Biomedical subjects

B J McCarthy

Publications and source records attributed to B J McCarthy.

At least 19 recordsLinked to original sources

PubMed2001

Altering the fine specificity of an anti-Legionella single chain antibody by a single amino acid insertion.

Antibody engineering provides the potential to clone and manipulate antibody genes to produce fragments with altered specificity. We have produced an anti- Legionella single chain fragment with broader specificity towards Legionella serotypes than the parent monoclonal antibody. Using this relationship between the parent monoclonal and the recombinant antibody derived from it as a model, we attempted to identify those residues responsible for this change in fine specificity. Sequence analysis of this recombinant antibody revealed the deletion of a conserved residue, Asp101, in the CDR-H3 region. Using site-directed mutagenesis, we have created a mutant form of this single chain fragment with an aspartic acid insertion mutation at position 101 of the antibody heavy chain. This mutant scFv demonstrates improved specificity compared to the wild-type recombinant antibody, indicating an important role for Asp101.

Amino Acid Sequence↗

PubMed2001

Trends in incidence of primary brain tumors in the United States, 1985-1994.

Brain tumor incidence has increased over the last 20 years in all age groups, both overall and for specific histologies. Reasons attributed to these increases include increase in lymphoma due to HIV/AIDS, introduction of computed tomography/magnetic resonance imaging, and changes in coding/classification. The purpose of this study was to describe overall and histologic-specific incidence trends in a population-based series of primary benign and malignant brain tumors. Data from the Central Brain Tumor Registry of the United States from 1985 through 1994 were used to determine incidence trends in the broad age groups 0-19, 20-64, and > or = 65 years, both overall and for selected histologies. Poisson regression was used to express trends as average annual percentage change. Overall, incidence increased modestly (annual percentage change 0.9%, 95% confidence interval, 0.4, 1.4). When lymphomas were excluded, this result was not statistically significant (annual percentage change 0.5%, 95% confidence interval, -0.1, 1.1). Specific histologies that were increasing were lymphomas in individuals aged 20 to 64 years and in males aged 65 years or older, ependymomas in the population aged 20 to 64 years, nerve sheath tumors in males, and pituitary tumors in females. Increases that were not specific to any population subgroup were seen for glioblastoma, oligodendrogliomas, and astrocytomas, excluding not otherwise specified (NOS) tumors. Corresponding decreases were noted for NOS, astrocytoma NOS, and glioma NOS. Increasing incidence trends for lymphomas were consistent with previous literature. Improvements in diagnostic technology in addition to changes in classification and coding were likely to be responsible for decreases seen in incidence of NOS subgroups and corresponding increases in glioma subgroups. In contrast, the increases identified for ependymomas, nerve sheath tumors, and pituitary tumors were less likely to be artifacts of improvements in diagnosis, and they warrant further study.

Adolescent↗

PubMed2001

Current epidemiological trends and surveillance issues in brain tumors.

The absence of an overall increase in incidence rates for all primary brain tumors since the 1950s argues against a recently introduced environmental tumorigen impacting these tumors. Historical increases in brain cancer mortality and incidence rates appear to be leveling off following the widespread introduction of CT and MRI scans, indicating that increases in overall rates of malignant tumors are likely to be an artifact of diagnosis and reporting issues. Further studies are needed to understand those tumor types with rates that do appear to be increasing among adults; specifically lymphomas, nerve sheath tumors, pituitary tumors and ependymomas. Patterns of incidence by race, ethnicity, socioeconomic status, and seasonal and regional variation would assist in directing relevant new research questions. Filling in the gap of information on patterns for prevalent, second primaries and metastatic tumors may be useful in understanding the public perception regarding brain tumor rates and would be a valuable addition to healthcare planning tools.

Brain Neoplasms↗

PubMed2001

Improving surveillance for maternal and perinatal health in 2 districts of rural Tanzania.

OBJECTIVES: As part of a community-based reproductive health project in rural Tanzania, a maternal and perinatal health care surveillance system was established to monitor pregnancy outcomes. This report presents preliminary results. METHODS: Village health workers were trained to collect data during health education visits to pregnant and postpartum women. Maternal and fetal or infant survival or deaths were tracked on a community monitoring board. RESULTS: Among 904 pregnancies, the fetoneonatal mortality rate was 69.4 deaths per 1000 live births and fetal deaths; 4 maternal deaths occurred. Intrapartum and early neonatal deaths of infants with birthweights of 1500 g or greater represented a large proportion of deaths. CONCLUSIONS: These preliminary results will be used to prioritize project interventions, including increasing access to skilled delivery care.

