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Biomedical subjects

C Thomas

Publications and source records attributed to C Thomas.

At least 343 records · Page 19Linked to original sources

Evaluation of nucleolus organizer regions (NORs) by automatic image analysis: a contribution to standardization.

This study summarizes our experiences with the silver staining of nucleolus organizer regions (AgNORs) in a total of 580 tumours from ten different tissues. In contrast to other investigators, we made use of automatic image analysis for the evaluation of AgNORs. This provided good reproducibility as determined by the standard cumulative means technique and intra-observer (r1) and inter-observer (r2) agreement in 30 benign (r1 = 0.83-0.95, r2 = 0.76-0.92) and 50 malignant tissue samples (r1 = 0.72-0.85, r2 = 0.51-0.78). By using a series of staining times on sections from 30 tissue blocks taken from the ten types of tissue investigated, considerable variation in the argyrophilic staining of NORs in different tissues and in different blocks from one tumour was shown. The mean AgNOR area of resting lymphocytes or connective tissue cells within tissue blocks of the same organ system varied up to four-fold, even though identical staining times had been used. The most suitable silver reaction time which rendered a good diagnostic difference in the AgNOR content of benign and malignant tissue ranged, for example, in the breast cancer specimens, from 23 to 35 min. We therefore conclude that the staining time has to be adjusted to the individual silver-binding characteristics of each tissue block or even each section. The use of internal staining standards like lymphocytes or connective tissue cells in the same tissue section is mandatory. This, in turn, is most precisely controlled by morphometry.

Humans↗

Health services use among the elderly under alternative health service delivery systems.

This article compares patterns of health care utilization for hospitalizations and ambulatory care in a sample of 1855 urban, elderly, community residents who report obtaining their health care from one of four types of arrangements: a fee-for-service (FFS) physician, a hospital-based health maintenance organization, a network model HMO, or a preferred provider organization (PPO). Utilization rates reported by respondents at six month intervals over three years were adjusted for health and socioeconomic characteristics of enrollees. PPO plan members consistently have mean and total lengths of hospital stay one-third to one-half those of the others. Although rates of use of particular categories of ambulatory care vary across systems of care, total ambulatory care rates are highest for network model HMO plan members. Specific features of alternative delivery systems, rather than general model types, may have an impact on utilization rates and the costs of care.

Aged↗

The emergence of depressive symptoms in late life: the importance of declining health and increasing disability.

Despite considerable progress in the epidemiology of late life depressive disorders, the determinants and course of late life depressive symptoms remain unclear. The apparent reciprocal relationship between depression and disability, a consistent finding in cross-sectional studies further confounds efforts to estimate the importance of depressive symptoms in the elderly. In a longitudinal study of 1457 aged community residents who completed the Center for Epidemiologic Studies Depression scale at baseline and 24 months later, a significant level of depressive symptoms emerged in 163 respondents (11%), while 1080 (74%) remained symptom free. Unlike other studies, we found that the number of medical conditions, social support, life events, and demographic characteristics contributed little to distinguish those with emerging symptoms from those who remained symptom free. However, increasing disability and declining health preceded the emergence of depressive symptoms and accounted for seventy percent of the variance explained by discriminant analysis. These findings have etiologic implications for both the course and determinants of depression in late life.

Aged↗

Transitions between community and nursing home residence in an urban elderly population.

Over the course of a three year observation and study period, some 6% of a representative community residing urban elderly population were admitted to nursing homes. Nearly half of this group were still living in nursing homes at the end of this observation period. One third had died after entering the nursing home, and the remaining people had returned to their own homes in the community. These three groups had significantly different mean lengths of stay in nursing homes; nearly two years for those whose stays were more permanent, 50 days for those whose stays were short-term, and 153 days on average for those who died following admission. At baseline, the three groups also tended to have different patterns of health, functional and social characteristics. The short term stayers and those who died following admission to a nursing home differed from respondents who did not enter nursing homes--primarily in terms of prior living arrangements and levels of social support. The permanent stayers differed from the two other nursing home sub-groups, and from community residents, in that they tended to be older and more functionally and mentally impaired. However, at baseline they appeared at less risk to expire than those people who later died following admission to nursing homes. Clinical and research implications based on these findings are discussed.

Aged↗

Unreimbursed expenses for medical care among urban elderly people.

Out-of-pocket medical expenditures were examined among a sample of 400 low-to-moderate income Medicare recipients living in the Bronx for a twelve month period in 1986-87. Using three different measures of magnitude, the most significant expenses were for Medicare and private insurance premiums, medications, and dental care. The mean percent of per capita income spent out-of-pocket for medical care (including health care premiums) was 11.0%. Elderly people who spend over 12% of their own income on medical care include those in the poorest health, those with annual incomes under $15,000, people living with spouses or others, and those using a private physician as a primary source of medical care.

