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D McGee

Publications and source records attributed to D McGee.

At least 37 records · Page 2Linked to original sources

Characterization of fully 2'-modified oligoribonucleotide hetero- and homoduplex hybridization and nuclease sensitivity.

The nuclease stability and melting temperatures (Tm) were compared for fully modified oligoribonucleotide sequences containing 2'-fluoro, 2'-O-methyl, 2'-O-propyl and 2'-O-pentyl nucleotides. Duplexes formed between 2' modified oligoribonucleotides and RNA have typical A-form geometry as observed by circular dichroism spectroscopy. Modifications, with the exception of 2'-O-pentyl, were observed to increase the Tm of duplexes formed with complementary RNA. Modified homoduplexes showed significantly higher Tms, with the following Tm order: 2'-fluoro:2'fluoro > 2'-O-propyl:2'-O-propyl > 2'-O-methyl:2'-O- methyl > RNA:RNA > DNA:DNA. The nuclease stability of 2'-modified oligoribonucleotides was examined using snake venom phosphodiesterase (SVPD) and nuclease S1. The stability imparted by 2' modifications was observed to correlate with the size of the modification. An additional level of nuclease stability was present in oligoribonucleotides having the potential for forming secondary structure, but only for 2' modified oligoribonucleotides and not for 2'-deoxy oligoribonucleotides.

Base Sequence↗

Distribution of anthropometric variables and the prevalence of obesity in populations of west African origin: the International Collaborative Study on Hypertension in Blacks (ICSHIB).

A survey of the prevalence of hypertension and associated risk factors including obesity was carried out among persons of West African heritage currently living in societies at different stages of social, economic and technological development. We present here the distribution of several anthropometric variables and the prevalence of obesity in these populations. Using a standard protocol with centralized training of field staff, 7,439 men and women aged 24 to 75 from six multinational sites were recruited and examined. Although men were taller, women were more obese across sites. Body mass index (BMI) and consequently the prevalence of overweight and obesity increased with westernization from rural African subsistence farming communities to suburban Chicago. Average BMI increased with age until about age 54, and then began to decline or at least level off. The mean BMI for African-American men and women was 27.1kg/m2 and 30.8kg/m2, respectively. Men displayed high levels of centripetal fatness, measured as the waist-to-hip ratio (WHR), compared to the women across site. Based on the US Department of Agriculture guidelines, 22.6% and 56.9% of the African-American men and women had elevated WHR. Although account must be taken of the important contribution of an individual's genetic background, this multinational study of persons with similar heritage clearly shows the potent impact of current environmental factors on the distribution and level of obesity.

Adult↗

High-risk obstetric nursing role: perinatal nurse practitioner.

This article chronicles the development of the perinatal nurse practitioner (PNNP) role in providing care to high-risk obstetric patients in ambulatory and inpatient settings. Factors in the health care delivery system as well as the philosophic basis of the role are discussed. This role was modeled after neonatal nurse practitioners. Curriculum examples and role competencies are identified. Four programs are currently in existence with several more in the planning stages

Clinical Competence↗

Four-year review of cigarette ingestions in children.

The objective of our study was to assess the demographics, incidence, types of symptoms, and outcomes of cigarette product ingestions in children. The study was a retrospective database review. Seven hundred children under six years of age ingesting cigarettes or cigarette butts reported to a Poison Control Center between 1988 and 1991. Among 143 patients (20.4%) with symptoms, vomiting was the only symptom in 138 (98.6%) and occurred in less than 20 minutes in 104 (74.3%). The five remaining patients (two with vomiting, three without) developed transient lethargy or irritability that completely resolved. Forty-four of 700 patients ingested potentially toxic amounts and were referred to the emergency department; three were lost to follow-up. Initially asymptomatic patients never developed symptoms. Symptomatic patients improved without sequelae. No patient developed seizures. We concluded that significant toxicity from the ingestion of cigarette products in children is rare. Vomiting within 20 minutes is the most common symptom. Its absence predicts a favorable outcome, even when large amounts are suspected to have been ingested.