Adult↗

PubMed2000

Type 1 diabetes in offspring of parents with type 1 diabetes: the tip of an autoimmune iceberg?

The objective of the present study was to examine the prevalence of self-reported autoimmune diseases among offspring of type 1 fathers, type 1 diabetic mothers, and non-diabetic parents. Type 1 diabetic probands (n=265; mean age=42 yr), who were ascertained from the Children's Hospital of Pittsburgh Registry for 1950-1964, recently participated in the Familial Autoimmune and Diabetes Study. Non-diabetic probands (n=96), identified from voter registration lists and matched by age, race, median income, and duration of residence in the Pittsburgh area, were also enrolled. Offspring of type 1 diabetic probands were more likely to have a reported autoimmune disease (5.8% vs. 2.4%; p=0.067) than offspring of non-diabetic probands. Half the cases in the diabetic families were disorders other than type 1 diabetes, (e.g., rheumatoid arthritis, Crohn's disease, etc.). Stratification by parental gender revealed a marginally higher risk for type 1 diabetes among offspring of type 1 diabetic fathers compared to mothers (4.9% vs. 3.4%; p=0.38, respectively, through age 20 yr). However, the risk for other autoimmune disorders was statistically significantly increased among offspring of type 1 diabetic mothers (0% vs. 6.2%; p=0.02, respectively, through age 20 yr). These data suggest that offspring of type 1 diabetic parents may be at high risk of developing other autoimmune disorders during childhood, with pediatric diabetes representing the 'tip of an autoimmune iceberg'. The observed risk differences by parental gender, which have also been reported for other autoimmune disorders, warrant further investigation.

Journal Article↗

PubMed2000

Epidemiology of brain tumors.

Primary brain tumor incidence and survival patterns are emerging, assisted by progress in molecular classification. Evidence is accumulating to suggest that infectious diseases may affect the risk of developing a brain tumor, although data require clarification. Other promising research directions include evaluating the role of diet and allergic conditions in reducing brain tumor risk.

Brain Neoplasms↗

PubMed2000

Talking rot ... and mildew on textiles.

Nature has evolved some very elegant elementary mechanisms for re-cycling of organic substances in the environment. These processes are normally beneficial. This article describes why microorganisms may attack textiles during production and in use, causing financial losses, and what can be done to prevent this happening.

Animals↗

PubMed1999

Does inadequate prenatal care contribute to growth retardation among second-born African-American babies?

The authors evaluated the relation between adequacy of prenatal care and risk of delivery of full term small-for-gestational-age (SGA) infants. Data were derived from maternally linked birth certificates for 6,325 African-American women whose first two pregnancies ended in singleton, full term live births in Georgia from 1989 through 1992. The authors used stratified analysis to assess the effect of prenatal care on the risk of having an SGA baby in the second pregnancy among women with and without an SGA baby in their first pregnancy. The group of women with a history of SGA birth may be more likely to include persons for whom SGA delivery is related to factors, such as genetics, that are not amenable to intervention by prenatal care. Inadequate prenatal care was not associated with the risk of SGA delivery among women who had previously delivered an SGA baby. In unadjusted analyses, inadequate prenatal care was associated with an increased risk of delivering a full term SGA baby in the second pregnancy among women whose first baby was not SGA (risk ratio = 1.28; 95% confidence interval: 1.05, 1.55). The association did not persist when data were adjusted for confounding variables (odds ratio = 1.11; 95% confidence interval: 0.89, 1.38). Regardless of outcome in the first pregnancy, adequate prenatal care did not reduce the risk of full term SGA birth among second pregnancies in this population.

Adolescent↗

PubMed1999

The conditional probability of survival of patients with primary malignant brain tumors: surveillance, epidemiology, and end results (SEER) data.

