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Biomedical subjects

D Nelson

Publications and source records attributed to D Nelson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics.

BACKGROUND: Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined. METHODS: In this multicenter study, we identified 61 children who had been hospitalized for diabetic ketoacidosis within a 15-year period and in whom cerebral edema had developed. Two additional groups of children with diabetic ketoacidosis but without cerebral edema were also identified: 181 randomly selected children and 174 children matched to those in the cerebral-edema group with respect to age at presentation, onset of diabetes (established vs. newly diagnosed disease), initial serum glucose concentration, and initial venous pH. Using logistic regression we compared the three groups with respect to demographic characteristics and biochemical variables at presentation and compared the matched groups with respect to therapeutic interventions and changes in biochemical values during treatment. RESULTS: A comparison of the children in the cerebral-edema group with those in the random control group showed that cerebral edema was significantly associated with lower initial partial pressures of arterial carbon dioxide (relative risk of cerebral edema for each decrease of 7.8 mm Hg [representing 1 SD], 3.4; 95 percent confidence interval, 1.9 to 6.3; P<0.001) and higher initial serum urea nitrogen concentrations (relative risk of cerebral edema for each increase of 9 mg per deciliter [3.2 mmol per liter] [representing 1 SD], 1.7; 95 percent confidence interval, 1.2 to 2.5; P=0.003). A comparison of the children with cerebral edema with those in the matched control group also showed that cerebral edema was associated with lower partial pressures of arterial carbon dioxide and higher serum urea nitrogen concentrations. Of the therapeutic variables, only treatment with bicarbonate was associated with cerebral edema, after adjustment for other covariates (relative risk, 4.2; 95 percent confidence interval, 1.5 to 12.1; P=0.008). CONCLUSIONS: Children with diabetic ketoacidosis who have low partial pressures of arterial carbon dioxide and high serum urea nitrogen concentrations at presentation and who are treated with bicarbonate are at increased risk for cerebral edema.

Age Factors↗
PubMed2001

Increased vascular endothelial growth factor expression in human hearts with microvascular fibrin.

We have shown that microvascular changes that promote fibrin deposition in human cardiac allografts adversely affect clinical outcome. However, some allografts exhibit phenotypic changes in capillaries following the deposition of fibrin, which subsequently provide a significant survival advantage. The mechanism(s) involved in these capillary changes is(are) unknown. Similarly, although we have shown a significant temporal relationship between microvascular fibrin deposition and vascular endothelial growth factor (VEGF) immunoreactivity in cardiac allografts, the cellular source and relative changes in VEGF gene expression under these conditions are not known. Using immunocytochemical techniques, biopsies devoid of fibrin deposition lacked detectable VEGF immunoreactivity, whereas biopsies with fibrin deposition showed VEGF immunoreactivity in cardiocytes, interstitium, and some microvessels. By in situ hybridization, biopsies without microvascular fibrin deposition showed faint VEGF hybridization signals confined primarily to cardiocytes. In biopsies with fibrin deposition, strong VEGF hybridization signals were detected in cardiocytes, arteriolar smooth muscle cells were occasionally labeled, and endothelial cells were rarely labeled. By quantitative RT-PCR, biopsies with fibrin deposition (n=5) relatively expressed approximately three-fold more VEGF mRNA than biopsies without fibrin deposition (n=5 P=0.02). Serum VEGF titers also were greater (P=0.01) in recipients with fibrin deposition (372.9+/-66.7 pg/ml n=18) compared to recipients without fibrin deposition (172.1+/-25.0 pg/ml n=16). Collectively, these results support the hypothesis that increased myocyte-derived VEGF production following microvascular fibrin deposition in transplanted human hearts may act in a paracrine manner to promote activational and phenotypic changes in capillaries that provide a survival advantage for the allografts.

Biopsy↗
PubMed2001

Triple-bonded unsaturated fatty acids are redox active compounds.

Unsaturated fatty acids with triple bonds are used as inhibitors of unsaturated fatty acid metabolism or cytochrome P450 reactions because they are believed to be chemically inert. In this paper we use in vitro cytochrome C reduction to show that two commonly used triple-bonded unsaturated fatty acids are in fact potent electron transfer agents and could affect the multiple cellular systems that are redox-modulated.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed2001

Intravenous cocaine increases plasma epinephrine and norepinephrine in humans.

