Biomedical subjects

R Ness

Publications and source records attributed to R Ness.

At least 19 recordsLinked to original sources

PubMed2004

Evidence for the functional activity of hypoxia-inducible transcription factors overexpressed in preeclamptic placentae.

Placentas from women with preeclampsia overexpress the hypoxia-inducible transcription factor proteins, HIF-1alpha and -2alpha (Rajakumar 2001, Biol Reprod 64; p499-506 and p1019-1020). As a first step in evaluating whether HIF-alpha overexpressed in preeclamptic placentae is capable of transactivation, we tested its ability to bind to the DNA hypoxia response element (HRE). Six pairs of normal and preeclamptic placentae obtained by cesarean section were investigated. Three biopsy sites per placenta were analyzed. We first confirmed HIF-1alpha protein overexpression in the preeclamptic placentae using Western analysis. The ratios of the arbitrary densitometry units for HIF-1alpha protein from the preeclamptic and normal placentae (PE/NP) in the three biopsy sites were: 1.9 +/- 0.3, 1.7 +/- 0.2 and 1.8 +/- 0.2, each p < 0.05 vs 1.0. (A ratio of >1.0 indicates that HIF-1alpha protein expression in placentas of women with PE exceeds that in placentas of NP women.) Conventional methods for extracting nuclear proteins and subsequent analysis by electrophoretic mobility shift assay were not suited for the frozen, archived samples (data not shown). Therefore, we employed DNA affinity chromatography using a biotinylated oligonucleotide representing the HRE of the erythropoietin gene coupled to streptavidin-coated Dynabeads. The HRE-bound proteins were then characterized by Western blot analysis. The PE/NP ratios of HRE-bound HIF-1alpha in the three biopsy sites from the six pairs of normal and preeclamptic placentae were 1.7 +/- 0.2, 2.1 +/- 0.4 and 2.4 +/- 0.5, each p < 0.05 vs 1.0. Having established DNA-binding potential at least in vitro, we subsequently analyzed three proteins that have been shown to be regulated by HIF-alpha as downstream, molecular markers of HIF-1alpha activity in vivo. VEGF receptor Flt-1 and Flk-1 play key roles in angiogenesis. Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis. All three genes contain functional HRE in their promoter sequences. Total proteins were extracted from the same biopsy samples that were used for total and HRE-bound HIF-1alpha. Using specific antibodies we performed Western analysis and the levels of these three proteins were quantitated. The Flt-1 and tyrosine hydroxylase proteins were significantly higher, and Flk-1 significantly lower in placentae from preeclamptic compared to normal pregnancies. In summary, HIF-1alpha protein overexpressed in preeclamptic placentae is capable of binding to its DNA recognition sequence in vitro, and modulates gene expression in vivo.

Adult↗

PubMed2001

A review of adverse pregnancy outcomes and formaldehyde exposure in human and animal studies.

We examine the potential for reproductive and developmental effects from formaldehyde exposure. Formaldehyde is unlikely to reach the reproductive system in humans in concentrations sufficient to cause damage since it is rapidly metabolized and detoxified upon contact with the respiratory tract. While there are effects seen in in vitro studies or after injection, there is little evidence of reproductive or developmental toxicity in animal studies under exposure levels and routes relevant to humans. Most of the epidemiology studies examined spontaneous abortion and showed some evidence of increased risk (meta-relative risk=1.4, 95% CI 0.9-2.1). We found evidence of reporting biases and publication biases among the epidemiology studies and when these biases were taken into account, we found no evidence of increased risk of spontaneous abortion among workers exposed to formaldehyde (meta-relative risk=0.7, 95% CI 0.5-1.0). The small number of studies on birth defects, low birth weight, and infertility among formaldehyde workers; the limitations in the design of these studies; and the inconsistent findings across these studies make it difficult to draw conclusions from the epidemiology data alone. However, information from experimental studies and studies of metabolism indicate reproductive impacts are unlikely at formaldehyde exposures levels observed in the epidemiology studies.

