Multiple bone lesions resembling a metastatic origin. An unexpected diagnosis.

Lytic and blastic lesions have been associated to malignant tumours, such as solid cancer (breast cancer, renal cancer, prostate cancer, malignant melanoma or thyroid tumours). Although a mixed pattern with lytic and blastic lesions is due to metastatic tumour, this is not the only possible origin. The following case shows a systematic. This case report shows the number of tests that were made in order to discover the origin of osteolytic and osteoblastic lesions and it is notable that there is not an occult neoplasia on every occasion.

[Prevalence and characteristics of metabolic syndrome among HIV-infected patients from a Mediterranean cohort]. / Síndrome metabólico en pacientes infectados por el virus de la inmunodeficiencia humana en una cohorte del área mediterránea.

BACKGROUND AND OBJECTIVE: The objective of this study was to estimate the prevalence and characteristics of the metabolic syndrome in patients with HIV infection from a Mediterranean cohort. PATIENTS AND METHOD: Cross-sectional study performed in consecutive HIV-infected patients attended in an outpatient's HIV clinic at the Mediterranean coast of Spain. Metabolic syndrome was defined according to the International Diabetes Federation (IDF) new diagnostic criteria. RESULTS: We analyzed data from 210 patients, 160 (76.19%) of whom were undergoing antiretroviral therapy. Most of them (47.14%) were receiving combinations of non-nucleoside reverse transcriptase inhibitors, whereas 22.8% of them were being treated with protease inhibitors. The prevalence of metabolic syndrome was 11.42% (95% CI, 6.89%-15.97%). Hypertriglyceridemia was present in 68 (32.38%) patients and low HDL-cholesterol levels were observed in 98 (46.6%). Body mass index [OR = 1.40; 95% CI, 1.21-1.62; p = 0.001] and age [OR = 1.062; 95% CI, 1.018-1.108; p = 0.001] were independently associated with metabolic syndrome. CONCLUSIONS: Patients with HIV infection from this Mediterranean cohort had a low prevalence of metabolic syndrome. Body mass index and age are the main factors associated with this syndrome.

[Insulin resistance in HIV-infected patients receiving long-term therapy with efavirenz, lopinavir/ritonavir and atazanavir]. / Resistencia insulínica en pacientes con infección por el VIH en tratamiento prolongado con efavirenz, lopinavir/ritonavir y atazanavir.

BACKGROUND AND OBJECTIVE: To assess the presence of insulin resistance in human immunodeficiency virus (HIV)-infected patients receiving long-term antiretroviral therapy. PATIENTS AND METHOD: Cross-sectional study in consecutive HIV-infected patients treated with regimens containing efavirenz, lopinavir/ritonavir or atazanavir. Insulin resistance was assessed by HOMA (Homeostasis Model Assessment). RESULTS: We analyzed 47 patients, 18 on treatment with efavirenz, 17 with lopinavir/ritonavir and 12 with atazanavir. Patients treated with lopinavir/ritonavir had higher insulinemia than those treated with efavirenz (p = 0.007) or atazanavir (p = 0.020). The HOMA index was also higher in subjects treated with lopinavir/ritonavir than in those receiving efavirenz (p = 0.07) or atazanavir (p = 0.028). Insulin resistance was found in 5 (10.6%) patients, 4 among those receiving lopinavir/ritonavir, one among those treated with efavirenz and none among subjects receiving atazanavir (p = 0.065). In the logistic regression analysis, the antiretroviral regimen was associated with risk of insulin resistance. CONCLUSIONS: A substantial number of patients on antiretroviral therapy may have insulin resistance according to the HOMA index. Alterations of the hydrocarbonated metabolism appear to be more likely to occur in patients receiving regimens with lopinavir/ritonavir.

Occult lymphadenopathic Kaposi's sarcoma associated with severe pulmonary hypertension: A clinical hint about the potential role of HHV-8 in HIV-related pulmonary hypertension?

