Primary care groups and research networks: opportunities for R&D in context.
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Evidence-Based Medicine↗
Biomedical subjects
P Thomas
Publications and source records attributed to P Thomas.
[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology].
PURPOSE: Determine the response to, and toxicity of docetaxel (Taxotere) in patients (pts) with inoperable non-small-cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy. PATIENTS AND METHODS: Twenty-seven patients with stage IIIB or IV NSCLC, having received one platinum-containing regimen were treated with 100 mg/m2/3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with prednisolone and diosmin was given in all patients. Antitumoral activity was assessable in 21/27 pts. Median age: 52 years; WHO performance status 0-1: 77% pts, stage IV disease: 63% pts. RESULTS: 6/21 eligible pts (24%) achieved a partial response to treatment [C.I 95%: 5.6-42]. Median time to progression: 2.9 months, median survival: 8.5 months with a median follow-up of 23.7 months (range: 13.5-27). Hematologic toxicity: grade 3-4 neutropenia: 75% pts, febrile neutropenia: 11% cycles. Non hematologic toxicities: fluid retention, rash, alopecia, sensory neuropathy, asthenia, and nail changes. CONCLUSION: Docetaxel (Taxotere) administered at 100 mg/m2/3 weeks has relevant clinical activity against platinum treated NSCLC pts. Neutropenia is the main toxicity.
Adenocarcinoma↗
[Phase II study of docetaxel in inoperable advanced non small cell lung cancer].
The purpose is to determine the response to, and toxicity of docetaxel (Taxotère) in patients with inoperable non small cell lung cancer (NSCLC), previously untreated. Seventy patients with stage IIIB or IV NSCLC were treated by 100 mg/m2/ 3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with diosmine and prednisolone was given in all patients: 66/70 were eligible and 55/70 were assessable for antitumoral activity. Median age: 63 years, WHO performans status 0-1: 83%, stage IV: 96%. For eligible patients, 17/66 (26%) achieved an objective response: 1 complete response and 16 partial response (IC 95% = 15-36). With a median follow-up of 23.4 months (range 14.9-28.7), for evaluable patients, the median response duration was 8 months, the median time to progression 4 months, and the median survival time 10 months. The median number of administered cycles is 5 (range 1-12). The estimate one year survival rate was 47%. Seventy-six patients presented neutropenia (grade 3-4); febrile neutropenia was observed in 7% of cycles. Non haematological toxicities are: fluid retention related to docetaxel (2.9%), diarrhea (6%), nausea-vomiting (4%), asthenia (3%), nail changes (6%). Docetaxel (Taxotère) administered at 100 mg/m2/3 weeks has relevant clinical activity in previously untreated NSCLC with a acceptable toxicity.
Adult↗
[Solar urticaria: pre-PUVA UVA desensitization].
BACKGROUND: Solar urticaria is an uncommon disorder sometimes difficult to treat. It is characterized by the occurrence of typical whealing reactions on exposed skin a few minutes after sun exposure. The reactions resolve 1 to 5 hours after sun exposure ceases. We report a case evolving over several years, unresponsive to antihistamines and successfully treated by PUVAtherapy performed after UVA desensitization. CASE REPORT: For 3 years, a 22-year-old man developed erythema and itchy wheals at each solar exposure. The lesions appeared on all exposed areas including those usually exposed (face and hand) even in winter. An antihistamine regimen given for several weeks (cetirizine, loratadine) was ineffective. One trial of PUVA therapy led to an urticarial reaction of the entire body. Phototesting showed the minimal whealing dose for UVA was 0.4 J/cm(2). Phototherapy was therefore started by segmentary UVA irradiation at an initial dose of 0.1 J/cm(2). Exposure was then progressively increased allowing initiation of the PUVAtherapy on the 9(th) day with a dose of 0.5 J/cm(2) without whealing reaction. Slow increment PUVA therapy was able to induce good tolerance to sun exposure. DISCUSSION: Solar urticaria may sometimes have a deleterious effect on normal daily life. Severe cases are characterized by a whealing reaction after minimal sun exposure, even on regularly exposed skin. Antihistamines can provide some symptom relief in many patients, but high doses are required. If antihistamines are ineffective, PUVA therapy is indicated. Pre-PUVA UVA desensitization is often necessary. However, exposure to UVA alone has to be repeated every 24 to 48 hours to maintain the refractory state. The advantage of PUVA therapy is a more long lasting protection allowing weekly maintenance sessions.
Adult↗
Constructed wetlands as a tool for sewage and stormwater pollution control.
