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Biomedical subjects

J Johnson

Publications and source records attributed to J Johnson.

At least 109 records · Page 6Linked to original sources

Emergence of dual resistance to zidovudine and lamivudine in HIV-1-infected patients treated with zidovudine plus lamivudine as initial therapy.

Presence of mutations associated with resistance to zidovudine or lamivudine was determined in isolates of HIV-1 obtained after long-term follow-up of 64 infected individuals who received zidovudine, lamivudine, or both drugs as initial antiretroviral therapy. Zidovudine resistance mutations were less frequent in isolates from patients treated with combination lamivudine plus zidovudine compared with zidovudine alone, but these mutations accumulated over time. Phenotypic resistance to both drugs was found in isolates from 3 of 23 patients. In 3 other patients, lamivudine-resistant virus detected at week 12 was replaced by wild-type virus after longer follow-up, which correlated with a return to baseline levels of plasma HIV-1 RNA. These results show that dual resistance to zidovudine and lamivudine develops over time despite the delayed emergence of zidovudine-resistant mutations. These results also suggest a selective advantage in vivo for HIV-1 species that are wild-type at RT codon 184.

Amino Acid Sequence↗

DNA flow cytometry does not predict 5- or 10-year recurrence rates for T1-2 node-negative breast cancer.

BACKGROUND: A small proportion of T1 or T2 node-negative breast cancer tumors will recur in patients by 5 years, and more by 10 years. Results of recent studies have suggested improvement in overall survival with administration of adjuvant chemotherapy to all patients. More sensitive and specific methods are needed to identify patients at highest risk for recurrence who might benefit most from adjuvant therapy, saving others from unnecessary treatment. Some investigators have suggested DNA flow cytometry as a method to discriminate patients at greatest risk for recurrence. HYPOTHESIS: DNA flow cytometry has predictive value for breast cancer recurrence in node-negative patients. METHODS: The cancer registry of a medium-sized university-affiliated hospital was used to identify patients with T1-2 N0 M0 breast cancer treated with a uniform surgical approach and no adjuvant therapy who had completed at least 5 years of follow-up or had recurrence. Flow cytometric analysis was performed on paraffin-embedded specimens. RESULTS: Of 115 patients, 92 (80%) had disease-free survival without recurrence and 23 (20%) had recurrence. Comparison of diploid and nondiploid tumors for likelihood of recurrence revealed no association (P = .79). Furthermore, the DNA index and S-phase fraction were not significantly different between recurrent and nonrecurrent groups. CONCLUSIONS: The likelihood of recurrence of small node-negative breast cancers after mastectomy cannot be accurately predicted on the basis of DNA flow cytometric analysis. Traditional methods for determining risks-such as nuclear and histological grade, lymph node status, and tumor size-seem to be more useful. Sentinel lymph node biopsy techniques may increase the detection of micrometastases.

Breast Neoplasms↗

Drug-induced hemolysis: cefotetan-dependent hemolytic anemia mimicking an acute intravascular immune transfusion reaction.

Numerous cases of drug-induced hemolytic anemia have been described in patients treated with penicillin or cephalosporin. Second and third generation cephalosporins are more commonly implicated in hemolytic reactions than first generation cephalosporins. We report a case of severe cefotetan-induced hemolytic anemia in a previously healthy 46-year-old woman undergoing an elective hysterectomy. The patient received 2 g of intravenous cefotetan intraoperatively and subsequently at 12 and 24 h post-operatively. She complained of diarrhea and fever on the third post-operative day and was seen in her gynecologist's office on the fifth post-operative day (hemoglobin = 10.5 g/dL). On the seventh post-operative day, she complained of fever and soreness around the suprapubic catheter site and was given a prescription for 500 mg oral cephalexin four times a day. The next day she was seen in the gynecologist's office and reported feeling better. Ten days after the operation her fatigue worsened and her hemoglobin was 4.8 g/dL. She was transfused with 3 units of packed red blood cells (PRBC) and was given 1 g of cefotetan intravenously. During the transfusion of the second unit of PRBC nursing staff observed gross hemoglobinuria and she subsequently developed acute renal failure. Laboratory chemistry parameters were consistent with severe acute hemolysis. The patient's direct antiglobulin test was reactive and her serum reacted with cefotetan-coated red blood cells (RBCs) and serum plus soluble cefotetan reacted with untreated RBCs. The titration endpoint of the serum against cefotetan-coated RBCs was 40,960, while the serum plus soluble cefotetan against uncoated RBCs was 2,560. This case of severe cefotetan-induced hemolysis was complicated by an acute hemolytic event that occurred during the transfusion of PRBC. Clinical and transfusion service staff must consider drug-induced hemolysis in the differential diagnosis of acute anemia.