Abnormalities, Drug-Induced↗

PubMed1999

Screening for hepatocellular carcinoma in patients with cirrhosis in the United States: results of a national survey.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the dreaded complications of cirrhosis. Although there are no randomized controlled studies showing improved survival with screening, patients with cirrhosis are screened for HCC. Little is known about the practice of HCC screening in the United States. Our aim was to describe the practice of HCC screening in patients with cirrhosis in the United States. METHODS: In March 1998, we mailed a standard questionnaire to 1021 physician members of the American Association of Study for Liver Diseases and the same questionnaire was re-sent to nonrespondents 4 weeks later. RESULTS: We received a response from 554 members (54%). After excluding those not involved in active adult patient care, 473 responses were eligible for analysis. Eighty-four percent of the respondents routinely screened patients with cirrhosis for HCC (screening respondents). Nearly half of the screening respondents limited the HCC screening to patients with high-risk etiologies such as hepatitis B or C or hemochromatosis. Although alpha-fetoprotein (99.7%) and ultrasound (93%) were the two most frequently used screening methods, a sizable proportion of the screening respondents (25%) used abdominal computed tomography for routine screening. On multivariate analysis, the following variables predicted screening for HCC by the respondents: seeing more than one new cirrhotic per week (odds ratio [OR]: 5.4, 95% confidence interval [CI]: 2.5-11.7); practicing for < 10 yr (OR: 4.0, 95% CI: 1.2-13.4); an opinion that screening is cost-effective (OR: 6.4, 95% CI: 1.6-25); an opinion that screening prolongs survival (OR: 5.7, 95% CI: 1.8-17.9); and an opinion that not screening poses malpractice liability (OR: 9.3, 95% CI: 4.2-20.8). CONCLUSIONS: The majority of respondents routinely screen patients with cirrhosis for HCC. Approximately half of the screening respondents limit their screening to only patients with high-risk etiologies. On multivariate analysis, several variables predicted screening for HCC by the respondents.

Adult↗

PubMed1997

Leptomeningeal cells modulate the neurite growth promoting properties of astrocytes in vitro.

Leptomeningeal cells migrate into the lesion cavity after stab wounds to the adult mammalian central nervous system (CNS) and interact with astrocytes that form a new glia limitans. However, it is not known if leptomeningeal cells alter the ability of astrocytes near the lesion to support axon growth. In this study, we have used an in vitro approach to assess leptomeningeal cell-astrocyte interactions in a model that resembles the interactions of these cells in vivo. We cultured rat cortical astrocytes on top of monolayers of leptomeningeal cells or astrocytes. Differences in the morphology, neurite growth promoting properties, and expression of various extracellular matrix molecules and beta 1-integrin were assessed. Astrocytes acquired a long slender morphology when plated on leptomeningeal cells. Functionally, astrocytes cultured on top of leptomeningeal monolayers supported less neurite growth. Similar results were also obtained when astrocyte monolayers were treated with leptomeningeal cell-conditioned medium. Quantitative immunofluorescence labeling showed a reduction in cell surface bound laminin on astrocytes plated on leptomeningeal monolayers. Qualitative assessment of the immunofluorescence labeling showed an increase in matrix-like deposits of tenascin-C and chondroitin sulfate proteoglycan under similar culture conditions. This study provides the first direct evidence that leptomeningeal cells reduce the neurite growth promoting properties of astrocytes. These results suggest that interactions with leptomeningeal cells may 1) induce the formation of the slender astrocyte processes that form parallel to the lesion wall after penetrating injuries to the CNS; and 2) contribute along with other factors to alter astrocytes near the site of injury to a state that is less permissive for axon growth and regeneration.

Animals↗

PubMed1996

Data-gathering tools for "real world" clinical settings: a multisite feasibility study.

OBJECTIVE: To determine the mental health needs and optimal treatments for children and families in "real world" settings, data-gathering strategies are needed that can be easily implemented across a variety of clinical settings. To address this need, the authors developed and piloted a "clinician-friendly" questionnaire that includes demographic, psychosocial, medical, and family history variables, such as those routinely gathered in standard clinical evaluations. METHOD: Optical scanning technology was used to encode data from more than 1,900 children, including 1,458 consecutive referrals in four military child psychiatry clinics, 285 consecutive admissions to a civilian psychiatric state hospital, 71 pediatric patients, and a community sample of 113 children. RESULTS: Despite geographic and logistic obstacles, clinical data were reliably obtained across multiple settings. Data analyses revealed meaningful differences across samples in subjects' presenting complaints, and a range of psychosocial, demographic, and background variables. Data were characterized by an apparently high degree of accuracy and completeness. CONCLUSIONS: Findings illustrate the importance and feasibility of standardized data-gathering approaches in routine clinical settings and clarify the hazards as well as the opportunities afforded by these research approaches. Such data-gathering tools appear to have significant merit and deserve further implementation and testing across a range of clinical and research settings.

