[Mortality, cardiovascular risk, and health status in a male cohort initiated in 1968. The Manresa study]. / Mortalidad, riesgo cardiovascular y estado de salud actual de una cohorte de varones iniciada en el año 1968. Estudio Manresa.

OBJECTIVES: To analyse mortality and its causes in the Manresa male cohort followed over 42 years; to compare the initial risk of cardiovascular mortality with actual mortality; and to describe the health status of the participants at the end of the study. METHODS: Prospective observational study, in which an analysis of the cumulative incidence of mortality was performed. The association of cardiovascular risk factors with mortality was calculated with a logistic regression analysis of mixed effect. The risk of mortality of individuals was evaluated and compared with true cardiovascular mortality using ROC curves. At the end of the study, a descriptive analysis of CVRF and health status of participants in the last survey was performed. RESULTS: The number of deaths was 457 (43%). Cumulative incidence for cardiovascular diseases was 10.6%. Cardiovascular risk factors significantly associated with cardiovascular mortality were age, cholesterol, and smoking. The use of risk score charts for cardiovascular mortality was found to be useful, and there were no differences between tables. In the last health screening of cardiovascular risk factors levels in an elderly population, a high prevalence was found of hypertension and of regular physical activity, together with a low prevalence of smoking. CONCLUSIONS: Cardiovascular mortality remained high, although it has become the second cause after tumoural diseases. The comparison of predictions from cardiovascular mortality risk tables with actual mortality rates in our area over more than 4 decades demonstrated the importance of assessing cardiovascular risk in the adult population.

Epigallocatechin-3-gallate treatment reduces thermal hyperalgesia after spinal cord injury by down-regulating RhoA expression in mice.

BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent found in green tea. It has been reported that may be a natural agent for reducing thermal and mechanical pain after nervous system injuries. However, the molecular pathways implicated in these beneficial effects have not been completely elucidated. This study aimed to assess the EGCG treatment effects on thermal hyperalgesia, spinal cord gliosis and modulation of Ras homologue gene family member A (RhoA), fatty acid synthase (FASN) and tumour necrosis factor alpha (TNF-α) expression after spinal cord contusion in mice. METHODS: Animals were subjected to a spinal cord contusion. Thirty minutes after contusion and daily during the first week post-surgery, animals were treated with EGCG or dimethyl sulfoxide-saline (DMSO-saline). At 7 and 14 days post-operation, motor recovery was evaluated using the Basso Mouse Scale, and nociceptive response was evaluated using the Hargreaves test. Furthermore, at 14 days, the expression of RhoA, FASN and TNF-α proteins was quantified in the lesion site of spinal cord by Western blot technique. Finally, spinal cord samples were processed by immunohistochemical techniques for observing astrocytes, microglia and afferent nerve fibres. RESULTS: At short time, EGCG treatment reduced significantly thermal hyperalgesia but had no effect on locomotor recovery in spinal cord injured mice. Furthermore, EGCG treatment down-regulated the RhoA, FASN and TNF-α proteins expression, and decreased astro- and microglia reactivity in spinal cord. CONCLUSION: These findings suggest that at short time EGCG treatment reduces thermal hyperalgesia and gliosis via FASN and RhoA pathway, causing a decrease in cytokines in spinal cord.

Soluble fatty acid synthase relates to bone biomarkers in prepubertal children.

