Search PubMed⌕ Search

Biomedical subjects

D S Miller

Publications and source records attributed to D S Miller.

At least 181 records · Page 10Linked to original sources

Psychosocial correlates of survival in advanced malignant disease?

Prospective studies of the general population have isolated specific social and psychological factors as independent predictors of longevity. This study assesses the ability of these factors, plus two others said to influence survival in patients with cancer, to predict survival and the time to relapse after a diagnosis of cancer. Patients with unresectable cancers (n = 204) were followed to determine the length of survival. Patients with Stage I or II melanoma or Stage II breast cancer (n = 155) were followed to determine the time to relapse. Analysis of data on these 359 patients indicates that social and psychological factors individually or in combination do not influence the length of survival or the time to relapse (P less than 0.10). The specific diagnosis (F = 2.0, P = 0.06), performance status (F = 0.66, P = 0.62), extent of disease (F = 1.12, P = 0.89), and therapy (F = 1.08, P = 0.35) were also unrelated to the psychosocial factors studied. Although these factors may contribute to the initiation of morbidity, the biology of the disease appears to predominate and to override the potential influence of life-style and psychosocial variables once the disease process is established.

Attitude↗

A psychological analysis of cancer patients and their next-of-kin.

A supportive family environment is thought to enhance the capacity of cancer patients to adapt to their illness and treatment. But families, like patients, vary in their ability to cope with the impact of a cancer diagnosis in a family member and in their ability to fulfill the patient's needs. Increased understanding of the interrelationships between the family's and patient's responses to illness is of fundamental importance to the care of the patient with cancer. A heterogeneous sample of 201 cancer patients and their relatives were studied to determine compatibility of psychological status and to isolate clinical and demographic variables associated with psychological distress. Self-report tests of anxiety, mood disturbance, and mental health were applied. Despite large individual variation, the psychological status of patients and their matched relatives was closely correlated. The patient's treatment status affected both patients and their next-of-kin. Psychological well-being worsened according to whether patients were receiving follow-up care, active treatment, or palliative therapy. These data suggest a mutuality of psychological response between patients and their families. Supportive intervention for the patient or relative who manifests distress, therefore, should benefit both. Because patients and relatives involved with palliative treatment are most in need of psychological assistance, particular attention should be paid to this group, as is attempted in hospice care.

Adult↗

Increased body fat due to elevated energetic efficiency following chronic administration of inhibitors of sympathetic nervous system activity.

The effects on energy balance of drugs known to inhibit the sympathetic nervous system at different sites and with various modes of action were studied in lean mice of the CFLP strain. Metabolizable energy intake was monitored continuously over seven-week experimental periods and energy expenditure was determined by the comparative carcass method as well as by measurements of 24-hour oxygen consumption. Administration of either propranolol, phenoxybenzamine, clonidine, or mecamylamine had no influence on energy balance nor on body composition. On the other hand, administration of alpha-methyl para tyrosine, reserpine, and bethanidine, ie, drugs capable of reducing the levels of noradrenaline at sympathetic terminals, resulted in significant increases in body fat by 38%, 24%, and 46% respectively: this effect was brought about by a reduction in the metabolic rate of these drug-treated groups and the efficiency of energy utilization (both gross and net) was increased by three to nine times. These studies indicate that chronic administration of drugs that act at the receptor level to inhibit sympathetic activity fail to influence metabolic rate, thereby suggesting that thermogenesis under noradrenaline control may involve mechanisms other than the alpha and beta classification of adrenergic receptors. Nonetheless, the ability of some drugs which both reduce noradrenaline levels and decrease metabolic rate would support the concept of an important role of the sympathetic nervous system in the overall control of thermogenesis and in energy balance regulation.

Adipose Tissue↗

Blood chemistry changes in food-deprived herring gulls.