Severe pulmonary hypertension (PH) mimicking idiopathic PH is an increasingly recognized complication of human immunodeficiency virus (HIV) infection. PH shares several histopathologic features with Kaposi's sarcoma (KS), the most common malignancy in AIDS patients, and molecular evidence of the vasculotropic Kaposi's sarcoma-associated herpesvirus or human herpesvirus 8 (HHV-8) has been found in the lung tissue of patients with the disease. Although the prevalence of HHV-8 infection is increased among HIV-infected patients, no clinical association between KS and PH has ever been reported. Herein, we described a 30-year-old HIV-infected female co-infected with HHV-8 who developed severe PH coincident with occult KS. The clinical presentation of KS was unusual and remained masqueraded for years as an indolent cervical lymphadenopathy, without the typical cutaneous lesions. This is the first ever-reported case of PH associated with KS. Although the co-occurrence of both diseases in this patient could have been just a coincidence, the observation may also indicate that a relationship between HHV-8 infection and HIV-associated PH exists. Coinfection with HHV-8 and occult lymphadenopatic KS should be considered in HIV-infected patients developing PH.

Prediction of neuropsychiatric adverse events associated with long-term efavirenz therapy, using plasma drug level monitoring.

BACKGROUND: Data on long-term central nervous system (CNS) toxicity associated with efavirenz therapy are scarce, and risk factors remain largely unknown. We aimed to determine whether monitoring the plasma concentration of efavirenz could predict neuropsychiatric adverse events associated with long-term therapy with efavirenz. METHODS: We performed a longitudinal study involving 17 consecutive human immunodeficiency virus (HIV)-infected subjects with virological suppression after at least 6 months of antiretroviral therapy with an efavirenz-containing regimen. Efavirenz plasma concentrations were measured at study entry and at different time points through an 18-month study period. RESULTS: Median duration of efavirenz therapy before study entry was 18 months (range, 6-27 months). Ten (58.8%) of the patients experienced CNS-related adverse effects, ranging from insomnia and abnormal dreams to depression with suicidal ideation. In 4 (23.5%) of the cases, CNS toxicity led to efavirenz discontinuation. Mean (+/- standard deviation) plasma levels were higher for patients experiencing neuropsychiatric symptoms (5.10 +/- 2.15 microg/mL vs. 2.79 +/- 1.31 microg/mL; P = .024). A plasma level of 2.74 microg/mL had a sensitivity of 90.9% and specificity of 72% to predict CNS toxicity (area under the curve, 0.839; 95% confidence interval, 0.73-0.95; P < .0001). Patients having efavirenz plasma concentrations > 2.74 microg/mL at any time point of the study were 5.68 times more likely to experiencing CNS toxicity than were other patients (95% confidence interval, 1.97-16.37). CONCLUSIONS: In patients with HIV infection receiving long-term therapy with efavirenz-containing antiretroviral regimens, CNS toxicity is related to efavirenz plasma levels. Patients achieving higher plasma levels are at increased risk of experiencing neuropsychiatric adverse events.

Fulminant hepatitis and fatal toxic epidermal necrolysis (Lyell disease) coincident with clarithromycin administration in an alcoholic patient receiving disulfiram therapy.

Disulfiram is widely used in the treatment of chronic alcoholism. Adverse drug reactions with fatal outcome following disulfiram therapy are infrequent, and hepatic failure accounts for most of them. Since disulfiram is a cytochrome P450 (CYP450) enzyme system inhibitor, numerous interactions with several drugs metabolized in the liver have been reported. Like disulfiram, clarithromycin inhibits a CYP450 isoenzyme, but, despite its widespread use for the treatment of respiratory tract infections, no interactions with disulfiram have been described as yet. We report a case of fatal toxic epidermal necrolysis (Lyell disease) and fulminant hepatitis shortly after starting treatment with clarithromycin in a patient who was receiving disulfiram. This is the first case of such a severe dermatosis in a patient receiving either disulfiram or clarithromycin therapy. The temporal relationship between drug administration and clinical symptoms in this case suggests a probable interaction between the 2 drugs.

