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Biomedical subjects

C Thomas

Publications and source records attributed to C Thomas.

At least 127 records · Page 7Linked to original sources

Age differences in care practices and outcomes for hospitalized patients with cancer.

OBJECTIVE: To identify age group differences in care practices and outcomes for seriously ill hospitalized patients with malignancy. DESIGN: Prospective cohort study (SUPPORT project). SETTING: Five United States teaching hospitals; data was gathered between 1989 and 1994. SUBJECTS: Nine hundred twenty five older (age > or = 65 years), 983 middle aged (age = 45-64 years), and 274 younger (age = 18-44 years) hospitalized patients receiving care for non-small cell lung cancer, colon cancer metastasized to the liver, or multi-organ system failure associated with malignancy. MEASUREMENTS: Care practices and patient outcomes were determined from hospital records. Length of survival was identified using the National Death Index. After adjusting for important variables, including severity of illness (i.e., SUPPORT model estimate for 2-month survival, cancer condition), hospital site, selection to intervention and sociodemographic variables, age group differences in care practices and outcomes were identified using general linear models. RESULTS: Older patients with cancer had lower resource utilization during hospitalization (P < .04) and were less likely to receive cancer-related treatments (i.e., chemotherapy, platelet infusions, scheduled intravenous medications) than middle-aged and young-adult patients in the first week of hospitalization (P < or = .01). More care topics were discussed with older patients and their families then with younger patients and their families (P < .001). Length of stay and total hospital costs were lower for older and middle-aged patients than for younger patients. Although more older patients had discussions about transfer to hospice (P < .001), older patients were no more likely to be discharged with supportive care (inpatient hospice or home with home/ hospice care). Older patients died sooner than middle-aged patients (P < .01). CONCLUSIONS: Patient age influenced care decisions and outcomes. Older patients (age > or = 65 years) received less aggressive care, had more discussions about care decisions, and died sooner than younger patients with cancer. Younger patients had longer stays, higher hospital costs, and greater probability of rehospitalization. Although well over half of patients died within 6 months of hospitalization, few patients in any age group were discharged with supportive care. Future studies should examine age differences in palliation, as well as acute care of cancer patients across inpatient and ambulatory care settings and should assess quality of care at the end of life.

Adult↗

Development of a serological test for Haemophilus ducreyi for seroprevalence studies.

We developed a new enzyme immunoassay (rpEIA) for use in determining the seroprevalence of chancroid. Three highly conserved outer membrane proteins from Haemophilus ducreyi strain 35000 were cloned, overexpressed, and purified from Escherichia coli for use as antigens in the rpEIA. Serum specimens from patients with and without chancroid were assayed to determine optimum sensitivity and specificity and to establish cutoff values. On the basis of these data, rpEIA was found to be both sensitive and specific when used to test a variety of serum specimens from patients with genital ulcers and urethritis and from healthy blood donors.

Antibodies, Bacterial↗

Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload.

BACKGROUND: The mechanism of iron absorption by the intestine and its transfer to the main iron storage site, the liver, is poorly understood. Recently an iron carrier was cloned and named DMT1 (divalent metal transporter 1). AIMS: To determine the level of DMT1 gene expression and protein distribution in duodenum and liver. METHODS: A DMT1 cRNA and antibody were produced and used in in situ hybridisation and immunohistochemistry, respectively, in rats in which the iron stores were altered by feeding diets with normal, low, and high iron content. RESULTS: Duodenal DMT1 mRNA was low in crypts and increased at the crypt-villus junction in iron deficient and control rats; it fell in the iron loaded state. Staining for DMT1 protein was not detected in crypts. In villus enterocytes, protein staining was localised to the microvillus membrane in iron deficiency, in the cytoplasm and to a lesser extent in the membrane in controls, and entirely in the cytoplasm of iron loaded animals. Liver DMT1 mRNA was distributed evenly across hepatocytes. DMT1 protein staining was observed on hepatocyte plasma membranes, with highest values in the iron loaded state, lower values in control animals, and none after iron depletion. CONCLUSIONS: Results are consistent with a role for DMT1 in the transmembrane transport of non-transferrin bound iron from the intestinal lumen and from the portal blood.

Animals↗

Gene expression of divalent metal transporter 1 and transferrin receptor in duodenum of Belgrade rats.