Blood chemistry changes caused by food-stress was measured in fledgling herring gulls (Larus argentatus). Increases of corticosterone, T3, free fatty acids, glucose, cholesterol and alpha-amino n-butyric acid were observed. Significant decreases were found in the concentrations of 14 of the 26 free amino acids studied.

Amino Acids↗

A comparative study of the effects of white sugar, unrefined sugar and starch on the efficiency of food utilization and thermogenesis.

Energy balance studies with weanling rats and mice were carried out to investigate the chronic effects of diets containing white sugar, unrefined sugar, and starch as sole carbohydrate on body composition and energetic efficiency. The results show no significant differences in energetic efficiency and in body composition of both rats and mice fed the different carbohydrate diets. However, there is a tendency for the sugar-fed animals to have higher metabolizable energy intakes, but rarely was this sufficient to increase body energy since there were corresponding increases in metabolic rate. These studies indicate that differences in energy balance between sugar and starch are small and that any increase in thermogenesis that occurred in some of the groups fed sugar-rich diets was in response to the higher energy intake rather than due to a lower efficiency of utilization of sucrose per se.

Animals↗

Problems with the use of "weight for height" tables.

Two sets of "weight for height" reference data that are widely used internationally for children and adolescents (NCHS) and for adults (Fogarty) show a marked discontinuity such that young adults might be considered obese by one set and underweight by the other. In view of the need for continuous data for the nutritional assessment of populations, a compromise set of reference values is proposed, calculated from the NCHS data, which is considered the more reliable of the two sets. The proposed values are a single set, which may be applied to all ages and to both sexes: they are close to the Fogarty data for tall adults but for shorter adults there remains a discrepancy, which may represent an error in the Fogarty data.

Adolescent↗

Cronkhite Canada syndrome: a new hypothesis.

The occurrence of Cronkhite Canada syndrome in a 78 year old man is described. The presence of total gastrointestinal mucosal atrophy with nail loss is reported for the first time. It is suggested that the polyps represent residues of aged cells with no absorptive function and that the condition results from the loss of normal proliferative stimuli or acquired resistance to them. The primary biochemical abnormality may be in the affected epithelia but the changes here could alternatively be secondary to failure of synthesis or release of growth factors.

Aged↗

Modulation of lysyl oxidase substrate specificity by the oleate anion.

Extracts of bovine ligamentum nuchae have been assayed for lysyl oxidase activity using as substrates soluble elastin and soluble collagen labeled with tritiated lysine. The assays were performed in the presence and absence of sodium oleate. At 0.8 mM, oleate decreased activity with elastin more than 50% and enhanced activity with collagen to approximately 200% that of controls without oleate. The results show that this hydrophobic anion modulates lysyl oxidase specificity in crude extracts and suggests a mechanism for modifying activity in tissues.

Amino Acid Oxidoreductases↗

A functional role for opioid peptides in the differential secretion of vasopressin and oxytocin.

The presence of opioid peptides and opiate receptors in the hypothalamo-neurohypophysial system, as well as the inhibitory effects of enkephalins and beta-endorphin on release of oxytocin and vasopressin have been well documented. The physiological importance of opioid peptides in this classical neurosecretory system, however, has remained illusive. In the present study we tested the effects of naltrexone on the plasma concentrations of oxytocin and vasopressin during dehydration, hemorrhage and suckling in the conscious rat. We obtained evidence supporting the hypothesis that opioid peptides inhibit oxytocin release and thereby promote the preferential secretion of vasopressin when it is of functional importance to maintain homeostasis during dehydration and hemorrhage. Our data support the concept that the coexistence of a neuromodulator and a neurohormone in the same neuron, as demonstrated for vasopressin with dynorphin or leucine-enkephalin, serves to regulate the differential release of two biologically different, yet evolutionarily-related, neurohormones, e.g. oxytocin and vasopressin, from the same neuroendocrine system.

Animals↗

Psychosocial status in chronic illness. A comparative analysis of six diagnostic groups.