SUMMARY: Circulating soluble fatty acid synthase (FASN, a key enzyme in de novo biosynthesis of fatty acids, expressed in both adipocytes and osteoblasts) is clinically related to a less favorable bone profile in healthy prepubertal children. Soluble FASN may participate in the reciprocal regulation between fat and bone metabolism. INTRODUCTION: Fatty acid synthase (FASN), a key enzyme in de novo biosynthesis of fatty acids, is expressed in adipocytes and osteoblasts. We hypothesized that FASN may participate in the crosstalk between fat and bone. To this aim, we studied the relation between circulating soluble FASN (an extracellular FASN that reflects previously intracellular enzymatic activity) and adipose tissue and bone biomarkers in prepubertal children. METHODS: Circulating soluble FASN, total and high molecular weight (HMW) adiponectin, bone biomarkers [osteocalcin (OC), uncarboxylated osteocalcin (ucOC), C-terminal cross-linked telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP)], and a profile of energy metabolism [body fat, insulin resistance and secretion (HOMA), serum lipids] were assessed in 84 asymptomatic prepubertal children (44 girls, 40 boys, age 6.8 ± 0.1 year). Serum 25-OH Vitamin D (Vit D) was additionally measured. RESULTS: Circulating soluble FASN increased with increasing HMW adiponectin (r = 0.29, p = 0.01) and decreasing serum Vit D (r = -0.21, p < 0.05), and was related to a less favorable bone profile, showing negative associations with bone-derived metabolic parameters [total OC (r = -0.33, p = 0.002) and ucOC (r = -0.37, p < 0.0001)] and a positive association with the CTX-to-BSAP ratio (r = 0.31, p < 0.01). These correlations were not explained by age, gender, body fat, insulin resistance or secretion or serum lipids; however, they were predominant in those subjects with Vit D levels below the population median. CONCLUSIONS: Circulating soluble FASN relates to both adipose tissue and bone biomarkers in prepubertal children, with associations that are dependent on Vit D concentrations. These findings suggest that FASN may participate in the crosstalk between fat and bone metabolism.

Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation.

Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.

Novel anti-fatty acid synthase compounds with anti-cancer activity in HER2+ breast cancer.

Fatty acid synthase (FASN) expression and activity has emerged as a common phenotype in most human carcinomas, including breast cancer, and its expression is tightly linked to HER2 signaling pathways. The development of inhibitors of FASN activity has consequently appeared as a novel antitarget modality for treating cancer. However, the clinical use of FASN inhibitors, such as cerulenin, C75, and epigallocatechin 3-gallate (EGCG), is limited by anorexia and induced body weight loss or by its low in vivo potency and stability. Here, we summarize the design and development of G28UCM, the lead-compound of a novel family of synthetic FASN inhibitors, with both in vitro and in vivo activity in a human breast cancer model of FASN(+) and HER2(+) .

Prevalence evolution and impact of cardiovascular risk factors on allograft and renal transplant patient survival.

OBJECTIVE: The prevalence of traditional cardiovascular risk factors in renal transplantation is high. Studying the evolution of cardiovascular risk factors over time may help us to design better strategies to control them. The relative impact of traditional cardiovascular risk factors on allograft survival and mortality in transplant recipients is not clear. This study was performed to determine the incidence and risk factors for allograft survival and mortality among renal transplant patients. PATIENTS AND METHODS: We enrolled 250 patients who had undergone transplantation between 1980 and 2004. They were followed for various periods, and we analyzed the impact of traditional and nontraditional risk factors on renal allograft survival. RESULTS: The prevalence of hypertension was >80% during all the follow-up periods. Blood pressure diminished, antihypertensive drug prescription increased, and 15% of patients had adequate blood pressure control during follow-up. The prevalence of pretransplant diabetes mellitus was 6.8%; the incidence of posttransplant diabetes mellitus (PTDM) was 14.2%. The prevalence of PTDM increased over the course of patient evolution. The prevalence of dyslipidemia was in all cases >70%; total cholesterol and low-density lipoprotein (LDL)-cholesterol decreased; prescription of statins increased; and the percentage of patients with good lipid control also increased. The 25% prevalence of active smoking at the time of transplantation decreased to 13.6% at 10 years posttransplantation. The mean patient follow-up was 8 +/- 4.6 years. Sixty-five patients (26%) lost their grafts and 40 (16%) died during follow-up. Donor age, exercise, diastolic blood pressure, renal function, and albumin levels were independent risk factors for graft loss. Charlson comorbidity index at transplantation, recipient and donor ages, exercise, diastolic blood pressure, and LDL-cholesterol posttransplantation were independent risk factors for mortality among renal transplant recipients. CONCLUSION: Blood pressure and lipid control improved during follow-up, however, insufficiently among renal transplant patients. The prevalence of diabetes gradually increased, and the incidence of smoking cessation was low. Diastolic blood pressure, exercise, and albuminemia were the most significant modifiable cardiovascular risk factors for renal allograft survival. Diastolic blood pressure, LDL-cholesterol level, and exercise were the most relevant modifiable cardiovascular risk factors for the survival of renal transplant patients.

