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Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 145 records · Page 8Linked to original sources

An estimation of radiation doses to benthic invertebrates from sediments collected near a Canadian uranium mine.

A new method is described for calculating radiation doses to benthic invertebrates from radionuclide concentrations in freshwater sediment. Both internal and external radiation doses were estimated for all 14 principal radionuclides of the uranium-238 decay series. Sediments were collected from three sites downstream of a uranium mining operation in northern Saskatchewan, Canada. Sediments from two sites, located approximately 1.6 and 4.4 km downstream from mining operations, yielded absorbed doses to both larval midges, Chironomus tentans, and adult amphipods, Hyalella azteca, of 59-60 and 19 mGy/year, respectively, compared to 3.2 mGy/year for a nearby control site. External beta radiation from protactinium-234 (234Pa) and alpha radiation from uranium (U) contributed most of the dose at the impacted sites, whereas polonium-210 (210Po) was most important at the control site. If a weighting factor of 20 was employed for the greater biological effect of alpha vs. beta and gamma radiation, then total equivalent doses rose to 540-560 mGy/year at the site closest to uranium operations. Such equivalent doses are above the 360-mGy/year no-observed-effect level for reproductive effects in vertebrates from gamma radiation exposure. Data are not available to determine the effect of such doses on benthic organisms, but they are high enough to warrant concern. Detrimental effects have been observed in H. azteca at similar uranium concentration in laboratory toxicity tests, but it remains unclear whether the radiotoxicity or the chemotoxicity of uranium is responsible for these effects.

Animals↗

[Study of methicillin-resistant Staphylococcus aureus colonization among intermediate-care facility patients].

PURPOSE: Prevalence of methicillin-resistant Staphylococcus aureus is high in the Poitiers teaching hospital, particularly in the intermediate care facilities. We performed a survey of methicillin-resistant Staphylococcus aureus colonization in the intermediate care facilities and 265 patients were included. METHODS: Nasal, cutaneous and wound swab cultures were done at the time of admission and at the time of the patients' departure. A decolonization procedure of methicillin-resistant Staphylococcus aureus carriers was performed using nasal application of fusidic acid and different soaps for the skin. At entry, 17.7% of patients were methicillin-resistant Staphylococcus aureus carriers (of at least one location). At departure, 30.4% were methicillin-resistant Staphylococcus aureus carriers. Among methicillin-resistant Staphylococcus aureus non-carriers at entry, 24.3% became methicillin-resistant Staphylococcus aureus carriers. RESULTS: The principal risk factor of carriage was the initial presence of a wound (RR = 3.6). The incidence rate of methicillin-resistant Staphylococcus aureus infection among the 265 patients included was 3%. CONCLUSION: The systematic screening of patients at the time of admission is expensive and isolation technically hard to manage in the intermediate care facilities. The risk factor we found in this study allow us to propose a 'light' screening limited to patients with wounds.

Aged↗

Surgical management of metachronous bronchial carcinoma.

OBJECTIVE: To assess the results of surgery for the treatment of metachronous bronchial carcinoma. METHODS: From 1985 to 1999, 38 patients were operated on for a metachronous lung carcinoma, accordingly to the criteria of Martini. All tumors were staged using the new International Classification System revised in 1997. RESULTS: Diagnosis of the second cancer was done at radiological follow-up in 30 asymptomatic patients. Seventeen metachronous locations were ipsilateral. Histology of the metachronous lesion was the same as that of the first tumour in 23 patients (60%). The first resection was a lobectomy (n=35), a pneumonectomy (n=2) and a carinal resection (n=1). The second one was a wedge resection (n=7), a segmentectomy (n=3), a lingulectomy (n=2), a lobectomy (n=9), a bilobectomy (n=1), and a pneumonectomy (n=16). There were five in-hospital deaths (13%). Completion pneumonectomy was performed in 15 patients, with one postoperative death (7%). The overall estimated 5 and 10-years actuarial survival rates from the treatment of the first cancer were 70 and 47% respectively. The 5-year survival rate after the treatment of the second cancer was 32% (median survival: 31 months), including the operative mortality. Survival was negatively affected by a resection interval of less than 2 years and the performance of atypical lung sparing pulmonary resection for the treatment of the second cancer. CONCLUSIONS: Good long-term results are achievable by the means of a second pulmonary resection in selected patients with metachronous lung cancer. Optimal cancer operations should be applied whenever functionally possible.

