Diagnosis of occult hepatitis C without the need for a liver biopsy

The diagnosis of occult hepatitis C virus (HCV) infection is based on the presence of HCV‐RNA in the liver. This study aimed to evaluate the use of combining non‐invasive assays to diagnose occult HCV. A total of 122 patients with occult HCV (HCV‐RNA in the liver without detectable anti‐HCV and serum HCV‐RNA) and 45 patients with cryptogenic chronic hepatitis (without HCV‐RNA in the liver and negative for anti‐HCV and serum HCV‐RNA) were included. HCV‐RNA was tested in peripheral blood mononuclear cells (PBMCs) and in 2 ml of ultracentrifuged serum. Anti‐core HCV was examined by a non‐commercial enzyme‐linked immunosorbent assay. All controls were negative for the three HCV markers studied. Among patients with occult HCV, 36% were anti‐core HCV positive, 57% had serum HCV‐RNA after ultracentrifugation, and 61% had HCV‐RNA in PBMCs. Combining the results of the assays, 91% of the patients were positive for at least one marker. Intrahepatic HCV‐RNA load was significantly higher in patients who were positive simultaneously for the three HCV markers than in patients who were negative for all markers (P = 0.006) and than in those with one or two HCV markers (P = 0.039). Replication of HCV in liver was detected more frequently in patients with three (93%, P = 0.002), two (82%, P = 0.001), and one HCV marker (73%, P = 0.011) than in those without markers (27%). In conclusion, testing for all these markers allows diagnosis of occult HCV without the need for a liver biopsy and these assays may help to elucidate the clinical significance of occult HCV infection. J. Med. Virol. 82:1554–1559, 2010. © 2010 Wiley‐Liss, Inc.     

Outcome of older critically ill patients: a matched cohort study

BACKGROUND: Admission of older patients to intensive care units is a controversial issue. OBJECTIVE: To estimate age-associated mortality of critically ill patients. METHODS: A prospective matched cohort study in the Medical-Surgical Intensive Care Unit of a tertiary hospital was conducted. We included 100 consecutive patients older than 70 years admitted to the intensive care unit (cases) and 100 patients younger than 70 years (controls). The matching criterion was the severity of illness at admission to the intensive care unit as estimated by the simplified acute physiological score (SAPS II) without including age in its calculation. RESULTS: Mortality in the intensive care unit was higher, but not statistically significant, in the older group: 26% vs. 19% (p = 0.23). Patients older than 70 years had a longer duration of mechanical ventilation (median 7 vs. 3 days) and longer stay in the intensive care unit (median 8 vs. 5 days). There were no differences in organ dysfunctions, except for a higher incidence of respiratory failure in the older group (p < 0.001). The use of invasive procedures was similar in both groups. There were more orders for the withholding/withdrawal of treatment in patients older than 70 years (9 vs. 3%, p = 0.07). CONCLUSION: In our study, age was not related with a significant higher mortality. In the older patients included in our study the survival was greater than 70% with a similar resource utilization except for a longer stay in the intensive care unit.     

Oestradiol-17beta inhibits tamoxifen-induced LHRH self-priming blocking hormone-dependent and ligand-independent activation of the gonadotrope progesterone receptor in the rat

In the rat, administration of tamoxifen (TX) in the absence of oestrogen (E) induces LHRH self-priming, the progesterone receptor (PR)-dependent property of LHRH that increases gonadotrope responsiveness to itself. The oestrogen-dependent PR can be phosphorylated/activated by progesterone (P4) and, in the absence of the cognate ligand, by intracellular LHRH signals, particularly cAMP/protein kinase A. We have recently found that oestradiol-17beta (E2), acting on a putative membrane estrogen receptor-alpha in the gonadotrope, inhibits this agonist action of TX. This study investigated the mechanism by which E2 inhibits TX-elicited LHRH self-priming using both incubated pituitaries from TX-treated ovariectomized (OVX) rats and anterior pituitary cells from OVX rats cultured with TX. It was found that (1) in addition to the inhibitory effect on TX-elicited LHRH self-priming, E2 blocked P4 and adenylyl cyclase activator forskolin augmentation of LHRH-stimulated LH secretion, and (2) E2 did not affect the increasing action of TX on gonadotrope PR expression or pituitary cAMP content. Furthermore, inhibition of protein phosphatases with okadaic acid suppressed E2 inhibition of TX-elicited LHRH-induced LH secretion, while stimulation of protein phosphatases with ceramide blocked TX-induced LHRH self-priming. Together, these results indicated that membrane ER-mediated E2 inhibition of the TX-stimulated LHRH self-priming pathway involves a blockade of gonadotrope PR phosphorylation/activation, but not a deficient response of PR to phosphorylases. Results also suggested that the inhibitory effect of E2 on TX-induced LHRH self-priming is exerted through modulation of cellular protein phosphatase activity in the gonadotrope.     