Cocaine has been shown to activate the sympathoadrenal system in both animal and human studies. Controlled human studies have found inconclusive results regarding whether acute cocaine treatment elevates plasma epinephrine and norepinephrine concentrations. The purpose of this study was to investigate whether commonly abused doses of cocaine increase plasma epinephrine and norepinephrine concentrations in humans, in a double-blind, placebo-controlled study. Five male cocaine users were given an intravenous injection of 0.46 mg/kg dose of cocaine or placebo, on two consecutive days. Plasma epinephrine and norepinephrine concentrations were significantly increased in response to cocaine injection compared to placebo. Peak plasma epinephrine and norepinephrine concentrations were reached 3 and 12 min after cocaine injection, respectively. While changes in epinephrine levels following cocaine were correlated with systolic blood pressure and heart rate changes, changes in plasma norepinephrine were correlated with diastolic blood pressure and heart rate changes following cocaine administration. These results suggest that plasma epinephrine and norepinephrine can be used as a measure for cocaine induced sympathoadrenal system activation.

Adult↗
PubMed2001

Use of consumer ratings for quality improvement in behavioral health insurance plans.

BACKGROUND: The Consumer Assessment of Behavioral Healthcare Services (CABHS) survey collects consumers' reports about their health care plans and treatment. The use of the CABHS to identify opportunities for improvement, with specific attention to how organizations have used the survey information for quality improvement, is described. METHODS: In 1998 and 1999, data were collected from five groups of adult patients in commercial health plans and five groups of adult patients in public assistance health plans with services received through four organizations (one of three managed behavioral health care organizations or a health system). Patients who received behavioral health care services during the previous year were mailed the CABHS survey. Non-respondents were contacted by telephone to complete the survey. RESULTS: Response rates ranged from 49% to 65% for commercial patient groups and from 36% to 51% for public assistance patients. Promptly getting treatment from clinicians and aspects of care most influenced by health plan policies and operations, such as access to treatment and plan administrative services, received the least positive responses, whereas questions about communication received the most positive responses. In addition, questions about access- and plan-related aspects of quality showed the most interplan variability. Three of the organizations in this study focused quality improvement efforts on access to treatment. DISCUSSION: Surveys such as the CABHS can identify aspects of the plan and treatment that are improvement priorities. Use of these data is likely to extend beyond the behavioral health plan to consumers, purchasers, regulators, and policymakers, particularly because the National Committee for Quality Assurance is encouraging behavioral health plans to use a similar survey for accreditation purposes.

Adolescent↗
PubMed2001

Superovulation and intrauterine insemination in cases of treated mild pelvic disease.

PURPOSE: Our purpose was to examine the effect of treated mild pelvic disease on the outcome of superovulation with intrauterine insemination (SO/IUI). METHODS: Three hundred cycles of SO/IUI were retrospectively reviewed for 118 women with laparoscopically treated minimal/mild endometriosis and 67 cycles for 28 women with minimal/mild distal tubal disease/adnexal adhesions and compared with 265 cycles in 111 couples with idiopathic infertility. RESULTS: The monthly fecundity rate (MFR) of 6.8% and live birth rate (LBR) of 6% in the endometriosis group were significantly lower (P = 0.002) than those in the idiopathic infertility group (MFR = 13.5%, LBR = 12.1%). The 10.9% MFR and 7.5% LBR in the minimal/mild tubal/adnexal disease were not significantly different from those in the other two groups. CONCLUSIONS: MFR and LBR were higher after SO/IUI in idiopathic infertility compared to those for treated mild/minimal endometriosis or mild/minimal tubal/adnexal adhesions. However, SO/IUI still remains a reasonable option for both these groups prior to IVF-ET.

Adnexal Diseases↗
PubMed2001

The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor.

