Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway

Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease. Serum levels of 7α-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients (either normocholesterolemic or hypercholesterolemic) with primary biliary cirrhosis and in control subjects. To evaluate cholesterol synthesis, serum levels of lathosterol were measured, and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols. In normocholesterolemic patients with primary biliary cirrhosis, lathosterol was significantly lower than in normocholesterolemic controls (P < 0.05) whereas no difference was found between hypercholesterolemic patients and hypercholesterolemic controls. Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls (P < 0.01). In patients with primary biliary cirrhosis, serum 7α-hydroxycholesterol was slightly higher than in controls. 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls (P < 0.05) and a significant linear correlation (r = 0.771; P < 0.001) was found between 27-hydroxycholesterol and cholesterol. In contrast, in patients with primary biliary cirrhosis, high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol. Our data confirm that in patients with primary biliary cirrhosis, cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7α-hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients.—Del Puppo, M., M. Galli Kienle, M. L. Petroni, A. Crosignani, and M. Podda. Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway. J. Lipid Res. 1998. 39: 2477–2482

The EuroLifeNet Study: How Different Microenvironments Influence Personal Exposure to PM 2.5 among High-School Students in Milan A. Borgini et al

Abstract Background: Epidemiological studies show that long-term exposure to PM is associated with an increased risk of cancer. The EuroLifeNet study measured the personal exposure to PM 2.5 in 90 pupils attending three schools in Milan, using a portable nephelometer, over a three-week period spanning November and December 2006. Background levels explained 40% of the variability of the exposure. Methods: As a second part of that study we analyzed the role of different microenvironments as determinants of personal exposure to PM 2.5 . Results: Exposure was influenced by the time of day, zone of the city and different microenvironments. Exposure was higher indoors than out, and indoors it was higher in the kitchen, particularly during cooking. In outdoor environments exposure was higher at bus stops where road traffic was heavy. Conclusions: Even though background concentration can be a good predictor of personal exposure to PM, students&apos; personal exposure is strongly influenced by different microenvironments and should be considered in population studies. The EuroLifeNet experience gives a contribution to personal exposure measure methodology

On the universality of the Discrete Nonlinear Schroedinger Equation

We address the universal applicability of the discrete nonlinear Schroedinger equation. By employing an original but general top-down/bottom-up procedure based on symmetry analysis to the case of optical lattices, we derive the most widely applicable and the simplest possible model, revealing that the discrete nonlinear Schroedinger equation is ``universally'' fit to describe light propagation even in discrete tensorial nonlinear systems and in the presence of nonparaxial and vectorial effects.Comment: 6 Pages, to appear in Phys. Rev.

Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension.</p> <p>Case presentation</p> <p>We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy.</p> <p>Conclusion</p> <p>We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.</p

Iatrogenic intoxication of a feline by bupivacaine hidrochloride

O Cloridrato de Bupivacaína é um anestésico local do tipo amida de ação duradoura que, quando administrado em altas doses ou por vias inadequadas, pode acarretar efeitos tóxicos aos sistemas nervoso central (SNC) e cardiocirculatório. Este trabalho visa a relatar o quadro clínico desenvolvido por um felino, da raça siamesa, de 8 meses, do sexo feminino, intoxicado pela administração iatrogência de cloridrato de bupivacaína, trazido ao Hospital Veterinário Mundo Animal, apresentando quadro convulsivo, evoluindo para depressão do SNC e alterações cardiovasculares; bem como a terapia instituída no controle dos sinais apresentados. Foi instituída terapêutica de suporte, ventilação com oxigênio a 100%, controle das convulsões com o uso de benzodiazepínicos e controle do edema pulmonar e efusões pleurais e pericárdicas com o uso de furosemida. O paciente evoluiu positivamente, recebendo alta após 5 dias.Bupivacaine hidrochloride is a long duration amida type local anesthesic. When high doses were administrated it can cause toxicity to the nervous system and cardiocirculatory system. This report describes the clinical signs of a cat intoxicated by iatrogenic administration of bupivacaine hidrochloride. The patient was brought to Hospital Veterinário Mundo Animal presenting convulsions, developing depression of central nervous system and cardiovascular changes. It was established therapeutic support, ventilation with oxygen to 100%, control of seizures with the use of benzodiazepines and control of pulmonary edema and pleural and pericardic efusions with the use of furosemide. The patient has positive developments, getting high after 5 days

Intoxicação Iatrogênica de um felino por Cloridrato de Bupivacaína

O Cloridrato de Bupivacaína é um anestésico local do tipo amida de ação duradoura que, quando administrado em altas doses ou por vias inadequadas, pode acarretar efeitos tóxicos aos sistemas nervoso central (SNC) e cardiocirculatório. Este trabalho visa a relatar o quadro clínico desenvolvido por um felino, da raça siamesa, de 8 meses, do sexo feminino, intoxicado pela administração iatrogência de cloridrato de bupivacaína, trazido ao Hospital Veterinário Mundo Animal, apresentando quadro convulsivo, evoluindo para depressão do SNC e alterações cardiovasculares; bem como a terapia instituída no controle dos sinais apresentados. Foi instituída terapêutica de suporte, ventilação com oxigênio a 100%, controle das convulsões com o uso de benzodiazepínicos e controle do edema pulmonar e efusões pleurais e pericárdicas com o uso de furosemida. O paciente evoluiu positivamente, recebendo alta após 5 dias

Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population

Background &amp; Aims: Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to be measured. Methods: The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age-and sex-specific mortality rates recorded in Italy for person-years adequate for the enrolment period. The standardized mortality ratio (SMR) determined the relative risk of death over that of the age and sex matched general population. Results: Overall, 28/181 patients followed-up for a median period of 9.6 years (range 1-25 years) died. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3-94.8) and 62.9% (95% CI, 45.9-75.9), respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a SMR = 1.00 (95% CI, 0.72-1.35), with an SMR for non-SVR patients of 3.85 (95% CI,, for untreated of 3.01 (95% CI, 2.64-3.42) and for decompensated of 6.70 (95% CI,. Conclusions: Patients with compensated HCV cirrhosis achieving SVR by IFN obtain a main benefit levelling their survival curve to that of the general population. Wider applicability of IFN-free regimens will possibly make this achievement more generalizable

Consistency and accuracy of diagnostic cancer codes generated by automated registration: comparison with manual registration

BACKGROUND: Automated procedures are increasingly used in cancer registration, and it is important that the data produced are systematically checked for consistency and accuracy. We evaluated an automated procedure for cancer registration adopted by the Lombardy Cancer Registry in 1997, comparing automatically-generated diagnostic codes with those produced manually over one year (1997). METHODS: The automatically generated cancer cases were produced by Open Registry algorithms. For manual registration, trained staff consulted clinical records, pathology reports and death certificates. The social security code, present and checked in both databases in all cases, was used to match the files in the automatic and manual databases. The cancer cases generated by the two methods were compared by manual revision. RESULTS: The automated procedure generated 5027 cases: 2959 (59%) were accepted automatically and 2068 (41%) were flagged for manual checking. Among the cases accepted automatically, discrepancies in data items (surname, first name, sex and date of birth) constituted 8.5% of cases, and discrepancies in the first three digits of the ICD-9 code constituted 1.6%. Among flagged cases, cancers of female genital tract, hematopoietic system, metastatic and ill-defined sites, and oropharynx predominated. The usual reasons were use of specific vs. generic codes, presence of multiple primaries, and use of extranodal vs. nodal codes for lymphomas. The percentage of automatically accepted cases ranged from 83% for breast and thyroid cancers to 13% for metastatic and ill-defined cancer sites. CONCLUSION: Since 59% of cases were accepted automatically and contained relatively few, mostly trivial discrepancies, the automatic procedure is efficient for routine case generation effectively cutting the workload required for routine case checking by this amount. Among cases not accepted automatically, discrepancies were mainly due to variations in coding practice

Descriptive epidemiology of selected birth defects, areas of Lombardy, Italy, 1999

<p>Abstract</p> <p>Background</p> <p>Birth defects are a leading cause of neonatal and infant mortality in Italy, however little is known of the etiology of most defects. Improvements in diagnosis have revealed increasing numbers of clinically insignificant defects, while improvements in treatment have increased the survival of those with more serious and complex defects. For etiological studies, prevention, and management, it is important to have population-based monitoring which provides reliable data on the prevalence at birth of such defects.</p> <p>Methods</p> <p>We recently initiated population-based birth defect monitoring in the Provinces of Mantova, Sondrio and Varese of the Region of Lombardy, northern Italy, and report data for the first year of operation (1999). The registry uses all-electronic source files (hospital discharge files, death certificates, regional health files, and pathology reports) and a proven case-generation methodology, which is described.</p> <p>The data were checked manually by consulting clinical records in hospitals. Completeness was checked against birth certificates by capture-recapture. Data on cases were coded according to the four-digit malformation codes of the International Classification of Diseases, Ninth Revision (ICD-9). We present data only on selected defects.</p> <p>Results</p> <p>We found 246 selected birth defects in 12,008 live births in 1999, 148 among boys and 98 among girls. Congenital heart defects (particularly septal defects) were the most common (90.8/10,000), followed by defects of the genitourinary tract (34.1/10, 000) (particularly hypospadias in boys), digestive system (23.3/10,000) and central nervous system (14.9/10,000), orofacial clefts (10.8/10,000) and Down syndrome (8.3/10,000). Completeness was satisfactory: analysis of birth certificates resulted in the addition of two birth defect cases to the registry.</p> <p>Conclusion</p> <p>This is the first population-based analysis on selected major birth defects in the Region. The high birth prevalences for septal heart defect and hypospadias are probably due to the inclusion of minor defects and lack of coding standardization; the latter problem also seems important for other defects. However the data produced are useful for estimating the demands made on the health system by babies with birth defects.</p

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist