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Biomedical subjects

L Price

Publications and source records attributed to L Price.

At least 37 records · Page 2Linked to original sources

WAIS-III reliability data for clinical groups.

Reliability estimates for psychological tests are almost always reported for nonclinical populations (e.g., the normative samples). Such practice will no longer be sufficient as the new standards for testing call for an adequate assessment of psychometric properties within the specific population being tested. The purpose of this study was to provide internal consistency reliability estimates for clinical groups on the Wechsler Adult Intelligence Scale-Third Edition. The study included data from 403 clinical participants composed of 10 groups of adults recruited as part of the WAIS-III clinical validity studies. Split-half reliability coefficients were obtained for these groups replicating the procedure used in the WAIS-III. With 8 of the clinical groups, the split-half reliability coefficients were comparable to, or even higher than, those reported for the WAIS-III standardization sample. In general, the split-half coefficients for the Verbal subtests tended to be higher than the coefficients for the Performance subtests. The high magnitude and general pattern of these coefficients demonstrate that the WAIS-III scales do not include additional error variance above and beyond what is reported in the WAIS-III-WMS-III Technical Manual when it was used to assess certain clinical groups. For the ADHD/ADD and learning disabilities groups, however, the internal consistencies coefficients of some subtests were relatively lower, although not statistically significant, than the normative sample. These findings may reflect more heterogeneity within the groups. The implications for assessment and for using alternate methods of determining the psychometric properties in these populations are discussed.

Adolescent↗

Prospective validation of renal function-based carboplatin dosing in children with cancer: A United Kingdom Children's Cancer Study Group Trial.

PURPOSE: Carboplatin dosing in adults with cancer is based on renal function. The purpose of the current study was to validate a previously developed pediatric carboplatin-dosing formula. PATIENTS AND METHODS: Thirty-eight pediatric patients were randomized to receive a carboplatin dose calculated according to surface area or a renal function-based dosing formula. On the next course of therapy, the alternative dosing method was used for each patient. Carboplatin pharmacokinetics (based on free plasma platinum concentrations) were measured after both courses. RESULTS: The mean observed areas under the carboplatin concentration-versus-time curve (AUCs) after renal function- and surface area-based dosing were 98% and 95% of the target AUCs, respectively. The variation in the observed AUC was significantly less after renal function-based dosing (F test, P =.02), such that 74% of courses had an observed AUC within +/- 20% of the target value, versus 49% for courses after dosing according to surface area. Only one of 22 courses at the center with the most experience with renal function-based dosing was associated with an AUC outside +/- 20% of the target value, versus nine of 22 courses after surface area-based dosing in the same center. There was a relationship (r(2) =.71) between carboplatin AUC and thrombocytopenia in 10 neuroblastoma patients treated with a combination of carboplatin, vincristine, etoposide, and cyclophosphamide. CONCLUSION: Renal function-based carboplatin dosing in children results in more consistent drug exposure than surface area-based drug administration.

Adolescent↗

Plasma coenzyme Q(10) in children and adolescents undergoing doxorubicin therapy.

The objective of this study was to test the hypothesis that doxorubicin treatment for cancer in childhood and adolescence causes a dose-related decrease in the concentration of plasma coenzyme Q(10). The concentration of plasma coenzyme Q(10) was measured before and after administration of doxorubicin in six patients, and before and after chemotherapy in six patients undergoing treatments that did not include doxorubicin. There was a significant increase in the concentration of plasma coenzyme Q(10) in post-treatment samples compared to pre-treatment samples in patients treated with doxorubicin (P=0.008; n=32), whereas there were no significant changes in plasma coenzyme Q(10) concentrations in patients treated with chemotherapy that did not include doxorubicin. (P=0.770; n=30). We hypothesise that the increase in plasma coenzyme Q(10) that was observed in patients undergoing doxorubicin treatment is due to release of coenzyme Q(10) from apoptotic or necrotic cardiac tissue. We conclude that the cardiotoxicity due to doxorubicin therapy does not involve acute myocardial depletion of coenzyme Q(10).

Adolescent↗

A controlled study of virtual reality exposure therapy for the fear of flying.

Fear of flying (FOF) affects an estimated 10-25% of the population. Patients with FOF (N = 49) were randomly assigned to virtual reality exposure (VRE) therapy, standard exposure (SE) therapy, or a wait-list (WL) control. Treatment consisted of 8 sessions over 6 weeks, with 4 sessions of anxiety management training followed by either exposure to a virtual airplane (VRE) or exposure to an actual airplane at the airport (SE). A posttreatment flight on a commercial airline measured participants' willingness to fly and anxiety during flight immediately after treatment. The results indicated that VRE and SE were both superior to WL, with no differences between VRE and SE. The gains observed in treatment were maintained at a 6-month follow up. By 6 months posttreatment, 93% of VRE participants and 93% of SE participants had flown. VRE therapy and SE therapy for treatment of FOF were unequivocally supported in this controlled study.

