital mortality (p=.007) and 3-month mortality (p=.05). CONCLUSIONS: The clinical profile of the patients is currently similar to that previously reported, but their clinical progression was poorer. Overall compliance with the clinical guidelines for drug treatment was low, and only appropriate use of systemic steroids was associated with a reduction in early mortality and in medium-term readmissions.

Anticoagulant treatment of medical patients with complex clinical conditions. / Tratamiento anticoagulante en pacientes médicos con situaciones clínicas complejas.

There is scarce available information on the treatment or prophylaxis with anticoagulant drugs of outpatients with medical diseases and complex clinical conditions. There are no clinical practice guidelines and/or specific recommendations for this patient subgroup, which are frequently treated by internists. Complex clinical conditions are those in which, due to comorbidity, age, vital prognosis or multiple treatment with drugs, a clinical situation arises of disease-disease, disease-drug or drug-drug interactions that is not included within the scenarios that commonly generate the scientific evidence. The objective of this narrative review is collecting and adapting of the clinical guidelines recommendations and systematic reviews to complex clinical conditions, in which the direct application of recommendations based on studies that do not include patients with this complexity and comorbidity could be problematic.

Pneumocystis jirovecii infection in patients with acute interstitial pneumonia. / Infección por Pneumocystis jirovecii en pacientes con neumonía intersticial aguda.

OBJECTIVE: Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP. SUBJECTS AND METHODS: The presence of P. jirovecii in bronchoalveolar lavage fluid in the four confirmed cases of AIP identified in a tertiary-care hospital over a period of nine years was studied using a 2-step nested-PCR protocol assay. RESULTS: P. jirovecii was identified in the four cases. None of them had HIV infection. Two of the patients were treated empirically with trimethoprim-sulfamethoxazole, the only survivor was being one of them. CONCLUSIONS: Our data suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to evaluate the role of the pathogen in the physiopathology of this disease.

Delphi-RAND consensus of the Spanish Society of Internal Medicine on the controversies in anticoagulant therapy and prophylaxis in medical diseases. INTROMBIN Project (Uncertainty in thromboprophylaxis in internal medicine). / Consenso Delphi-RAND de la Sociedad Española de Medicina Interna sobre controversias en terapia y profilaxis anticoagulante en enfermedades médicas. Proyecto INTROMBIN (INcertidumbre en TROMBoprofilaxis en Medicina INterna).

The aim of this study was to determine the opinion of internists on the management of anticoagulation and thromboembolism prophylaxis in complex clinical scenarios in which the risk-benefit ratio of surgery is narrow and to develop a consensus document on the use of drugs anticoagulant therapy in this patient group. To this end, we identified by consensus the clinical areas of greatest uncertainty, a survey was created with 20 scenarios laid out in 40 clinical questions, and we reviewed the specific literature. The survey was distributed among the internists of the Spanish Society of Internal Medicine (SEMI) and was completed by 290 of its members. The consensus process was implemented by changing the Delphi-RAND appropriateness method in an anonymous, double-round process that enabled an expert panel to identify the areas of agreement and uncertainty. In our case, we also added the survey results to the panel, a methodological innovation that helps provide additional information on the standard clinical practice. The result of the process is a set of 19 recommendations formulated by SEMI experts, which helps establish guidelines for action on anticoagulant therapy in complex scenarios (high risk or active haemorrhage, short life expectancy, coexistence of antiplatelet therapy or comorbidities such as kidney disease and liver disease), which are not uncommon in standard clinical practice.

Dynamic colonisation by different Pneumocystis jirovecii genotypes in cystic fibrosis patients.

