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Biomedical subjects

J Johnston

Publications and source records attributed to J Johnston.

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

Transitions to independent living after ABI.

One of the most challenging questions facing service providers and policy makers alike is the appropriate level of supervision for adults living in the community following a brain injury. In a 3-year province-wide study of people entering the community following brain injury rehabilitation, four individuals (out of 22 studied) made a transition from fully supervised living to lower levels of formal supervision during their first year in the community. The present study seeks to provide more information about these four individuals, the factors that allowed them to move to lower levels of supervision, and the perceived success of that transition. For each participant, the interviews conducted over the 1 year period in the initial study were reviewed in detail for information about independent living. In addition, each participant was interviewed again for this study, along with his significant other and three of the community programme staff who were most closely involved with his transition. To summarize, factors most salient in the success of transition included: (1) Roles and relationships of family and programme personnel; (2) staying away from drugs and alcohol; (3) availability of structured daily activities, including productive activity or community programme; (4) financial management; and (5) emotion and behaviour self-control. Secondary themes related to successful community living also included the availability of transportation and prior experience with community living since the onset of brain injury. These results offer the experience of four individuals in moving towards independent living. As such, they provide a starting point for further discussions of the process of supporting individuals to pursue the ultimate goal of independent living.

Accidents, Traffic↗
PubMed1999

The emergence of decreased susceptibility to vancomycin in Staphylococcus epidermidis.

BACKGROUND: Coagulase-negative staphylococci (CNS) are the major cause of nosocomial bloodstream infection. Emergence of vancomycin resistance among CNS is a serious public health concern, because CNS usually are multidrug-resistant, and glycopeptide antibiotics, among which only vancomycin is available in the United States, are the only remaining effective therapy. In this report, we describe the first bloodstream infection in the United States associated with a Staphylococcus epidermidis strain with decreased susceptibility to vancomycin. METHODS: We reviewed the hospital's microbiology records for all CNS strains, reviewed the patient's medical and laboratory records, and obtained all available CNS isolates with decreased susceptibility to vancomycin. Blood cultures were processed and CNS isolates identified by using standard methods; antimicrobial susceptibility was determined by using minimum inhibitory concentration (MIC) and disk-diffusion methods. Nares cultures were obtained from exposed healthcare workers (HCWs) to identify possible colonization by CNS with decreased susceptibility to vancomycin. RESULTS: The bloodstream infection by an S. epidermidis strain with decreased susceptibility to vancomycin occurred in a 49-year-old woman with carcinoma. She had two blood cultures positive for CNS; both isolates were S. epidermidis. Although susceptible to vancomycin by the disk-diffusion method (16-17 mm), the isolates were intermediate by MIC (8-6 microg/mL). The patient had received an extended course of vancomycin therapy; she died of her underlying disease. No HCW was colonized by CNS with decreased susceptibility to vancomycin. CONCLUSIONS: This is the first report in the United States of bloodstream infection due to S. epidermidis with decreased susceptibility to vancomycin. Contact precautions likely played a role in preventing nosocomial transmission of this strain, and disk-diffusion methods may be inadequate to detect CNS with decreased susceptibility to vancomycin.

Anti-Bacterial Agents↗
PubMed1999

Productive infection of human peripheral blood mononuclear cells by feline immunodeficiency virus: implications for vector development.

Feline immunodeficiency virus (FIV) is a lentivirus causing immune suppression and neurological disease in cats. Like primate lentiviruses, FIV utilizes the chemokine receptor CXCR4 for infection. In addition, FIV gene expression has been demonstrated in immortalized human cell lines. To investigate the extent and mechanism by which FIV infected primary and immortalized human cell lines, we compared the infectivity of two FIV strains, V1CSF and Petaluma, after cell-free infection. FIV genome was detected in infected human peripheral blood mononuclear cells (PBMC) and macrophages at 21 and 14 days postinfection, respectively. Flow cytometry analysis of FIV-infected human PBMC indicated that antibodies to FIV p24 recognized 12% of the cells. Antibodies binding the CCR3 chemokine receptor maximally inhibited infection of human PBMC by both FIV strains compared to antibodies to CXCR4 or CCR5. Reverse transcriptase levels increased in FIV-infected human PBMC, with detection of viral titers of 10(1.3) to 10(2.1) 50% tissue culture infective doses/10(6) cells depending on the FIV strain examined. Cell death in human PBMC infected with either FIV strain was significantly elevated relative to uninfected control cultures. These findings indicate that FIV can productively infect primary human cell lines and that viral strain specificity should be considered in the development of an FIV vector for gene therapy.

