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D Nelson

Publications and source records attributed to D Nelson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Sex and menstrual cycle differences in the subjective effects from smoked cocaine in humans.

To investigate sex and menstrual cycle effects in response to cocaine administration, data from existing studies were analyzed. First, responses to a single delivery of 0.4 mg/kg smoked cocaine were investigated. Women reported lower ratings for measures of paranoid/suspicious and heart racing/pounding than did men. In addition, women in the luteal phase reported diminished ratings for a measure of feel high than did both women in the follicular phase of the menstrual cycle and men. Second, responses to up to 6 deliveries of 0.4 mg/kg smoked cocaine were investigated. Women, compared with men, had lower ratings on feel high, heart racing/pounding, and feel stimulated. Results suggest that there are significant sex and menstrual phase differences in the subjective effects of cocaine.

Adult↗
PubMed1999

Withdrawal and pre-menstrual symptomatology during the menstrual cycle in short-term smoking abstinence: effects of menstrual cycle on smoking abstinence.

This study employs a rigorous inpatient laboratory setting to test the hypothesis that withdrawal symptomatology in short-term smoking cessation in women is increased in the late luteal phase when pre-menstrual symptomatology is the highest. Twenty-one female smokers with clinical, anatomical, and hormonal verification of their menstrual cycle phase were randomized to either a smoking abstinence group (n = 16) or a continued smoking group (n = 5). Participants were admitted to the General Clinical Research Center during alternate phases of their cycle for two 7-day admissions with a 1-month interim period when they resumed smoking. Dependent measures, i.e., Minnesota Nicotine Withdrawal Scale scores, Questionnaire on Smoking Urges scores and Pre-menstrual Assessment Form scores were collected during 2 days of baseline and 5 days of smoking deprivation. Smoking behavior was documented by self-report, breath CO levels and saliva cotinine measurements. Withdrawal symptomatology was not affected by menstrual cycle phase during short-term cessation in spite of increased pre-menstrual changes seen in the late luteal phase. In addition, no phase effect on smoking behavior was detected and cigarette consumption remained stable across the cycle in both groups. These results suggest that for some smoking cessation studies, complex strategies to control for menstrual cycle effects may not be necessary. However, Smoking Urges scores did suggest increased desire to smoke and desire to relieve negative affect in the late luteal phase when women have higher pre-menstrual symptomatology. This suggests women may have greater difficulty quitting smoking in late luteal phase, and it seems prudent to recommend that women quit during the follicular phase of their cycle.

Adult↗
PubMed1999

Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat.

PURPOSE: The limitation of current urinary tumor markers is the low specificity and positive predictive value, which clinically manifests as a high false-positive rate. We analyzed the false-positive data of 2 urinary tumor markers, NMP22 and the BTA stat tests. We examined the clinical categories of the false-positive results, established relative exclusion criteria, and recalculated the specificity and positive predictive value after using the exclusion criteria. MATERIALS AND METHODS: A total of 278 symptomatic patients who presented to a urology clinic were asked to submit a single voided urine sample. Each sample was divided into 3 aliquots of which 1 was stabilized with the NMP22 test kit stabilizer and assayed for NMP22, 1 was tested for BTA stat and 1 was sent for cytological examination. All patients subsequently underwent office cystoscopy and bladder biopsy if indicated. RESULTS: Of the 278 symptomatic patients 112 presented with microscopic hematuria, 77 gross hematuria and 89 chronic symptoms of urinary frequency or dysuria. Of 34 cases (12%) of histologically confirmed bladder cancer NMP22 detected 28 (82.4%), BTA stat 23 (67.7%) and cytology only 10 (29.4%). When atypical cytologies were considered positive, cytology then detected 19 cases (55.9%). Elevated NMP22 values were positive in 28 cases and false-positive in 44 for a specificity of 82% and a positive predictive value of 38.9%. Similarly, BTA stat test was positive in 23 cases and false-positive in 43 for a specificity of 82.4% and a positive predictive value of 34.9%. When atypical cytologies were considered positive, the specificity and positive predictive value were 93% and 55.9%. Greater than 80% of the false-positive results were clinically categorized as benign inflammatory or infectious conditions, renal or bladder calculi, recent history of a foreign body in the urinary tract, bowel interposition segment, another genitourinary cancer or an instrumented urinary sample. A category of "no known pathology" was included in analysis as a control. History of ureteral stents or any bowel interposition segment had a 100% false-positive rate. Exclusion of all 6 clinical categories improved the specificity and positive predictive value of NMP22 (95.6%, 87.5%) and BTA stat (91.5%, 69.7%), and was similar to urinary cytology. CONCLUSIONS: Awareness and exclusion of the categories of false-positive results can increase the specificity and enhance the clinical usefulness of NMP22 and BTA stat tests. Similarly, treating an atypical cytology as positive can enhance the sensitivity and usefulness of urinary cytology.