Adult↗

Differentiation of clinical Helicobacter pullorum isolates from related Helicobacter and Campylobacter species.

BACKGROUND: Helicobacter pullorum, first detected in the liver and intestinal contents of poultry, was defined as a new species in 1994. This organism has since been isolated from humans with gastroenteritis. Phenotypic as well as genotypic methods have been used to identify H. pullorum associated with cases of human disease. MATERIALS AND METHODS: Clinical isolates were submitted for identification to the National Laboratory for Enteric Pathogens by Provincial Public Health Laboratories within Canada. Phenotypic characterization was conducted using a variety of growth and biochemical tests including oxidase, catalase, indoxyl acetate, H2S production in triple sugar iron (TSI) agar, antimicrobial susceptibility testing, and fatty acid analysis. Genotypic identification was performed using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis of a 1-kb fragment of the Helicobacter 16S rRNA gene. RESULTS: During the last 7 years (1993-1999) a total of 11 isolates of H. pullorum were detected from patients with gastroenteritis for inclusion in this study. Typically, these isolates were oxidase and catalase positive, produced optimal growth at 42 degrees C, and produced H2S in TSI. Of these 11 isolates, 1 showed DNase activity, while another did not produce H2S in TSI, and only 2 showed tolerance to 1% bile. Antimicrobial susceptibility assays indicated that 6 of the 11 strains were resistant to nalidixic acid. The fatty acid profiles of the isolates were similar to each other and provided a distinguishing profile from the other related species. Genetically identical and distinct species-specific restriction fragment-length polymorphism (RFLP) patterns were produced using the restriction enzymes Bsr I and Dde I. CONCLUSION: Phenotypic and genotypic procedures were used to identify H. pullorum. Interspecies phenotypic variability was apparent and supported the use of a polyphasic approach for identification. Similarities to the more prominent human pathogens Campylobacter coli and C. lari were also noted. The use of a combination of phenotypic and, in particular, genotypic markers for H. pullorum should prove valuable both for epidemiological investigations and for the diagnosis of disease related to this emerging human pathogen.

Campylobacter↗

Dependency in older people recently admitted to care homes.

OBJECTIVE: to investigate dependency and general health status of a cohort of older people admitted to residential or nursing homes for long-term care. METHOD: we assessed 308 people aged over 65 years within 2 weeks of admission for long-term care to one of 30 nursing or residential homes in north-west England. Dependency was assessed using the Barthel activities of daily living index and the Crichton Royal Behaviour Rating Scale. We collected information from the homes' records on diagnosed conditions and current medication. RESULTS: 50% of the cohort were in a 'low dependency' band (Barthel score 13 - 20): 31% of those in nursing homes and 71% of those in residential homes. In nursing homes, low-dependency residents were more likely to be self-funding than those with higher dependency. Of a number of broad diagnostic groupings, only a diagnosis of dementia was associated with nursing- rather than residential-home admission. Of 47 residents who scored 9 or less on the Mini-Mental State Examination (indicating severe cognitive impairment), 85% had no diagnosis of dementia, neurological disorder or other psychiatric disorder. DISCUSSION: the high proportion of new admissions of subjects with low dependency needs raises questions about the effective targeting of resources and about management of the boundary between home-based and institutional care. The existence of an important group of self-funded, low-dependency new admissions to nursing homes suggests a need to provide better assessment and placement services for those who are financially independent of local authorities. Many new admissions had conditions which might benefit from rehabilitation but there were almost no therapy staff in the studied homes. In some cases where severe cognitive impairment was evident, there was no evidence that the result of any formal pre-admission psychiatric evaluation had been communicated to nursing or care staff.

Aged↗

Hypogonadism in patients treated with intrathecal morphine.

OBJECTIVE: The objective of this study was to investigate the hypothalamic-pituitary-gonadal response to intrathecal opioids. PATIENTS: Thirty patients receiving intrathecal morphine for chronic nonmalignant pain were studied for clinical and biochemical evidence of hypogonadism. Ten men and 10 postmenopausal women with chronic pain of similar duration but who were not receiving any form of opioid therapy acted as control subjects. RESULTS: Men and both premenopausal and postmenopausal women had evidence of hypogonadism with low levels of serum testosterone or estrogen coupled with low levels of pituitary gonadotrophins. Control subjects had hormone levels in the expected range for their sex and age. Two men demonstrated recovery after ceasing intrathecal opioid therapy. CONCLUSIONS: Hypogonadotrophic hypogonadism is a common complication of intrathecal opioid therapy in both men and women.

Adult↗

Dose-related nephrotoxicity of carboplatin in children.

