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Biomedical subjects

T M King

Publications and source records attributed to T M King.

At least 19 recordsLinked to original sources
PubMed1997

A clinical trial to evaluate the effect of vitamin C supplementation on in vitro mutagen sensitivity. The University of Texas M. D. Anderson Clinical Community Oncology Program Network.

Mutagen sensitivity, as measured by an in vitro assay, has been described as a risk factor for the development of several tobacco-related epithelial cancers. In vitro studies have indicated that sensitivity to the clastogenic effects of bleomycin on chromosomes was reduced with the introduction of ascorbic acid in a dose-dependent relationship. We report the results of a randomized clinical trial to determine whether increasing levels of oral ascorbic acid could reduce the levels of mutagen sensitivity. For this study, we recruited 228 healthy smokers from 21 centers around the country through the Clinical Community Oncology Program. Each individual was randomly assigned to one of four daily regimens: placebo, 1 g of ascorbic acid, 2 g of ascorbic acid, or 4 g of ascorbic acid. Treatments were administered for 16 weeks. Assessment of mutagen sensitivity was made at baseline and at weeks 4, 16, and 20 (4 weeks after cessation of treatment). Serum ascorbic acid levels were measured at baseline and at weeks 4 and 16. Demographic and risk factor data were collected at baseline and at each-measurement point. Analyses measured the differences of mutagen sensitivity levels across the four treatment arms, as well as investigating the correlation between serum ascorbic acid level and mutagen sensitivity levels in individuals. We did not find a dose-response relationship between ascorbic acid intake and mutagen sensitivity. Additionally, we did not find an association between serum ascorbic acid levels and mutagen sensitivity.

Administration, Oral↗
PubMed1996

Morphological and electrophysiological properties of neurons in an area of the chick brain involved in learning.

The intermediate, medial part of the hyperstriatum ventrale (IMHV) is an area of the avian forebrain which is essential for two forms of early learning in the domestic chick. We have developed an in vitro slice preparation which contains part of the IMHV and have found that the electrophysiological properties of the area show a considerable degree of plasticity. In particular, age and prior learning appear to modify the properties of single neurons recorded intracellularly. We have used the in vitro slice preparation to make intracellular recordings from 38 single neurons in the IMHV and have then dye-injected each cell to find out whether there is any relationship between electrophysiological and morphological characteristics. The basic membrane properties of each neuron were measured. Responses to standard electrical stimuli, delivered extracellularly, were also recorded, and each neuron was classified on this basis. Finally, the presence or absence of spontaneously occurring bursts of EPSPs was noted. At the end of recording biocytin was injected into the cell. After the tissue had been processed, each cell was drawn. The area of the cell body was measured, the number of dendrites was counted, and dendritic extent and branching were estimated. Each cell was also classified as 'spiny' or 'non-spiny'. We found that neurons displaying one particular type of response to external stimulation possessed a well defined set of morphological and electrical properties. In addition, three parameters--electrical resistance, somatic area, and the presence or absence of dendritic spines--were related to specific subsets of anatomical and physiological characteristics. The possible relevance of these findings to the plasticity of the IMHV is discussed.

Animals↗
PubMed1996

Inheritance of susceptibility to bleomycin-induced pulmonary fibrosis in the mouse.

Based on the range of patient responses to treatment, and on animal studies, it is hypothesized that individual variation in sensitivity to bleomycin-induced pulmonary fibrosis is controlled genetically. A genetic model has been developed by (a) establishing a distinct difference in bleomycin-induced lung damage in two inbred strains of mice [parental generation: C57BL/6J (fibrosis-prone phenotype) and C3Hf/Kam (fibrosis-resistant phenotype)] and (b) characterizing inheritance of the fibrosing phenotype in the F1 (first filial) and F2 (F1 intercross; second filial) generations derived from the parental strains. Male mice received 100 mg/kg and female mice 125 mg/kg of bleomycin via s.c. osmotic minipump. The animals were sacrificed 8 weeks after treatment or when their breathing rate indicated respiratory distress. The percentage of lung with fibrosis for each mouse was quantified with image analysis of a histological section of the left lung. The mean percentage of fibrosis for the C57BL/6J males was 8.4 +/- 0.8% (SE) and 4.4 +/- 0.8% for females, and the C3Hf/Kam mice of either sex did not present the fibrosing lesion (mean score, 0%). Significant difference (P = 6 x 10(-6)) was measured in percentage of fibrosis between the two strains of F1 males, but not F1 females (P = 0.38), suggesting the presence of an X-linked factor associated with the fibrosing phenotype. From an ANOVA the X-linked factor is estimated to contribute 19% of the fibrosis phenotype. A genetic model of two or three loci controlling the fibrosing phenotype is proposed from the data of the parental, F1, and F2 generations. The mouse model demonstrates that susceptibility to bleomycin-induced pulmonary fibrosis is a heritable trait controlled by a few genetic loci.

