Enumeration in Alzheimer's disease and other late life psychiatric syndromes

Previous studies suggest that visual enumeration is spared in normal aging but impaired in abnormal aging (late stage Alzheimer's disease, AD), raising the task's potential as a marker of dementia. Experiment 1 compared speeded enumeration of 1-9 random dots in early stage AD, vascular dementia (VAD), depression, and age-matched controls. Previous deficits were replicated but they were not specific to AD, with the rate of counting larger numerosities similarly slowed relative to controls by both AD and VAD. Determination of subitizing span was complicated by the surprisingly slower enumeration of one than of two items, especially in AD patients. Experiment 2 showed that AD patients' relative difficulty with one item persisted with further practice and extended to the enumeration of targets among distractors. However, it was abolished when pattern recognition was possible (enumerating dots on a die). Although an enumeration test is unlikely to help differentiate early AD from other common dementias, the unexpected pattern of patients' performance challenges current models of enumeration and requires further investigation.     

Estimating the incidence of first unprovoked seizure and newly diagnosed epilepsy in the low-income urban community of Northern Manhattan, New York City

Purpose : To estimate the incidence and mortality associated with first unprovoked seizure or newly diagnosed epilepsy in a low-income, predominantly Hispanic community in Northern Manhattan, New York City.
Methods : We performed a population-based study to determine the incidence of first unprovoked seizure or newly diagnosed epilepsy. Participants were Northern Manhattan residents seen at area hospitals and nursing homes between 2003 and 2005. Cumulative probability of mortality and standardized mortality ratios (SMRs) were also calculated.
Results : Among 209 incident cases identified, 123 (58.9%) presented with an incident single unprovoked seizure. A total of 138 (66.0%) participants were Hispanic and 94 (45.0%) had a median household income under $15,000/year. The overall age and sex-adjusted incidence of all unprovoked seizures was 41.1 (95%CI = 35.4–46.8) per 100,000 person-years. Higher incidence was observed in low-income groups. Incidence among Hispanics was similar to that of non-Hispanic whites and non-Hispanic blacks. The cumulative probability of mortality was 17% (95%CI = 12–24%) by 3 years after diagnosis and was significantly greater in females and in those with an identified etiology. SMRs were significantly increased for all groups with respect to age, Hispanic ethnicity, middle and high income, partial seizure type, and remote symptomatic etiology. Idiopathic/cryptogenic and progressive symptomatic etiologies, low income, gender, and non-Hispanic ethnicity were not associated with a significantly increased SMR.
Conclusion : Incidence of first unprovoked seizure or newly diagnosed epilepsy did not differ by race-ethnicity. Although lower income was associated with higher incidence, higher income was associated with an increased SMR. Future research should examine reasons for differential incidence by income.     

Noise pollution on an acute surgical ward

INTRODUCTION

This study was undertaken to measure and analyse noise levels over a 24-h period on five general surgical wards.

PATIENTS AND METHODS

Noise levels were measured on three wards with four bays of six beds each (wards A, B and C), one ward of side-rooms only (ward D) and a surgical high dependency unit (ward E) of eight beds. Noise levels were measured for 15 min at 4-hourly intervals over a period of 24 h midweek. The maximum sound pressure level, baseline sound pressure level and the equivalent continuous level (LEq) were recorded. Peak levels and LEq were compared with World Health Organization (WHO) guidelines for community noise. Control measurements were taken elsewhere in the hospital and at a variety of public places for comparison.

RESULTS

The highest peak noise level recorded was 95.6 dB on ward E, a level comparable to a heavy truck. This exceeded all control peak readings except that recorded at the bus stop. Peak readings frequently exceeded 80 dB during the day on all wards. Each ward had at least one measurement which exceeded the peak sound level of 82.5 dB recorded in the supermarket. The highest peak measurements on wards A, B, C and E also exceeded peak readings at the hospital main entrance (83.4 dB) and coffee shop (83.4 dB). Ward E had the highest mean peak reading during the day and at night – 83.45 dB and 81.0 dB, respectively. Ward D, the ward of side-rooms, had the lowest day-time mean LEq (55.9 dB). Analysis of the LEq results showed that readings on ward E were significantly higher than readings on wards A, B and C as a group (P = 0.001). LEq readings on ward E were also significantly higher than readings on ward D (P < 0.001). Day and night levels differ significantly, but least so on the high dependency unit.

CONCLUSIONS

The WHO guidelines state that noise levels on wards should not exceed 30 dB LEq (day and night) and that peak noise levels at night should not exceed 40 dB. Our results exceed these guidelines at all times. It is likely that these findings will translate to other hospitals. Urgent measures are needed to rectify this.     

