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Biomedical subjects

J Johnson

Publications and source records attributed to J Johnson.

At least 199 records · Page 11Linked to original sources
PubMed1997

Reductions in HIV-1 disease progression for zidovudine/lamivudine relative to control treatments: a meta-analysis of controlled trials.

OBJECTIVES: Four randomized double-blind trials have demonstrated that zidovudine/lamivudine (ZDV/3TC) reduces HIV RNA and raises CD4 counts relative to control treatments (ZDV or ZDV/zalcitabine (ddC)]. A meta-analysis of the clinical events in these trails was conducted to determine whether treatment with ZDV/3TC was also associated with a clinical benefit. DESIGN: The four trials, ZDV/3TC versus ZDV (NUCA3001, NUCB3001, NUCB3002) or versus ZDV/ddC (NUCA3002), were run concurrently, using the same doses of ZDV and 3TC. SETTING: Investigational sites in Europe and North America. PATIENTS: The trials recruited 972 HIV-1-positive, male and female patients aged > or = 18 years, with CD4 counts of 100-500 cells x 10(6)I. Two trials were for ZDV-naive patients and two were for ZDV pre-treated patients. MAIN OUTCOME MEASURES: Progression to first new Centers for Disease Control and Prevention (CDC) B or C event was compared between all ZDV/3TC arms and all control (ZDV, ZDV/ddC) arms. RESULTS: A total of 118 patients progressed to a first new CDC B/C event during the four trials, while 28 progressed to a new CDC event. Meta-analysis of the trials showed a 49% reduction in progression to new CDC B/C events (relative risk, 0.509; 95% confidence interval, 0.365-0.710; P < 0.0001) and a 66% reduction in progression to new CDC C events (relative risk, 0.344; 95% confidence interval, 0.169-0.700; P = 0.003) for the ZDV/3TC patients relative to the control patients. Reductions in progression to CDC B/C disease were seen in subgroups of naive and pre-treated patients, those with high and low CD4 counts and symptomatic and asymptomatic patients. CONCLUSIONS: ZDV/3TC combination treatment delays the progression of CDC B/C disease compared with control treatments. In view of the low incidence of CDC C events, the results for progression to CDC C disease should be interpreted with caution.

Adolescent↗
PubMed1997

Psychopathology in male and female HIV-positive and negative injecting drug users: longitudinal course over 3 years.

OBJECTIVE: To evaluate the impact of HIV illness on psychiatric and psychosocial functioning over 3 years in a sample of male and female HIV-positive injecting drug users (IDU), with a comparison group of HIV-negative male and female IDU. DESIGN: As part of a multidisciplinary study, 121 men (69 HIV-positive, 52 HIV-negative) and 66 women (36 HIV-positive, 30 HIV-negative) were evaluated semiannually for seven visits. Attrition, unrelated to sex or serostatus, was 33%. RESULTS: At baseline, rates of major depression and dysthymia ranged from 15% (HIV-negative men) to 33% (HIV-positive men and HIV-negative women). Global impairment was in the range found in psychiatric patients (mean Global Assessment of Functioning scores, 46-51). Higher levels of social support and less social conflict were independently associated with decreased distress and improved global functioning among both men and women. For both HIV-positive groups, degree of improvement over time was related to degree to HIV progression: those who remained healthier in terms of CD4 count and illness stage showed more improvement. HIV-seronegative status was associated with less distress for men but not for women. Overall, women reported higher levels of psychiatric distress than men. CONCLUSIONS: High rates of psychopathology were found in this IDU cohort, independent of HIV status and sex. Although rates of psychopathology, injecting drug use and distress declined slightly during the study, they remained elevated; accordingly, psychiatric services are indicated for this population.

Cohort Studies↗
PubMed1997

Effects of cardiac allograft vasculopathy on myocardial blood flow, vasodilatory capacity, and coronary vasomotion.

