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Biomedical subjects

M Gerrard

Publications and source records attributed to M Gerrard.

At least 19 recordsLinked to original sources

Acute neurotoxicity in children with advanced stage B-non-Hodgkin's lymphoma and B-acute lymphoblastic leukaemia treated with the United Kingdom children cancer study group 9002/9003 protocols.

We reviewed the pattern of acute neurotoxicity in children with B-non-Hodgkin's lymphoma (B-NHL) and B-acute lymphoblastic leukaemia (ALL) treated with the UKCCSG 9002/9003 protocols. Among 175 patients, 21 (12%) developed acute neurotoxicity: 9002 protocol (n=11/112) and 9003 (n=10/63). There were 20 boys and the median age was 10 years. Patients with neurological symptoms due to other causes were excluded. Acute neurological symptoms developed following induction chemotherapy in 7 patients, or after a more intensive course of chemotherapy containing high-dose methotrexate (n=14). Nine patients required their chemotherapy to be altered because of the acute neurotoxicity. One patient died of cerebral haemorrhage but none of the remaining six deaths was attributed to acute neurotoxicity. We conclude that acute neurotoxicity is common in children treated with the 9002/9003 protocols and tends to be transient. Intrathecal and systemic chemotherapy including high-dose methotrexate is probably the most common predisposing factor. Modification of subsequent chemotherapy is not invariably necessary.

Acute Disease↗

Use of basiliximab in pediatric liver transplantation for Langerhans cell histiocytosis.

This report describes a 16-month-old girl with multi-system Langerhans cell histiocytosis (LCH), who developed end-stage liver disease despite intensive chemotherapy. She underwent a liver transplant at 28 months of age while receiving maintenance chemotherapy for bony lesions. In view of previous reports of a high incidence of acute cellular rejection and post-transplant lymphoproliferative disease (PTLD) in children transplanted for LCH, basiliximab was added to the post-transplant immunosuppression regime of tacrolimus and prednisolone. Sixteen months post-transplant, she has had no episodes of acute rejection or PTLD and her LCH has remained in remission. Current literature regarding liver transplantation (LTx) for LCH and the use of basiliximab in pediatric LTx is reviewed.

Antibodies, Monoclonal↗

Congenital alveolar rhabdomyosarcoma: clinical and molecular distinction from alveolar rhabdomyosarcoma in older children.

BACKGROUND: Congenital alveolar rhabdomyosarcoma (RMS) is extremely rare and invariably fatal with current therapy. Its clinical presentation is unusual and is distinct from RMS in older children, with > 50% of patients presenting with multiple cutaneous metastases. To the authors' knowledge, the biology of this condition has not been studied to date. METHODS: The clinical and pathologic findings of four cases of congenital RMS are presented along with those of other cases found in the literature. Molecular analysis was undertaken to detect the characteristic chromosomal translocations of alveolar RMS in three cases with suitable material. RESULTS: To the authors' knowledge, there are no recorded survivors of congenital alveolar RMS. Clinical and histopathologic findings in four patients with congenital alveolar RMS are detailed along with treatment responses. It now is recognized that tumor specific translocations can be detected in the majority of cases of alveolar RMS using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. However, detailed molecular analysis using RT-PCR was unable to detect the presence of either the classic t(2;13) or variant t(1;13) translocation in three cases analyzed at the molecular level. CONCLUSIONS: To the authors' knowledge the optimal treatment for this rare tumor is not known. The longest survivor in the current series underwent myeloablative therapy with peripheral stem cell support, suggesting that more intensive treatment may be of value in this rare condition. None of the three tumors analyzed by RT-PCR harbored characteristic RMS translocations. The molecular biology of this highly malignant and aggressive congenital tumor appears to be different from alveolar RMS in older children and warrants further investigation.

Female↗

Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia and B-cell non-Hodgkin's lymphoma treated with the UKCCSG 9003/9002 protocols.

