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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 91 records · Page 5Linked to original sources
PubMed2001

Ethylene glycol-mediated tubular injury: identification of critical metabolites and injury pathways.

Ethylene glycol (EG) intoxication produces multisystem organ injury, including acute renal failure. Although EG must be metabolized to toxic intermediates to induce organ damage, the specific metabolite(s) responsible and the underlying pathogenic mechanisms remain poorly defined. To explore these issues, isolated mouse proximal tubular segments (PTSs) were incubated with either varying doses of EG or its prime metabolites (glycolate, glycoaldehyde, glyoxylate, or oxalate for 15 to 60 minutes). Injury was assessed by the percentage of lactate dehydrogenase (LDH) release, LDH destruction, adenosine triphosphate (ATP) depletion, or membrane phospholipid degradation. Toxicities were also assessed in cultured HK-2 cells over 18 hours (by MTT assay). EG, glycolate, and oxalate did not induce overt PTS injury. Conversely, glyoxylate and glycoaldehyde were highly toxic, causing profound ATP depletion and LDH release. Glycoaldehyde also caused enzyme (LDH) and selected phospholipid degradation (phosphatidylethanolamine, phosphatidylserine). These changes were not seen with glyoxylate treatment. Acidosis (pH 6.8) and glycine (2 mmol/L) each blocked glyoxylate, but not glycoaldehyde toxicity, indicating differing injury pathways. Only glycoaldehyde and glyoxylate induced marked HK-2 cell death. We conclude that glycoaldehyde and glyoxylate are the principal metabolites responsible for EG nephrotoxicity and do so by causing ATP depletion and phospholipid and enzyme destruction. Glycine and acidosis, by-products of EG metabolism, can attenuate glyoxylate-mediated injury. This suggests that naturally occurring but incomplete protective pathways may be operative during the evolution of EG cytotoxicity.

Adenosine Triphosphate↗
PubMed2001

Supported treadmill ambulation training after spinal cord injury: a pilot study.

OBJECTIVES: To conduct a pilot study of weight-supported ambulation training after incomplete spinal cord injury (SCI), and to assess its safety. DESIGN: Quasiexperimental, repeated measures, single group. SETTING: Veterans Affairs medical center. PATIENTS: Three subjects with incomplete, chronic, thoracic SCIs; 2 classified as D on the American Spinal Injury Association (ASIA) impairment scale and 1 as ASIA impairment scale C. INTERVENTION: Subjects participated in 12 weeks of training assisted by 2 physical therapists. The training consisted of walking on a treadmill while supported by a harness and a pneumatic suspension device. Support started at 40% of body weight and a treadmill speed of.16kmph, and progressed by reducing support and increasing treadmill speed and continuous treadmill walking time up to 20 minutes. Training was conducted for 1 hour per day, 5 days per week for 3 months. Treadmill walking occurred for 20 minutes during the sessions. MAIN OUTCOME MEASURES: Gait function (speed, endurance, walking status, use of assistive device and orthotics); oxygen costs of walking; brain motor control assessment; self-report indices; ASIA classification; muscle function test; and safety. RESULTS: All 3 subjects increased gait speed (.118m/s initially to.318m/s after training 12wk), and gait endurance (20.3m/5min initially to 63.5m/5min). The oxygen costs decreased from 1.96 to 1.33mL x kg(-1) x m(-1) after 12 weeks of training. CONCLUSIONS: This pilot study suggests that supported treadmill ambulation training can improve gait for individuals with incomplete SCIs by using objective gait measures. The self-report indices used have promise as patient-centered outcome measures of this new form of gait training. A larger, controlled study of this technique is warranted.

Activities of Daily Living↗
PubMed2001

Prospective assessment of tizanidine for spasticity due to acquired brain injury.

