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Biomedical subjects

K Bradbury

Publications and source records attributed to K Bradbury.

At least 19 recordsLinked to original sources

Predictors of unintentional injuries to school-age children seen in pediatric primary care.

OBJECTIVE: To identify predictors of unintentional injury to school-age children seen in pediatric primary care. METHODS: Members of a managed health care system (295 children ages 5-11 years and their mothers) participated. We used Time 1 measures of child, maternal, and family functioning and health care utilization to predict rates of unintentional child injury for the following year. Multiple regression analyses were performed to identify variables contributing to prospective injury rates. RESULTS: The final regression model included eight Time 1 variables and accounted for 21% of the variance in Time 2 injury rates. Significant predictors of increased injury liability were younger child age, more children at home, child behavior problems, child social competence, three indices of reduced child health, and maternal anxiety. CONCLUSIONS: We discuss the utility of these predictors for pediatric psychologists in targeting primary care preventive interventions to families at risk for unintentional child injury.

Child↗

Prevention of medication errors. Developing a continuous-quality-improvement approach.

Medication errors can be a serious problem that exposes patients to preventable risks. Although medication errors are often considered primarily a nursing issue, every health care provider plays an important role in medication error prevention. A continuous quality improvement philosophy with involvement of a multidisciplinary team is the optimal method for identifying and correcting the causes of medication errors. Careful analysis of the medication distribution system and identification of system flaws is an integral part of the continuous quality improvement process.

Hospitals, Teaching↗

Generation of a human hybridoma producing a pure anti-HLA-A2 monoclonal antibody.

We report the production and characterization of a human monoclonal IgM hybridoma antibody recognizing antigen HLA-A2. B lymphocytes obtained from the peripheral blood of a multiparous volunteer 1 week postpartum were transformed in vitro by Epstein-Barr virus, screened by a microlymphocytotoxicity assay, and electrofused with the heterohybridoma fusion partner, K6H6/B5. A specifically anti-A2 secreting hybridoma cell line. MBW1, was then identified and cloned. The cytotoxic IgM antibody produced showed complete correlation (r = 1.00) with the A2 antigen on a large panel of unrelated donors' lymphocytes, and no cross-reactivity with A28, Aw68, or Aw69 antigens was observed.

Antibodies, Monoclonal↗

Effect of pituitary gonadotrophins on proliferation of primary cultures of human ovarian stroma.

Proliferation of ovarian stromal cells is a common phenomenon in peri- and post-menopausal ovaries. It is generally assumed to be secondary to the rise in circulating gonadotrophins at the menopause, though the process by which it occurs is poorly understood. This study aimed to examine the effect of menopausal levels of pituitary gonadotrophins on the growth of primary cultures of ovarian stroma. A culture system was developed using primary explants of ovarian stroma on a collagen substrate. The effect of follicle stimulating hormone (FSH; 10(-5) g/l) and luteinizing hormone (LH; 10(-5) g/l) on the proliferation of cultures derived from the cortices and medullae of ten ovaries was evaluated using a dual radiothymidine labelling technique. FSH was stimulatory to cortical cultures from 9/10 ovaries and medullary cultures from 7/10 ovaries, while LH was stimulatory to cortical cultures from 6/9 ovaries and medullary cultures from 5/10 ovaries. The responsiveness of the cultures did not correlate with the degree of hyperplasia in vivo. This study demonstrates that pituitary gonadotrophins may modulate the growth of stromal cells in culture, and thus may play a role in the process whereby stromal proliferation occurs in peri- and post-menopausal ovaries.

Adult↗

Multiple sclerosis: effects of activated T-lymphocyte-derived products on organ cultures of nervous tissue.

Supernatants from multiple sclerosis (MS) T-lymphocytes cause damage to both myelin and glial cells in cerebellar cultures assessed visually and by radiolabel release. Control T-lymphocytes, even after phytohaemagglutinin (PHA) stimulation, yielded supernatants which induced only slight damage, and at later times patients with other neurological diseases (OND) gave variable results. These differences suggest that MS T-lymphocytes are pre-activated in vivo to produce demyelinating factors while control T-lymphocytes are not pre-activated to the same extent. The visual evidence of activation of cerebellar macrophage-like cells was a common finding after MS T-lymphocyte supernatant treatment but there was no correlation with the severity of demyelination. There was a positive correlation between the percentage IL-2 receptor-bearing lymphocytes and the degree of supernatant-induced in vitro demyelination.