Aged↗

Is lung cancer surgery justified in patients with direct mediastinal invasion?

OBJECTIVE: To assess the results of the surgical treatment of patients with stage IIIB non-small cell lung carcinoma (NSCLC) invading the mediastinum (T4). METHODS: Twenty-nine patients were operated on from 1986 to 1999. Histology was squamous cell carcinoma in 17 patients, adenocarcinoma in eight, large cell carcinoma in two and neuroendocrinal carcinoma in two. Three patients received a preoperative chemotherapy (n = 2) or radiochemotherapy (n = 1). The lung resection consisted of a pneumonectomy in 25 patients and a lobectomy in four. The procedure was extended to one of the following structures: superior vena cava (SVC) (n = 17), aorta (n = 1), left atrium (n = 5) and carina (n = 6). Seventeen patients had a postoperative regimen including radiochemotherapy (n = 12), radiotherapy (n = 4), or chemotherapy (n = 1). RESULTS: Complete R0 resection was achieved in 25 patients, whereas four patients had a microscopically (n = 1) or macroscopically (n = 3) residual disease. The operative mortality rate was 7% (n = 2). Non-fatal major complications occurred in eight patients (28%). Overall 5-year survival rate was 28% (median 11 months), including the operative mortality. The median survival of the 18 patients with an N0 or N1 disease was 16 months whereas the median survival of the 11 patients with an N2 disease was 9 months. At completion of the study, 22 patients have died, two postoperatively and 10 from pulmonary causes without evidence of cancer. CONCLUSIONS: Surgical management of T4 NSC lung cancer invading the mediastinum should be considered, in the absence of N2 disease, when a complete resection is achievable.

Adenocarcinoma↗

Postoperative complications in relation with induction therapy for lung cancer.

OBJECTIVES: The purpose of this study was to evaluate the risk of lung cancer surgery following induction chemotherapy and/or radiotherapy. METHODS: This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA, n = 25); temporary functional impairment (two stages IB and two stages IIIA (N2), n = 4); and doubtful resectability (stage IIIB (T4), n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received two to four cycles of chemotherapy (average 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (range 20--60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in four patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were four re-operations (6%): three for bronchial fistula and one for bleeding. Thirty-five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSIONS: Surgery for lung cancer after induction chemotherapy and/or radiotherapy is associated with an increased risk. If the mortality seems 'acceptable', the morbidity rate, however, is high.

Blood Transfusion↗

Bilateral bronchioloalveolar lung carcinoma: is there a place for palliative pneumonectomy?

OBJECTIVE: Bronchioloalveolar lung carcinoma (BAC) is characterized by bronchial and lymphatic dissemination explaining multifocal and bilateral spreading. Bilateral BAC is usually considered as a contraindication to surgery. Regarding poor efficacy of symptomatic and oncological treatments, we hypothesized that surgery might play a role to palliate hypoxemia associated with serious intrapulmonary shunting, as well as continuous bronchorrhea. METHODS: We retrospectively studied here four consecutive patients, who underwent palliative pneumonectomy. RESULTS: The shunt was confirmed again at the time of the surgery by a pulmonary artery occlusion demonstrating immediate improvement in arterial oxygen saturation from 89% at baseline to 98% after occlusion. Lung resections consisted of a left pneumonectomy in three cases and a right pneumonectomy in one. PaO(2) levels under 5l/min oxygen therapy improved dramatically when comparing preoperative data (mean 50.5 mmHg) to post-operative results (mean 150 mmHg). One patient died postoperatively. Three patients, who experienced an uneventful immediate post-operative course, received chemotherapy after surgery. Improvement of quality of life is testified by the absence of both symptoms and any need for oxygen therapy for few months. Disabling symptoms reappeared at 1, 8 and 10 months. Survival of these patients was 3, 12 and 18 months. CONCLUSIONS: These results support the interest of consideration of a surgical resection for highly selected patients presenting with bilateral BAC and severe intrapulmonary shunting.

Adenocarcinoma, Bronchiolo-Alveolar↗

Alterations in the GnRH-LH system in relation to gonadal stage and Aroclor 1254 exposure in Atlantic croaker.