Regulation of iron absorption is thought to be mediated by the amount of iron taken up by duodenal crypt cells via the transferrin receptor (TfR)-transferrin cycle and the activity of the divalent metal transporter (DMT1), although DMT1 cannot be detected morphologically in crypt cells. We investigated the uptake of transferrin-bound iron by duodenal enterocytes in Wistar rats fed different levels of iron and Belgrade (b/b) rats in which iron uptake by the transferrin cycle is defective because of a mutation in DMT1. We showed that DMT1 in our colony of b/b rats contains the G185R mutation, which in enterocytes results in reduced cellular iron content and increased DMT1 gene expression similar to levels in iron deficiency of normal rats. In all groups the uptake of transferrin-bound iron by crypt cells was directly proportional to plasma iron concentration, being highest in iron-loaded Wistar rats and b/b rats. We conclude that the uptake of transferrin-bound iron by developing enterocytes is largely independent of DMT1.

Animals↗

Minimizing discomfort with surface neuromuscular stimulation.

The purpose of this study was to evaluate the effects of stimulus parameters, electrode types, and electrode positions on the perception of discomfort during lower extremity surface neuromuscular stimulation. Ten normal and eight neurologically impaired (four incomplete spinal cord and four stroke) subjects were enrolled. Neurologically impaired subjects had some sensation, although it was often reduced. Parameters of the stimulation were varied in a way that produced the same level of ankle dorsiflexion, as measured with a goniometer. Discomfort was assessed after each stimulation with a 0-10 verbal scale (0, no discomfort; 10, worst pain). Increasing the pulse frequency was associated with increased discomfort for subjects in both groups (p > 0.05). Increasing the pulse duration was associated with increased discomfort in the neurologically impaired subjects (p > 0.05), but not in the normal subjects (p > 0.05). The electrode size and type had no effects on discomfort (p > 0.05). Stimulation of the peroneal nerve over the fibular head was better tolerated than the direct motor point stimulation of the tibialis anterior motor point (p < 0.05). The data suggest that to minimize discomfort, surface stimulation should be applied over nerves rather than motor points, and frequency and pulse duration should be set as low as possible for a given degree of contraction.

Adult↗

Malignant craniopharyngioma.

Craniopharyngiomas are histologically and cytologically benign epithelial tumors of the central nervous system that may be locally aggressive and tend to recur after excision. Malignant change in craniopharyngiomas is extremely rare; we found only 4 such reports in the literature. In this report, we describe a case of squamous cell carcinoma arising in a previously benign craniopharyngioma in a 42-year-old woman. The patient was diagnosed with craniopharyngioma in 1982; during the subsequent 15 years she experienced 7 tumor recurrences, for which surgical resections and 3 courses of radiotherapy were performed. In 1998, the tumor recurred with involvement of the nasal cavity and sphenoid and ethmoid sinuses. Histologic evaluation revealed foci of typical adamantinomatous craniopharyngioma associated with a moderately differentiated squamous cell carcinoma. The transition of typical craniopharyngioma to squamous cell carcinoma was well demonstrated, suggesting that carcinoma arose from the underlying craniopharyngioma. Radiation may have been a contributing factor to carcinogenesis in this case.

Adult↗

Eosinophil count in nasal secretions of subjects with and without nasal symptoms.

The aim of this paper, based on a cross-sectional study of 129 patients with nonallergic chronic nasal symptoms and 40 healthy controls, was to examine the leucocyte differential count in nasal secretions as a diagnostic test. Nasal secretions were collected using preweighed suction glass canulas under controlled conditions (-100Pa, 30 sec). Leucocyte and differential counts were performed using a Thoma hemocytometer and on cytospin slides after May-Grünwald-Giemsa staining. The percentage of eosinophils (Eo) was significantly higher in patients (mean +/- SEM: 15.1 +/- 2.3%) than in controls (5 +/- 2.6%) (p < 0.04). Comparison of the frequency distribution of the percentage of Eo in patients and controls clearly showed a subgroup of patients presenting with nasal secretion hypereosinophilia, and allowed us to set the positivity criterion at Eo = 20%. Diurnal variations in Eo count in 11 controls and 8 patients confirmed the value of the cutoff point. In 28 patients with nasal polyposis who underwent surgery, a correlation was found between secretion and tissue eosinophelia (r = 0.58, p = 0.001). Patients with nasal secretion hypereosinophilia had no more leucocytes in their secretions than healthy controls, the increase in eosinophils being balanced by a decrease in neutrophils. In patients without hypereosinophilia, the number of leucocytes per milligram of secretion was four times higher (8672 +/- 2521) than in the controls (2020 +/- 823) (p = 0.06) (cut-off point = 2500 leu/mg). These data show that the nasal cytogram can be modified either in qualitative or quantitative way, probably depending on the underlying inflammatory process.