Impact of hepatitis C infection on long-term mortality of injecting drug users from 1990 to 2002: differences before and after HAART

OBJECTIVE: To assess the impact of HIV and hepatitis C virus (HCV) infection on long-term mortality in injecting drug users (IDU). DESIGN: Community-based prospective cohort study. METHODS: Mortality data from follow-up in clinical sites and the Mortality Registry by December 2002 were collected for 3247 IDU who attended three centres for voluntary counselling and testing for HIV/AIDS, HCV and hepatitis B virus (HBV) in 1990-1996. Mortality rates by Poisson regression were adjusting for age, sex, duration of drug use, education, HBV and calendar period (1990-1997 and 1998-2002). RESULTS: Overall, 11.2% were HIV/HCV negative, 43.7% positive only for HCV and 45.1% positive for both. During 26 772 person-years of follow-up, 585 deaths were detected (2.19/100 person-years). Before 1997, HIV/HCV-positive subjects had a five-fold increase in risk of death [relative risk (RR), 5.4; 95% confidence interval (CI), 2.5-11.4] compared with those negative for both; after 1997, a three-fold increase was observed (RR, 2.7; 95% CI, 1.7-4.2). Being HCV positive/HIV negative was not associated with an increase in the risk of death either before (RR, 1.3; 95% CI, 0.6-2.9) or after (RR, 1.2; 95% CI, 0.8-1.9) 1997 compared with HCV/HIV negative. While increases in mortality were seen in those HCV/HIV negative (RR, 1.6; 95% CI, 0.7-3.7) and those only positive for HCV (RR, 1.5; 95% CI, 1.0-2.1), a 20% reduction among coinfected IDUs was observed after 1997 (interaction P = 0.033). CONCLUSIONS: HCV/HIV coinfection has had a large impact on mortality in IDU. After 1997, mortality increased in HIV negative/HCV positive subjects and decreased in HIV positive/HCV positive.     

Health-related quality of life and appropriateness of knee or hip joint replacement

BACKGROUND: We studied the association between explicit appropriateness criteria for total hip joint replacement (THR) and total knee replacement (TKR) with changes in health-related quality of life of patients undergoing these procedures. METHODS: Prospective observational study of 1576 consecutive patients with diagnoses of osteoarthritis on waiting lists to undergo THR or TKR. Explicit appropriateness criteria using the RAND appropriateness method were applied. Patients completed 2 questionnaires that measured health-related quality of life, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), before the procedure and 6 months afterward. RESULTS: Patients who were considered appropriate candidates for these procedures had greater improvements than those who were considered inappropriate candidates in all 3 WOMAC domains (pain, functional limitation, and stiffness; THR: 43.0, 40.6, and 40.4 vs 14.7, 19.1, and 15.9; TKR: 34.9, 32.5, and 30.2 vs 23.2, 18.9, and 17.1; P<.001 for all comparisons). Patients who underwent THR and were judged to be appropriate candidates had greater improvements in the physical function, role-physical, bodily pain, and social function domains of the SF-36 than those judged to be inappropriate candidates (34.4, 35.1, 33.1, and 26.6 vs 19.6, 9.2, 5.7, and 7.0; P = .04, P = .03, P < .001, and P < .001, respectively). Appropriate candidates for TKR demonstrated greater improvement in the social function domain of the SF-36 after the procedure than those deemed inappropriate candidates (19.9 vs 7.9; P = .004) but not in the other domains of functional status. CONCLUSIONS: These results suggest a direct relationship between explicit appropriateness criteria and better health-related quality-of-life outcomes after THR and TKR surgery. Our results support the use of these criteria for clinical guidelines or evaluation purposes.     

Construct and criterion validity of the SF‐12 health questionnaire in patients with acute myocardial infarction and unstable angina

Background The aim of the study was to determine the construct and criterion validity of the 12‐item short‐form questionnaire (SF‐12) in coronary patients with either acute myocardial infarction or unstable angina in Spain. Method A total of 186 patients hospitalized with coronary heart disease have been studied. The construct validity has been analysed by means of the association between the SF‐12v.1 and sociodemographic and clinical variables; and the criterion validity was tested by the correlations between 36‐item short‐form question (SF‐36) and SF‐12 summary scores. The equivalence between both health questionnaires was examined by means of the proportion of variance in the SF‐36 physical and mental component summary (PCS‐36 and MCS‐36) scores explained by the 12 items adjusted by age and sex. Results The validation result was as expected: female patients and those with poor education level, worse mental health, unstable angina, cardiovascular risk factor and co‐morbidity obtained a lower score in the SF‐12. The correlations between SF‐36 and SF‐12 summary scores were high. The equivalence between the SF‐12 and SF‐36 was good, because the models explained 87% of the variation in PCS‐36 score and 93% of the variation in MCS‐36. Conclusion The SF‐12 is a valid tool in studies assessing health‐related quality of life in coronary patients. The use of the SF‐12 may be especially useful in patients where the clinical situation make difficult the application of the longer instrument.     

