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Showing papers by "University of Tennessee Health Science Center published in 2000"


Journal ArticleDOI
24 Mar 2000-Science
TL;DR: The nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome is determined using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map.
Abstract: The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

6,180 citations


Journal ArticleDOI
TL;DR: The results support the reliability and psychometric (as well as clinical) validity of the Female Sexual Function Index (FSFI) in the assessment of key dimensions of female sexual function in clinical and nonclinical samples and suggest important gender differences in the patterning of femaleSexual function in comparison with similar questionnaire studies in males.
Abstract: This article presents the development of a brief, self-report measure of female sexual function. Initial face validity testing of questionnaire items, identified by an expert panel, was followed by a study aimed at further refining the questionnaire. It was administered to 131 normal controls and 128 age-matched subjects with female sexual arousal disorder (FSAD) at five research centers. Based on clinical interpretations of a principal components analysis, a 6- domain structure was identified, which included desire, subjective arousal, lubrication, orgasm, satisfaction, and pain. Overall test-retest reliability coefficients were high for each of the individual domains (r=0.79 to 0.86) and a high degree of internal consistency was observed (Cronbach’s alpha values of 0.82 and higher) Good construct validity was demonstrated by highly significant mean difference scores between the FSAD and control groups for each of the domains (p<0.001). Additionally, divergent validity with a scale of marital satisfactio...

5,183 citations


Journal ArticleDOI
TL;DR: ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months' corrected age, and factors significantly associated with decreased morbidity included increased birth weight, female gender, higher maternal education, and white race.
Abstract: Objectives. The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401–1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes. Study Design. A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months9 corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome. Results. Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 ± 135 g, mean gestation (best obstetric dates) 26 ± 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index Conclusion. ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months9 corrected age.

1,117 citations


Journal ArticleDOI
TL;DR: The results show that the receptor-binding specificity of the HA is altered early after the transmission of an avian virus to humans and pigs and, therefore, may be a prerequisite for the highly effective replication and spread which characterize epidemic strains.
Abstract: Interspecies transmission of influenza A viruses circulating in wild aquatic birds occasionally results in influenza outbreaks in mammals, including humans. To identify early changes in the receptor binding properties of the avian virus hemagglutinin (HA) after interspecies transmission and to determine the amino acid substitutions responsible for these alterations, we studied the HAs of the initial isolates from the human pandemics of 1957 (H2N2) and 1968 (H3N2), the European swine epizootic of 1979 (H1N1), and the seal epizootic of 1992 (H3N3), all of which were caused by the introduction of avian virus HAs into these species. The viruses were assayed for their ability to bind the synthetic sialylglycopolymers 3'SL-PAA and 6'SLN-PAA, which contained, respectively, 3'-sialyllactose (the receptor determinant preferentially recognized by avian influenza viruses) and 6'-sialyl(N-acetyllactosamine) (the receptor determinant for human viruses). Avian and seal viruses bound 6'SLN-PAA very weakly, whereas the earliest available human and swine epidemic viruses bound this polymer with a higher affinity. For the H2 and H3 strains, a single mutation, 226Q-->L, increased binding to 6'SLN-PAA, while among H1 swine viruses, the 190E-->D and 225G-->E mutations in the HA appeared important for the increased affinity of the viruses for 6'SLN-PAA. Amino acid substitutions at positions 190 and 225 with respect to the avian virus consensus sequence are also present in H1 human viruses, including those that circulated in 1918, suggesting that substitutions at these positions are important for the generation of H1 human pandemic strains. These results show that the receptor-binding specificity of the HA is altered early after the transmission of an avian virus to humans and pigs and, therefore, may be a prerequisite for the highly effective replication and spread which characterize epidemic strains.

