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Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 127 records · Page 7Linked to original sources

High or low doses of almitrine bismesylate in ARDS patients responding to inhaled NO and receiving norepinephrine?

OBJECTIVE: To evaluate the effects on oxygenation and pulmonary haemodynamics of almitrine bismesylate (AB) 5 microg/kg per minute and 16 microg/kg per minute in ARDS patients responding to and receiving inhaled NO (iNO) and presenting septic shock requiring norepinephrine, while no difference was observed in a previous trial including iNO responders and nonresponders. DESIGN: Prospective, cohort study. SETTING: Adult medico-surgical intensive care unit of a university hospital. PATIENTS: Fifteen patients with ARDS receiving and responding to iNO (10 ppm) and presenting septic shock requiring norepinephrine (mean 0.5+/-0.45 microg/kg per minute, range 0.08- 2.08). INTERVENTIONS: The protocol consisted of two consecutive phases in a fixed order: continuous intravenous infusion of AB 5 microg/kg per minute for 30 min, and continuous intravenous infusion of AB 16 microg/kg per minute for 30 min. MEASUREMENTS AND MAIN RESULTS: AB 5 microg/kg per minute significantly increased PaO2/FiO2 ( P<0.05) compared with iNO alone [160 (range 77-450) mmHg vs 122 (range 70-225) mmHg]. AB 16 microg/kg per minute produced a greater increase of PaO2/FiO2 ( P<0.05) when compared with 5 microg/kg per minute [227 (range 84-501) mmHg]. AB did not improve shunt at any dose regimen. AB produced an increase in mean pulmonary arterial pressure (MPAP) from 22+/-5 to 25+/-4 mmHg ( P<0.03). MPAP did not significantly increase between the two doses. Pulmonary vascular resistances and other haemodynamic and respiratory parameters were not affected by almitrine bismesylate. CONCLUSIONS: These results suggest that it is possible to obtain a further improvement in oxygenation by increasing AB infusion rate in ARDS patients iNO responders receiving norepinephrine. Due to the potential deleterious effects of AB, this strategy should be used in the most severely hypoxaemic patients.

Administration, Inhalation↗

The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros.

The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution.

Journal Article↗

Clinical features of latent inhibition in schizophrenia.

Paradigms of Latent Inhibition (LI) are inter-species and derived from learning theories. They are considered as tools which allow the attentional processes to be studied. The absence of LI is interpreted as difficulty in discriminating relevant and irrelevant stimuli. Abolition of LI has been shown in acute schizophrenics. The objectives of our study were partly to validate an LI paradigm, based on a contingency detection between two stimuli, in healthy subjects, and partly to analyse LI in schizophrenics. The study included 105 subjects (65 patients and 40 controls). Patients fulfilled the DSM IV diagnosis of schizophrenia. 35 in the acute phase and 30 in the chronic phase. We observed a loss of LI for acute schizophrenics, and an enhancement of LI for chronic schizophrenics. The variations in LI are interpreted from the perspective of a disturbance in the attentional processes. The LI status in acute schizophrenics appears to correlate with the clinical criteria with a prognostic value (low intensity of the negative dimension, late age at the first hospitalization). Moreover, the enhancement of LI correlates with the negative dimension of schizophrenic disease. This correlation is found in acute and chronic schizophrenics. It suggests that the variations of LI may be an indicator of adaptive strategies to a cognitive dysfunction specific to schizophrenia.

Adult↗

The use of fibre-optic transillumination in general dental practice.

OBJECTIVE: To assess the use of fibre-optic transillumination (FOTI) as a diagnostic tool in general dental practice. DESIGN: A cross-over quantitative study for the diagnosis of approximal carious lesions by two clinical methods with a qualitative component. SUBJECTS AND METHODS: Seven GDPs were trained to use FOTI as an adjunct to their usual clinical examination to diagnose approximal caries. After 12 weeks of use in their practices four of the GDPs took part in two assessment sessions, set a week apart, using 29 volunteer patients. Each patient was examined on two separate occasions by each GDP using either their standard clinical examination technique alone or supplemented by FOTI examination. The order of the techniques was randomised. Radiographs of each patient were also examined separately. An experienced FOTI user also examined the patients to provide a benchmark. From standard charts the number of enamel and dentinal lesions on approximal surfaces was summed and comparisons made between the techniques. Six GDPs took part in one-to-one interviews. MAIN OUTCOME MEASURES: Mean numbers ofcarious lesions recorded by each clinician using each technique. RESULTS: There was a trend for all GDPs to find more enamel and dentinal lesions using FOTI, than with their standard clinical examination with or without radiographs. All GDPs found the FOTI technique a useful adjunct. They used FOTI in different ways and found a variety of uses for it other than caries diagnosis. CONCLUSIONS: The

Cross-Over Studies↗

Partial characterization of matrix components interacting with cartilage proteoglycans.