Aged↗

Controlled study of the impact of educational home visits by pharmacists to high-risk older patients.

Lack of information about medications coupled with high rates of utilization complicates compliance with medication regimens and increases the risk of adverse effects among older adults. We undertook a study of the efficacy of community-based interventions by pharmacists in a randomly-allocated one-half of a sample of 284 older adults considered to be at high risk for medication-related problems. Information and attitudes towards prescription and over-the-counter medications did not differ significantly between the intervention and comparison groups, either before or after the pharmacist interventions. However, visits to physicians were significantly less in the intervention group, suggesting an important if unexpected impact on health-related behavior.

Aged↗

Assessment of nucleolar organizer regions by automatic image analysis in breast cancer: correlation with DNA content, proliferation rate, receptor status and histopathological grading.

The value of automatic image analysis in the investigation of nucleolus regions (AgNOR) has been examined in tissue sections of 52 malignant and 30 benign breast lesions. Determination of the AgNOR number per cell alone revealed a considerable overlap between benign (range 1.2-3.8) and malignant specimens (range 1.5-16.2). They differed however, highly significantly (P less than 0.001) in their AgNOR sizes. In benign breast disorders the mean AgNOR area per tumour ranged from 0.22 microns2 to 1.07 microns2 (mean 0.39 microns2), whereas in carcinomas AgNOR sites ranged from 0.05 microns2 to 0.22 microns2 (mean 0.09 microns2). AgNOR counts showed a good correlation with histopathological grade (P less than 0.05), aneuploidy (P less than 0.01), proliferation rate as determined by Ki67 immunostaining (P less than 0.01), as well as oestrogen and progesterone receptor content (P less than 0.01). Image analysis proved to be advantageous over AgNOR counting alone as it facilitated the standardization of the AgNOR technique itself and thus, significantly improved its diagnostic specifity.

Breast Neoplasms↗

Popliteal lymph node enlargement and antibody production in the mouse induced by zimeldine and related compounds with varying side chains.

Structural requirements for induction of draining lymph node responses by the antidepressant drug zimeldine ((Z)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl)allylamine) in mice were determined by comparison of its activity with that of metabolites and analogues having different side chains. Mice received 1.0 mg of the compounds into the hind footpad and the popliteal lymph nodes (PLN) were removed 7 days later to determine weight, cell number and antibody production. Compounds with a methylated (Z)-(homo)allylamine side chain induced a marked PLN weight gain in C57BL/6 mice and a significant increase of the PLN cell number and of the IgM and IgG production per 10(6) PLN cells in BALB/c mice. Moderate PLN weight increase, but no significant antibody formation was induced by the doubly demethylated zimeldine metabolite, while compounds without an aliphatic amine or having a saturated side chain lacked significant activity in all assays. The (E)-diastereomer of zimeldine induced significantly less PLN weight gain than zimeldine in C57BL/6 mice, but an equal increase of PLN cell number in BALB/c mice. IgM and IgG responses to the (E)-diastereomer were moderate and absent, respectively. The antihistaminic drug, brompheniramine, having a saturated side chain and a 2-pyridyl ring, induced less PLN weight and cell gain than zimeldine and failed to increase antibody formation. The capacity of the compounds to induce PLN responses appeared not related to their pharmacological potential to inhibit the reuptake of serotonin and noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Induction of popliteal lymph node enlargement and antibody production in the mouse by pyridylallylamines related to zimeldine.

The role of the para-brominated phenyl ring of the allylamine antidepressant drug, zimeldine, in its immunomodulating activity was studied by comparing local lymph node responses of mice to analogues with various phenyl ring substituents. The compounds (1.0 mg) were injected into the hind footpad and weight and cell number of the popliteal lymph node (PLN) and antibody production by PLN cells were determined 7 days later. Zimeldine and the para-trimethylsilylated and ortho-para-chlorinated compounds induced a marked PLN weight gain in C57BL/6 mice. The para-chlorinated and meta-brominated analogues were significantly less effective, while the para-fluorinated and the unsubstituted analogue failed to trigger PLN weight gain. The same range of potency of the compounds was seen when increases of PLN cell number in BALB/c mice and increases of IgM production by a fixed number of BALB/c PLN cells were determined. The IgG production on a per cell basis was not increased by the fluorinated and the unsubstituted compounds, while the remaining compounds stimulated the IgG production to a similar extent. Plots of the lipophilicity of the para-substituted compounds against their ability to induce PLN weight and cell gain showed a fair correlation, but induction of antibody formation tended to be counteracted at too high lipophilicity. No correlation between pharmacologic and immunologic activity of the compounds could be found. Data indicate that lipophilicity grossly favours PLN enlargement, but the divergent responses to the equilipophilic 3- and 4-brominated compounds, suggest conformational restraints as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Urinary excretion of prostaglandins during infancy and childhood: influence of age, sodium restriction and posture.

