Gene therapy for Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder arising from loss of dopaminergic neurons in the substantia nigra pars compacta and subsequent depletion of striatal dopamine levels, which results in distressing motor symptoms. The current standard pharmacological treatment for PD is direct replacement of dopamine by treatment with its precursor, levodopa (L-dopa). However, this does not significantly alter disease progression and might contribute to the ongoing pathology.

Intrapartum assessment of fetal well-being: any role for a fetal admission test?

Objective: To determine whether the fetal admission test is predictive of intrapartum complications.

Methods: We studied the fetal heart rate tracings of women in spontaneous labor at 37-42 weeks' gestation from 1 November 2001 to 31 March 2002. The study population was subdivided based on reactivity defined as > or = 15 beats/min for > or = 15 s, reactivity redefined as > or = 10 beats/min for > or = 10 s, variability, presence of late and/or variable decelerations, and reassuring fetal admission test; and compared for various labor outcome variables.

Delirium and dehydration: some fluid for thought?

Delirium is a frequent complication of advanced cancer. It is characterized by cognitive deficits and behavioral disturbance, and therefore can potentially result in severe symptom distress and impeded communication between patient and family and between patient and medical staff. The reversibility of delirium depends on its underlying causes.

Delirium in patients with advanced cancer.

Managing delirium is of major importance in end-of-life care and frequently gives rise to controversies and to clinical and ethical dilemmas. These problems arise from a number of causes, including the sometimes-poor recognition or misdiagnosis of delirium despite its frequent occurrence. Delirium generates major symptomatic of distress for the patient, consequent stress for the patient's family, the potential to misinterpret delirium symptomatology, and behavioral management challenges for health care professionals.

Effect of liquid feeding weaned pigs on growth performance to harvest.

Four experiments were undertaken to examine the effect of feeding postweaning diets as dry pelleted feed, fresh liquid feed, acidified liquid feed, and fermented liquid feed on pig performance from weaning (26 d) to harvest. In Exp. 1 (n = 12 replicates) and 2 (n = 10 replicates), the treatments were 1) dry pelleted feed and 2) fresh liquid feed.

E-cadherin and the differentiation of mammalian vestibular hair cells.

E-cadherin is expressed in vestibular, mechanosensory epithelia during early embryonic development. During late embryonic and neonatal stages it is expressed in supporting cells but down-regulated in differentiating sensory hair cells. We used a conditionally immortal cell line (UB/UE-1) from the neonatal mouse utricle to test the hypothesis that constitutive expression of E-cadherin inhibits the progression of hair cell differentiation.

The panorama of opioid-related cognitive dysfunction in patients with cancer: a critical literature appraisal.

Background: Opioids have an essential role in the management of pain in cancer patients, particularly those with advanced disease. Cognitive dysfunction is a recognized complication of opioid use. However, misconceptions and controversy surround the nature and prevalence of its occurrence.

The impact of delirium on the circadian distribution of breakthrough analgesia in advanced cancer patients.

Most cancer patients will experience pain requiring opioid therapy during their illness. Standard opioid therapy includes fixed scheduled doses and so-called "rescue" doses for breakthrough pain. Circadian rhythms seem to influence the expression of pain and the responsiveness to analgesic medication.

Quantitative comparison of expression with adeno-associated virus (AAV-2) brain-specific gene cassettes.

This study compared a range of mammalian CNS expression cassettes in recombinant adeno-associated virus (AAV-2) vectors using strong endogenous promoter sequences, with or without a strong post-regulatory element and polyadenylation signal. Changes in these elements led to transgene expression varying by over three orders of magnitude. In experiments conducted in primary cell culture and in >100 stereotactically injected rats, we observed highly efficient and stable (>15 months) gene expression in neurons and limited expression in glia; the highest expression occurred with endogenous, nonviral promoters such as neuron-specific enolase and beta-actin.

Equianalgesic dose ratios for opioids. a critical review and proposals for long-term dosing.

