Enhanced systemic transgene expression after nonviral salivary gland transfection using a novel endonuclease inhibitor/DNA formulation.

Gene transfer to the major salivary glands is an attractive method for the systemic delivery of therapeutic proteins. To date, nonviral gene transfer to these glands has resulted in inadequate systemic protein concentrations. We believe that identification of the barriers responsible for this inefficient transfection will enable the development of enhanced nonviral gene transfer in salivary glands and other tissues.

The effect of IM ketorolac tromethamine on bleeding time: a prospective, interventional, controlled study.

Opiates, although effective analgesics, have significant adverse side effects. Ketorolac, the only parental nonsteroidal antiinflammatory drug available for use in the United States does not cause significant respiratory depression or hypotension, but it is a reversible inhibitor of platelet aggregation with a theoretical increased bleeding risk, which limits its use. The objective of this study was to determine the effect of a single intramuscular dose of 60 mg ketorolac on 4-hour bleeding times in healthy volunteers.

Hepatitis A booster vaccination: is there a need?

Hepatitis A is one of the most common vaccine-preventable infectious diseases in the world. Effective vaccines against hepatitis A have been available since 1992, and they provide long-term immunity against the infection. However, there is no worldwide consensus on how long protection will last or whether there will be a need for hepatitis A virus (HAV) booster vaccinations in the future.

The Gene Pill and its therapeutic applications.

Gene delivery represents a revolutionary therapeutic approach with the potential for sustained protein production by the human body, leading to a convenient and effective method for systemic delivery of protein drugs. In this review, advantages of an orally administered DNA formulation, Gene Pill, are presented. Unlike previously described DNA delivery approaches, the Gene Pill enables DNA delivery in a non-invasive manner, leading to the secretion of therapeutic proteins into a patient's blood, supplanting the need for injection of therapeutic protein products.

Peptide nucleic acids targeted to the amyloid precursor protein.

The depositing in brain of amyloid beta peptide (Abeta), which is formed by the cleavage of amyloid precursor protein (APP), is likely an etiologic factor in Alzheimer's disease (AD). Of the different forms of Abeta, Abeta(1-42) causes fibril formation and increases aggregation at elevated levels, which can lead to neuronal death. It is hypothesized that if the levels of Abeta, particularly Abeta(1-42), were reduced, then the onset of AD would be slowed or possibly prevented.

Selective tolerance to the hypothermic and anticataleptic effects of a neurotensin analog that crosses the blood-brain barrier.

NT69L, a neurotensin analog that crosses the blood-brain barrier, reduces body temperature, reverses apomorphine-induced climbing, haloperidol-induced catalepsy, and D-amphetamine- and cocaine-induced locomotor activity in rats. In this study we tested the development of tolerance to these effects of NT69L in rats. The blockade of apomorphine-induced climbing behavior and D-amphetamine- and cocaine-induced hyperactivity seen after a single acute injection did not show significant change with repeated daily injections of NT69L.

The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections.

Background: The relationship between previous antimicrobial treatments and infection with drug-resistant Helicobacter pylori is unknown.

Objectives: To determine whether previous use of antimicrobial agents predicts subsequent antibiotic resistance of H. pylori and whether resistance affects treatment outcome.

Neurotensin analog NT77 induces regulated hypothermia in the rat.

The potential use of hypothermia as a therapeutic treatment for stroke and other pathological insults has prompted the search for drugs that can lower core temperature. Ideally, a drug is needed that reduces the set-point for control of core temperature (T(c)) and thereby induces a regulated reduction in T(c). To this end, a neurotensin analog (NT77) that crosses the blood brain barrier and induces hypothermia was assessed for its effects on the set-point for temperature regulation in the Sprague-Dawley rat by measuring behavioral and autonomic thermoregulatory responses.

Comparison of different HCV viral load and genotyping assays.