Animals↗
PubMed1996

Electrophysiological correlates of prior training: an in vitro study of an area of the avian brain which is essential for early learning.

Day-old domestic chicks will peck at any small, distinct object, such as a metal bead. One-trial passive avoidance learning can be established by coating the metal bead with methyl anthranilate (MeA) and allowing the birds to peck it once, after which they conspicuously avoid it. We have used birds successfully trained not to peck metal beads, and a control set of chicks where the training beads were innocuously dipped in water. Brain slices were prepared from both groups, containing the left, intermediate, medial part of the hyperstriatum ventrale (IMHV)--a region essential for this form of early learning. The electrophysiological properties of neurones in the IMHV were examined in vitro. Neurones recorded intracellularly in slices taken from MeA-trained birds had higher membrane resistances than did cells from water-trained controls. MeA training was also associated with an increased incidence of spontaneous, large EPSPs. Field responses to local electrical stimulation appeared to be somewhat greater in MeA-trained birds than in water-trained controls. In contrast, field potentials proved harder to potentiate with a burst of relatively high frequency stimulation in MeA-trained birds: the change in amplitude was less in MeA-trained birds, and there was less variability than in slices from water-trained controls.

Analysis of Variance↗
PubMed1996

Comparison of methods for survival analysis of dependent data.

Analysis of dependent survival data by conventional partial likelihood methods produces unbiased estimates of the regression coefficients but incorrectly estimates their variance. Here we compared the conventional partial likelihood methods with two alternative methods for analyzing dependent survival data. The first alternative method estimated the regression coefficient by the partial likelihood approach but adjusted the variance to account for clustering. The second alternative method used marginal likelihoods to estimate both the regression coefficient and its variance. We evaluated the performance of the three methods using simulated and actual data. Simulated data were used to examine bias, efficiency, type I errors, and power. An Old Order Amish genealogy was analyzed under these models to illustrate their performance on real data. The simulation study showed that all three methods provided unbiased estimates of the regression coefficient, but the efficiency of the estimated regression coefficient varied according to the simulation conditions. The standard partial likelihood method showed increasing type I error as the dependence increased within clusters. Both alternative methods had acceptable levels of type I errors at all dependence levels. In the analysis of genealogic data, the regression coefficient was similar in the three methods showing stable estimates of the regression coefficients. The variance estimates from the alternative methods were slightly different from the conventional method, suggesting a flow level of dependence. This study displays the effect of violating the independence assumption and provides guidelines for using alternative statistical methods.

Analysis of Variance↗
PubMed1996

Effect of systemic steroids on ileal pouch-anal anastomosis in patients with ulcerative colitis.

BACKGROUND: Long-term steroid therapy predisposes to postsurgical complications, especially in patients with inflammatory bowel disease. PURPOSE: This study was undertaken to determine incidence of early septic complications after ileal pouch-anal anastomosis (IPAA) in patients who are undergoing prolonged steroid therapy. METHODS: We reviewed charts of 692 patients undergoing restorative proctocolectomy and IPAA to treat ulcerative colitis. Incidence of early (within 30 days) septic complications and sepsis-related reoperations, in patients who were having high-dose (>20 mg of prednisone per day) and low-dose steroid therapy (<20 mg of prednisone per day) for more than one month before surgery, was compared with patients who were not receiving steroid therapy. Follow-up included an annual questionnaire and physical examination. RESULTS: Patients without steroid dose data recorded were excluded (n = 21). Of the 671 remaining patients, 310 received no steroids, 169 received low-dose steroids, and 192 received high-dose steroids. These three groups were similar in gender composition, age at surgery, types of anastomosis (stapled or handsewn), and incidence of diabetes mellitus, peripheral vascular disease, and obesity. Early septic complications were found in 18 (6 percent), 14 (8 percent), and 12 (6 percent) patients without steroid therapy, those having low-dose steroid therapy, and those having high-dose steroid therapy (P = 0.57), respectively. Sepsis- related reoperation rate (P = 0.73) and number of sepsis-related pouch excisions (P = 0.79) did not differ between groups. In patients undergoing IPAA without ileostomy, early septic complications were found in one (3.8 percent), two (20 percent), and five (50 percent) patients without steroid treatment, low-dose steroid therapy, and high-dose steroid therapy (P = 0.004), respectively. CONCLUSION: In patients who are undergoing IPAA with diversion for ulcerative colitis, prolonged systemic steroid therapy before surgery is not associated with increased septic complications.