Assumptions that psychological attributes are specific to particular diagnoses characterize many investigations of chronically ill patients. We studied 758 patients, each of whom had one of six different chronic illnesses, to determine and compare their scores on the Mental Health Index. Five groups of physically ill patients (with arthritis, diabetes, cancer, renal disease, or dermatologic disorders) did not differ significantly from one another or from the general public, but all had significantly higher scores for psychological status when compared with the sixth group, patients under treatment for depression. There was a significant direct relation between higher mental-health scores and advancing age across all patient populations. Patients with recently diagnosed illness in all groups had poorer mental-health scores than did patients whose illness had been diagnosed more than four months previously. A direct relation between declining physical status and mental-health scores was observed. These results suggest that psychological adaptation among patients with chronic illnesses is remarkably effective and fundamentally independent of specific diagnosis.

Adult↗

Varicella vaccine trials in healthy children. A summary of comparative and follow-up studies.

Beginning in 1979, OKA and KMcC strains of varicella zoster virus (VZV) vaccine were administered to 369 healthy seronegative children in a sequence of ten comparative clinical trials. Postimmunization clinical reactivity was minimal with the OKA vaccines but was unacceptably high (32%) with the KMcC passage-40 vaccine. Ninety-three percent to 100% immunogenicity was noted by fluorescent antibody assay and in vitro lymphocyte proliferation to VZV antigens. Follow-up studies demonstrated persistence of antibody and in vitro lymphocyte proliferation responses and protection or modification of infection nine to 48 months after immunization. Only five episodes of mild varicella occurred in children in whom seroconversion had occurred. These episodes were noted after at least 281 known varicella exposures. Vaccine virus reactivation as zoster had not occurred in any child.

Adolescent↗

Unimpaired thermogenic response to noradrenaline in genetic (ob/ob) and hypothalamic (MSG) obese mice.

The thermogenic response to noradrenaline administration was investigated at 25 degrees C in two models of obese mice (genetic ob/ob obesity of the ' QEC ' strain and monosodium-glutamate-induced obesity) and in their respective lean littermates. Subcutaneous injections of a low dose of noradrenaline (100 micrograms/kg body wt.) elevated metabolic rate by about 30% in both obese models but not in their respective lean counterparts. In contrast, the increase in metabolic rate after injections of a high dose of noradrenaline (600 micrograms/kg body wt.) was of a similar magnitude in both lean and obese animals: metabolic rate was increased by 70-80%. These results indicate that the overall whole body thermogenic capacity is unimpaired at room temperature in this ' QEC ' strain of ob/ob mice and in the hypothalamic damaged obese mice. Obesity in these models is therefore not associated with a reduced ability to respond to noradrenaline but could rather be due to a failure to release noradrenaline.

Animals↗

Artifacts caused by cell microinjection.

The effects of microinjection on Rana pipiens oocytes were determined using cryomicrodissection to measure Na, K, water, and injected radiolabeled sucrose (in gelatin) in the nucleus, animal, and vegetal ooplasm and injected bolus (reference phase, RP). The results point to potential problems in the interpretation of microinjection experiments. When oocytes were injected and incubated in Ringer's solution, nucleus, ooplasm, and RP lost K and sucrose and gained Na. Patterns of loss and gain were complex but were consistent with continuous solute leakage at the injection site causing artifactual intracellular diffusion gradients. In spite of leakage, oocytes completed scheduled meiotic maturation when exposed to progesterone. When oocytes were microinjected and incubated in paraffin oil (a medium in which polar solutes cannot exchange), nuclear and ooplasmic Na, K, and water concentrations remained identical to those in uninjected cells. Neither microinjection per se nor the injected bolus affected intraoocytic solute distributions. These findings imply that, after microinjection in aqueous media, metabolites are lost from and redistribute in cells, and that these artifactual changes are inadequately reflected in the ability of the cell to carry out a complex process. They also show that injection artifacts can be avoided by injecting and incubating cells under paraffin oil.