Background: We report an interlaboratory comparison of methods for the determination of hepatitis C virus (HCV) serum load and genotype between a recently, established molecular laboratory at the Alaska Native Medical Center (ANMC) and two independent laboratories using different assays. At ANMC, a Real-time quantitative RT-PCR amplification methodology (QPCR) has been developed in which HCV viral loads are determined by interpolation of QPCR results to those of standards calibrated to the World Health Organization (WHO) First International Standard for HCV. HCV genotype is subsequently determined by direct sequencing of the DNA fragment generated from the QPCR assay.

Hepatitis A vaccine: immunogenicity following administration of a delayed immunization schedule in infants, children and adults.

Current immunization schedules for hepatitis A vaccine specify administration of a booster within 6-12 or 6-18 months of the primary dose. However, there may be circumstances that disrupt this schedule and the efficacy of administering a booster beyond the recommended time is a practical concern for healthcare providers. In this study, a booster was administered to 268 participants (137: <18 years old), an average of 27 months (range 20-31) after the primary dose.

Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers.

Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration.

Innovations in gastro-intestinal endoscopy: endoscopic antireflux therapies for gastro-oesophageal reflux disease.

Background: Gastro-oesophageal reflux disease (GORD) is a common disorder which significantly impairs the quality of life. Recently a number of endoscopic antireflux procedures have been described, with a view to the management of GORD, thus obviating the need for long-term proton pump inhibitors and the cost and potential risk of laparoscopic Nissen fundoplication.

Aim: To evaluate the status of new techniques using gastro-intestinal endoscopy for the management of GORD.

Balancing tissue perfusion demands: cardiovascular dynamics of Cancer magister during exposure to low salinity and hypoxia.

Decapod crustaceans inhabit aquatic environments that are frequently subjected to changes in salinity and oxygen content. The physiological responses of decapod crustaceans to either salinity or hypoxia are well documented; however, there are many fewer reports on the physiological responses during exposure to these parameters in combination. We investigated the effects of simultaneous and sequential combinations of low salinity and hypoxia on the cardiovascular physiology of the Dungeness crab, Cancer magister.

Endocinch therapy for gastro-oesophageal reflux disease: a one year prospective follow up.

Background: Gastro-oesophageal reflux disease (GORD) is, in the main, treated with either proton pump inhibitor (PPI) drugs or a Nissen fundoplication operation. Recently, BARD developed Endocinch, a device used to place sutures just below the oesophagogastric junction (OGJ) to treat GORD.

Aim: To evaluate the long term benefit of the Endocinch technique in patients seen up to 12 months post procedure.

Slaving: solvent fluctuations dominate protein dynamics and functions.

Protein motions are essential for function. Comparing protein processes with the dielectric fluctuations of the surrounding solvent shows that they fall into two classes: nonslaved and slaved. Nonslaved processes are independent of the solvent motions; their rates are determined by the protein conformation and vibrational dynamics.

A change of heart: cardiovascular development in the shrimp Metapenaeus ensis.

The larval development of penaeid shrimp is among the most complicated in crustaceans. In Metapenaeus ensis, there are six naupliar, three protozoeal and three mysid larval instars, followed by postlarval development. Irregular heartbeat begins late in naupliar instar 6.

Impact of recurrent epidemics of hepatitis a virus infection on population immunity levels: Bristol Bay, Alaska.

The dynamics of population-based immunity were examined by using serologic surveys of 7 villages in rural Alaska between 2 epidemics of hepatitis A virus (HAV) and after the second epidemic (1988-1990). Among persons aged 2-30 years, the overall age-adjusted prevalence of antibody to HAV (anti-HAV) was 51% in 1983 and 49% in 1993 (P=.506).

Time-limited psychotherapy in the community mental health team.

A community mental health team is offering clients short-term focal psychotherapy in the local area. Many clients find the team's base easier to attend than a central unit, and, with good communication and co-operation from other health-care professionals, the relevant clinical nurse specialist is able to make good progress, as indicated by the case study described here.