Although asymptomatic carriers of Pneumocystis jirovecii with cystic fibrosis (CF) have been described previously, the molecular epidemiology of P. jirovecii in CF patients has not yet been clarified. This study identified the distribution and dynamic evolution of P. jirovecii genotypes based on the mitochondrial large-subunit (mt LSU) rRNA gene. The mt LSU rRNA genotypes of P. jirovecii isolates in 33 respiratory samples from CF patients were investigated using nested PCR and direct sequencing. Three different genotypes were detected: 36.3% genotype 1 (85C/248C); 15.1% genotype 2 (85A/248C); 42.4% genotype 3 (85T/248C); and 6% mixed genotypes. Patients studied during a 1-year follow-up period showed a continuous colonisation/clearance cycle involving P. jirovecii and an accumulative tendency to be colonised with genotype 3.

Prediction and biochemical characterization of intrinsic disorder in the structure of proteolysis-inducing factor/dermcidin.

Proteolysis-inducing factor/dermcidin (PIF/DCD) is a novel human gene, located on chromosome 12, locus 12q13.1, that encodes a secreted 110-amino acid protein. Two transcripts for the protein have been identified in normal skin, breast, placenta and brain, and in various primary and metastatic tumor cells. The putative native-state structure of PIF/DCD has not been resolved. Here, we describe some biochemical features of the soluble recombinant 11-kDa protein produced in Escherichia coli. The native 11-kDa polypeptide displayed an anomalous mobility on 1% SDS-PAGE under reduced conditions and appeared as a single approximately 16-kDa band. Under nonreduced conditions, we detected by mass spectrometry, the presence of multiple peaks corresponding to m/z values of 21 kDa, which we confirmed as a dimeric form with a disulfide bridge between cysteine 34 of each 11-kDa monomer. The native protein exhibited an unusually high susceptibility to proteolytic attack by trypsin, and up to 13 peptides derived from its C-terminus were produced after 5 min of incubation. The secondary structure analysis of PIF/DCD native protein in aqueous solution, by circular dichroism spectroscopy, revealed regions with non-well-defined secondary structure but that acquired alpha-helix and beta-sheet secondary structures in the presence of TFE/water mixtures and micellar and non-micellar SDS molecules. By using PONDR, DisEMBL, DisProt, and GlobPlot computational predictors, we identified a long disorder region at the N-terminus of PIF/DCD amino acid sequence. This segment (from 19-50 residues) is critical for some of its biological activities, including neuron survival. This result is coherent with successive failure of crystallization of the protein. Taken together, these data suggest that the disorder and order transition may be relevant for some biological functions of PIF/DCD.

Pneumocystis jirovecii colonisation in patients with interstitial lung disease.

A prospective study was conducted to determine the prevalence of colonisation by Pneumocystis jirovecii in 80 consecutive patients who required bronchoscopy and bronchoalveolar lavage (BAL) following suspicion of interstitial lung disease (ILD). The mtLSU rRNA gene of P. jirovecii was identified by nested PCR in BAL samples. Patients with ILDs were divided into three groups: group A comprised those with idiopathic interstitial pneumonias; group B comprised those with sarcoidosis; and group C comprised those with other ILDs. The overall prevalence of P. jirovecii carriage was 33.8%, with colonisation rates of 37.8%, 18.8% and 37% in groups A, B and C, respectively (p not significant). There were more smokers among the carriers, but there were no other significant differences between carriers and non-carriers. The high prevalence of P. jirovecii carriers found among immunocompetent patients with ILDs in Spain suggests a possible role of P. jirovecii in the natural history of these diseases.

Investigation of the functional role of active site loop II in a hypoxanthine phosphoribosyltransferase.