Anemia, Hemolytic↗

Structure of the asparagine-linked sugar chains of porcine kidney and human urine cerebroside sulfate activator protein.

The specific sugar residues and their linkages in the oligosaccharides from pig kidney and human urine cerebroside sulfate activator proteins (saposin B), although previously hypothesized, have been unambiguously characterized. Exhaustive sequential exoglycosidase digestion of the trimethyl-p-aminophenyl derivatives, followed by either matrix-assisted laser desorption/ionization and/or mass spectrometry, was used to define the residues and their linkages. The oligosaccharides were enzymatically released from the proteins by treatment with peptidyl-N-glycosidase F and separated from the proteins by reversed-phase high-performance liquid chromatography (HPLC). Reducing termini were converted to the trimethyl-p-aminophenyl derivative and the samples were further purified by normal-phase HPLC. The derivatized carbohydrates were then treated sequentially with a series of exoglycosidases of defined specificity, and the products of each digestion were examined by mass spectrometry. The pentasaccharides from pig kidney and human urine protein were shown to be of the asparagine-linked complex type composed of mannose-alpha 1-6-mannose-beta 1-4-N-acetylglucosamine-N-acetylglucosamine(alpha 1-6-fucose). This highly degraded structure probably represents the final product of intra-lysosomal exoglycosidase digestion. Oligosaccharide sequencing by specific exoglycosidase degradation coupled with mass spectrometry is more rapid than conventional oligosaccharide sequencing. The procedures developed will be useful for sequencing other oligosaccharides including those from other members of the lipid-binding protein class to which cerebroside sulfate activator belongs. (c) 2000 John Wiley & Sons, Ltd.

Animals↗

Psychometric development of a multidimensional measure of weight-related attitudes and behaviors.

Most weight control programs facilitate weight loss by encouraging participants to adopt healthy eating patterns and increase physical activity. There is a need for a relatively brief measure of eating habits and physical activity that could be used to evaluate changes in behavior during weight loss treatment. The purpose of this series of four studies was to develop and validate such a measure, which was subsequently named the Weight Loss Behavior Scale (WLBS). Study 1 (n = 533) included item and scale development and examination of the WLBS's factor structure and internal consistency. Study 2 (n = 226) evaluated the test-retest reliability and convergent validity of its subscales. Study 3 examined their reliability and internal consistency scales in a predominantly overweight sample (n = 36). Study 4 evaluated the WLBS as a treatment outcome measure in a weight loss intervention (n = 50). Study 1 found that the WLBS contained five internally consistent and stable factors: 1) Concern with Dieting and Weight, 2) Exercise, 3) Overeating, 4) Avoidance of Fattening Foods and Sweets, and 5) Emotional Eating. Study 2 found convergent validity for the WLBS by assessing the correlation of its factors/scales with established inventories of comparable constructs, e.g., dietary restraint, disinhibited eating, and physical activity. Test-retest reliability of the five scales was also supported in this second study. In Study 3, support for the internal consistency and test-retest reliability of the WLBS among overweight individuals was found. Study 4 found that all scales significantly changed in the expected directions after a 5-month behavioral weight loss treatment. The findings from this series of studies suggest that the WLBS is a reliable and valid self-report inventory of cognitive and behavioral scales associated with weight control that can be utilized as an outcome measure for weight loss interventions.