BACKGROUND: Coronary vasculopathy is the third leading cause of death 1 year after cardiac allograft transplantation. This study was designed to assess the hemodynamic effects of transplant vasculopathy on myocardial blood flow and vasomotion. METHODS AND RESULTS: Thirty-two patients were studied 1 to 2 years after cardiac transplantation by use of positron emission tomography (n = 32), intravascular ultrasound (n = 26), coronary angiography (n = 32), and endomyocardial biopsy (n = 32). Twenty healthy individuals served as control subjects. Quantitative intravascular ultrasound was used to compute coronary lumen area, intimal thickness, and intimal index [Intima Area/(Intima + Lumen Area)]. Myocardial blood flow was quantified with the use of 13N-ammonia/positron emission tomography. Mean myocardial blood flow was higher in the transplant patients than in control subjects (0.94 +/- 0.26 versus 0.68 +/- 0.16 mL.min-1.g-1 P < .0005). Cold increased myocardial blood flow to 0.79 +/- 0.18 mL.min-1.g-1 in control subjects but not in patients (0.98 +/- 0.36 mL.g-1.min-1). Hyperemic myocardial blood flow was lower in patients than in control subjects (1.69 +/- 0.78 versus 2.30 +/- 0.32 mL.min-1.g-1; P < .05) and was inversely related to maximal intimal thickness and intimal index (all P < .05). The myocardial flow reserve was reduced in patients (1.82 +/- 0.55 versus 3.45 +/- 1.03; P < .0001). CONCLUSIONS: The degree of intimal thickening is correlated with abnormalities in coronary function in patients with diffuse cardiac allograft vasculopathy. The reduction in vasodilatory capacity and the abnormal blood flow response to cold suggest abnormalities in endothelium-dependent and -independent coronary vasodilation in transplant recipients.

Cold Temperature↗
PubMed1997

A follow-up study of job strain and heart disease among males in the NHANES1 population.

Several studies have associated heart disease with job strain, defined as low job control and high job demands. We have studied incident heart disease (519 cases) and job strain among 3,575 males in NHANES1 survey who were currently employed at baseline in the early 1970s, and followed through 1987. Scores for job control and job demands were assigned to each subject based on current occupation at baseline. Controlling for conventional risk factors, we found no excess risk for those with the highest strain (lowest control and highest demands, rate ratio 1.08). Those with highest job control did have significantly decreased risk (rate ratio 0.71, 95% CI 0.54-0.93). In blue-collar workers (58% of subjects) there was a significant inverse trend in risk with increasing job demands. Control for level of physical activity did not change this finding. A combination of high control and demand was protective among blue-collar workers (odds ratio 0.69, 0.48-0.99). Our findings suggest that class-specific analyses are needed in studying job stress, and that "active" blue-collar workers with high control and high demand are protected against heart disease. The "job demand" variable may measure whether work is challenging rather than fast-paced. Our findings are limited by the use of assigned job scores based on job title.

Follow-Up Studies↗
PubMed1997

Neuromuscular fatigue in prostate cancer patients undergoing radiation therapy.

OBJECTIVE: To determine the etiology of fatigue in prostate cancer patients undergoing radiation therapy (RT). METHODS: Thirteen prescreened men (60 to 76 years in age, 58 to 130 kg in body weight) were evaluated for neuromuscular fatigue (NMF) of the tibialis anterior (TA) muscle, cardiopulmonary fatigue (CPF), and psychological-subjective fatigue (PSF) at 1 to 2 weeks before RT (Pre), at the end of 8 weeks of RT (RT), and at 5 to 6 weeks after completion of RT (Post). OUTCOME MEASURES: For NMF, the TA muscle was fatigued by sustained isometric contraction at 80% of maximum voluntary contraction for 60 seconds on a force dynamometer. Neuromuscular efficiency (NME) expressed as a ratio of isometric force (in Newtons) and respective integrated electromyograms were measured. For CPF, stress testing was performed on a treadmill using the modified Bruce protocol. Piper Fatigue Scale, Beck Depression Inventory, and Epworth Sleepiness Scale were administered to evaluate PSF. DATA ANALYSIS: Paired t tests, single factor analysis of variance, and nonparametric analysis. RESULTS: At RT, there was a significant decline in NME of TA at the beginning (18.4%, p < .01) and the end (29.2%, p < .001) of sustained muscle contraction for 60 seconds. Post values were lower but nonsignificant in comparison with Pre values. NME recovered within 5 to 6 weeks after RT. No abnormalities were detected in CPF or PSF. No correlation was found between the decline in NME and psychological status of the patients. CONCLUSION: Results provide definitive evidence of transient decline in NME in prostate cancer patients at the completion of RT. The effect seems to be specific for neuromuscular performance alone and is independent of the cardiovascular or psychological status of the patients.