Decision Trees↗

Does heart transplantation confer additional benefit over medical therapy to patients who have waited > 6 months for heart transplantation?

OBJECTIVES: This study compared the survival of patients with heart failure who have waited > 6 months for heart transplantation with that patients who undergo heart transplantation after a similarly prolonged waiting period. BACKGROUND: There are little data describing outcome in patients with severe heart failure who have waited for extended periods of time on the heart transplant waiting list. METHODS: Sixty-three consecutive patients who spent > 6 months on the heart transplant waiting list were examined. Mean (+/- SD) age was 53 +/- 9 years, mean left ventricular ejection fraction was 19 +/- 6%, and all were taking digoxin and diuretic and vasodilator agents. Patients who underwent transplantation during the follow-up period were censored from the pretransplantation analysis, and their survival was examined as part of the posttransplantation phase of the study. RESULTS: Of the 63 original patients examined, 25 underwent transplantation, 10 during inotropic or mechanical circulatory support. The pretransplantation mortality rate was 6% at 6 months after the 6-month milestone on the waiting list, 12% at 12 months and 22% at 18 months. The posttransplantation mortality rate was 5% at 6 months, 10% at 12 months and 24% at 18 months. There were no differences in survival at any time between the two phases of the study. CONCLUSIONS: Survival of patients who have survived > 6 months on the heart transplant waiting list is generally good. Although heart transplantation did not appear to confer additional survival advantage over medical therapy, a large proportion of the patients who underwent transplantation were critically ill at the time of transplantation and would undoubtedly have died of progressive heart failure had they not undergone transplantation. We conclude that heart transplantation should still be considered a therapeutic alternative in patients with heart failure even after a prolonged waiting period on the heart transplant waiting list.

Actuarial Analysis↗

Familial aggregation of cardiovascular diseases in African-American pedigrees.

Familial aggregation of cardiovascular diseases and diabetes has been consistently demonstrated. However, virtually all of the evidence on the familial patterns of these diseases has come from white population samples. This study evaluates the level of familial excess risk among first degree relatives of 232 African-American pedigrees which included 1,420 individuals recruited from the Chicago, IL, area. Excess disease risk was observed among relatives (parents and offsprings) of affected probands compared to relatives of unaffected probands for coronary heart disease (odds ratio [OR] = 5.30; 95% confidence interval [CI] = 2.51-11.23); hypertension (OR = 1.98; CI = 1.41-2.80); stroke (OR = 3.24; CI = 1.08-9.70); and diabetes (OR = 2.95; CI = 1.55-5.62). The results of this study clearly show that coronary heart disease, hypertension, stroke, and diabetes aggregate in some African-American families and not others. Unaffected relatives of persons suffering from these diseases should be encouraged to have their blood pressure, lipid, and blood glucose levels measured at frequent intervals. These recommendations are particularly urgent in African-American communities because of the disproportionately high morbidity and mortality experienced from cardiovascular diseases and diabetes.

Adult↗

Determinants of incident non-insulin-dependent diabetes mellitus among blacks and whites in a national sample. The NHANES I Epidemiologic Follow-up Study.