B-Lymphocytes↗

Late Niemann-Pick disease with neurovisceral storage: a classification problem.

A 51 year old man presented in 1969 with slowly progressive cerebellar ataxia of unknown origin. He was admitted to hospital aged 68 after a fall, and a ruptured spleen was removed at laparotomy. Histological analysis of the spleen suggested Niemann-Pick disease, which was subsequently confirmed. He deteriorated and died of bronchopneumonia shortly afterwards: subdural haemorrhage with storage material in neurones was found at necropsy. This late onset case of Niemann-Pick disease with neurovisceral storage is unusual and may represent a variant.

Age Factors↗

Use of antimicrobial agents in a university teaching hospital. Evolution of a comprehensive control program.

A comprehensive control program for utilization of anti-microbial agents in a large tertiary university teaching hospital regulates both dosage and duration of therapy and requires the prior approval of an infectious disease specialist for utilization of restricted antimicrobial agents. Benefits of the program include more cost-effective antimicrobial therapy and increased physician education in the use of these drugs. Gross savings in pharmacy costs for antibiotics during the first year of the program (1985) amounted to +483,032 for an average monthly savings of +40,252. Gross savings for 1986 were +211,786 with monthly savings of +17,648. The control of the use of one agent may lead to overuse of another agent. Antimicrobial prescribing patterns of physicians are quickly influenced by changing regulations of the program. An ongoing surveillance and review program of in-hospital utilization of antimicrobial agents is necessary to maintain effective and flexible controls.

Administration, Oral↗

Pharmacokinetic properties of mezlocillin in ambulatory elderly subjects.

Twelve healthy ambulatory elderly subjects (mean age, 73-78 years) randomly received either a 4-g or 5-g dose of mezlocillin intravenously. One week later the regimen was repeated and patients crossed over to the other dose. Peak serum concentrations were 165 mg/L and 281 mg/L for the 4-g and 5-g doses, respectively. For both doses, differences in t1/2 beta (1.32 hr vs 1.13 hr), AUC (275 mg.hr/L vs 403 mg.hr/L), CL (207 mL/min vs 174 mL/min), CLR (59 mL/min vs 45 mL/min), CLNR (152 mL/min vs 130 mL/min) were not statistically significant. The differences in Varea (22.4L vs 168.8L, P less than or equal to .01) and Cmax (216.6 mg/L vs 317 mg/L, P less than or equal to .05) were statistically significant. Comparison with pharmacokinetic parameters obtained in younger subjects following the 5-g dose reveals that in the elderly the AUC, Varea, and CLNR are higher whereas the CL and CLR are lower. The elderly demonstrated an increase in nonrenal clearance compared with young subjects that is not fully compensatory. The increased AUC in the elderly group suggests that clinical studies examining mezlocillin doses and dose intervals in the treatment of serious infections are warranted in infected elderly patients.

Aged↗

Cost-benefit analysis of an aminoglycoside monitoring service.

The clinical and financial impact of an aminoglycoside monitoring service was determined. All patients admitted to a 74-bed general medicine unit and treated with tobramycin or gentamicin during a six-month study period were eligible for the study. The first three months served as a control period during which pharmacists used published audit criteria and modifications of those criteria to monitor the appropriateness of gentamicin and tobramycin use in patients but did not attempt to intervene in aminoglycoside prescribing. During the next three months, pharmacists provided physicians with recommendations for choice of drug, coordinated blood sampling times, and designed individualized dosage regimens for all patients treated with gentamicin or tobramycin. Data for financial analysis were obtained from pharmacy profiles and medical records, and the cost:benefit ratio for the service was calculated. A total of 118 patients were included in the study. Significant improvements in appropriateness of tobramycin therapy, adequacy of loading dose, frequency of monitoring for ototoxicity, and serum concentration monitoring were noted in the intervention group. Despite an increase in gentamicin use from 20% in the control group to 61% in the intervention group, the incidence of aminoglycoside toxicity did not increase significantly. The cost:benefit ratio was 1.13, which indicates that the service is an appropriate use of resources. The aminoglycoside monitoring service had a favorable impact on the use and cost of aminoglycoside antibiotics. Expansion of the service to all areas of the hospital served by satellite pharmacies could reduce drug expenditures by as much as $55,000 per year.

Aminoglycosides↗

Comparison of in vitro demyelination and cytotoxicity of humoral factors in multiple sclerosis and other neurological diseases.