Antigens, Neoplasm↗
PubMed1999

Adaptation to hypoxia alters energy metabolism in rat heart.

The present study characterized metabolic changes in the heart associated with long-term exposure to hypoxia, a potent stimulus for pulmonary hypertension and right ventricular hypertrophy. When anesthetized rats adapted to chronic hypoxia spontaneously respired room air, their mean right intraventricular peak systolic pressure (RVSP) was twice that in normal control animals with the same arterial PO2. RVSP was linearly related to right ventricular mass (r = 0.78). Oxidative capacity (O2 consumption) of homogenates of right and left ventricles from both groups of rats was measured with one of the following substrates: pyruvate, glutamate, acetate, and palmitoyl-L-carnitine. Oxidation of all substrates was significantly greater in the left than in the right ventricle in normal rats but not in hypoxia-adapted animals, where it was the same, within the experimental error. O2 consumption by the left ventricle was greater in control than in experimental rats, but right ventricular O2 consumption was similar in the two groups. Maximal reaction velocity of cytochrome-c oxidase was about the same in the two ventricles, and there were no significant differences between control and hypoxia-adapted animals. HPLC analyses showed significantly higher aspartate levels and aspartate-to glutamate concentration ratios in both ventricles of hypoxic rats than in corresponding tissues from controls, indicative of a decreased flux through the malate-aspartate shuttle under conditions of O2 limitation. Myocardial glutamine levels were lower in hypoxic rats, and glutamine-to-glutamate concentration ratios decreased, although primarily in the pressure-overloaded right ventricle. These findings indicate that normal energy metabolism in the left ventricle differs from that in the right and that the differences, particularly those of amino acid metabolism, are markedly influenced by chronic exposure to hypoxia.

Adaptation, Physiological↗
PubMed1999

Development of a consumer survey for behavioral health services.

A consumer survey was designed to assess the quality of mental health and substance abuse services and evaluate insurance plans that provide such services. This paper describes the development of the Consumer Assessment of Behavioral Health Services instrument, which began with a review of existing consumer satisfaction surveys and input from several groups working toward development of nationally standardized satisfaction instruments. Consumer focus groups were used to ensure that all the important domains of quality were included, and group members were interviewed to ensure that all items on the instrument were understandable. Results of a pilot test conducted with 160 consumers, 82 enrolled in Medicaid plans and 78 in commercial plans, suggested that the survey was able to distinguish between the two groups in terms of evaluations of their care and insurance plans. Future efforts will focus on further testing of larger, more diverse samples and on developing scoring and reporting formats for the survey that will be useful to consumers and purchasers in choosing behavioral health services and plans.

Consumer Behavior↗
PubMed1999

Localization and characterization of antithrombin in human kidneys.

Antithrombin is a serine protease inhibitor that is critical in maintaining a thromboresistant vasculature. The association between low serum antithrombin concentration and renal disease suggests that the kidney plays a role in the conservation of plasma antithrombin. We used immunohistochemical techniques to determine the spatial distribution, heparin binding characteristics, and intracellular and intercellular localization of antithrombin in biopsy specimens (n = 53) of human donor kidneys obtained at the time of transplantation. In the renal cortex, double antibody techniques demonstrated the presence of intracellular antithrombin in proximal tubule epithelial cells. The reactivity was granular and was co-localized with vesicle-like structures. Distal and collecting tubules did not demonstrate intraepithelial antithrombin reactivity. No tubule structures in the medullary region demonstrated intracellular antithrombin, but all these structures showed intense basement membrane antithrombin reactivity. Double antibody techniques also demonstrated that the heparin binding domain of intraepithelial antithrombin was occupied. Semiquantitative scores for intraepithelial antithrombin were significantly decreased in renal biopsy specimens obtained 30 min after anastomosis compared with biopsies from the same organ obtained before anastomosis. These findings suggest that antithrombin, probably in association with heparin or heparan sulfate, is internalized by renal proximal epithelial cells. Although the ultimate fate of intraepithelial antithrombin is not known, this may represent a mechanism by which the kidney helps to maintain plasma antithrombin concentrations.