Although traditionally surface water pollution control measures in many countries of the world have been restricted to sewage effluent discharges, now it has become necessary to apply control measures to stormwater pollution as well. Constructed wetlands are considered as natural systems that provide a low cost maintenance and low energy natural treatment option for sewage and stormwater. They are especially suited for polishing effluent from existing or new sewage treatment plants, or providing treatment for septic tank effluent, by removing organic matter, suspended solids, nutrients, pathogens and heavy metals. This paper describes some important issues relating to the design of constructed wetlands and provides a summary of a pilot study with constructed wetlands for sewage treatment.
Australia↗
Cheilitis due to nickel contact allergy in a trumpet player.
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Adult↗
Is it juvenile myoclonic epilepsy?
A 21-year old man with marked developmental delay was referred for the diagnosis of myoclonic jerks (MJ), which were sometimes responsible for sudden falls without loss of consciousness, that had begun 2 years before, and for a recent generalized tonic-clonic seizure preceded by a cluster of MJ. Physical examination revealed a small stature, bilateral pyramidal signs, severe mental retardation, and retinis pigmentosa. Etiological factors for this encephalopathy were not found (muscle and skin biopsies, karyotype and extensive blood chemistry). Waking interictal EEG showed a normal background activity and generalized poly-spike-and wave (PSW) discharges. Photic stimulation disclosed a marked photoparoxysmal response, sometimes associated with myoclonic jerks. Three spontaneous jerks accompanied by a burst of generalized PSW were recorded on awakening from a nap. The MRI disclosed wide ventricles, a thin corpus callosum, brainstem atrophy and a so-called "redundant gyration"; these changes were evocative of acquired perinatal damage. Juvenile myoclonic epilepsy (JME) was diagnosed and valproate was started resulting in complete control of seizures. During a 5-year follow-up, the patient has remained seizure-free and the EEG consistently normal. In our opinion, JME can be diagnosed in very uncommon settings, including patients with significant brain damage, as long as all the other criteria for the diagnosis are present.
Adult↗
[Hospital information systems ineffectiveness in costing ambulatory chemotherapy in pulmonary oncology].
The real cost of medical consumption was compared with the proportion of medication consumption of (the) GHM n(o) 681 (homogeneous group of patients, chemotherapy for cancer in day care) in the French case mix system (PMSI). For those patients in our thoracic oncology unit (Sainte-Marguerite Hospital, Marseille, France), the real medication cost was calculated from prices paid by the hospital, then compared to the expected expenditures for the medication consumption of the GHM 681, i.e. 678 French francs (24.1% of the 225 ISA points (synthetic activity index)). Over a period of 2 months in 1998, 87 patients (mean age 63 +/- 11) had 194 chemotherapy sessions in day care, with multi-drug therapy in 38 cases. Vinorelbine or gemcitabine represented 81% of the single drug chemotherapy. In 84% of the single drug and 76% of the multi-drug chemotherapy, the real cost of medication consumption was above the allocated budget. The mean cost for single drug chemotherapy was 1722 FF and 2920 FF for multi-drug chemotherapy. The budget allocated by the PMSI shows a deficit in the most cases. To avoid a restriction in the use of some drugs, it appears that the French system of budget evaluation needs to be improved.
Aged↗
Frozen shoulder.
Stiffness is a consistent but nonspecific symptom of primary frozen shoulder, a condition defined by restriction of passive motion in all planes without glenohumeral abnormalities on plain radiographs. Since the first description by Duplay in 1872, theories and descriptions of the lesions have varied over time and across authors, with the main target of the condition being reported as the subacromial bursa in some studies and the rotator interval in others. Recent publications have pointed out similarities with Dupuytren's contracture. Magnetic resonance imaging has helped to understand the lesions by showing a specific pattern of postgadolinium enhancement during the first few months after symptom onset. Pain relief is the main objective of therapy. Oral medications have not been adequately evaluated, with the exception of glucocorticoids, which hasten the resolution of nighttime pain to a modest degree. Intra-articular glucocorticoid injections are effective and are best performed under arthrographic control. It has been suggested that intra-articular glucocorticoid injections should be combined with joint capsule distension. An additional injection into the subacromial bursa has been found useful in patients with refractory pain. Motion range recovery is not always complete after 18 to 24 months and can be improved by physiotherapy. Methodological difficulties have precluded demonstration in formal studies of the undeniable benefits of physiotherapy. Joint capsule distension, and even more so arthroscopic capsulotomy with gentle mobilization, have provided promising results in patients with persistent stiffness, although the optimal time for performing these techniques remains to be determined.
Bursitis↗
Noninvasive assessment of airway inflammation in children: induced sputum, exhaled nitric oxide, and breath condensate.
