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Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 217 records · Page 12Linked to original sources

Assessment of ileal pouch inflammation by single-stool calprotectin assay.

PURPOSE: Assessment of inflammation within the ileal pouch to establish a diagnosis of "pouchitis" requires both pouch endoscopy and biopsy because there can be a poor correlation between macroscopic and histologic assessments of inflammation. A simplified diagnostic test would be of clinical advantage. Calprotectin is a stable myelomonocytic protein, measurable in feces. It quantitatively relates to inflammation within the gastrointestinal tract. This study was designed to compare single and 24-hour stool measurements of calprotectin in patients with and without evidence of ileal pouch inflammation with endoscopic, histologic, and immunohistochemical indices. METHODS: Twenty-four-hour stool collections were made in ileal pouch patients, 9 with and 15 without (7 with ulcerative colitis and 8 with familial polyposis coli) evidence of pouch inflammation. First-morning stool concentration and total 24-hour calprotectin were quantified by use of a single step enzyme-linked immunosorbent assay. Biopsies from the reservoir were taken for conventional histology and scoring of intraepithelial neutrophil infiltrate. Cells positive for CD3, CD45RO, CD14, and CD15 within the lamina propria were quantified by use of immunohistochemistry. RESULTS: The mean first-morning stool calprotectin concentration correlated with the 24-hour level (r = 0.91; P = <0.0001). The median single-stool calprotectin concentrations were 39 mg/l, 4 mg/l, and 8.5 mg/l (normal range, 0.2-10 mg/l) in patients with inflamed, noninflamed ulcerative colitis, and familial adenomatous polyposis, respectively. All nine patients with endoscopic and histologic evidence of pouch inflammation had raised stool calprotectin. Two of 15 patients without evidence of pouch inflammation had abnormal stool calprotectin. Single-stool calprotectin concentration correlated with the percentage of mature granulocytes (CD15; r = 0.46; P = 0.04) and activated macrophages (CD14; r = 0.65; P = 0.006), but not memory T cells (CD45RO; r = -0.05; P = 0.4) within the lamina propria. CONCLUSION: Single first-morning stool calprotectin levels provide a quantitative measure of pouch inflammation, which may be helpful in the diagnosis and assessment of pouchitis.

Biomarkers↗

IgE binding to unique hazelnut allergens: identification of non pollen-related and heat-stable hazelnut allergens eliciting severe allergic reactions.

BACKGROUND: Usually hazelnut allergic patients suffer from the tree pollen associated oral allergy syndrome (OAS) caused by cross-reactive structures. Anaphylactic reactions elicited by hazelnuts happen rarely but are of high clinical significance. Considering that hazelnuts are ingredients in processed foods, hazelnuts may play an important role as hidden allergens for these high risk patients. Therefore, we analyzed the IgE reactivity of a young woman with severe allergic reactions after ingestion of hazelnuts without any association to tree pollen allergy. AIM OF THE STUDY: The aim of this study was to identify and characterize these potent hazelnut-specific allergens. We compared these allergens to structures displayed by sera from patients with a completely or partially non pollen-related hazelnut allergy and with birch pollen-related hazelnut allergy. None of the sera had a clinical history of anaphylaxis. Special emphasis was placed on the heat stability and cross-reactivity of these allergens. METHODS/RESULTS: Using Western blotting with extract from birch pollen and EAST inhibition techniques we were able to show that the allergens in the serum sample of the young woman were not cross-reactive with birch pollen. Immunoblot experiments with extracts from native and heated hazelnuts and EAST inhibition tests further characterized these allergens to be heat-stable. Unlike the IgE binding pattern of the sera from the patients with pollen-related hazelnut allergy, low molecular weight proteins below 10 kDa were identified by the sera from the patients without pollinosis. CONCLUSIONS: Since the binding pattern of the serum sample of the young woman was different from that of the sera from patients without pollen allergy but less severe symptoms, we assume an association between single non pollen-dependent hazelnut allergens in the low molecular range and severe allergic reactions. These results enable us to approach a subgroup of hazelnut allergens which we believe to be responsible for anaphylactic reactions in hazelnut allergic patients after ingestion of heat-stable hazelnut structures in processed food stuff, independent of pollinosis.

Allergens↗

Structural Organization of the Atlantic Croaker Connexin 32.2 Gene and Its 5' Flanking Region.