Adult↗

Americans' view of cancer.

This paper presents the concept of the town hall meeting and discusses how it can be used as a forum for those who have been touched by cancer. It can be a platform for people to express their views about cancer, not only in the community but also nationally. Empowerment is the hallmark of a town hall meeting. Those who are in leadership positions in health care and elected officials and community leaders are given the opportunity to hear the opinions of people who represent a broad-based constituency of individuals affected by cancer. The idea of holding a town hall meeting was first introduced in the cancer community by the National Coalition for Cancer Survivorship NCCS) as a means of identifying issues, exchanging information and considering creative solutions to problems. The first town hall meeting was held in 1994 in conjunction with the NCCS annual assembly. Since then, utilizing the guidelines set forth by the NCCS, 30 or more town hall meetings have been held across the United States. Cancer survivors have, by and large, been responsible for garnering the necessary support for conducting a town hall in their local area. Organizations such as the American Cancer Society, the Leukemia Society of America, hospitals, clinics, pharmaceutical and healthcare companies and also noncancer groups, such as the YMCA, churches, and radio/T.V. stations, join with the cancer survivors in organizing the meeting, planning related displays, and advertising the event. In 1998, seven town hall meetings were sponsored jointly by OnCare and NCCS in advance and support of the upcoming THE MARCH- Coming Together To Conquer Cancer, a national rally held in Washington, D.C. in September 1998. Attendees at the meetings included not only cancer survivors and their families, but also healthcare professionals, local and state legislators, community leaders and the media. Results of the 1998 town hall meetings are discussed and compared with the topics identified during the meetings held in 1994-1996. Town hall participants were outspoken about what is needed in America if cancer is truly to become the nation's healthcare priority. They are asking for equal access to quality care, increases in financial backing for research, and more support for cancer advocacy efforts. Benefits of holding town hall meetings are identified.

Health Services Accessibility↗

Effect of preoperative interventions on outcome following liver resection in a rat model of cirrhosis.

BACKGROUND/AIMS: High morbidity and mortality rates in cirrhotic patients undergoing resections for hepatocellular malignancies underscore the need for identifying a therapy that will decrease fibrosis or enhance hepatic regenerative activity in the perioperative period. Thus, in the present study, 104 carbon tetrachloride-induced cirrhotic rats received either saline (untreated cirrhotic controls) or one of the following agents that have been reported to decrease hepatic fibrosis or increase hepatic regeneration; pentoxifylline, ciprofloxacin or a traditional Chinese herbal remedy (TCHR). Twelve additional rats served as healthy, non-cirrhotic controls. METHODS: Treatments were administered daily by gavage for 4 weeks followed by a 70% partial hepatectomy. Hepatic fibrosis was documented at the time of surgery by computer-assisted quantitation of collagen content. Liver function and hepatic regenerative activity were documented 24 h post partial hepatectomy by serum bilirubin determinations and a combination of 3[H]-Thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) quantitation, respectively. RESULTS: Compared to untreated cirrhotic controls (8.1 +/- 0.7%), fibrosis was significantly reduced in the pentoxifylline- and ciprofloxacin-treated groups (4.6 +/- 0.2%, p<0.005 and 5.5 +/- 0.6%, p<0.05) but unchanged in the TCHR-treated group (6.6 +/- 11.0%). Post-operatively, total serum bilirubin levels were lower in the pentoxifylline (1.40 +/- 0.15 mg/dl,p<0.01) and ciprofloxacin (1.87 +/- 0.25 mg/dl, p<0.05)-treated groups, but unchanged in the TCHR group (2.20 +/- 0.45 mg/dl), when compared to untreated cirrhotic controls (3.00 +/- 0.37 mg/dl). Hepatic regenerative activity was also significantly improved in the pentoxifylline-treated group (17.8 +/- 2.2 versus 9.9 +/- 1.9 DPM/microg DNA in untreated cirrhotic controls, p<0.05), but unchanged in the ciprofloxacin (16.1 +/- 1.8 DPM/microg DNA) and TCHR (10.9 +/- 1.2 DPM/microg DNA)-treated groups. PCNA protein determinations were in keeping with the 3[H]-Thymidine results CONCLUSIONS: Pre-operative pentoxifylline holds promise as a useful therapeutic intervention for patients with cirrhosis requiring hepatic resection.