816 citations


Journal ArticleDOI

810 citations


Journal ArticleDOI
TL;DR: It is concluded that environmental factors, simulated by certain in vitro conditions, transiently confer NSC-like attributes on astrocytes during a critical period in CNS development.
Abstract: The mammalian brain contains a population of neural stem cells (NSC) that can both self-renew and generate progeny along the three lineage pathways of the central nervous system (CNS), but the in vivo identification and localization of NSC in the postnatal CNS has proved elusive. Recently, separate studies have implicated ciliated ependymal (CE) cells, and special subependymal zone (SEZ) astrocytes as candidates for NSC in the adult brain. In the present study, we have examined the potential of these two NSC candidates to form multipotent spherical clones—neurospheres—in vitro. We conclude that CE cells are unipotent and give rise only to cells within the glia cell lineage, although they are capable of forming spherical clones when cultured in isolation. In contrast, astrocyte monolayers from the cerebral cortex, cerebellum, spinal cord, and SEZ can form neurospheres that give rise both to neurons and glia. However, the ability to form neurospheres is restricted to astrocyte monolayers derived during the first 2 postnatal wk, except for SEZ astrocytes, which retain this capacity in the mature forebrain. We conclude that environmental factors, simulated by certain in vitro conditions, transiently confer NSC-like attributes on astrocytes during a critical period in CNS development.

737 citations


Journal ArticleDOI
TL;DR: It is suggested that the skin neuroendocrine system acts by preserving and maintaining the skin structural and functional integrity and, by inference, systemic homeostasis.
Abstract: The classical observations of the skin as a target for melanotropins have been complemented by the discovery of their actual production at the local level. In fact, all of the elements controlling the activity of the hypothalamus-pituitary-adrenal axis are expressed in the skin including CRH, urocortin, and POMC, with its products ACTH, α-MSH, and β-endorphin. Demonstration of the corresponding receptors in the same cells suggests para- or autocrine mechanisms of action. These findings, together with the demonstration of cutaneous production of numerous other hormones including vitamin D3, PTH-related protein (PTHrP), catecholamines, and acetylcholine that share regulation by environmental stressors such as UV light, underlie a role for these agents in the skin response to stress. The endocrine mediators with their receptors are organized into dermal and epidermal units that allow precise control of their activity in a field-restricted manner. The skin neuroendocrine system communicates with itself and wi...

659 citations


Journal ArticleDOI
TL;DR: Treatment with metronidazole did not reduce the occurrence of preterm labor, intraamniotic or postpartum infections, neonatal sepsis, or admission of the infant to the neonatal intensive care unit.
Abstract: Background Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence. Methods To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis (as diagnosed on the basis of vaginal Gram's staining and pH) prevents preterm delivery, we randomly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo. The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks' gestation. The primary outcome was the rate of delivery before 37 weeks' gestation. Results Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram's staining in the metronidazole group (77.8 percent) and 321 of 859 women in the placebo group (37.4 percent). Data on the time and characteristics of delivery were available fo...

602 citations



Journal ArticleDOI
TL;DR: This work has shown that activation of the motor-related cortical areas in the basal ganglia regulates the activity of the output nuclei of the basalganglia in the neocortex.
Abstract: How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. In...

555 citations


Journal ArticleDOI
TL;DR: In this paper, an affinity reagent designed to interact with the active site of γ-secretase was shown to be able to bind to heterodimeric forms of presenilins, polytopic proteins that are mutated in hereditary Alzheimer's.
Abstract: The β-amyloid precursor protein (β-APP), which is involved in the pathogenesis of Alzheimer’s disease, and the Notch receptor, which is responsible for critical signalling events during development, both undergo unusual proteolysis within their transmembrane domains by unknown γ-secretases. Here we show that an affinity reagent designed to interact with the active site of γ-secretase binds directly and specifically to heterodimeric forms of presenilins, polytopic proteins that are mutated in hereditary Alzheimer’s and are known mediators of γ-secretase cleavage of both β-APP and Notch. These results provide evidence that heterodimeric presenilins contain the active site of γ-secretase, and validate presenilins as principal targets for the design of drugs to treat and prevent Alzheimer’s disease.

