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Biomedical subjects

C D Mitchell

Publications and source records attributed to C D Mitchell.

At least 19 recordsLinked to original sources
PubMed2006

Childhood acute lymphoblastic leukemia and infections in the first year of life: a report from the United Kingdom Childhood Cancer Study.

The United Kingdom Childhood Cancer Study was designed to examine the relation between childhood cancer and preceding exposure to infectious diseases. The authors analyzed the relation between diagnosis (1991-1996) of acute lymphoblastic leukemia (ALL) at ages 2-5 years and clinically diagnosed infections in infancy. Almost all study children (96% of both cases and controls) were taken to a general practitioner for a non-immunization-associated visit at least once before their first birthday. Children diagnosed with ALL had significantly more clinically diagnosed infectious episodes in infancy than did controls; the average number of episodes was 3.6 (95% confidence interval (CI): 3.3, 3.9) versus 3.1 (95% CI: 2.9, 3.2). This case-control difference was most apparent in the neonatal period (< or =1 month); 18% of controls and 24% of ALL cases were diagnosed with at least one infection (odds ratio = 1.4, 95% CI: 1.1, 1.9; p < 0.05). Cases who had more than one neonatal infectious episode tended to be diagnosed with ALL at a comparatively young age; the mean age at ALL diagnosis was 37.7 months for cases with two or more episodes versus 45.3 months for cases with only one episode or none (p < 0.01). These findings support the hypothesis that a dysregulated immune response to infection in the first few months of life promotes transition to overt ALL later in childhood.

Age of Onset↗
PubMed2006

Factors associated with HIV prevalence in a pre-partum cohort of Zambian women.

An ongoing study of mother-to-child human herpes virus-8 (HHV-8) transmission in Zambian women (n = 3160) allowed us to examine the association of medical injections with HIV serostatus while simultaneously accounting for other factors known to be correlated with HIV prevalence. Multi-method data collection included structured interviews, medical record abstraction, clinical examinations, and biological measures. Medically administered intramuscular or intravenous injections in the past five years (but not blood transfusions) were overwhelmingly correlated with HIV prevalence, exceeding the contribution of sexual behaviours in a multivariable logistic regression. Statistically significant associations with HIV also were found for some demographic variables, sexual behaviours, alcohol use, and sexually transmitted diseases (STD). The results confirmed that iatrogenic needle exposure, sexual behaviour, demographic factors, substance use, and STD history are all implicated in Zambian women's HIV+ status. However, the disproportionate association of medical injection history with HIV highlights the need to investigate further and prospectively the role of health-care injection in sub-Saharan Africa's HIV epidemic.

Alcohol Drinking↗
PubMed2005

Relationships between perinatal and maternal characteristics and hepatoblastoma: a report from the UKCCS.

Within the context of a national population-based case-control study--the United Kingdom Childhood Cancer Study (UKCCS)--we aimed to explore relationships between perinatal and maternal factors and childhood hepatic tumours, for participants with data available from medical records. 26/28 children with hepatic tumours (22/24 hepatoblastomas, 4/4 hepatocellular carcinomas (HCC)) and 4753 age- and sex-matched controls were included. Polyhydramnios was associated with 0.9% of control pregnancies and 13.6% of case pregnancies (Odds Ratio (OR)=28.64, 95% Confidence Interval (CI)=6.94-118.21, P<0.0001); eclampsia or severe pre-eclampsia complicated the pregnancies of 16.7% of mothers whose children developed hepatoblastoma compared with 0.5% of control pregnancies (OR=52.50, 95% CI=10.75-257.05, P<0.0001). Three children with hepatoblastoma weighed <1500 g at birth, two of whom weighed <1000 g (OR for birthweight <1500 g=69.00, 95% CI=11.98-397.17, P<0.0001). Of children with hepatoblastoma, 50% (11/22) had records of congenital anomalies, as did two of their mothers. Three mothers of children with hepatoblastoma had diagnoses of cancer--two of papillary carcinoma of the thyroid and one of acute lymphoblastic leukaemia (ALL). Paediatricians and others should be alert to the possibility of familial or genetic syndromes in children with hepatoblastomas. Potential links between maternal pre-eclampsia, low birthweight and subsequent malignancy merit further investigation. Hepatoblastoma is an extremely rare childhood tumour, but understanding the mechanism(s) underlying severe pre-eclampsia and eclampsia may also shed light on factors that contribute to the development of hepatoblastoma.

Carcinoma, Hepatocellular↗
PubMed2005

Epidemiological characteristics of human herpesvirus-8 infection in a large population of antenatal women in Zambia.