Exposure of Atlantic croaker (Micropogonias undulatus) to the polychlorinated biphenyl mixture (Aroclor 1254, PCB; 1 mg/kg body wt/day for 30 days) during the early-recrudescence phase of the gonadal cycle results in the impairment of LH secretion and gonadal growth. In order to determine whether impairment was due to disruption of the stimulatory GnRH neuroendocrine pathway, we compared various parameters of the GnRH-LH system in early recrudescing vs. spermiating (mature) fish. Seabream GnRH (GnRH) content in the preoptic anterior hypothalamic area (POAH) and pituitary, pituitary GnRH receptor concentrations, and basal and GnRH analog (GnRHa)-induced LH secretion were significantly higher in gonadally mature croaker compared to early-recrudescing fish. In a subsequent experiment, the effects of PCB on the same neuroendocrine indices were investigated during the gonadal recrudescence phase of croaker. PCB exposure during the period of testicular maturation prevented the natural increase in GnRH content in the POAH but not in the pituitary. This finding suggests that PCB may impair GnRH synthesis in the POAH. The number of pituitary GnRH receptors also remained significantly lower in the PCB-exposed group, which was likely due to an impairment of GnRH release. The GnRH content in the POAH, number of pituitary GnRH receptors, and LH secretion in the PCB-exposed group were comparable to those in early-recrudescing fish, suggesting an impairment of normal maturation of the GnRH-LH system during the gonadal recrudescence phase. This impairment may be due to a direct action of PCB on GnRH neurons and/or indirectly via interference with other neurotransmitter pathways that modulate GnRH function.

Animals↗

Gonadotropic control of ovarian follicle maturation: the two-stage concept and its mechanisms.

Most research on the control of oocyte maturation by luteinizing hormone (LH) in teleosts and amphibians has focused on the production and action of maturation-inducing hormone (MIH), the follicular hormone that directly triggers the resumption of oocyte meiosis. However, current information indicates that LH regulates maturation in two stages, and that 'oocyte maturation' can be appropriately described within the broader context of 'ovarian follicle maturation'. During the first stage of maturation the follicle (somatic) cells acquire the ability to produce MIH and the oocyte to respond to MIH (i.e. oocyte maturational competence, OMC), whereas in the second stage the follicle cells produce MIH and, consequently, the oocyte is released from meiotic arrest. A number of factors such as insulin-like growth factor-I, serotonin, and others may mediate or modulate the OMC-inducing action of LH. Like the acquisition of MIH-producing ability, the acquisition of OMC requires activation of the protein kinase A pathway. Two major cellular events associated with OMC acquisition are increases in homologous and heterologous gap junction contacts and in oocyte MIH receptor activity. The increased oocyte MIH receptor activity is presumably associated with OMC acquisition, but the significance of changes in gap junction contacts is at present uncertain. To eliminate inconsistency and ambiguity associated with current terminology we propose that the term, ovarian follicle (or oocyte) maturation be used for teleosts without qualifiers such as 'final' to define the first and second stages of follicular maturation.

Animals↗

Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of haematologic toxicity.

BACKGROUND: The incidence of haematologic toxicity of valproate (VPA) ranges from 1% to 32% and consists mainly of asymptomatic, dose-dependent thrombopenia. We describe a potentiation of haematologic side-effects of nitroso-urea (NU) when prescribed in association with VPA. PATIENTS AND METHODS: We followed a cohort of 70 patients (58 men, 22 women, mean age: 56 years, range 20-75 years). Patients with high-grade gliomas were treated with up-front chemotherapy regimen consisting of fotemustine (d3: 100 mg/m2), cisplatin (d1-3: 33 mg/m2) and etoposide (d1-3: 75 mg/m2) followed by whole brain radiotherapy at progression. Sixty patients required anti-epileptic drugs (AED) for either a single, well-documented epileptic seizure, or immediatly initiated after neurosurgical procedures. AED included VPA (35 of 60), phenobarbital (PB) (17 of 60), carbamazepine (CBZ) (2 of 60) and phenytoin (PHT) (3 of 60). Two patients had both PB and CBZ and one PB and PHT. RESULTS: Haematologic toxicity (grade 3-4 thrombopenia, neutropenia or both) was observed in 37 of 70 (52.85%) patients. Among them 24 (65%) had VPA. Group C were patients treated with fotemustine alone with or without VPA (23 patients). CONCLUSION: When prescribed in association with a fotemustine-cisplatin regimen, VPA treatment results in a three-fold higher incidence of reversible thrombopenia, neutropenia or both. Haematologic side-effects decrease after AED modification during the continued chemotherapy. This adverse event should be managed with caution.