Adolescent↗
PubMed1996

Stapled ileal pouch anal anastomoses are safer than handsewn anastomoses in patients with ulcerative colitis.

BACKGROUND: One of the theoretic advantages of using a stapled versus handsewn ileal pouch anal anastomosis (IPAA) in restorative proctocolectomy is a reduction in septic complications. We performed this study to compare the incidence of early septic complications in patients undergoing restorative proctocolectomy with stapled or handsewn IPAA. PATIENTS AND METHODS: A chart review of 692 patients undergoing restorative proctocolectomy for treatment of ulcerative colitis was performed. The incidence of early septic complications in patients having stapled IPAA was compared to that in patients having handsewn IPAA. Follow-up studies included an annual questionnaire and physical examination. RESULTS: Of the 692 patients, 238 had handsewn IPAA and 454 had stapled IPAA; these two groups were similar in sex, duration of disease, age at surgery, and type of surgical procedure performed. In the handsewn IPAA group, 25 patients (10.5%) had 32 septic complications, and 24 required 89 reparations. In 7 patients, the pouch was excised. In the stapled IPAA group, 21 patients (4.6%) had 23 septic complications, and 14 required 40 reparations. One patient needed pouch excision. There were more patients (P=0.0001) with early septic complications, and more (P<0.0001) pouch excisions because of these complications, in patients with handsewn IPAA than in patients with stapled IPAA. The sepsis-related reoperation rates did not differ significantly. CONCLUSIONS: The stapled technique for IPAA has fewer septic complications and results in fewer sepsis-related pouch excisions, in our hands, than the handsewn technique technique, for treating patients with ulcerative colitis.

Adolescent↗
PubMed1995

Age and the effects of 2-D,L-amino-5-phosphonovalerate in an area of the chick forebrain which is essential for early learning.

The intermediate, medial part of the hyperstriatum ventrale (IMHV) is a region of the avian forebrain which is known to be essential for early learning in the domestic chick. The IMHV in an in vitro slice preparation displays two forms of synaptic plasticity. The incidence of both varies with age and is maximal between 3 and 5 days post-hatch. Since NMDA receptors are critical for at least one of these plasticities, we have investigated the relationship between age and the contribution of NMDA receptors to the field response evoked by local, low-frequency stimulation and have found that the magnitude of the NMDA-dependent component of the response varies with age peaking between 3 and 5 days post-hatch. Spontaneous neural activity, recorded intracellularly, can be completely and reversibly silenced by NMDA receptor blockade and the incidence of spontaneous activity also varies with age, peaking between 3 and 5 days. These results suggest that the IMHV contains NMDA receptors which can be activated near resting membrane potential. Either the efficiency or the numbers of these receptors is maximal at a specific point in development and their peak activity coincides with a peak in synaptic plasticity. These characteristics are similar to those reported for young mammals.

Age Factors↗
PubMed1995

Use of exact and adjusted liability scores to detect genes affecting common traits.

We used the Haseman-Elston sib-pair test to screen for linkage of markers to genes for disease susceptibility in the simulated data as given in Problem 2 of GAW9. We applied the analysis to the underlying quantitative liability trait (Q1), other covariates of Q1 (Q2-Q4), and the dichotomous affection status trait. In addition, we analyzed the residual Q1 after adjusting for the covariates. Using the sib-pair linkage test, we identified a large region of chromosome 5 affecting the residual value of Q1, a region of chromosome 2 affecting Q3, and a region of chromosome 1 possibly affecting Q2. The analysis of the dichotomous traits did not reveal any regions to be significant. This is likely to be due to lack of information since the families were not selected through affected probands.

Analysis of Variance↗
PubMed1995

Association and linkage with quantitative traits.

This paper examines two approaches for the analysis of quantitative traits: (1) association studies and (2) linkage studies. The trait studied was Q1 from simulated Problem 2 data set in Genetic Analysis Workshop 9. Our purpose was to evaluate associations present in the data, to identify nongenetic and genetic predictors of the trait, and to explore the simulated genome for linkage. Through the association study, we found evidence for the primary major gene associated with this trait. The linkage study found evidence of residual genetic effect acting through other traits. Adjustments of Q1 for Q2 and Q3 led to a failure to find significant effects of MG2 and MG3. This supports the suggestion that adjustment for genetically influenced traits for effects of other genetic traits can reduce the power to detect major gene effects. In summary, we detected the major gene directly associated with the trait of interest through association studies. Linkage analysis detected evidence for two other genes associated to a lesser degree with the trait.