Changes in body fat composition after 1 year of salvage therapy with lopinavir/ritonavir-containing regimens and its relationship with lopinavir plasma concentrations.

OBJECTIVE: To determine whether an association existed between lopinavir (LPV) plasma concentrations and changes in body fat composition. DESIGN: A prospective, non-randomized study. SETTING: HIV clinic of a University Hospital. SUBJECTS, PARTICIPANTS: HIV-infected subjects who had virological failure on protease inhibitor-containing regimens. Twenty-two consecutive patients were enrolled, 19 completed 24 weeks of treatment and 16 completed the full 48-week study period. INTERVENTION: Patients were treated with LPV/ritonavir (LPV/r) in combination with other antiretroviral agents. LPV trough plasma concentrations were measured at baseline and weeks 4, 8, 12, 24, 36 and 48. Body fat composition was quantified by computerized tomographic scanning at baseline, and weeks 24 and 48. RESULTS: LPV trough concentrations correlated with absolute and proportional changes in limb fat from baseline to week 48. Significant differences were found in mean LPV trough concentrations between patients losing less than 5% of limb fat, those experiencing a limb fat loss between 5 and 20%, and those losing more than 20% at week 24 [mean (SD), 4.67 (1.67); 8.57 (1.77); 9.49 (2.67) microg/ml, respectively; P=0.013] and week 48 [mean (SD), 4.5 (2.24); 7.04 (1.77); 9.7 (2.8) microg/ml, respectively; P=0.027]. Most patients losing more than 5% of limb fat during LPV/r therapy had mean LPV trough concentrations > or = 8 microg/ml. CONCLUSIONS: In patients receiving salvage therapy with LPV/r there was an association between LPV plasma trough concentrations and limb fat loss. The risk of peripheral limb fat loss may be greater among patients achieving higher LPV trough concentrations.

A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL).

BACKGROUND: When blood pressure (BP)-lowering efficacy is assessed by measurements taken in a clinic setting, angiotensin II-receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability. A search of MEDLINE to date, however, reveals no randomized, double-blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients ( > 200) with essential hypertension. OBJECTIVE: This study compared 24-hour BP reduction and BP control, as assessed by ABPM, in patients with mild to moderate essential hypertension treated with irbesartan or enalapril. The relative tolerability of the 2 treatments was also evaluated. METHODS: This was a multicenter, randomized, double-blind study in patients with mild to moderate essential hypertension (office diastolic BP [DBP] 90-109 mm Hg or systolic BP [SBP] 140-179 mm Hg). After a 3-week, single-blind placebo washout phase, patients with a mean daytime DBP > or = 85 mm Hg, as measured by ABPM between 10 AM and 8 PM, were randomized to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were 150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was > or = 90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment; patients achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered responders. The ABPM criterion for BP control, independent of clinic values, was achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment; patients achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered responders, in dependent of clinic values. RESULTS: A total of 238 patients were randomized to treatment, 115 to irbesartan and 123 to enalapril. The study population was approximately 52.0% female and 48.0% male, with a mean ( +/- SD) age of 52.7 +/- 10.6 years. The study was completed by 111 patients in the irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115 patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients). BP reductions were similar in the 2 groups, both as measured in the clinic (DBP, 12.7 +/- 8.8 mm Hg irbesartan vs 12.4 +/- 7.4 mm Hg enalapril; SBP, 19.0 +/- 14.1 mm Hg vs 17.5 +/- 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 +/- 8.5 mm Hg vs 8.8 +/- 8.5 mm Hg: SBP, 14.7 +/- 14.7 mm Hg vs 12.6 +/- 13.1 mm Hg). As assessed by ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115) for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3% (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2% enalapril) was not statistically different between groups, although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan (24.6% vs 9.2%, respectively; P = 0.026), essentially because of the higher incidence of cough (8.1% vs 0.9%). CONCLUSIONS: As assessed by ABPM, irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d. Based on the number of treatment-related adverse events, irbesartan was better tolerated than enalapril.