Animals↗
PubMed1999

Simultaneous pancreas-kidney transplantation at the University of Pittsburgh.

Analysis of the SPK program at the University of Pittsburgh has led to a number of observations: 1. Under tacrolimus-based immunosuppression, without antibody induction, it has been possible to achieve (a) One- and 3-year actuarial patient survival rates of 98% and 95% (b) One- and 3-year actuarial kidney survival rates of 95% and 87% (c) One- and 3-year actuarial pancreas survival rates of 86% and 80% 2. Steroid withdrawal has been achieved in over half of the successfully transplanted recipients, with excellent outcomes and a low rate (4.7%) of subsequent rejection. 3. Bone marrow augmentation has been associated with (a) less rejection (b) less pancreatic graft loss to rejection (c) an increased ability to withdraw steroids 4. Rejection has been associated with a rising serum lipase. 5. Renal allograft rejection in SPK patients with elevated serum lipase levels has been seen in the setting of normal renal function. 6. Enteric drainage has been associated with a reasonably low complication rate. 7. SPK transplantation is a successful therapeutic option in selected type I diabetics with end-stage renal disease.

Adult↗
PubMed1998

Pharmacodynamics of immediate and delayed effects of paclitaxel: role of slow apoptosis and intracellular drug retention.

The kinetics of the time-dependent antitumor effects of paclitaxel are not fully understood; some literature reports indicate a higher activity by prolonging treatment durations, whereas other reports indicate no enhancement under in vitro conditions. The present study was designed to address this controversy and to determine the mechanism of the higher cytotoxicity associated with longer treatment durations. Six human epithelial cancer cell lines (bladder RT4, breast MCF7, pharynx FaDu, ovarian SKOV3, and prostate PC3 and DU145) were used. To determine whether the higher activity observed for the longer treatment durations is due to a delayed exhibition of drug effects and/or a reflection of cumulative effects that required a continuous drug exposure, cells were treated with paclitaxel for 3-96 h and then either: (a) immediately processed for drug effect measurement; or (b) washed, incubated in drug-free medium, and processed for drug effect measurement at 96 h. The overall drug effect (i.e., combination of cytostatic and apoptotic effects) was determined by the sulforhodamine B assay, which measures the cellular protein. In addition, to determine whether apoptosis occurs with a time delay, apoptosis was measured in cells that were collected immediately after drug treatment for various durations or in cells that were treated with drugs for 3 h but collected at later time points. Apoptosis was determined using agarose gel electrophoresis and by measuring the cytoplasmic DNA-histone complex using ELISA. The contribution of the intracellularly retained drug to the delayed drug effect was studied by characterizing the kinetics of cellular drug uptake and efflux and by examining the effect of removal of the intracellularly retained drug. All six cell lines showed similar results, as follows: (a) paclitaxel produced cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment was terminated (delayed effect); (b) the immediate and delayed effects showed different pharmacodynamics. The immediate effect increased with treatment duration and drug concentration. For the delayed effect, all treatments produced the same maximum effect at 96 h, although treatments for < or = 12 h showed higher IC50s than longer treatments, whereas treatments for > or = 24 h showed indistinguishable IC50s; (c) treatment for as brief as 3 h was sufficient to induce apoptosis, which occurred with a lag time of about 24 h, although longer treatments produced a greater extent of apoptosis; (d) The intracellular and extracellular concentrations reached an equilibrium at approximately 5 h, which rules out slow and/or insufficient uptake as the cause of the lower effects at shorter treatment times (i.e., < 24 h); (e) upon removal of drug-containing medium, the amount of drug retained intracellularly was about 10% of the applied dose and was reduced to approximately 0.5% after three successive washes, separated by 3-h equilibration periods; and (f) the delayed effect of the 3-h treatment was largely due to the drug retained intracellularly, whereas the delayed effect of the 24 h treatment was independent of the drug retained intracellularly. In conclusion, in human epithelial cancer cells, paclitaxel-induced cytotoxicity occurred after termination of drug treatment, which was partly due to the slow manifestation of apoptosis and partly due to the significant amount of drug retained intracellularly. Based on these findings and recognizing that some previous studies measured the immediate effect whereas the other studies measured the delayed effect, we propose that the conflicting data in the literature regarding the effect of treatment duration on paclitaxel activity under in vitro conditions are in part due to the different pharmacodynamics of the immediate and delayed drug effects. Furthermore, differences in the delayed effects for treatments of < 24 h and the minimal differences for treatments of > or = 24 h indicate that th

Animals↗
PubMed1998

Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia.

