Effect of adrenomedullin on c-Met receptor expression after reserpine-induced gastric damage in the rat

Here, we show an increase in c-Met receptor expression during reserpine-induced gastric damage in the rat, as assessed by immunohistochemistry. Pretreatment of animals with adrenomedullin prevented this increase in c-Met expression. c-Met immunoreactivity was localized in gastric glands. c-Met immunoreactivity was associated with increased phosphorylation of c-Met receptor and extracellular signal-regulated kinase (ERK(1/2)). Our results suggest that both adrenomedullin and c-Met act as parallel defence mechanisms during pharmacologically induced gastric mucosa injury.     

Hepatitis C virus infection associated with liver-kidney microsomal antibody type 1 (LKM1) autoantibodies in children

OBJECTIVE: To evaluate the clinical pattern and evolution of chronic hepatitis C in children with liver/kidney microsomal antibody type 1 autoantibodies (LKM1). STUDY DESIGN: A multicenter, retrospective study, including the following groups of children with hepatitis C virus infection: (1). 21 consecutive LKM1-positive patients, (2). 42 age- and sex- matched LKM1-negative patients, and (3). 4 interferon-induced LKM1-positive cases. LKM1 reactivity to human microsomes and recombinant cytochrome P450IID6 (CYP2D6) was assayed by immunoblotting. RESULTS: Clinical and biochemical features overlapped in LKM1-positive and LKM1-negative children, but a fibrosis score >3 (range 0-6) was significantly more frequent (P =.04) in the former. Reactivity to microsomal protein and CYP2D6 was significantly (P =.02) associated with LKM1 titers >or=1:320 and was found in 39% of patients, including severe cases and both children (of 4 treated) who achieved a sustained alanine aminotransferase (ALT) normalization after steroid treatment. Five of 7 LKM1-positive children treated with interferon had an ALT exacerbation. CONCLUSIONS: LKM1-positive hepatitis C in children is characterized by a wide spectrum of biochemical, serologic, and histologic features. Whether autoimmunity may contribute to liver damage in a subgroup of patients with more severe liver disease, high LKM1 titers, and reactivity to CYP2D6 is a question deserving further investigation.     

Clinical features and progression of perinatally acquired hepatitis C virus infection

The purpose of this prospective-retrospective study was to provide information about the clinical features and progression of hepatitis C virus (HCV) infection transmitted perinatally. Seventy children born to HCV infected woman were enrolled consecutively in five European centers between 1990 and 1999, provided they had HCV RNA in the serum during the first year of life and/or were still anti-HCV positive at 18 months. Sixty-two infants were followed up to 24 months of age or more (range, 24 months-11 years; average, 4.8 +/- 2.3 years). A wide range of ALT elevation was observed in 93% of the infants in the first year of life. During the follow-up, a sustained ALT normalization with loss of HCV RNA was seen in 12/62 (19%) of the children within 30 months of life; 66% of the infants had developed an ALT peak greater than 5x normal at onset (vs. 28% of children with persistent viremia; P < 0.05), and 50% had HCV genotype 3 (vs. 17% of viremic children). Conversely the cumulative probability of chronic progression was 81%. Chronic infection was asymptomatic and liver disease was mild in all 11 children who underwent a biopsy. In conclusion the early stage of acquired perinatally HCV infection is characterized by a wide range of ALT abnormalities, suggesting the interaction of multiple host and virus factors. The chronic progression rate of infection is high, but the associated liver disease is usually mild. High ALT levels at onset seem to offer greater opportunity of biochemical remission and loss of viremia during follow-up.     

Clinical and therapeutic aspects of diabetic nephropathy

The prognosis of renal survival in both type 1 and type 2 diabetes mellitus is not benign. Several factors characterize the increase in the risk of developing renal damage in diabetic patients, distinguished in diabetes-related factors, genetic factors and other factors. DIAGNOSIS: Diagnosis requires standard annual urinalysis and dipstick for albumin. In patients with negative urine dipstick, the routine approach is to evaluate the albumin/creatinine ratio (ACR) in the first voided urine. The degree of renal impairment is assessed by an annual evaluation of the glomerular filtration rate (GFR) by the Cockroft/Gault formula in normoalbuminuric patients. In patients with overt nephropathy this evaluation needs to be more frequent. THERAPY: A thorough therapeutic approach, in both the early and later stages of diabetic nephropathy, is fundamental because of the increased risk of morbidity and mortality. Renal damage (and the natural history of the disease) is approached on three different levels. Primary prevention, in patients with no clinical and biochemical signs of renal damage, is a strict glycemic control by oral antidiabetic agents or insulin, as required, together with the maintenance of blood pressure (BP) levels < 130/85 mmHg, preferably using ACE-inhibitors. Secondary prevention aims to prevent or slow the progresssion from micro- to macroalbuminuria. BP control is the first-line approach, along with a strict glycemic control. At this stage, it is necessary to use other anti-hypertensive agents besides ACE-inhibitors to achieve optimal BP levels of 130/85 mmHg. Tertiary prevention addresses the reduction in the rate of renal failure progression by optimal BP control, a slightly hypoproteic diet and the control of dyslipidemia, in the presence of a (non-fundamental) euglycemic state. PROMISING NEW TRENDS IN DIABETIC NEPHROPATHY TREATMENT: a pharmacological blockade of endothelin and/or sympathetic system, an amelioration of hypoxia by correcting reduced hemoglobin levels, an interference with the formation and accumulation of advanced glycosilation end-products (AGE). Finally, the manipulation of the sex hormone balance, genetic screening for a predisposition to progressive renal dysfunction and, eventually, gene therapy complete the scenario for future approaches to this major complication of diabetic disease.     