Adult↗

Retaining the aortic fat pad during cardiac surgery decreases postoperative atrial fibrillation.

BACKGROUND: Atrial arrhythmias are a common and serious complication of cardiac surgical procedures. Reports describing pericardiac neurogenic tissue led us to hypothesize that removal of the aortic fat pad could cause an autonomic imbalance and contribute to atrial arrhythmias following cardiac surgery. METHODS: Patients (n=131) underwent either conventional cardiopulmonary bypass surgery (CPB) or off-pump coronary artery bypass (OPCAB) surgery. The aortic fat pad was either left intact or removed. The incidence of de novo atrial arrhythmias during the patient's hospital stay was tabulated. Patients with peri-operative myocardial infarction or pre-existing atrial or supraventricular arrhythmias were excluded. RESULTS: Demographics, preoperative medications, ASA and NYHA classifications, and complication rates (other than for atrial arrhythmias) did not differ among the groups. The STS-predicted mortality was higher in the CPB/Fat-Pad-Removed group (2.23 +/- 1.89) than in either the OPCAB/Fat-Pad-Intact (1.09 +/- 0.80) or OPCAB/Fat-Pad-Removed (1.02 +/- 0.62) groups (p < 0.05). Atrial arrhythmias were present in 19 of 131 patients (14.5%). Logistic regression demonstrated a significantly elevated atrial arrhythmia rate when the fat pad was removed (odds ratio = 3.49, 95% bounds = 1.09 to 11.18, p = 0.035). Neither the pump status nor the cross product of pump status by fat pad status were significant in this pilot study. CONCLUSIONS: Retaining the aortic fat pad during coronary artery bypass surgery is correlated with a decreased incidence of postoperative atrial arrhythmias.

Adipose Tissue↗

Treatment of fluconazole-refractory oropharyngeal candidiasis with itraconazole oral solution in HIV-positive patients.

This open-label, multicenter trial evaluated the efficacy and safety of a new oral solution formulation of itraconazole in HIV+/AIDS patients with fluconazole-refractory oropharyngeal candidiasis. Seventy-four HIV+/AIDS patients with mycologically confirmed oropharyngeal candidiasis who failed fluconazole therapy (200 mg/day) were treated with 100 mg of itraconazole oral solution administered twice daily (200 mg/day) for 14 days. Patients who demonstrated an incomplete response to treatment were treated for an additional 14 days (28 days total). Clinical responders were eligible for participation in a separate 6-month maintenance protocol. If they declined further treatment, responders were monitored for 6 weeks posttreatment. The primary efficacy parameter was clinical response (i.e., no lesions or symptoms) at end of treatment. Fungal cultures were performed at baseline and at the end of treatment. Among the 74 patients who had mycologically confirmed, fluconazole-unresponsive, oropharyngeal candidiasis at baseline, 41 (55%) achieved a clinical response by day 28. The median time to response was 7 days (range, 7 to 28 days). Candida albicans was the most common pathogen isolated, either alone (62%) or in combination with another Candida species (31%). All 22 patients who entered the optional, off-therapy, 6-week follow-up phase relapsed; mean time to relapse was 13 days. Itraconazole oral solution was well-tolerated; adverse events were predominantly gastrointestinal disturbances. This trial demonstrates that itraconazole oral solution is a useful therapy in the treatment of HIV-infected patients with fluconazole-refractory oropharyngeal candidiasis.

AIDS-Related Opportunistic Infections↗

The neuroprotective agent SR 57746A abrogates experimental autoimmune encephalomyelitis and impairs associated blood-brain barrier disruption: implications for multiple sclerosis treatment.