The charge content of aqueous suspensions of milled cartilage samples was determined by a colloid titration technique using a particle charge detector, and the data were compared with estimates from chemical analyses. Results indicated a close correlation between charge content determined by titration and that estimated by chemical analyses for samples of nasal septa only (a nonarticular cartilage). Such correlation did not hold for articular cartilages (metacarpalphalangeal joint and patella); extraction of these tissues with 0.1 or 1.2 M NaCl markedly increased the availability of the negative groups. Protein analysis, by SDS--PAGE, of the 1.2 M extracts indicated the presence of basic proteins, some of collagenous origin, such as chondrocalcin and proline-arginine-rich protein, and some of noncollagenous proteins such as pleiotrophin and histone-H2b. These data thus suggest electrostatic interactions between these basic proteins and the negative groups of proteoglycans. Such interactions would have an important effect on the osmotic properties and in the organization of cartilage.

Animals↗

Heterogeneous RNA-binding protein M4 is a receptor for carcinoembryonic antigen in Kupffer cells.

Here we report the isolation of the recombinant cDNA clone from rat macrophages, Kupffer cells (KC) that encodes a protein interacting with carcinoembryonic antigen (CEA). To isolate and identify the CEA receptor gene we used two approaches: screening of a KC cDNA library with a specific antibody and the yeast two-hybrid system for protein interaction using as a bait the N-terminal part of the CEA encoding the binding site. Both techniques resulted in the identification of the rat heterogeneous RNA-binding protein (hnRNP) M4 gene. The rat ortholog cDNA sequence has not been previously described. The open reading frame for this gene contains a 2351-base pair sequence with the polyadenylation signal AATAAA and a termination poly(A) tail. The mRNA shows ubiquitous tissue expression as a 2.4-kilobase transcript. The deduced amino acid sequence comprised a 78-kDa membrane protein with 3 putative RNA-binding domains, arginine/methionine/glutamine-rich C terminus and 3 potential membrane spanning regions. When hnRNP M4 protein is expressed in pGEX4T-3 vector system in Escherichia coli it binds (125)I-labeled CEA in a Ca(2+)-dependent fashion. Transfection of rat hnRNP M4 cDNA into a non-CEA binding mouse macrophage cell line p388D1 resulted in CEA binding. These data provide evidence for a new function of hnRNP M4 protein as a CEA-binding protein in Kupffer cells.

Amino Acid Sequence↗

Laser altimetry of small-scale features on 433 Eros from NEAR-Shoemaker.

During the Near Earth Asteroid Rendezvous (NEAR)-Shoemaker's low-altitude flyover of asteroid 433 Eros, observations by the NEAR Laser Rangefinder (NLR) have helped to characterize small-scale surface features. On scales from meters to hundreds of meters, the surface has a fractal structure with roughness dominated by blocks, structural features, and walls of small craters. This fractal structure suggests that a single process, possibly impacts, dominates surface morphology on these scales.

Journal Article↗

Mutations in the carcinoembryonic antigen gene in colorectal cancer patients: implications on liver metastasis.

Carcinoembryonic antigen (CEA) expression is used clinically to monitor patients with colorectal and other cancers. A subset of patients have extraordinarily high CEA levels that cannot be attributed solely to tumor load. We have shown mutations in the region of CEA (PELPK motif) responsible for its hepatic clearance in three of eight patients with high CEA levels. We used denaturing high-performance liquid chromatography to provide evidence of polymorphism in these patients. These mutations were scored by DNA cycle sequencing and shown to be heterozygous. The patients with mutations in the PELPK motif showed remarkably reduced circulatory clearance rates in an animal model. A patient without mutation in the region showed normal clearance rates. Mutations in PELPK may affect structural stability and binding affinity to the Kupffer cell receptor in the liver. These studies have implications for the role of CEA as a facilitator of hepatic metastasis.