Journal ArticleDOI
TL;DR: Pharmacologic interventions with angiotensin converting enzyme inhibitor or AT1 receptor antagonist has proven effective in attenuating scar tissue metabolic activity and minimizing adverse accumulation of fibrous tissue in noninfarcted myocardium.
Abstract: Infarct scar, a requisite to the rebuilding of necrotic myocardium following myocardial infarction (MI), has long been considered inert. Earlier morphologic studies suggested healing at the infarct site was complete within 6-8 weeks following MI and resultant scar tissue, albeit necessary, was acellular and simply fibrillar collagen. Utilizing molecular and cellular biologic technologies, recent studies indicate otherwise. Infarct scar is composed of phenotypically transformed fibroblast-like cells, termed myofibroblasts (myoFb) because they express alpha-smooth muscle actin (alpha-SMA) and these microfilaments confer contractile behavior in response to various peptides and amines. These cells are nourished by a neovasculature and are persistent at the MI site, where they are metabolically active expressing components requisite to angiotensin (Ang) peptide generation, including converting enzyme, receptors for AngII and transforming growth factor (TGF)-beta1. They continue to elaborate fibrillar type I collagen. Their generation of these peptides contribute to ongoing scar tissue collagen turnover and to fibrous tissue formation of noninfarcted myocardium. Infarct scar contraction accounts for its thinning and its tonus may contribute to abnormal ventricular chamber stiffness with diastolic dysfunction. Infarct scar is a dynamic tissue: cellular, vascularized, metabolically active and contractile. Pharmacologic interventions with angiotensin converting enzyme inhibitor or AT1 receptor antagonist has proven effective in attenuating scar tissue metabolic activity and minimizing adverse accumulation of fibrous tissue in noninfarcted myocardium.

Journal ArticleDOI
TL;DR: Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN and Randomized trials are needed to evaluate the role of these common therapies.
Abstract: Objectives. In the era before widespread use of inhaled nitric oxide, to determine the prevalence of persistent pulmonary hypertension (PPHN) in a multicenter cohort, demographic descriptors of the population, treatments used, the outcomes of those treatments, and variation in practice among centers. Study Design. A total of 385 neonates who received ≥50% inspired oxygen and/or mechanical ventilation and had documented evidence of PPHN (2D echocardiogram or preductal or postductal oxygen difference) were tracked from admission at 12 Level III neonatal intensive care units. Demographics, treatments, and outcomes were documented. Results. The prevalence of PPHN was 1.9 per 1000 live births (based on 71 558 inborns) with a wide variation observed among centers (.43–6.82 per 1000 live births). Neonates with PPHN were admitted to the Level III neonatal intensive care units at a mean of 12 hours of age (standard deviation: 19 hours). Wide variations in the use of all treatments studied were found at the centers. Hyperventilation was used in 65% overall but centers ranged from 33% to 92%, and continuous infusion of alkali was used in 75% overall, with a range of 27% to 93% of neonates. Other frequently used treatments included sedation (94%; range: 77%–100%), paralysis (73%; range: 33%–98%), and inotrope administration (84%; range: 46%–100%). Vasodilator drugs, primarily tolazoline, were used in 39% (range: 13%–81%) of neonates. Despite the wide variation in practice, there was no significant difference in mortality among centers. Mortality was 11% (range: 4%–33%). No specific therapy was clearly associated with a reduction in mortality. To determine whether the therapies were equivalent, neonates treated with hyperventilation were compared with those treated with alkali infusion. Hyperventilation reduced the risk of extracorporeal membrane oxygenation without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventilation) and an increased use of oxygen at 28 days of age. Conclusions. Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies.