Gonadotropic hormone stimulates the accumulation of connexin (Cx) 32.2 messenger RNA in ovaries of the marine teleost Atlantic croaker. This effect can be mimicked by protein kinase A (PKA) activators and blocked by PKA inhibitors as well as protein kinase C (PKC) stimulators. However, the mechanisms of Cx32.2 gene regulation are unknown. In this study, we determined the structure of the Cx32.2 gene as a first step toward characterizing the regulatory mechanisms of Cx32.2 gene expression. A cosmid library of croaker genomic DNA was screened with a Cx32.2 complementary DNA probe. One positive clone was subcloned and sequenced. The Cx32.2 gene contained two exons and one intron. The first exon contained a portion of the 5' untranslated region (UTR), and the second exon contained the remaining 5' UTR, the amino acid coding region, and the 3' UTR. The distal 5' flanking region also contained a sequence homologous to a different croaker Cx gene, Cx32.7, but it is unclear if this sequence constitutes a pseudogene or an exon of the Cx32.7 gene. The 5' flanking region of the Cx32.2 gene contained two core cyclic AMP response elements (CRE, CGTCA) and one full-consensus activating protein- (AP)-1 binding site (AGTCAG). The distal core CRE was associated with a sequence that enhances CRE activity (GAGC). A third core CRE site was present in the intron. These findings are consistent with the following hypotheses: the induction of ovarian Cx32.2 mRNA levels by gonadotropic hormone is at least partly mediated by CRE-dependent activation of the Cx32.2 gene, and the inhibition of basal and gonadotropic-hormone-stimulated ovarian Cx32.2 mRNA by PKC is due to negative effects on transcription via the AP-1 transcription factor complex. This study is the first to characterize the structure and putative response elements of the 5' flanking region of fish Cx genes.

Journal Article↗

A clinical evaluation of a locking orthodontic facebow.

Standard orthodontic facebows may accidentally detach from the appliance buccal tubes at night; this could reduce the effectiveness of extra oral traction and occasionally cause an injury. To try and prevent facebow detachment at night a facebow with a locking mechanism was introduced. This study assessed the ability of 706 consecutively treated patients to learn to wear and use this facebow. The facebows were fitted in 9 different practices supervised by 12 orthodontists. Data from the patients and orthodontists were collected over a 2-year period and covered approximately 166,550 nights. All the orthodontists were able to fit and adjust the facebow; a total of 697 patients successfully used the facebow. Accidental detachment of the facebow at night was reported to be less than 1%. This indicates a significant improvement in the safety of the facebow and should help to improve compliance by increasing the number of hours of wear achieved by the patients.

Accident Prevention↗

Androgen binding profiles of two distinct nuclear androgen receptors in Atlantic croaker (Micropogonias undulatus).

In the present study, the binding affinities of 28 androgens for two nuclear androgen receptors (AR), termed AR1 and AR2, in Atlantic croaker (Micropogonias undulatus) brain and ovarian tissues, respectively, were determined using competitive binding assays. The 5alpha-reduction of steroids, in general, increased the metabolite's binding affinity for AR2 while decreasing it for AR1. In addition, few androgens bound to AR1 with high affinity and modifications to the basic 3-ketone,4-ene,17beta-hydroxy structure of testosterone usually reduced its binding affinity for AR1. However, androgens with ketone groups at the 3- and 17-position bound with high affinity to AR1 provided that the androgen had either a 5alpha-reduced A-ring or a third ketone group at the 11-position. This suggests that there may be several high affinity conformations that AR1 can occupy depending upon whether an androgen possesses a ketone or a hydroxyl group at the 17-position. The binding of androgens to AR2 showed a more predictable pattern, 5alpha-reduced steroids bound better than 4-ene steroids and any changes to the basic 3-keto,17-hydroxy motif of 5alpha-dihydrotestosterone lowered the binding affinity of a steroid. However, these structural changes often caused only minor decreases in binding affinity, such that AR2 has a broader affinity for androgens and a greater affinity than AR1 for structurally diverse androgens. Widely different androgen binding affinities of AR1 and AR2 suggest that these two nuclear androgen receptors may mediate the physiological actions of different androgens in teleosts.

Androgen Antagonists↗

Identification by TEM and EELS of the products formed at the surface of a carbon electrode during its reduction in MClO4-EC and MBF4-EC electrolytes (M = Li, Na)

The electrochemical intercalation of lithium and sodium into graphite was carried out using a liquid electrolyte containing ethylene carbonate (EC) as solvent and MClO4 or MBF4 (M = Li, Na) as salts. The first intercalation of alkali metals into graphite is accompanied with irreversible reactions attributed to the reduction of the electrolyte. These reactions contribute to the development of a passivating layer, formed on graphite surface prior to intercalation. This layer is impervious to solvent molecules but allows alkali ions to diffuse through its bulk. The surface chemistry of the electrodes was characterized using transmission electron microscopy (image, selected area electron diffraction) as well as EELS. The effect of the nature of the alkali salts on the properties of the passivating layer is studied.