Adolescent↗

PubMed1996

Admission criteria for inpatient substance abuse/dependence rehabilitation: implications for managed care.

In view of recent trends toward the replacement of traditional inpatient rehabilitation programs with nonresidential services, we examined the extent to which patients currently admitted to inpatient rehabilitation for alcohol or drug abuse/dependence met published criteria suggesting a preferential need for inpatient or residential care. Over 90% of almost 300 veterans with a primary DSM-III R diagnosis of alcohol or substance abuse/dependence, admitted to six New York Metropolitan Area Veterans Administration Medical Centers for inpatient rehabilitation, met at least one criterion dimension considered indicative of a need for such services, with over two-thirds meeting two or more dimensions. These findings suggest a continuing need for initial primary inpatient or residential rehabilitation for such patients.

Adult↗

PubMed1994

Tenascin in the injured rat optic nerve and in non-neuronal cells in vitro: potential role in neural repair.

The distribution of tenascin was examined in the lesioned adult rat optic nerve and central nervous system (CNS) non-neuronal cells in vitro, by means of a double immunofluorescence technique. Tenascin-like immunoreactivity is localized to the leptomeninges and astrocytes that border the site of optic nerve transection. Anti-tenascin labeling was observed as early as 24 hours after transection, when it appeared as a fine interface between leptomeninges and neural tissue. The anti-tenascin labeling increased in the cells at this border zone during the next 2 weeks, and disappeared 18-21 days after transection. In vitro studies further confirmed that both astrocytes and leptomeningeal cells express tenascin as detected by immunofluorescence labeling with anti-tenascin antibodies. However, the pattern of immunolabeling associated with the two cell types differed. Astrocytes showed exclusively punctate labeling of the cell surface, while leptomeningeal cells showed mainly coarse, fibrillary, matrix-like deposits. Astrocytes and leptomeningeal cells remained segregated when cocultured. In these cultures, an increased amount of the fibrillary, matrix-like deposits of tenascin was also observed in the region of the interface between astrocytes and leptomeningeal cells when these two cell types contact each other. Given the antiadhesive and antispreading properties of tenascin, these in vivo and in vitro results suggest that tenascin might play a role in the initial segregation of leptomeningeal cells from neural tissue at the site of CNS trauma during the first 2 weeks after injury, i.e., prior to the formation of a fully differentiated glia limitans. Therefore, tenascin may influence the early stages in the formation of the glia limitans, and thus prevent the indiscriminate migration of leptomeningeal cells into CNS tissue after injury.

Animals↗

PubMed1994

The acute effects of a rapid medical detoxification upon dysphoria and other psychopathology experienced by heroin abusers.

Self-reported dysphoria, personality disorder traits, and subjective opioid withdrawal symptoms were assessed in 30 opioid abusers before and after a rapid medical detoxification from heroin. Subject exclusion criteria reflected an effort to control for potential sources of affective change that were extraneous to the effect of detoxification. Subjects received few rehabilitative services during their 12-day inpatient hospitalization, and were not permitted visitors or off-ward privileges. At the preadmission assessment, they reported elevated levels of dysphoria and personality disorder traits, as well as opioid withdrawal symptoms. The results indicate that clinically significant declines in symptoms of dysphoria, opioid withdrawal symptoms, and personality disorder traits occur during the course of a rapid medical detoxification. Dysphoric and opioid withdrawal symptom abatement was most pronounced between the preadmission and admission assessments. These factors should be considered in the clinical diagnosis and treatment, as well as in research about psychiatric comorbidity of these substance abusers.

Adult↗

PubMed1993

Organic mood syndrome associated with detoxification from methadone maintenance.

OBJECTIVE: The authors delineate the clinical characteristics of mood state changes that occur in stable opioid-dependent patients undergoing therapeutic detoxification from methadone maintenance treatment. METHOD: Twenty-four patients participated in a blinded protocol for gradual methadone dose reduction that included weekly assessments of affective state using the Profile of Mood States (POMS) as well as weekly assessments of signs and symptoms of opioid withdrawal. Data obtained before methadone dose reduction and during the 2-week period of maximal dysphoric symptoms were compared. Changes in affective and opioid withdrawal measures were compared in patients who differed in their success in completing the detoxification regimen. RESULTS: Sustained increases in POMS scores of greater than 20 points were observed in 12 of the 24 patients during the course of detoxification. The emergence of symptoms of dysphoria was accompanied by insomnia, loss of appetite, and somatic complaints consistent with symptoms of opioid withdrawal but only minimal levels of objective signs of withdrawal. Greater changes from baseline in mood state and opioid withdrawal measures occurred in patients who were unable to complete the detoxification regimen. CONCLUSIONS: The development of an organic mood syndrome is a common occurrence in patients undergoing slow detoxification from methadone maintenance treatment and is associated with a poor outcome.