Clinicians involved in the opioid pharmacotherapy of cancer-related pain should be acquainted with a variety of opioids and be skilled in the selection of doses when the type of opioid or route of administration needs changing. The optimal dose should avoid under-dosing or overdosing, both associated with negative outcomes for the patient. Although equianalgesic dose tables are generally used to determine the new doses in these circumstances, the evidence to support the ratios indicated in these tables largely refers to the context of single dose administration.

Electrogastrography: a non-invasive measurement of gastric function.

Background: Electrogastrography (EGG) is the non-invasive measurement of gastric electrical activity. With the development of modern technology, improved recording and automated analysis, it is a reliable and accurate technique for the measurement of gastric myoelectrical activity providing information about the frequency and regularity of the gastric slow wave.

Aim: The aim of this report is to evaluate its role in clinical practice.

The isolated hypertensive lower oesophageal sphincter: audit in a specialist unit.

The hypertensive lower oesophageal sphincter (HLOS) is a distinct clinical entity defined by a lower oesophageal sphincter (LOS) pressure > or = 30mmHg and normal LOS relaxation and oesophageal peristalsis. The clinical, physiological, and radiological details of 27 patients with HLOS diagnosed in a 3-year period were reviewed. The reasons for referral included: gastro-oesophageal reflux disease (GORD) (33%), dysphagia (18.

c-Jun promotes neurite outgrowth and survival in PC12 cells.

We investigated the function of c-Jun in PC12 cells by transfecting them with a plasmid containing a c-Jun cDNA transcription cassette. Transfected cells expressed high levels of c-Jun mRNA and protein and demonstrated an increase in both AP-1 DNA binding and gene activation. The c-Jun over-expressing cells showed marked neurite outgrowth but no evidence of spontaneous cell death.

Scleral remodeling during the development of and recovery from axial myopia in the tree shrew.

Purpose: Recent investigations have suggested that scleral thinning in mammalian eyes with axial myopia is a consequence of the loss of scleral tissue, rather than the redistribution of existing tissue as the eye enlarges. The present study investigated whether further changes in the distribution and metabolism of scleral tissue occur during the process of recovery from axial myopia. Scleral glycosaminoglycan (GAG) synthesis and content as well as scleral dry weight changes were monitored as indicators of remodeling in myopic and recovering tree shrew sclerae.

Clinical utility, factor analysis, and further validation of the memorial delirium assessment scale in patients with advanced cancer: Assessing delirium in advanced cancer.

Background: Delirium is a common neuropsychiatric complication in patients with advanced cancer. The Memorial Delirium Assessment Scale (MDAS) is a recently developed 10-item severity rating instrument. The purpose of the current prospective study was to further assess the clinical utility, factor structure, and validity of the MDAS in a relatively homogeneous population of patients with advanced cancer.

Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.

Context: Delirium impedes communication and contributes to symptom distress in patients with advanced cancer. There are few prospective data on the reversal of delirium in this population.

Objectives: To evaluate the occurrence, precipitating factors, and reversibility of delirium in patients with advanced cancer.

Symptoms are a poor indication of severity of reflux in Barrett's oesophagus.

AIMS: Patients with Barrett's oesophagus have increased acid and duodenogastric reflux and impaired motility compared with non-Barrett's patients with reflux disease. Impaired sensitivity to acid infusion and distension have also been described, but the relationship of this visceral response to symptoms is unclear. A symptom index was used to compare Barrett's and non-Barrett's patients with reflux.

An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy.

The brain is generally considered immunoprivileged, although increasing examples of immunological responses to brain antigens, neuronal expression of major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific brain protein, the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor. After peroral administration of the AAV vaccine, transgene expression persisted for at least 5 months and was associated with a robust humoral response in the absence of a significant cell-mediated response.

Differentiation of mammalian vestibular hair cells from conditionally immortal, postnatal supporting cells.

We provide evidence from a newly established, conditionally immortal cell line (UB/UE-1) that vestibular supporting cells from the mammalian inner ear can differentiate postnatally into more than one variant of hair cell. A clonal supporting cell line was established from pure utricular sensory epithelia of H2k(b)tsA58 transgenic mice 2 d after birth. Cell proliferation was dependent on conditional expression of the immortalizing gene, the "T" antigen from the SV40 virus.