Journal ArticleDOI
TL;DR: Successful nonoperative management was associated with higher blood pressure and hematocrit, and less severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and quantity of hemoperitoneum.
Abstract: Background: Nonoperative management of blunt injury to the spleen in adults has been applied with increasing frequency. However, the criteria for nonoperative management are controversial. The purpose of this multi-institutional study was to determine which factors predict successful observation of blunt splenic injury in adults. Methods: A total of 1,488 adults (>15 years of age) with blunt splenic injury from 27 trauma centers in 1997 were studied through the Multi-institutional Trials Committee of the Eastern Association for the Surgery of Trauma. Statistical analysis was performed with analysis of variance and extended X 2 test. Data are expressed as mean ± SD; a value of p 15 were successfully observed. Frequency of immediate operation correlated with American Association for the Surgery of Trauma (AAST) grades of splenic injury: I (23.9%), II (22.4%), III (38.1%), IV (73.7%), and V (94.9%) (p < 0.05). Of patients initially managed nonoperatively, the failure rate increased significantly by AAST grade of splenic injury: I (4.8%), II (9.5%), III (19.6%), IV (33.3%), and V (75.0%) (p < 0.05). A total of 60.9% of the patients failed nonoperative management within 24 hours of admission; 8% failed 9 days or later after injury. Laparotomy was ultimately performed in 19.9% of patients with small hemoperitoneum, 49.4% of patients with moderate hemoperitoneum, and 72.6% of patients with large hemoperitoneum. Conclusion: In this multicenter study, 38.5% of adults with blunt splenic injury went directly to laparotomy. Ultimately, 54.8% of patients were successfully managed nonoperatively; the failure rate of planned observation was 10.8%, with 60.9% of failures occurring in the first 24 hours. Successful nonoperative management was associated with higher blood pressure and hematocrit, and less severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and quantity of hemoperitoneum.

Journal ArticleDOI
TL;DR: It is shown that p120 selectively inhibits RhoA activity in vitro and in vivo, suggesting a mechanism for regulating the recruitment and exchange of RHoA at nascent cell–cell contacts.
Abstract: RhoA organizes actin stress fibres and is necessary for cell transformation by oncogenes such as src and ras. Moreover, RhoA is implicated in cadherin clustering during the formation of adherens junctions. The catenin p120 has also been implicated in cadherin clustering through an unknown mechanism. Here we show that p120 selectively inhibits RhoA activity in vitro and in vivo. RhoA inhibition and the interaction of p120 with cadherins are mutually exclusive, suggesting a mechanism for regulating the recruitment and exchange of RhoA at nascent cell-cell contacts. By affecting RhoA activation, p120 could modulate cadherin functions, including suppression of invasion, neurite extension and junction formation.

Journal ArticleDOI
TL;DR: In this article, the safety and efficacy of laparoscopic ventral and incisional hernias were evaluated in 415 patients who were scheduled to undergo either open surgery or Laparoscopic surgery.
Abstract: Background: Recurrence rates after primary repair of ventral and incisional hernias range from 25% to 52%. Recurrence after open surgery is less likely if mesh is used, but the wide fascial dissection and required flap creation increase complication rates. Laparoscopic techniques offer an alternative. Study Design: To assess the safety and efficacy of laparoscopic ventral and incisional herniorrhaphy, we reviewed the records of all our patients who underwent such a procedure from November 1993 to August 1999. A laparoscopic approach was attempted in all patients considered to require a mesh repair. Patient demographic characteristics, operative details, and outcomes were recorded. Results: Of 415 patients scheduled to undergo laparoscopic ventral or incisional herniorrhaphy, conversion to an open procedure was necessary in 8. All the remaining 407 patients (205 men and 202 women; mean age 53.2 years; range 13 to 88 years) were included in the study. Mean fascial defect size was 100.1 cm 2 (range 1 to 480 cm 2 ). In 97% of patients, expanded polytetrafluoroethylene mesh was used. Mean operating time was 97 minutes (range 11 to 270 minutes). Mean estimated blood loss was 35 mL (range 10 to 150 mL). Average hospital stay was 1.8 days (range 0 to 17 days). There were 53 complications (13.0%), including cellulitis of a trocar site, infection requiring mesh removal, prolonged suture pain, persistent seroma, intestinal injury, hematoma or postoperative bleeding, prolonged ileus, urinary retention, respiratory distress, fever, intraabdominal abscess, and trocar site herniation. There were no deaths. During a mean followup time of 23 months (range 1 to 60 months), there were 14 hernia recurrences (3.4%), 6 in patients in whom only a stapling device (no sutures) had been used to secure the mesh to the abdominal wall. Conclusions: Laparoscopic repair was completed in 98.1% of patients in whom it was attempted. The complication rate was acceptable. A short hospital stay and minimal blood loss were documented. The recurrence rate was 3.4%. Laparoscopic ventral and incisional hernia repair appear to be safe and effective.

