Enzymatic cytochemistry,DNA ploidy and AgNOR quantitation in hepatocellular nodules of uncertain malignant potential in liver cirrhosis

Conventional histological examination of echo-guided biopsy specimens can be inconclusive in small nodular lesions in cirrhotic livers. We investigated the diagnostic potential of cytochemical analysis of dipeptidyl-peptidase IV (DPP IV), of image analysis of nuclear DNA content, and of interphase silver-stained nucleolar organizer regions (AgNORs) in 12 cases of small (13- to 29-mm in diameter) hepatic nodules visualized in cirrhotic patients by ultrasonography. All cases underwent an echo-guided liver biopsy at the time of detection and in none of them were histological signs of malignancy found. Characterization with the above-mentioned techniques was always done at the time of histological examination. These patients underwent a mean (±sd) follow-up of 27.0 (±11.2) months after biopsy, with repeated ultrasound (US) examinations. In the seven patients with subsequent neoplastic growth, DPP IV score was altered in five of six; the fraction of mononucleated polyploid cells was altered in six of seven; and the AgNOR quantity exceeded the cutoff value of 4 m² in five of five cases. Among the five lesions whose US appearance remained unchanged during the follow-up, only one abnormality (AgNORs) was found in one case. The combined cytochemical analysis of DPP IV, nuclear DNA content, and quantitative evaluation of interphase AgNORs in biopsy samples may contribute to the differential diagnosis of hepatocellular nodules of uncertain type in the cirrhotic liver.This work was supported by grants from the Ministero per l'Università e la Ricerca Scientifica (fondi 40% e 60%) andA.I.R.C. (Milano).     

Twiddler's syndrome and pectoral stimulation in a patient with dual-site unipolar atrial pacing.

Twiddler's syndrome is a rare condition of pacemaker rotation; when associated with unipolar pacing it could provoke extracardiac muscular stimulation. We report a case of an obese woman who unintentionally reversed her triple-chamber, dual-site unipolar atrial pacemaker, implanted for the prevention of paroxysmal atrial fibrillation. The extracardiac pectoral stimulation was due to unipolar atrial stimulation. The polarity mode was not programmable and output reduction was unsuccessful. Thus, the problem was resolved noninvasively by means of external manual rotation of the pacer. At 24 months of follow-up, the patient was still free of symptoms.     

An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene

Adenoviral (Ad)-mediated in vivo gene transfer and expression are limited in part by cellular immune responses to viral-encoded proteins and/or transgene immunogenicity. In an attempt to diminish the former responses, we have previously developed and described helper-dependent (HD) Ad vectors in which the viral protein coding sequences are completely eliminated. These HD vectors have up to 37 kb insert capacity, are easily propagated in a Cre recombinase-based system, and can be produced to high concentration and purity (>99.9% helper-free vector). In this study, we compared safety and efficacy of leptin gene delivery mediated by an HD vector (HD-leptin) and a first-generation E1-deleted Ad vector (Ad-leptin) in normal lean and ob/ob (leptin-deficient) mice. In contrast to evidence of liver toxicity, inflammation, and cellular infiltration observed with Ad-leptin delivery in mice, HD-leptin delivery was associated with a significant improvement in associated safety/toxicity and resulted in efficient gene delivery, prolonged elevation of serum leptin levels, and associated weight loss. The greater safety, efficient gene delivery, and increased insert capacity of HD vectors are significant improvements over current Ad vectors and represent favorable features especially for clinical gene therapy applications.     

Health care costs and costs associated with changes in work productivity among persons with systemic lupus erythematosus

Objective

To estimate health care costs and costs associated with changes in work productivity among persons with systemic lupus erythematosus (SLE) in the US.

Methods

Data were derived from the University of California, San Francisco Lupus Outcomes Study. Participants provided information on their health care resource use and employment. Cost estimates were derived for both direct health care costs and costs related to changes in work productivity. Direct health care costs included costs for hospitalizations, emergency department services, physician visits, outpatient surgical procedures, dialysis, and medications. Productivity costs were estimated by measuring changes in hours of work productivity since diagnosis of SLE; these estimates were also compared with normal US population data.

Results

For the total population of participants, the mean annual direct cost was $12,643 (2004 US dollars). The mean annual productivity cost for subjects of employment age (≥18 and <65 years) was $8,659. The mean annual total cost (direct and productivity) for subjects of employment age was $20,924. Regression results showed that greater disease activity, longer disease duration, and worse physical and mental health were significant predictors of higher direct costs; older age predicted lower direct costs. Older age, greater disease activity, and worse physical and mental health status were significant predictors of higher costs due to changes in work productivity.

Conclusion

Both direct health care costs and costs associated with changes in work productivity are substantial and both represent important contributors to the total costs associated with SLE.     

HIV-Related Stigma among People with HIV and their Families: A Qualitative Analysis

We examined the interconnectedness of stigma experiences in families living with HIV, from the perspective of multiple family members. Semi-structured interviews were conducted with 33 families (33 parents with HIV, 27 children under age 18, 19 adult children, and 15 caregivers). Parents were drawn from the HIV Cost and Services Utilization Study, a representative sample of people in care for HIV in US. All of the families recounted experiences with stigma, including 100% of mothers, 88% of fathers, 52% of children, 79% of adult children, and 60% of caregivers. About 97% of families described discrimination fears, 79% of families experienced actual discrimination, and 10% of uninfected family members experienced stigma from association with the parent with HIV. Interpersonal discrimination seemed to stem from fears of contagion. Findings indicate a need for interventions to reduce HIV stigma in the general public and to help families cope with stigma.