Malignant mesothelioma (MM) is a solid tumor largely unresponsive to conventional therapies. Immunological gene therapy shows promise in murine models and human clinical trials; however, the role of surgery in combination with gene therapy has not been widely studied. The aim of this study was to determine if debulking surgery improved the effectiveness of gene therapy in a murine MM model. Mice were subcutaneously inoculated with the MM cell line, AC29, at two different sites, 4 days apart, to allow a surgical and distal site tumor to develop. Once tumors were established, the surgical site tumor was debulked and vaccination of syngeneic tumor transfectants encoding genes for IL-4, IL-2, GM-CSF, B7-1 or allogeneic MHC molecules commenced at a site away from both tumors, and tumor growth was measured. Neither debulking surgery nor gene therapy alone delayed tumor growth. However, there was a clear delay of tumor growth when debulking surgery was combined with vaccination of tumor transfectants expressing B7-1 or high levels of GM-CSF. Combinations of these two transfectants did not lead to a synergistic effect. This study demonstrates that debulking surgery can augment the immunostimulatory effects of immunological gene therapy and can delay tumor growth. This has implications for the future design of human gene therapy trials for solid tumors such as MM.

Animals↗
PubMed2001

Prevalence of evaluation for latex allergy and association with practice characteristics in United States dermatologists: results of a cross-sectional survey.

BACKGROUND: Natural rubber latex allergy is a potentially life-threatening, immunoglobin E (IgE) mediated reaction. Despite great strides in identification of high-risk groups, methods for diagnosis remain limited in the United States and most evaluations are performed by allergists. OBJECTIVE: The objective of this study was to estimate the prevalence of evaluation for latex allergy and association with practice characteristics in United States dermatologists. METHODS: A cross-sectional survey of one third of United States Fellows of the American Academy of Dermatology. RESULTS: The survey response rate was 43%. Of responding dermatologists, 17% stated that they evaluate patients for latex allergy, most commonly with a radioallergosorbent (RAST) or use test. Only 3.6% stated that they perform prick or scratch tests for latex allergy in their office, and most of these dermatologists (86%) prepare their own latex prick test solutions. Evaluation for latex allergy was significantly associated with patch testing, photopatch testing, an interest in contact dermatitis, and number of contact dermatitis books owned, but not with number of years in practice. CONCLUSIONS: Most United States dermatologists do not evaluate patients for latex allergy, most likely because of lack of available antigens and because methods for diagnosing latex allergy are not familiar to most dermatologists.

Cross-Sectional Studies↗
PubMed2001

Use of the pediatric symptom checklist in strategies to improve preventive behavioral health care.

OBJECTIVE: The purpose of this study was to examine the utility of the Pediatric Symptom Checklist (PSC) in identifying youth at risk of behavioral health problems and to develop strategies to meet their mental health needs. METHODS: The PSC was completed by the parents of 570 children aged two to 18 years at three urban health centers in Massachusetts. Follow-up interviews were conducted with the parents of 95 of the children. Multidisciplinary teams held case conferences to review the cases of 43 of the 95 children who were interviewed and who were determined to have moderate to severe behavioral health problems. RESULTS: Of the 570 children in the screening sample, 144 (25 percent) had moderate to severe behavioral health problems, as indicated by a positive score on the PSC, and 2 percent had a serious emotional disturbance. Of the 297 pre-school-aged children (younger than six years), 67 (23 percent) received a positive score. Of the 283 school-aged children (age six and older) from both English- and Spanish-speaking families, 77 (27 percent) received a positive score. About one-third of the severely emotionally disturbed youth were receiving some mental health treatment, but only 20 percent were rated by the multidisciplinary team as receiving adequate treatment. CONCLUSIONS: The study provided further support for the validity and reliability of the PSC and confirmed the results of earlier studies that found a high level of unmet needs for mental health services among this population. Use of the PSC in this study promoted an increase in referrals for children in need.

Adolescent↗
PubMed2001

pH-regulated secretion of a glyceraldehyde-3-phosphate dehydrogenase from Streptococcus gordonii FSS2: purification, characterization, and cloning of the gene encoding this enzyme.