Noninvasive markers of airway inflammation are needed for use in research and clinical practice in childhood asthma. Induced sputum and exhaled nitric oxide are well established as direct markers of inflammation for use in asthma research. Sputum can be induced from children of >6 yrs using inhalation of hypertonic saline, and, if appropriate, can be combined with an assessment of airway responsiveness to hypertonic saline. The success rate of sputum induction in children is 68-100%. Most studies have processed sputum using the plug selection method, and show that the dominant cell in sputum from normal children is the macrophage, and that the upper normal limit for sputum eosinophils in children is 2.5%. The inflammatory response in childhood asthma is characterized by elevated numbers of sputum eosinophils, and eosinophil cationic protein concentration, as well as increased nitric oxide and hydrogen peroxide levels in exhaled breath. Sputum eosinophils correlate with objective markers of disease severity in steroid-naive children with asthma, and in severe asthma. Inflammatory marker levels are lower in children using glucocorticosteroids. Induced sputum and exhaled gases are important markers of inflammation in childhood asthma. The clinical utility of these markers warrants further study.
Breath Tests↗
Immediate fright reaction: an essential criterion in the development of posttraumatic stress disorder (PTSD).
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Accidents, Traffic↗
[Postoperative complications after radiochemotherapy or chemotherapy for bronchial cancers].
OBJECTIVE: The purpose of this study was to evaluate the risk of lung cancer surgery, following induction chemo 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 (2 stages IB and 2 stages IIIA [N2]; n = 4); doubtful resectability (stage IIIB [T4]; n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received 2 to 4 cycles of chemotherapy (average = 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (20 to 60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in 4 patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were 4 reoperations (6%): 3 for bronchial fistula and 1 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%). CONCLUSION: Surgery for lung cancer after induction chemo and/or radiotherapy is associated with an increased risk. While the mortality seems "acceptable", the morbidity rate however is high.
Adult↗
[Depression after age 50. Synthesis].
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Age Factors↗
Cell surface stability of gamma-aminobutyric acid type A receptors. Dependence on protein kinase C activity and subunit composition.
Type A gamma-aminobutyric acid receptors (GABA(A)), the major sites of fast synaptic inhibition in the brain, are believed to be composed predominantly of alpha, beta, and gamma subunits. Although cell surface expression is essential for GABA(A) receptor function, little is known regarding its regulation. To address this issue, the membrane stability of recombinant alpha(1)beta(2) or alpha(1)beta(2)gamma(2) receptors was analyzed in human embryonic kidney cells. Alpha(1)beta(2)gamma(2) but not alpha(1)beta(2) receptors were found to recycle constitutively between the cell surface and a microtubule-dependent, perinuclear endosomal compartment. Similar GABA(A) receptor endocytosis was also seen in cultured hippocampal and cortical neurons. GABA(A) receptor surface levels were reduced upon protein kinase C (PKC) activation. Like basal endocytosis, this response required the gamma(2) subunit but not receptor phosphorylation. Although inhibiting PKC activity did not block alpha(1)beta(2)gamma(2) receptor endocytosis, it did prevent receptor down-regulation, suggesting that PKC activity may block alpha(1)beta(2)gamma(2) receptor recycling to the cell surface. In agreement with this observation, blocking recycling from endosomes with wortmannin selectively reduced surface levels of gamma(2)-containing receptors. Together, our results demonstrate that the surface stability of GABA(A) receptors can be dynamically and specifically regulated, enabling neurons to modulate cell surface receptor number upon the appropriate cues.
Cell Line↗
Redefined nomenclature for members of the carcinoembryonic antigen family.
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Alternative Splicing↗
Identification of an inhibitory Zn2+ binding site on the human glycine receptor alpha1 subunit.