The excess incidence of non-insulin-dependent diabetes mellitus noted among African Americans in the past two decades may be attributable to variations in the distribution of specific risk factors, or the impact of these risk factors may differ by ethnicity or sex. Over the 16 years (1971-1987) of the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study, 880 incident cases of diabetes mellitus developed among 11,097 white and black participants who were between the ages of 25 and 70 years at baseline. There were substantial differences among the four race/sex groups with respect to age at baseline, as well as marked differences in the distribution of several major risk factors for diabetes, including obesity, subscapular and triceps skinfold thickness, blood pressure, income, activity, and educational level. The age-adjusted incidence of diabetes over the course of the study was 15.0% among black women, while it was 10.9% among black men. White women and men experienced similar, more moderate risks of 7.0% and 6.9%, respectively. The 100% excess risk among black women and the 50% excess among black men can in large measure explain the recent marked increase in diabetes rates in the black community. Furthermore, at nearly every level of obesity, blacks had a higher risk of diabetes than whites, suggesting that other factors contributed to risk. A significant interaction between race and body mass index (weight (kg)/height(m)2) was likewise demonstrated in multivariate analysis. Baseline age, race, body mass index, and ratio of subscapular skinfold to triceps skinfold were significantly related to incident diabetes, both overall and in separate models for men and women; in the entire cohort and in women alone, blood pressure, activity level, and education also contributed to risk. Other interactions were tested but were not found to be important. Despite sampling difficulties and inconsistencies in the data, the NHANES I Epidemiologic Follow-up Study provides evidence that the associations of anthropometric and sociodemographic variables with diabetes may vary among subgroups which have different mean levels and distributions of these risk factors.

Adult↗

Evaluation of 2'-modified oligonucleotides containing 2'-deoxy gaps as antisense inhibitors of gene expression.

We have used a previously described 17-mer phosphorothioate (Monia, B.P., Johnston, J.F., Ecker, D. J., Zounes, M.A., Lima, W.F., and Freier, S.M. (1992) J. Biol. Chem. 267, 19954-19962) for structure-function analysis of 2'-sugar modifications including 2'-O-methyl, 2'-O-propyl, 2'-O-pentyl, and 2'-fluoro. These modifications were analyzed for hybridization affinity to complementary RNA and for antisense activity against the Ha-ras oncogene in cells using a highly sensitive transactivation reporter gene system. Hybridization analysis demonstrated that all of the 2'-modified oligonucleotides hybridized with greater affinity to RNA than an unmodified 2'-deoxy oligonucleotide with the rank order of affinity being 2'-fluoro > 2'-O-methyl > 2'-O-propyl > 2'-O-pentyl > 2'-deoxy. Evaluation of antisense activities of uniformly 2'-modified oligonucleotides revealed that these compounds were completely ineffective in inhibiting Ha-ras gene expression. Activity was restored if the compound contained a stretch of at least five 2'-deoxy residues. This minimum deoxy length correlated perfectly with the minimum length required for efficient RNase H activation in vitro using partially purified mammalian RNase H enzyme. These chimeric 2'-modified/deoxy phosphorothioates displayed greater antisense potencies in inhibiting Ha-ras gene expression, compared with the unmodified uniform deoxy phosphorothioate. Furthermore, antisense potency correlated directly with affinity of a given 2' modification for it's complementary RNA. These results demonstrate the importance of target affinity in the action of antisense oligonucleotides and of RNase H as a mechanism by which these compounds exert their effects.

Base Composition↗

Clonal chromosome abnormalities in human breast carcinomas. I. Twenty-eight cases with primary disease.

Cytogenetic analysis was performed on a selected series of short-term cultures of primary breast carcinomas from 28 patients. All patients had histopathologically confirmed malignancies, with the majority (25/28 cases) demonstrating infiltrating ductal carcinoma. All 28 cases evidenced clonal chromosome abnormalities, with 10/28 displaying only numeric aberrations, whereas 18/28 displayed clonal structural alterations. In near-diploid tumors the most common numeric changes were -17 and -19. However, trisomy 7 was the only numeric change in two near-diploid tumors. Structural chromosome alterations were primarily isochromosomes, apparent terminal deletions, and unbalanced non-reciprocal translocations. Chromosomes I (10/18-56%) and 6 (8/18-44%) were most frequently altered in this series. Breakpoints of clonal structural abnormalities were shown to cluster to several chromosome segments, including 1p22-q11, 3p11, 6p11-13, 7p11-q11, 8p11-q11, and 19q13. Analysis of the gain or loss of specific chromosome segments revealed that the most consistent tendency was over-representation of 1q, 3q, and 6p.