Adult↗

PubMed1992

The relationship between wrist position, grasp size, and grip strength.

In the first part of this study, the position assumed by a normal wrist during unconstrained maximal grip and the relationship between wrist position and grip strength were investigated in 20 healthy subjects. Grip strength and wrist position were recorded in the self-selected position and then again while the subjects voluntarily deviated the wrist randomly into flexion, extension, or radial or ulnar deviation of 10 to 15 degrees. The self-selected position was 35 degrees of extension and 7 degrees of ulnar deviation. Grip strength was significantly less in any position of deviation from this self-selected position, even after accounting for fatigue. With the wrist in only 15 degrees of extension or in neutral radio-ulnar deviation, grip strength was reduced to two thirds to three fourths of normal. Sex did not affect wrist position. The dominant wrists were within 5 degrees of the nondominant ones but were relatively less extended and in more ulnar deviation. Grip strength is significantly reduced when wrist position deviates from this self-selected optimum position. In the second part of the study, the effect of grasp size on this self-selected position was studied in 21 subjects. The degree of wrist extension was inversely and linearly related to how large a setting on the Jamar dynamometer was used. This was true regardless of hand size, although the effect was more significant for smaller hands. Radial and ulnar deviations were not affected by handle position. A minimum of 25 degrees of wrist extension was required for optimum grip strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Neuropsychological and neurological manifestations of HIV-1 dementia in drug users.

The cognitive and motor deficits associated with human immunodeficiency virus-1 (HIV-1) infection have been studied using neurological examination and neuropsychological tests. However, drug users with HIV-1 infection generally have been excluded from such studies. Forty-four well-characterized drug users stratified by Centers for Disease Control staging were administered a standardized neurological examination and a battery of neuropsychological tests under single-blind conditions designed to minimize the acute effects of psychoactive substances. The results of the blind neurological examination were consistent with the previously ascertained clinical staging of HIV-1 infection. The pattern of neuropsychological deficits across HIV-1 states was similar to those found in cohorts of homosexual men.

AIDS Dementia Complex↗

PubMed1992

Auditory event-related potentials in HIV-1 infection: a study in the drug-user risk group.

Features of event-related potentials (ERPs) may be sensitive and clinically useful markers of central nervous system infection by the human immunodeficiency virus (HIV-1); however, this application has not been studied in the risk group of intravenous drug users. Auditory ERPs generated by an "oddball" paradigm were analyzed for 39 male drug abusers as part of a multimodal assessment. Stage of HIV-1 infection was associated with prolongations of P1, N1, and P3 components of the ERP waveform. Only patients with full acquired immunodeficiency syndrome showed statistically significant increases in waveform prolongations. Specific neuropsychological deficits were not related to waveform latency prolongations.

AIDS Dementia Complex↗

PubMed1992

The dysphoria of heroin addiction.

Levels of dysphoria and opioid dependence were assessed in 54 male patients with heroin addiction applying for drug treatment. During a period of naturalistic heroin use, symptom measures of dysphoria and of spontaneous opioid withdrawal reported by these patients were highly correlated. Upon admission to treatment, levels of dysphoria and opioid withdrawal were assessed before and after a pharmacological challenge with either 0.4 mg naloxone or placebo. Signs and symptoms of opioid withdrawal and symptoms of dysphoria increased in patients following naloxone, but not placebo administration. Naloxone-induced changes in symptoms of dysphoria were correlated with changes in opioid withdrawal as assessed by both subjective and objective measures. These findings suggest that dysphoric mood states in heroin addicts may be, in part, pharmacological sequelae of their drug dependence. Dysphoria due to opioid withdrawal may contribute to the initiation and maintenance of heroin use, and to the high rates of syndromal affective disorders reported in this population.

Adolescent↗

PubMed1992

Obesity in Pima Indians. Distribution characteristics and possible thresholds for genetic studies.