Antithrombins↗
PubMed1999

Comparative cleavage sites within the reactive-site loop of native and oxidized alpha1-proteinase inhibitor by selected bacterial proteinases.

Human alpha1-proteinase inhibitor (alpha1-PI) is responsible for the tight control of neutrophil elastase activity which, if down regulated, may cause local excessive tissue degradation. Many bacterial proteinases can inactivate alpha1-PI by hydrolytic cleavage within its reactive site, resulting in the down regulation of elastase, and this mechanism is likely to contribute to the connective tissue damage often associated with bacterial infections. Another pathway of the inactivation of alpha1-PI is reversible and involves oxidation of a critical active-site methionine residue that may influence inhibitor susceptibility to proteolytic inactivation. Hence, the aim of this work was to determine whether this oxidation event might affectthe rate and pattern of the cleavage of the alpha1-PI reactive-site loop by selected bacterial proteinases, including thermolysin, aureolysin, serralysin, pseudolysin, Staphylococcus aureus serine proteinase, streptopain, and periodontain. A shift of cleavage specificity was observed after alpha1-PI oxidation, with a preference for the Glu354-Ala355 bond by most of the proteinases tested. Only aureolysin and serralysin cleave the oxidized form of alpha1-PI faster than the native inhibitor, suggesting that bacteria which secrete these metalloproteinases may specifically take advantage of the host defense oxidative mechanism to accelerate elimination of alpha1-PI and, consequently, tissue degradation by neutrophil elastase.

Amino Acid Sequence↗
PubMed1999

Interventions in a heart transplant recipient with a histrionic personality disorder.

Organ transplantation is a psychosocially demanding process. Patients must undergo a comprehensive evaluation to await a donor organ that may never become available. After transplantation, recipients must deal with the acceptance of a new organ and comply with a medical regimen that includes numerous medications, follow-up exams, and procedures. Emotional well-being is monitored throughout the transplant process. However, despite the best of efforts and thorough pretransplant bio-psycho-social evaluations, it is possible for patients to have significant psychopathology that remains undetected. Following the stress of transplantation, such patients may present with exacerbation of symptomatology, which has the potential to negatively affect compliance and long-term outcome.

Adaptation, Psychological↗
PubMed1999

Patient characteristics associated with vasectomy reversal.

PURPOSE: More than 30 million couples throughout the world are using vasectomy as a method of birth control. It is estimated that up to 6% of men who undergo voluntary sterilization will eventually request reversal, despite the high cost and relatively low success rate of the procedure. We identified characteristics that predict which vasectomy patients may request reversal. We also examined the cost and effectiveness of pre-vasectomy sperm cryopreservation followed by intrauterine insemination as an alternative method of achieving pregnancy. MATERIALS AND METHODS: We reviewed medical charts of 365 patients who underwent vasectomy and 290 who underwent vasectomy reversal between 1990 and 1997. Data were collected on patient age at the time of vasectomy, religion, occupation, wife employment status, number of marriages, number of children, reason for reversal, and number of years between vasectomy and reversal. Based on previously reported values, pregnancy rates and cost per successful pregnancy were estimated for vasectomy reversal surgery, and compared with a calculated cost per pregnancy for sperm cryopreservation and intrauterine insemination. RESULTS: Patient factors significantly associated with increased vasectomy reversal included younger age at time of vasectomy (p < 0.001) and a wife who worked outside the home (p < 0.001). Vasectomy reversal occurred 12.5 times more often (95% confidence interval [CI] 7.6 to 20.7) in men who underwent vasectomy in their 20s than in men who were older. Men whose wives were not employed requested reversal 0.48 times as often (95% CI 0.33 to 0.71) as those whose wives worked. Men who were younger at vasectomy tended to wait longer before reversal (median 10 years) than other patients (p < 0.001). At 10 years our calculated pregnancy rates and cost per pregnancy were 44% and $12,727 for vasectomy reversal, and 41% and $9,512 for intrauterine insemination with banked sperm (3 attempts). CONCLUSIONS: Patients who requested vasectomy reversal most often chose voluntary sterilization at a younger age. We believe that younger men should be given better pre-vasectomy counseling. However, the success rate and cost-effectiveness of sperm cryopreservation before vasectomy, with subsequent intrauterine insemination, may make this nonsurgical alternative desirable for younger couples who choose vasectomy even when properly informed about reversal rates.