Mortalidad prematura y años potenciales de vida perdidos relacionados con el consumo de alcohol en España y en las comunidades autónomas en el año 2004

ObjectiveThe aim of this study is to analyse premature deaths due to alcohol consumption in 2004 in Spain and its different Autonomous Communities.DesignUsing data on deaths that can be attributed to alcohol consumption in 2004 for Spain and its different Autonomous Communities, the Potential Years of Life Lost (PYLL) were calculated up to the age of 70 for each diagnostic category, by sex and 5-year age groups.SettingSpain: 17 Autonomous Communities, Ceuta and Melilla.ParticipantsData on deaths that can be attributed to alcohol consumption in 2004 for Spain and its different Autonomous Communities.MeasurementsThe number of PYLL, the percentage of PYLL, and average PYLL.ResultsDuring 2004, 118,411 PYLL were lost, 4 times higher in males than in females, the average PYLL per death being attributable to alcohol was 22.6 years (ranging from 34.7 in Ceuta and 20.2 in Asturias). Acute causes (68% of the PYLL), and in particular unintentional accidents (47.9 of the PYLL), were the main causes that contributed to premature death related to alcohol consumption in Spain and in each of Spanish Autonomous Communities.ConclusionsThe estimation of the PYLL shows the great impact that alcohol consumption has on the premature death rate in Spain ant the Spanish Autonomous Communities. Given that alcohol consumption is an avoidable cause of death, the adoption of preventive measures aimed at reducing consumption, as well as the early detection and treatment of possible alcohol related problems is vital.     

Skin prick test predictive value on the outcome of a first known egg exposure in milk-allergic children

Children with milk allergy have higher incidence of other food allergies, especially egg allergy. The objective of this study was to ascertain the accuracy of the prick test in children with IgE-mediated milk allergy for diagnosing egg allergy. Children under the age of 1 yr who came consecutively to Allergy Department 2003–05, and were diagnosed with IgE-mediated milk allergy were selected for this study. Egg introduction was completely avoided until the age of 14 months when clinical history, skin prick tests (SPT), specific-IgE antibodies determination and egg challenge test were performed. One hundred and four milk-allergic children were included. At least one positive prick test to any egg allergen was found in 65 out of the 104 (62.5%). Thirty-eight (36.5%) were allergic to egg proteins as well. Prick tests with egg white and ovomucoid (OVM) had the best diagnostic performances showing the largest areas under the receiver operating characteristic curve. The optimal diagnosis cut-off point was 6 mm for egg white and 5 mm for OVM. The positive likelihood ratios for these cut-off points were: 2.95 (95% CI: 1.74–4.99) for egg white prick test, and 20 (95% CI: 2.9–143.7) for OVM prick test. Children with specific IgE-mediated cow's milk allergy must be closely followed as a risk group for egg allergy. Early diagnosis is necessary and the SPT has shown itself to be a very useful tool for diagnosing immediate IgE reactions to egg on first known exposure.     

Effect of thyroid hormone–nitric oxide interaction on tumor growth,angiogenesis, and aminopeptidase activity in mice

This study evaluated the effects of thyroid hormone–NO interaction on tumor development, vascularization, vascular endothelial growth factor (VEGF), and aminopeptidase (AP) activity in a murine model of implanted Lewis’s carcinoma. Experiments were performed in male CBA-C57 mice. Animals were untreated (controls) or treated with: T₄, the antithyroid drug methimazole, the NO inhibitor L-NAME, T₄?+?L-NAME, methimazole?+?NAME, the αvß3 integrin antagonist tetrac, T₄?+?tetrac, the iNOS inhibitor aminoguanidine (AG), and T₄ + AG; all treatments were for 6 weeks except for tetrac, administered for the last 11 days. Mice were subcutaneously inoculated with 1?×?10⁶ exponentially growing Lewis carcinoma 3LL cells into the dorsum. Study variables 9 days later were tumor weight (TW), Hb content, an index of tumor vascularization, VEGF, and AP activity. T₄ produced parallel increases in TW and angiogenesis. L-NAME reduced TW and angiogenesis in control, hyperthyroid, and hypothyroid mice, whereas AG had no effect on these variables. Tetrac arrested TW in normal and T₄-treated mice but did not decrease angiogenesis in T₄-treated animals. Negative correlations were found between TW and AP activity in tumors from control hyper- and hypothyroid groups and an inverse relationship was observed between TW and AP activities in tetrac-treated mice. T₄ enhances TW and angiogenesis, in which NO participates, but requires activation of integrin αvß3 to promote carcinogenesis. NO blockade reduces TW, regardless of the thyroid status. Thyroid hormone negatively modulates AP activity in the tumor. Accordingly, blockade of the membrane TH receptor αvß3 integrin reduces TW associated with an increase in AP activity.