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Biomedical subjects

D J MacDonald

Publications and source records attributed to D J MacDonald.

At least 19 recordsLinked to original sources
PubMed2004

Essential fatty acids and phospholipase A2 in autistic spectrum disorders.

A health questionnaire based on parental observations of clinical signs of fatty acid deficiency (FAD) showed that patients with autism and Asperger's syndrome (ASP) had significantly higher FAD scores (6.34+/-4.37 and 7.64+/-6.20, respectively) compared to controls (1.78+/-1.68). Patients with regressive autism had significantly higher percentages of 18:0,18:2n-6 and total saturates in their RBC membranes compared to controls, while 24:0, 22:5n-6, 24:1 and the 20:4n-6/20:5n-3 ratio were significantly higher in both regressive autism and ASP groups compared to controls. By comparison, the 18:1n-9 and 20:4n-6 values were significantly lower in patients with regressive autism compared to controls while 22:5n-3, total n-3 and total dimethyl acetals were significantly lower in both regressive autism and ASP groups compared to controls. Storage of RBC at -20 degrees C for 6 weeks resulted in significant reductions in highly unsaturated fatty acid levels in polar lipids of patients with regressive autism, compared to patients with classical autism or ASP, or controls. Patients diagnosed with both autism and ASP showed significantly increased levels of EPA ( approximately 200%) and DHA ( approximately 40%), and significantly reduced levels of ARA ( approximately 20%), 20:3n-6 and ARA/EPA ratio in their RBC polar lipids, when supplemented with EPA-rich fish oils, compared to controls and non-supplemented patients with autism. Patients with both regressive autism and classical autism/Asperger's syndrome had significantly higher concentrations of RBC type IV phospholipase A2 compared to controls. However, patients with autism/ASP, who had taken EPA supplements, had significantly reduced PLA2 concentrations compared to unsupplemented patients with classical autism or ASP.

Asperger Syndrome↗
PubMed2004

Effects of a cancer genetics education programme on clinician knowledge and practice.

BACKGROUND: Many clinicians lack adequate knowledge about emerging standards of care related to genetic cancer risk assessment and the features of hereditary cancer needed to identify patients at risk. OBJECTIVE: To determine how a clinical cancer genetics education programme for community based clinicians affected participant knowledge and changed clinical practice. METHODS: The effects of the programme on participant knowledge and changes in clinical practice were measured through pre and post session knowledge questionnaires completed by 710 participants and practice impact surveys completed after one year by 69 out of 114 eligible annual conference participants sampled. RESULTS: Respondents showed a 40% average increase in specific cancer genetics knowledge. Respondents to the post course survey reported that they used course information and materials to counsel and refer patients for hereditary cancer risk assessment (77%), shared course information with other clinicians (83%), and wanted additional cancer genetics education (80%). CONCLUSIONS: There was a significant immediate gain in cancer genetics knowledge among participants in a targeted outreach programme, and subset analysis indicated a positive long term effect on clinical practice. Clinician education that incorporates evidence based content and case based learning should lead to better identification and care of individuals with increased cancer risk.

Curriculum↗
PubMed2000

Hereditary cancers in children and ethical and psychosocial implications.

This article describes the application of genetic testing of children for hereditary cancers and the resultant ethical and psychosocial implications. Basic cancer genetics concepts are reviewed. Specific hereditary cancers that may affect children are described along with case examples and recommendations for nursing practice.

Adenomatous Polyposis Coli↗
PubMed2000

Directional wall strength in saccular brain aneurysms from polarized light microscopy.

The aneurysm wall, which must withstand arterial blood pressure, is composed of layered collagen. Wall strength is related to both collagen fiber strength and orientation. When the aneurysm enlarges, the amount and organization of the collagen fibers change, potentially increasing the risk of rupture. We studied the directional organization and molecular strength of the collagen fibers layer by layer across the walls of four aneurysms in order to measure their mechanical integrity. The technique incorporates the birefringent properties of collagen, enabling us to use linearly polarized light for measuring the orientation of the fibers, and the Sénarmont compensator to measure the birefringence and thus mechanical strength. Intact aneurysms were obtained at autopsy, fixed at physiological pressure, sectioned at 4 microm, and stained with 0.05% picrosirius red. By combining birefringence and orientation data we estimated tensile strength as a function of direction on the aneurysmal wall. The average breaking strength of the wall ranged from 0.73 to 1.9 MPa. Comparing the weakest to the strongest direction, the breaking strength varied by a factor of up to 2X, implying a significant degree of mechanical anisotropy.

