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Biomedical subjects

C A Clarke

Publications and source records attributed to C A Clarke.

At least 19 recordsLinked to original sources
PubMed2001

Expert review of the diagnosis and histologic classification of Hodgkin disease in a population-based cancer registry: interobserver reliability and impact on incidence and survival rates.

BACKGROUND: The reliability of Hodgkin disease (HD) diagnosis and histologic classification is an ongoing concern but has not been evaluated in a population-based case series in 20 years. Yet, diagnostic error in cancer registry data used in surveying HD occurrence may produce statistics that misrepresent incidence, mortality, or survival. METHODS: Uniform pathology review was attempted for all 395 women ages 19--79 years with incident HD reported to a population-based cancer registry in 1988--94. Agreement between original registry and review diagnoses was measured with positive predictive values and kappa statistics. Incidence rates and survival probabilities were computed based on registry and review diagnoses. RESULTS: Registry and review diagnosis agreed for 245 of the 362 reviewed cases. Positive predictive values varied by histologic subtype (nodular sclerosis, 95%; lymphocyte predominance, 69%; mixed cellularity, 58%; lymphocyte depletion, 0%; not otherwise specified, 40%), but agreement was good overall (kappa, 0.66, 95% confidence interval, 0.56--0.76). Eleven patients were determined not to have HD; all were older than age 44 years. Hodgkin disease incidence rates differed for original and review diagnoses only in older women, for whom registry rates slightly overestimated incidence. Five-year survival rates did not differ for registry and review data overall or by age group. CONCLUSIONS: For most adult women patients, the diagnosis of HD was confirmed on review, reflecting the very good agreement between registry and review diagnoses for nodular sclerosis, the most common subtype. Thus, cancer registry statistics for this time period can provide accurate estimates of disease patterns for HD overall and for the nodular sclerosis variant. For other histologic subtypes, rates may be unreliable, and HD occurrence overall may be less dependable in populations with larger proportions of these subtypes.

Adult↗
PubMed2001

Epstein-Barr virus and survival after Hodgkin disease in a population-based series of women.

BACKGROUND: Epstein-Barr virus (EBV) positive Hodgkin disease (HD), as defined by the presence of EBV genes or gene products in the malignant cells, differs epidemiologically from EBV negative HD. However, survival patterns for EBV-defined HD have not been well studied. To determine if EBV status influenced survival time after HD, the authors investigated a large, population-based series of female patients. METHODS: For 311 female patients living in the Greater San Francisco Bay Area who were aged 19-79 years with HD diagnosed between mid-1988 and 1994, histopathologically rereviewed archived biopsy specimens were assayed for EBV with immunohistochemistry and in situ hybridization. The 53 subjects with EBV positive and the 258 with EBV negative HD were observed for vital status through 1998; overall survival was analyzed with Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Epstein-Barr virus positive HD patients were older, received diagnosis at a later stage, and were less likely to have nodular sclerosis histology than EBV negative patients. Deaths were reported for 21 (40%) EBV positive and 37 (14%) EBV negative patients. No survival differences were observed between EBV positive and negative women aged 19-44 years, but survival was significantly poorer in women aged 45-79 years with EBV positive HD. Regression analysis confirmed this strong negative effect of EBV positive status on survival (hazard ratio for death, 3.0; 95% confidence interval, 1.5-6.2) as unrelated to age, stage at diagnosis, or tumor histology. CONCLUSIONS: This study found a marked survival disadvantage for EBV positive HD in older but not young adult women. These findings suggest influences of both EBV status and age on HD survival, as well as pathogenesis.

Adult↗
PubMed2001

Age-specific survival after Hodgkin's disease in a population-based cohort (United States).

OBJECTIVE: To examine risk factors for disease-specific survival in young and older adults diagnosed with Hodgkin's disease (HD) in a representative case series of adequate size for detecting effect modification by age group. METHODS: For 5630 young adults (ages 15-44) and 2424 older adults (ages 45 and older) diagnosed with HD and reported to the population-based Surveillance, Epidemiology, and End Results program of the National Cancer Institute between 1983 and 1995, Kaplan-Meier survival curves were constructed and Cox proportional hazards regression used to evaluate the influences of age, sex, race/ethnicity, histologic subtype, Ann Arbor stage at diagnosis, and calendar year on hazard of disease-specific death. RESULTS: The effects of most previously studied risk factors for HD death were different for young and older adults. Age was not associated with disease-specific survival in young adults, but in older adults, 1-year increases in age elevated the relative hazard of HD death by 4 6%. Male sex was related to outcome in young but not older adults, and Ann Arbor stage and B-symptom status exhibited markedly different relationships to survival by age. Older adult patients with and without B-symptoms had different hazards of mortality and had to be assessed separately. CONCLUSIONS: Factors associated with disease-specific survival were different for young and older adults with HD. These findings provide further support for two etiologically and clinically distinct disease entities.