Journal Article↗

[Status epilepticus with confusional symptomatology].

Non-convulsive confusional status epilepticus (NCSE) is classically separated into two forms on the basis of the ictal EEG, i.e., absence status (AS) and complex partial status epilepticus (CPSE). The diagnosis is difficult on the basis of clinical semiology alone, and requires emergency EEG investigation. Absence status, or 'petit mal' status, is a polymorphic condition that can complicate many epileptic syndromes, and is the most frequently encountered form of NCSE. It is characterized by confusion of varying intensity, associated in 50% of cases with bilateral periocular myoclonias. The EEG shows ictal generalized paroximal activity; normalization is obtained after benzodiazepine injection. In AS, there is a significant nosographic heterogeneity. Four groups can be distinguished: i) typical AS occurs in the context of a generalized idiopathic epilepsy; ii) atypical AS occurs in patients with symptomatic or cryptogenic generalized epilepsies; iii) 'de novo' AS (of late onset) is characterized by toxic or metabolic precipitating factors in middle-aged subjects with no previous history of epilepsy; iv) AS with focal characteristics occurs in subjects with a pre-existing or newly diagnosed partial epilepsy, mostly of extra-temporal origin. The majority of cases are in fact transitional forms between these four groups. CPSE is characterized by continuous or rapidly recurring complex partial seizures which may involve temporal and/or extratemporal regions. Cyclic disturbance of consciousness is characteristic of CPSE of temporal lobe origin, which requires vigorous treatment to prevent recurrence or cognitive sequelae. CPSE of frontal lobe origin is a diagnostic challenge: it is rare, the symptoms are unusual, and the patients should be documented extensively. A focal frontal lesion is revealed in one-third of cases.

Confusion↗

Anti-CD20 monoclonal antibody therapy in Epstein-Barr Virus-associated B cell lymphoma following lung transplantation.

Post-transplant lymphoproliferative disease is a complication of bone marrow and solid organ transplantation, mostly associated with Epstein-Barr virus infection and chronic immunosuppression. Even if spontaneous resolution after cessation of immunosuppressive therapy can be observed, the prognosis of this disorder is usually poor with a low response to specific treatment. We describe a case of B-cell lymphoma of the nasopharynx occurring 6 months after double-lung transplantation. In spite of its monoclonal nature, anti-CD 20 monoclonal antibody given in the presence of reduced immunosuppression resulted in a complete response. The patient also received "consolidation" radiation therapy to prevent the recurrence. The treatment was well tolerated with minimal side effects. The patient was asymptomatic and had a well functioning graft more than 1 year after therapy.

Adult↗

Is the clinical expression of late-life depression influenced by brain changes? MRI subcortical neuroanatomical correlates of depressive symptoms.

BACKGROUND: "Vascular depression" has recently been proposed. It is characterized by magnetic resonance imaging (MRI) T2-weighted subcortical lesions, a late onset of first episode of depression, and reduced heritability; a cerebrovascular etiology is suggested. The validity of "vascular depression" might be strengthened if an association was found between the subcortical lesions used to define it and particular depressive symptoms. METHODS: A blinded cross-sectional examination of DSM-III-R depressive symptoms (American Psychiatric Association, 1987) and MRI T2-weighted subcortical lesions in 44 patients with late-life depression. RESULTS: Many associations were found; however, because of multiple comparisons, their significance is viewed with caution. The most robust finding was that psychomotor retardation was independently related to total white-matter score. The odds of showing psychomotor retardation was increased 1.9 times for every point increase in severity of white-matter change. CONCLUSION: In late-life depression the clinical expression of the depression is influenced by the pattern of MRI T2-weighted subcortical lesions. This gives some validity to the concept of an MRI-defined "vascular" subtype of late-life depression and strengthens the argument for including neuroimaging in the classification of late-life depression.

Aged↗

Intolerance of osteosynthesis material: evidence of dichromate contact allergy with concomitant oligoclonal T-cell infiltrate and TH1-type cytokine expression in the peri-implantar tissue.