Cardiovascular risk factors in diabetic patients with renal transplants.

There is a progressive increase in cardiovascular events post-renal transplantation and diabetes mellitus (DM) is one of the major cardiovascular risk factors. The objective of this study was to analyze the prevalence of cardiovascular risk factors and nonfatal cardiovascular events among renal transplant recipients, according to the status of their carbohydrate metabolism. We studied 214 renal transplant recipients, among whom 18% diabetic and 82% were nondiabetic. The 16% prevalence of cardiovascular events were higher among the posttransplantation DM (PTDM) group (33%) compared with the other groups, 19% in pre-renal transplantation DM, 17% in altered baseline glycemia, and 13% in normal patients. Diabetic renal transplant recipients showed a greater prevalence of pretransplantation ischemic cardiopathy when they were older and had a higher pretransplantation body mass index (BMI) a heavier smoking habit, significantly increased microinflammation markers, and a greater need for antihypertensive and hypolipidemic treatment. Renal transplant recipients with altered baseline glycemia show greater BMI after transplantation, as well as higher Hb1Ac than patients with normoglycemia.

Myeloablation enhances engraftment of transduced murine hematopoietic cells, but does not influence long-term expression of the transgene.

To investigate to what extent myeloablation, graft size, and ex vivo manipulation influence the engraftment and long-term survival of transduced murine hematopoietic cells, groups of C57BL/6J (CD45.2) mice receiving total body irradiation (TBI) (1-9 Gy) or no irradiation were transplanted with either transduced bone marrow (BM) cells, at two cell doses, or with fresh BM cells from B6/SJL (CD45.1) congenic mice. Short (40 days) and long-term (5 months) engraftment and transgene expression were measured by FACS analysis. No donor cells were detected in the hematopoietic tissues of non-myeloablated mice, whereas in the irradiated animals, levels of engraftment correlated well with the dose of TBI administered. Similar percentages of transgene-expressing cells were found in the grafted hematopoietic cells of all groups of mice, regardless of the dose of TBI administered or the level of engraftment achieved. This suggests that the engrafted animals could become tolerant to the transgene product (enhanced green fluorescent protein, EGFP). Our results indicate that TBI facilitates the engraftment of manipulated hematopoietic cells in a dose-dependent manner, that mice engrafted with EGFP(+) hematopoietic cells probably acquire tolerance to EGFP, and that increasing the graft size and reducing the ex vivo manipulation required for retroviral gene transfer of hematopoietic cells also enhances their engrafting potential.

A new case of acute idiopathic frosted branch angiitis in Europe.

CASE REPORT: A 20-year-old male with no history of any systemic or eye disease developed loss of visual acuity in both eyes. White exudates surrounding the retinal veins from the posterior pole to the periphery, retinal edema and hemorrhages in both eyes were evident on ophthalmoscopy. Fluorescein angiography showed leakage of the dye from the veins and extensive staining of the vein walls. A diagnosis of acute frosted branch angiitis was made. Systemic examination revealed axillary, submandibular and inguinal lymphadenopathies. VCA IgM antibody for Epstein-Barr virus was negative and IgG positive. Biopsy was taken of an axillary lymph node; a non-specific inflammatory reaction was found on anatomopathologic study. The patient was started on 90 mg prednisolone daily. After two weeks retinal vasculitis had improved and the lymphadenopathies soon resolved. Small, hard exudates were present in the posterior pole during absorption of the retinal edema and resolution of the vascular inflammation. Systemic prednisolone were reduced progressively and definitively withdrawn two months later. The patient's visual acuity was 20/25 in both eyes. No fibrotic scar tissue or atrophic lesions were noted in either fundus. CONCLUSIONS: We report a new case of acute frosted branch angiitis with an onset and favorable clinical course similar to previous reports. We found the additional presence of lymphadenopathies but have been unable to establish a possible causal agent. To our knowledge, apart from a recent case of frosted branch angiitis-like response in Greece, the present case is the first reported in western Europe.