Journal ArticleDOI
TL;DR: In this article, the authors compared rates and severity of gestational hypertension and preeclampsia, as well as perinatal outcomes when these complications develop, between women with twin gestations and those with singleton gestations.

Journal ArticleDOI
15 Feb 2000-Virology
TL;DR: The available evidence supports the notion of differences in pathogenicity of H9N2 viruses in the different lineages and suggests that viruses possessing genome segments similar to 1997 H5N1-like viruses are potentially pathogenic in mammals.

Journal ArticleDOI
TL;DR: It is shown that p19(ARF) can act independently of the Mdm2-p53 axis in tumor surveillance, and interacts with other targets to inhibit cell proliferation in the absence of MDM2.
Abstract: The p19ARF tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53 and Mdm2 or p53 alone, demonstrating that p19ARF can act independently of the Mdm2-p53 axis in tumor surveillance. Reintroduction of ARF into TKO mouse embryo fibroblasts (MEFs), but not into those lacking both p53 and ARF, arrested the cell division cycle in the G1 phase. Inhibition of the retinoblastoma protein had no effect on the ability of ARF to arrest TKO MEFs. Thus, in the absence of Mdm2, p19ARF interacts with other targets to inhibit cell proliferation.

Journal ArticleDOI
TL;DR: Analysis of the 1999 swine H3N2 isolates showed that the internal gene complex of the triple-reassortant viruses was associated with three recent phylogenetically distinct human-like hemagglutinin (HA) molecules, which supports continued surveillance of U.S. swine populations for influenza virus activity.
Abstract: During 1998, severe outbreaks of influenza were observed in four swine herds in the United States. This event was unique because the causative agents, H3N2 influenza viruses, are infrequently isolated from swine in North America. Two antigenically distinct reassortant viruses (H3N2) were isolated from infected animals: a double-reassortant virus containing genes similar to those of human and swine viruses, and a triple-reassortant virus containing genes similar to those of human, swine, and avian influenza viruses (N. N. Zhou, D. A. Senne, J. S. Landgraf, S. L. Swenson, G. Erickson, K. Rossow, L. Liu, K.-J. Yoon, S. Krauss, and R. G. Webster, J. Virol. 73:8851–8856, 1999). Because the U.S. pig population was essentially naive in regard to H3N2 viruses, it was important to determine the extent of viral spread. Hemagglutination inhibition (HI) assays of 4,382 serum samples from swine in 23 states indicated that 28.3% of these animals had been exposed to classical swine-like H1N1 viruses and 20.5% had been exposed to the triple-reassortant-like H3N2 viruses. The HI data suggested that viruses antigenically related to the double-reassortant H3N2 virus have not become widespread in the U.S. swine population. The seroreactivity levels in swine serum samples and the nucleotide sequences of six additional 1999 isolates, all of which were of the triple-reassortant genotype, suggested that H3N2 viruses containing avian PA and PB2 genes had spread throughout much of the country. These avian-like genes cluster with genes from North American avian viruses. The worldwide predominance of swine viruses containing an avian-like internal gene component suggests that these genes may confer a selective advantage in pigs. Analysis of the 1999 swine H3N2 isolates showed that the internal gene complex of the triple-reassortant viruses was associated with three recent phylogenetically distinct human-like hemagglutinin (HA) molecules. Acquisition of HA genes from the human virus reservoir will significantly affect the efficacy of the current swine H3N2 vaccines. This finding supports continued surveillance of U.S. swine populations for influenza virus activity.