Adult↗
PubMed1999

The wallstent I and II for malignant esophageal obstruction.

The Wallstent I and II esophageal endoprostheses are effective in the palliation of malignant esophageal obstruction and the closure of digestive-respiratory fistulas. The author reviews the evolution of the Wallstent esophageal endoprosthesis and techniques for successful insertion, and summarizes the published literature with regard to clinical outcomes of the European and American Wallstent designs.

Biocompatible Materials↗
PubMed1999

"Lifepoint": a case study in using social science community identification data to guide the implementation of a needle exchange program.

The public health benefits of needle exchange programs (NEPs) are well known. NEPs lower risk factors for HIV transmission by providing injection drug users (IDUs) with clean syringes and needles; harm reduction materials; and referrals to drug, sexually transmitted disease, mental health, and medical treatment facilities. While exchange programs continue to be implemented, there have been few reports illustrating how social science and community assessment research can be used to guide the development of NEPs. Using the Lifepoint needle exchange program in Milwaukee as a case study, this paper shows how social science methods can be used to understand IDU culture through the community identification process, link qualitative and observational findings to program decision making, and guide the implementation and operation of a needle exchange. The community identification process showed that there were different IDU subcultures in the city indicating that the NEP would need to be tailored to meet the distinctive needs of multiple drug use networks. Ethnographic field observations and key informant and systems representative interviews resulted in a two-stage NEP planning process that included a community task force on IDUs and of the development of methods to operationalize community assessment findings into the operating plan of the NEP. This process illustrates the importance of integrating a systematic community analysis in the planning of a NEP.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Tubular antithrombin at transplantation determines subsequent renal allograft function.

BACKGROUND: Antithrombin is found in the microvasculature and tubules of normal and transplanted human kidneys. Although depletion of vascular antithrombin is associated with renal allograft dysfunction, neither the distribution nor clinical significance of tubular antithrombin is known. METHODS: Changes in tubular antithrombin in biopsy specimens (n=41) obtained from donor kidneys at transplantation were studied immunohistochemically. The relationship between these changes and subsequent graft function was analyzed. RESULTS: Granular intracellular antithrombin was found only within the proximal tubular epithelium. Allografts with depleted tubular antithrombin at transplantation (n=20) had significantly greater plasma creatinine concentrations at posttransplant days 3 (P < 0.001) and 5 (P < 0.03) than allografts with normal tubular antithrombin (n=21). Indeed, depletion of tubular antithrombin at transplantation correlated with the degree of graft dysfunction at 3 days after transplantation. CONCLUSIONS: Depleted tubular antithrombin at transplantation is associated with reduced early graft function, and this may identify patients at risk of a complicated follow-up.

Antithrombins↗
PubMed1998

Comparative properties of two cysteine proteinases (gingipains R), the products of two related but individual genes of Porphyromonas gingivalis.

Proteolytic enzymes produced by Porphyromonas gingivalis are important virulence factors of this periodontopathogen. Two of these enzymes, referred to as arginine-specific cysteine proteinases (gingipains R), are the product of two related genes. Here, we describe the purification of an enzyme translated from the rgpB/rgp-2 gene (gingipain R2, RGP-2) and secreted as a single chain protein of 422 residues. The enzyme occurs in several isoforms differing in pI, molecular mass, mobility in gelatin zymography gels, and affinity to arginine-Sepharose. In comparison to the 95-kDa gingipain R1, a complex of catalytic and hemagglutinin/adhesin domains, RGP-2 showed five times lower proteolytic activity, although its activity on various P1-arginine p-nitroanilide substrates was generally higher. Gingipains R amidolytic activity, but not general proteolytic activity, was stimulated by glycyl-glycine. However, in cases of limited proteolysis, such as the inactivation of alpha-1-antichymotrypsin, glycyl-glycine potentiated inhibitor cleavage. In contrast, alpha-1-proteinase inhibitor was not inactivated by gingipains R and only underwent proteolytic degradation during boiling in reducing SDS-polyacrylamide gel electrophoresis treatment buffer. Similarly, native type I collagen was completely resistant to cleavage by gingipains but readily degraded after denaturation. Together, these data explain much of the controversy regarding gingipains structure and substrate specificity and indicate that these enzymes function as P. gingivalis virulence factors by proteolysis of selected target proteins rather than random degradation of host connective tissue components.