The influences of age, sodium restriction and posture on 24-hour urinary excretion of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF 2 alpha), 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha) and thromboxane B2 (TXB2) were investigated in 111 healthy children and youngsters in the age between 1 day and 16 years. A considerable degree of variation was found in normal 24-hour urinary prostaglandin excretion in all age groups. There was no significant effect of age on the urinary excretion of prostaglandins when data were corrected for body surface area. In addition, sodium restriction and posture had no influence on the excretion of PGE2, PGF 2 alpha, 6-keto-PGF 1 alpha and TXB2. Our results indicate that in the first days of life the kidney already has the capacity to synthesize prostaglandins in amounts comparable to older children.

Adolescent↗

Comparison of methohexital and isoflurane on neurologic outcome and histopathology following incomplete ischemia in rats.

Using a rat model of incomplete cerebral ischemia the effects of isoflurane (iso) and methohexital (metho) were compared with those of 70% nitrous oxide controls (N2O). Two levels of incomplete cerebral ischemia were produced by right carotid occlusion plus hypotension for 30 min: moderate = 30 mmHg, FIO2 = 0.30; severe = 25 mmHg, FIO2 = 0.20. The iso doses (1 and 2 MAC) and metho doses (0.01 and 0.1 mg.kg-1.min-1) were tested at each ischemic level. These iso and metho doses were selected because without ischemia they produced similar decreases in cerebral oxygen consumption (CMRO2) compared with that produced in N2O controls. In the absence of ischemia, the electroencephalogram (EEG) was suppressed by 0.01 mg.kg-1.min-1 metho and 1 MAC iso and showed burst-suppression with 0.1 mg.kg-1.min-1 metho and 2 MAC iso. The EEG was further depressed by ischemia under all anesthetic conditions. Neurologic outcome was evaluated for 3 days following incomplete cerebral ischemia by using a graded deficit score (0 = normal, 5 = death associated with stroke). Following moderate ischemia all four anesthetic treatments improved outcome compared with N2O controls, but after severe ischemia only 2 MAC iso significantly improved outcome. Neurohistopathology was evaluated on a scale of 0 to 40, 24 h after ischemia. The neurohistopathology score was significantly improved by all four anesthetic treatments compared with N2O following moderate ischemia and was better with 2 MAC iso compared with 0.1 mg.kg-1.min-1 metho after both moderate and severe ischemia. These results show that both iso and metho improve outcome from cerebral ischemia compared with that associated with N2O, but only 2 MAC iso resulted in an improved outcome following severe ischemia. This difference in outcome between the two anesthetics may be related to greater neuronal depression with iso, which may occur with little difference in cerebral metabolic depression.

Animals↗

Brain lactate and neurologic outcome following incomplete ischemia in fasted, nonfasted, and glucose-loaded rats.

The neurologic outcomes following incomplete cerebral ischemia in rats treated by fasting, nonfasting, or glucose administration (6 ml/kg of 50% glucose solution intraperitoneal) were compared. Rats were anesthetized with 1.4% inspired isoflurane in air and incomplete ischemia was produced by temporary unilateral carotid occlusion and hypotension of 30 mmHg for 30 min. The rats were recovered and neurologic outcome was scored every 8 h for 3 days using a 6-point scale ranging from 0 (normal) to 5 (death associated with stroke). Brain histopathology was scored using a four-point scale on 19 of 30 rats surviving the 3-day postischemic neurologic examination and was correlated with neurologic deficit scores. Fasted rats had plasma glucose concentrations of 79 +/- 7 mg/100 ml (mean +/- SE) during ischemia and a significantly better neurologic outcome (P less than 0.001) than glucose-loaded rats (plasma glucose = 496 +/- 43 mg/100 ml). Nonfasted rats had blood glucose values (292 +/- 28 mg/100 ml) and deficit scores not significantly different from fasted but better than glucose-loaded rats (P = 0.054). Brain histology showed the greatest neuronal damage in caudate followed by hippocampus and cortical tissue. Histopathologic evaluation showed a correlation of r = 0.87 (P less than 0.01) with neurologic outcome. In separate experiments brain samples were collected at the end of the ischemic period in each of the experimental groups and regional tissue lactate and brain phosphocreatine and adenosinetriphosphate (ATP) concentrations were measured. Ischemic tissue lactate was similar in fasted, nonfasted, and glucose-loaded rats in caudate and hippocampus but was significantly higher in glucose loaded rats in cortical and thalamic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Ganglionic blockade improves neurologic outcome from incomplete ischemia in rats: partial reversal by exogenous catecholamines.