Journal ArticleDOI
TL;DR: Unlike prednisone withdrawal, CsA withdrawal in select patients seems to impart little risk of long-term graft failure, and there was no evidence of between-study heterogeneity for either acute rejection or graft failure in the prednis one withdrawal trials by a chi(2) test.
Abstract: . Since the publication of previous meta-analyses of cyclosporine (CsA) and prednisone withdrawal in renal transplant recipients, several additional randomized controlled trials with longer follow-up have been reported. Currently, in nine prednisone withdrawal trials ( n = 1461), the proportion of patients with acute rejection was increased by 0.14 (95% confidence interval = 0.10 to 0.17, P n = 1899), the relative risk (RR; RR = 1.0 indicates no risk) of graft failure after withdrawal was also increased (RR = 1.40; range, 1.09 to 1.70, P = 0.012). There was no evidence of between-study heterogeneity for either acute rejection or graft failure in the prednisone withdrawal trials by a χ 2 test ( P > 0.05). In 10 CsA withdrawal trials ( n = 1049), the proportion of patients with acute rejection was increased by 0.11 (0.07 to 0.15, P n = 1151), the RR of graft failure after CsA withdrawal was 1.06 (95% confidence interval, 0.82 to 1.29, P = 0.646), but a χ 2 test indicated that there was study heterogeneity. However, there was no evidence of heterogeneity in the six studies ( n = 632) with at least 4.0 yr (5.8 ± 1.7) of follow-up (RR = 0.92; range, 0.64 to 1.20, P = 0.569) or in the seven trials ( n = 962) published in peer-reviewed journals (RR = 0.95; range, 0.70 to 1.20 P = 0.682). Finally, in three trials ( n = 259) that compared CsA and prednisone withdrawal, there was a nonsignificant trend for less graft failure with CsA withdrawal (RR = 0.63; range, 0.08 to 1.16, P = 0.190). Thus, unlike prednisone withdrawal, CsA withdrawal in select patients seems to impart little risk of long-term graft failure.

Journal ArticleDOI
TL;DR: Clean intermittent catheterization is the safest bladder management method for spinal cord injured patients in terms of urological complications and has a significant detrimental impact on the economic status of the health care system.

Journal ArticleDOI
TL;DR: In this paper, it was shown that a primary visual area and a primary somatosensory-somatomotor area are present in the avian Wulst; these areas are likely to be homologous to their counterparts in mammals.

Journal ArticleDOI
TL;DR: Biotinylated dextran amines (BDA) are highly sensitive tools for anterograde and retrograde pathway tracing studies of the nervous system and can, therefore, be readily used in ultrastructural studies.