Amino Acid Sequence↗

Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel and carboplatin in the treatment of previously untreated patients with metastatic small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were aged 18 to 75 years with an Eastern Cooperative Oncology Group (ECOG) score < or = 2 and life expectancy > or = 12 weeks. Paclitaxel (200 mg/m(2)) was infused over 3 hours, before carboplatin (area under the curve [AUC] 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. Prednisolone, dexchlorpheniramine, and ranitidine were standard premedication. Response to treatment was assessed every two cycles, and nonresponding patients were withdrawn from the trial to receive standard chemotherapy. RESULTS: Of the 50 patients entering the study, 48 and 46 patients were assessable for toxicity and response, respectively. The overall response rate was 65%, with complete responses in three patients. Five patients had stable disease (11%) and 11 patients experienced progressive disease (24%). Median survival was 38 weeks, and median duration of response was 20 weeks. One-year survival was 22.5%. For a total of 232 cycles, grade 3 and 4 toxicity was 33% for neutropenia, 3.5% for thrombocytopenia, and 4% for anemia. Four patients had neutropenic fever (one toxic death). Nonhematologic toxicity was mainly grade 1 and 2 paresthesia (21% of patients); grade 3 myalgia/arthralgia was observed in 6.5% of patients. CONCLUSION: First-line chemotherapy with paclitaxel and carboplatin in metastatic SCLC achieved a response rate and survival similar to standard regimens. With 1-day administration and a tolerable toxicity profile, this combination merits further investigation.

Adult↗

Family, Alzheimer's disease and negative symptoms.

BACKGROUND: The aim of this study is to look at the correlation between the presence of apathy measured by Marin's scale and family complaints related to withdrawal and the loss of motivation, or depression. The multicentre study was performed on 58 non-demented elderly people, 132 outpatients with Alzheimer's-type dementia, as well as their main caregiver. METHODS: After agreement of the patients and the family, the patients were assessed using different scales: Cornell's for depression, Marin's for apathy, MMS for cognitive disorders, and IRG for dependence. At the same time, two self-administered questionnaires were given to the patients' families: one concerning a list of complaints scored from 1 to 4 relating to various disorders and the other addressing the boundary ambiguities translated from Boss' questionnaire. The 58 non-demented people were 81.20 years old+/-13.75. One hundred and thirty-two demented patients were included: 39 men and 93 women. The mean age was 79.47 years+/-9.03. RESULTS: The first family complaint relates to the loss of motivation (65%). Apathy and depression occur more frequently in dementia, in particular when the MMS is degraded. Depression and apathy attracted a high complaint score. In our study the score of boundary ambiguity is higher among patients with a weak cognitive status. A high level of ambiguity is accompanied by a high score of family complaints. When the family complaint concerning the loss of motivation is present, apathy is significantly more common. Family complaints about withdrawal and loss of motivation are frequently present, and are congruent with the actual presence of apathy in the patient. It bears witness to the distress felt by families faced with the loss of ability noted in the demented person. The family's difficulties are increased by the patient's depression.

Affective Symptoms↗

Effects of maturation-inducing hormone on heterologous gap junctional coupling in ovarian follicles of Atlantic croaker.

A previous ultrastructural study of heterologous (granulosa cell-oocyte) gap junction (GJ) contacts in ovarian follicles of Atlantic croaker suggested that these contacts disappear late during the process of resumption of oocyte meiosis. This observation suggested that, unlike scenarios proposed for a number of other species, uncoupling of GJ is not necessary for the onset of meiotic resumption in croaker follicles. However, the functionality of heterologous GJ contacts and the temporal association between maturation-inducing hormone (MIH)-induced changes in heterologous coupling and resumption of oocyte meiosis have not been examined in Atlantic croaker. These questions were addressed with a cell-cell coupling assay that is based on the transfer of a GJ marker, Lucifer Yellow, from oocytes to granulosa cells. Follicle-enclosed oocytes injected with Lucifer Yellow allowed transfer of the dye into the follicle cell layer, thus confirming that there is functional heterologous coupling between the oocyte and the granulosa cells. Dye transfer was observed in vitellogenic, full-grown/maturation-incompetent, and full-grown/maturation-competent follicles. Treatment of maturation-competent follicles with MIH caused a time-dependent decline in the number of follicles transferring dye. However, although GJ uncoupling in some of the follicles was observed before germinal vesicle breakdown (GVBD, index of meiotic resumption), about 50% of the follicles maintained the ability to transfer dye even after GVBD had occurred. Further, a known GJ inhibitor (phorbol 12-myristate 13-acetate) blocked heterologous GJ within a time frame similar to that seen with MIH but without inducing any of the morphological changes (including GVBD) associated with follicular maturation. In conclusion, uncoupling of heterologous GJ seems insufficient and unnecessary for the onset of meiotic resumption in ovarian follicles of Atlantic croaker.