Adult↗

Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Français de Pneumo-Cancérologie (GFPC) Protocol 95-1.

PURPOSE: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis. PATIENTS AND METHODS: One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m2 on day 1 and vinorelbine 30 mg/m2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids. (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B). RESULTS: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with 1 complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities. CONCLUSIONS: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.

Adult↗

Molecular analysis of T-cell clonality with concomitant specific T-cell proliferation in vitro in nickel-allergic individuals.

BACKGROUND: The peripheral blood mononuclear cells (PBMC) of individuals with nickel contact allergy are reported to proliferate to a varying degree upon nickel stimulation in vitro. Different phenotypes of the T cells involved are described. With regard to preferential use of the T-cell receptor (TCR), analysis of the several families of the TCR-gamma gene allows rearrangement evaluation of all T cells regardless of predominant surface expression of TCR alpha/beta. METHODS: The PBMC of 10 nickel-allergic and five nonallergic individuals were cultured for 4 days in the presence of either medium, PHA, NiSO4, or tetanus toxoid (TT). Proliferation was measured by radioactive thymidine uptake and expressed as stimulation index (SI). T-cell clonality was assessed by analysis of the TCR-gamma chain gene, including the use of PCR with a primer combination covering the four main groups (Vgamma1-8, Vgamma9, Vgamma10, and Vgamma11) of the variable region of the TCR-beta chain gene. RESULTS: In the allergic individuals, proliferation to NiSO4 was significantly (P<0.05) higher than in nonallergics (mean SI: 18.05/17.87 vs 0.67/2.27). In unstimulated and PHA-stimulated cultures, there was a random TCR spectrum in both groups. In contrast, in nickel-allergic individuals or individuals with recent TT-booster, oligoclonality could be observed in the correspondingly stimulated cultures. CONCLUSION: In addition to proliferation assay, analysis of T-cell clonality may be a further means to characterize clinical hypersensitivity reactions on the basis of antigen-dependent oligoclonal T-cell expansion, as in the case of tissue-infiltrating lymphocytes.

Adult↗

GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1.

Controlling the number of functional gamma-aminobutyric acid A (GABA(A)) receptors in neuronal membranes is a crucial factor for the efficacy of inhibitory neurotransmission. Here we describe the direct interaction of GABA(A) receptors with the ubiquitin-like protein Plic-1. Furthermore, Plic-1 is enriched at inhibitory synapses and is associated with subsynaptic membranes. Functionally, Plic-1 facilitates GABA(A) receptor cell surface expression without affecting the rate of receptor internalization. Plic-1 also enhances the stability of intracellular GABA(A) receptor subunits, increasing the number of receptors available for insertion into the plasma membrane. Our study identifies a previously unknown role for Plic-1, a modulation of GABA(A) receptor cell surface number, which suggests that Plic-1 facilitates accumulation of these receptors in dendritic membranes.

Adaptor Proteins, Signal Transducing↗

Foetal haemoglobin in homozygous sickle cell disease: a study of patients with low HBF levels.

High foetal haemoglobin (HbF) levels are believed to ameliorate the manifestations of homozygous sickle cell (SS) disease. The corollary implies that patients with low HbF levels should have more severe clinical courses. We investigated this in a retrospective study of 50 Jamaican patients with steady-state HbF levels below 1% compared with a control group (A) of 54 subjects with steady-state HbF levels between 2.5 and 3.4% (around the 25th centile for our population), and a second control group (B) of 60 patients with steady-state HbF levels between 4.6 and 5.2% (around the 50th centile). Comparisons across the groups indicated significantly fewer females in the study group (16, 50 and 57%, respectively). Examination for haematological trends across the groups showed positive linear trends for haemoglobin (Hb) (P=0.004), packed cell volume (PCV) (P=0.01), mean cell volume (MCV) (P= < 0.001), mean cell haemoglobin (MCH) (P= < 0.001) and a negative trend for haemoglobin A2 (P=0.03). Clinically, there were no differences in the incidence of painful crises, abdominal crises and the acute chest syndrome, but leg ulcers were significantly less frequent in the study group (P=0.04). Therefore low HbF levels do not appear to increase the clinical severity of SS disease and may be protective against leg ulceration.

Adolescent↗