A comparison of organic laying hen feed formulations.
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Amino Acids↗
Biomedical subjects
S Pritchard
Publications and source records attributed to S Pritchard.
Interethnic variability in human drug responses.
The scientific study of interethnic differences in responses to drugs has been extant for 80 years. Many of these differences have been described at the phenotypic level, and some have been explained by genetic factors. However, it is frequently difficult to disentangle accurately the hereditary and environmental influences in phenotypic comparisons. This is where the recent developments in knowledge of the genes responsible for drug receptors are starting to make a big impact. The beta 2 adrenoceptor is described; it has three genetic polymorphisms. The different genotypes influence responses to agonists such as albuterol (Salbutamol). New gene frequency data including those for Saudi Arabians, Indians, and Africans are shown. The expanding body of knowledge about genetic (and interethnic) variability in drug receptors is likely to be important in clinical medicine.
Ethnicity↗
NHS library and information services in Wales.
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Cooperative Behavior↗
Differences in dose scheduling as a factor in the etiology of anthracycline-induced cardiotoxicity in Ewing sarcoma patients.
Clinical observation suggested a high prevalence of cardiac morbidity and mortality in children with Ewing sarcoma (ES) treated at B.C.'s Children's Hospital. We therefore compared 30 patients treated for Ewing sarcoma between 1978 and 1991 with 26 soft tissue sarcoma (STS) patients treated with similar chemotherapy over the same period of time. All patients were evaluated for cardiac function using echocardiography. Shortening fraction (SF) and left ventricular mass index (Massl) were compared before and after treatment. The role of chest irradiation, dose concentration (DC) of adriamycin (AD), total mean doses of AD, cyclophosphamide (CY) and actinomycin (AC) were analysed. SF for patients with ES and STS postchemotherapy was significantly lower (P < .001 and P = 0.0004, respectively) than pretreatment values. Postchemotherapy SF for ES was lower than STS (P = 0.0097). Massl for each group did not change significantly. Six of the ES patients had postchemotherapy SF of < 0.20, with three in congestive failure, two cardiac deaths and one heart transplant. One additional ES patient had sick sinus syndrome and needed a pacemaker. Among the STS patients only one had SF < .20 and none were symptomatic. There were no significant differences in the mean AD, CY and AC doses for ES versus STS. The difference in the DC of AD for ES (mean 744) compared to STS (mean = 362) was significant (P = < 0.001). Regression analysis indicated a trend for decreasing SF with increasing DC (P = 0.017). Chest irradiation did not appear to increase the likelihood of cardiotoxicity. ES patients had a higher prevalence of cardiac dysfunction compared to STS. Studies are required to evaluate the importance of the components of DC, i.e., size of the individual dose and frequency of administration of AD, and to look at other possible factors in the causation of cardiomyopathy in ES.
Anthracyclines↗
Cytogenetic and molecular genetic analysis of a pediatric pleomorphic sarcoma reveals similarities to adult malignant fibrous histiocytoma.
Cytogenetic and molecular genetic studies were performed on a pleomorphic sarcoma removed from the left atrium of a 15-year-old girl. Histologic analysis was consistent with a storiform-pleomorphic malignant fibrous histiocytoma (MFH). Although MFH is the most common soft-tissue sarcoma of late adulthood. It is extremely rare in childhood and its existence in the pediatric population remains controversial. Cytogenetic analysis revealed several alterations previously associated with adult MFH, including abnormalities of chromosomal bands 11p11 and 19p13. Moreover, the tumor demonstrated homogeneously staining regions (HSR) and double minute chromosomes (dmin) suggestive of gene amplification. We therefore screened the case for amplification of genes localized to chromosomal bands 12q13-14, including the putative protooncogenes MDM2, CDK4, SAS, CHOP, and CLI, which are frequently amplified and overexpressed in adult MFH. Southern and Northern blot analysis confirmed the coamplification of MDM2, CDK4, SAS, and CHOP. To our knowledge, such coamplification studies of the 12q13-14 amplicon have not been previously detected in pediatric MFH. Our results provide cytogenetic and molecular genetic evidence that pediatric and adult MFH are histogenetically related entities.