OBJECTIVE: To determine if orally delivered tizanidine will control spastic hypertonia due to acquired brain injury. DESIGN: Randomized, double-blind, placebo-controlled, crossover design, with 2 8-week treatment arms separated by a 1-week washout period at baseline. Patients were randomly assigned to receive tizanidine or a matching placebo. SETTING: Tertiary care outpatient and inpatient rehabilitation center attached to a university hospital. PARTICIPANTS: Seventeen persons recruited in a consecutive manner, 9 of whom had suffered a stroke and 8 a traumatic brain injury, and had more than 6 months of intractable spastic hypertonia. INTERVENTION: Over a 6-week period, subjects were slowly titrated up to their maximum tolerated dose (up to 36 mg/d). Following a 1-week drug taper and 1-week period in which no study drug was administered, patients were then crossed over to the other study medication following an identical titration regime. MAIN OUTCOME MEASURES: Subjects were evaluated for dose and effect throughout the trial as well as for side effects. Data for Ashworth rigidity scores, spasm scores, deep tendon reflex scores, and motor strength were collected on the affected upper extremity (UE) and lower extremity (LE). Differences over time were assessed via descriptive statistics, Friedman's analysis, and Wilcoxon's signed-rank. Data are reported as the mean +/- 1 standard deviation. RESULTS: Following 4 weeks of treatment when subjects reached their maximal tolerated dosage, the average LE Ashworth score on the affected side decreased from 2.3 +/- 1.4 to 1.7 +/- 1.1 (p <.0001). The spasm score decreased from 1.0 +/- 0.9 to 0.5 +/- 0.8 (p =.0464), while the reflex score was not statistically significant decreasing from 2.2 +/- 1.0 to 2.0 +/- 1.1 (p =.0883). The average UE Ashworth score on the affected side decreased from 1.9 +/- 1.1 to 1.5 +/- 0.9 (p <.0001). There was no significant change in the UE spasm and reflex scores. While there were positive placebo effects on motor tone, the active drug was still significantly better than placebo for decreasing LE tone (p =.0006) and UE tone (p =.0007). With a reduction in motor tone, there was an increase in motor strength (p =.0089). The average dosage at 4 weeks was 25.2mg/d. CONCLUSION: Tizanidine is effective in decreasing the spastic hypertonia associated with acquired brain injury, which is dose-dependent. There are limitations on its use due to side effects related to drowsiness.

Administration, Oral↗
PubMed2001

Immunogenicity of hepatitis A vaccination in decompensated cirrhotic patients.

Hepatitis A virus (HAV) vaccination is recommended in chronic liver disease because of an increased morbidity and mortality associated with HAV superinfection. However, data regarding the efficacy of HAV vaccination in patients with advanced chronic liver disease is limited. We assessed the efficacy of a standard HAV vaccination schedule in decompensated chronic liver disease in comparison with compensated disease and defined clinical predictors associated with seroconversion. Eighty-four anti-HAV antibody-negative patients, 49 with compensated liver disease, and 35 with decompensated disease were enrolled. Seroconversion was measured by qualitative and quantitative anti-HAV antibody measurements 1 month after each vaccine dose, and univariate/multivariate analysis was performed to define clinical predictors associated with seroconversion. One month after the primary dose, 71.4% of patients with compensated liver disease had detectable anti-HAV antibody compared with 37.1% with decompensated liver disease (P <.05). One month after the booster dose, 98% of compensated patients seroconverted compared with 65.7% with decompensated disease (P <.05). The median serum antibody concentration in compensated liver disease was 76.4 mIU/mL at month 1 and 327.91 mIU/mL at month 7 compared with 20.0 mIU/mL and 102.57 mIU/mL, respectively, in decompensated disease. On multivariate analysis, Child-Pugh class was the only factor predicting response to vaccination. Seroconversion after HAV vaccination was significantly less common in decompensated liver disease and the presence of advanced disease (Child-Pugh class B/C) predicted a lower response rate. These findings indicate that the response to HAV vaccination in chronic liver disease is optimal when targeted to patients before the development of hepatic decompensation.

Adult↗
PubMed2001

Public health advocacy--determining a role for staff of a public hospital.