Analysis of Variance↗
PubMed1995

Higher lung cancer risk for younger African-Americans with the Pro/Pro p53 genotype.

A restriction fragment length polymorphism in codon 72 of the p53 gene has been implicated in lung cancer risk, although the functional significance of the polymorphism has not been determined. This association was examined in 109 lung cancer cases (67 African-American and 42 Mexican-American) and 114 controls (74 African-American and 40 Mexican-American) identified from a molecular epidemiological study of lung cancer. The susceptible Pro/Pro genotype was associated with a 1.56-fold higher risk of lung cancer in African-Americans and a 1.95-fold in Mexican-Americans, although neither estimate was statistically significant. In fact, the prevalence of the Pro/Pro genotype was only 2.5% in Mexican-American controls, compared with 20.3% for African-American controls. Patients with the susceptible genotype appeared to have earlier age at diagnosis and lower mean cigarette pack-year exposures than did patients with the Arg/Arg or Arg/Pro genotypes. Risk estimates for the susceptible genotype were 11.29 (1.1, 111.3) for patients < 53 years of age and 14.1 (1.5, 130.6) for patients who reported < 30 pack-years of smoking. The Pro/Pro genotype was not associated with elevated risk in older patients, nor with heavier smokers. If Pro/Pro is a susceptible genotype, the lower prevalence evident in Mexican-Americans may partly explain their lower rates of lung cancer.

Aged↗
PubMed1994

Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract.

BACKGROUND: Second malignant tumors in patients successfully treated for an initial cancer of the upper aerodigestive tract are an important cause of morbidity and mortality. Biologic markers capable of identifying high-risk subgroups of patients who could be targeted for intensive clinical surveillance, therefore, have immense therapeutic and prognostic relevance. We previously demonstrated in a pilot study of 84 patients with cancers of the upper aerodigestive tract that mutagen sensitivity was a significant predictor of risk of developing second malignant tumors. PURPOSE: We extended the study to include 278 patients diagnosed with previously untreated cancers of the upper aerodigestive tract from 1987 to August 1993. METHODS: For each patient, base-line (pretreatment) mutagen sensitivity was measured in vitro in 50 metaphases established from peripheral lymphocyte cultures. Patients with an average of more than 1 chromosomal break/cell were deemed mutagen hypersensitive. Cox proportional hazards analysis was used to predict the risk of developing second malignant tumors associated with mutagen sensitivity. RESULTS: Overall, 44% of the case group exhibited mutagen hypersensitivity. There were no differences in the distribution of mutagen hypersensitivity by site, sex, stage of disease, or smoking status. There were 17 synchronous and 11 metachronous cancers, of which 15 (54%) were smoking-related malignancies. Sixteen (13.1%) of the mutagen-sensitive patients developed second malignant tumors, compared with 12 (7.7%) of the nonsensitive patients. The mean break/cell value (+/- SD) for patients developing second malignant tumors was 1.17 (+/- 0.54), compared with 0.98 (+/- 0.44) for patients with only one cancer (P = .04). Mutagen hypersensitivity conferred a relative risk of 2.67 (95% confidence interval = 1.22-5.79) of developing second malignant tumors. CONCLUSIONS: Mutagen hypersensitivity increases the risk of developing second malignant tumors. IMPLICATIONS: Future research should focus on the molecular mechanisms underlying mutagen sensitivity.

Adult↗
PubMed1993

NMDA-receptors and potentiation in an area of avian brain essential for learning.

The intermediate medial part of the hyperstriatum ventrale (IMHV), part of the avian forebrain, is essential for early learning in the domestic chick. Persistent potentiation (PP) can sometimes be induced in the IMHV in vitro. One can predict success from events which occur during the stimulation (1 min at 5 Hz) which is used for induction: the original response must be transiently replaced by a later, slower response (the LPSR). The LPSR has a comparatively high threshold of activation, its rate of development is inversely related to magnesium concentration and it can be eliminated by NMDA antagonists, as can the induction of PP. PP in the IMHV is therefore dependent upon NMDA receptors and the LPSR represents the activation of these receptors.

Animals↗
PubMed1993

Effect of laboratory or clerical error on presymptomatic risk calculations for Huntington disease: a simulation study.

