Saturation prostate biopsy with periprostatic block can be performed in office

PURPOSE: Recent reports of saturation prostate biopsy performed in the operating room with the patient under anesthesia have shown increased cancer detection rates over repeat office based prostate biopsy. We report equivalent success and tolerability of saturation biopsy in the office using local anesthesia. MATERIALS AND METHODS: We performed 24 core saturation prostate biopsies in 15 patients using periprostatic local anesthesia. Before biopsy 20 cc 2% lidocaine (10 cc per side) were injected under ultrasound guidance into the periprostatic nerve entry into the prostate bilaterally. After measurements were made a random 24 core prostate biopsy was performed using a spring loaded biopsy gun. Pain was determined using a visual analog scale to assess tolerability. RESULTS: Complete 24 core biopsies were successful and well tolerated in all 15 patients. Cancer detected in 5 patients (33%) was clinical stage T1C. Mean prostate specific antigen before biopsy was 11.2 ng./dl. (range 5 to 24.1). The indication for biopsy was elevated prostate specific antigen after a previous normal biopsy in 12 patients. In 2 patients prostatic intraepithelial neoplasia was noted on a previous biopsy and in 1 previous atypia was identified on biopsy. The mean visual analog scale pain score was 0.7 (range 0 to 3). Prolonged minor hematuria greater than 5 days in duration occurred in 3 cases requiring no intervention. No other complications occurred. Nerve sparing was not more difficult in the single patient who underwent radical prostatectomy. CONCLUSIONS: Saturation prostate biopsy is well tolerated in the office setting with the patient under local anesthesia. The additional risk, time and cost of performing these procedures in the operating room using anesthesia may be safely avoided.     

An analysis of multiple staging management strategies for carcinoma of the esophagus: computed tomography,endoscopic ultrasound,positron emission tomography,and thoracoscopy/laparoscopy

BACKGROUND: This study compares the health care costs and effectiveness of multiple staging options for patients with esophageal cancer. Techniques studied included computed tomographic (CT) scan, endoscopic ultrasound with fine-needle aspiration biopsy (EUS-FNA), positron emission tomography (PET), thoracoscopy/laparoscopy, and combinations of these. METHODS: A decision-analysis model was constructed to compare different staging strategies. Costs were derived from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases and from other Medicare reimbursement rates. Life expectancies were obtained from the 1973-1996 SEER database and adjusted for quality of life. Cost and effectiveness measures were discounted at 0% and 3% per year. Sensitivity and specificity measures were obtained from the published literature and a parallel prospective clinical trial, and all key variables were subjected to sensitivity analyses. RESULTS: Under baseline assumptions, CT + EUS-FNA was the most inexpensive strategy and offered more quality-adjusted life-years, on average, than all other strategies with the exception of PET + EUS-FNA. The latter was slightly more effective but also more expensive. The marginal cost-effectiveness ratio for PET + EUS-FNA was $60,544 per quality-adjusted life-year. These findings were robust and changed very little in all of the sensitivity analyses. CONCLUSIONS: The combination of PET + EUS-FNA should be the recommended staging procedure for patients with esophageal cancer, unless resources are scarce or PET is unavailable. In these instances, CT + EUS-FNA can be considered the preferred strategy.     

Linkage and association with type 1 diabetes on chromosome 1q42

Type 1 diabetes is a complex disorder with multiple genetic loci and environmental factors contributing to disease etiology. In the current study, a human type 1 diabetes candidate region on chromosome 1q42 was mapped at high marker density in a panel of 616 multiplex type 1 diabetic families. To facilitate the identification and evaluation of candidate genes, a physical map of the 7-cM region surrounding the maximum logarithm of odds (LOD) score (2.46, P = 0.0004) was constructed. Genes were identified in the 500-kb region surrounding the marker yielding the peak LOD score and evaluated for polymorphism by resequencing. Single-nucleotide polymorphisms (SNPs) identified in these genes as well as other anonymous markers were tested for allelic association with type 1 diabetes by both family-based and case-control methods. A haplotype formed by common alleles at three adjacent markers (D1S225, D1S2383, and D1S251) was preferentially transmitted to affected offspring in type 1 diabetic families (nominal P = 0.006). These findings extend the evidence supporting the existence of a type 1 diabetes susceptibility locus on chromosome 1q42 and identify a candidate region amenable to positional cloning efforts.     

Environmental air toxics: role in asthma occurrence?

