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Biomedical subjects

D C Hughes

Publications and source records attributed to D C Hughes.

50 records · Page 3Linked to original sources

RAS mutations in patients following cytotoxic therapy for lymphoma.

The occurrence of Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukaemia (AML) following cytotoxic therapy for neoplastic disease is well recognised. RAS mutations are common in patients with MDS and AML. To determine whether these lesions are found as early markers of secondary disease, we have studied the incidence of RAS mutations in the peripheral blood of 70 patients in complete remission from lymphoma. Patients were treated by standard chemotherapy regimes and/or localised radiotherapy. Treatment had been given 6 months to 14 1/2 years previously and no patient showed any sign of residual disease. Genomic DNA from peripheral blood leukocytes was amplified in vitro at target codons of N, K and H RAS genes, and mutations detected by hybridisation with oligonucleotide probes. RAS mutations were detected in 9 subjects. One patient with an N12 valine (Val) substitution had been in complete remission from Hodgkin's disease (HD) for 9 years. DNA from this patient registered in a nude mouse tumorigenicity assay (NMT). The N12 Val mutation was not detected in the original tumour tissue from the same patient. A second patient in remission from HD showed evidence of co-existent N12 cysteine (Cys) and N13 valine (Val) substitutions which were not detected in presentation material or unaffected tissues. All patients are currently haematologically normal, indicating that clones of mutant RAS bearing cells may be detected prior to any overt sign of disease.

Animals↗

Social support and the outcome of major depression.

One hundred and fifty middle-aged and elderly adults with a diagnosis of major depression were assessed initially as in-patients, and were reinterviewed 6-32 months later. Both size of social network and subjective social support were significant predictors of depressive symptoms at follow-up, with baseline depression scores and other predictors of outcome status statistically controlled. Subjective social support was most strongly associated with major depression; this effect was significantly stronger for middle-aged than older adults, and for men than women. Differences in the effects of marital status, size of social network, and subjective social support also suggest the importance of distinguishing between involvement in and quality of interpersonal relationships.

Adult↗

ras mutations in human melanotic lesions: K-ras activation is a frequent and early event in melanoma development.

We have used polymerase chain reaction (PCR), an amplification procedure, and oligonucleotide hybridization to detect ras gene point mutations in DNA from melanoma tumor samples. Genomic DNA was examined from 40 specimens of melanotic lesions, including benign nevi, primary melanomas, lymph node metastases, and systemic metastases. Adjacent normal skin or peripheral blood was analyzed as control material in 28 cases. ras mutations were detected overall in 25% of malignant tumors. In addition, mutations of all three ras genes were detected. We observed ras mutations in 2 of 4 benign atypical nevi (2 X K12), 4 of 22 primary melanomas (3 X K12, 1 X H12, 1 X N61), and 4 of 14 secondary (5 X K12, 1 X N61) tumors. One with a primary melanoma had concurrent K12 and H12, and two patients with secondary tumors had concurrent K12/N61 and K12 Asp/K12 Val mutations, respectively, making a total of 10 of 40 (25%) patients with ras mutations. This is the first demonstration of K-ras mutations in human melanoma. The presence of K-ras mutations in nevi, putative melanoma precursors, suggests that ras activation may be an early event in melanoma development. No correlation between tumor thickness and the presence of a ras mutation was observed.

Adult↗

Maternal and child health services for medically indigent children and pregnant women.

Millions of low-income children and women of childbearing age are completely uninsured. Medicaid, the nation's largest public health financing program for the poor, is an inadequate resource for uninsured families with children. By 1984, the program served only 46% of the poor and near-poor, down from 65% in 1976. To assess the availability of maternity and pediatric services for low income uninsured women and children, a survey of 51 Title V Maternal and Child Health agency officials was conducted in 1986. While nearly all states (48) offer some prenatal care programs for indigent women, restrictive eligibility requirements and limited distribution meant that these programs reached only a small proportion of those in need. Only one state, Massachusetts, offered a truly statewide program to all uninsured pregnant women with incomes under 185% of the poverty level. Twenty-three states reported the existence of inpatient maternity programs for indigent women. Yet these, too, were extremely limited. Sixteen programs restricted funds either to women who participated in certain designated maternity programs or else only to those who were identified as high risk prior to the labor and delivery period. Fifteen state agencies reported that hospitals were denying admission to women about to deliver. Another 13 reported that hospitals were denying admission to women not yet in "active" labor. Six additional states were aware of patient dumping but did not identify the specific populations that were affected. Forty-six states reported the existence of pediatric outpatient programs. However, the majority (30) offered only "well-child" care. Seven states maintained pediatric programs limited to only certain ages of children; three of these imposed an age requirement as low as 2 years or younger. Only two states reported the availability of any pediatric inpatient programs financed or administered by Title V agencies other than those for children with special health care needs.

Child↗

Age differences in life events: a multivariate controlled analysis.

Effects of age on the distribution of specific life events experienced during the past year by community-based adults were examined controlling for sex, race, education, marital status, and place of residence. The controlled analyses were done using logistic regression. Data were gathered via personal interview from 3,798 respondents ages eighteen years and over who participated in the Epidemiologic Catchment Area (ECA), community survey from North Carolina. Respondents were placed in one of four age groups. The percentage of respondents reporting each of the nineteen events examined ranged from 0.5 percent for death of spouse to 19.1 percent for death of loved one. Age was an important predictor in the controlled analysis for thirteen of the seventeen life events examined. A majority of differences occurred between the youngest and oldest age groups. Age differences were not found for illness of one week or more involving activity limitation.