Animals↗

Cost-effectiveness of mental health services for persons with a dual diagnosis: a literature review and the CCMHCP. The Cost-Effectiveness of Community Mental Health Care for Single and Dually Diagnosed Project.

People suffering from comorbid mental illness and substance abuse disorders (the dually diagnosed) are thought to constitute large portions of clients treated as outpatients by public-sector community-based mental health providers. These providers dispense units of ambulatory mental health services and treatments incrementally to maintain clients in the community and out of psychiatric hospitals. Community maintenance is one step, albeit critical, toward quitting drugs and eventual abstinence. Thus, there is a need for information that compares the effectiveness and cost of such services on dually diagnosed clients to identify appropriate low-cost high-yield treatment and service options and packages. This article provides a review of the literature on the effectiveness of ambulatory mental health services and recent emergent reports of cost-effectiveness of programs for the dually diagnosed, paying special attention to the gray areas and gaps. This article also describes a new project; an inexpensive add-on to an existing community mental health center. The project will be examining over 4 years of data to compare influence and cost of different ambulatory mental health services and treatments delivered to a matched pair group of clients with dual disorders and those with only mental illness. The intention of this project is not only to address gray areas and gaps in the literature, but also to inform a more rational deployment of mental health services.

Community Mental Health Services↗

Regulation of glutathione S-transferase enzymes in primary cultures of rat hepatocytes maintained under various matrix configurations.

Primary rat hepatocytes were cultured under various matrix and media conditions and examined after 1 week for the expression and regulation of cytosolic glutathione S-transferase (GST) enzymes. Striking effects on cell morphology were observed in relation to the different matrix conditions, whereas media effects were less prominent. Hepatocytes cultured in serum-free Dulbecco's modified Eagle's medium (DMEM) or modified Chee's medium (MCM) maintained similar levels of total GST protein regardless of the matrix configuration or corresponding cell integrity. However, HPLC analysis showed a differential expression pattern of individual GST subunits in both a time- and medium-dependent fashion. A variable, but pronounced, matrix and medium effect was observed on the induction of total GST expression by various prototypical inducers. Dexamethasone (10 microM) induced subunits A2, M1 and M2 in a medium- and matrix-dependent fashion, whereas phenobarbital (100 microM) induced significantly only subunit A2. beta-Naphthoflavone (50 microM) suppressed all GST subunit expression except subunit P1, which was induced in a matrix- and medium-dependent fashion. These studies show that total basal level expression of GSTs in vitro is reflective of a concomitant increase in mu and pi class subunits and a decrease in alpha class subunits. Moreover, the matrix and medium conditions influence both the basal and inducible expression of GST subunits in cultured rat hepatocytes.

Animals↗

Longitudinal study of vascular remodeling in coronary arteries after heart transplantation.

Cross-sectional studies by intravascular ultrasound (IVUS) in heart transplant recipients have suggested that vascular remodeling occurs in coronary arteries years after transplant. However, no reports describe vascular remodeling in the same cohort of patients studied prospectively using morphometric analysis (10 evenly spaced images obtained from a slow pullback from the left anterior descending coronary artery). Morphometric analysis better reflects total vessel anatomy compared with previously reported site (2 to 3 images) analysis. We reviewed 20 patients studied by IVUS at 2 months, 1 year, 2 years, and 3 years after heart transplant.Over time, the coronary artery luminal area decreased from baseline level of 12.0 mm(2) to a 3-year mark of 9.7 mm(2) (p = 0.02). Vessel shrinkage was seen in 16/20 patients. After an initial rise in intimal parameters (maximal intimal thickness, intimal index, and plaque area) from baseline to 1 year, we found a significant decrease in intimal parameters between Year 1 and Year 3 after transplant. For example, plaque area decreased from 2.05 mm(2) at 1 year post-transplant to 1.48 mm(2) by 3 years post-transplant (p = 0.05). In a majority of heart transplant patients, early intimal thickening in the first year post-transplant is accompanied by constrictive remodeling. Over the subsequent 2 years, further constrictive remodeling is seen despite a decrease in intimal area.