Adult↗
PubMed1998

Genetic predisposition testing for cancer: effects on families' lives.

Genetic testing to identify a predisposition to the development of cancer affects not only the person undergoing DNA analysis but also his or her entire family. Multiple complex issues arise in conjunction with the clinical application of this new tool for assessing cancer risk. Counseling families regarding genetic risk is multifaceted and requires genetic knowledge that may go beyond the expertise of the health care provider. The article describes the psychosocial effects of cancer predisposition testing on families, ethical and social concerns of cancer risk testing, and implications for nurses in counseling individuals and families considering predisposition testing.

Adolescent↗
PubMed1997

Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer.

BACKGROUND: Germ-line mutations in the BRCA1 and BRCA2 genes predispose women to breast cancer. BRCA1 mutations are found in approximately 12 percent of women with breast cancer of early onset, and the specific mutation causing a deletion of adenine and guanine (185delAG), which is present in 1 percent of the Ashkenazi Jewish population, contributes to 21 percent of breast cancers among young Jewish women. The contribution of BRCA2 mutations to breast cancer of early onset is unknown. METHODS: Lymphocyte specimens from 73 women with breast cancer diagnosed by the age of 32 were studied for heterozygous mutations of BRCA2 by a complementary-DNA-based protein-truncation assay, followed by automated nucleotide sequencing. In addition, specimens from 39 Jewish women with breast cancer diagnosed by the age of 40 were tested for specific mutations by an allele-specific polymerase chain reaction. RESULTS: Definite BRCA2 mutations were found in 2 of the 73 women with early-onset breast cancer (2.7 percent; 95 percent confidence interval, 0.4 to 9.6 percent), suggesting that BRCA2 is associated with fewer cases than BRCA1 (P=0.03). The specific BRCA2 mutation causing a deletion of thymine (6174delT), which is found in 1.3 percent of the Ashkenazi Jewish population, was observed in 1 of the 39 young Jewish women with breast cancer (2.6 percent; 95 percent confidence interval, 0.09 to 13.5 percent), indicating that it has a small role as a risk factor for early-onset breast cancer. Among young women with breast cancer, there are BRCA2 mutations that cause truncation of the extreme C terminus of the protein and that may be functionally silent, along with definite truncating mutations. CONCLUSIONS: Germ-line mutations in BRCA2 contribute to fewer cases of breast cancer among young women than do mutations in BRCA1. Carriers of BRCA2 mutations may have a smaller increase in the risk of early-onset breast cancer.

Adult↗
PubMed1997

The oncology nurse's role in cancer risk assessment and counseling.

OBJECTIVE: To provide a comprehensive overview of the role of the oncology nurse in cancer risk assessment and counseling. DATA SOURCES: Review articles, research studies, and book chapters. CONCLUSION: New genetic discoveries are changing how risk for some cancers is being determined and managed. Cancer risk counseling and genetic testing are emerging components of clinical care. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses will have an increasingly important role in casefinding, risk assessment, education, counseling, psychosocial support, health advocacy, and the coordination of services and referrals for cancer risk management. In addition, nurses can conduct research on the effects of these new genetic applications on individuals and families, and educate others about the implications of this evolving field.

Genetic Counseling↗
PubMed1997

Presymptomatic and predisposition genetic testing: ethical and social considerations.

OBJECTIVE: To provide an overview of the ethical and social concerns that are raised by the use of new genetic tests in asymptomatic persons. DATA SOURCES: Review articles, research studies and legislation related to genetic testing. CONCLUSIONS: Predisposition and presymptomatic testing is possible to any age for adult onset disorders if a mutation is known. Testing without early effective interventions is controversial, especially prenatally and in children. Issues of privacy, discrimination, stigmatization and emotional stress are potential problems. Informed consent is essential before deciding to test. Awareness of the implications of testing can enhance the nurse's advocacy role. IMPLICATIONS FOR NURSING PRACTICE: More studies are necessary to identify the impact of presymptomatic testing on adults and children. Nursing research to identify the family concerns, and to develop effective educational, counseling, and supportive interventions would make a valuable contribution.