The National Urban Air Toxics Research Center (NUATRC) hosted its first scientific workshop in 1994 that focused on possible relationships between air toxics and asthma. From that meeting came recommendations for future research including a need for more complete individual personal exposure assessments so that determinations of personal exposures to pollutants could be made. In the spring of 2001, NUATRC held a second such workshop to review progress made in this area during the intervening 7 years. Peer-reviewed articles from the workshop are published in this issue of (italic)Environmental Health Perspectives Supplements(/italic). As in 1994, academic, government, and industry scientists participated. Dave Guinnup of the Environmental Protection Agency discussed the nature of air toxics, their definition, and the basis for federal regulation. George Leikauf from the University of Cincinnati reviewed the 1994 workshop and subsequent research in this field. Current research funded by NUATRC that is addressing individual personal exposure was presented by Clifford Weisel (Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey), Patrick Kinney (Columbia University) and Candis Claiborn (Washington State University). David Corry from Baylor College of Medicine highlighted new insights into asthma pathogenesis while Stephen Redd from the Centers for Disease Control presented an overview of asthma epidemiology as well as the societal costs of the disease. Mary White (Agency for Toxic Substances and Disease Registry) discussed recent epidemiologic investigations by public health agencies into community concerns about asthma and hazardous air pollutants. David Peden (University of North Carolina) reviewed scientific studies into the links between asthma and air toxics as well as criteria air pollutants. In a session on occupational asthma, Lee Petsonk (National Institute for Occupational Safety and Health) discussed risk factors for work-related asthma, whereas Ralph Delfino (University of California, Irvine) addressed limitations of extrapolating from occupational asthma to asthma in the general population. These presentations were followed by panel discussions focusing on future research programs, both for NUATRC and similar research institutions. Recommendations for future research included improved assessments of personal exposure to air toxics as well as research focused on specific hazardous air pollutants. The latter recommendation was based on medical literature that suggests certain pollutants from the list of 188 air toxics are most likely to adversely affect respiratory health.     

Seasonal variations in injury rates during US Army Basic Combat Training

OBJECTIVES: Previous literature suggests that injury rates during physical activity may be higher in the summer than in the fall or winter, possibly due to the greater amount or intensity of physical activity in the summer. This study examined seasonal differences in injury incidence during US Army Basic Combat Training, where physical activity was similar at all times of the year. METHODS: Four independent groups of subjects (total n = 1543 men and 1025 women) were investigated, two training in the summer and two training in the fall. Injury data were obtained from a retrospective review of the subjects' medical records at the conclusion of the 8 week training program. RESULTS: For men, the corrected relative risk of suffering an injury or a time loss injury in the summer was, respectively, 2.0 [95% confidence interval (CI) = 1.7-2.4] and 2.5 (95% CI = 1.9-3.0) times higher than in the fall. For women, the corrected relative risk of suffering an injury or time-loss injury in the summer was, respectively, 1.4 (95% CI = 1.3-1.6) and 1.7 (95% CI = 1.5-2.0) times higher than in the fall. These risks were essentially unchanged after adjustment for subject physical characteristics (age, stature, body mass, body mass index) and physical fitness (push-ups, sit-ups and 2 mile run), indicating that the summer season was an injury risk factor independent of these variables. Linear correlations (r-values) between maximal daily temperature and injury incidence ranged from 0.92 to 0.97, indicating a strong relationship between these two variables. CONCLUSIONS: These data suggest that injury incidence among physically active individuals is higher in the summer than in the fall and that environmental temperature may provide a partial explanation for this finding.     

Antibiotic use and upper respiratory infections: a survey of knowledge, attitudes, and experience in Wisconsin and Minnesota

BACKGROUND: Public attitudes and expectations contribute to inappropriate antibiotic prescribing and antibiotic resistance. This study assessed knowledge, attitudes, and experiences regarding antibiotic use for respiratory infection or illness. METHODS: Random-digit-dialing telephone surveys of adults and parents of children <5 years old were conducted in Wisconsin and Minnesota during 1999. RESULTS: The survey was completed by 405 adults and 275 parents of children <5 years old. The median age was 32 years for parents and 50 years for adults. Seven percent of parents and 17% of adults believed that antibiotics are never or almost never necessary for bronchitis. More than 70% in each group believed that antibiotics are needed for green or yellow nasal drainage, and nearly half of respondents believed that they knew whether an antibiotic was needed before seeing a physician. Exposure to multiple information sources on antibiotic resistance in the past 6 months was independently associated with a knowledge score greater than or equal to the median for nine questions. CONCLUSIONS: The general public has misconceptions regarding indications for antibiotic use, and this may contribute to inappropriate prescribing. Providing multiple and varied antibiotic-related informational messages may increase knowledge of appropriate antibiotic prescribing and decrease patient demand for antibiotics.     