Adenocarcinoma↗
PubMed1997

A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin's disease at presentation and relapse.

About one fourth of patients with Hodgkin's disease relapse after therapy. The mechanisms that lead to resistance to treatment in these patients are poorly understood. The authors describe the differential protein expression of p53, proliferating cell nuclear antigen (PCNA), and p21 at initial presentation and relapse, and discuss their role in disease progression and resistance to therapy. Thirty-four patients with Hodgkin's disease who had relapsed after standard chemotherapy and radiotherapy regimens were assessed for the expression of p53 protein, PCNA, and p21 protein (waf/cip 1). In 14 of these cases, sequential biopsies performed both at presentation and at relapse were available for the study. Seventy-five percent of the cases were positive for the p53 protein. Tumors at relapse had higher p53 and PCNA scores than those at initial presentation. In the paired samples, a significant increase was noted in the number of p53 and PCNA-positive cells and in the intensity of staining with p53 antibody. Six of seven paired samples tested for p21 showed an increased p21 expression at relapse. These results suggest that, at relapse, Reed-Sternberg (RS) cells and their variants positive for p53, PCNA, and p21 are increased in number and individually have an increased expression of p53, PCNA, and p21 proteins. These findings suggest that therapy failure and relapse may, at least in part, be associated with altered p53, p21, and PCNA pathways. HUM PATHOL 28:549-555. This work was carried out during an exchange fellowship program at the National Cancer Institute, Bethesda. There are no restrictions on its use

Adolescent↗
PubMed1997

An automated multidimensional screening approach for rapid method development in high performance liquid chromatography.

Despite enormous advancements in the area of high performance liquid chromatography (HPLC) in recent years, method development remains a major challenge. This is primarily due to the unknown nature of the matrix material which sometimes is difficult to characterize (e.g. biological matrices). To improve the efficiency of method development a multidimensional screening approach was presented. This approach was based on two major steps: (1) a matrix spiked with drug was eluted from a large number of columns, each under different mobile phase compositions, to provide the preliminary selectivity-separation information; (2) this information was then used to compose column switching pairs (each pair consisted of a preparatory column followed by an analytical column) and the elution profile was evaluated to determine the suitable clean up and quantitation conditions. An example was provided using ethyl 3,5-bis(acetylamino)-2,4,6-triiodobenzoate (EEDA), an X-ray enhancement agent, in human plasma. Since the HPLC system was fully automated the data generation time, and consequently the method development time, can be significantly reduced.

Acetonitriles↗
PubMed1997

Posterior cruciate recession in total knee arthroplasty.

Incremental recession of the posterior cruciate ligament (PCL), as a part of ligamentous balancing in total knee arthroplasty, is critical if the PCL is too tight. This study was undertaken to evaluate any possible untoward effects of PCL recession. Twenty-one patients who underwent simultaneous bilateral total knee arthroplasty between 1988 and 1992 with a PCL recession performed only on one side (necessary to balance the knee) served as the study group. The average follow-up period was 4 years. The patients were evaluated subjectively, by manual physical testing, by radiography, and by KT-1000 arthrometry (Medmetric, San Diego, CA). There were no significant differences between the recessed and nonrecessed knees. The conclusion is that PCL recession is appropriate and safe long-term for the patient in whom the PCL is found to be too tight at the time of knee arthroplasty.

Aged↗
PubMed1997

Progesterone acts through protein kinase C to remodel the cytoplasm as the amphibian oocyte becomes the fertilization-competent egg.