Adolescent↗
PubMed2001

Epidemiologic trends in HIV-associated lymphomas.

Infection with HIV increases the risk of developing non-Hodgkin lymphoma and, to a lesser extent, Hodgkin disease. The introduction of highly active antiretroviral therapy (HAART) in 1996 changed the natural history of HIV disease, but the HIV-infected population also has changed in composition. Accordingly, the epidemiology of HIV-associated lymphomas now differs from that observed in the first 15 years of the HIV epidemic. In populations with access to HAART, reductions in lymphoma risk have been reported for NHL and suggested for Hodgkin disease, but long-term risks are as yet unknown. Lymphomas are increasingly common cancers in persons with HIV and are fatal in most patients, warranting continued attention to their incidence and etiology.

Antiretroviral Therapy, Highly Active↗
PubMed1997

Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study.

OBJECTIVE: To monitor pregnancies in women with pre-existent insulin dependent diabetes for pregnancy loss, congenital malformations, and fetal growth in a geographically defined area of north west England. DESIGN: Population cohort study. SETTING: 10 maternity units in Cheshire, Lancashire, and Merseyside which had no regional guidelines for the management of pregnancy in diabetic women. SUBJECTS: 462 pregnancies in 355 women with insulin dependent diabetes from the 10 centres over five years (1990-4 inclusive). MAIN OUTCOME MEASURES: Numbers and rates of miscarriages, stillbirths, and neonatal and postneonatal deaths; prevalence of congenital malformations; birth weight in relation to gestational age. RESULTS: Among 462 pregnancies, 351 (76%) resulted in a liveborn infant, 78 (17%) aborted spontaneously, nine (2%) resulted in stillbirth, and 24 (5%) were terminated. Of the terminations, nine were for congenital malformation. The stillbirth rate was 25.0/1000 total births (95% confidence interval 8.9 to 41.1) compared with a population rate of 5.0/1000, and infant mortality was 19.9/1000 live births (5.3 to 34.6) compared with 6.8/1000. The prevalence of congenital malformations was 94.0/1000 live births (63.5 to 124.5) compared with 9.7/1000 in the general population. When corrected for gestational age, mean birth weight in the sample was 1.3 standard deviations greater than that of infants of non-diabetic mothers. Infants with congenital malformations weighed less than those without. CONCLUSION: In an unselected population the infants of women with pre-existent insulin dependent diabetes mellitus have a 10-fold greater risk of a congenital malformation and a fivefold greater risk of being stillborn than infants in the general population. Further improvements in the management of pregnancy in diabetic women are needed if target of the St Vincent declaration of 1989 is to be met.

Abortion, Spontaneous↗
PubMed1997

Preventing Rhesus D haemolytic disease of the newborn by giving anti-D immunoglobulin: are the guidelines being adequately followed?

OBJECTIVE: To ascertain whether anti-D immunoglobulin is being administered to Rhesus D negative women in accordance with the 1991 recommendations for its use to cover all events which may result in fetomaternal haemorrhage. DESIGN: The notes of women delivered in 1994 were examined for compliance with the 1991 recommendations. SETTING: Seven maternity units using a central antenatal screening service. PARTICIPANTS: Nine hundred and twenty-two Rhesus D negative women delivered in these seven hospitals. MAIN OUTCOME MEASURES: The prescription, dosage and indications for administration of anti-D immunoglobulin to women during pregnancy and in the puerperium. RESULTS: Postnatal anti-D immunoglobulin was given in appropriate doses to more than 95% of women who required it. Omissions mainly arose from confusion among women who recently had received antenatal treatment with anti-D immunoglobulin. The 1991 recommendations for antenatal administration were less closely followed. Abdominal trauma was covered in only 20% of cases. An inadequate dosage of 250 i.u. was given to 25 women for antepartum haemorrhage after 20 weeks of gestation. The purpose of the Kleihauer test was sometimes poorly understood, with a 'negative' result interpreted as a reason not to give anti-D immunoglobulin. CONCLUSION: Closer adherence to the 1991 recommendations might further reduce the incidence of Rhesus D immunisation below the current 1%. It is suggested that more careful application of the recommendations should be evaluated before considering either routine antenatal prophylaxis, or the European recommendation of a larger dose (1000-1500 i.u.), both of which would increase the requirements for this limited resource.