Adenocarcinoma, Mucinous↗

Clonal chromosome abnormalities in human breast carcinomas. II. Thirty-four cases with metastatic disease.

Cytogenetic analysis was performed on a selected series of short-term cultures from 34 patients with documented metastatic breast carcinoma. The majority of tumor cells were hyperdiploid, with clonal structural alterations observed in 94% of patients (32/34). The most common numeric changes were -2, -15, and -18. Chromosome 20 was the most frequently over-represented (in near-3n tumors only). Clonal structural chromosome alterations included isochromosomes, terminal deletions, and, most frequently, unbalanced non-reciprocal translocations. Chromosomes most often involved in structural rearrangements included 1, 7, 11, and 6 (accounting for 24.7%, 10.3%, 9.1%, and 7.0% of breakpoints, respectively). When the breakpoints of clonal structural abnormalities were analyzed, they were shown to cluster to several chromosome segments, including 1p11-q21, 7pter, 11p12-q12, and 6q11-21. An analysis of the net gain or loss of specific chromosome segments was also performed, with the most consistent tendency observed being the over-representation of 1q, 6p, 7, and 11. The most frequent losses included 1p, 6q, 7, and 11q.

Adult↗

Age- and gender-related differences in 24-hour esophageal pH monitoring of normal subjects.

Twenty-four-hour esophageal pH monitoring is currently the most sensitive test for diagnosing gastroesophageal reflux. Little is known, however, about the effect of aging and gender on esophageal acid exposure in asymptomatic individuals. Thirty asymptomatic volunteers underwent 24-hr esophageal pH monitoring. Fifteen were < 65 years (eight female, seven male) and 15 were > or = 65 years (seven female, eight male). In this asymptomatic group no significant difference was seen by age, while males were found to have significantly more esophageal acid exposure than females. The need for sex-specific normal 24-hr pH monitoring values is suggested. Thirty percent of these asymptomatic subjects were abnormal by conventional 24-pH criteria. The clinical importance of these "silent refluxers" is unknown.

Adult↗

Prospective study of the frequency and size distribution of polyps missed by colonoscopy.

An important determinant in interpreting the results of colorectal polyp chemoprevention trials is the rate of polyps missed during colonscopic examination. We prospectively examined 90 patients by tandem colonoscopy performed by two alternating examiners. In 69 (76.7%) patients, 221 neoplastic lesions were documented histologically. Of a total of 58 lesions detected in 31 patients, no neoplastic lesion greater than or equal to 10 mm in size was missed; 16% of diminutive (less than or equal to 5 mm) neoplastic polyps and 12.3% of medium-sized (6-9 mm) neoplastic polyps were missed by the first examiner. We conclude that an experienced colonoscopist will miss about 15% of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation. Large (greater than or equal to 10 mm) polyps were rarely missed, however, with the "miss" rate in our study equal to 0, with a 95% confidence limit of 4.64%.

Adult↗

Plasma lipoproteins in healthy octogenarians: lack of reduced high density lipoprotein cholesterol levels: results from the Framingham Heart Study.