Adult↗
PubMed1997

Heterozygous ATM mutations do not contribute to early onset of breast cancer.

Ataxia telangiectasia (AT) is a recessive syndrome, including cerebellar degeneration, immunologic defects and cancer predisposition, attributed to mutations in the recently isolated ATM (ataxia telangiectasia, mutated) gene. AT is diagnosed in 1/40,000 to 1/100,000 live births, with carriers calculated to comprise approximately 1% of the population. Studies of AT families have suggested that female relatives presumed to be carriers have a 5 to 8-fold increased risk for developing breast cancer, raising the possibility that germline ATM mutations may account for approximately 5% of all breast cancer cases. The increased risk for breast cancer reported for AT family members has been most evident among younger women, leading to an age-specific relative risk model predicting that 8% of breast cancer in women under age 40 arises in AT carriers, compared with 2% of cases between 40-59 years. To test this hypothesis, we undertook a germ-line mutational analysis of the ATM gene in a population of women with early onset of breast cancer, using a protein truncation (PTT) assay to detect chain-terminating mutations, which account for 90% of mutations identified in children with AT. We detected a heterozygous ATM mutation in 2/202 (1%) controls, consistent with the frequency of AT carriers predicted from epidemiologic studies. ATM mutations were present in only 2/401 (0.5%) women with early onset of breast cancer (P = 0.6). We conclude that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer.

Adult↗
PubMed1996

Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: analysis of a clinic-based population.

Five to ten percent of individuals with melanoma have another affected family member, suggesting familial predisposition. Germ-line mutations in the cyclin-dependent kinase (CDK) inhibitor p16 have been reported in a subset of melanoma pedigrees, but their prevalence is unknown in more common cases of familial melanoma that do not involve large families with multiple affected members. We screened for germ-line mutations in p16 and in two other candidate melanoma genes, p19ARF and CDK4, in 33 consecutive patients treated for melanoma; these patients had at least one affected first or second degree relative (28 independent families). Five independent, definitive p16 mutations were detected (18%, 95% confidence interval: 6%, 37%), including one nonsense, one disease-associated missense, and three small deletions. No mutations were detected in CDK4. Disease-associated mutations in p19ARF, whose transcript is derived in part from an alternative codon reading frame of p16, were only detected in patients who also had mutations inactivating p16. We conclude that germ-line p16 mutations are present in a significant fraction of individuals who have melanoma and a positive family history.

Base Sequence↗
PubMed1996

Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer.

BACKGROUND: Mutations in a germ-line allele of the BRCA1 gene contribute to the familial breast cancer syndrome. However, the prevalence of these mutations is unknown in women with breast cancer who do not have the features of this familial syndrome. We sought BRCA1 mutations in women who were given a diagnosis of breast cancer at an early age, because early onset is characteristic of a genetic predisposition to cancer. METHODS: Clinical information and peripheral-blood mononuclear cells were obtained from 418 women from the Boston metropolitan area in whom breast cancer was diagnosed at or before the age of 40. A comprehensive BRCA1 mutational analysis, involving automated nucleotide sequencing and a protein-truncation assay, was undertaken in 30 of these women, who had breast cancer before the age of 30. In addition, the BRCA1 mutation 185delAG, which is prevalent in the Ashkenazi Jewish population, was sought with an allele-specific polymerase-chain-reaction assay in 39 Jewish women among the 418 women who had breast cancer at or before the age of 40. RESULTS: Among 30 women with breast cancer before the age of 30, 4 (13 percent) had definite, chain-terminating mutations and 1 had a missense mutation. Two of the four Jewish women in this cohort had the 185delAG mutation. Among the 39 Jewish women with breast cancer at or before the age of 40, 8 (21 percent) carried the 185delAG mutation (95 percent confidence interval, 9 to 36 percent). CONCLUSIONS: Germ-line BRCA1 mutations can be present in young women with breast cancer who do not belong to families with multiple affected members. The specific BRCA1 mutation known as 185delAG is strongly associated with the onset of breast cancer in Jewish women before the age of 40.