[Secular trends in smoking according to educational level between 1986 and 1996: The MONICA study. Catalonia]. / Tendencias seculares del tabaquismo según el nivel educativo entre 1986 y 1996: estudio MONICA-Cataluña.

OBJECTIVE: To describe trends from 1986-1996 in the prevalence of cigarette smoking between ages 25 to 64 in the MONICA-Catalonia study, according to educational level, and to validate these trends biochemically. METHODS: Three cross-sectional surveys in independent random samples of the general population of central Catalonia area carried out in 1986-88, 1990-92 and 1994-96 following the World Health Organization's MONICA protocol. Serum thiocyanate was determined by the Bowler method. RESULTS: A total of 2,571, 2,934 and 3,485 men and women were examined with response rates of 74, 67 and 72% in each survey respectively. The age-adjusted cigarette smoking prevalence decreased in men by 5.1% (95% CI: 1.5 to 8.7) and increased in women by +8.5% (95% CI: +5.6 to +11.4). The prevalence was 46.5% in men and 23.9% in women in 1994-96. The greatest decrease was in men aged 55-64 (9.9%) and the greatest increase was in women aged 35-44 (+14.8%). These trends were confirmed by serum thiocyanate levels, which decreased from 78.9 to 73.9 µmol/l (p = 0.07) in men and increased from 43.7 to 49.8 µmol/l (p < 0.01) in women during the study period. Cigarette smoking increased in less educated women (+10%) and decreased in university women (6%), while cigarette smoking in men decreased irrespective of educational level. Serum thiocyanate levels confirmed the relationship with educational level. CONCLUSIONS: The prevalence of cigarette smoking decreased in men between 1986 and 1996 but remained high in 1996. Women showed a pattern of progressive adoption of smoking, especially those with lower educational level.

[Risk factors and coronary morbimortality in a Mediterranean industrial cohort over 28 years of follow-up. The Manresa Study]. / Factores de riesgo y morbimortalidad coronaria en una cohorte laboral mediterránea seguida durante 28 años. Estudio de Manresa.

OBJECTIVE: To study the incidence and mortality of coronary heart disease (CHD) and all-cause mortality in a cohort of men followed during 28 years, and their association with serum cholesterol, systolic blood pressure, glycemia, cigarette smoking and body mass index measured at baseline. RESEARCH DESIGN AND METHODS: A cohort of 1,059 men aged 30 to 59 years and free of cardiovascular diseases at baseline in 1968, was examined every five years until 1988. The last examination was performed in 1996. Information was collected in 96.4% of the participants. RESULTS: Incidence and mortality rates from CHD and from all-causes of death per 105 person-years of observation were 499.80, 235.80 and 925.33, respectively. At the end of follow-up, high levels of serum cholesterol and smoking were independently associated with the incidence and mortality from CHD adjusted for age, blood pressure, glycemia and BMI. Serum cholesterol, hyperglycemia and smoking were independently associated with all-cause mortality. CONCLUSIONS: In this industrial cohort of men, with a relatively low incidence of CHD, smoking and serum cholesterol at baseline were independently associated with the incidence of CHD over 28 years of observation.

Efficient transduction of human hematopoietic repopulating cells generating stable engraftment of transgene-expressing cells in NOD/SCID mice.