This study explored the public health advocacy role of staff employed at a major South Australian specialist public hospital that had made an organisational commitment to health promotion. It was concluded that staff did have a role to play in public health advocacy, though the issues pursued primarily related to disease and injury prevention rather than the broader social determinants of health. Staff gained valuable experience in the political processes of public health advocacy. The hospital had to develop organisational infrastructures to support staff so they could undertake public health advocacy on behalf of the hospital. It was also necessary for the hospital to implement other changes in order to 'get its own house in order' before issues could be addressed in the broader community.

Community Health Planning↗
PubMed2001

The comparative effectiveness of conventional and digital image libraries.

Before introducing a hospital-wide image database to improve access, navigation and retrieval speed, a comparative study between a conventional slide library and a matching image database was undertaken to assess its relative benefits. Paired time trials and personal questionnaires revealed faster retrieval rates, higher image quality, and easier viewing for the pilot digital image database. Analysis of confidentiality, copyright and data protection exposed similar issues for both systems, thus concluding that the digital image database is a more effective library system. The authors suggest that in the future, medical images will be stored on large, professionally administered, centrally located file servers, allowing specialist image libraries to be tailored locally for individual users. The further integration of the database with web technology will enable cheap and efficient remote access for a wide range of users.

Databases as Topic↗
PubMed2001

Health promoting hospitals: a typology of different organizational approaches to health promotion.

This paper draws on a review of the literature about the types of health promotion activities conducted by health promoting hospitals and an observation of how some Australian hospitals have structured the organizational arrangements to be more health promoting. This paper also draws on the experiences of one of the authors (A.J.) in managing and evaluating an organizational change process at a major specialist hospital in Adelaide, South Australia, that sought to re-orientate the hospital towards placing more emphasis on health promotion. From these three sources, a typology of four approaches of organizational arrangement to health promotion is presented. These approaches are: 'doing a health promotion project'; 'delegating it to the role of a specific division, department or staff'; 'being a health promotion setting'; and 'being a health promotion setting and improving the health of the community'. For the re-orientation of the specialist hospital to occur and be sustainable, the research indicated that over the case study period of 1994-1998 there had to be strong organizational commitment to change, supported at multiple levels of the organization, and reflected in policy and practice change. The paper concludes that more evaluative research of this type will be important if the rhetoric of healthy settings is to become a reality.

Attitude of Health Personnel↗
PubMed2001

Pulse oximetry in sickle cell anemia.

OBJECTIVES: To determine whether pulse oximetry is accurate and if it correlates with arterial blood gas saturation in pediatric patients with sickle cell anemia. DESIGN: Prospective, comparative study using a convenience sample of patients with sickle cell anemia who had simultaneous arterial blood gas sampling and pulse oximetry. SETTING: Children's Memorial Hospital, a large tertiary care pediatric hospital in Chicago, IL. Patients selected from the emergency department and the pediatric intensive care unit. PATIENTS: Twenty-four consecutive patients with sickle cell anemia who had simultaneous arterial blood gas sampling and pulse oximetry. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients had a total of 70 simultaneous pulse oximeter and blood gas pair samples. Each patient's initial pulse oximeter/blood gas pair was used in the statistical analysis. Three patients had venous samples and were excluded from comparison, leaving 21 arterial blood gas/pulse oximeter pairs for analysis. The pulse oximeter correlated well with the cooximeter-measured arterial saturation (r(2) =.74). The pulse oximeter significantly underestimated saturation by a mean of -1.6% (95% confidence interval, -0.3 to -3; p =.03). CONCLUSIONS: Pulse oximetry correlates well with cooximeter-measured saturation in patients with sickle cell anemia. Pulse oximetry significantly underestimates true arterial saturation, but the bias is clinically insignificant. Pulse oximetry can be used reliably to estimate the arterial oxygen saturation in patients with sickle cell anemia.

Adolescent↗
PubMed2001

Randomised controlled trial of prophylactic etamsylate: follow up at 2 years of age.