The fertilization-competent Xenopus egg undergoes a contraction of its cortex towards the apex of the pigmented animal hemisphere within 10 min of fertilization. Evidence suggests that protein kinase C (PKC) is involved in the assembly of this contractile network and we show that PKC is rapidly activated as a result of exposure of oocytes to progesterone. Xenopus oocytes contain at least five different isotypes of PKC. Three actin-binding proteins (i.e. vinculin, talin and ankyrin) appear to play an early role in the assembly of the contractile network and one of the proteins (vinculin) becomes phosphorylated shortly after progesterone treatment as the contractile network is assembling. Our results indicated that progesterone acts through a phospholipase to activate PKC and that PKC participates in the remodeling of the cytoplasmic compartment as the oocyte becomes the egg.

Actins↗
PubMed1997

Spinal anesthesia versus intravenous sedation for transvaginal oocyte retrieval: reproductive outcome, side-effects and recovery profiles.

Transvaginal ultrasonically guided oocyte retrieval is commonly performed as part of in vitro fertilization efforts. The impact of anesthetic management on patient outcome from this procedure has not been well characterized. At our institution, patients are offered a choice of either heavy intravenous sedation or spinal anesthesia with minimal or no sedatives. In this pilot study, we retrospectively reviewed the anesthetic management, reproductive outcome and recovery room experience for all patients having oocyte retrieval during a 2-year interval (n = 95). Fifty-one oocyte retrievals were performed under spinal anesthesia, while 44 patients received solely intravenous sedatives. Both groups had similar reproductive outcomes. The intravenous sedation group required a significantly longer period until recovery room discharge criteria were met (P = 0.03), and were more likely to have postoperative emetic episodes (46% versus 6% in the spinal anesthesia group: P < 0.01). Two unplanned hospital admissions occurred in the intravenous sedation group: both were related to uncontrolled nausea and vomiting. We conclude that spinal anesthesia may have advantages over intravenous sedation for oocyte retrieval.

Journal Article↗
PubMed1997

Acute and chronic antidepressant drug treatment in the rat forced swimming test model of depression.

The forced swimming test (FST) is a widely used behavioral screen in rodents that is both sensitive and selective for clinically effective antidepressant drugs. However, antidepressant drugs produce changes in the FST within 24 hr of treatment, in contrast to weeks required for the recovery from clinical depression, and high doses seem to be required to produce effects in most animal tests. This study examined behavioral effects in the FST after subacute and chronic treatment with low doses (1-5 mg/kg) of antidepressant drugs to determine whether chronic treatment produced behavioral effects at doses that were ineffective after subacute treatment. The antidepressants studied were desipramine, a selective norepinephrine uptake inhibitor, and fluoxetine, a selective serotonin uptake inhibitor. The results indicated that low doses of desipramine and fluoxetine produced different behavioral patterns in the FST, but only after chronic administration. The results strengthen the validity of the FST as a behavioral screen for antidepressant drugs with features similar to an animal model of depression.

Acute Disease↗
PubMed1997

Correspondence between the effect of zidovudine plus lamivudine on plasma HIV level/CD4 lymphocyte count and the incidence of clinical disease in infected individuals. North American Lamivudine HIV Working Group.

OBJECTIVES: To investigate whether apparently beneficial changes in plasma HIV RNA level and CD4 lymphocyte count that are induced by antiretroviral therapy are associated with a corresponding clinical benefit. METHODS: For 620 patients in two randomized, double-blind trials of lamivudine (3TC) and zidovudine (ZDV) plasma HIV RNA and CD4 lymphocyte count changes were compared in patients randomized to 3TC plus ZDV and patients randomized to other treatment arms. The effect of therapy on the HIV RNA level and CD4 count was compared with the effect of therapy on clinical endpoints over the same time period. RESULTS: Median baseline values for all subjects were 42 420 copies/ml for HIV RNA and 277 x 10(6)/l for CD4 count. During the trial a significantly lower HIV RNA level and higher CD4 count was sustained in the ZDV/3TC group compared with the other group, with a difference in the median area under the curve from baseline per month of follow-up of 0.38 log10 copies/ml HIV RNA and 0.18 log2 x 10(6)/l CD4 cells (P < 0.001 in each case). For patients who were initially asymptomatic or in CDC stage B, the adjusted relative hazard (RH) of AIDS for a twofold lower CD4 count was 3.14 [95% confidence interval (CI), 1.44-6.83] and for a 10-fold higher HIV RNA level was 3.22 (1.20-8.59). The RH progression to AIDS expected with ZDV/3TC compared with the control treatments, given the observed effects of treatment on CD4 cell counts and HIV RNA levels, is 0.52, whereas the observed value was 0.16 (0.03-0.74). After adjustment for HIV RNA and CD4 changes over time the observed RH of progression to AIDS for ZDV/3TC treatment compared with controls was increased to 0.36 and was no longer significant (95% CI, 0.07-1.85). CONCLUSION: In this analysis of two trials, the effects of ZDV/3TC in reducing plasma HIV RNA and raising peripheral blood CD4 counts were associated with concurrent clinical benefits and the effect of treatment on these markers could account for at least part of the clinical benefits of therapy that were observed.