Hypoxanthine phosphoribosyltransferases (HPRTs) are of biomedical interest because defects in the enzyme from humans can result in gouty arthritis or Lesch-Nyhan syndrome, and in parasites these enzymes are potential targets for antiparasite chemotherapy. In HPRTs, a long flexible loop (active site loop II) closes over the active site during the enzyme catalyzed reaction. Functional roles for this loop have been proposed but have yet to be substantiated. For the present study, seven amino acids were deleted from loop II of the HPRT from Trypanosoma cruzi to probe the functional role of this active site loop in catalysis. The mutant enzyme (Deltaloop II) was expressed in bacteria, purified by affinity chromatography, and kinetic constants were determined for substrates of both forward (purine salvage) and reverse (pyrophosphorolysis) reactions catalyzed by the enzyme. Loop II deletion resulted in moderate (0.6-2.7-fold) changes in the Michaelis constants (K(m)s) for substrates other than pyrophosphate (PP(i)), for which there was a 5.8-fold increase. In contrast, k(cat) values were severely affected by loop deletion, with rates that were 240-840-fold below those for the wild-type enzyme. Together with previously reported structural data, these results are consistent with active site loop II participating in transition-state stabilization by precise positioning of the substrates for in line nucleophilic attack and in the liberation of PP(i) as a product of the salvage reaction.

The effect of temperature on the structure of vinblastine-induced polymers of purified tubulin: detection of a reversible conformational change.

Addition of the antimitotic drug vinblastine to solutions of purified tubulin induces the formation of helical polymers whose structure and type of aggregation is determined by the concentration of magnesium. While paracrystalline arrangements of single coils are observed at low concentrations of the ion, for concentrations higher than 6 mM free double-coiled spirals are obtained, which are indistinguishable from those obtained in the presence of microtubule-associated proteins (MAPs). This result is consistent with a similar effect of magnesium and MAPs in neutralizing negative charges on the tubulin molecule and so allowing for lateral contacts between protofilaments. The effects that temperature has on the structure of both types of polymers, free spirals or paracrystals, have been monitored using time-resolved X-ray solution scattering. This study shows that a temperature increase: (1) affects the length and lateral aggregation of the spirals in the paracrystalline sample; (2) induces a reversible increase of the helical pitch in both types of polymers that closely follows the temperature change; (3) produces an irreversible aggregation of some of the protein in both types of polymers; and (4) can induce a reversible transformation from one type of structure to the other when the concentration of Mg2+ is in the boundary between the two ranges. We suggest that the changes in pitch are due to a temperature-induced conformational change of the tubulin molecule. This effect may be related to the structural modifications that result in the temperature-induced assembly of microtubules in vitro under normal conditions of assembly.

Low resolution structure of microtubules in solution. Synchrotron X-ray scattering and electron microscopy of taxol-induced microtubules assembled from purified tubulin in comparison with glycerol and MAP-induced microtubules.

The structure of microtubules has been characterized to 3 nm resolution employing time-resolved X-ray scattering. This has revealed detailed structural features of microtubules not observed before in solution. The polymerization of highly purified tubulin, induced by the antitumour drug taxol, has been employed as a microtubule model system. This assembly reaction requires Mg2+, is optimal at a 1:1 taxol to tubulin heterodimer molar ratio, proceeds with GTP or GDP and is intrinsically reversible. The X-ray scattering profiles are consistent with identical non-globular alpha and beta-tubulin monomers ordered within the known helical surface lattice of microtubules. Purified tubulin-taxol microtubules have a smaller mean diameter (approx. 22 nm) than those induced by microtubule associated proteins or glycerol (approx. 24 nm), but nearly identical wall substructure to the resolution of the measurements. This is because the majority of the former consist of only 12 protofilaments instead of the typical 13 protofilaments, as confirmed by electron microscopy of thin-sectioned, negatively stained and ice-embedded taxol microtubules. It may be concluded that taxol induces a slight reduction of the lateral contact curvature between tubulin monomers. The main fringe pattern observed in cryo-electron micrographs is consistent with a simple 12 protofilament 3-start skewed lattice model. Cylindrical closure of this lattice can be achieved by tilting the lattice 0.8 degrees with respect to the microtubule axis. The closure implies a discontinuity in the type of lateral contacts between the tubulin monomers (regardless of whether these are of the -alpha-beta- or the -alpha-alpha-/-beta-beta- type), which indicates that lateral contacts and the subunit specificity of taxol binding are, to a large degree, equivalent.

Prevalence of colonisation and genotypic characterisation of Pneumocystis jirovecii among cystic fibrosis patients in Spain.

Pneumocystis jirovecii colonisation may occur among cystic fibrosis (CF) patients because of their underlying pulmonary disease. A wide epidemiological analysis was performed among CF patients from Spain to assess the prevalence of P. jirovecii colonisation and the distribution of different genotypes. P. jirovecii was identified by nested PCR targeting the mitochondrial large-subunit rRNA gene from sputum samples or oropharyngeal washes. The genotype was determined by direct sequencing. The prevalence of P. jirovecii colonisation among 88 consecutive CF patients was 21.5%. The polymorphisms identified were 85C/248C (45.4%), 85T/248C (27.2%) and 85A/248C (18.1%); in one case, a mix of genotypes was found. Colonisation was more frequent in subjects aged < 18 years (25.5% vs. 15.1%). Among the patients studied, 20.8% received treatment with azithromycin; all of these patients were colonised with P. jirovecii, but none developed Pneumocystis pneumonia (PcP) during a 1-year follow-up period. Concordance in the colonisation status of siblings suggested a common source of infection or person-to-person transmission.

Purification of a 6.5 kDa protease inhibitor from Amazon Inga umbratica seeds effective against serine proteases of the boll weevil Anthonomus grandis.

A 6.5 kDa serine protease inhibitor was purified by anion-exchange chromatography from the crude extract of the Inga umbratica seeds, containing inhibitor isoforms ranging from 6.3 to 6.7 kDa and protease inhibitors of approximately 19 kDa. The purified protein was characterized as a potent inhibitor against trypsin and chymotrypsin and it was named I. umbratica trypsin and chymotrypsin inhibitor (IUTCI). MALDI-TOF spectra of the IUTCI, in the presence of DTT, showed six disulfide bonds content, suggesting that this inhibitor belongs to Bowman-Birk family. The circular dichroism spectroscopy indicates that IUTCI is predominantly formed by unordered and beta-sheet secondary structure. It was also characterized, by fluorescence spectroscopy, as a stable protein at range of pH from 5.0 to 7.0. Moreover, this inhibitor at concentration of 75 microM presented a remarkable inhibitory activity (60%) against digestive serine proteases from boll weevil Anthonomus grandis, an important economical cotton pest.

Visceral leishmaniasis in HIV-1-infected individuals: a common opportunistic infection in Spain?

OBJECTIVE: To investigate the epidemiological, clinical and biological features of visceral leishmaniasis (VL) in patients with HIV-1 infection. DESIGN: Retrospective study. SETTING: Three university hospitals in southern Spain. PATIENTS: Forty-seven adult patients with VL and HIV-1 infection diagnosed between January 1986 and November 1991. RESULTS: Forty-five out of the 47 (96%) cases were diagnosed in the last 2 years. Fever (87%), hepatomegaly (74%), splenomegaly (72%) and pancytopenia (77%) were the most common presenting features. Most patients (79%) were strongly immunocompromised when VL was diagnosed, and were in stage IV of the Centers for Disease Control classification; 87% had a CD4 lymphocyte count < 200 x 10(6)/l. However, VL was the first severe infection diagnosed in 10 cases. Significant titres (> 1:40) of antileishmanial antibodies were detected by indirect immunofluorescence in five out of 16 (31%) cases only. Clinical response to the therapy was difficult to assess. Microbiological response was achieved in only 38% of the patients evaluated. CONCLUSIONS: Leishmaniasis is a relatively common infection in HIV-1-infected individuals in southern Spain. Its clinical picture is quite uniform and it can be the first opportunistic infection in individuals with HIV-1. In endemic areas, a high index of clinical suspicion should be maintained in order to avoid underdiagnosis of leishmaniasis.