Epidemiology of end-stage renal disease in an interregional perspective: Registries of Puglia and Basilicata, southern Italy

BACKGROUND: This report on the 1994-1998 Dialysis and Transplantation Registry (DTR) of Puglia and Basilicata provides the first epidemiological profile of ESRD in southern Italy. METHODS: Frequency measures of patients in renal replacement therapy (RRT) were computed for Puglia and Basilicata (inhabitants: 4,086,422 and 610,000 respectively). Hazard ratios (HR) of death in relation to sex, age, educational level, primary nephropathies, and modality of dialysis, were estimated by applying the Cox model to patients starting dialysis as first RRT in 1994-1998 in Puglia. RESULTS: The prevalence of treated ESRD in Puglia was 881 per million population (p.m.p.) (dialysis: 721 p.m.p.) in 1998, 713 p.m.p. (dialysis: 617 p.m.p.) in 1994. In Basilicata the prevalence of ESRD was 795 p.m.p. (dialysis: 669 p.m.p.) in 1998, 636 p.m.p. (dialysis: 575 p.m.p.) in 1994. Mean age at start of dialysis of incident cases of Puglia was 60 yr (median: 64 yr). Figures of diabetes, vascular diseases, and glomerulonephritis, were: 16%, 21%, 17%. Out of 2,152 incident patients on dialysis for at least one month, 293 started with peritoneal dialysis (PD). A 60-70% higher risk of death was observed for diabetic nephropathy and PD. In the Puglia/Basilicata DTR pooled analysis, lower educational level was associated with a 60% increased mortality risk. CONCLUSIONS: The associations of PD and low education with the risk of death are very likely to be due to comorbid conditions, unavailable in these databases as in most regional and national DTR. By looking at variations of rates and outcomes among areas, potential improvements of local DTR for planning and research uses are discussed.     

De-escalation therapy in ventilator-associated pneumonia

OBJECTIVE: To evaluate de-escalation of antibiotic therapy in patients with ventilator-associated pneumonia. DESIGN: Prospective observational study during a 43-month period. SETTING: Medical-surgical intensive care unit. PATIENTS: One hundred and fifteen patients admitted to the intensive care unit with clinical diagnosis of ventilator-associated pneumonia. All the episodes of ventilator-associated pneumonia received initial broad-spectrum coverage followed by reevaluation according to clinical response and microbiology. Quantitative cultures obtained by bronchoscopic examination or tracheal aspirates were used to modify therapy. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-one episodes of ventilator-associated pneumonia were diagnosed. Change of therapy was documented in 56.2%, including de-escalation (the most frequent cause) in 31.4% (increasing to 38% if isolates were sensitive). Overall intensive care unit mortality rate was 32.2%. Inappropriate antibiotic therapy was identified in 9% of cases and was associated with 14.4% excess intensive care unit mortality. Quantitative tracheal aspirates and bronchoscopic samples (58 protected specimen brush and three bronchoalveolar lavage) were associated with 32.7% and 29.5% intensive care unit mortality and 29.3% and 34.4% de-escalation rate. De-escalation was lower (p < .05) in the presence of nonfermenting Gram-negative bacillus (2.7% vs. 49.3%) and in the presence of late-onset pneumonia (12.5% vs. 40.7%). When the pathogen remained unknown, half of the patients died and de-escalation was not performed. CONCLUSION: De-escalation was the most important cause of antibiotic modification, being more feasible in early-onset pneumonia and less frequent in the presence of nonfermenting Gram-negative bacillus. The impact of quantitative tracheal aspirates or bronchoscopic techniques was comparable in terms of mortality.     

FRAIL Questionnaire Screening Tool and Short-Term Outcomes in Geriatric Fracture Patients

Objectives

There are limited screening tools to predict adverse postoperative outcomes for the geriatric surgical fracture population. Frailty is increasingly recognized as a risk assessment to capture complexity. The goal of this study was to use a short screening tool, the FRAIL scale, to categorize the level of frailty of older adults admitted with a fracture to determine the association of each frailty category with postoperative and 30-day outcomes.