Adult↗

Treatment of chronic hepatitis C with amantadine.

Hepatitis C is usually treated with interferon or a combination of interferon and ribavirin, but these agents have numerous side effects, and interferon must be given by injection three time a week. An alternative oral medication would be a welcome advance for treating hepatitis C. Amantadine has been reported to have the potential to produce viral suppression in patients with hepatitis C. To gain further knowledge about the effects of amantadine on hepatitis C, we treated 24 patients for 3-12 months (average = 5.5 months; median = 4.5 months) with 100 mg amantadine twice daily. Twelve patients had stage 3 or 4 fibrosis on biopsy. Eleven patients had a fall in viral titer, but complete viral suppression was not seen in any patient. Three patients had no viral titer obtained after treatment, but their elevated transaminase levels did not change with treatment. Of the 15 patients with a decrease in enzyme levels, only two patients had normalization. Six patients had side effects during the treatment, but in only one was amantadine stopped solely because of side effects. Based on these results and a literature review, we do not believe amantadine is an effective single agent for the treatment of chronic hepatitis C.

Adult↗

Acceptability of green soybeans as a vegetable entity.

A profile of the sensory characteristics of green soybean and consumer intent of purchasing the product were determined. Thirty-one green soybean genotypes from maturity groups III to VI harvested between R6 and R7 were frozen, boiled, shelled, and evaluated for color, texture, sweetness, nuttiness, beaniness, oiliness, aftertaste and overall eating quality by three sensory panels. Results showed highly significant (p <0.01) variabilities among the genotypes in all sensory parameters and highly significant correlations among several parameters. The green soybeans, when boiled, ranged from lightly green to green, were slightly resistant to chewing, slightly nutty, slightly beany, not oily, imparted a pleasant aftertaste and had a fairly good overall eating quality. The green soybeans would be potentially acceptable as a vegetable in the frozen state and for use in recipes. When selecting genotypes for production, consideration should be given to the sensory attributes of the genotypes, because there was significant variability among the characteristics of the green soybeans, and several characteristics together enhanced the overall acceptability of the vegetable soybeans. To further increase the acceptability of green soybeans as a vegetable, geneticists need to consider breeding a vegetable soybean that has as many desirable sensory attributes as possible.

Chemical Phenomena↗

Epstein-Barr virus association in classical Hodgkin's disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed-Sternberg cells.

BACKGROUND: Most Epstein-Barr virus (EBV) associated lymphoproliferative disorders have high proliferation indices. However, classical Hodgkin's disease (cHD) is heterogeneous, with respect to proliferation index of the Reed-Sternberg cell (RS cell), and EBV association. Hence, we investigated whether cHD with and without EBV-association differ with respect to the proliferation index of the RS cells. Further we investigated whether this would have a bearing on patients survival. PATIENTS AND METHODS: We investigated 110 cases of cHD for: a) EBV association by immunohistochemical demonstration of EBV-latent membrane protein-1 and EBV encoded nuclear RNA 1 by mRNA in situ hybridisation; b) Proliferating cell nuclear antigen (PCNA) expression in the RS cells. RESULTS: EBV association was noted in 86 of 110 cases (78%). Higher PCNA expression (P = 0.004) and younger age (P = 0.001) correlated independently with EBV association. The 10 year relapse free survival (RFS) of EBV+ and EBV- patients were 60% and 44%, respectively (P = 0.03). The 10 year overall survival (OS) of EBV+ and EBV- patients were 85% and 64%, respectively (P = 0.03). EBV association maintained its significant impact on RFS and OS within Cox proportional hazard model. CONCLUSIONS: Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in cell cycle. Hence, RS cells in EBV associated cHD would be more responsive to chemotherapy and radiotherapy associated DNA damage. Thus, EBV-association provides survival advantage to cHD patients treated with standard chemotherapy and radiotherapy protocols.