Comprehensive data describing epidemiological characteristics of the human herpesvirus-8 or Kaposi's sarcoma-associated herpesvirus (HHV-8 or KSHV) infection among pregnant women in a central sub-Saharan Africa are not available. This study determined virus prevalence estimates and the risk factors associated with HHV-8 infection. Cross-sectional, enrollment visit data were analyzed from a prospective cohort study of perinatal transmission of HHV-8 in Lusaka, Zambia. Exposure data were obtained via structured interview, physical examination, medical chart review, and laboratory testing. Among 3,160 antenatal women serologically screened for HHV-8 between September 1998 and October 2000, 40.2% were seropositive. The HHV-8 positive women were more likely to be co-infected with HIV-1 than those who were HHV-8 negative (34% vs. 26%; P < 0.0001). Of 154 variables evaluated by logistic regression analyses, only three risk factors, have emerged as independent predictors of HHV-8 positive serology: diagnosis of genital warts, HIV-1 co-infection and primary education. The association of HHV-8 infection with genital warts and HIV-1 co-infection suggests heterosexual transmission of HHV-8. HIV-1 infection may also act as a marker for particular behaviors, which could be sexual in nature, that are associated with both HIV-1 and HHV-8 transmission. Since HHV-8 facilitates development of AIDS-related Kaposi's sarcoma (KS), the results of this study could be utilized to identify specific population groups of pregnant women who are at increased risk for this disease.

Adolescent↗
PubMed2005

Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial.

Corticosteroids are an essential component of treatment for acute lymphoblastic leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in the maintenance phase of therapy. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of the central nervous system (CNS) compared with prednisolone. Substitution of dexamethasone for prednisolone in the treatment of ALL might, therefore, result in improved event-free and overall survival. Children with newly diagnosed ALL were randomly assigned to receive either dexamethasone or prednisolone in the induction, consolidation (all received dexamethasone in intensification) and continuation phases of treatment. Among 1603 eligible randomized patients, those receiving dexamethasone had half the risk of isolated CNS relapse (P = 0.0007). Event-free survival was significantly improved with dexamethasone (84.2% vs. 75.6% at 5 years; P = 0.01), with no evidence of differing effects in any subgroup of patients. The use of 6.5 mg/m(2) dexamethasone throughout treatment for ALL led to a significant decrease in the risk of relapse for all risk-groups of patients and, despite the increased toxicity, should now be regarded as part of standard therapy for childhood ALL.

Adolescent↗
PubMed2001

Lateralized cognitive deficits in children following cerebellar lesions.

The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development.

Cerebellar Neoplasms↗
PubMed2001

Incidental memory and navigation in panoramic virtual reality for electronic commerce.

Recently much effort has been dedicated to designing and implementing World Wide Web sites for virtual shopping and e-commerce. Despite this effort, relatively little empirical work has been done to determine the effectiveness with which different site designs sell products. We report three experiments in which participants were asked to search for products in various experimental e-commerce sites. Across the experiments participants were asked to search in either QTVR (QuickTime Virtual Reality), hypertext, or pictorially rich hypertext environments; they were then tested for their ability to recall the products seen and to recognize product locations. The experiments demonstrated that when using QTVR (Experiments 1, 2, and 3) or pictorial environments (Experiment 2), participants retained more information about products that were incidental to their goals. In two of the experiments it was shown that participants navigated more efficiently when using a QTVR environment. The costs and benefits of using 3D virtual environments for on-line shops are discussed. Actual or potential applications of this research include support for the development of e-commerce design guidelines.

Adult↗
PubMed2000

Effect of prenatal zidovudine on disease progression in perinatally HIV-1-infected infants.

OBJECTIVE: To determine the influence of prenatal zidovudine (ZDV) prophylaxis on the course of HIV- 1 infection in children by comparing the clinical outcome of infants born to HIV- 1-seropositive mothers who did versus those who did not receive ZDV during pregnancy. METHODS: Medical records of HIV-1-seropositive mothers and their infants were reviewed retrospectively. Participants were divided according to maternal ZDV use: no ZDV (n = 152); ZDV (n = 139). The main outcome measure was rapid disease progression (RPD) in the infant, defined as occurrence of a category C disease or AIDS-related death before 18 months of age. RESULTS: HIV vertical transmission rates were significantly different (no ZDV versus ZDV: 22.3% versus 12.2%; p = .034). Among infected infants, the RPD rate was 29.4% in the no ZDV group compared with 70.6% in the ZDV group (p = .012), and prematurity was significantly associated with a higher risk of RPD (p = .027). CONCLUSIONS: The rate of RPD was significantly higher among perinatally infected infants born to HIV-infected mothers treated with ZDV than among infected infants born to untreated mothers. The decreased proportion of infected infants with nonrapid disease progression in the former group might be related to the ability of ZDV to block intrapartum transmission preferentially and also to nonrapid disease progression resulting from intrapartum transmission.