Genetic low density lipoprotein (LDL) deficiency and high density lipoprotein (HDL) excess have been associated with enhanced longevity. This investigation assessed the prevalence of lipoprotein abnormalities in octogenarians free of clinical evidence of cardiovascular disease (CVD) in the Framingham Heart Study. Plasma lipid and lipoprotein cholesterol determinations were carried out by standard techniques between 1971 and 1974. Participants who were free of clinical evidence of CVD in an examination approximately 10 years later (1981 to 1982) had their lipoprotein values tabulated based on the earlier examination. There were 106 women and 57 men who met these criteria, with mean ages of 83.3 and 82.9 years, respectively, at examination 16 (called cases). Mean levels (+/- SEM) of LDL cholesterol in cases were 152 +/- 3 mg/dL for women, and 147 +/- 5 mg/dL for men. For HDL cholesterol, these values were 57 +/- mg/dL for women and 46 +/- 2 mg/dL for men. These values were not statistically different from those of other study subjects (who did not meet the CVD criteria or were decreased) or middle-aged controls. In contrast, HDL cholesterol levels below the tenth percentile of normal were not observed in any male cases and in only 1.0% of female cases (P less than .05) as compared with observations in control subjects. The data are consistent with the concept that there is not an overrepresentation of either decreased LDL cholesterol or elevated HDL cholesterol values in subjects who subsequently become healthy octogenarians, but that these subjects are exceedingly unlikely to have reduced HDL cholesterol levels.

Aged↗

The relationship of dietary fat and cholesterol to mortality in 10 years: the Honolulu Heart Program.

This report examines the relationship of dietary fat and dietary cholesterol to mortality during a 10-year surveillance of a cohort of men of Japanese descent residing in Hawaii. The consumption of dietary fat (measured in grams) is related inversely and significantly to total mortality. No significant relationships exist between grams of dietary fat and any of the specific causes of death examined. No significant relationships are found between dietary saturated fatty acids (SFA, measured in grams) or dietary cholesterol (measured in milligrams) and any of the specific causes of death examined. In contrast, percentage of calories as fat is related inversely not only to total mortality, but to cancer mortality and to stroke mortality; and it is related directly to coronary heart disease (CHD) mortality. Percentage of calories as SFA is related inversely to cancer mortality and to stroke mortality, and it is related directly to CHD mortality. Only the relationship to stroke mortality remains significant in multivariate analysis if calories from alcohol are excluded from the computation. Dietary cholesterol per 1000 calories is related directly to CHD mortality. While these data provide support for the diet-heart hypothesis, they also suggest that men with low fat intakes have a higher total mortality rate than men with higher fat intakes. This increased risk, due to an excess risk of death from stroke and cancer, indicates that there is no overall beneficial effect from a low fat diet in this cohort.

Aged↗

The results of logistic analyses when the variables are highly correlated: an empirical example using diet and CHD incidence.

We provide an example which includes highly correlated variables in multivariate logistic analyses relating four nutrients to the incidence of coronary heart disease in 10 years for over 7000 men. Paradoxical results occur for both the inferences to be drawn and variable selection. Different models exist which show that any particular variable both is and is not related significantly to coronary heart disease incidence, and step-up and step-down variable selection algorithms provide drastically different results.

Coronary Disease↗

Psychosocial processes and general susceptibility to chronic disease.

The concept of general susceptibility to disease has developed as a unifying explanation for the findings that a variety of diseases are associated with certain social and cultural situations. This hypothesis was tested in a prospective study of 4251 men of Japanese ancestry in Hawaii who answered a psychosocial questionnaire in 1971. The seven-year incidence rates of coronary heart disease, stroke, cancer, and all deaths during the period December 1971-January 1979 were analyzed for association with individual questions and five summary scores measuring geographic and generational mobility, sociocultural and spousal inconsistency, and social networks. Among all questions and summary scores measuring mobility and inconsistency, there was only one statistically significant association with any disease, and this association was in the opposite direction to that predicted by the hypothesis. The measures of social networks were not associated with either the incidence of stroke, cancer, or all diseases combined, but were associated with coronary heart disease, as reported in detail earlier. The authors examined the joint interaction of the postulated stressful processes of mobility and inconsistency with the protective effects of social networks, with special attention to the men in the highest levels of mobility and inconsistency. They found no significant associations, and thus there was no support for the hypothesis that social networks are especially protective among persons in the highest levels of mobility and inconsistency. The inclusion of known health hazards, cigarette smoking, and high systolic blood pressure levels did not alter these findings.

Aged↗