In an attempt to develop efficient procedures of human hematopoietic gene therapy, retrovirally transduced CD34(+) cord blood cells were transplanted into NOD/SCID mice to evaluate the repopulating potential of transduced grafts. Samples were prestimulated on Retronectin-coated dishes and infected with gibbon ape leukemia virus (GALV)-pseudotyped FMEV vectors encoding the enhanced green fluorescent protein (EGFP). Periodic analyses of bone marrow (BM) from transplanted recipients revealed a sustained engraftment of human hematopoietic cells expressing the EGFP transgene. On average, 33.6% of human CD45(+) cells expressed the transgene 90 to 120 days after transplantation. Moreover, 11.9% of total NOD/SCID BM consisted of human CD45(+) cells expressing the EGFP transgene at this time. The transplantation of purified EGFP(+) cells increased the proportion of CD45(+) cells positive for EGFP expression to 57. 7% at 90 to 120 days after transplantation. At this time, 18.9% and 4.3% of NOD/SCID BM consisted of CD45(+)/EGFP(+) and CD34(+)/EGFP(+) cells, respectively. Interestingly, the transplantation of EGFP(-) cells purified at 24 hours after infection also generated a significant engraftment of CD45(+)/EGFP(+) and CD34(+)/EGFP(+) cells, suggesting that a number of transduced repopulating cells did not express the transgene at that time. Molecular analysis of NOD/SCID BM confirmed the high levels of engraftment of human transduced cells deduced from FACS analysis. Finally, the analysis of the provirus insertion sites by conventional Southern blotting indicated that the human hematopoiesis in the NOD/SCID BM was predominantly oligoclonal.

[Incidence, mortality and risk factors for stroke in the Manresa Study: 28 years of follow-up]. / Accidente vascular cerebral: incidencia, mortalidad y factores de riesgo en 28 años de seguimiento. Estudio de Manresa.

INTRODUCTION AND OBJECTIVES: The information concerning stroke mortality is limited in Spain, and the information on morbidity is even scarcer similarly to other countries. This is true also for the decrease of frequency observed in the last decades. The objective of this paper is to provide data in the incidence, mortality and cardiovascular risk factors associated to stroke in our surrounding through by the prolonged observation of a working population. MATERIAL AND METHODS: In the Manresa Study, which began in 1968, a cohort of 1,059 men, from 30 to 59 years old, was followed for 28 years. We recorded new cases of fatal and nonfatal stroke and the relationship between stroke incidence and risk factors of cardiovascular disease found in the initial examination. RESULTS: Incidence rate for stroke was 183 x 100,000 per year, 64% of the cases were registered after they turned 60 years of age. Mortality rate due to stroke was 88 x 100,000 per year, 91.6% of fatal cases were over 60 years old. Factors associated to the stroke morbimortality incidence were age, high blood pressure and overweight. In a bivariate regression model, stroke mortality was found significantly associated to the presence of atrial fibrillation, diabetes, hypercholesterolemia and tobacco smoking. CONCLUSIONS: Stroke frequency rates in the Manresa cohort are ranged at a medium level compared to data from other general population studies. The role of atrial fibrillation in the stroke morbimortality has been confirmed. The associated factors, age, high blood pressure and overweight, are similar role to that which was found in other research studies. The priorities in the cerebrovascular disease prevention in our surroundings are discussed.

Retroviral gene transfer into human hematopoietic cells: an in vitro kinetic study.

BACKGROUND AND OBJECTIVE: Successful gene therapy applications require optimized strategies to increase gene transfer efficiency into hematopietic progenitor cells (HPCs) with long-term repopulating ability. One of the issues that needs to be clarified is how hematopoietic cells proliferate, differentiate and express the transgene after each cycle of transduction. We investigated the kinetics of cell expansion, CD34 antigen expression and transduction efficiency of human hematopoietic cells in culture conditions commonly used in retroviral gene transfer protocols. DESIGN AND METHODS: Purified CD34+ cells from cord blood (n=5) or leukapheresis products (n=9) and a retroviral vector encoding an enhanced version of the green fluorescent protein (EGFP) were used. Target cells were exposed daily to vector-containing supernatants and a combination of interleukin 3 (IL-3), interleukin 6 (IL-6), stem cell factor (SCF) and Flt3-ligand (FL). Cell samples were harvested from the cultures and analyzed at 24 hour intervals for seven consecutive days. RESULTS: We found that CD34+ cells proliferated and differentiated under our culture conditions. The number of genetically modified cells increased after each cycle of transduction. Median numbers of cells positive for both CD34 and EGFP increased steadily over the culture period, but after day four most of the EGFP+ cells had a low CD34 expression. INTERPRETATION AND CONCLUSIONS: Culturing and transducing CD34+ cells for longer periods of time under these conditions might be detrimental for ex vivo gene transfer applications since the transduced cells are likely to have a decreased potential for long-term engraftment and repopulation in vivo.