Anti-HIV Agents↗
PubMed2000

Gram-negative bacillary bacteremia in human immunodeficiency virus type 1-infected children.

BACKGROUND: HIV-infected children are particularly susceptible to serious bacterial infections including Gram-negative bacillary bacteremia (GNB). However, the information available on GNB in these children is limited. METHODS: Retrospective review of hospital charts of HIV-infected children with GNB diagnosed between 1980 and 1997. The association between bacteremic episodes, degree of immunosuppression, HIV severity, medical treatment and clinical outcome was assessed. RESULTS: Of 680 HIV-infected children, 72 (10.6%) had 95 episodes of GNB. Statistical analyses were restricted to data from the first episode. The mean age (+/-SD) at diagnosis of GNB was 2.5 +/- 2.7 years (median, 1.6). The predominant organisms were Pseudomonas aeruginosa (26.4%), nontyphoidal Salmonella (15.3%), Escherichia coli (15.3%) and Haemophilus influenzae (12.5%). The relative frequency, per 5-year interval, of P. aeruginosa bacteremia steadily increased from 13% during 1980 through 1984 to 56% during 1995 through 1997. There were no cases of H. influenzae bacteremia after January 1, 1990. Eighty percent of GNB developed in children with AIDS and 72.2% developed in those with severe immunosuppression. Hypogamma-globulinemia and neutropenia were present in only 4.9 and 10.4% of first episodes, respectively. The overall case-fatality rate of GNB was 43.0%, and in children younger than 12 months it was 54.2%. CONCLUSIONS: A diagnosis of AIDS and/or severe immunosuppression was associated with increased risk of GNB, especially among younger children. Because of the high mortality of GNB, a broad spectrum antimicrobial therapy that effectively covers these organisms should be promptly instituted when bacteremia is suspected in HIV-infected children.

Bacteremia↗
PubMed1997

Translin recognition site sequences flank chromosome translocation breakpoints in alveolar rhabdomyosarcoma cell lines.

Alveolar rhabdomyosarcoma is characterized by a t(2;13)(q35;q14) chromosome translocation, which leads to the fusion of the PAX3 and the FKHR genes. The resulting fusion gene encodes a chimeric protein which has aberrant transcriptional activity. We report the molecular definition of the genomic breakpoints on both derivative chromosomes in one case and the derivative chromosome 13 breakpoints in two other cases. The DNA sequences adjacent to the breakpoints on the derivative chromosome 13 are remarkable for their resemblance to recognition sequences for the protein translin. Gel shift analyses confirm that these sequences bind translin. These findings suggest that translin may not only be important in the genesis of chromosomal translocations in lymphoid malignancy, but also in translocations found in solid tumours.

Base Sequence↗
PubMed1996

Interphase fluorescence in situ hybridization detection of t(2;13)(q35;q14) in alveolar rhabdomyosarcoma--a diagnostic tool in minimally invasive biopsies.

The identification of t(2;13)(q35;q14) is a useful aid in the accurate diagnosis of rhabdomyosarcoma, distinguishing it from other small round cell tumours and supporting the distinction between alveolar and embryonal forms. Cytogenetic analysis is difficult and with the increased use of minimally invasive biopsy methods and primary chemotherapy, adequate tumour material is not always available. To overcome these difficulties, two-colour interphase fluorescence in situ hybridization (FISH) to detect t(2;13)(q35;q14) was developed and its utility in assessing minimally invasive biopsies was investigated. Two cosmid clones which mapped proximal or distal to the breakpoint region 13q14 and one yeast artificial chromosome clone that mapped distal to the 2q35 breakpoint were identified. In interphase cells containing t(2;13)(q35;q14), the configuration of cosmid and yeast artificial chromosome signals demonstrated the presence of the translocation. Five cases of rhabdomyosarcoma were analysed by interphase FISH. The t(2;13)(q35;q14) was detected in all four alveolar tumours and was confirmed by cytogenetics in two cases, but was absent in one embryonal tumour. This sensitive detection method is applicable to minimal amounts of fresh or frozen tumour.

Adolescent↗
PubMed1996

Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group.

The current dosage of zidovudine for children is 180 mg/m2 every 6 h. To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m2/dose) or low-dose (90 mg/m2/dose) zidovudine (double-blind). Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance. Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months. Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter. In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m2/dose will result in substantial cost savings and should be the recommended dose.

AIDS Dementia Complex↗
PubMed1994

Conservative surgery in multimodal therapy for pelvic rhabdomyosarcoma in children.