This study investigated changes and the time course of these changes in renal function in children following treatment with carboplatin, and identified risk factors for nephrotoxicity. Glomerular and proximal renal tubular function were investigated before and up to 2 years after treatment in 23 children who received carboplatin. The main findings were reduced glomerular filtration rate (GFR), and increased renal tubular loss of magnesium, manifested by a low serum magnesium (S Mg). The mean fall in GFR was 22 ml min(-1) 1.73 m(-2) (P = 0.012), and in S Mg it was 0.17 mmol l(-1) (P = 0.0077). No patient had a clinically important reduction in GFR, and only one patient had symptomatic hypomagnesaemia. GFR and S Mg did not change over time after completion of treatment. Cumulative dose (CD) of carboplatin was inversely related to mean S Mg at the end of treatment (P = 0.031), and directly related to the fall in S Mg (P < 0.001). Calculated cumulative area under the plasma concentration versus time curve (AUC) of carboplatin was inversely related to S Mg after treatment (P = 0.004). Dose intensity (DI) of carboplatin was not shown to be related to S Mg following treatment. CD, AUC and DI of carboplatin were not related to GFR, nor change in GFR, after treatment. High CDs of carboplatin may be associated with evidence of renal damage qualitatively similar to but less severe than that caused by cisplatin. GFR and SMg should be carefully monitored when high CDs of carboplatin are used, or if carboplatin is combined with other nephrotoxic chemotherapy.

Adolescent↗

Cyclophosphamide metabolism in children with Fanconi's anaemia.

Although patients with Fanconi's anaemia (FA) exhibit a heightened sensitivity to DNA cross-linking agents, modified doses of CY continue to be used in their conditioning prior to BMT. We measured the pharmacokinetics and metabolism of CY in six children with FA using an established high performance thin layer chromatography technique. CY doses ranged between 5 and 20 mg/kg (median 10 mg/kg). The median CY clearance was 0.6 l/h/m2 (range 0.4-1.1 l/h/m2), t1/2 was 8.1 h (range 6.7-9.5 h) and volume of distribution was 0.19 l/kg (range 0.16-0.34 l/kg), respectively. These results contrast with those previously reported from a comparable group of non-FA children in whom the median CY clearance was 3.2 l/h/m2 (range 2-5 l/h/m2) (P = 0.035), t1/2 was 2.4 h (range 2-3.8 h) (P = 0.035) and volume of distribution 0.5 l/kg (range 0.26-0.95 l/kg) (NS). Unlike the control group in whom the presence of inactive metabolites of CY was common, metabolites could not be found in any FA patient. The enhanced sensitivity of children with FA to CY may in part result from altered drug metabolism.

Bone Marrow Transplantation↗

Cisplatin dose rate as a risk factor for nephrotoxicity in children.

The purpose of the study was to evaluate the incidence, risk factors and changes in severity with time of cisplatin nephrotoxicity in children. A total of 35 children underwent measurement of glomerular filtration rate (GFR) and tubular function after completion of cisplatin chemotherapy. No child received ifosfamide. A clinically relevant 'nephrotoxicity score' was derived from GFR and serum magnesium. Follow-up studies were performed in 16 children at 1 year and in 15 at 2 years after cisplatin. Considerable interpatient variability in nephrotoxicity was observed. Treatment was modified in three patients because of nephrotoxicity. GFR was low in 18 out of 31 patients. Proximal nephron toxicity caused hypomagnesaemia in ten patients and hypocalcaemia in five patients. Elevated urinary N-acetylglucosaminidase excretion was seen in 22 out of 30 children, indicating subclinical tubular toxicity. Nephrotoxicity was less severe in children who received cisplatin courses at a dose rate of 40 mg m(-2) day(-1) than in those who received higher dose rates (P < 0.005), but there was no correlation with total dose received. Follow-up studies revealed partial recovery of GFR (P < 0.05). Glomerular and proximal nephron toxicity are common in children treated with cisplatin, and more severe at higher dose rates. Despite partial recovery of GFR, the long-term outcome of nephrotoxicity remains unknown and careful monitoring of chronic toxicity is necessary.

Adolescent↗

A study of the feasibility and accuracy of pharmacokinetically guided etoposide dosing in children.

Pharmacokinetically guided dosing was performed in nine paediatric patients receiving etoposide. Doses on day 2 of a 2- or 3-day schedule were adapted on the basis of the day-1 area under the plasma etoposide concentration vs time curve (AUC). The day-1 AUC was estimated using a limited sampling model and the day-2 target AUC defined by the etoposide dose-AUC relationship observed in 33 children. Target AUC values (4.6-8.2 mg ml(-1) x min) were achieved with a high degree of precision and with little bias (mean error 11% and root mean squared error 15% respectively). Pharmacokinetic parameters were similar to those reported previously in children, although interpatient pharmacokinetic variability was less than that observed previously: plasma clearance, 23 (18-26) ml min(-1) m(-2); volume of distribution at steady state (Vdss), 6.0 (3.9-8.9) l m(-2); t(1/2) 254 (127-550) min (median and range). This study has demonstrated that pharmacokinetically guided dosing with etoposide is feasible. However, pharmacokinetically guided dosing is likely to be of most benefit in patients with abnormalities of renal or hepatic function, or in children with prior exposure to cisplatin.

