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Biomedical subjects

L W Smith

Publications and source records attributed to L W Smith.

At least 19 recordsLinked to original sources

Symptoms of illness in late adulthood are related to childhood social deprivation and misfortune in men but not in women.

Experiencing adverse life events during childhood may increase vulnerability to physical illnesses and psychological disorders during adulthood. We developed an Early Life Events Questionnaire (ELEQ) with 12 scales and administered it to 92 relatively healthy elderly individuals (29 men and 63 women). A canonical-correlation analysis of the 12 ELEQ scales and physical and psychological symptoms revealed a significant canonical correlation. The results indicate that those who grew up in a family with a harsh climate and whose affiliation needs were not met tended to have more psychological and physical symptoms in old age. Regression analysis revealed that, in men, early life events accounted for 42% of the variance in physical symptoms and 39% in psychological symptoms. No significant relationship, however, was found between ELEQ scales and health outcomes in women. These results suggest that women may be less vulnerable than men to the adverse health consequences of childhood deprivation and other misfortunes.

Age Factors

Primary culture of adult mouse lung fibroblasts in serum-free medium: responses to growth factors.

We report a completely serum-free system for primary culture of fibroblasts from explants of adult mouse lung tissue which permits bioassays for cytokine activity to be performed using unselected populations of cells at low passage number, without interference by serum binding proteins or interacting growth factors. Cultures were established on collagen-coated surfaces in medium MCDB 201 containing albumin, transferrin, epidermal growth factor, lipids, prostaglandin E1, vitamin E, and reducing agents. The cells were morphologically and ultrastructurally typical of fibroblasts in culture and demonstrated expression of vimentin and induction of expression of desmin in culture. Proliferation of the cells was reproducible between different primary cultures and was growth factor dependent. Both cycling and growth-arrested cells exhibited increased DNA synthesis when stimulated with epidermal growth factor, platelet-derived growth factor, or basic fibroblast growth factor, which functioned as complete mitogens, but did not respond to insulin, tumor necrosis factor or interleukin-1 beta. Maximal induction of DNA synthesis by epidermal growth factor required the continued presence of the mitogen in the culture medium. These results cannot be satisfactorily explained by the competence-progression model of responses to mitogenic stimuli but support and extend the findings of other studies using diploid fibroblasts.

Animals

Chromosome abnormalities in human epithelial ovarian malignancies.

Karyotypic analysis of tumor specimens from 29 patients with untreated epithelial ovarian carcinoma was performed at the University of Kentucky Medical Center. Twenty-three of the twenty-nine tumors had adequate cells for analysis. Seventeen of these tumors exhibited chromosome abnormalities. Chromosome alterations were complex, with an average of seven different abnormal chromosomal patterns per tumor (range 2-14). Chromosomes 1 and 11 were the most commonly involved, being abnormal in 89 and 83% of tumors, respectively. Chromosomes 3 and 7 were also frequently abnormal. In contrast to invasive tumors, alterations in chromosomes 1 and 11 were not seen in the two tumors of borderline malignant potential. Evidence for DNA amplification of IGF2, Ha-ras-1, and c-ets was not observed. Amplification of the c-erbB-2 oncogene was present in two tumors. These findings indicate that multiple karyotypic abnormalities occur in untreated epithelial ovarian malignancies, with chromosomes 1 and 11 being the most frequently abnormal. These data also suggest that alterations of these chromosomes may be associated with the biologically aggressive behavior of frankly invasive ovarian tumors.

Adult

Internal vs. external determinants of coping responses to stressful life-events in the elderly.

Coping appears to function in the relationship between stressful life-events and health. Factors that may influence an individual's use of a particular coping strategy, however, are not well understood. Coping consistency within individuals and across situations was examined in a longitudinal study of 74 independently living elderly persons, as were the effects of the type of event experienced, appraisal of its degree of threat, and demographic variables on coping behaviour. Correlational analyses indicated that coping responses were more a function of event type than of an individual's consistent style. A number of distinct life-events were associated with particular types of coping responses. The degree of threat, one's expectation of the changeability of an event, and one's appraisal of possible courses of action were also correlated with specific coping behaviours. Age was negatively correlated with problem-focused coping and total number of coping responses. This study suggests that the type of stressful event an individual experiences may be a more important general determinant of one's coping response than is one's overriding propensity to cope in a particular way.