BACKGROUND: Five-year survival estimates in standard cancer reports provide a general description of disease outcome that is useful for surveillance and comparison purposes. However, for cancer survivors these overall survival rates may be discouraging, and the relevant question regarding an individual is this: Once he or she has survived for a specified period of time, what is the probability of survival over the next period of time? METHODS: To address this, conditional survival rates by histology for malignant brain tumor survivors were estimated using the SEER public use data and the Portable Survival System, with 19,105 brain and other nervous system patients diagnosed between 1979 and 1993. Given that the survival curve declines more rapidly in the first 2 years than in subsequent years, conditional probabilities of surviving 5 years given survival to 2 years and 95% confidence intervals (CIs)were calculated. As age is a strong prognostic factor for these tumors, conditional probabilities were also estimated by categories of age. RESULTS: Estimated 2- and 5-year relative survival rates for patients with malignant brain and other CNS tumors were 36.2% and 27.6%; however, the conditional probability of surviving to 5 years, given survival to 2 years, reaches 76.2% (95% CI: 74.8-77.6). Conditional probabilities varied by histology and age at diagnosis. The conditional probability of surviving 5 years after surviving 2 years was 67.8% (95% CI: 62.6-73.1) for patients with anaplastic astrocytomas, 36.4% (95% CI: 31.9-41.6) for patients with glioblastomas, and 79.8% (95% CI:75.3-84.1) for patients with medulloblastomas. CONCLUSIONS: Conditional probabilities provide important and encouraging information for those who are brain tumor survivors. The utility of these estimates for other time intervals and other cancers or diseases should be considered.

Adult↗

PubMed1999

Temporal trends in spontaneous abortion associated with Type 1 diabetes.

The objective of this study was to investigate temporal changes in the reported rates of spontaneous abortion associated with Type 1 diabetes. Individuals from the Children's Hospital of Pittsburgh Type 1 Diabetes Registry for 1950-1964 (n=495) completed a self-report reproductive history questionnaire in 1981 that was updated in 1990. Data from both surveys, which proved to be valid and reliable, were utilized for this report. More spontaneous abortions (26.8 vs. 7.7%, P<0.001), stillbirths (4.7 vs. 1.2%, P<0.001) and induced abortions (7.0 vs. 0.9%, P<0.001) were reported for Type 1 diabetic women than for the non-diabetic partners of Type 1 diabetic men. A significant temporal decline in the rates of spontaneous abortion for Type 1 diabetic women was observed (< or = 1969: 26.4%; 1970-1979: 31.0%; 1980-1989: 15.7%; P<0.05). No differences were apparent for the non-diabetic partners of Type 1 diabetic men (< or = 1969: 4.2%; 1970-1979: 9.5%; 1980-1989: 5.7%; P>0.05). Temporal changes in medical care for women with diabetes (i.e. self-monitoring of glycemic control) may have contributed to a recent reduction in spontaneous abortions associated with maternal Type 1 diabetes.

Abortion, Spontaneous↗

PubMed1999

Descriptive epidemiology of primary brain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990-1994.

The Central Brain Tumor Registry of the United States (CBTRUS) obtained 5 years of incidence data (1990-1994)--including reports on all primary brain and CNS tumors--from 11 collaborating state cancer registries. Data were available for 20,765 tumors located in the brain, meninges, and other CNS sites, including the pituitary and pineal glands. The average annual incidence was estimated at 11.5 cases per 100,000 person-years. The higher incidence of tumors in male patients (12.1 per 100,000 person-years) than in female patients (11.0 per 100,000 person-years) was statistically significant (P < 0.05); the higher incidence in whites (11.6 per 100,000 person-years) compared with blacks (7.8 per 100,000 person-years) was statistically significant (P < 0.05). The most frequently reported histologies were meningiomas (24.0%) and glioblastomas (22.6%). Higher rates for glioblastomas, anaplastic astrocytomas, oligodendrogliomas, anaplastic oligodendrogliomas, ependymomas, mixed gliomas, astrocytomas not otherwise specified, medulloblastomas, lymphomas, and germ cell tumors in male than in female patients were statistically significant (P < 0.05), with relative risks (RR) ranging from 1.3 to 3.4. Meningiomas were the only tumors with a significant excess in females (RR = 0.5). We noted higher occurrence rates in whites than in blacks for the following histologies: diffuse astrocytomas, anaplastic astrocytomas, glioblastomas, oligodendrogliomas, ependymomas, mixed gliomas, astrocytomas NOS, medulloblastomas, nerve sheath tumors, hemangioblastomas, and germ cell tumors, with RRs ranging from 1.5 to 3.4. Racial differences in occurrence rates were not observed for predominately benign meningiomas or pituitary tumors. This study represents the largest compilation of data on primary brain and CNS tumors in the United States. Standard reporting definitions and practices must be universally adopted to improve the quality and use of cancer registry data.

Adolescent↗

PubMed1999

Centralized databases available for describing primary brain tumor incidence, survival, and treatment: Central Brain Tumor Registry of the United States; Surveillance, Epidemiology, and End Results; and National Cancer Data Base.