Anti-HIV Agents↗
PubMed1997

Teaching pharmacology to advanced practice nursing students: issues and strategies.

A pharmacology course should prepare the advanced practice nursing student to understand the cellular mechanisms of drug action and physiologic outcomes (pharmacodynamics); mechanisms of absorption, distribution, metabolism, and excretion of drugs (pharmacokinetics); and the clinical use of drugs in the diagnosis, prevention, and treatment of disease (pharmacotherapeutics). The goal of a pharmacology course for advance nursing practice is to provide practitioners with knowledge that provides a rational basis for pharmacologic management of patients with complex health problems. A pharmacology course should teach the student the principles of pharmacology along with the process of pharmacologic reasoning.

Curriculum↗
PubMed1997

Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.

The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.

Amino Acid Sequence↗
PubMed1997

The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor I kappa B.

The NIM1 (for noninducible immunity) gene product is involved in the signal transduction cascade leading to both systemic acquired resistance (SAR) and gene-for-gene disease resistance in Arabidopsis. We have isolated and characterized five new alleles of nim1 that show a range of phenotypes from weakly impaired in chemically induced pathogenesis-related protein-1 gene expression and fungal resistance to very strongly blocked. We have isolated the NIM1 gene by using a map-based cloning procedure. Interestingly, the NIM1 protein shows sequence homology to the mammalian signal transduction factor I kappa B subclass alpha. NF-kappa B/I kappa B signaling pathways are implicated in disease resistance responses in a range of organisms from Drosophila to mammals, suggesting that the SAR signaling pathway in plants is representative of an ancient and ubiquitous defense mechanism in higher organisms.

Amino Acid Sequence↗
PubMed1997

Treatment of gastrointestinal cytomegalovirus infection with twice-daily foscarnet: a pilot study of safety, efficacy, and pharmacokinetics in patients with AIDS.

Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

In vitro inhibition of Cryptosporidium parvum infection by human monoclonal antibodies.

Cryptosporidium parvum infection of the small epithelial intestine causes unremitting diarrhea and malabsorption that can lead to chronic and sometimes fatal illness in patients with AIDS. The illness may be ameliorated by passive oral immunoglobulin therapy. The objective of this study was to produce anti-Cryptosporidium human monoclonal antibodies for evaluation as potential therapy. All human monoclonal cell lines that produced C. parvum antibodies were originally generated from the peripheral blood lymphocytes of a human immunodeficiency virus-seronegative woman. She had recovered from C. parvum infection and had a high specific antibody titer. Hybridization of these lymphocytes with a tumor cell line was accomplished by hypo-osmolar electrofusion. Twelve clones were identified by enzyme-linked immunosorbent assay (ELISA) as secreting anti-Cryptosporidium antibodies after the initial hybridization. From the 12 positive clones, two high antibody-secreting clones, 17A and 17B, were maintained in long-term culture. A second hybridization produced two other human monoclonal cell lines, EC5 and BB2. Human monoclonal antibody from the first two cell lines bound to C. parvum sporozoites and oocysts by immunofluorescence. The ability of human monoclonal antibodies to inhibit C. parvum infection in vitro was assessed by using a human enterocyte cell line, HT29.74. The antibodies of the four different human hybridomas inhibited infection by 35 to 68% (P < 0.05) compared to a control irrelevant human monoclonal antibody derived in a similar fashion. Human monoclonal antibodies are candidate molecules for immunotherapy of C. parvum infection.

Animals↗