Twenty-six children with B-cell acute lymphoblastic leukaemia (B-ALL) or Murphy Stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) progressed or relapsed after first-line therapy with a short, intensive multiagent chemotherapy regimen [United Kingdom Childhood Cancer Study Group (UKCCSG) 9003] (n = 62) or a slightly less intensive regimen (UKCCSG 9002) (n = 112). Eight patients (4.6%) never achieved complete remission (CR) and 18 (10.3%) relapsed. Second-line therapy resulted in remission for eight patients (30%). All patients initially treated with the 9003 protocol died. Three patients (11.5%) in the 9002 group, including one who never achieved CR in the primary site, are alive after second-line therapy. This study confirms that the prognosis of relapsed or refractory B-ALL/B-NHL is poor and exceptionally so if relapse occurred less than 6 months from diagnosis. High-dose therapy with stem cell rescue was used in only seven patients; its role needs to be studied further.

Antineoplastic Combined Chemotherapy Protocols↗

Colorectal carcinoma in children and adolescents--a report of seven cases.

Between 1981 and 1997 seven children and adolescents (5 boys and 2 girls) were treated for colorectal carcinomas in two paediatric centres. The case notes of the patients were studied to determine the presentation, clinical findings, prognosis and the differences of colorectal carcinomas in the young patients compared to adults. Carcinoma of the colon and rectum is uncommon in this age group and has a poor prognosis. The age range was 9 - 15 years, mean age 11.8 years. All segments of the large bowel were represented as sites of the primary tumour. Vague abdominal pain, vomiting and weight loss were the commonest presenting symptoms. The duration of symptoms varied from one month to twelve months (median: four months). Contrast enema was the most useful diagnostic investigation. Five patients had Dukes' stage C and two had Dukes' stage D tumour. Mucin-secreting adenocarcinoma was the commonest histological diagnosis. Five patients had complete resection, two had palliative procedures. Post-operative chemotherapy was given to six patients and two had post-operative radiotherapy.

Adenocarcinoma↗

Mature B-cell lymphoma/leukemia in children and adolescents: intergroup pathologist consensus with the revised European-American Lymphoma Classification.

BACKGROUND: The Revised European-American Lymphoma (R.E.A.L.) Classification criteria were evaluated in the international protocol FAB LMB 96 Treatment of Mature B-cell Lymphoma/Leukemia: A SFOP LMB 96/CCG-5961/UKCCSG NHL 9600 Cooperative Study. This includes B-lineage lymphomas: Burkitt's lymphoma (including ALL-L3); high-grade B-cell lymphoma, Burkitt-like; diffuse large B-cell lymphoma (excluding anaplastic large cell Ki-1 lymphoma). PATIENTS AND METHODS: Cases were independently reviewed by eight hematopathologists from the three cooperative national groups (two SFOP, two CCG, four UKCCSG), without prior discussion of classification criteria or guidelines for case rejection. Consensus diagnosis was determined by each national cooperative group, and final consensus diagnosis established when at least two national consensus diagnoses were in agreement, or following group agreement at a multiheaded microscope. RESULTS: Two hundred eight cases were reviewed, with final consensus diagnosis established in two hundred three. The percent agreement of each group's national consensus diagnosis with final consensus diagnosis was 86%, 86% and 71%. The percent agreement of the group's national consensus diagnosis with final consensus diagnosis for Burkitt's and diffuse large B-cell lymphoma were 88% and 80%, respectively, but only 42% for Burkitt-like lymphoma. CONCLUSIONS: International panel review of mature B-cell lymphoma/leukemia in children and adolescents highlighted difficulties in subclassification, particularly with Burkitt-like, which is a 'provisional entity' in the R.E.A.L. Classification. The absence of previous discussion of classification and guidelines for case rejection may in part explain the discrepancy between pathologists. These results underline that morphology may need to be complemented by other studies, such as molecular genetic and cytogenetics, to discriminate between the mature B-cell lymphomas.

Adolescent↗

Protection and vulnerability processes relevant for early onset of substance use: a test among African American children.

This research tested predictions from a self-regulation model of factors relevant for early onset of tobacco and alcohol use with a community sample of 889 African American children (mean age = 10.5 years). Criterion variables were peer substance use, willingness to use substances, and resistance efficacy (intention to refuse substance offers). Structural modeling indicated effects of temperament dimensions were mediated through self-control and risk-taking constructs, which were related to school involvement, life events, and perceived vulnerability to harmful effects of substances. Peer use was predicted by life events, poor self-control, and parent-child conflict; willingness was predicted by life events, risk taking, and (inversely) parental support; and resistance efficacy was predicted by perceived vulnerability and (inversely) poor self-control. Findings are discussed with reference to theoretical models of early protection and vulnerability processes.

Black or African American↗

Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol.