Streptococcus gordonii and other viridans streptococci (VS) are primary etiologic agents of infective endocarditis, despite being part of the normal oral microflora. Recently, a surface-bound glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been found on the cells of all tested streptococcal species, where it has been implicated as a virulence factor. In contrast, we observed that a soluble extracellular GAPDH was the major secreted protein from S. gordonii FSS2, an endocarditis strain. The biochemical properties and gene sequence of S. gordonii GAPDH are almost identical to those of other streptococcal GAPDHs. Growth at defined pHs showed that secretion of GAPDH is regulated by environmental pH. GAPDH was primarily surface-associated at growth pH 6.5 and shifted to > 90% secreted at growth pH 7.5. Others have identified S. gordonii promoters that are up-regulated by a pH shift similar to that experienced by organisms entering the blood stream (neutral) from the oral cavity (slightly acid). Analysis of our results suggests that secretion of GAPDH may be a similar adaptation by S. gordonii.

Adaptation, Physiological↗
PubMed2001

Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension.

OBJECTIVE: To assess short-term and long-term responses to treatment with pulmonary vasodilators in patients with sarcoidosis-related pulmonary hypertension. METHODS: A prospective, observational study was performed on eight patients with moderate-to-severe sarcoidosis-related pulmonary hypertension. Patients underwent a short-term vasodilator trial, using inhaled nitric oxide (iNO), IV epoprostenol, and/or oral calcium-channel blockers. A favorable short-term response was considered a > or = 20% decrease in pulmonary vascular resistance (PVR). Five patients received long-term treatment with iNO (with one patient receiving epoprostenol in addition) and underwent follow-up hemodynamic and/or 6-min walk testing. Two patients received long-term treatment with calcium-channel blockers. RESULTS: Baseline (+/- SE) mean pulmonary artery pressure (mPAP) was 55 +/- 4 mm Hg and PVR was 896 +/- 200 dyne.s.cm(-5). A favorable short-term response was seen in seven of eight patients receiving iNO, four of six patients receiving epoprostenol, and two of five patients receiving calcium-channel blockers. With iNO, PVR decreased 31 +/- 5% (p = 0.006) and mPAP decreased 18 +/- 4% (p = 0.003); with epoprostenol, PVR decreased 25 +/- 6% (p = 0.016) and mPAP decreased 6 +/- 2% (p = not significant). Decreased systemic vascular resistance was the only significant response to treatment with calcium-channel blockers. Follow-up 6-min walk test results improved in all five patients receiving long-term treatment with iNO. Follow-up hemodynamic responses in three patients showed preserved vasoresponsiveness. These three patients subsequently died, as did the two patients receiving calcium-channel blockers. The two remaining patients continue to receive iNO. CONCLUSION: In the short term, pulmonary hypertension in patients with sarcoidosis is responsive to treatment with pulmonary vasodilators; these patients may benefit from long-term iNO therapy.

Administration, Inhalation↗
PubMed2001

Screening and monitoring for bladder cancer: refining the use of NMP22.

PURPOSE: While detecting bladder cancer, bladder tumor markers demonstrate improved sensitivity compared with urinary cytology but the current limitation is the low specificity and positive predictive value, that is high false-positive rate. We examined the clinical categories of the false-positive results, established relative exclusion criteria, and recalculated the specificity and positive predictive value of this assay with these criteria. MATERIALS AND METHODS: A total of 608 patients considered at risk for bladder cancer presented to a urology clinic and submitted a single urine sample. Of the 608 patients 529 (87%) presented with de novo hematuria or chronic voiding symptoms without a diagnosis of bladder cancer. There were 79 (13.0%) patients being monitored with a known history of bladder cancer. Each urine sample was examined via cytology, urinalysis, culture and NMP22 protein assay. All patients underwent office cystoscopy, and transurethral resection and/or biopsy if a bladder tumor was suspected. RESULTS: Of the 608 patients 226 (37.2%) presented with microscopic hematuria, 143 (23.5%) with gross hematuria and 239 (39.3%) had chronic symptoms of urinary frequency or dysuria. There were 52 (8.6%) patients who had histologically confirmed bladder cancer. Of these 52 cancers NMP22 detected 46 (88.5%), whereas cytology identified only 16 (30.8%). When atypical cytology was considered positive, cytology detected 32 (61.5%) cases. In the 135 patients with increased NMP22 values the 46 identified tumors were accompanied by 89 false-positive values yielding a specificity of 83.9% and a positive predictive value of 34.1%. These false-positive results were divided into 6 clinical categories. Exclusion of these categories improved the specificity and positive predictive value of NMP22 to 99.2% and 92.0%, respectively, yielding results similar to urinary cytology (99.8% and 94.1%). CONCLUSIONS: Awareness and exclusion of the categories of false-positive results can increase the specificity and positive predictive value of NMP22, enhancing the clinical use of this urinary tumor marker.