Percutaneous fluoroscopically guided placement of peritoneal dialysis catheters--a 10-year experience

Peritoneal dialysis (PD) catheters maybe inserted surgically or percutaneously. Since 1997, 209 patients in our unit have had a PD catheter inserted percutaneously with fluoroscopic guidance. Data on all these PD catheters were collected prospectively on a PROTON computer database. 5/209 (2.4%) insertion attempts were abandoned. 204 catheters were successfully placed giving an initial technical success of 97.6%. 200/204 catheters were used for dialysis. 13/200 (6.5%) catheters developed early exit site infections; 12/13 were successfully treated and dialysis proceeded uneventfully. 3/200 (1.5%) catheters developed early peritonitis; 1/3 was removed as antibiotic treatment was unsuccessful. 10/200 (5%) catheters developed an early leak; 2/10 did not resolve with conservative therapy and were removed. 14/200 (7%) catheters did not allow sufficient fluid entry for PD; all 14 had migrated out of the pelvis and were removed. In total, 18/200 (9%) catheters were removed in the first 2 months due to these early complications. The remaining 182/200 (91%) were fully functional for PD. Technical survival (excluding patient death with a functioning catheter and successful kidney transplantation) at 1, 2, and 5 years was 77%, 61%, and 31%, respectively. Our 10 year experience of PD catheters inserted percutaneously with fluoroscopic guidance demonstrates a high technical success and a low complication rate. The data presented may be used as the standard for this technique.     

Therapeutic potential of neuronal two-pore domain potassium-channel modulators

Two-pore domain potassium (K2P) channels are expressed in cells throughout the body and give rise to leak potassium currents which control the excitability of these cells. Although not inhibited by classical potassium channel-blocking drugs, such as tetraethylammonium and 4-aminopyridine, K2P channels are regulated by a diverse array of pharmacological mediators. There are six main families of K2P channels and among these certain members of the TREK family (ie, TREK-1 and TREK-2) are activated by general anesthetic agents such as halothane, xenon and nitrous oxide. In addition, all members of the TREK familyare activated by neuroprotective agents, such as riluzole, polyunsaturated fatty acids and lysophospholipids, suggesting that these channels play an important role in neuroprotection. TREK channels are also inhibited by chlorpromazine, local anesthetics and the antidepressant fluoxetine. Furthermore, all members of the TASK family are inhibited by cannabinoids and local anesthetics, and TASK-3 is selectively inhibited by ruthenium red. Thus, the diversity and physiological importance of K2P channels suggest that the development of selective compounds to target these proteins has therapeutic potential for CNS disorders such as stroke, depression and epilepsy.     

Immunotoxicity of trenbolone acetate in Japanese quail

Trenbolone acetate is a synthetic androgen that is currently used as a growth promoter in many meat-exporting countries. Despite industry laboratories classifying trenbolone as nonteratogenic, data showed that embryonic exposure to this androgenic chemical altered development of the immune system in Japanese quail. Trenbolone is lipophilic, persistent, and released into the environment in manure used as soil fertilizer. This is the first study to date to assess this chemical's immunotoxic effects in an avian species. A one-time injection of trenbolone into yolks was administered to mimic maternal deposition, and subsequent effects on the development and function of the immune system were determined in chicks and adults. Development of the bursa of Fabricius, an organ responsible for development of the humoral arm of the immune system, was disrupted, as indicated by lower masse, and smaller and fewer follicles at day 1 of hatch. Morphological differences in the bursas persisted in adults, although no differences in either two measures of immune function were observed. Total numbers of circulating leukocytes were reduced and heterophil-lymphocyte ratios were elevated in chicks but not adults. This study shows that trenbolone acetate is teratogenic and immunotoxic in Japanese quail, and provides evidence that the quail immune system may be fairly resilient to embryonic endocrine-disrupting chemical-induced alterations following no further exposure posthatch.     

Adverse drug reactions in hospitals: a narrative review

The serious nature of adverse drug reactions (ADRs) has been highlighted in a number of instances over the last forty years, the most recent of these being the occurrence of serious thrombotic events with the use of COX-2 inhibitors. ADRs are estimated to be between the 4(th) and 6(th) leading cause of death in the USA, with fatal ADRs occurring in 0.32% of patients. A recent UK study showed that 6.5% of hospital admissions were related to ADRs. ADRs can therefore be regarded as a significant public health and economic problem. There is an urgent need to develop better preventive strategies to reduce the burden of ADRs. Because ADRs can affect any bodily system, can have many different clinical presentations, and are of widely variable severity, prevention will not be easy and will have to be multifactorial in its approach. This paper reviews the epidemiology of ADRs in hospitals and evaluates the research that has been undertaken to date to prevent ADRs.     