Adolescent↗
Cytochrome P450 CYP3A5 in the human anterior pituitary gland.
The cytochromes P450 are a key group of enzymes involved in the metabolism of xenobiotics and several biologically active endogenous compounds. The expression of CYP3A5 has been identified by reverse transcriptase-polymerase chain reaction in human pituitary gland and shown by immunohistochemistry to be localized to growth hormone containing cells of the anterior pituitary gland. This is the first direct identification of an individual P450 subfamily in the pituitary gland and the presence of CYP3A in the pituitary gland may play a role in regulating growth hormone secretion.
Aged↗
Obstructive lung disease in children after allogeneic bone marrow transplantation.
Obstructive lung disease (OLD) has been described as a significant complication after allogeneic bone marrow transplantation (BMT). The incidence of OLD in adults appears to be low (approximately 3%), but there is little data for children. We analyzed 89 consecutive pediatric allogeneic BMTs, > or = 1.5 years post-BMT, performed at British Columbia's Children's Hospital from 1980 to 1992 for evidence of OLD. Diagnosis of OLD was based on clinical findings (nonproductive cough, wheezing, and dyspnea with no evidence of infection), pulmonary function tests (FEV1 < 80% and FEF25-75% < 60% predicted), lung biopsy, and computed tomography scan. Sixty-seven of the 89 children evaluated survived > or = 90 days and were classified as at risk for OLD. Thirteen of 67 (19.4%), developed OLD, 3 of which were transient. The development of OLD was strongly associated with the following high-risk groups: chronic graft-versus-host disease (GVHD) (37.1% OLD), increased donor age, acute GVHD, and either mismatched related or matched unrelated donor transplants. No correlation was found with methotrexate prophylaxis for GVHD, total body irradiation, or cytomegalovirus reactivity in either donor or recipient and the development of OLD. Further analysis of only children with chronic GVHD showed that liver involvement by GVHD before the onset of OLD (57.9%) was the only other significant predictive factor. We observed an overall increased prevalence of OLD in children compared with that previously reported in adults. Further studies are required to confirm whether age is a risk factor for development of OLD after allogeneic BMT.
Acute Disease↗
Intensive conditioning regimen for bone marrow transplantation in children with high-risk haematological malignancies.
Between September 1987 and May 1991, 21 children aged 10 months to 15 years (median 9 years) underwent bone marrow transplantation (BMT) for advanced haematological malignancies using a conditioning regimen consisting of total body irradiation (TBI), etoposide 1.8 g/m2 by continuous infusion, and cyclophosphamide 2 g/m2 on 3 consecutive days. The patients included 14 with acute lymphoblastic leukaemia (ALL), 1 with chronic myeloid leukaemia (CML), 1 with juvenile CML, 4 with non-Hodgkin's lymphoma and 1 with acute nonlymphocytic leukaemia. Eleven had an allogeneic BMT from an HLA-matched sibling, and 1 from an unrelated donor. Nine patients received 4-hydroperoxycyclophosphamide purged autologous marrow. Median time to myeloid engraftment (ANC > 500/microliters) was 19 days in allogeneic BMT patients and 28 days in autologous BMT patients (P < .01). Mucositis was the major regimen-related toxicity (RRT). GI toxicity in the form of diarrhoea affected ten patients and five had veno-occlusive disease of the liver. Two patients had mild bladder toxicity and one died of renal toxicity. There was no CNS or cardiac toxicity. There was no significant difference in the incidence of toxicity according to the type of BMT (autologous or allogeneic), total dose, or sequence of TBI. With a median follow-up of 44 months, ten patients are alive (6/12 allogeneic BMT patients and 4/9 autologous BMT patients). Of the 11 deaths, four were related to toxicity (2 aspergillus, 1 haemorrhage following liver biopsy, and 1 from haemolytic-uraemic syndrome), and 4/12 allogeneic and 4/9 autologous BMT patients died from relapsed disease. This conditioning regimen is well tolerated in children, demonstrating mild and reversible RRT.