Aged↗
PubMed2000

Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis.

PURPOSE: To conduct a systematic review and quantitative meta-analysis of the therapeutic efficacy and tolerability of Pygeum africanum in men with symptomatic benign prostatic hyperplasia. METHODS: Studies were identified through the search of Medline (1966 to 2000), Embase, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. Randomized trials were included if participants had symptomatic benign prostatic hyperplasia, the intervention was a preparation of P. africanum alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacologic therapies for benign prostatic hyperplasia, and treatment duration was at least 30 days. Two investigators independently extracted key data on design features, subject characteristics, and therapy allocation. RESULTS: A total of 18 randomized controlled trials involving 1,562 men met the inclusion criteria and were analyzed. Many studies did not report results in a method that permitted meta-analysis. Only 1 of the studies reported a method of treatment allocation concealment, although 17 were double-blinded. The mean study duration was 64 days (range 30 to 122). Compared with placebo in 6 studies, P. africanum provided a moderately large improvement in the combined outcome of urologic symptoms and flow measures as assessed by an effect size defined by the difference of the mean change for each outcome divided by the pooled standard deviation for each outcome (-0.8 SD [95% confidence interval (CI): -1.4 to -0.3]). Summary estimates of individual outcomes were also improved by P. africanum. Men were more than twice as likely to report an improvement in overall symptoms (risk ratio = 2.1, 95% CI: 1.40 to 3.1). Nocturia was reduced by 19% and residual urine volume by 24%; peak urine flow was increased by 23%. Adverse effects due to P. africanum were mild and similar to placebo. The overall dropout rate was 12% and was similar for P. africanum (13%), placebo (11%), and other controls (8%; P = 0.4 versus placebo and P = 0.5 versus other controls). CONCLUSIONS: The literature on P. africanum for the treatment of benign prostatic hyperplasia is limited by the short duration of studies and the variability in study design, the use of phytotherapeutic preparations, and the types of reported outcomes. However, the evidence suggests that P. africanum modestly, but significantly, improves urologic symptoms and flow measures. Further research is needed using standardized preparations of P. africanum to determine its long-term effectiveness and ability to prevent complications associated with benign prostatic hyperplasia.

Fatty Alcohols↗
PubMed2000

In vivo cross-presentation of a soluble protein antigen: kinetics, distribution, and generation of effector CTL recognizing dominant and subdominant epitopes.

Cross-presentation of exogenous Ags via the MHC class I pathway is now recognized for its role in self-tolerance, tumor immunity, and vaccine development. However, little is known about the in vivo distribution and kinetics of cross-presented protein Ags, nor the subsequent development of CTL effector responses to dominant or subdominant epitopes. We examined the location and duration of cross-presented Ag by using 5,6-carboxy-succinimidyl-fluorescein ester-labeled T cells from class I-restricted Ag-specific TCR mice. Comparisons of results from an in vitro (51)Cr release CTL assay with an in vivo CTL assay provided physiologically relevant insights into the functional capacities of CTL specific for epitopes with differing affinities. These data demonstrate that efficient cross-presentation of a dominant class I-restricted Ag is dose related and remains largely localized, but not limited to the draining lymph nodes for up to 3 wk following a single injection of soluble protein. Within this period, dominant peptide-specific CTL are fully functional in vivo throughout the secondary lymphoid system. However, no in vivo responses are seen to a subdominant or cryptic epitope. Prolonging Ag cross-presentation via use of IFA promoted persisting in vivo dominant epitope-specific CTL activity and revealed dose-responsive precursor CTL to the subdominant, but not to a cryptic epitope. Analysis of functional in vivo CTL responses demonstrated that, in the presence of strong ongoing responses to the dominant peptide, lytic activity of CTL directed at weaker epitopes is undetectable.

Adjuvants, Immunologic↗