Adolescent↗

Major depression with melancholia: a comparison of middle-aged and elderly adults.

Patients admitted to an inpatient psychiatric service were screened to identify middle-aged (35 to 50 years of age) and elderly (60 years of age and over) patients suffering from a major depressive episode with melancholia. Thirty-seven subjects (18 middle-aged and 19 elderly) were identified. Criteria symptoms for depression and symptoms specifically associated with melancholic or endogenous depression did not differ across age groups, with few exceptions. Major depression with melancholia in this hospitalized population was symptomatically similar in the middle-aged and elderly. The syndrome is therefore relatively common on this inpatient service and should be easily recognized.

Adult↗

Organizational position and perceptions of problems in a nursing home.

This paper examines perceptions of problems expressed by persons living and working in a 100-bed skilled nursing home. Data were obtained from administrative staff, professional and nonprofessional nursing staffs, therapy staff, auxiliary staff, and residents by means of interview, observation, and analyses of records. The relationship between perceptions of problems and location within the organization and the scope and content of roles played was studied. We sought to ascertain the extent to which members agree or disagree with one another as to what are problems, to locate areas of agreement and disagreement, and to relate the results to the broader issue of the quality of care provided elderly institutionalized persons. Position and associated roles of members were found to be related to perceptions of problems. Differential perceptions of the numbers of problems and their priority were observed. Some problems were mentioned more frequently than others. Perceptions of problems varied both within and between organizational units. A person's location within the nursing home was related to the identification of problems as important and the frequency with which different problems were mentioned.

Adult↗

A statistical analysis of the classification of depression in a mixed community and clinical sample.

Depressive symptoms in three samples are assessed using grade-of-membership analysis to clarify the distribution of depressive symptoms across traditional affective diagnoses. The technique is used to examine whether depressive symptoms and symptoms frequently associated with depressive disorders cluster into recognizable syndromes or pure types that parallel current operational diagnoses. Three hundred and ninety subjects were studied to address the question: among a mixed population with a range of depressive symptoms, will syndromes resembling endogenous depression and demoralization emerge from the range of presentation of depressive symptoms? A single pure type is nearly identical to the DSM-III classification of major depression with melancholia. No such pure type emerged that resembled demoralization.

Adult↗

Abbreviating the Duke Social Support Index for use in chronically ill elderly individuals.

The 35-item Duke Social Support Index (DSSI) measures multiple dimensions of social support and has been used extensively in cross-sectional and longitudinal studies of aging. Epidemiological studies of chronically ill, frail elderly individuals often wish to include a measure of social support. However, most multidimensional measures (including the DSSI) are long and may exhaust the patient, especially when included in an often already congested interview schedule. The authors have developed two abbreviated versions of the DSSI (23-item and 11-item) that capture the essential components of social support related to mental health outcomes and use of health services in treating elderly individuals with nonpsychiatric medical illness.

Adaptation, Psychological↗

Paradigms and paradoxes: mouse (and human) models of genetic deafness.

Mouse models have proved valuable tools in the analysis of human genetic disorders. The identification of the genes mutated in classical mouse mutants and the analysis of the phenotype of mutants following targeted gene disruption have provided some clarification of the development and functioning of the inner ear. A number of these genes also play a role in human deafness. Analysis of mutations in both human and mouse deafness genes has identified a number of distinct phenomena that contribute to the observed phenotype.

Animals↗

Prenatal care and public policy: lessons for promoting women's health.

One of the most notable health-related legislative achievements of the 1980s was the expansion that transformed Medicaid from a medical assistance program for a relatively small group of the very poorest mothers meeting strict categorical criteria to a health program for low-income uninsured, pregnant women and their children, regardless of work status or family composition. Yet Medicaid coverage remains unavailable to millions of poor and uninsured women who are significantly less likely to obtain needed care without health insurance. Among the factors that help explain why Medicaid was not simultaneously expanded for uninsured women are our nation's longstanding reluctance to provide public assistance except to individuals deemed "deserving" based on the circumstances that led to their indigency. Another factor is the special value our culture places on pregnancy, which permits pregnant women who do not meet the definitions of the "deserving" to transcend those restrictions. Finally, while data served as an effective tool in the campaign for pregnant women's coverage, comparable data related to nonpregnant women are limited. Nonetheless, the lessons from the Medicaid expansion are helpful in efforts to improve women's access to care in general.

Female↗

Managed care and children: an overview.

This article lays the foundation for the other articles in this journal issue, which examine the effect of managed health care arrangements on a particular population: children. Although managed care has been used to finance and deliver health care services for decades, the meaning of this term often has been unclear to health care consumers and practitioners because new forms of managed care have evolved rapidly. The one consistent and unifying concept across all managed care arrangements is that enrollees obtain care from a network of participating health care providers who contract with the managed care organization and abide by the organization's rules. The uncertainty of what managed care is has made it difficult to measure the effect of these arrangements on health service delivery and health outcomes, especially in the pediatric population, where the development of outcome and quality measures lags behind that for adults. The incentives posed by managed care suggest both potential advantages and disadvantages to these arrangements for children. On the positive side, managed care enrollment may offer a "medical home" for primary care services to children who otherwise would obtain only episodic care; improve the coordination of health care services; and encourage more preventive health services. On the negative side, under capitated reimbursement, health plans have an incentive to enroll only healthy children with the lowest expected health care expenditures, and providers have an incentive to offer fewer services than may be appropriate. Managed care also may limit enrollees' choice of providers, particularly for specialty care. Despite the paucity of information about the effect of managed care on the delivery of pediatric health services and on child health outcomes, children are disproportionately being enrolled in managed care plans.

Adult↗