The authors investigated the effects of nitrous oxide (N2O), ganglionic blockade, and combined infusion of epinephrine and norepinephrine (0.1 microgram.kg-1.min-1 each) on neurologic outcome and brain histopathology in a model of incomplete cerebral ischemia in the rat. Thirty-eight Sprague-Dawley rats were assigned to one of four groups: group 1 (n = 10) received 70% N2O in O2; group 2 (n = 12) received 70% N2O in O2, plus ganglionic blockade; and group 3 (n = 10) received 70% N2O in O2, plus ganglionic blockade and catecholamine infusion. In groups 1-3, ischemia was produced by right carotid occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Group 4 (n = 6) received 70% N2O in O2 and hemorrhagic hypotension without carotid occlusion for 30 min. At the end of ischemic and nonischemic hypotension, the carotid artery was unclamped and the blood slowly reinfused. Neurologic outcome was evaluated for a 5-day period with a graded deficit score (0 = normal to 39 = stroke-related death). Brain histopathology was evaluated in coronal section at the level of the caudate nucleus according to a 6-point scale, from 0 = normal to 5 = total hemispheric infarction. Arterial blood gases, pH, and body temperature were kept constant in all groups. Compared to N2O alone (group 1), treatment with ganglionic blockade (group 2) decreased plasma catecholamines by 75% and significantly improved neurologic outcome from incomplete cerebral ischemia (P less than 0.05). Administration of exogenous epinephrine and norepinephrine in the presence of N2O and ganglionic blockade (group 3) worsened neurologic outcome compared to group 2 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Open fronted safety cabinets in ventilated laboratories.

Open fronted Class I and II microbiological safety cabinets (MSCs) are required by the British Standard 5726 to provide similar levels of operator protection (viz. 10(5). In laboratories that are naturally ventilated large numbers of both types of cabinets have been shown to exceed this requirement consistently over a number of years. The designs of some mechanically ventilated laboratories, however, produce excessive turbulence and draughts that can prejudice containment at the front aperture. On-site commissioning tests to determine operator protection factor are now well established and are recognized as being essential to the setting up of all open fronted cabinets in both ventilated and unventilated laboratories. This paper shows that where environmental conditions induce unsatisfactory cabinet containment, adjustments to air supply and exhaust systems can be made which will enable both Class I and II cabinets to produce operator protection factors in excess of 10(5). When compatibility is achieved between the local environment and the cabinets it is demonstrated that disturbances at the front aperture, caused by operator working procedures or by disturbances due to personnel movement within the room, have similar effects on both Class I and II cabinets. Once performance levels have been satisfactorily achieved, regular containment testing has shown that consistent performance can be maintained. These aspects of open fronted safety cabinet performance are discussed in relation to ventilated laboratories suitable for work with the human immunodeficiency virus (HIV). Of paramount importance in the future is the necessity to design laboratory air systems that will be compatible with satisfactory safety cabinet performance--a relatively new requirement in ventilation system specifications.

Bacteriological Techniques↗

Hypothermia versus ethanol: neurologic outcome after incomplete cerebral ischemia in midazolam-anesthetized rats.

We examined neurologic outcome after incomplete cerebral ischemia in rats treated with hypothermia versus ethanol, two techniques that decrease brain metabolism. All animals, including control rats, received a baseline midazolam anesthetic. Ischemia was produced by right carotid artery occlusion combined with hemorrhagic hypotension to a mean arterial pressure of 30 mm Hg for 30 min. Neurologic outcome was evaluated for 3 days after ischemia using a 5-point scale. In separate studies, cerebral blood flow (CBF) was measured using radioactive microspheres, and cortical oxygen consumption (CMRO2) was calculated from the blood flow data and the arteriovenous oxygen difference. Hypothermia to 31 degrees C decreased CBF 50% and CMRO2 52% compared with control rats, and significantly improved outcome. Although ethanol decreased CBF 35% and CMRO2 22%, it did not improve outcome from stroke compared with control rats. These results suggest that hypothermia protects the brain from ischemia and that ethanol does not, despite a decrease in CMRO2.

Journal Article↗

[AgNOR cytometry by means of automatic image analysis--a contribution to standardization].

The silver staining of nucleolar organizer regions (AgNORs) was evaluated in a total of 697 tumours from ten different tissues. By means of qualitative light microscopy, type, duration and delay of fixation proved to be influential in determining the AgNOR result. For standardization of the AgNOR technique, staining time series in 30 tissue blocks of the ten types of tissue were evaluated using digital image analysis. The silver incubation time which rendered the most distinct diagnostic difference in the AgNOR content of benign and malignant tissue varied considerably. Accordingly, staining time has to be adjusted to the individual argyrophilia of each tissue block or tissue section, for which the use of internal staining standards such as lymphocytes or connective tissue was found to be mandatory. For routine purposes, the appropriate silver incubation time is achieved if AgNORs are visible as black dots mainly within the nucleoli of proliferating cells.

Autoanalysis↗