Erythroblastosis, Fetal↗
PubMed1993

Cloning and analysis of the murine Fanconi anemia group C cDNA.

Fanconi anemia (FA) is one of a group of disorders characterized at the cellular level by a combination of hypersensitivity to DNA-damaging agents, chromosomal instability, and defective DNA repair. Clinical features of FA include pancytopenia, often accompanied by specific congenital malformations, and a predisposition to leukemia. Since the hematological manifestations are the critical defect in terms of prognosis, FA is a candidate disease for gene replacement therapy, and the development of a mouse model system is essential for the initial stages of this work. Previously, we have cloned the gene defective in FA group C by complementation of the intrinsic sensitivity of FA cells to DNA cross-linking agents. We have now cloned the murine homologue of the human FACC cDNA. The mouse cDNA (Facc) shares 79% amino acid sequence similarity with the human gene product. The expression of the mouse cDNA in human FA(C) cells restores the cellular drug sensitivity to normal levels. Thus, the function of the protein has been conserved despite the significant sequence divergence. PCR analysis of mouse tissue RNA reveals that the gene is expressed in all adult tissues, while in situ RNA hybridization experiments show tissue specific expression at late stages of fetal development. Cross-hybridizing sequences exist in DNA from other mammals, chicken and Drosophila. These results support the hypothesis that the FACC gene product has a role in a basic aspect of cellular protection against DNA damaging agents and that this function has been conserved during evolution.

Amino Acid Sequence↗
PubMed1990

The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H]flunitrazepam autoradiography.

The GABA/benzodiazepine receptor complex in the basal ganglia of primates treated with the neurotoxin n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been studied by semi-quantitative autoradiography with [3H]flunitrazepam ([3H]FNZ). Systemic treatment with MPTP produced a stable and lasting parkinsonian condition, with pronounced bradykinesia, akinesia and tremor. In the lateral segment of the globus pallidus (GPL) there was a significant reduction of [3H]FNZ binding compared with non-treated animals. There were no significant changes in the [3H]FNZ binding in the caudate nucleus, putamen and medial globus pallidus (GPM). This suggests that MPTP-treatment increases GABA release within the GPL exclusively. In view of the available evidence suggesting increased striatal output, and reduced unit activity within the GPL of the MPTP-treated primate, it seems likely that the striatal GABAergic output to the GPL is overactive in this model of Parkinson's disease. Furthermore, as there is no evidence for a change in GABA function within the GPM using this measure, the striatal neurones which innervate the GPM may be differentially affected by loss of dopamine innervation. In line with structural evidence and extrastriatal dopamine receptor distribution this suggests that the two striatopallidal systems are functionally heterogeneous. A hemi-parkinsonian primate model has also been used in this study. This model was produced by injection of MPTP directly into one carotid artery. The substantia nigra pars compacta (SNc) was destroyed on the injected side alone, and consequently the appearance of parkinsonian symptoms was confined to the contralateral side. [3H]FNZ binding in the GPL appears to be bilaterally reduced in this model, suggesting an interaction between the treated and non-treated side of the brain. In addition there is increased binding in the putamen and GPM with respect to the non-treated side of the brain. The increased [3H]FNZ binding in the GPM of the unilateral model may be due to the greater disruption of the nigropallidal and/or nigrostiatal dopamine neurones relative to the systemic model. The former would have the effect of uncoupling D1 dopamine receptors located on the terminals of striatal efferents from nigropallidal dopamine input, and as D1 dopamine receptors are implicated in the presynaptic control of GABA release from the terminals of striatal efferents, this would consequently reduce the level of GABA release in the GPM. The latter possibility would suggest that striatopallidal neurones projecting to GPM are more resistant to the effects of dopaminergic denervation than those projecting to GPL.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