Publications

OBJECTIVE

Progressive familial intrahepatic cholestasis type 1 (PFIC1) is a rare, autosomal, recessive, inherited disease resulting from mutations in the ATP8B1 gene which is expressed at high levels in the small intestine and pancreas and at lower levels in the liver. Given this expression pattern, patients might be expected to have a pancreatic phenotype. Although pancreatitis and steatorrhea have been reported in patients with PFIC1, the available data on pancreatic function are not fully convincing. Therefore, the objective of this study was to assess exocrine pancreatic function in patients with PFIC1.

MATERIAL AND METHODS

Three subjects with a diagnosis of PFIC1 were included in the study. The diagnosis was confirmed by molecular analysis of ATP8B1. Prior to surgical treatment (biliary diversion), two patients had steatorrhea and in the third patient, a borderline value for fecal fat excretion was documented. In one patient, liver transplantation also was subsequently performed. Exocrine pancreatic secretion was assessed by the use of fecal elastase-1 and chymotrypsin tests. Fecal lipase concentrations were determined in order to exclude isolated lipase deficiency. Other typical diagnostic procedures were performed annually.

RESULTS

The results of the fecal tests were within the normal range. None of the three patients experienced any episodes that could be related to acute or chronic pancreatitis. Laboratory tests including serum amylase and lipase tests were always normal. Abdominal ultrasonography findings did not show any pancreatic pathology.

CONCLUSIONS

Pancreatic secretion in the study patients with progressive familial intrahepatic cholestasis type 1 was normal. The observed steatorrhea was not related to pancreatic insufficiency.

The worldwide epidemic of HIV continues to expand in many regions of the world, particularly in southern Africa, South and Southeast Asia, East Asia and Eastern Europe and Central Asia. Estimates are that at the end of 2005 there were 38.6 million persons living with HIV infection and that 4.1 million new infections and 2.8 million deaths from HIV occurred during the year. Regionally different patterns predominate from generalized heterosexual epidemics in sub-Saharan Africa and parts of the Caribbean to mixes of epidemics in which transmission among injection drug users, their sexual partners, commercial sex workers and their partners intersect. Multilateral and bilateral antiretroviral access campaigns, such as the World Health Organization's 3 x 5 initiative, have resulted in broader access to live-saving therapy for infected persons in low- and middle-income countries, but several million infected people who are clinically eligible for antiretroviral therapy remain untreated. The public health challenge worldwide is to keep the uninfected and to treat and care for those who have already been infected.

OBJECTIVES

To determine the effects of aging on the toxicity of sidestream tobacco smoke, the complex chemical mixture that enters the air from the lit end of burning cigarettes and constitutes the vast bulk of secondhand smoke.

DESIGN

Statistical analysis of data from controlled experimental exposures of Sprague Dawley rats to fresh and aged (for more than 30 minutes) sidestream smoke for up to 90 days followed by histological sectioning of the respiratory epithelium. The data were obtained from a series of experiments conducted at Philip Morris' formerly secret INBIFO (Institut für Biologische Forschung) laboratory in Germany.

RESULTS

Using total particulate material as the measure of smoke exposure, aging sidestream cigarette smoke for at least 30 minutes increases its toxicity fourfold for 21 day exposures and doubles the toxicity for 90 day exposures, relative to fresh sidestream smoke.

CONCLUSIONS

These results help explain the relatively large biological effects of secondhand smoke compared to equivalent mass doses of mainstream smoke.

OBJECTIVE

An enhanced stress and coping model was used to explain depression among HIV-positive women in healthcare and community settings where highly active anti-retroviral treatment (HAART) was commonplace.

METHOD

HIV-infected women in four cities (N=978) were assessed, cross-sectionally, for mental and physical health, stress, social support, and other background factors.

RESULTS

Self-reported level of depressive symptomatology was high. Number of physical symptoms, illness intrusiveness, and perceived stress were positively associated with depressed mood, while coping self-efficacy and social support were negatively associated. Stress mediated the effect of health status on depression and coping self-efficacy mediated the effect of psychosocial resources on depression. Our enhanced stress and coping model accounted for 52% of variance in depressive symtpomatology.

CONCLUSIONS

Interventions focused on improving coping self-efficacy, bolstering social supports, and decreasing stress in the lives of HIV-positive women may help to reduce the negative effects of HIV disease on mood.

OBJECTIVES

To analyze the trend of dextromethorphan abuse in California and to compare these findings with national trends.