Characteristics of three databases--the Central Brain Tumor Registry of the United States (CBTRUS) database; the Surveillance, Epidemiology and End Results (SEER) database; and the National Cancer Data Base (NCDB)--containing information on primary brain tumors are discussed. The recently developed population-based CBTRUS database comprises incidence data on all primary brain tumors from 11 collaborating state registries; however, follow-up data are not available. SEER, the population-based gold standard for cancer data, collects incidence and follow-up data on malignant brain tumors only. While not population-based, the NCDB identifies newly diagnosed cases and conducts follow-up on all primary brain tumors from hospitals accredited by the American College of Surgeons. The NCDB is the largest of the three databases and also contains more complete information regarding treatment of these tumors than either the SEER or CBTRUS databases. Additional strengths and limitations of each of these are described, and their judicious use for supporting research, education, and health care planning is encouraged.

Brain Neoplasms↗

PubMed1998

Are we underestimating rates of vaginal birth after previous cesarean birth? The validity of delivery methods from birth certificates.

Previous studies of birth certificates have not fully evaluated how accurately they identify delivery methods that have a historical component, such as repeat cesarean and vaginal birth after previous cesarean (VBAC). The authors used linked Georgia birth certificates for first and second deliveries to examine the accuracy of four reported delivery methods in the second pregnancy: vaginal (without previous cesarean), VBAC, primary cesarean, and repeat cesarean, as well as an indicator of a previous cesarean. From the immediate birth certificates, the delivery method for each of the two births was classified as vaginal (V) or cesarean section (CS), which produced possible sequences of V-V, CS-V, V-CS, and CS-CS. The delivery method for the second births to 106,049 women from 1989 through 1992 was reviewed, taking into account the historical information from the linked certificates regarding the first births. Only 42.0% of women with a CS-V sequence were correctly designated on the second birth certificate as a VBAC; 79.3% of women with a V- CS sequence were correctly designated as primary cesarean. From 1980 through 1988, birth certificates contained a check box indicating a previous cesarean (but no VBAC box). During this period, only 75.5% of 25,491 women with a previous cesarean were so designated on the birth certificate. These findings suggest that cross-sectional vital records data substantially underestimate VBAC and primary cesarean rates.

Birth Certificates↗

PubMed1998

Late effects in survivors of bone tumors.

Today more than 71% of children with cancer are surviving their disease. This is because of improved treatment including aggressive combination therapy and better supportive care measures. The majority of patients with bone tumors are now being treated with surgery, chemotherapy, and radiation therapy, resulting in an increase in numbers of long-term survivors. This aggressive therapy, however, has increased the risk of developing late effects. This article reviews some of these late effects in survivors of bone tumors diagnosed in childhood or adolescence. Areas that are explored include cardiac, infections, second operations, second malignant neoplasms, renal, auditory, fertility, pulmonary, functional, and psychosocial outcomes. The need for long-term follow-up clinics is also addressed.

Antineoplastic Agents↗

PubMed1998

Factors associated with survival in patients with meningioma.

OBJECT: To explore factors affecting the survival rate in patients with meningiomas, the authors used the National Cancer Data Base (NCDB), which includes tumors from approximately 1000 hospitals participating in the American College of Surgeons tumor registry program. METHODS: Analysis included over 9000 cases diagnosed from 1985 to 1988 and 1990 to 1992. Survival estimates were computed and prognostic factors were identified using a proportional hazards model. The overall 5-year survival rate was 69% and it declined with patient age. This rate was 81% in patients aged 21 to 64 years and 56% for patients 65 years of age or older. When patients were grouped by the histological type of their tumors, those with benign tumors had an overall 5-year survival rate of 70%, whereas the overall 5-year survival rates in patients with atypical and malignant meningiomas were 75% and 55%, respectively. Prognostic factors for benign tumors included age at diagnosis, tumor size, whether treated surgically, hospital type, and radiation therapy; for malignant tumors, the prognostic factors included: age at diagnosis, whether treated surgically, and radiation therapy. These factors were statistically significant. The 5-year rate for recurrence of symptoms (regardless of the method of treatment) was 19.2% for those with benign tumors and 32.4% for those with malignant tumors. In patients whose benign tumor had been completely removed, the 5-year rate of tumor recurrence was 20.5%. CONCLUSIONS: Although not population-based, the NCDB has the potential for providing pertinent information regarding patient characteristics and methods of treatment for benign, as well as malignant, brain tumors.

Activities of Daily Living↗

PubMed1997

Analysis of serpin inhibitory function by mutagenesis of ovalbumin and generation of chimeric ovalbumin/PAI-2 fusion proteins.

