Search PubMed⌕ Search

Biomedical subjects

L Price

Publications and source records attributed to L Price.

At least 37 records · Page 2Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

Platinum-DNA adduct formation in leucocytes of children in relation to pharmacokinetics after cisplatin and carboplatin therapy.

Platinum (Pt)-DNA adducts were measured in peripheral blood leucocytes (PBLs) from 24 children with solid tumours after standard cisplatin and/or carboplatin treatment. The relationship between Pt-DNA adduct levels and pharmacokinetics of cisplatin and carboplatin was investigated. Adduct measurements were performed by competitive enzyme-linked immunosorbent assay (ELISA) and plasma unbound Pt concentrations were measured by atomic absorption spectrophotometry (AAS). There was considerable interindividual variation in Pt-DNA adduct level that was weakly correlated (r2 = 0.32) with the area under the unbound drug concentration vs time curve (AUC) at 6 h after the start of cisplatin infusion, indicating that the variation in Pt-DNA adduct levels was primarily determined by factors other than AUC. No clear relationship between AUC and adduct levels was seen at 24 and 48 h after cisplatin or at 6, 24 or 48 h after carboplatin. Carboplatin produced lower levels of immunoreactive adducts than did cisplatin (1.3 +/- 0.6 nmol Pt g-1 DNA vs 3.2 +/- 1.7 nmol Pt g-1 DNA), despite a 20-fold higher unbound drug AUC for carboplatin (8.0 +/- 3.5 mg ml-1 min vs 0.4 +/- 0.2 mg ml-1 min). This study demonstrates that, after cisplatin and carboplatin treatment the drug-target interaction is determined by both pharmacokinetic and, predominantly, cellular factors. Intrinsic differences between the two complexes, primarily reactivity, probably explain the lower adduct levels observed after carboplatin treatment.

Adolescent↗
PubMed1997

Conservative management of small adenomata in ulcerative colitis.

OBJECTIVE AND METHODS: Patients with chronic ulcerative colitis may develop colitis-related dysplasia and/or sporadic adenomata. Differentiating between these two processes is important because they may dictate different therapeutic approaches. Although distinguishing features of sporadic adenomata versus colitis-related dysplasia have been suggested previously on an a priori basis, they have never been verified by follow-up analysis. We have identified six chronic ulcerative colitis patients whose discrete adenomata were managed conservatively, with subsequent continuation in their surveillance programs. RESULTS: Mean patient age was 69 yr with a mean 21.3 yr of ulcerative colitis. Surveillance endoscopy of 63 patient-yr duration yielded 24 adenomata. A mean follow-up after the initial adenoma diagnosis was 7.2 yr with no carcinoma identified (including the examination of one prophylactic colectomy specimen). One patient, with a 34-yr history of ulcerative colitis and a single sporadic adenoma subsequently developed dysplasia of flat mucosa 14 months later. CONCLUSIONS: Our findings concur with previous reports and indicate that small, discrete adenomata with morphology identical to those seen in the general population occur in patients with ulcerative colitis. Such lesions in patients older than 45 yr, with tubular or tubulovillous architecture and low-grade dysplasia, are effectively treated by polypectomy only and are not necessarily an indication for colectomy. However, sporadic adenomata and colitis-related dysplasia can develop metachronously. It is suggested that subsequent to a diagnosis of sporadic adenoma in a patient with chronic ulcerative colitis, surveillance should increase to colonoscopic examination every 6 to 12 months.

Adenoma↗
PubMed1997

Cyclophosphamide and ifosfamide metabolites in the cerebrospinal fluid of children.

Although both cyclophosphamide (CP) and ifosfamide (IF) are used in the treatment of central nervous system tumors, little is known about the concentration of either drug or their metabolites in the cerebrospinal fluid (CSF) of children. The concentrations of the parent oxazaphosphorine and its principal metabolites were measured simultaneously in the plasma and CSF of 25 children. Twenty-one patients received CP for the treatment of either acute lymphoblastic leukemia, non-Hodgkin's lymphoma, or medulloblastoma, and 4 children received IF for the treatment of rhabdomyosarcoma. A high degree of interpatient variation was seen in terms of the CSF concentration of CP and the CSF:plasma ratio. The CSF:plasma ratio was greater for IF than for CP (P < 0.001). In contrast to IF, where the majority of metabolites was measured in the CSF, no child receiving CP had detectable metabolites. Children receiving dexamethasone had lower concentrations of CP in the CSF (P = 0.04). The CSF:plasma ratio for isophosphoramide mustard was greater than that for either parent drug or any other metabolite. These results demonstrate that IF enters the CSF to a greater extent than CP in children. The ability of both IF and CP and their metabolites to cross the blood-brain barrier may be reduced by dexamethasone.

Adolescent↗
PubMed1996

Risk factors for ifosfamide nephrotoxicity in children.

BACKGROUND: Risk factors for long-term nephrotoxicity after ifosfamide for childhood cancers are not fully known. We have studied patient-related and treatment-related risk factors for chronic ifosfamide nephrotoxicity. METHODS: A group of 23 children who had received ifosfamide at age 2.1-16.2 years (median 6.9) for various cancers were assessed for nephrotoxicity, at 1-28 (2) months after the end of treatment, by renal function testing, laboratory values, and a grading score (none, mild, moderate, severe). No patient had received cisplatin or undergone nephrectomy. 13 children were reassessed at 10-26 (23) months; eight had died and two were not evaluable. The median total ifosfamide dose was 100.8 (9.0-160.4) g/m2 over a median of 15 courses every 3 weeks as a 48-72 h continuous intravenous infusion (in 22 cases), with mesna and hydration. FINDINGS: Glomerular filtration rate was below normal in ten (45%) of 22 evaluable children; their rate was 61-85 mL/min per 1.73 m2. Proximal tubular toxicity led to hypophosphataemic rickets and/or renal tubular acidosis in six children, and distal tubular toxicity caused nephrogenic diabetes insipidus in one. Of the risk factors analysed by multiple regression, only total ifosfamide dose was associated with proximal tubular toxicity. Only two of ten evaluable patients who received under 100 g/m2 developed moderate nephrotoxicity, whereas six of ten who received over this dose had moderate or severe nephrotoxicity. INTERPRETATION: High total ifosfamide dose was the only risk factor we identified. Although inter-patient variability was high, cumulative doses of 100 g/m2 or higher should be avoided in children with cancer.

Adolescent↗
PubMed1996

Mutagenesis studies of interleukin-8. Identification of a second epitope involved in receptor binding.

Interleukin-8 (IL-8) is a dimeric, C-X-C chemokine, produced by a variety of cells and which elicits proinflammatory responses from the neutrophil. As a prelude to drug design, we have investigated the interactions between IL-8 and its receptor by preparing a number of single-site mutants of IL-8 and determining their activity in receptor-binding and functional assays. In order to define the binding surface as precisely as possible, we have used chemical shifts obtained from nuclear magnetic resonance spectroscopy to screen mutant proteins for structural changes which affect regions of the IL-8 surface remote from the site of mutation. In addition to a previously recognized sequence, Glu4-Leu5-Arg6 in the N-terminal peptide, we have identified a second epitope comprising a contiguous group of non-sequential, solvent-exposed, hydrophobic residues, Phe17, Phe2l, Ile22, and Leu43. These two receptor-binding regions are separated by over 20 A in the IL-8 structure and are important both for receptor binding and function. In addition, we have shown through the production of a covalently linked IL-8 dimer, that subunit dissociation is not necessary for biological activity.

Amino Acid Sequence↗