Social phobia and the recall of autobiographical memories

Although cognitive theories of anxiety suggest that anxious individuals are characterized by the biased tendency to recall negative experiences with perceived threat, few empirical studies have confirmed this notion. To investigate personal memories associated with threatening experiences, individuals with socio phobia (n=16) and nonanxious individuals (n=17) completed an autobiographical memory-cueing procedure. Participants were presented with 15 social threat words and 15 neutral words, and they recorded the first specific memory that came to mind. Autobiographical memories were coded for specificity and affective tone. There were no group differences in the extent to which participants retrieved specific memories. A greater number of memories cued by social threat words were characterized by negative affect in the social phobia group than in the nonanxious group. However, examination of the means suggests that this effect was small and most likely not of practical significance. It is suggested that memory biases toward threat are not a prominent part of cognitive symptoms that characterize individuals with social phobia.     

Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology

In individuals with Alzheimer's disease (AD), there is a two-fold elevation in the serum concentrations of the gonadotropins, luteinizing hormone (LH), and follicle stimulating hormone compared to age-matched controls. Whether this plays a role in disease pathogenesis is unclear. Nonetheless, gonadotropins are known to cross the blood brain barrier and the highest density of gonadotropin receptors in the brain are found within the hippocampus. We report for the first time the localization of LH in the cytoplasm of pyramidal neurons. In addition, we find a significant increase in LH in the cytoplasm of pyramidal neurons and neurofibrillary tangles of AD brain compared to age-matched control brain. Whereas the functional consequences of increased neuronal LH are unknown, it is notable that LH is primarily localized to those neurons that are known to be vulnerable to Alzheimer's disease-related neurodegeneration. Elevated serum and cortical neuron levels of LH, coupled with the decline in sex steroid production, could play important roles in the pathogenesis of AD.     

Relationship between low-dose amphetamine-induced arousal and extracellular norepinephrine and dopamine levels within prefrontal cortex

Despite the well-known and potent arousal-enhancing effects of amphetamine (AMPH)-like stimulants, the neurobiological substrates of AMPH-induced arousal have rarely been examined explicitly. Available evidence suggests the possible participation of noradrenergic and/or dopaminergic systems in the arousal-enhancing actions of AMPH-like stimulants. The current studies examined the extent to which low-dose AMPH-induced increases in waking are related to AMPH-induced increases in extracellular norepinephrine (NE) and dopamine (DA) levels within the prefrontal cortex (PFC), as measured by in vivo microdialysis. Vehicle injections elicited brief epochs of waking. Vehicle-induced waking was closely associated with a brief and moderate (50% above baseline) increase in NE levels. DA levels were less sensitive to the arousing actions of vehicle injections, with maximal increases of approximately 25% above baseline observed. 0.15 mg/kg and 0.25 mg/kg AMPH increased time spent awake, which resulted primarily from increases in quiet waking. Although the magnitude of the waking response did not differ substantially between the two doses across time, a trend for a more rapid recovery to baseline waking levels was observed at the higher dose, possibly suggesting the development of a relatively rapid-onset tolerance to the wake-promoting actions of AMPH at this dose. At the 0.15 mg/kg dose, AMPH elicited maximum increases of approximately 175% and 125% above baseline levels for NE and DA, respectively. The time course of AMPH-induced increases in waking closely paralleled the time course of AMPH-induced increases in both NE and DA efflux. These observations are consistent with the hypothesis that both increased DA and NE efflux contribute to the low-dose behavioral effects of AMPH-like stimulants, including the arousal-enhancing actions of these drugs. Additionally, these observations also suggest a possibly greater sensitivity of NE efflux, relative to DA, to moderately arousing conditions including low-dose AMPH-like stimulant administration.     

RANTES stimulates inflammatory cascades and receptor modulation in murine astrocytes

Oligodendroglia and Schwann cells synthesize myelin-specific proteins and lipids for the assembly of the highly organized myelin membrane of the motor-sensory axons in the central (CNS) and peripheral nervous system (PNS), respectively, allowing rapid saltatory conduction. The isoforms of the main myelin proteins, the peripheral myelin basic isoproteins (MBP) and the integral proteolipid proteins, PLP and DM20, arise from alternative splicing. Activation of a cryptic splice site in exon III of plp leads to the deletion of 105 bp encoding the PLP-specific 35 amino acid residues within the cytosolic loop 3 of the four-transmembrane domain (TMD) integral membrane protein. To study the different proposed functions of DM20 during the development of oligodendrocytes and in myelination, we targeted the plp locus in embryonic stem cells by homologous recombination by a construct, which allows solely the expression of the DM20 specific exon III sequence. The resulting dm20(only) mouse line expresses exclusively DM20 isoprotein, which is functionally assembled into the membrane, forming a highly ordered and tightly compacted myelin sheath. The truncated cytosolic loop devoid of the PLP-specific 35 amino acid residues, including two thioester groups, had no impact on the periodicity of CNS myelin. In contrast to the PLP/DM20-deficient mouse, mutant CNS of dm20(only) mice showed no axonal swellings and neurodegeneration but a slow punctuated disintegration of the compact layers of the myelin sheath and a rare oligodendrocyte death developing with aging.