1. Whole-cell glycine-activated currents were recorded from human embryonic kidney (HEK) cells expressing wild-type and mutant recombinant homomeric glycine receptors (GlyRs) to locate the inhibitory binding site for Zn2+ ions on the human alpha1 subunit. 2. Glycine-activated currents were potentiated by low concentrations of Zn2+ (<10 microM) and inhibited by higher concentrations (>100 microM) on wild-type alpha1 subunit GlyRs. 3. Lowering the external pH from 7.4 to 5.4 inhibited the glycine responses in a competitive manner. The inhibition caused by Zn2+ was abolished leaving an overt potentiating effect at 10 microM Zn2+ that was exacerbated at 100 microM Zn2+. 4. The identification of residues involved in the formation of the inhibitory binding site was also assessed using diethylpyrocarbonate (DEPC), which modifies histidines. DEPC (1 mM) abolished Zn2+-induced inhibition and also the potentiation of glycine-activated currents by Zn2+. 5. The reduction in glycine-induced whole-cell currents in the presence of high (100 microM) concentrations of Zn2+ did not increase the rate of glycine receptor desensitisation. 6. Systematic mutation of extracellular histidine residues in the GlyR alpha1 subunit revealed that mutations H107A or H109A completely abolished inhibition of glycine-gated currents by Zn2+. However, mutation of other external histidines, H210, H215 and H419, failed to prevent inhibition by Zn2+ of glycine-gated currents. Thus, H107 and H109 in the extracellular domain of the human GlyR alpha1 subunit are major determinants of the inhibitory Zn2+ binding site. 7. An examination of Zn2+ co-ordination in metalloenzymes revealed that the histidine- hydrophobic residue-histidine motif found to be responsible for binding Zn2+ in the human GlyR alpha1 subunit is also shared by some of these enzymes. Further comparison of the structure and location of this motif with a generic model of the GlyR alpha1 subunit suggests that H107 and H109 participate in the formation of the inhibitory Zn2+ binding site at the apex of a beta sheet in the N-terminal extracellular domain.
Amino Acid Sequence↗
A paraxial exclusion zone creates patterned cranial neural crest cell outgrowth adjacent to rhombomeres 3 and 5.
Cranial neural crest cell migration is patterned, with neural crest cell-free zones adjacent to rhombomere (R) 3 and R5. These zones have been suggested to result from death of premigratory neural crest cells via upregulation of BMP-4 and Msx-2 in R3 and R5, consequent to R2-, R4-, and R6-derived signals. We reinvestigated this model and found that cell death detected by acridine orange staining in avian embryos varied widely numerically and in pattern, but with a tendency for an elevated zone centered at the R2/3 boundary. In situ hybridization of BMP-4 mRNA resolved to centers at R3 and R5 but Msx-2 resolved to the R2/3 border with only a faint smear from R5 to R6. Outgrowth of neural crest cells was less in isolated R3 cultures than in R1+2, R2, and R4 cultures, but R3 showed neither a decrease in outgrowth of neural crest cells nor an increase in cell death when cocultured with R1+2, R2, or R4. In addition, in serum-free culture, exogenous BMP-4 strikingly reduced neural crest cell outgrowth from R1+2 and R4 as well as R3. Thus we cannot confirm the role of intraneural cell death in patterning rhombomeric neural crest outgrowth. However, grafting quail R2 or R4 adjacent to the chick hindbrain demonstrated a neural crest cell exclusion zone next to R3 and R5. We suggest that one important pattern determinant for rhombomeric neural crest cell migration involves the microenvironment next to the neural tube.
Animals↗
Trends in perinatal transmission of HIV/AIDS in the United States.
CONTEXT: Since 1994, the US Public Health Service (PHS) has recommended routine, voluntary prenatal human immunodeficiency virus (HIV) testing and zidovudine therapy to reduce perinatal HIV transmission. OBJECTIVE: To describe trends in incidence of perinatal AIDS and factors contributing to these trends, particularly the effect of PHS perinatal HIV recommendations. DESIGN, SETTING, AND PARTICIPANTS: Analysis of nationwide AIDS surveillance data and data from HIV-reporting states through June 1998. MAIN OUTCOME MEASURES: Trends in AIDS by year of diagnosis, incidence rates of AIDS and Pneumocystis carinii pneumonia (PCP) among infants younger than 1 year from US natality data for birth cohorts 1988 to 1996; expected number of infants with AIDS from national serosurvey data; and zidovudine use data from selected HIV-reporting states. RESULTS: Perinatal AIDS cases peaked in 1992 and then declined 67% from 1992 through 1997, including an 80% decline in infants and a 66% decline in children aged 1 to 5 years. Rates of AIDS among infants (per 100000 births) declined 69%, from 8.9 in 1992 to 2.8 in 1996 compared with a 17% decline in births to HIV-infected women from 1992 (n = 6990) to 1995 (n = 5797). Among infants, PCP rates per 100000 declined 67% (from 4.5 in 1992 to 1.5 in 1996), similar to the decline in other AIDS conditions. The percentage of perinatally exposed children born from 1993 through 1997 whose mothers were tested for HIV before giving birth increased from 70% to 94%; the percentage who received zidovudine increased from 7% to 91%. CONCLUSIONS: According to these data, substantial declines in AIDS incidence were temporally associated with an increase in zidovudine use to reduce perinatal HIV transmission, demonstrating substantial success in implementing PHS guidelines. Reductions in the numbers of births and effects of therapy in delaying AIDS do not explain the decline.
AIDS-Related Opportunistic Infections↗