[Changes in the spectrum of morbidity and mortality in hospital admissions of HIV infected patients during the HAART era]. / Cambios en el espectro de la morbilidad y la mortalidad de los ingresos hospitalarios de los pacientes con infección por el virus de la inmunodeficiencia humana durante la era del tratamiento antirretroviral de gran actividad.

BACKGROUND AND OBJECTIVE: After the introduction of highly active antiretroviral therapy (HAART), there was a decrease in hospital admissions and mortality associated with human immunodeficiency virus (HIV) infection. The objective of this study was to analyze the changes in mortality and morbidity during the HAART era. PATIENTS AND METHOD: We reviewed 1,343 hospital admissions from 610 HIV-infected patients between January 1995 and December 2000. We analyzed the morbidity and mortality figures at the pre-HAART last biennium (1995-1996) and those at the first and second HAART biennium (1997-1998, HAART-1, and 1999-2000, HAART-2). RESULTS: Hospital admissions due to AIDS-defining illnesses decreased throughout the HAART era, whereas admissions caused by non-AIDS-defining illnesses increased (p < 0.001) with a significant growth in the frequency of respiratory tract infections (p = 0.004), digestive tract diseases (p < 0.001) and liver diseases (p = 0.03). There was a declining trend in hospital mortality throughout the study period. AIDS-defining illnesses decreased from the pre-HAART biennium to the HAART-1 and -2 periods (p = 0.03), whereas liver diseases increased (p = 0.03). CONCLUSIONS: In the HAART era, hospital admissions and mortality due to AIDS-defining illnesses continue to decrease. Nevertheless, there is a steady increase in the number of admissions and deaths of patients with non-AIDS-defining illnesses.

Diagnostic accuracy of clinical criteria for identifying systolic and diastolic heart failure: cross-sectional study.

OBJECTIVE: To determine the validity and clinical usefulness of clinical criteria in the diagnosis of systolic and diastolic heart failure. DESIGN: Cross-sectional diagnostic study. METHODS: 216 patients admitted consecutively to the cardiology section of an academic hospital with a suspected diagnosis of heart failure in a period of 12 months. A definite diagnosis of heart failure (echocardiographic diagnostic criteria of left ventricular dysfunction) was cross-matched with the results obtained using the test under investigation (Framingham clinical diagnostic criteria for heart failure). Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for positive test result (LR+) and likelihood ratio for negative test result (LR-) were calculated and used to construct clinical decision-making diagrams. RESULTS: The Framingham clinical criteria are very sensitive (92%) and moderately specific (79%). The diagnosis of heart failure was ruled out with a good LR- (0.1) but the diagnosis was confirmed with only a low level of evidence as the LR+ was 4.3. The main difference found between systolic and diastolic heart failure is that in the case of systolic failure the disease is ruled out conclusively (0.04), whereas in the case of diastolic failure the change in probability generated is at the borderline between conclusive and moderate (0.1). CONCLUSION: The absence of the Framingham clinical criteria rules out the diagnosis of heart failure, particularly in the case of systolic heart failure. However, the presence of these criteria do not necessarily confirm the diagnosis, which may be based in echocardiography.

Prediction clinical profile to distinguish between systolic and diastolic heart failure in hospitalized patients.