Adult↗
PubMed1996

Perception of breast cancer risk among women in breast center and primary care settings: correlation with age and family history of breast cancer.

BACKGROUND: A great deal of information about breast cancer risk is available to the public. The accuracy of impressions formed from this information is unknown. METHODS: A total of 750 women attending a breast center and 112 women attending a primary care office completed written surveys of their perceptions of average population risk, personal lifetime risk, and personal 10-year risk of getting breast cancer. Data sufficient to apply the Gail model were obtained, and a calculated estimate of risk was generated. Ratios of perceived to calculated risk were correlated with the respondent's age, family history of breast cancer, and location in a breast center or primary care office. RESULTS: Women in both practice settings overestimated population risk by more than twofold. Eighty percent overestimated personal lifetime risk by more than 50% and 35% by more than fivefold. Only 7% significantly underestimated risk. Ten-year risk estimates were even more inaccurate, with 69% overestimating risk by more than fivefold, 46% by more than 10-fold, and 17% by more than 20-fold. Results from a primary care population were nearly identical. Women at the extremes of age were most inaccurate in estimating risk. It was surprising that family history had little impact on perception of personal risk. CONCLUSIONS: Women in both breast center and primary care settings have a fals:ly high perception of both short-term and long-term breast cancer risk. Health care providers should recognize these misconceptions and be aware that many women may benefit from risk counseling.

Adult↗
PubMed1985

A pilot study of the frequency and significance of placental villitis.

The prevalence of inflammatory villous lesions was determined in a prospective study of 120 consecutive placentas. Cord blood IgM level was measured as an indicator of fetal intrauterine infection, and the birthweights of the infants were noted. Ten cases of villitis were found. Two infants had elevated cord blood IgM and one of them also had amniotic infection. As only one case of villitis had corroborative evidence of transplacental intrauterine infection, 90% of the lesions require an alternative explanation. The severity of the lesions correlated with the presence of low birthweight. The quality of the inflammatory infiltrate was also considered. Only one case included plasma cells; the remainder showed lymphohistiocytic infiltration. The case with plasmacytic infiltration was the one with elevated cord blood IgM. It is concluded that placental villitis is usually not an infective condition and its aetiology remains unknown.

Birth Weight↗
PubMed1984

Enzyme immunoassay for pregnancy-associated plasma protein-A.

This enzyme immunoassay procedure for pregnancy-associated plasma protein type A involves a "sandwich"-type system in microtitration plates. One can detect 0.27 mg of the protein per liter of serum, with a between-batch CV of 10.2%, and the antiserum used does not cross react with any of the other placentally derived proteins. A reference interval for the last trimester of pregnancy is presented. The procedure described is suitable for studying the behavior of this protein during pregnancy.

Cross Reactions↗
PubMed1983

A prospective study of three biochemical fetoplacental tests: serum human placental lactogen, pregnancy-specific beta 1-glycoprotein, and urinary estrogens, and their relationship to placental insufficiency.

The relationship between abnormal biochemical fetoplacental test results and placental insufficiency was studied in a group of high-risk obstetric patients. The urinary estrogen: creatinine ratio and serum human placental lactogen (hPL) and pregnancy-specific beta 1-glycoprotein (SP1) were measured in more than 1,600 patients. Fifty-one patients were found to have abnormal biochemical results, and the placentas from these patients were sent for the assessment of placental insufficiency by pathologic examination, which was expressed as a placental insufficiency score. Low hPL was found to be the best biochemical indicator of placental insufficiency, and 84% of the patients with a low level of hPL had an elevated placental insufficiency score. The combination of low levels of hPL and urinary estrogen was found to be the best indicator of placental insufficiency associated with retarded intrauterine growth, and 83% of the patients who had low results in both of these tests had elevated placental insufficiency scores and were delivered of light-for-dates infants. The measurement of SP1 was found to be of limited value in detecting retarded growth, but patients with low SP1 values showed an increased incidence of fetal hypoxia. Attention is drawn to the fact that the discrepancies that occur in the various estimations are not necessarily due to artifact, and specific pathologic processes which could account for some of the anomalous results are identified.

Apgar Score↗