Linked markers are useful in prenatal diagnosis as well as presymptomatic diagnosis in late age-of-onset diseases such as Huntington disease (HD). It is widely assumed that most laboratory or clerical errors will be detected because of incompatibility of marker haplotypes within the family. However, errors in marker phenotypes that are compatible but wrong may result in a consultand being given an incorrect risk estimate. We have addressed this issue using simulated marker data in pedigrees similar to those seen in our HD testing program. In Family Structure I (an 11-member, 3-generation family), a particular family was more likely to be detected as inconsistent than incorrectly assigned. In a small nuclear family (Family Structure IV), fewer errors would be detected, and more would appear consistent but give incorrect risk estimates (e.g., low risk misclassified as noninformative or high). Given the presence of tight linkage, risk estimates are often calculated based on a small number of relatives. However, these computer simulations demonstrated that increasing the number of relatives typed decreases the probability that the family will remain consistent with an error present, and, therefore, decreases the probability of an incorrect assignment of risk. It is important to decrease the level of such errors by duplicated readings of raw marker data and validation of computer input.

Computer Simulation↗
PubMed1993

[Rubber band ligation in the management of hemorrhoids].

During one year from November 1990 to October 1991, 1005 patients of hemorrhoids visited VGH-Kaohsiung. Among different treatments of hemorrhoid, rubber band ligation was most commonly used, with which 66% patients were treated. The follow-up at least one month in duration, discovered much improvement with this ligation in patients symptoms such as prolapse, anal bleeding and anal soiling, etc. The success rate reached higher than 90% for the first, second and third degree of hemorrhoids. About one third of 4th degree hemorrhoid got improved after ligation of their internal hemorrhoids. Except for pain feeling in the anus, the occurrence rate of other complications such as hemorrhage, anal thrombosis, constipation or dysuria was very low. With the exception of hemorrhoid of 4th degree or with large skin tag, this simple and highly successful management is the first choice for the treatment of hemorrhoids.

Adult↗
PubMed1992

Cystic fibrosis patients bearing both the common missense mutation Gly----Asp at codon 551 and the delta F508 mutation are clinically indistinguishable from delta F508 homozygotes, except for decreased risk of meconium ileus.

The glycine-to-aspartic acid missense mutation at codon 551 (G551D), which is within the first nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator (CFTR), is the third most common cystic fibrosis (CF) mutation, with a worldwide frequency of 3.1% among CF chromosomes. Regions with a high frequency correspond to areas with large populations of Celtic descent. To determine whether G551D confers a different phenotype than does delta F508, the most common CF mutation, we studied 79 compound heterozygotes for G551D/delta F508, from nine centers in Europe and North America. Each subject was matched, by age and sex, with a delta F508 homozygote from the same center. A retrospective cohort analysis was performed on the following outcome parameters: age at diagnosis, sweat chloride, meconium ileus at birth, height, weight, weight for height, FVC, FEV1, chest X-ray score, pseudomonas colonization, pancreatic sufficiency, and Shwachman clinical score. There was less meconium ileus among the G551D/delta F508 compound heterozygotes (relative risk 0.33; 95% confidence interval .13-.86), as well as a trend toward later age at diagnosis of pancreatic insufficiency. No statistically significant difference was found between the groups for any other parameter. These results suggest that the CF genotype can be a predictor of pancreatic and intestinal phenotype. Prenatal counseling for the two genotype groups should differ only with respect to probability of meconium ileus. Clinical outcome (after survival of meconium ileus) for G551D/delta F508 compound heterozygotes and delta F508 homozygotes is indistinguishable; therefore, prognostic counseling should not differ.

Adolescent↗
PubMed1990

[Two-phase test of fecal occult blood screening for colorectal cancer].

The detection of colorectal cancer in an early curable stage has become the focus of considerable interest recently. A two-phase test using both guaiac test and Hemolex latex immuno-agglutination test was applied for fecal occult blood screening of colorectal cancer. A total of 4,725 veterans aging 60 to 69 years were registered, and 2,176 persons (average age 66 years) completed the test giving a compliance rate of 46%. The positive rates of both tests were accounted 20.5% and 6.7% respectively. Five hundred and forty five persons had positive reaction for at least one of the tests. Of these, 90 had a follow up diagnosis with colonoscopy or combined with barium enema. Three rectal adenocarcinomas were detected, of which only one was positive by guaiac test, but two by Hemolex test. A rectal carcinoid was found by rectodigital examination. It was negative by both tests. Nineteen cases were detected to have one or more polyps in colon or rectum, of which only 6 were positive by guaiac test, but 18 by Hemolex test. Hemolex test using antibody against human hemoglobin is based on latex agglutination reaction. It is more sensitive and specific than guaiac test. Moreover, no dietary restriction is required. In the view point of cost-effectiveness, mass screening for colorectal cancer in general public is not recommended, but hospital-based screening for high risk group is still worthwhile to study.

Age Factors↗