BACKGROUND: In recent decades, the growing incidence of patients with heart failure who have preserved systolic function, underlines the need to differentiate between heart failure due to diastolic dysfunction and that due to systolic dysfunction. OBJECTIVE: To develop a prediction profile of clinical parameters that enables clinicians to differentiate between patients with systolic and diastolic heart failure. METHODS: 164 patients admitted for congestive heart failure to the cardiology department of an academic tertiary care hospital, whose left ventricular systolic and diastolic function had been evaluated echocardiographically and who satisfied the Framingham criteria for heart failure, were prospectively recruited. All patients answered a questionnaire which included, in addition to other clinical variables, the Framingham criteria. RESULTS: Patients with diastolic heart failure (61.6%) were more likely to be older, female, and to present left ventricular hypertrophy (LVH), with a lower proportion of smokers, alcohol drinkers, coronary disease, q wave and left bundle branch block (all p<0.005). The predicting model obtained on the logistic regression analysis was very significant, with three variables and 72.3% of correct predictions (x(2) value=40,457, p<0.001). These three variables, predictors of diastolic as opposed to systolic heart failure, were female sex (OR=3.546), left ventricle hypertrophy (OR=4.011) and absence of coronary disease (OR=3.547). CONCLUSION: Three variables which can be easily evaluated, female sex, left ventricular hypertrophy and presence or absence of coronary disease, may enable clinicians to differentiate between patients with systolic or diastolic heart failure.

Fatal infection due to larval cysts of cestodes (neurocysticercosis and hydatid disease) in human immunodeficiency virus (HIV) infected patients in Spain: report of two cases.

There is little information on infections caused by larval cestodes in patients with human immunodeficiency virus (HIV) infection in developed countries. Two infections by larval cestodes were found in 714 HIV-infected patients studied from 1998 to 2004 at the Hospital General Universitario de Elche in Spain (Mediterranean Coast). The first patient was a Colombian immigrant diagnosed as having neurocysticercosis, and subsequently found to have HIV infection. The second case was an HIV-infected Spanish patient who developed hydatid disease of the liver, lung and peritoneum. Both patients died. Although infrequent, infections by larval cestodes constitute a cause of disease in HIV-infected patients in developed countries, and might be linked with a more severe presentation.

The influence of age and gender on the population-based incidence of community-acquired pneumonia caused by different microbial pathogens.

OBJECTIVES: To determine the population-based incidence of community-acquired pneumonia (CAP) in adults and to assess the relative importance of age and gender on the incidence of infections caused by different microbial pathogens. METHODS: A two-year prospective study in a well-defined geographic area of the Spanish Mediterranean coast. RESULTS: The overall incidence rate of CAP was 12 cases (95% CI 11.25-13.45) per 10,000 person-years. Incidence rates increased by age (p<0.0001) and they were higher in males (16 versus 9 cases per 10,000 person-years; p<0.0001). The rate was especially high among males aged > or = 75 years (87 cases per 10,000 person-years). The incidence of pneumococcal pneumonia increased significantly with ageing and it was particularly high among people aged > or = 75 years (10 cases per 10,000 person-years). Very elderly people had also a 15-fold higher incidence of CAP associated with influenza virus and a 5-fold higher incidence of infections by Chlamydophila spp., than young adults. The incidence of infections with Legionella pneumophila also increased with age and it was 10 times higher in males. In contrast, the incidence of pneumonia caused by Mycoplasma pneumoniae was unrelated to age and gender. CONCLUSIONS: Age and gender have a strong influence on the overall incidence of CAP and on the incidence of pneumonia caused by the main microbial pathogens, including not only Streptococcus pneumoniae, but also influenza virus, Chlamydophila spp. and L. pneumophila. Ageing is associated with a higher risk of acquiring pneumonia by S. pneumoniae, influenza virus and Chlamydophila spp., whereas male gender increases greatly the incidence of L. pneumophila and Chlamydophila spp.

Lopinavir plasma concentrations and changes in lipid levels during salvage therapy with lopinavir/ritonavir-containing regimens.