Adaptation, Psychological

Particle size reduction during initial mastication of forages by dairy cattle.

Four experiments were conducted with dairy cattle to determine the effects of initial feed particle size and moisture content on particle size of ingested masticates. Three mature Holstein cows were used in either latin square or Youden square designs. Samples of masticated and ingested boli were collected at the cardiac opening through a ruminal fistula between 0 and 5, 5 and 10 and 10 and 15 min after meal initiation. In Exp. 1, masticate log mean particle sizes (LMPS) (ln microns, log normal distribution) were 3.50, 3.53 and 3.50 for corn silage, fine-chopped alfalfa haylage and coarse-chopped alfalfa haylage, respectively. In Exp. 2, boli LMPS for ground, chopped and long alfalfa hay were 3.11, 3.76 and 4.09, respectively. Boli LMPS in Exp. 3 for ground, chopped and long timothy hay were 2.93, 3.12 and 3.03, respectively. Exp. 4 compared the effect of addition of water to produce 30%, 47%, 64% and 82% DM in chopped alfalfa hay. Boli LMPS were 3.66, 3.56, 3.64 and 3.68 for the respective alfalfa hay DM contents. Feed LMPS was not reduced during mastication in Exp. 4, nor were there differences in LMPS due to time after feeding. Boli LMPS was affected by feed particle size of alfalfa hay, but there was no effect of feed particle size on masticate particle size in timothy hay. The magnitude of particle size reduction during mastication appears to be dependent on forage type and is not dependent totally on initial feed particle size and DM content of forages.

Animal Feed

Supersensitivity and changes in the active population of beta adrenoceptors in rat right atria in early sepsis.

We have investigated the effect of sepsis induced by cecal ligation and puncture on the chronotropic actions of beta adrenoceptor agonists on isolated right atria. The present findings show that right atria obtained from rats in an early stage of sepsis were supersensitive to the chronotropic actions of the beta-agonists, isoproterenol (ISO), fenoterol (FEN) and prenalterol (PREN). The supersensitivity to the chronotropic actions of ISO and FEN was much greater than that which developed to PREN. The positive chronotropic actions of isobutylmethylxanthine and forskolin were not affected by sepsis. The receptor subtypes mediating the responses to ISO, FEN and PREN by control and septic right atria were characterized by functional assays using selective beta-1 and beta-2 antagonists. The results showed that the chronotropic response produced by all three agonists on right atria obtained from control rats were mediated by beta-1 receptors. In contrast, the chronotropic actions of ISO and FEN on atria from septic rats were mediated by what appears to be beta-2 receptors and those of PREN by beta-1 receptors.

1-Methyl-3-isobutylxanthine

In vitro cardiac function in early sepsis.

The involvement of the myocardium in the injury resulting from bacteremia has been somewhat controversial. Recently, some investigators have suggested that the transition from an early stage of sepsis, in which the cardiovascular system is stable and mortality is relatively low, to the late or preterminal stage of sepsis is a result of cardiac dysfunction. Here, however, data are presented to show that contractile defects and loss of myocardial reserve occur even early during a septic episode, i.e., at a time when cardiac output is elevated or normal. Efforts to determine the mechanism of the cardiac dysfunction are described. These entail studies of whole heart performance under conditions of varying the calcium availability for contraction and assessment of subcellular organelle function. The data indicate that calcium dyshomeostasis may at least partially contribute to the cardiac dysfunction of sepsis. The in vivo adequacy of cardiac function probably results from the capacity of the myocardium in early sepsis to respond to catecholamine support of chronotropy and inotropy.

Animals

Angiotrophic lymphoma. Presentation in uterine vessels with cytogenetic studies.

An unusual case of angiotrophic lymphoma diagnosed initially in the uterus is described. Immunohistochemical studies documented the intravascular tumor cells in the myometrium to be of B lymphocytic origin. The patient's bone marrow was hypercellular, and cytogenetic studies of the aspirate revealed a subpopulation of cells with multiple clonal chromosomal abnormalities. To our knowledge, this is the first case to document abnormal cytogenetic findings in this uncommon malignancy.

B-Lymphocytes

Avoidant coping predicts psychological disturbance in the elderly.