DESIGN

A 6-year retrospective review.

SETTING

California Poison Control System (CPCS), American Association of Poison Control Centers (AAPCC), and Drug Abuse Warning Network (DAWN) databases from January 1, 1999, to December 31, 2004.

PARTICIPANTS

All dextromethorphan abuse cases reported to the CPCS, AAPCC, and DAWN. The main exposures of dextromethorphan abuse cases included date of exposure, age, acute vs long-term use, coingestants, product formulation, and clinical outcome. Main Outcome Measure The annual proportion of dextromethorphan abuse cases among all exposures reported to the CPCS, AAPCC, and DAWN databases.

RESULTS

A total of 1382 CPCS cases were included in the study. A 10-fold increase in CPCS dextromethorphan abuse cases from 1999 (0.23 cases per 1000 calls) to 2004 (2.15 cases per 1000 calls) (odds ratio, 1.48; 95% confidence interval, 1.43-1.54) was identified. Of all CPCS dextromethorphan abuse cases, 74.5% were aged 9 to 17 years; the frequency of cases among this age group increased more than 15-fold during the study (from 0.11 to 1.68 cases per 1000 calls). Similar trends were seen in the AAPCC and DAWN databases. The highest frequency of dextromethorphan abuse occurred among adolescents aged 15 and 16 years. The most commonly abused product was Coricidin HBP Cough & Cold Tablets.

CONCLUSIONS

Our study revealed an increasing trend of dextromethorphan abuse cases reported to the CPCS that is paralleled nationally as reported to the AAPCC and DAWN. This increase was most evident in the adolescent population.

Pulmonary emphysema results from the loss of intricate alveolar architecture and progressive simplification of small and highly effective gas-exchanging units into large, inefficient cyst-like spaces. Because of the loss of alveolar gas-exchanging units and the capillary bed within them, blood oxygen levels eventually fall and pressures within the pulmonary circulation rise. Recent insights from genetically manipulated mouse models have refined our understanding of the molecular events that prevent or promote the development of pulmonary emphysema. Capitalizing on an improved molecular understanding of emphysema with improved therapeutics has the potential to enhance both the survival and quality of life of patients with this common lung disease.

For patients with acute lung injury, positive pressure mechanical ventilation is life saving. However, considerable experimental and clinical data have demonstrated that how clinicians set the tidal volume, positive end-expiratory pressure, and plateau airway pressure influences lung injury severity and patient outcomes including mortality. In order to better identify ventilator-associated lung injury (VALI), clinical investigators have sought to measure blood-borne and airspace biological markers of VALI. At the same time, several laboratory-based studies have focused on biological markers of inflammation and organ injury in experimental models in order to clarify the mechanisms of ventilator-induced lung injury (VILI) and VALI. This review summarizes data on biological markers of VALI and VILI from both clinical and experimental studies with an emphasis on markers identified in patients and in the experimental setting. This analysis suggests that measurement of some of these biological markers may be of value in diagnosing VALI and in understanding its pathogenesis.

UNLABELLED

Although mechanical hyperalgesia associated with medical procedures is the major source of severe pain in burn-injured patients, little is known about its underlying mechanism. One reason for this has been the lack of a model for mechanical hyperalgesia at the site of injury. We have modified an established partial-thickness burn model in the rat to produce long-lasting primary mechanical hyperalgesia, which is present from the first measurement at 0.5 h, reaches a maximum at 3 days, and is still significant after 7 days. Because nerve growth factor (NGF), which is elevated in burn-injured tissue, produces mechanical hyperalgesia and activates protein kinase C (PKC)-epsilon, a key mediator in inflammatory and neuropathic pain, we used this model to evaluate the role of the NGF receptor, tyrosine-receptor kinase A (TrkA), and PKC-epsilon in burn-induced primary mechanical hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides to TrkA and PKC-epsilon, starting 3 days before inducing a burn injury, caused dose-related decrease of burn-induced primary mechanical hyperalgesia. In addition, intradermal injection of a PKC-epsilon-selective inhibitor eliminated hyperalgesia. Our model provides a method to elucidate the underlying mechanism of burn-injury pain as well as to screen for targets for novel analgesic treatments of this important clinical condition.

PERSPECTIVE

This manuscript presents the first model of thermal injury-induced mechanical hyperalgesia which mimics prolonged duration of clinical burn injury pain. We also perform proof of concept experiments demonstrating that our model provides a method to elucidate the mechanism of this important clinical condition.