PIP: Physicians examined the records of 47 adults with visceral leishmaniasis (VL) and HIV-1 infection who were patients at 3 urban teaching hospitals in the Andalucia region in southern Spain between January 1986 and November 1991. They wanted to identify the clinical, biological, and epidemiological features of VL in HIV-1 positive patients. 96% of the cases were diagnosed with both infections during the last 2 years of the study period and 79% between January and November 1991. All the patients had risk factors for HIV infection (65.9% IV drug use, 21.3% sexual contact, and 12.8% blood transfusion). 70% exhibited the classic symptoms of VL (fever, enlarged liver and spleen, and depressed counts of blood cells). Most patients were already very immunocompromised when VL was diagnosed. 87% had a total lymphocyte count of less than 1000 x 1 million/1 and a CD4 lymphocyte count of less than 200 x 1 million/1. In fact, 66% had full blown AIDS prior to diagnosis of VL. VL was the first severe infection in 10 cases. 68% also suffered from opportunistic infections, especially candidiasis, extrapulmonary tuberculosis, and Pneumocystis carinii pneumonia. Microscopic examination of Leishmania amastiogotes in tissue samples led to a diagnosis in 94% of cases, isolation of motile amastigotes in culture of bone marrow aspirate in 2%, and microscopic and culture in 4%. Just 46% completed a full course of treatment (pentavalent antimony, allopurinol, and/or pentamidine). Only 38% had a microbiological response. Immunofluorescence detected sizeable titers (1:40) of antileishmanial antibodies in just 31% of cases. 17% experienced clear clinical improvement. Physicians in endemic areas should consider VL in every HIV-1 infected patient with fever, hepatosplenomegaly, or hematological abnormalities to avoid underdiagnosis of leishmaniasis.

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.

Crystallization and preliminary X-ray diffraction analysis of gingipain R2 from Porphyromonas gingivalis in complex with H-D-Phe-Phe-Arg-chloromethylketone.

Gingipain R2 is a 50 kDa proteinase from the oral pathogenic bacterium Porphyromonas gingivalis. This proteinase, which displays no significant sequence homology to any protein previously analyzed by X-ray crystallography, has been crystallized using the vapor diffusion method. Two different crystal forms were obtained from a solution containing polyethylene glycol (MW 8,000) (space group P2(1)2(1)2(1)) or magnesium sulfate (space group R3) as precipitating agent. Complete diffraction data sets have been collected up to 2.0 and 2.9 A resolution, respectively. Cell dimensions are a = 51.9 A, b = 79.9 A, and c = 99.6 A (P2(1)2(1)2(1)), and a = b = 176.6 A, and c = 143.4 A (R3). Considerations of the possible values of Vm accounts for the presence of one monomer per asymmetric unit in the case of the orthorhombic crystal form, whereas the rhombohedral crystal form, together with the analysis of the self-rotation function, could accommodate a tetramer in the asymmetric unit.

Pneumocystis jiroveci genotypes in the Spanish population.

This study describes the genotype distribution of Pneumocystis jiroveci in 79 respiratory samples obtained from 15 patients with acquired immunodeficiency syndrome (AIDS) with P. jiroveci pneumonia and 64 human immunodeficiency virus-negative subjects with different chronic pulmonary diseases. The genotyping was based in analysis of 2 independent genetic loci: the mitochondrial large subunit ribosomal RNA (mt LSU rRNA) fragment (assessed by direct sequencing) and the gene for dihydropteroate synthase (DHPS; assessed by restriction fragment-length polymorphism). The mt LSU rRNA analysis revealed the presence of 3 different polymorphisms for both populations. The major genotype, 85C/248C, was found to be significantly higher in patients with AIDS and P. jiroveci pneumonia than in patients with pulmonary disease. The rate of genotypes 85A/248C and 85T/248C was similar in both groups. The analysis of DHPS genotypes assesses the prevalence of its 4 possible genotypes, with 35.5% of genotypes related to sulfa resistance. The data suggest a common source of infection between both groups.

Crystallization and preliminary X-ray diffraction analysis of proline iminopeptidase from Xanthomonas campestris pv. citri.