Ovalbumin is a non-inhibitory serpin which lacks the ability to undergo the S --> R transition or conformational change. Amino acid residues in the hinge region (P11 to P14) of ovalbumin and other non-inhibitory serpins differ from the concensus sequence of this region of inhibitory serpins, and have been proposed to be responsible for lack of inhibitory properties, particularly the P14 charged residue. Site directed mutagenesis using PCR overlap extension was performed on these residues in ovalbumin to create a mutant with three amino acid changes, R340T, V342A and V343A. However analysis of the mutant recombinant ovalbumin with the consensus residues failed to show inhibitory activity or decreased stability, indicating that the hinge region alone is not responsible for lack of inhibition. A series of three fusion proteins were then constructed by replacing varying C-terminal regions of ovalbumin with the corresponding region of the inhibitory ov-serpin PAI-2 in order to further analyse serpin inhibitory function. Fusion proteins F1 and F2 contained approximately 16% and 35% PAI-2, respectively. This resulted in the replacing of structural features such as the reactive site loop, hinge region and beta sheet strands 5A and 6A. However both fusion proteins showed no inhibitory activity with the PAI-2 target protease urokinase (uPA) and no decrease in stability as analysed by transverse urea gradient (TUG) gels. The third chimeric fusion protein constructed (F3) contained 64% PAI-2 and did demonstrate inhibition of uPA, SDS-PAGE stable complex formation with uPA and increased instability on TUG gels. Structural differences between the inactive F2 and active F3 include the replacement of helix F and beta sheet strand 3A of ovalbumin with those of PAI-2, suggesting that these features may have a key role in serpin beta-sheet opening and inhibitory function.

Amino Acid Sequence↗

PubMed1997

Constructing reproductive histories by linking vital records.

Certificates of 1,449,287 live births and fetal deaths filed in Georgia from 1980 through 1992 were linked to create chronologies that, excluding induced abortions and ectopic pregnancies, constituted the reproductive experience of individual women. The authors initially used a deterministic method (whereby linking rules were not based on probability theory) to link as many records as possible, knowing that some of the linkages would be incorrect. They subsequently used a probabilistic method (whereby evaluation of linkages was developed from probability theory) to evaluate each linkage, and they broke those that were judged to be incorrect. Of the 1.4 million records, 38% did not link to another record. From the remaining records, 369,686 chains of two or more events were constructed. The longest chain included 12 events. Of the chains, 69% included two events; 22% included three events. Longer chains tended to have lower scores for probable validity. The probability-based evaluation of chains affected 3.0% of the records that had been in chains at the end of the deterministic linkage. A greater percentage of records in longer chains were affected by the evaluation. Unfortunately, the small subset of records that were the most difficult to link tended to overrepresent groups with the greatest risk of adverse pregnancy outcomes. Researchers contemplating a similar linkage can anticipate that, for the majority of records, linkage can be accomplished with a relatively straightforward, deterministic approach.

Adolescent↗

PubMed1997

Patterns of prenatal care initiation in Georgia, 1980-1992.

OBJECTIVE: To determine whether characteristics in a woman's first pregnancy were associated with the trimester in which she initiated prenatal care in her second pregnancy. METHODS: Data for white and black women whose first and second pregnancies resulted in singleton live births between 1980 and 1992 were obtained from Georgia birth certificates (n = 177,041). Adjusted relative risks (RRs) for early prenatal care in the second pregnancy were computed by logistic regression models that included trimester of prenatal care initiation, infant outcomes, or maternal conditions in the woman's first pregnancy as the exposure and controlled for maternal age, education, child's year of birth, interval between first and second pregnancy, presence of father's name on the birth certificate, and the interaction between prenatal care and education. Models were stratified by race. RESULTS: Women of both races who initiated prenatal care in the first trimester of their first pregnancies were more likely than those with delayed care to initiate prenatal care in the first trimester of their second pregnancies (RR = 1.25 and 1.63 for white and black women educated beyond high school, respectively). Both white and black women who delivered a baby with very low birth weight (RR = 1.06 and 1.15, respectively) or who suffered an infant death (RR = 1.09 and 1.31, respectively) in their first pregnancies were more likely than those who did not experience these events to begin prenatal care in the first trimester of their second pregnancies. CONCLUSION: Women with some potentially preventable adverse infant outcomes tend to obtain earlier care in their next pregnancy. Unfortunately, women who delayed prenatal care in their first pregnancy frequently delay prenatal care in their next.

Female↗