Adolescent↗
Thalidomide in the management of chronic graft-versus-host disease in children following bone marrow transplantation.
Chronic graft-versus-host disease (GVHD) is the major complication in patients surviving > 100 days post-allogeneic bone marrow transplantation and occurs in 30% of pediatric patients. It is most prevalent 1-2 years post-transplant. Treatment involves corticosteroids and other immunosuppressive therapy which may affect growth and increase the likelihood of infectious complications. We report five children with severe corticosteroid-dependent chronic GVHD treated with thalidomide 12-25 mg/kg/day. Response to therapy was based on resolution of symptoms of chronic GVHD and withdrawal of other immunosuppressive therapy. All the children showed clinical response to thalidomide with cessation or diminution in other immunosuppressive medication. Side-effects were minimal and no patient developed peripheral neuropathy. All patients are alive 48-65 months post-transplantation. Thalidomide is a safe and effective drug for the treatment of chronic GVHD in children and may avoid the use of long-term corticosteroid therapy.
Adolescent↗
Early prediction of anthracycline cardiomyopathy using standard M-mode and digitized echocardiography.
In this study, we attempted to identify echocardiographic findings that can be used as early predictors of left ventricular dysfunction due to anthracyclines in 26 pediatric oncology patients. Retrospective review identified six patients (group 1 mean anthracycline dose = 337 +/- 123 mg/m2) who developed clinical evidence of cardiomyopathy and 20 consecutive patients followed prospectively (group 2 mean anthracycline dose = 298 +/- 102 mg/m2) who did not. All of the patients had serial m-mode echocardiography before and at approximately every 50 mg/m2 of anthracycline treatment depending on the dosage schedule. The following measurements were recorded: left ventricular dimensions and wall thickness, indices of left ventricular function, including systolic time intervals, shortening fraction, and ejection fraction. Using digitized echocardiography, the following parameters were recorded: peak and normalized systolic and diastolic velocities of the left ventricular chamber, posterior and septal wall velocities, and percent of posterior wall thickening. Variations from established normal longitudinal bounds and actual changes from pre-anthracycline values were compared for the two groups throughout the course of therapy. At 70 mg/m2 of anthracycline, group 1 showed significant deterioration in shortening fraction (mean change = 8.8 versus 2.5, p = .03), left ventricular velocity in diastole (2.9 versus 0.21, p = .04), left ventricular normalized velocity in systole (.65 versus 0.03, p = .02), and left ventricular normalized velocity in diastole (1.15 versus 0.002, p = .04) compared to group 2. These values were mostly compensated by 125 mg/m2, but they slowly deteriorated again at higher doses of anthracycline, leading to the appearance of clinical evidence of cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Singleness: a very viable option.
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Christianity↗
Safety of children in temporary accommodation.
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Accident Prevention↗
Growth and development following marrow transplantation for leukemia.
One hundred forty-two patients between the ages of 1 and 17 years who survived disease-free more than 1 year after marrow transplantation for hematologic malignancy had growth and development evaluations from one to 14 years posttransplant (median 4 years). Prior to transplant all children received multiagent chemotherapy and 55 also received central nervous system irradiation, but none had growth and development evaluations. Marrow transplant preparation included high-dose chemotherapy and total body irradiation (TBI) given as a single dose of 9.2 to 10.0 Gy (79 patients) or as fractionated doses of 2.0 to 2.25 Gy/d for six to seven days (63 patients). After transplant abnormal thyroid function was present in 39%. Stimulated 11-desoxycortisol levels were subnormal in 24% of patients evaluated. Growth hormone (GH) deficiency was present in 17 of 25 children who received previous cranial irradiation. Partial GH deficiency was present in 4 of 25 who received previous cranial irradiation and in 6 of 18 who had not received cranial irradiation. Height velocity was decreased in all patients. After transplant, height was significantly influenced by chronic graft-v-host disease and single-dose TBI. Sixty-eight percent had delayed development of secondary sexual characteristics. Gonadal failure occurred in nearly all who were postpubertal at transplant. While it is not possible to determine how many of these endocrine abnormalities occurred as a result of treatment administered prior to transplantation, these data do demonstrate that children who become long-term survivors after marrow transplantation for hematologic malignancy have endocrine abnormalities that adversely affect growth and development.