BACKGROUND: We report on a 37-year-old man without history of previous allergic disease who developed an aseptic intolerance reaction to a chromium-cobalt alloy, with local discomfort, loosening, and absence of fracture healing. Both in vivo and in vitro allergoimmunologic diagnostic tests were performed. METHODS: Patch testing was done with a European standard series. Specific serum IgE was measured by CAP-FEIA. In addition to immunohistology (APAAP method), peri-implantar tissue was further analyzed by PCR to determine T-cell-receptor-gamma rearrangement and thus the potential clonal (antigen-driven) T-cell repertoire. The actual tissue mRNA expression for IL-4, IL-6, and IFN-gamma was visualized by RT-PCR. RESULTS: Skin testing gave a delayed-type reaction to dichromate. Specific serum IgE to natural rubber latex and grass pollen was found--but without clinical symptoms. Immunohistology revealed a monocytic and dense T-cell infiltrate. The latter, instead of being random, showed an oligoclonal T-cell receptor rearrangement. In addition, there was TH1-type mediator expression (IL-6 and IFN-gamma, but not IL-4). CONCLUSIONS: Skin test, examination of peri-implantar tissue, and the prompt healing after replacement of the osteosynthesis material suggest an allergic reaction. PCR analysis of peri-implantar tissue can further help to identify and understand allergy-mediated implant intolerance reactions.

Adult↗

Structural brain lesions do not influence the prognosis of juvenile myoclonic epilepsy.

OBJECTIVES: In juvenile myoclonic epilepsy (JME) neuroimaging procedures are usually unnecessary but are often performed following the first generalized tonic-clonic seizure before a specific diagnosis has been reached. Our aim was to evaluate the influence of abnormal findings on the clinical presentation and prognosis of JME. MATERIAL AND METHODS: We retrospectively analyzed all medical records of JME patients first referred in two epilepsy centers (Marseilles, Nice) between 1981 and 1998. RESULTS: Among 170 consecutive unselected newly diagnosed JME patients, neuroimaging was performed in 82 cases (MRI: 22, CT: 75, including MRI+CT: 15). In 4 subjects, specific neurological abnormalities had justified neuroimaging: severe head trauma after the onset of JME (2, both with lesions related to the trauma), multiple sclerosis with onset after JME (1, with normal MRI before the onset of multiple sclerosis and abnormal, specific findings later), severe mental retardation (1, with diffuse MRI changes but a typical electro-clinical presentation and evolution). In the other 78 cases, 9 had abnormal findings: common arachnoid cyst (3), mild diffuse cerebral atrophy and ventricular enlargement (1), mild ventricular enlargement only (3), septum lucidum cavum (1), mildly increased T2 signal in the left temporal lobe (1). Abnormal neuroimaging did not influence therapeutic decisions or prognosis. CONCLUSIONS: These data confirm that neuroimaging procedures should not be routinely performed in patients with typical JME, unless additional neurological problems, that are unrelated to the diagnosis of epilepsy, occur.

Adolescent↗

Dynamics of genotypic structure in clonal Rhododendron ferrugineum (Ericaceae) populations.

Two populations of Rhododendron ferrugineum growing at subalpine level in the Pyrenees (France) were studied in two sites (Bethmale and Mourtis). Identification and delimitation of genets were inferred from amplified fragment length polymorphism (AFLP) markers, along a closure gradient (from meadow to more closed heath) in each site. Surface and age of genets, genotypic diversity (Simpson's index D), 'proportion distinguishable' genotypes and genetic relationships between genets were then estimated. Amplification of the 312 DNA samples with three selective primer pairs gave a mean of 98 detectable peaks (i.e. bands) per sample, with size ranging from 60 to 300 bp. In total 60% (Bethmale) and 70% (Mourtis) of the peaks were polymorphic, and a total of 31 and 23 multilocus genotypes were identified, in Bethmale and Mourtis, respectively. We inferred that pioneer genotypes began arriving 110 years ago mainly over a 40-year period in the Mourtis meadow, and began about 130 years ago over a 100-year period in the Bethmale meadow. After this pioneer stage, populations extended vegetatively. Two different patterns of genotypic dynamics can be identified. At Bethmale, population closure could have led to a dramatic loss of genets and to the selection of highly genetically related genotypes. In contrast, at Mourtis, genotypic diversity and genet density did not change fundamentally along the closure gradient. However the range of genetic diversity diminished from the open to the closed situation, suggesting that thinning could have occurred in the past.

Ecology↗

Clinical correlations of alpha2,6-sialyltransferase expression in colorectal cancer patients.