From July 1990 to March 1996, 112 children with stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) with up to 70% FAB L3-type blasts (n = 42) in the bone marrow without central nervous system (CNS) disease were treated on the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol (identical to the French LMB 84). The median age was 8.3 years. There were 81 boys and 31 girls. According to the extent of the primary disease, patients were sub-staged into three groups: IIIA with unresectable abdominal tumour (n = 39); IIIB with abdominal multiorgan involvement (n = 57) and IIIX with extra-abdominal primary lymphoma often presenting as pleural effusion (n = 16). Univariate and multivariate analyses were carried out to evaluate the prognostic significance of lactate dehydrogenase (LDH) level at diagnosis, the sub-stage and the time to achieve complete remission (CR). With a median follow up of 48 months (range 12-92), the overall and event free survival (EFS) is 87% (95% confidence interval (CI) 79.2-92.1 %) and 83.7% (95% CI 76.3-89.2%) respectively. Six patients (5.4%) never achieved CR, of whom one is alive following high-dose therapy. Eight patients (7.1%) relapsed after achieving CR, three are alive after second-line therapy. There were three early toxic deaths (2.7%), mainly from infection, and one late death from a second cancer. There was no significant difference in EFS according to LDH level at diagnosis, the sub-stage or the time to CR. This study confirms the overall good prognosis and low rate of toxic deaths in patients with advanced B-NHL treated with this intensive regimen. No significant difference in EFS according to the sub-stage, the time to achieve CR or LDH level at diagnosis making it difficult to identify a group that should not receive intensive therapy.

Adolescent↗

Self-esteem, self-serving cognitions, and health risk behavior.

The current article reviews prospective and experimental research on the relation between self-esteem and perceptions of vulnerability. These studies demonstrate that individuals with high self-esteem who engage in risk behavior often utilize a variety of self-serving cognitive strategies that protect them from fully acknowledging their vulnerability to the potential negative consequences of their behavior; e.g., they minimize their estimates of personal risk and overestimate the prevalence of the risk behavior among their peers. The article also provides data on an additional self-serving cognitive strategy employed by adolescents with high self-esteem--alteration of perceptions of others' reactions to their own risk behavior. Finally, the article reviews the emerging literature on the relation between these cognitive strategies and maladaptive health behavior, and proposes that whether these strategies are maladaptive depends on the nature of the threat and the availability of opportunities to engage in compensatory self-enhancement.

Adolescent↗

Laboratory-supported influenza surveillance in Victorian sentinel general practices.

Laboratory-supported influenza surveillance is important as part of pandemic preparedness, for identifying and isolating candidate vaccine strains, for supporting trials of anti-influenza drugs and for refining the influenza surveillance case definition in practice. This study describes the implementation of laboratory-supported influenza surveillance in Victorian sentinel general practices and provides an estimate of the proportion of patients with an influenza-like illness proven to have influenza. During 1998 and 1999, 25 sentinel general practices contributed clinical surveillance data and 16 metropolitan practices participated in laboratory surveillance. Serological, virus-antigen detection, virus culture and multiplex polymerase chain reaction procedures were used to establish the diagnosis of influenza. Two laboratories at major teaching hospitals in Melbourne provided additional data on influenza virus identification. General practice sentinel surveillance and laboratory identification of influenza provided similar data on the pattern of influenza in the community between May and September. The clinical suspicion of influenza was confirmed in 49 to 54 per cent of cases seen in general practice.

Adolescent↗

The effect of risk communication on risk perceptions: the significance of individual differences.

The purpose of this paper is to address the literature on the relation between risk communication and the initiation of health behavior change. More specifically, we examine the evidence that providing risk information is an effective way to change risk perceptions, as well as the more limited evidence that altering risk perceptions influences risk behavior. The paper discusses significant developments in the research on these issues, describes specific studies that represent trends in this research, and discusses methodologic issues important to the development of the field. Although there are relatively few studies that demonstrate causal links between risk communication and behavior change, recent developments in the field point to the importance of tailoring risk communications to the individual characteristics of targets. Such tailoring has taken a variety of forms, including providing individualized feedback concerning risk status or genetic vulnerability and assessing readiness for behavior change. Future intervention efforts should combine individualized risk status feedback with assessment of individual differences in previous behavior and acceptance of personal vulnerability.