AIM: To assess the role of etamsylate in reducing the risk of haemorrhagic brain damage and its consequences. DESIGN: Follow up of babies recruited into a randomised controlled trial. METHODS: A total of 334 infants born before 33 weeks gestation in France and Greece were randomly allocated within the first four hours of birth either to receive etamsylate or to act as controls. The principal outcomes in the trial were death or impairment and/or disability at the age of 2 years. RESULTS: Fifty nine children were lost to follow up. A total of 115 (34%) either died or had some impairment or disability, and 88 (26%) either died or had severe impairment or disability at 2 years of age. These outcomes did not differ significantly between the two randomised groups: relative risks and 95% confidence intervals 1.14 (0.78 to 1.4) and 1.17 (0.82 to 1.68) respectively. The findings were similar for all the prespecified subgroup analyses stratified by key prognostic factors at trial entry: country of birth, gestational age < or >or= 29 weeks, inborn or outborn, age < or >or= 1 hour, and with or without cerebral scan abnormality. CONCLUSION: These findings do not support the use of etamsylate. Other strategies need to be evaluated for the prevention of mortality and morbidity in these vulnerable infants.

Child Health Services↗
PubMed2001

Educational and behavioural problems in babies of 32-35 weeks gestation.

AIM: To identify incidence of school and behaviour problems at age 7 years in children born between 32 and 35 weeks gestation, and investigate perinatal risk factors. METHOD: The study population consisted of all children born at 32-35 weeks gestation to mothers resident in Oxfordshire in 1990. General practitioners, parents, and teachers were asked about health, behaviour, and education by postal questionnaire. Teachers rated children on level of function in six areas using a five point scale. They also completed the Strengths and Difficulties behaviour questionnaire. Perinatal risk factors were identified for children with poor school performance using a univariate and multivariate analysis. RESULTS: Teacher responses were obtained for 117 (66%) of the 176 children in the cohort. Twenty nine (25%) required support from a non-teaching assistant, five (4%) had required a statement of special educational needs, and three (3%) were at special school. Poor outcome was reported for 32% in writing, 31% in fine motor skills, 29% in mathematics, 19% in speaking, 21% in reading, and 12% in physical education. On the behaviour questionnaire, 19% of the cohort achieved an abnormal hyperactivity score (population norm 10%). Multivariate analysis showed perinatal variables that remained significant, independent of other variables; they were discharge from the special care baby unit > 36 weeks postconceptional age (odds ratio 4.15; 95% confidence interval 1.43 to 12.05) and male sex (odds ratio 3.88; 95% confidence interval 1.42 to 10.6). CONCLUSION: Up to a third of children born between 32 and 35 weeks gestation may have school problems. As there are larger numbers in this gestational category compared with smaller babies, this finding has implications for educational services.

Adult↗
PubMed2001

Role of ecNOS-derived NO in mediating TNF-induced endothelial barrier dysfunction.

We tested the hypothesis that endothelial cell nitric oxide synthase (ecNOS) mediates the tumor necrosis factor (TNF)-alpha-induced increase in nitric oxide (NO) and albumin permeability in pulmonary microvessel endothelial monolayers (PEM). PEM lysates were analyzed for ecNOS mRNA (RT-PCR), ecNOS protein (Western immunoblot), NO levels (NO, the oxidation product of NO), and barrier function (albumin clearance rate). PEM were incubated with TNF (50 ng/ml) for 0.5, 2, 4, and 24 h. TNF induced a decrease in ecNOS mRNA at 2, 4, and 24 h. TNF induced an acute (0.5 h) increase followed by a protracted decrease (4-24 h) in ecNOS protein levels. The other NOS isotypes, inducible and brain NOS, could not be detected in the PEM using RT-PCR and Western blot assay. ecNOS antisense oligonucleotide decreased ecNOS protein, which prevented the increase in NO and albumin permeability at TNF-4 h. Spermine-NONOATE, the NO agonist, ablated the protective effect of ecNOS antisense oligonucleotide on albumin permeability in response to TNF-4 h. However, ecNOS antisense oligonucleotide had no effect on the TNF-induced increase in albumin permeability at 24 h despite prevention of the increase in NO. The data indicate that the isotype ecNOS mediates generation of NO and the acute (i.e., 4 h) barrier dysfunction; however, the prolonged (i.e., 24 h) increase in the TNF-induced increase in endothelial permeability is independent of NO.