We have previously demonstrated a link between alpha2,6-Sialyltransferase (alpha2,6-ST; E.C. 2.4.99.1) expression and differentiation of colon tumors. So far, information is not available relative to the expression of alpha2,6-ST in tumors and the survival of patients with colorectal cancer. We have examined the expression of alpha2,6-ST in a variety of colorectal adenocarcinomas (n = 46) at different stages of differentiation (G1 to G3) by immunoperoxidase assay using monoclonal antibody (MAb) 6B9. Clinical outcome of the patients in a 5-year follow-up study has been correlated with the expression of alpha2,6-ST in tumors surgically removed from the same patients. No significant difference in the alpha2,6-ST expression was noted when age, sex, and tumor locations (colon, rectum) were included as parameters. However, 52% of the moderate (G2) and well-differentiated (G1) adenocarcinomas showed stronger alpha2,6-ST expression compared with poorly differentiated (G3) adenocarcinomas. Notably, absence to moderate levels of tumor alpha2,6-ST expression was correlated with 100% survival in patients with stage I and II tumors compared with 64% survival in patients with strong tumor alpha2,6-ST expression (p < 0.01). These studies suggest a negative correlation between the expression of alpha2,6-ST in tumors and a good clinical outcome in colorectal cancer patients.

Adenocarcinoma↗

Influenza immunization coverage in older hospitalized patients during winter 1998-99 in Carmarthenshire, UK.

OBJECTIVE: to determine the coverage of influenza vaccination in hospitalized elderly patients in view of the 1998 recommendations of the UK Department of Health, and the reasons for refusal in those unvaccinated. DESIGN: questionnaire-based interview. SETTING: acute elderly-care wards in a district general hospital in South Wales, UK. SUBJECTS: 443 consecutive patients aged over 65 hospitalized during December 1998 and January 1999. RESULTS: of 383 patients in whom influenza vaccination was recommended according to Department of Health guidelines, only 48% received it during the winter of 1998-99. The commonest reason given by those unvaccinated was lack of information from the general practitioner (in 26% of cases). Other reasons were concern about vaccine side effects (21%), perceived good health (16%) and concern about vaccine efficacy (11%). CONCLUSIONS: influenza vaccine uptake in high-risk older hospitalized patients is still unsatisfactory. Improved education of the health-care staff and the general public about the benefits of vaccine is necessary to improve uptake.

Aged↗

Dominant partial epilepsies. A clinical, electrophysiological and genetic study of 19 European families.

Nineteen families with autosomal dominant partial epilepsy were analysed clinically and electrophysiologically in detail. Seventy-one patients were studied as well as 33 non-epileptic at-risk family members. We subdivided the families into those with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (n = 8), familial temporal lobe epilepsy (n = 7) and autosomal dominant partial epilepsy with variable foci (n = 4). However, the application of this nosology to certain families was difficult in cases of non-specific or conflicting clinical and electrophysiological evidence. This was underscored by the observation by depth electrode recordings in one patient that a so-called ADNFLE may originate in an extrafrontal area. The evolution of familial partial epilepsies, which exhibit great intrafamilial variability, is not always benign. The level of pharmacoresistance may reach 30%, close to that seen in classical cryptogenic partial epilepsies. The familial character of a partial epilepsy may be unrecognized in small families as some affected members may have only EEG abnormalities and are clinically asymptomatic, which reflects incomplete clinical penetrance. In view of the recent discoveries of mutations in the alpha4 nicotinic acetylcholine receptor subunit in a few families with ADNFLE, this genetic study focused on genes encoding nicotinic receptor subunits and a candidate region on chromosome 10q. No mutation was detected in the alpha4 and 012 nicotinic acetylcholine receptor subunits. Positive but not significant lod scores were obtained in four families with markers from the candidate region on chromosome 10q.

Adolescent↗

Computer-assisted venous occlusion plethysmography in the diagnosis of acute deep venous thrombosis.

Suspicion of deep venous thrombosis (DVT) is a common reason for acute medical admission. The clinical diagnosis is difficult, and thus significant numbers are investigated and found to be normal. Provision of 24-h radiology is costly, and there may be a delay in investigation. We assessed computer-assisted venous occlusion plethysmography as a screening test for DVT, compared with standard radiology. The test has the advantage of being performed on the ward and if reliable would significantly reduce the number of radiological investigations required. We enrolled 215 consecutive patients presenting with the possible diagnosis of DVT, of whom 144 had technically adequate plethysmography results. Plethysmography had a sensitivity of 96% (95%CI 88-99%) and a negative predictive value of 97% (95%CI 91-99%). Patients excluded because of technically inadequate results were older (by a mean 7 years, p=0. 003). Computer-assisted venous occlusion plethysmography is a non-invasive method of rapidly screening for DVT which may be safely used as an initial screening test. The test is less useful in older patients, or patients unable to keep still for a period of 2 min.

Acute Disease↗