OBJECTIVES: Oxygen-free radicals and lipid hydroperoxides may have an aetiological role in the development of lesions in the central nervous system in patients with Alzheimer's disease and in those with vascular dementia. This study aimed to make a cross-sectional comparison of blood markers of oxidative stress in two groups of patients with these disorders and a control group. DESIGN: Cross-sectional comparative study. SETTING: Established memory clinics in Cardiff organized by a University Department of Geriatric Medicine within an acute care NHS Trust. METHODS: Following a dietary assessment, postprandial venous blood samples were obtained from the following: 25 subjects with probable Alzheimer's disease (AD) (mean age 74.3; 10 F, 15 M); 17 subjects with probable vascular dementia (VD) (mean age 75.5; 5 F, 12 M); and 41 controls (mean age 73.4; 24 F, 17 M) for measurement of circulating lipid peroxides (LP), total antioxidant capacity (TAC), vitamin C (VitC), vitamin E (VitE) and beta-carotene (BC). RESULTS: Plasma levels of VitC were significantly lower in subjects with vascular dementia compared with controls (VD, 6.5 (4.8, 8.2); controls, 10.0 (8.38, 11.6); VD vs controls, p = 0.015), but no significant difference was seen between controls and patients with Alzheimer's disease (AD, mean 8.3 (6.2, 10.4)). VitE levels were significantly lower in subjects with AD compared with controls (31.1 (28.2, 34.0) vs 36.0 (32.8, 39.2), p = 0.035). BC levels were similar in subjects with AD and controls, but significantly elevated in those with VD (AD, 0.28 (0.2, 0.34); VD, 0.40, (0.27, 0.53); controls, 0.28 (0.22, 0.34); VD vs controls, p = 0.046). There were no significant differences in LP or TAC between the three groups. CONCLUSIONS: Subjects with dementia attributed to Alzheimer's disease or to vascular disease have a degree of disturbance in antioxidant balance which may predispose to increased oxidative stress. This may be a potential therapeutic area for antioxidant supplementation.

Aged↗
PubMed1998

Preclinical evaluation of the effects of a novel antisense compound targeting C-raf kinase in mice and monkeys.

CGP 69846A (ISIS 5132) is an antisense phosphorothioate oligodeoxynucleotide which targets human C-raf kinase and is currently being developed as an antineoplastic agent. The toxicity of this compound was evaluated in mice and monkeys following repeated i.v. injections or infusions for 4 weeks at doses up to 100 mg/kg. Because CGP 69846A is inactive in the mouse, ISIS 11061, the murine-specific homologue targeting C-raf kinase mRNA was evaluated concurrently with CGP 69846A to assess the potential toxicity associated with reduced C-raf expression. There were no toxicities that differentiated ISIS 11061 from CGP 69846A in mice. Effects in mice included hepatomegaly and hepatocellular degeneration at the high dose of 100 mg/kg CGP 69846A that potentially resulted in lethality. Other effects which were observed at 20 and 100 mg/kg included mononuclear cell infiltrates in multiple organs, extramedullary hematopoiesis in the spleen and liver, an increase in bone marrow cellularity, an increase in white blood cells, a decrease in platelet counts, and Kupffer cell hyperplasia. These alterations were reversible following a recovery period. No adverse effects in mice were observed with doses < or = 10 mg/kg. In monkeys, administration of 10 mg/kg of CGP 69846A was associated with effects observed with other P = S ODNs, namely, prolongation of activated partial thromboplastin time (APTT) and activation of complement. These effects were transient and correlated with plasma concentrations of CGP 69846A. Below a concentration of 35 micrograms/ml of intact CGP 69846A the prolongation of APTT was less than 50% and levels of complement split products were not increased. All monkeys tolerated complement activation with no evidence of treatment-related clinical signs. Complement and coagulation were not affected by the lower doses of 1 and 3 mg/kg. No histopathology or alteration in hematology or serum chemistry was induced by doses up to 10 mg/kg in monkeys. The plasma and tissue deposition of CGP 69846A were characterized in mice and monkeys and toxicity was dependent on dose of CGP 69846A. In the present preclinical evaluation of toxicity in mice and monkeys, CGP 69846A is well tolerated at doses targeted for clinical trials. Toxicities induced by CGP 69846A in monkeys and mice occurred at doses of 10 mg/kg and greater. Effects induced by CGP 69846A were not unique and have been observed previously with other phosphorothioate oligodeoxynucleotides.

Animals↗
PubMed1998

A transitional living environment for persons with brain injuries: staff and client perceptions.