Communication↗

The effect of peers' alcohol consumption on parental influence: a cognitive mediational model.

OBJECTIVE: The current study was designed to elucidate familial and social influences on adolescent alcohol consumption by testing three hypotheses derived from the prototype/willingness model of adolescent risk behavior: (1) parents' prototypes of adolescent drinkers affect adolescent consumption through their impact on adolescents' prototypes, (2) strong parent-child relationships are associated with acceptance of parental influence regarding drinking and thus with less adolescent drinking and (3) association with peers who drink dilutes parental influence over adolescents' alcohol consumption. METHOD: Two hundred sixty-six rural adolescents, ages 15 through 17 at Time 1, and their parents and siblings completed questionnaires about drinking behavior and drinking-related cognitions at 1-year intervals for 3 years. RESULTS: Structural equation models provided evidence of transmission of prototypes of adolescent drinkers from parents to adolescents and evidence that these prototypes mediate adolescent alcohol consumption. They also provide evidence that although parents' prototypes and parent-adolescent relationships are important in shaping the adolescents' drinking, association with peers who drink significantly attenuates this influence. CONCLUSIONS: These data suggest that parents can influence their children's drinking, but that this influence has more of an impact if the adolescent is not involved in a drinking-conducive peer environment. The current analyses also suggest that the process of becoming an adolescent drinker involves an active rejection of parents' influence rather than a passive movement away from parents' attitudes and beliefs-a process that is accelerated by association with peers who drink.

Adolescent↗

Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1.

A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.

Chromosomes, Human, Pair 17↗

Reasoned action and social reaction: willingness and intention as independent predictors of health risk.

Three studies are described that assess elements of a new model of adolescent health-risk behavior, the prototype/willingness (P/W) model (F. X. Gibbons & M. Gerrard, 1995, 1997). The 1st analysis examined whether a central element of the prototype model, behavioral willingness, adds significantly to behavioral expectation in predicting adolescents' smoking behavior. The 2nd set of analyses used structural-equation-modeling procedures to provide the 1st test of the complete model in predicting college students' pregnancy-risk behavior. Finally, the 3rd study used confirmatory factor analysis to assess the independence of elements of the model from similar elements in other health behavior models. Results of the 3 studies provided support for the prototype model and, in particular, for 2 of its primary contentions: (a) that much adolescent health-risk behavior is not planned and (b) that willingness and intention are related but independent constructs, each of which can be an antecedent to risk behavior.

Adolescent↗

Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003 protocol.

From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high-dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15 fractions) was recommended in patients with overt CNS disease. One patient with Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and BM, three; and jaw, one) 4-11 months after diagnosis and two patients never achieved complete remission (CR). All have died. In seven of the patients who relapsed, treatment had been modified or delayed because of poor clinical condition. Seven patients (11%) died of toxicity 11 days to 4 months after diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3 years), 43 patients (69%) survive in CR. This study confirms the effectiveness of this regimen with regard to the relapse rate (16%), although the rate of toxic death is of concern.

Adolescent↗

Costello syndrome: two cases with embryonal rhabdomyosarcoma.

Costello syndrome is a well delineated mental retardation syndrome of unknown aetiology in which the occurrence of benign tumours, especially papillomata, is recognised. We report two children in whom the diagnosis of Costello syndrome was made in the first months of life, who both developed a retroperitoneal embryonal rhabdomyosarcoma. Although not previously reported, the occurrence of this relatively uncommon childhood tumour in two girls with Costello syndrome suggests that an increased risk of malignancy may be part of this condition. The genetic basis of this susceptibility requires further clarification.

Child, Preschool↗

Effect of sexual motivation on men's risk perception for sexually transmitted disease: there must be 50 ways to justify a lover.

Recent research has incorporated situational factors into assessment of risk. Working from a rational appraisal framework, however, these studies have not emphasized contextual features that might introduce motivated risk assessment. In the current study, participants (N = 40 male undergraduates) lowered their risk perceptions for STDs following the induction of a sexual motivation. In an initial baseline condition, participants estimated the risk of contracting STDs from partners with relatively high- or low-risk sexual histories. In a subsequent trial, participants repeated the imagery task while viewing photographs that were high or low in sex appeal. As predicted, participants reduced their risk perceptions when they viewed photographs high in sex appeal. The only necessary precondition was the presence of nondiagnostic information from which they could construct biased risk estimates.

Adult↗