Adhesins, Bacterial↗
PubMed1998

Inactivation of alpha1-proteinase inhibitor as a broad screen for detecting proteolytic activities in unknown samples.

The need for a quick, simple screening method for the detection of general proteolytic activity prompted us to determine whether cleavage within the reactive site loop region (RSL) of alpha1-proteinase inhibitor (alpha1-PI), a well-characterized member of the serpin family known to be susceptible to proteolytic inactivation, can be utilized for this purpose. Inactivation of alpha1-PI in the RSL region can be measured by loss of residual inhibitory capacity of alpha1-PI against its target proteinase. While we originally utilized this assay to detect a new proteinase from culture supernatants of Porphyromonas gingivalis, the feasibility of extending this assay to scan for proteolytic activity from other systems was also assessed. As an example, we found that the serine proteinase from Staphylococcus aureus (SSP) had virtually the same catalytic efficiency in inactivating alpha1-PI in our assay as it did in the hydrolysis of the synthetic substrate Z-Phe-Leu-Glu-pNA (kcat/Km value of 2 x 10(4) M-1 s-1 vs 2.6 x 10(4) M-1 s-1, respectively). Additionally, in both assays activity could be readily detected in less than a 1 h incubation at SSP concentrations in the picomolar range. This assay is unique in that proteinases which hydrolyze peptide bonds within the RSL of alpha1-PI can readily be detected as measured by loss of alpha1-PI inhibitory activity.

Amino Acid Sequence↗
PubMed1998

Cotinine: effects with and without nicotine.

The purpose of this study was to examine the effects of the metabolite of nicotine, cotinine, in comparison to the effects of the nicotine patch, and a combination thereof during cigarette abstinence. More specifically, this study examined the effects of cotinine on physiological measures, subjective measures assessing craving, withdrawal symptoms and mood, and performance measures. A between-subject, 2 x 2 factorial design was used, with the daily administration of a 15-mg nicotine patch (Nicotrol) versus placebo patch as one factor and 80 mg of oral cotinine fumarate versus placebo drug as the other factor. Baseline measures were obtained while the subjects smoked cigarettes on an ad lib basis for 1 week. Subjects (n = 106) were then randomly assigned to one of four treatment conditions and for the next 14 days were required to be abstinent from cigarettes and take the study drugs. Cotinine administration, with or without nicotine patch, produced serum cotinine concentrations 3 4 times higher than during ad lib smoking. Results showed a reduction of self-reported tobacco withdrawal symptoms using the nicotine patch alone. Cotinine alone had no effect on withdrawal symptoms. However, when nicotine patch was combined with cotinine, the beneficial effect of the nicotine patch on withdrawal symptoms was absent. Therefore, cotinine appears to antagonize the effects of nicotine in the alleviation of withdrawal symptoms at concentrations higher than that attained from normal smoking. This effect does not appear to be mediated by changes in nicotine disposition.

Administration, Topical↗
PubMed1998

Effects of cotinine on cigarette self-administration.

Previous studies have shown that cotinine, a metabolite of nicotine, antagonizes some of the effects of nicotine. One study showed that cotinine eliminates the beneficial effects of the nicotine patch in reducing cigarette withdrawal symptoms. The purpose of this study was to examine the effects of various doses of cotinine on cigarette self-administration. Subjects were randomly assigned to one of three doses of cotinine fumarate (40, 80 and 160 mg) and placebo, each for a period of 10 days, in a randomized order. Outcome variables included measures of nicotine intake and subjective responses to smoked cigarettes. Results showed no differences in the number of cigarettes smoked, carbon monoxide levels, and weights of cigarette butts across the various doses of cotinine and placebo. However, higher nicotine serum levels were observed in the 160 mg cotinine fumarate condition compared to placebo and to 40 mg cotinine fumarate. No systematic effects of cotinine on subjective responses to cigarettes were observed. Cotinine appears potentially to have a selective modulatory effect on nicotine withdrawal symptoms but not on cigarette smoking.

Adult↗