In a prospective study of 81 independently living elderly persons, information on coping strategy in response to a stressful life event was used in a canonical analysis to examine the relationship between coping factors and health status measures. A canonical correlation of .53 (28% of variance) indicated that those who responded to stressful life events with self-blame, wishful thinking, and avoidance tended to be more symptomatic 4 months later. In a regression analysis, avoidant coping significantly contributed to the prediction of psychological disturbance at the time of the second interview (R2 = .22, p less than .05). Coping strategy, however, did not significantly contribute to the prediction of physical health status during the interval examined. These results are generally consistent with the notion that coping strategies modulate the influence of life events on health and well-being but underscore the possibility that such relationships may differ depending on whether physical or psychological health status is being predicted.

Adaptation, Psychological

A shortened MMPI useful for psychiatric screening of the non-institutionalized elderly.

We compared the reliability of the Faschingbauer Abbreviated MMPI (the FAM) to the standard MMPI with a sample of non-institutionalized, independently living elderly individuals. FAM items were extracted from the standard MMPIs of 83 middle-class men and women with a mean age of 74 years. Results indicate that the FAM is correlated highly with the MMPI. Although statistically significant differences were found between the FAM and MMPI forms on some scales, 77% of the profile pairs were judged to satisfy interpretive reliability criteria, and for the profiles that were rejected the FAM was not found to overestimate or underestimate any MMPI scale systematically. The potential value of the FAM as a screening device for elderly individuals who are living in the community is addressed.

Adaptation, Psychological

Abnormal alveolar epithelial repair associated with failure of resolution in experimental streptococcal pneumonia.

We describe an experimental model in Wistar rats of non-resolving bronchopneumonia evoked by Streptococcus pneumoniae type 25. In contrast to a model of resolving streptococcal pneumonia that we have previously described, morphological studies reveal that in this model, there is significant early damage to type 1 pneumocytes which progresses to necrosis, leaving isolated areas of denuded alveolar basement membrane. Furthermore, there is accompanying degeneration and necrosis of a proportion of the type 2 pneumocytes, and alveolar epithelial repair by proliferation and differentiation of these cells appears to be retarded. Isolated, hypertrophic, and hyperplastic foci of type 2 pneumocytes persist as the acute inflammatory response subsides, and organization progresses with proliferation and emigration of fibroblasts into the lumina of alveoli and terminal bronchioles. The resultant lesion is morphologically indistinguishable from bronchiolitis obliterans organizing pneumonia. We hypothesize that the abnormal outcome in this model of pneumonia is a consequence of the failure of proliferating type 2 pneumocytes to transform into type 1 pneumocytes and thus maintain the integrity of the alveolar epithelial surface.

Animals

Postcardiotomy delirium: conclusions after 25 years?

Although postcardiotomy delirium has been studied widely, there are few data about the current prevalence, compared to that reported in the late 1960s. There have been few efforts to replicate early observations. The authors review the literature using meta-analysis to combine the results of 44 studies. They examined the relationships between postcardiotomy delirium and 28 hypothesized risk variables. The prevalence of postcardiotomy delirium has remained fairly constant over time at 32%. There was no difference in the total prevalence of postcardiotomy delirium reported in studies that used interviews versus chart reviews. Sex, previous psychiatric illness, intelligence, and time on bypass failed to correlate with postcardiotomy delirium, and age correlated with it only slightly. Correlation coefficients of more than 0.30 were found only for noncongenital heart disease and postoperative EEG abnormality. Preoperative psychiatric intervention had the highest correlation with postcardiotomy delirium (r = -0.60).

Cardiac Surgical Procedures

A review of the use of intrinsically 14C and rare earth-labeled neutral detergent fiber to estimate particle digestion and passage.

Methodology that allows simultaneous measurement of dynamic events affecting NDF digestion in passage from the rumen should improve our understanding of factors influencing intake and digestion. Ideally, particle flow is measured with a marker indelibly attached to or intrinsically part of the feed. If flow measurements are to reflect physiological conditions, marked and unmarked feed must be digested and passed with identical fractional rates. Application of 14C-labeled plant fiber to the study of ruminal dynamics has been slow because of expense and difficulty in producing 14C-labeled plant material. Recently, alfalfa was intrinsically labeled with 14C under field conditions to produce plant material similar in composition to unlabeled material. Carbon-14 specific activity was similar in all particle sizes, and in indigestible and digestible NDF. Greater concentrations of ytterbium (Yb) were associated with smaller vs larger particles. Larger differences in turnover rates among animals than differences attributable to treatments force comparisons of markers to be made within animal or with in vitro systems. The uncertainty about how extrinsic markers respond under various environments resulting from interaction of feed properties and gut function, and the high error inherent in measuring dynamic systems, raise serious questions on the interpretability of results. Advantages of 14C-labeled NDF over other markers include simultaneous measurements of particle breakdown, digestion and passage rates as well as the potential to study microbial attachment, VFA, CO2 and CH4 production and rate of incorporation of labeled metabolites into tissues.