The distribution and nature of serum factors causing in vitro demyelination and glial lysis were investigated in multiple sclerosis (MS), other neurological diseases (OND), ill control and control groups. MS sera were unique in affecting only CNS myelin and glia whereas stroke and Guillain-Barré syndrome (GBS) sera brought changes to both CNS and PNS tissue. Through both visual scoring of myelin damage and the quantitative measurement of radiolabel release from cerebellar cultures, it was evident that the MS and OND groups have similar myelino- and cytotoxic effects. This may reflect MS and OND sera sharing similar humoral factors. 74% MS, 68% OND and 22% of control scores were above a score threshold designed to exclude culture handling trauma effects. When classified by their current disease state MS patients with severe and mild disease yielded higher in vitro scores than did those with moderate disease who comprised an older age group. No other clinical features of MS patients gave any association with in vitro serum effects. The rare demonstration of bound Fab IgG in cultures after MS serum tests indicates that immune mechanisms are unlikely to make a large contribution to serum-induced demyelination and cellular change in vitro.

Central Nervous System Diseases↗

New approach to study of in vitro toxicity of multiple sclerosis and other sera.

The in vitro effects of MS and control sera were quantified by the measurement of radiolabel released from myelinated cultures of rat cerebellum and compared with a visual assessment of myelin damage. Radiolabel release gave a sensitive index of serum effects in vitro which was free of the score assignment decisions that are associated with the visual assessment of myelin damage. Examination of the patterns of radiolabel release elicited by MS and control sera on cultures labelled with either L-[5-3H]tryptophan or galacto-D-[6-3H]cerebroside indicates that MS serum effects are not simply a stronger expression of the weak control serum effects.

Animals↗

Role of complement in demyelination in vitro by multiple sclerosis serum and other neurological disease sera.

Multiple sclerosis (MS) sera can demyelinate and cause selective cellular changes to organ cultures of rodent CNS which suggests possible immunoglobulin involvement. The complement dependence of this serum action was investigated using complement-inactivating agents and radiolabelled rat cerebellar cultures. After heat inactivation at 56 degrees C, the in vitro effects of MS, chronic relapsing experimental allergic encephalomyelitis (cr-EAE) and Guillain-Barré syndrome (GBS) sera were severely reduced or eliminated as measured by radiolabel release. On introducing a source of fresh complement, the cr-EAE and GBS serum effects were largely restored whereas MS serum effects remained suppressed. Inactivation of serum complement with mercaptoethanol and Zymosan was associated with marked reduction in serum myelinotoxicity; some restoration of in vitro effects was possible on adding fresh complement although this occurred to a greater extent with cr-EAE and GBS than with MS sera. Inactivation of the alternative complement pathway brought a limited reduction in MS serum activity in vitro which was not restored with fresh complement. It is concluded that complement is involved only to a limited extent in MS serum myelinotoxic effects and that MS serum effects in vitro are due to several components of which thermolabile substances make a significant contribution and are as yet uncharacterised.

Animals↗

Ethanolamine glycerophospholipid formation by decarboxylation of serine glycerophospholipids in myelinating organ cultures of cerebellum.

Serine decarboxylation as a source of glycerophospholipid ethanolamine is known to occur in mammals. However, early investigators failed to demonstrate the pathway in brain. In the present study serine is shown to be decarboxylated to glycerophospholipid ethanolamine in myelinating organ cultures of rat cerebellum up to 32 days in vitro. The pattern of incorporation of L-[3-14C]serine into culture phospholipids strongly suggests a precursor-product relationship between serine glycerophospholipids (SGP) and ethanolamine glycerophospholipids (EGP), with serine label appearing in the ethanolamine moiety of EGP. The time course of labelling was similar for both acid-stable and acid-labile EGP. In contrast DL-[1-14C]serine failed to label EGP significantly due to the loss of serine carbon C1 on decarboxylation. Through the systematic hydrolysis of phospholipids from cerebellar cultures incubated with L-[3-14C], it was clear that in SGP, acid-stable EGP, and acid-labile EGP greater than to 70% of radiolabel resides in the base moiety of each of these molecular species. It is proposed that serine decarboxylation as a source of EGP ethanolamine may be important in the early stages of brain development.

Animals↗

In vitro toxicity of MS sera correlates with new clinical signs.

In vitro toxicity of sera from 10 MS patients was followed for up to 3 years. Myelinotoxicity and cytotoxicity measured as radiolabel release from rat cerebellar explants were almost continuously higher in than in controls while peaks of radiolabel release were associated with the emergence of new clinical signs in the MS patients.

Adult↗