Proline iminopeptidase from Xanthomonas campestris pv. citri, displaying no significant sequence homology to any protein previously analyzed by X-ray crystallography, has been crystallized using the vapour diffusion method. Two different orthorhombic crystal forms (space group C222 and I222) were obtained from a solution containing NaCl or polyethylene glycol monomethyl ether (MW 5000) as precipitating agent for the native and lanthanum-derivatized protein, respectively. Complete diffraction data sets have been collected up to 2.6 A (native) and 3.0 A (lanthanum derivative) resolution. Cell dimensions are a= 147.2 A, b = 167.8 A, and c = 85.6 A (C222) and a = 146.7 A, b = 167.7 A, and c = 171.4 A (I222), respectively. Considerations of the possible values of V(m) and analysis of the self-rotation function of the native crystals account for the presence of one dimer per asymmetric unit, whereas a tetramer probably would occupy the smallest crystallographically independent crystal portion in the lanthanum-derivatized protein crystals.

Tumor necrosis factor beta and soluble APO-1/Fas independently predict progression to AIDS in HIV-seropositive patients.

The relationship between serum concentration of different components of the nerve growth factor/tumor necrosis factor (TNF) receptor family, including soluble APO-1/Fas (sAPO-1/Fas) and progression of HIV infection, was analyzed in a case-control study of individuals selected from a cohort of HIV-seropositive patients who were progressing or not progressing to AIDS while being treated with nucleoside analogs. HIV-seronegative healthy controls were also analyzed. The results showed that, despite close matching for immunologic (CD4 cell count, beta2-microglobulin concentration) and virologic (p24 antigen, detection of HIV syncytium-inducing phenotype, plasma HIV viremia) parameters, the baseline serum concentrations of TNF-beta and sAPO-1/Fas were statistically different between progressing and nonprogressing patients. In addition, serum concentrations of TNF-beta and sAPO-1/Fas showed the strongest independent predictive power for progression to AIDS in a multivariate conditional logistic regression model. Because TNF-beta and Fas were suggested to be mediators of antigen-induced cell death (AICD) in HIV infection and sAPO-1/Fas was hypothesized to protect lymphocyte against AICD, these data suggest an important pathogenetic role for AICD in the progression of HIV infection.

The role of serology in the diagnosis and prognosis of visceral leishmaniasis in patients coinfected with human immunodeficiency virus type-1.

To define the possible role of serology in the diagnosis and prognosis of visceral leishmaniasis (VL) in patients with human immunodeficiency virus type-1 (HIV-1) infection, the dynamics of humoral immune responses was investigated in 20 coinfected patients. Sequential sera obtained before, during, and after VL diagnosis were analyzed by an indirect immunofluorescent antibody test (IFAT), a recombinant ELISA (using the rK39 protein), and immunoblotting. During the active course of the disease, positive results were found by IFAT or ELISA in 22% of the cases and by immunoblotting in 78% of the cases. A great variability in the response was observed during the follow-up with a trend to more positive results near the time of VL diagnosis. Forty-six percent of the patients were positive by IFAT or ELISA on at least one time point before VL and 37.5% were positive during the period following treatment. These results confirm the limited usefulness of the IFAT and ELISA in the diagnosis of VL in coinfected patients and demonstrate their low ability to predict the development or the outcome of disease. In these patients, immunoblotting could be a useful tool for studying the natural course of leishmaniasis, although it has limited value for diagnosis or treatment control.

Climatic factors and Pneumocystis jiroveci infection in southern Spain.

The modes of infection and transmission of Pneumocystis jiroveci remain unclear. This study explored the relationship between the incidence of infection and climatic factors. In total, 536 cases of P. jiroveci infection were identified in the period 1994-1998, with an inverse correlation between the incidence of Pneumocystis pneumonia and the minimum mean ambient temperature (Spearman correlation coefficient: r - 0.30; p 0.02; ARIMA model: r - 0.250, p 0.07). The highest number of cases occurred in winter (anova test, p < 0.05), and there was a clear season-related incidence of P. jiroveci infection.