Animals↗
PubMed2001

Randomized, controlled trial of acetazolamide and furosemide in posthemorrhagic ventricular dilation in infancy: follow-up at 1 year.

OBJECTIVE: Posthemorrhagic ventricular dilation (PHVD) is a complication of intraventricular hemorrhage in preterm infants and is associated with a high risk of long-term disability. Furosemide and acetazolamide are used widely in the treatment of PHVD in the hope of avoiding the need for placement of a ventriculoperitoneal shunt, but these drugs have not been evaluated in a controlled trial. This article reports a multicenter, randomized, controlled trial designed to test the hypothesis that these drugs would reduce the rate of shunt placement (or death) and increase survival to 1 year of age without disability. METHODS: Between 1992 and 1996, 177 infants who were less than 3 months past term and had ventricular width >4 mm above the 97th centile following intraventricular hemorrhage were assigned randomly to either standard therapy or standard therapy plus drug therapy with acetazolamide (100 mg/kg/d) plus furosemide (1 mg/kg/d). Infants who were enrolled in the trial had a median gestational age of 28.6 weeks and were enrolled at a mean postnatal age of 3.6 weeks. Forty-four percent were reported to have a cerebral parenchymal lesion on ultrasound scan at randomization. The primary outcome measure of death or shunt placement (known in all but 1 infant) occurred in 56 of 88 infants who were allocated to drug plus standard therapy compared with 46 of 88 who were allocated to standard therapy. The risk ratio was 1.23 (95% confidence interval: 0.95-1.59). Neurodevelopmental outcome information at a corrected age of 1 year (known in all but 3 of 149 surviving infants) included disability or neuromotor impairment in 54 of 67 infants (81%) who were allocated to drug plus standard therapy and 52 of 69 infants (66%) who were allocated to standard therapy. Seventy-two of 85 infants (85%) who were allocated to drug therapy either died or were disabled or impaired at 1 year compared with 62 of 89 infants (70%) who were treated with standard therapy (risk ratio: 1.22; 95% confidence interval: 1.03-1.4376). The excess risk of these adverse outcomes was greater among infants who did not have a cerebral parenchymal lesion seen on ultrasound examination at trial entry. CONCLUSIONS: These results suggest that the use of acetazolamide and furosemide in preterm infants with PHVD is ineffective in decreasing the rate of shunt placement and is associated with increased neurologic morbidity. This treatment therefore cannot be recommended.

Acetazolamide↗
PubMed2000

Patient empowerment in secondary prevention of coronary heart disease.

Despite a large evidence base, the practice of secondary prevention in coronary artery disease is suboptimum and needs improvement. We have shown that although patient empowerment led to an increase in cholesterol checks, the action taken by health-care professionals as a result of these checks was poor.

Anticholesteremic Agents↗
PubMed2000

Purification, crystallisation and preliminary X-ray study of haemoglobin from Crocodilis palustris and Crocodilis porosus.

The unsolved three-dimensional structure of crocodile haemoglobin and its prospects as a blood substitute have led us to initiate the purification and crystallisation of haemoglobin molecules from crocodile species (Crocodilis palustris or mugger and Crocodilis porosus or salt water crocodile). The work has resulted in the prevention of polymerisation of naked haemoglobin molecules using N-ethylmaleimide or iodoacetamide. The purified monomeric haemoglobin molecule of C. porosus was crystallised in two different forms and X-ray diffraction data were collected up to 2 A resolution for both forms. Form I: a=53.62, b=53.55, c=103.77 A; beta=93.35 degrees, space group P2(1), Z=2. Form II: a=71.30, b=54.70, c=80.00 A; beta=106.4 degrees, space group P2(1), Z=2. Structure solution and rigid body refinement of form I data resulted in a model with R(free)=0.42 and R=0.35.

Alligators and Crocodiles↗