Journal ArticleDOI
TL;DR: Either prenatal GBS screening or a risk-based strategy could potentially prevent a substantial portion of GBS cases, and the severity of ampicillin-resistant E colisepsis and its occurrence after maternal antibiotics suggest caution regarding use ofAmpicillin instead of penicillin for GBS prophylaxis.
Abstract: Background. Early-onset group B streptococcal (GBS) prevention efforts are based on targeted use of intrapartum antibiotic prophylaxis (IAP); applicability of these prevention efforts to infections caused by other organisms is not clear. Methods. Multicenter surveillance during 1995 to 1996 for culture-confirmed, early-onset sepsis in an aggregate of 52 406 births; matched case-control study of risk factors for GBS and other sepsis. Results. Early-onset disease occurred in 188 infants (3.5 cases per 1000 live births). GBS (1.4 cases per 1000 births) andEscherichia coli (0.6 cases per 1000 births) caused most infections. GBS sepsis less often occurred in preterm deliveries compared with other sepsis. Compared with gestation-matched controls without documented sepsis, GBS disease was associated with intrapartum fever (matched OR, 4.1; CI, 1.2–13.4) and frequent vaginal exams (matched OR, 2.9; CI, 1.1–8.0). An obstetric risk factor—preterm delivery, intrapartum fever, or membrane rupture ≥18 hours—was found in 49% of GBS cases and 79% of other sepsis. IAP had an adjusted efficacy of 68.2% against any early-onset sepsis. Ampicillin resistance was evident in 69% of E coliinfections. No deaths occurred among susceptible E coliinfections, whereas 41% of ampicillin-resistant E coliinfections were fatal. Ninety-one percent of infants who developed ampicillin-resistant E coli infections were preterm, and 59% of these infants were born to mothers who had received IAP. Conclusions. Either prenatal GBS screening or a risk-based strategy could potentially prevent a substantial portion of GBS cases. Sepsis caused by other organisms is more often a disease of prematurity. IAP seemed efficacious against early-onset sepsis. However, the severity of ampicillin-resistant E colisepsis and its occurrence after maternal antibiotics suggest caution regarding use of ampicillin instead of penicillin for GBS prophylaxis.

Journal ArticleDOI
TL;DR: A range of tonic firing patterns are observed, suggesting that the characteristic spike sequences described for tonically active cholinergic neurons (TANs) recorded in vivo are intrinsic in origin.
Abstract: Neostriatal cholinergic interneurons produce spontaneous tonic firing in the absence of synaptic input. Perforated patch recording and whole-cell recording combined with calcium imaging were used in vitro to identify the intrinsic membrane properties underlying endogenous excitability. Spontaneous firing was driven by the combined action of a sodium current and the hyperpolarization-activated cation current (I(h)), which together ensured that there was no zero current point in the subthreshold voltage range. Blockade of sodium channels or I(h) established a stable subthreshold resting membrane potential. A tetrodotoxin-sensitive region of negative slope conductance was observed between approximately -60 mV and threshold (approximately -50 mV) and the h-current was activated at all subthreshold voltages. Calcium imaging experiments revealed that there was minimal calcium influx at subthreshold membrane potentials but that action potentials produced elevations of calcium in both the soma and dendrites. Spike-triggered calcium entry shaped the falling phase of the action potential waveform and activated calcium-dependent potassium channels. Blockade of big-conductance channels caused spike broadening. Application of apamin, which blocks small-conductance channels, abolished the slow spike afterhyperpolarization (AHP) and caused a transition to burst firing. In the absence of synaptic input, a range of tonic firing patterns are observed, suggesting that the characteristic spike sequences described for tonically active cholinergic neurons (TANs) recorded in vivo are intrinsic in origin. The pivotal role of the AHP in regulating spike patterning indicates that burst firing of TANs in vivo could arise from direct or indirect modulation of the AHP without requiring phasic synaptic input.

Journal ArticleDOI
TL;DR: Factors regulating growth of these compartments are reviewed and in particular signals involved in promoting adverse remodeling of intramyocardial coronary arteries and arterioles by fibrous tissue are reviewed.
Abstract: The normal myocardium is composed of a variety of cells: cardiac myocytes and noncardiomyocytes, which include endothelial and vascular smooth muscle cells and fibroblasts. Hypertensive heart disease involves a structural remodeling of muscular and nonmuscular compartments. It is not the quantity but rather the quality of myocardium that accounts for pathologic hypertrophy and predisposes to ventricular dysfunction and arrhythmias, which, in turn, confer increased risk of adverse cardiovascular events. Herein, factors regulating growth of these compartments are reviewed and in particular signals involved in promoting adverse remodeling of intramyocardial coronary arteries and arterioles by fibrous tissue.

