Men suffer vertebral fractures with similar spinal T-scores to women

OBJECTIVE: To evaluate the applicability of the WHO densitometric criteria for the diagnosis of spinal osteoporosis in men and to compare it with women with vertebral fractures, as well as to analyze the role of vertebral dimensions in the development of spinal fractures. METHODS: For these purposes we analyzed, using DXA, vertebral projected area and lumbar bone mineral density (BMD), as well as T and Z-scores in lumbar spine in a cohort of 66946 individuals; 2556 of these subjects had one or more atraumatic vertebral fracture (396 men and 2160 postmenopausal women). RESULTS: Men and women with fractures showed significantly lower mean BMD, T-score and Z-score values than individuals without fractures while vertebral dimensions were similar in both groups of patients. When comparing men and women with vertebral fractures, the former showed a significantly greater projected area (46.89+/-5.5 vs. 39.13+/-4.6 cm(2) p<0.001) and lumbar BMD (0.991+/- 0.21 vs. 0.938+/- t0.19 g/cm(2) p<0.001). However, the median lumbar T-score values were similar for both sexes (-2.3 in women vs. -2.2 in men; p: NS). In addition, a similar percentage of men and women with vertebral fractures showed T-score values <-2.5 in the lumbar spine (44% vs. 46%, p=NS). CONCLUSION: We conclude that although men with vertebral fractures have greater vertebral dimensions and BMD than women, the lumbar T-scores are similar. Therefore, it seems reasonable to adopt the same T-score values for the diagnosis of osteoporosis in men and women.     

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4

SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.     

Change of EPO treatment from subcutaneous epoetin to intravenous epoetin or darbepoetin alpha

This prospective, two-arm, clinical trial assesses the effectiveness in maintaining the levels of haemoglobin (Hb) between 11 and 13 g/d1 and the safety of changing the administration route (from subcutaneous to intravenous) of epoetin (rHuEPO) alpha at equidose versus a changeover to darbepoetin alpha, taking the exact equivalence in peptide mass between the two as referent in patients with chronic renal insufficiency (CRI) in haemodialysis. A total of 112 patients previously treated with epoetin and no dose modification during the 8 weeks prior to the study and stable levels of Hb were included. Of these, 92.1% finished the follow-up period (24 weeks). After changing the administration route of rHuEPO, a significant increase in the resistance index (REI, weekly dose per kilogram of weight/levels of hemoglobin) was observed with mean values of 2.73 (p < 0.018) and 4.37 (p < 0.001) after 16 and 24 weeks respectively, requiring an increase of the dose greater than 15% over the baseline in 6 1.1% of the patients. The changeover to, darbepoetin alpha, independently of the administration route, was accompanied by a decrease in REI starting in the 8th week (mean levels of 0.012, 0.018 and 0.023 after 8, 16 and 24 weeks respectively), significant (p < 0.001) at the 3 cutoff points of the study. The conversion factor increased significantly up to 1:260 in week 24. Both erythropoietic stimulating factors (EST) were well tolerated and no unexpected side effects were observed. In conclusion, treatment of anaemia with darbepoetin alpha in patients with CRI in haemodialysis previously treated with rHuEPO proved to be more effective than the use of epoetin intravenously, significantly improving the resistance index. In addition, the treatment with darbepoetin alpha was well tolerated in these patients.     

Do patient-related blood donors represent a threat to the safety of the blood supply?

BACKGROUND AND OBJECTIVES: Patient-related blood donors contribute to a significant proportion of the blood units collected in hospital-based blood banks. However, there is some concern on the safety of this kind of donation because of the possible existence of incentives for the donor to conceal deferrable risk factors, thus increasing the risk of donation within the window-period of transfusion-transmitted infections. We tested the hypothesis that if patient-related blood donors are less safe than community ones, the former would display both a higher prevalence of viral markers and a predominance of undisclosed risk-factors with low social acceptability. DESIGN AND METHODS: Comparison of virus reactivity rates against hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV), and the associated risk-factors, between patient-related and community donors who donated whole blood in our center during a five-year period. RESULTS: During the period under study 72,226 donors gave 149,944 whole blood units, of which 22,888 (15.3%) were provided by patient-related donors. There were 273 confirmed virus-reactive donations (15 anti-HIV, 148 anti-HCV and 110 HBsAg). The adjusted prevalence of virus reactivity was 19 (95% CI: 11-35) times higher in first-time donors than in repeat donors, 3.5 (95% CI: 2.3-4.1) times higher in donors > or = 30 years old than in younger ones, and 2.5 (95% CI: 1.9-3.2) times higher in patient-related donors than in community donors. With regard to deferrable risk-factors not disclosed at the time of donation, there was no significant difference between patient-related and community donors in the frequency of people who denied any risk-factor or who admitted intravenous drug use or high-risk sex. Past household contact with individuals having liver disease was significantly more frequent in patient-related donors than in community ones. INTERPRETATION AND CONCLUSIONS: Our results do not support the hypothesis that patient-related donors represent an increased risk of window-period donation because they conceal deferrable risk factors more frequently than community donors.     

TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13)

A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet- derived growth factor receptor-B gene on chromosome 5 and a novel ETS- like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.     

Complication associated with celiac disease

Enteropathy associated T cell lymphoma is the most serious complication of celiac sprue. The incidence of malignancy, in general, is approximately twofold greater in celiac disease than in the general population, but the risk of specific gastrointestinal malignancies is markedly increased. Lymphoma of the small intestine, comprises approximately 50% of the malignancies, and the most are of T-cell origin. We report a case of celiac disease associated T-cell Lymphoma of the jejunum in a woman. At the age of 33 the diagnosis of Celiac sprue was made, after institution of a gluten free diet the patient improved, but, fifteen year later, the patient begin with fever and abdominal pain. Laparotomy showed a perforation of the intestine by a tumour.     

Lack of evidence for protease evolution in HIV-1-infected patients after 2 years of successful highly active antiretroviral therapy

The mechanisms involved in maintaining a latent replication-competent integrated human immunodeficiency virus type 1 (HIV-1) reservoir after successful highly active antiretroviral therapy (HAART) have not been fully described. The objective of this study was to assess whether low-level, persistent HIV-1 replication can be detected in the protease gene, in 10 HIV-1-infected patients who have undergone 2 years of successful HAART. Peripheral blood mononuclear cells (PBMCs) were collected from 10 HIV-1-infected patients receiving a triple-drug combination therapy (2 nucleoside analogues and 1 protease inhibitor). HIV-1 RNA levels and CD4+ and CD8+ T cell counts were longitudinally determined during a follow-up period of 108 weeks. Similarly, proviral fragments of the protease-coding region, obtained at baseline and at week 108 of HAART, were amplified by polymerase chain reaction from PBMCs, and 10-25 individual clones were sequenced for each time point. Only 1 of 271 individual protease clones showed a major resistance substitution (M46I [patient D]). Phylogenetic analysis revealed that, in all patients, the genetic distances from the deduced most recent common ancestor, in samples obtained at week 108 of HAART, were not longer than those in samples obtained at baseline. Moreover, the pattern of amino acid divergence during therapy showed an absence of positive selection in the protease-coding region. Taken together, these results show a lack of clinically relevant evolution in the protease-coding region after 2 years of successful HAART.     

Progenitor cells in the adult pancreas

The beta-cell mass in the adult pancreas possesses the ability to undergo limited regeneration following injury. Identifying the progenitor cells involved in this process and understanding the mechanisms leading to their maturation will open new avenues for the treatment of type 1 diabetes. However, despite steady advances in determining the molecular basis of early pancreatic development, the identification of pancreatic stem cells or beta-cell progenitors and the molecular mechanisms underlying beta-cell regeneration remain unclear. Recent advances in the directed differentiation of embryonic and adult stem cells has heightened interest in the possible application of stem cell therapy in the treatment of type 1 diabetes. Drawing on the expanding knowledge of pancreas development, beta-cell regeneration and stem cell research, this review focuses on progenitor cells in the adult pancreas as a potential source of beta-cells.     

Clinical characteristics and long-term outcome in patients with heart failure complicating acute myocardial infarction

INTRODUCTION AND OBJECTIVES: To evaluate the clinical characteristics and prognosis of heart failure (HF) development in patients hospitalized for acute myocardial infarction (AMI). PATIENTS AND METHOD: Between May 1990 and March 2000, 836 consecutive patients were admitted with a diagnosis of AMI within 24 h of symptom onset. HF was defined as the presence of rales and a third heart sound with gallop, and evidence of pulmonary congestion on chest x-ray. It was diagnosed in 263 subjects (31.5%). RESULTS: The mean age of patients with HF (group 1) was 63.4 (11.4) years compared with 59.9 (11.6) years in those without HF (group 2) (P<.01). There were differences between groups 1 and 2 in history of diabetes (36% vs 20%; P<.001) or previous HF (9.2% vs 1.1%; P<.001). The reperfusion strategy used in patients with Q-wave infarction, with or without HF, was primary angioplasty in 15% and 14%, respectively (P=.81), and thrombolytic agents in 28% and 37%, respectively (P=.013). Patients with HF were more likely to develop recurrent angina (26.8% vs 19.6%; P=.02), pericarditis (17.5% vs 6.3%; P<.001), and atrial fibrillation (12.3% vs 5.1%; P<.01). In-hospital mortality in groups 1 and 2 was 15.6% and 2.3% (P<.001), respectively, and 10-year survival was 10% and 30%, respectively (P<.001). The variables associated with mortality were: age (HR=1.022; P<.001), hyperglycemia (HR=1.748 per 1.0-g/L increase; P<.001), leukocytosis (HR=1.035 per 1000-cell/.L increase; P<.001), and HF (HR=1.308; P=.028). CONCLUSIONS: AMI is still frequently complicated by HF, which increases short- and long-term morbidity and mortality. Heart failure, age, hyperglycemia, and leukocytosis at admission were independent predictors of mortality during follow-up.