We examined distribution characteristics of the body mass index (BMI; weight/height; kg/m2) in a sample of 1128 male and 1372 female Pima Indians aged 15-65 years. We found that women had a higher mean and variance of BMI than men. From commingling analyses, we determined that the distribution of BMI could be accounted for either by a single skewed distribution or by a mixture of multiple normal components. These component distributions may be used to define provisional thresholds in selecting families for genetic studies. To ensure genetic segregation of obesity predisposing genes in Pima families will require that some members have BMIs > or = 40 kg/m2.

Adolescent↗

PubMed1992

Clinical characteristics of naloxone-precipitated withdrawal in human opioid-dependent subjects.

Studies were conducted to investigate the clinical characteristics of naloxone-precipitated withdrawal in human opioid-dependent subjects. Each of 20 male patients stabilized on 24 mg of methadone daily received two i.v. pharmacological challenges: one with naloxone (0.05, 0.10, 0.15 and 0.20 mg; five patients each dose), and one with saline placebo. Measures of opioid withdrawal, affective state, cognitive performance and changes in autonomic parameters were assessed after each pharmacological challenge. Naloxone produced dose-dependent increases in opiate withdrawal scale scores and in symptoms of dysphoria as measured by the Profile of Mood States. Differences within subjects between naloxone and placebo infusions in Profile of Mood States scores were highly correlated with differences in opioid withdrawal as assessed by both subjective and objective rating scales. Naloxone also produced substantial increases in pulse, systolic and diastolic blood pressure and respiratory rate, as well as a small decrease in temperature. However, naloxone-induced changes from base-line values in these autonomic parameters correlated only modestly with other measures of opioid withdrawal. No differences between infusions were observed in two measures of cognitive performance (Stroop Color and Word Test, Digit Span Test). The results indicate that dysphoric mood states reflecting a broad range of affective experience must be considered as integral components of the naloxone-precipitated opioid withdrawal syndrome.

Adult↗

PubMed1991

Changes in commingled body mass index distributions associated with secular trends in overweight among Danish young men.

The authors present results from a novel approach to understanding recent secular trends in overweight in terms of changes in underlying component distributions. On the basis of an examination of two large overlapping samples of Danish young men (ns = 16,557 and 21,747) spanning birth cohorts 1939-1958, the authors found evidence for two-component distributions, normal and overweight, in all cohorts. In cohorts born after 1940, the authors observed an increase in the size of the overweight component with no corresponding changes in overall mean or component means. On the basis of these results and other published reports, the authors speculate that the secular increase in overweight may be understood as a differential response to environmental change that may be mediated by genotype. The net effect appears to have been an increased penetrance in obesity-prone Danish young men.

Adult↗

PubMed1991

Levels of opioid physical dependence in heroin addicts.

The levels of opioid physical dependence in a group of long-term heroin addicts were ascertained by measuring the severity of the opioid withdrawal syndrome before and after pharmacological challenge with either 0.4 mg naloxone or placebo. Prior to challenge, patients manifested some subjective symptoms but few objective signs of opioid withdrawal. Patients who received placebo (n = 18) showed a significant increase in the mean score on one of three rating scales used to assess opioid withdrawal. Patients who received naloxone (n = 58) showed significant increases in mean scores on all three rating scales, but this was due primarily to increases observed in a minority of patients. Sixty-one percent of patients failed to manifest clinically significant changes in subjective symptoms, and 74% of patients failed to manifest clinically significant changes in objective signs of opioid withdrawal following naloxone administration. The results suggest that a substantial subgroup of heroin addicts are able to use opioids regularly while maintaining relatively low levels of physical dependence.

Adult↗

PubMed1991

Inheritance of extreme overweight in black families.

We used complex segregation analysis to compare the genetic transmission of overweight in randomly selected black (N = 60) and white (N = 961) families. In both groups we found evidence for polygenic transmission. Major gene inheritance was strongly supported in whites and was marginally supported in blacks. Parameter estimates for black and white families were similar, suggesting that overweight is similarly transmitted in the black and white families we observed. There was evidence in both black and white families for high gene frequency and recessive gene expression. Extreme phenotypes common in black families may be the result of interactions between major genotype and polygenic or environmental factors; alternative explanations for differences in black and white families' transmission patterns are discussed. Replication with a larger group of black families is needed to confirm our findings.

Adolescent↗