Animals↗

Chlorinated hydrocarbons and biomarkers of exposure in wading birds and fish of the lower Rio Grande Valley, Texas.

During 1997 we evaluated reproductive success in colonial water birds nesting in the Lower Rio Grande Valley (LRGV), Texas, and correlated success with concentrations of contaminants in eggs. We also measured steroid hormones and gonadosomatic index (GSI) as biomarkers of endocrine effects in common carp (Cyprinus carpio). Nest and fledging success of green herons (Butorides virescens) and great egrets (Ardea alba) were similar to those found in other parts of North America; however, nesting success of black-crowned night-herons (Nycticorax nycticorax) was lower, very likely due to flooding of the nesting area. Except for DDE and toxaphene, all chlorinated pesticides in bird eggs were low and not of concern for negative effects on any of the three species. DDE was highest in green heron eggs and seemed to increase along a geographic gradient from west to east, with eggs from Falcon Reservoir containing low concentrations, and those at Los Indios containing the highest concentrations (approx. 11,000 ng/g WW), near or above the threshold for reproductive impairment. DDE levels in great egrets and black-crowned night-herons were below those that are associated with reproductive impairment. Mean DDE levels in carp at the JAS Farms site were above the threshold level suggested for predator protection. Toxaphene was detected in about 20% of the samples with high levels observed in green heron eggs from Los Indios (mean = 4,402 ng/g WW). These are the highest toxaphene levels reported in bird eggs in the LRGV. Toxaphene levels in fish ranged between 90 and 312 ng/g WW. In general, PCBs in bird eggs and fish tissue were low and at levels not of concern for reproductive effects. The greatest concentrations of testosterone and 11-ketotestosterone were detected in fish from the JAS Farms site, which also had the greatest concentrations of DDE. Increased androgen production and gonad development in fish at this site, relative to Pharr, could be possibly associated with endocrine disrupting effects of p,p'-DDE. DDE, toxaphene, PCBs, and hormones were highest in birds and fish from the eastern edge of the study area.

Abnormalities, Drug-Induced↗

Tetrabutylammonium: a selective blocker of the somatostatin-activated hyperpolarizing current in mouse AtT-20 corticotrophs.

To obtain a clearer understanding of the mechanisms by which somatostatin modulates stimulus-secretion coupling in neuroendocrine cells, we investigated the pharmacology of the somatostatin-activated inward rectifier in mouse pituitary tumour cells (AtT-20 corticotrophs). Individual AtT-20 cells displayed spontaneous, long-lasting action potentials that caused transient spikes in cytosolic [Ca2+] ([Ca]i). Application of 1-10 nM somatostatin led to membrane hyperpolarization and loss of [Ca]i spiking activity. Voltage-clamp recordings revealed that the somatostatin-induced hyperpolarization was due to an inwardly rectifying K+ current. Tetrabutyl-ammonium (TBA+) inhibited both outward and inward currents through the inward rectifier, whereas Cs+ blocked only inward current and tetraethylammonium (TEA+) was completely ineffective in blocking somatostatin-activated currents. However TEA+, but neither TBA+ nor Cs+, blocked voltage-gated outward currents. Correspondingly, TBA+ abolished the hyperpolarizing effects of somatostatin and, of the three K+ channel blockers, only TBA+ prevented the somatostatin-induced inhibition of [Ca]i spiking. TBA+ may thus prove a useful tool in elucidating the underlying mechanisms by which somatostatin affects the secretory activity of neuroendocrine cells.

Action Potentials↗

Exsanguinating hemoptysis revealing the absence of left pulmonary artery in an adult.

Isolated absence of a pulmonary artery is an exceptional cause of massive hemoptysis. We report a 35-year-old woman with agenesis of the left pulmonary artery who presented with exsanguinating hemoptysis that prompted angiography with the aim to embolize the bleeding vessels selectively. The procedure could not be completed because of the presence of an anterior spinal artery branching from the aberrant systemic-to-pulmonary circulation. The patient successfully underwent an emergent pneumonectomy.

Adult↗