Twenty-six previously untreated children, median age 3.4 years, with pelvic rhabdomyosarcoma (RMS) were seen between 1983 and 1988. Fourteen were girls. The planned strategy was to conserve pelvic organs, especially the bladder, by using primary chemotherapy, conservative surgery and, in most cases, radiotherapy. With a median follow-up of 71 months (range 34-103 months) overall survival was 73%, with no treatment-related death. The bladder salvage rate of 88% in survivors with bladder base/prostate primaries was much higher than that reported by the United States Intergroup Rhabdomyosarcoma Studies (IRS), though many of the preserved bladders did not function normally. We identified problems with both radiological and histological off-treatment monitoring. The overall accuracy of computerised tomographic (CT) scanning for prediction of tumour recurrence was only 81%, and endoscopic biopsies proved misleading in four of the ten bladder base/prostate patients monitored by serial cystoscopy. We conclude that a higher cure rate can be achieved by using intensive chemotherapy/radiotherapy and conservative surgery to treat children with pelvic RMS. Factors that might contribute to our favourable bladder salvage results, compared with those of the IRS, include (a) the fact that one of two specialist surgeons monitored and operated on all these patients and (b) our increasing awareness, during the study, that post-chemotherapy/radiotherapy histopathology and pelvic CT scan appearances may be misleading. Referral to paediatric centres with special experience of pelvic RMS may help raise the rate of bladder salvage in these children.

Adolescent↗
PubMed1994

Detection of pneumocystis DNA in nasopharyngeal aspirates of leukaemic infants with pneumonia.

The technique of polymerase chain reaction was used to detect Pneumocystis carinii DNA in nasopharyngeal secretions of three infants with leukaemia who had the clinical features of P carinii pneumonia. The use of this non-invasive technique allowed the early diagnosis and treatment of these infants whose protocols did not include the use of prophylactic co-trimoxazole.

DNA, Bacterial↗
PubMed1993

Chemotherapy in the management of infantile fibrosarcoma.

Infantile fibrosarcoma (IF) has traditionally been treated with surgery, which may have considerable morbidity. Chemotherapy has been suggested in order to reduce the need for extensive surgery. Nine children with histologically confirmed IF who received chemotherapy are described. Six children were treated with chemotherapy initially, two following conservative surgery, and one following recurrence after surgery. All received vincristine (V) and actinomycin D (A), and six received additional drugs including ifosfamide (I), cyclophosphamide (C), adriamycin (Ad), etoposide (E), and cisplatinum (CDDP). Objective responses were achieved in eight: three responded completely (CR), two responded partially (PR), which allowed conservative surgery, one had stable disease, one had an initial PR, but subsequently had tumour recurrence 1 month after cessation of treatment, necessitating further surgery and chemotherapy, and one had an initial PR but died following local and regional metastases. One child had no response to chemotherapy but is alive with stable residual disease. Thus, five of nine children achieved a CR--three with chemotherapy alone. With the inclusion of chemotherapy as part of their treatment, five children, for whom curative surgery may have resulted in amputation, remain alive with limbs intact. Chemotherapy including V and A should be given to infants with fibrosarcoma in whom curative surgery would be mutilating.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Insulin-like growth factor (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) in the plasma of children with Wilms' tumour.

Insulin-like growth factors (IGF)-I, -II and IGF binding protein-2 (IGFBP-2) have been measured in plasma of children with Wilms' tumour. The mean levels for total serum IGF-I and -II were not significantly altered in Wilms' tumour as compared with normal control plasma. However, the chromatographic profiles for IGF-I and -II in these groups were different with regard to the presence of IGF binding proteins and high molecular weight forms of IGFs; the high molecular weight form (9-15 kD) of IGF-II was significantly reduced in Wilms' tumour. Levels of IGFBP-2 were substantially elevated in serum from Wilms' tumour patients (1025 +/- 112 ng/ml compared with 416 +/- 44 ng/ml in controls), and inversely correlated with the levels of high molecular weight forms of IGF-II. We suggest that IGFBP-2 measurements might be of value as a marker for monitoring this type of tumour, either as an adjunct to diagnosis or surveillance of tumour growth during therapy.

Biomarkers, Tumor↗
PubMed1993

Diagnosis of Toxoplasma parasitemia in patients with AIDS by gene detection after amplification with polymerase chain reaction.

We sought evidence of toxoplasma parasitemia among 37 people with active or dormant Toxoplasma gondii infection or no evidence of infection. DNA was extracted from erythrocyte-free portions of blood samples, and the T. gondii B1 gene was amplified by the polymerase chain reaction. Evidence of T. gondii parasitemia was found in six patients with severe immunosuppression from AIDS and clinical evidence suggestive of or compatible with toxoplasmosis. Results were negative for patients unlikely to have active toxoplasmosis. Gene detection after amplification with the polymerase chain reaction is a promising test for detection of parasitemia, and parasitemia should be tested for in patients with AIDS and unexplained fever or central nervous system abnormalities.

AIDS-Related Opportunistic Infections↗