Adolescent↗

Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children's Cancer Study Group.

A phase I study of temozolomide administered orally once a day, on 5 consecutive days, between 500 and 1200 mg m(-2) per 28-day cycle was performed. Children were stratified according to prior craniospinal irradiation or nitrosourea therapy. Sixteen of 20 patients who had not received prior craniospinal irradiation or nitrosourea therapy were evaluable. Myelosuppression was dose limiting, with Common Toxicity Criteria (CTC) grade 4 thrombocytopenia occurring in one of six patients receiving 1000 mg m(-2) per cycle, and two of four patients treated at 1200 mg m(-2) per cycle. Therefore, the maximum-tolerated dose (MTD) was 1000 mg m(-2) per cycle. The MTD was not defined for children with prior craniospinal irradiation because of poor recruitment. Plasma pharmacokinetic analyses showed temozolomide to be rapidly absorbed and eliminated, with linear increases in peak plasma concentrations and systemic exposure with increasing dose. Responses (CR and PR) were seen in two out of five patients with high-grade astrocytomas, and one patient had stable disease. One of ten patients with diffuse intrinsic brain stem glioma achieved a long-term partial response, and a further two patients had stable disease. Therefore, the dose recommended for phase II studies in patients who have not received prior craniospinal irradiation or nitrosoureas is 1000 mg m(-2) per cycle. Further evaluation in diffuse intrinsic brain stem gliomas and other high-grade astrocytomas is warranted.

Adolescent↗

HIV risk behaviors associated with the injection process: multiperson use of drug injection equipment and paraphernalia in injection drug user networks.

This study examines drug acquisition and multiperson use of paraphernalia, drugs, and needles/syringes. Ethnographers observed 54 injection episodes in which IDUs were linked by HIV risk behaviors, and developed a typology of higher-risk, lower-risk, and nonsharing-risk networks. Multiperson use of injection paraphernalia or drug solution occurred in most injection events (94%). Serial use of syringes/needles occurred infrequently (14%) relative to "backloading" (37%) and reuse of paraphernalia (cookers 84%, cotton 77%, water 77%). Higher-risk injection networks were characterized by larger size and pooling of resources for drugs. Prevention messages must include avoiding reuse of injection paraphernalia and transfer of drug solution.

Anthropology, Cultural↗

Cisplatin pharmacokinetics in children with cancer.

Cisplatin is an important drug in the treatment of a number of paediatric cancers yet, despite widespread use, there are only very limited data on the pharmacokinetics of the drug in children. Cisplatin pharmacokinetics were studied in 21 patients following a 24 h infusion of 50-120 mg/m2 cisplatin. Total and free platinum (Pt) levels in plasma and Pt in urine, were measured by atomic absorption spectrophotometry. Pharmacokinetic parameters were determined by non-compartmental and compartmental analyses. There was 3-fold interpatient variability in free drug exposure (area under the plasma concentration versus time curve--AUC) for a given surface area-based dose of cisplatin. The mean (+/- SD) pharmacokinetic parameters for free Pt were: AUC 0.47 +/- 0.13 mg/ml.min/100 mg/m2, Vdss 12.5 +/- 2.7 l/m2, t1/2 39 +/- 9 min, Ke 0.019 +/- 0.006 min-1, Clrenal 62 ml/min/m2, Cltotal 233 +/- 455 ml/min/m2, Cpss 0.31 +/- 0.09 microgram/ml. The total free Pt clearance was 1.5-5.8-fold higher (3.4 +/- 1.0) than the glomerular filtration rate (GFR). The renal clearance of cisplatin was not related to GFR and cisplatin was subject to only limited urinary excretion (27% administered dose 0-48 h), indicating that there are other important pathways of clearance beside renal elimination. Patient and treatment heterogeneity precluded the investigation of pharmacokinetic-pharmacodynamic relationships; however, the degree of interpatient pharmacokinetic variability observed suggests that body surface area-based dosing of cisplatin in children is not satisfactory.

Adolescent↗

The influence of ifosfamide scheduling on acute nephrotoxicity in children.

Nephrotoxicity is a significant problem in children after treatment with ifosfamide. Acute changes in renal function were compared in 16 children receiving 9 g m(-2) of ifosfamide as a 72-h continuous infusion on one occasion and, on another course, divided into three 1-h infusions on consecutive days. Subclinical acute nephrotoxicity was demonstrated with both schedules, but there were no significant differences in severity.

Adolescent↗