Experimental autoimmune encephalomyelitis (EAE) is a T cell autoimmune disorder that is a widely used animal model for multiple sclerosis (MS) and, as in MS, clinical signs of EAE are associated with blood-brain barrier (BBB) disruption. SR 57746A, a nonpeptide drug without classical immunosuppressive properties, efficiently protected the BBB and impaired intrathecal IgG synthesis (two conventional markers of MS exacerbation) and consequently suppressed EAE clinical signs. This compound inhibited EAE-induced spinal cord mononuclear cell invasion and normalized tumor necrosis factor alpha and IFN-gamma mRNA expression within the spinal cord. These data suggested that pharmacological intervention aimed at inhibiting proinflammatory cytokine expression within the central nervous system provided protection against BBB disruption, the first clinical sign of EAE and probably the key point of acute MS attacks. This finding could lead to the development of a new class of compounds for oral therapy of MS, as a supplement to immunosuppressive agents.

Administration, Oral↗

Role of synaptic vesicle proton gradient and protein phosphorylation on ATP-mediated activation of membrane-associated brain glutamate decarboxylase.

Previously, we have shown that the soluble form of brain glutamic acid decarboxylase (GAD) is inhibited by ATP through protein phosphorylation and is activated by calcineurin-mediated protein dephosphorylation (Bao, J., Cheung, W. Y., and Wu, J. Y. (1995) J. Biol. Chem. 270, 6464-6467). Here we report that the membrane-associated form of GAD (MGAD) is greatly activated by ATP, whereas adenosine 5'-[beta,gamma-imido]triphosphate (AMP-PNP), a non-hydrolyzable ATP analog, has no effect on MGAD activity. ATP activation of MGAD is abolished by conditions that disrupt the proton gradient of synaptic vesicles, e.g. the presence of vesicular proton pump inhibitor, bafilomycin A1, the protonophore carbonyl cyanide m-chorophenylhydrazone or the ionophore gramicidin, indicating that the synaptic vesicle proton gradient is essential in ATP activation of MGAD. Furthermore, direct incorporation of (32)P from [gamma-(32)P]ATP into MGAD has been demonstrated. In addition, MGAD (presumably GAD65, since it is recognized by specific monoclonal antibody, GAD6, as well as specific anti-GAD65) has been reported to be associated with synaptic vesicles. Based on these results, a model linking gamma-aminobutyric acid (GABA) synthesis by MGAD to GABA packaging into synaptic vesicles by proton gradient-mediated GABA transport is presented. Activation of MGAD by phosphorylation appears to be mediated by a vesicular protein kinase that is controlled by the vesicular proton gradient.

Adenosine Triphosphate↗

Enantio- and diastereocontrolled dopamine D1, D2, D3 and D4 receptor binding of N-(3-pyrrolidinylmethyl)benzamides synthesized from aspartic acid.

Subreceptor selectivity tuning of N-(3-pyrrolidinyl)benzamides leading to the selective dopamine D3 ligand ent1h and the derivatives 1g and 1e/ent1e which preferably recognize human D2 or D4 receptors, respectively, is described. Binding profiles were controlled by both, absolute and relative configuration. The enantiopure target compounds were synthesized from aspartic acid.

Animals↗

Development of a database management/analysis system for field research activities within a coordinated research project.

There are several ways a database/analysis system can assist a scientist engaged in field research. Specifically, it can assist the scientist with accurate data collection and more rigorous data analyses. The database management portion of this system allows accurate data collection and provides easy data entry through the use of forms. In addition, it can provide the scientist with structured methods of error checking data entry and checking for implausible values and false zeros. The system can also assist the scientist with the organization of the data and provide easy methods of sorting, grouping, and selecting data for analysis. Data can then be exported to a data analysis program where the first step is data validation. A menu of analyses using examples from the coordinated research project (CRP) are demonstrated using statistical methods that test continuous and categorical data.

Analysis of Variance↗

Fatal Chaetomium cerebritis in a bone marrow transplant patient.

The number of opportunistic infections in the central nervous system (CNS) has been steadily increasing because of a rising number of immunocompromised patients. A rare form of CNS infection can be caused by Chaetomium species, one of the largest genera of saprophytic ascomycetes. The CNS lesions in the present case were caused by Chaetomium atrobrunneum. The main characteristic of almost all Chaetomium species is presence of hairs or setae covering the ascomata. Microbiological studies are the only definitive way to correctly identify this fungal organism. The rapid evolvement of the cerebral infection suggests that the brain tissue provides a favorable environment for growth and proliferation of these fungi. This is the second documented case of a fatal brain abscess caused by Chaetomium atrobrunneum, and the first case report in a bone marrow transplant patient.

Adult↗