Evolution of genotypic resistance to nucleoside analogues in patients receiving protease inhibitor-containing regimens.

The prevalence of genotypic resistance to nucleoside analogues (NA) was examined using a line probe assay (LiPA, Innogenetics, Spain) and a point mutation assay to test for codon 151 polymorphism in plasma from 34 individuals who had been exposed to NA for longer than 1 year. The testing was repeated in the same population after 6 months of being on a new potent protease inhibitor (PI)-containing antiretroviral combination. Only nine (47%) of the 19 patients initially carrying the codon 41 mutation restored zidovudine wild-type (WT) virus population. Similarly, eight (33%) out of 24 carrying the codon 215 mutation restored the wild-type variant. Two subjects carrying codon 74 didanosine mutation reverted to wild-type genotype, as well as two (18%) out of 11 harbouring the codon 184 lamivudine-resistant variant. To conclude, the extent to which drug recycling might be of benefit in subjects showing a restoration of genotypic sensitivity to former drugs needs to be explored.

High-titer retroviral vectors containing the enhanced green fluorescent protein gene for efficient expression in hematopoietic cells.

Retroviral vectors constitute the most efficient system to deliver and integrate foreign genes into mammalian cells. We have developed a producer cell line that yields high titers of amphotropic retroviral vectors carrying the enhanced green fluorescent protein (EGFP) gene, a codon humanized, red-shifted variant of the green fluorescent protein (GFP) gene, which can be used as a selectable marker. We have used a hybrid vector that has been shown to efficiently drive gene expression in hematopoietic cells. Virtually all murine and human cell lines and primary human hematopoietic cells tested were transduced with varying efficiency after incubation with vector-containing supernatants. Human CD34(+) cells obtained from cord blood or aphereses products were transduced using a protocol that involves daily addition of vector-containing supernatants for 6 consecutive days. At day 6, up to 16% of the cells expressed EGFP, as assessed by flow cytometry. Sorted EGFP-expressing cells were able to produce fluorescent hematopoietic colonies. EGFP's main advantages are its fast flow cytometry determination and the possibility of cell sorting and simultaneous evaluation of the transduction efficiency along with other phenotypic markers.

Detection of Mycoplasma pneumoniae by polymerase chain reaction in lung aspirates from patients with community-acquired pneumonia.

STUDY OBJECTIVE: This study was designed to evaluate the usefulness of polymerase chain reaction (PCR) to detect Mycoplasma pneumoniae DNA in samples obtained by transthoracic needle aspiration (TNA). DESIGN: Prospective study of cases. SETTING: A university hospital in Lleida, Spain. PATIENTS: A total of 101 unselected patients, admitted between January 1993 and March 1994 in the emergency department, with a clinical and radiologic picture of community-acquired pneumonia, and without contraindications for TNA application. INTERVENTIONS: Patients were studied with conventional diagnostic techniques for community-acquired pneumonia. In addition, a sample obtained by TNA was processed by the following methods: culture in standard media, culture in selective media for Legionella, detection of capsular antigens for Streptococcus pneumoniae and Haemophilus influenzae, and detection of M pneumoniae specific genome by PCR. RESULTS: Serologic data were not available in eight patients and were excluded from this analysis. M pneumoniae PCR amplification was possible in eight cases, well correlated with serologic responses indicating current infection. Samples from ten additional patients, negative by PCR, were found to be demonstrative of recent M pneumoniae infection by serologic study. Finally, in all the remaining 75 cases, including the 59 patients for whom a different microbial diagnosis was established, M pneumoniae PCR test gave negative results. CONCLUSION: This study indicates that PCR, applied to samples obtained by TNA, appears to be a moderately sensitive and highly specific method for rapid detection of M pneumoniae lung infection.

Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine.

A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.

Transthoracic needle aspiration in the study of pulmonary infections in patients with HIV.

STUDY OBJECTIVE: To evaluate the safety and efficacy of transthoracic aspiration with an ultrathin needle in the microbiologic diagnosis of pulmonary infections in HIV-infected patients. DESIGN: Retrospective review of cases. SETTING: A 500-bed teaching hospital in Lleida, Spain. PATIENTS: Forty-five HIV-infected patients admitted between March 1989 and March 1993 with clinical and roentgenographic evidence of pulmonary infection and without contraindications for transthoracic needle aspiration (TNA). INTERVENTIONS: Forty-seven TNAs were performed in the emergency room (20) or during hospitalization (27). The TNA procedures were done without premedication and without fluoroscopic guidance. Specimens were processed using routine microbiologic and cytologic techniques; in addition, polymerase chain reaction (PCR) for Pneumocystis carinii was carried out since March 1992. Development of adverse effects was carefully evaluated. RESULTS: The TNA was effective in 29 (62 percent) out of 47 procedures. The diagnosis was obtained for 14 of 15 patients with P carinii pneumonia, 8 out of 14 patients with bacterial pneumonia, and 4 out of 12 patients with tuberculosis. Other pathogens recovered were Nocardia asteroides, Cryptococcus neoformans, Rhodococcus equi, and Mycobacterium avium. No false-positive results were obtained. Pneumothorax developed in eight (17 percent) procedures, but only one procedure resulted in a pleural drainage; the incidence of other adverse effects was low and clinically irrelevant. CONCLUSION: Our study suggests that TNA can be a useful technique in establishing the etiologic diagnosis of pulmonary infections in HIV-infected patients, with a good sensitivity, high specificity, and relatively low incidence of serious complications, with TNA appearing as a reliable alternative to more uncomfortable methods.

Some determinants of body weight, subcutaneous fat, and fat distribution in 25-64 year old Swiss urban men and woman.

Data from a predominantly urban sample of 116 men and 130 women aged 25-64 years and collected in 1984/85 as a part of the Swiss WHO MONICA project, were analysed cross-sectionally to study the interrelationship between relative weight, subcutaneous fat and fat distribution, as well as the dependence of these anthropometric characteristics on behavioral and sociodemographic factors. Skinfold thicknesses were found to increase with age almost linearly in women, while in men they increased only before age 40 to 45. Subcutaneous fat was, but fat distribution was not, highly correlated with relative weight in both sexes. Alcohol consumption, healthy dietary habits (inversely), and exercise (inversely) were all significantly related to subcutaneous fat in men, while the relatively strongest predictors of female skinfold thicknesses were smoking (inversely), coffee consumption, and education (inversely). In multivariate analysis, environmental factors explained up to 10% of skinfold variance in male subjects and between 10 and 15% in females. Fat distribution was more influenced by environmental factors in men (about 8% of explained variance) than in women (about 4%). In men, truncal fat depended more on lifestyle that did upper arm fat, with smoking (directly) and exercise (inversely) being relatively most predictive of abdominal fat. We conclude that, although relative weight, subcutaneous fat, and fat distribution correlate intra-individually, they are not equivalent and interchangeable anthropometric characteristics. This is reflected by the varying associations of the three fatness indicators with age and environmental factors such as smoking, diet, exercise, and education. Gender seems to be an important modifying factor of environment-body fat-associations.(ABSTRACT TRUNCATED AT 250 WORDS)