Journal ArticleDOI
TL;DR: There has been a paradigm shift in the management of hemodynamically stable patients with blunt hepatic trauma, and nonoperative management significantly improves outcomes over operative management in terms of decreased abdominal infections, decreased transfusions, and decreased lengths of hospital stay.
Abstract: “While small lacerations of the liver substance may be, and no doubt are, recovered from without operative interference: if the laceration be extensive and vessels of any magnitude are torn, hemorrhage will, owing to the structural arrangement of the liver, go on continuously.” J.H. Pringle, 1908 1 Operative therapy has been the standard of care for liver injuries from the beginning of the century until the beginning of the 1990s. This has been based on the dual rationale of hemostasis and bile drainage. In 1991 we reported a prospective comparative trial of methods of liver drainage in 482 consecutive patients with liver injuries undergoing operative management. 2 In that trial it was shown that lack of bile drainage did not adversely affect outcome. A “paradigm shift” is said to occur when the rules governing a process are fundamentally changed, and such is the case with the treatment of liver injuries. Since the early 1980s, sporadic reports of adult patients with blunt hepatic trauma treated nonoperatively have appeared in the literature. 3–18 Two large series of nonoperative management, one of 495 patients collected from a literature review 19 and the other of 404 patients from the collective experience of 13 level 1 trauma centers, 20 were reported in 1995 and 1996, respectively. However, there were drawbacks to these larger studies. First, the numbers of patients from the individual series or centers were small (16–72 patients). Second, the criteria for nonoperative management were not uniform, so the percentage of patients with blunt hepatic injury who were treated nonoperatively varied from 17% to 60%. Finally, nearly all reports either described only the nonoperatively managed patients, or compared them with operatively managed patients in the same period. Those characteristics make it difficult to compare the results of operative versus nonoperative therapy because the groups are not comparable relative to the degree of hepatic injury. Similarly, we cannot draw valid conclusions about the total impact that this new method of management has had on the overall outcome of blunt hepatic trauma. In an attempt to address some of the questions about nonoperative management, we previously conducted a prospective pilot study in which all hemodynamically stable patients with blunt hepatic trauma, regardless of grade of injury or amount of hemoperitoneum, were managed nonoperatively. 17 The outcomes of nonoperatively managed patients were compared with a matched cohort of patients who had been operatively managed from the previous study. 2 Encouraged by the results, nonoperative management has been applied to all hemodynamically stable patients with blunt hepatic injury at our institution since that time. The current study consists of 661 consecutive patients with blunt hepatic trauma during the recent 5-year period during which all hemodynamically stable patients were managed nonoperatively. Results of management in the most recent cohort are compared with the two previous studies to assess the impact of this fundamental change in therapy. This study was performed to address two specific issues: first, the outcome of hemodynamically stable patients with blunt hepatic injury managed nonoperatively, and second, the impact of this approach on the outcome of all blunt hepatic injuries.

Journal ArticleDOI
TL;DR: These studies suggest that Pten negatively controls cell motility through its lipid phosphatase activity by down-regulating Rac1 and Cdc42.

Journal ArticleDOI
08 Dec 2000-Science
TL;DR: A tumor-derived K-cell line was induced to produce human insulin by providing the cells with the human insulin gene linked to the 5'-regulatory region of the gene encoding glucose-dependent insulinotropic polypeptide (GIP).
Abstract: Genetic engineering of non-beta cells to release insulin upon feeding could be a therapeutic modality for patients with diabetes. A tumor-derived K-cell line was induced to produce human insulin by providing the cells with the human insulin gene linked to the 5'-regulatory region of the gene encoding glucose-dependent insulinotropic polypeptide (GIP). Mice expressing this transgene produced human insulin specifically in gut K cells. This insulin protected the mice from developing diabetes and maintained glucose tolerance after destruction of the native insulin-producing beta cells.