Changes in breast cancer transcriptional profiles after treatment with the aromatase inhibitor, letrozole

OBJECTIVE: The aim of the study was to identify changes in tumour expression profiling associated with short-term therapy of breast cancer patients with letrozole. EXPERIMENTAL DESIGN: Microarray analysis was performed on RNA extracted from paired tumour core biopsies taken before and after 14 days of treatment with letrozole (2.5 mg/daily) in 58 patients. Changes in expression profile were identified by three different approaches on the basis of frequency of changes, magnitude of changes and significance analysis of microarray. RESULTS: No single gene was consistently changed by therapy in all cases. Fifty-two genes, however, were downregulated and 36 upregulated in at least 45 of the 58 cases. In terms of quantitative change, 46 genes showed at least a median 1.5-fold change in expression. Significance analysis of microarray identified 62 genes that were significantly changed by therapy (P<0.0001, 56 downregulated and six upregulated). All three approaches showed that greater numbers of genes were downregulated rather than upregulated. Merging data produced a total of 143 genes, which were subject to gene ontology and cluster analysis. The ontology of the 91 downregulated genes showed that they were functionally associated with cell cycle progression, particularly mitosis. In contrast, upregulated genes were associated with organ development, connective tissue extracellular matrix regulation and inflammatory response. Cluster analysis segregated the patients into four groups differing in patterns of gene expression. CONCLUSION: Genes have been identified which either change markedly or consistently in breast cancer after 14 days treatment with letrozole. These are new important data in understanding letrozole's molecular mechanism of action in breast cancers.     

Should We Add Clonidine to Local Anesthetic for Peripheral Nerve Blockade? A Qualitative Systematic Review of the Literature

BACKGROUND AND OBJECTIVES: Although clonidine has been shown to prolong analgesia in central neuraxial blocks, its use in peripheral nerve blocks remains controversial. We performed a systematic review of the current literature to determine the benefit of adding clonidine to peripheral nerve blocks. METHODS: A systematic, qualitative review of double-blind randomized controlled trials on the benefit of clonidine as an adjunct to peripheral nerve block was performed. Studies were identified by searching PubMed (www.ncbi.nlm.nih.gov/entrez) and EMBASE (www.embase.com) databases (July 1991 to October 2006) for terms related to clonidine as an adjunct to peripheral nerve blocks. Studies were classified as supportive if the use of clonidine demonstrated reduced pain and total analgesic consumption, or prolonged block duration versus negative if no difference was found. RESULTS: Twenty-seven studies were identified that met the inclusion criteria. Five studies included a systemic control group. The total number of patients reviewed was 1,385. The dose of clonidine varied from 30 to 300 mug. Overall 15 studies supported the use of clonidine as an adjunct to peripheral nerve blocks with 12 studies failing to show a benefit. Based on qualitative analysis, clonidine appeared to prolong analgesia when added to intermediate-acting local anesthetics for axillary and peribulbar blocks. CONCLUSIONS: Clonidine improves duration of analgesia and anesthesia when used as an adjunct to intermediate-acting local anesthetics for some peripheral nerve blocks. Side-effects appear to be limited at doses up to 150 mug. Evidence is lacking for the use of clonidine as an adjunct to local anesthetics for continuous catheter techniques. Further research is required to examine the peripheral analgesic mechanism of clonidine.     

Mechanistic influences for mutation induction curves after exposure to DNA-reactive carcinogens

A mechanistic understanding of carcinogenic genotoxicity is necessary to determine consequences of chemical exposure on human populations and improve health risk assessments. Currently, linear dose-responses are assumed for DNA reactive compounds, ignoring cytoprotective processes that may limit permanent damage. To investigate the biological significance of low-dose exposures, human lymphoblastoid cells were treated with alkylating agents that have different mechanisms of action and DNA targets: methylmethane sulfonate (MMS), methylnitrosourea (MNU), ethylmethane sulfonate (EMS), and ethylnitrosourea (ENU). Chromosomal damage and point mutations were quantified with the micronucleus and hypoxanthine phosphoribosyltransferase forward mutation assays. MNU and ENU showed linear dose-responses, whereas MMS and EMS had nonlinear curves containing a range of nonmutagenic low doses. The lowest observed effect level for induction of chromosomal aberrations was 0.85 microg/mL MMS and 1.40 microg/mL EMS; point mutations required 1.25 microg/mL MMS and 1.40 microg/mL EMS before a mutagenic effect was detected. This nonlinearity could be due to homeostatic maintenance by DNA repair, which is efficient at low doses of compounds that primarily alkylate N(7)-G and rarely attack O atoms. A pragmatic threshold for carcinogenicity may therefore exist for such genotoxins.