Animals

Inotropic sensitivity to beta-adrenergic stimulation in early sepsis.

In early sepsis, maintenance of in vivo cardiovascular performance is at least partly dependent on sympathetic support to hearts with intrinsic contractile defects. Yet prolonged sympathetic stimulation, as occurs in sepsis, would be expected to alter the heart's ability to respond to this stimulation. We have investigated myocardial inotropic sensitivity to beta-adrenergic stimulation in a model of sepsis in which animals, at the time studied, exhibited bacteremia, normal arterial blood pressure and cardiac output, elevated heart rate, and elevated plasma catecholamines. Intrinsic myocardial contractile function, as assessed by the maximal rate of left ventricular pressure development (LV dP/dtmax) in an isovolumically contracting heart preparation, was significantly depressed in septic animals. To determine whether hearts from septic animals could respond normally to beta-adrenergic stimulation, we studied inotropic response to a bolus of isoproterenol in these isolated hearts. With maximal isoproterenol stimulation, hearts from septic animals were able to attain the same dP/dtmax as were hearts from control animals. With lower levels of isoproterenol, there was also no difference in inotropic indexes between the two groups when response was expressed as a percent of the maximal increase in dP/dtmax achieved with isoproterenol. These results suggest that in early sepsis, despite intrinsic myocardial contractile dysfunction, the ability of the heart to modulate its inotropic state in response in beta-adrenergic stimulation is intact.

Animals

Acute and repeated dose inhalation toxicity of para-nitrophenol sodium salt in rats.

Para-Nitrophenol Sodium Salt (PNSP) has relatively low acute inhalation toxicity; the 4-hr Approximate Lethal Concentration in rats is greater than 4.7 mg/l. One subacute study was conducted at 0, 0.34 and 2.47 mg PNSP/l for ten 6-hr exposures. Darker urine, proteinuria and elevated creatinine and SGOT were seen after exposure and were still evident after 14 days recovery. Methemoglobinemia also was seen and was reversible at 0.34 mg/l after 14 days. In addition, exposure to 2.47 mg/l caused elevated erythrocytes, hemoglobin and hematocrit. A second subacute study at 0.03 and 0.13 mg PNSP/l showed reversible methemoglobinemia only at 0.13 mg/l. The repeated dose no-observable effect level was 0.03 mg/l. No compound-related pathologic changes were noted in any of the studies.

Administration, Inhalation

Feeding and management of dairy heifers for optimal lifetime productivity.

A total of 433 Holstein heifer calves were fed two different energy amounts from 6 wk of age to breeding weight to determine the effect of early nutrition and age at first calving on lifetime performance. A control group of 182 heifers was fed according to the Beltsville growth standard. A second group of 251 heifers was accelerated in growth by providing more energy during early development. Both groups of heifers were bred at a minimum weight of 340 kg. Average ages at first calving for control and accelerated heifers were 24.6 mo and 22.2 mo with corresponding 305-d first lactation unadjusted milk production values of 6985 and 6729 kg and unadjusted milk fat yields of 222 and 216 kg. Average 305-d milk production values through subsequent lactations for control and accelerated animals, were lactation 2, 7790, 7842 kg; lactation 3, 8200, 8330 kg; lactation 4, 9481, 9134 kg; lactation 5, 9865, 9588 kg; lactation 6, 9515, 10,108; lactation 7, 9661, 10,112. Average total milk yields over five lactations were 42,321 and 41,623 kg. Percentages of cows remaining in the herd after five lactations were 19 and 18 for control and accelerated animals. Reproductive problems, mastitis, and deaths accounted for 70% of cows leaving the herd and did not differ between treatment groups.

Animal Husbandry