Given increasing interest in social ecology and the impact of environmental factors upon rehabilitation outcomes, the purpose of this study was to begin to document the characteristics of a particular environment designed to meet the needs of persons with traumatic brain injuries. Staff and clients at the Transitional Living Centre of Kingston, Ontario (TLC), a community based post-acute rehabilitation programme providing both residential and day programmes for adults who have acquired brain injuries participated in this study by completing the Community-Oriented Programme Environment Scale (COPES). While COPES subscale scores for clients and staff were within the average range, the results of a multivariate analysis of variance indicated that client and staff perceptions of the TLC environment differed significantly on two subscales within the Personal Development Dimension (i.e., Personal Problem Orientation, Anger and Aggression) and on one subscale under the System Maintenance Dimension (i.e., Staff Control). The results of this study suggest that future research should consider the impact of staff and client perceptions on the effectiveness of the therapeutic environment of brain injury programmes.

Activities of Daily Living↗
PubMed1998

The definition of community integration: perspectives of people with brain injuries.

Despite considerable attention to community integration and related topics in the past decades, a clear definition of community integration continues to elude researchers and service providers. Common to most discussions of the topic, however, are three ideas: that integration involves relationships with others, independence in one's living situation and activities to fill one's time. The present study sought to expand this conceptualization of community integration by asking people with brain injuries for their own perspectives on community integration. This qualitative study resulted in a definition of community integration consisting of nine indicators: orientation, acceptance, conformity, close and diffuse relationships, living situation, independence, productivity and leisure. These indicators were empirically derived from the text of 116 interviews with people with moderate-severe brain injuries living in the community. Eighteen adults living in supported living programmes were followed for 1 year, to track their evolving definition of integration and the factors they felt were related to integration. The study also showed a general trend toward more positive evaluation over the year, and revealed that positive evaluation was frequently related to meeting new people and freedom from staff supervision. These findings are interpreted in the light of recommendations for community programmes.

Activities of Daily Living↗
PubMed1998

Neurologic factors associated with cognitive impairment in a rural elderly population in India: the Indo-US Cross-National Dementia Epidemiology Study.

Few reports exist of cognitive impairment and associated factors in developing countries. An age-stratified random sample of 388 men and women, 55 years and older, was drawn from a community-based population in the rural area of Ballabgarh in northern India. We classified as "cognitively impaired" those subjects who had scores below the 10th percentile of the population on a general mental status test (the Hindi Mental State Exam, HMSE) and, separately, on a memory test (Delayed Recall of a 10-Item Word List, DRWL). Three hundred seventy-six subjects also underwent a standardized neurologic history and examination. Neurologic factors associated with cognitive impairment, after adjusting for age, gender, and literacy, were history of impaired consciousness and findings of gait disturbance, diminished deep tendon reflexes, and the presence of at least one primitive reflex. We speculate that there may be unique risk factors in developing countries such as nutritional deficiencies leading to focal deficits and cognitive impairment.

Aged↗
PubMed1998

Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US study.

OBJECTIVE: To determine the prevalence of AD and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.

Aged↗
PubMed1998

Cleft palate formation in fetal Br mice with midfacial retrusion: tenascin, fibronectin, laminin, and type IV collagen immunolocalization.

OBJECTIVE: This study tested the hypothesis that altered craniofacial morphology does not affect the expression of extracellular matrix (ECM) molecules such as fibronectin (FN), laminin (LN), type IV collagen, and tenascin-C (TN) but is associated with failure of palatal shelf elevation and fusion concomitant with cleft palate formation. DESIGN: To test this hypothesis, a comparative immunohistological analysis of FN, LN, type IV collagen, and TN was undertaken on brachyrrhine (Br/Br) mice and normal (+/+) fetuses during secondary palate formation. Normal and Br/Br fetuses were collected at gestational days E13 and E14 (representing prefusion stages) and E15 and E18 (representing postfusion stages). Cryostat palatal sections (8 microm) were postfixed in methanol, washed, and stained with primary antibody. All sections were washed and coated with secondary antibody (swine-anti-rabbit IgG) and mounted with citifluor. RESULTS: Immunohistological analysis showed that LN and type IV collagen were located near the presumptive medial epithelial seam (MES) or edge (MEE) in +/+ or Br/Br fetuses, respectively. Fibronectin showed a homogeneous distribution at all stages in both groups of mice. In contrast, TN became localized below the presumptive MES or MEE in both groups of mice at E14. In +/+ animals at E15, TN dissipated and became confined to the oral basement membrane by E18. At E15 and E18 in cleft Br/Br mutants, TN stained beneath the MEE. CONCLUSION: Although the distributions of ECM molecules are similar during normal and cleft palatogenesis, differences in TN expression are associated with cleft palate formation.

Animals↗