Animals↗

Thermogenic drugs for the treatment of obesity: sympathetic stimulants in animal models.

Thirty-three drugs known to stimulate the sympathetic nervous system have been screened for thermogenic properties. The results presented are for seven of them. The drugs were tested in five animal models of obesity (genetic (mice and rats), hypothalamic (mice) and dietary (mice and rats] as well as in lean mice. Energy-balance studies were undertaken using the comparative-carcass technique as well as by measurement of daily oxygen consumption. All seven drugs in obese animals tended to reduce body-weight and fat without loss of body protein: they acted by increasing metabolic rate without increasing food intake. They were much less effective in lean animals. These findings lend support to the concept that obesity is due to a diminished activity of the sympathetic nervous system. Differences in the effectiveness of the drugs are discussed in relation to differences between the animal models of obesity. Ephedrine and tranylcypromine were found to be the most effective drugs in this series of experiments and a prima facie case is made for human clinical trials.

Animals↗

Solvent properties of ground substance studied by cryomicrodissection and intracellular reference-phase techniques.

Water, sodium, potassium, ATP, amino acids, and sugars are not uniformly distributed in Rana pipiens oocytes. Concentration differences exist between nucleus (germinal vesicle) and ooplasm and between animal and vegetal ooplasmic regions. The mechanisms responsible for these differences were investigated using intracellular reference-phase (iRP) analysis. The iRP is an artificial "organelle" that has the solvent properties of a dilute salt solution and is in diffusional equilibrium with water and solutes present in other cellular compartments. Ooplasm/iRP solute distributions show that ooplasm differs from ordinary aqueous solutions--exhibiting both solute exclusion and solute binding. Yolk platelets are an important cause of this behavior, largely because their proteins are present as hydrate crystals, which are rich in anionic sites and which interact intensely with associated water. Because of yolk's abundance, it obscures the solvent and binding properties of ooplasmic ground substance. The oocyte nucleus is yolk and organelle free and the nuclear envelope is readily permeable. Consequently, nucleus/iRP solute concentration differences reflect the binding and solvent properties of nuclear ground substance. Nucleoplasm binds approximately 19 meq of potassium. Furthermore, the monosaccharides, 3-O-methylglucose, L-glucose, and D-xylose, are selectively excluded, their nucleus/iRP concentration ratios averaging about 0.7; ratios for other solutes studied are unity. We interpret monosaccharide exclusion to mean that nuclear ground substance water is different in its "instantaneous" structure from ordinary saline water. Because of this difference, hydrogen bond interaction between nuclear water and certain sterically restricted solutes, of which ringed monosaccharides are examples, is reduced. Some implications of modified ground substance water and selective solute exclusion are discussed.

3-O-Methylglucose↗

Energy balance following sympathetic denervation of brown adipose tissue.

The effects of sham, bilateral surgical denervation or excision of interscapular brown adipose tissue on body composition and energetic efficiency were studied in young CFLP mice kept at 25 degrees C and fed a laboratory stock diet. A preliminary experiment showed that 15 weeks following surgery, total body fat was increased by 42% in the denervated group and by 72% in the excised group while body protein was unchanged. In another 7-week energy balance experiment, body fat was also significantly higher by 15 and 18% in the denervated and excised group, respectively, but metabolizable energy intake was slightly lower than that of sham controls. Determination of energy expenditure both by the comparative carcass slaughter technique and by measurement of daily oxygen consumption showed that the metabolic rate was reduced in the denervated nd excised groups. The capacity for thermogenesis, as measured by an increase in oxygen consumption following injections of noradrenaline (600 micrograms/kg body weight) was similar in energetic efficiency, and indicates an important role of the sympathetic nervous system in the regulation of animal heat production by brown adipose tissue and in the overall control of thermogenesis.

Adipose Tissue, Brown↗