Adolescent↗

T cell activation, apoptosis and cytokine dysregulation in the (co)pathogenesis of HIV and pulmonary tuberculosis (TB).

Immune parameters were compared in four groups of Ugandan subjects: HIV-and HIV+ adult patients with active pulmonary TB (HIV- PTB n = 38; HIV+ PTB n = 28), patients with HIV infection only (n = 26) and PPD+ healthy controls (n = 25). Compared with healthy controls, CD4 and CD8 T cells from patients with HIV and/or PTB expressed more activation markers (HLA-DR, CD38); their CD8 T cells expressed more CD95 (pre-apoptosis) and less CD28 (co-stimulatory receptor). Peripheral blood mononuclear cells (PBMC) of patients with either HIV or PTB were impaired in interferon-gamma (IFN-gamma) production upon antigenic stimulation. PTB (with or without HIV) was characterized by monocytosis, granulocytosis, increased transforming growth factor-beta 1 production and PPD-induced apoptosis. In vivo CD4 T cell depletion, in vitro increased spontaneous CD4 T cell apoptosis and defects in IFN-gamma responses upon mitogenic stimulation were restricted to HIV+ subjects (with or without PTB). Overlapping and distinctive immune alterations, associated with PTB and HIV, might explain mutual unfavourable influences of both diseases.

AIDS-Related Opportunistic Infections↗

The management of alloimmune neonatal thrombocytopenia.

Neonatal alloimmune thrombocytopenia (NAITP), defined as thrombocytopenia (platelet count < 150 x 10(9)/l) due to transplacentally acquired maternal platelet alloantibodies, occurs in approximately 1 per 1200 live births in a Caucasian population. In such a population, the majority (> 75 percent) of cases are due to fetomaternal incompatibility for the platelet specific alloantigen, HPA-1a (P1A1, Zwa). Incompatibility for the HPA-5b (Bra) alloantigen is the next most frequent cause of NAITP in Caucasians; much less common is NAITP due to incompatibility for HLA, blood group ABO or other platelet-specific antigens. In non-Caucasian populations (e.g. Orientals) HPA-1a incompatibility is a rare cause of NAITP and other alloantigens e.g. HPA-4b (Penb, Yuka) are implicated. The greatest clinical challenge relates to the antenatal management of pregnant women alloimmunized to the HPA-1a (P1A1, Zwa) antigen, and particularly the subset of such women who have a history of a previously affected infant with severe thrombocytopenia and/or intracranial hemorrhage (ICH). The risk of antenatal ICH in the fetus of such women is high enough to merit intervention, either weekly infusion of high-dose intravenous immunoglobulin G (IVIG) with or without corticosteroids given to the mother (the preferred approach in North American centres), or repeated in-utero fetal platelet transfusions (the preferred treatment approach in some European centres). Post-natal management of severely affected infants centres on the rapid provision of compatible antigen-negative platelets harvested from the mother or a phenotyped donor. The value of antenatal screening programs to detect 'at risk' alloimmunized women during pregnancy continues to be debated.

Adrenal Cortex Hormones↗

Managers forum

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Journal Article↗

Preventing traumatic brain injury: an innovative approach to outcomes assessment.

The purpose of this study was to investigate the usefulness of the state traffic violations database as an outcome measure for the Young Traffic Offenders Programme, a 1-day educational injury prevention programme for young people with speeding offences. The database provided a fine-grained, cumulative record of each driver's traffic offences and sanctions applied. A comparison of 92 programme participants and 87 non-treated individuals showed no significant between-group difference in rate of convictions after the target programme date, but each group declined significantly in rate of convictions over time. Younger males and individuals with a higher number of convictions initially were more likely to have higher conviction rates after the target date. These findings underscore the need to improve prevention programmes and highlight the potential usefulness of existing public datasets for outcome evaluation.

Accidents, Traffic↗