OBJECTIVE: To determine whether an association existed between lopinavir (LPV) plasma concentrations and changes in lipid levels. DESIGN: A prospective, nonrandomized study. SUBJECTS: HIV-infected subjects with virologic failure on protease inhibitor-containing regimens. Twenty-two consecutive patients were enrolled, 19 completed 24 weeks of treatment, and 16 completed the full 48-week study period. INTERVENTION Patients were treated with LPV/ritonavir (LPV/r) in combination with other antiretroviral agents. Subjects were evaluated at baseline and weeks 4, 8, 12, 24, 36, and 48. LPV trough plasma concentrations and lipid levels were measured. RESULTS: LPV trough concentrations were higher in patients experiencing grade 3 or higher lipid elevations (mean [SD]: 9.71 microg/mL (5.62) vs. 6.09 microg/mL (3.83); P = 0.002) and in those developing grade 2 or higher hypercholesterolemia (mean [SD]: 8.48 microg/mL [4.64] vs. 5.71 microg/mL [3.94]; P = 0.003). All patients developing grade 2 or higher cholesterol elevation had an LPV trough concentration at week 4 greater than 8 microg/mL. Significant positive correlations were found between LPV trough concentrations and changes in triglyceride and cholesterol levels. CONCLUSIONS: In patients receiving salvage therapy with LPV/r, there is an association between LPV plasma concentrations and lipid changes. Patients achieving higher LPV trough concentrations may be at greater risk of experiencing dyslipidemia. Further investigations are warranted to support a direct cause and effect relationship.

Resistencia insulínica en pacientes con infección por el VIH en tratamiento prolongado con efavirenz, lopinavir/ritonavir y atazanavir / Insulin resistance in HIV-infected patients receiving long-term therapy with efavirenz, lopinavir/ritonavir and atazanavir

Fundamento y objetivo: Estudiar la sensibilidad insulínica en pacientes con infección por el virus de la inmunodeficiencia humana (VIH) que reciben tratamiento antirretroviral prolongado. Pacientes y método: Se incluyó a pacientes consecutivos en tratamiento durante más de un año con efavirenz, lopinavir/ritonavir o atazanavir. La resistencia a la insulina se evaluó mediante el índice HOMA (Homeostasis Model Assessment). Resultados: Se analizó a 47 pacientes, 18 en tratamiento con efavirenz, 17 con lopinavir/ritonavir y 12 con atazanavir. Los tratados con lopinavir/ritonavir tuvieron una insulinemia más elevada que los que recibían efavirenz (p = 0,007) y atazanavir (p = 0,020), y un índice HOMA mayor que los tratados con efavirenz (p = 0,07) y atazanavir (p = 0,028). Presentaron resistencia insulínica 5 (10,6%) pacientes: 4 en el grupo de lopinavir/ritonavir, uno en el de efavirenz y ninguno en el de atazanavir (p = 0,065). En el análisis multivariante, la pauta de tratamiento antirretroviral fue el único predictor independiente de resistencia insulínica. Conclusiones: Una proporción apreciable de los pacientes que reciben tratamiento antirretroviral crónico presenta resistencia insulínica. Las alteraciones del metabolismo hidrocarbonado tienden a ser más marcadas en los tratados con lopinavir/ritonavir

Background and objetive: To assess the presence of insulin resistance in human immunodeficiency virus (HIV)-infected patients receiving long-term antiretroviral therapy. Patients and method: Cross-sectional study in consecutive HIV-infected patients treated with regimens containing efavirenz, lopinavir/ritonavir or atazanavir. Insulin resistance was assessed by HOMA (Homeostasis Model Assessment). Results: We analyzed 47 patients, 18 on treatment with efavirenz, 17 with lopinavir/ritonavir and 12 with atazanavir. Patients treated with lopinavir/ritonavir had higher insulinemia than those treated with efavirenz (p = 0.007) or atazanavir (p = 0.020). The HOMA index was also higher in subjects treated with lopinavir/ritonavir than in those receiving efavirenz (p = 0.07) or atazanavir (p = 0.028). Insulin resistance was found in 5 (10.6%) patients, 4 among those receiving lopinavir/ritonavir, one among those treated with efavirenz and none among subjects receiving atazanavir (p = 0.065). In the logistic regression analysis, the antiretroviral regimen was associated with risk of insulin resistance. Conclusions: A substantial number of patients on antiretroviral therapy may have insulin resistance according to the HOMA index. Alterations of the hydrocarbonated metabolism appear to be more likely to occur in patients receiving regimens with lopinavir/ritonavir