Adrenal Cortex↗
Reproduction of complex two-dimensional movements as a function of mode of presentation.
The experiment reported here examined the kinaesthetic reproduction of two-dimensional patterns from three different modes of presentation: kinaesthetic only, visual only and visual plus kinaesthetic. The patterns were open and consisted of three linear segments of different lengths. All reproductions tended to underestimate pattern size. Subjects who had received visual experience of the pattern with or without simultaneous kinaesthetic experience produced significantly greater underestimates than subjects who had not seen the patterns. This is discussed in terms of the dominance of vision over kinaesthesis, and differences in size perception in the two modalities. Least distortion of the pattern shape was found in the reproduction of subjects who had received both kinaesthetic and visual experience of the criterion.
Female↗
A simple technique for studying immunoglobulin synthesis by normal and malignant plasma cells in vitro.
Plasma cells from human marrows are saturated with C-14 labelled amino acids, harvested and recultured in unlabelled growth medium. The appearance of radioactivity in the growth medium then provides a simple and rapid measure of protein synthesis. The secreted radio-labelled material is characterized by isoelectric focusing and autoradiography in acrylamide gels, a technique which has advantages over established serological methods.
Autoradiography↗
Genesis of severe placental abruption.
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Abdominal Injuries↗
Intrathecal vincristine: an analysis of reasons for recurrent fatal chemotherapeutic error with recommendations for prevention.
PURPOSE: Accidental intrathecal vincristine instillation is usually a fatal error. The authors report an analysis of a patient and suggest means with which to reduce such errors. PATIENTS AND METHODS: A 7-year-old girl with recurrent acute lymphoblastic leukemia was inadvertently injected intrathecally with 1.5 mg vincristine. A detailed analysis of the events leading to this error and a review of all reported cases in the English literature were undertaken. RESULTS: Reasons for errors reported by us and other institutions included mistaking vincristine for an intended intrathecal drug, assuming vincristine was an additional drug to be injected, not checking physician orders, mistaken route of administration, and mislabeling of syringes. CONCLUSION: Intrathecal injection of vincristine may be the end-result of a series of systems errors. Protocol recommendations to reduce the likelihood of this error are presented.
Antineoplastic Agents, Phytogenic↗
Safety, tolerability, antiemetic efficacy, and pharmacokinetics of oral dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.
PURPOSE: The safety, antiemetic efficacy, and pharmacokinetics of single oral doses of dolasetron, a new highly selective 5-HT3 receptor antagonist, were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy. PATIENTS AND METHODS: A total of 32 children, ages 3 to 18 years, were enrolled in a nonrandomized, multicenter, open-label, dose-escalation study. Three oral dose levels (0.6, 1.2, or 1.8 mg/kg) were studied. Safety, efficacy, and pharmacokinetic parameters were assessed over 24 hours at each dosage level. RESULTS: The most effective dose was 1.8 mg/kg; 60% of the patients achieved a complete or major response (< or =2 emetic episodes in 24 hours). A complete response was achieved in 3 of 9 patients (33%) who received 0.6 mg/kg, 4 of 13 (31%) patients who received 1.2 mg/kg, and 5 of 10 (50%) patients who received 1.8 mg/kg of dolasetron. Overall, dolasetron was well tolerated. Adverse events were mild and similar to those reported in adults. Peak plasma concentrations (Cmax) of dolasetron's active reduced metabolite, MDL 74,156, were dose proportional and occurred, on the average, within 1 hour of oral administration. The half-life (t1/2) in plasma was approximately 6 hours for all dose levels, and the mean clearance (CLapp) was unrelated to dose. CONCLUSIONS: Oral dolasetron is safe and effective in reducing chemotherapy-induced nausea and vomiting, particularly at the 1.8-mg/kg dose level. These results support further evaluation of oral dolasetron in larger randomized clinical trials in the pediatric cancer population.
Administration, Oral↗