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Biomedical subjects

J Andre

Publications and source records attributed to J Andre.

At least 19 recordsLinked to original sources

Biomechanics, diagnosis, and treatment outcome in inflammatory myopathy presenting as oropharyngeal dysphagia.

AIMS: In patients with inflammatory myopathy and dysphagia, our aims were to determine: (1) the diagnostic utility of clinical and laboratory indicators; (2) the biomechanical properties of the pharyngo-oesophageal segment; (3) the usefulness of pharyngeal videomanometry in distinguishing neuropathic from myopathic dysphagia; and (4) clinical outcome. METHODS: Clinical, laboratory, and videomanometric assessment was performed in 13 patients with myositis and dysphagia, in 17 disease controls with dysphagia (due to proven CNS disease), and in 22 healthy age matched controls. The diagnostic accuracy of creatine kinase (CPK), erythrocyte sedimentation rate, antinuclear antibody, and electromyography (EMG) were compared with the gold standard muscle biopsy. The biomechanical properties of the pharyngo-oesophageal segment were assessed by videomanometry. RESULTS: Mean time from dysphagia onset to the diagnosis of myositis was 55 months (range 1-180). One third had no extrapharyngeal muscle weakness; 25% had normal CPK, and EMG was unhelpful in 28%. Compared with neurogenic controls, myositis patients had more prevalent cricopharyngeal restrictive disorders (69% v 14%; p=0.0003), reduced upper oesophageal sphincter (UOS) opening (p=0.01), and elevated hypopharyngeal intrabolus pressures (p=0.001). Videomanometric features favouring a myopathic over a neuropathic aetiology were: preserved pharyngeal swallow response, complete UOS relaxation, and normal swallow coordination. The 12 month mortality was 31%. CONCLUSIONS: The notable lack of supportive clinical signs and significant false negative rates for laboratory tests contribute to the marked delay in diagnosis. The myopathic process is strongly associated with restricted sphincter opening suggesting that cricopharyngeal disruption is a useful adjunct to immunosuppressive therapy. The condition has a poor prognosis.

Aged↗

A case of subungual reactive eccrine syringofibroadenoma.

Eccrine syringofibroadenoma (ESFA) is a rare eccrine tumor. We report the case of a 70-year-old woman who had presented a pincer nail deformity on the toes for 55 years and a left painless subungual tumor for 2 years. Histologic examination revealed branching anastomosing strands of epithelial cells with ductal structures in a fibrovascular stroma. The luminal cells showed positive staining for carcinoembryonic antigen, as in acrosyringeal cells and cells of dermal ducts. To our knowledge, our case is the first with a subungual location. In the context of chronic trauma due to a pincer nail, it may be classified in the reactive subtype recently described.

Adenoma, Sweat Gland↗

The twilight envelope: a user-centered approach to describing roadway illumination at night.

Visual recognition functions, such as acuity and contrast sensitivity, deteriorate rapidly over the declining luminances found during civil twilight. Thus civil twilight, a critical part of the transition between daylight and darkness, represents lighting conditions that may be useful to describe artificial illumination. Automotive headlamps project a three-dimensional beam that ranges from illumination levels comparable to daylight at the vehicle to the dark limit of civil twilight (3.3 1x) at some distance ahead. This twilight envelope is characterized as a distance beyond which foveal visual functions are severely impaired, and thus it provides a general, functional description of the useful extent of the headlamp beam. This user-centered approach to describing illumination is useful for characterizing visibility when driving at night or in other artificially lit environments. This paper discusses the twilight envelope approach and its application to intervehicle variations in headlamp systems. Actual or potential applications of this research include user-centered description of artificial illumination and driver/pedestrian safety education.

Accidents, Traffic↗

Coupling of a Rydberg electron capture ion source with a quadrupole mass filter.

The coupling of a Rydberg electron capture ion source with a Nermag R10-10H quadrupole mass filter is described. Details are given of the addition to this instrument of a creation cell for atoms excited in Rydberg states. Within the Nermag ion source, such atoms allow attachment of electrons of well-defined thermal energy. SF(6) was used for optimization of the main experimental parameters (gas pressures and voltages applied to the electrodes). The procedure by which Rydberg electron attachment was confirmed is described. A polychlorobiphenyl compound was used to illustrate the performance of this ionization technique. Ion formation was observed in the absence of fragmentation.

Gas Chromatography-Mass Spectrometry↗

Expression and characterization of glycosylated and catalytically active recombinant human alpha-galactosidase A produced in Pichia pastoris.

Fabry disease is an X-linked inborn error of glycolipid metabolism caused by deficiency of the lysosomal enzyme alpha-galactosidase A. This enzyme is responsible for the hydrolysis of terminal alpha-galactoside linkages in various glycolipids. An improved method of production of recombinant alpha-galactosidase A for use in humans is needed in order to develop new approaches for enzyme therapy. Human alpha-galactosidase A for use in enzyme therapy has previously been obtained from human sources and from recombinant clones derived from human cells, CHO cells, and insect cells. In this report we describe the construction of clones of the methylotrophic yeast Pichia pastoris that produce recombinant human alpha-galactosidase A. Recombinant human alpha-galactosidase A is secreted by these Pichia clones and the level of production is more than 30-fold greater than that of previously used methods. Production was optimized using variations in temperature, pH, cDNA copy number, and other variables using shake flasks and a bioreactor. Expression of the human enzyme increased with increasing cDNA copy number at 25 degrees C, but not at the standard growth temperature of 30 degrees C. The recombinant alpha-galactosidase A was purified to homogeneity using ion exchange (POROS 20 CM, POROS 20 HQ) and hydrophobic (Toso-ether, Toso-butyl) chromatography with a BioCAD HPLC Workstation. Purified recombinant alpha-galactosidase A was taken up by fibroblasts derived from Fabry disease patients and normal enzyme levels could be restored under these conditions. Analysis of the carbohydrate present on the recombinant enzyme indicated the predominant presence of N-linked high-mannose structures rather than complex carbohydrates.

Bioreactors↗

Improving our aim.

Bioethicists appearing in the media have been accused of "shooting from the hip" (Rachels, 1991). The criticism is sometimes justified. We identify some reasons our interactions with the press can have bad results and suggest remedies. In particular we describe a target (fostering better public dialogue), obstacles to hitting the target (such as intrinsic and accidental defects in our knowledge) and suggest some practical ways to surmont those obstacles (including seeking out ways to write or speak at length, rather than in sound bites). We make use of our own research into the way journalists quote bioethicists. We end by suggesting that the profession as a whole look into this question more fully.

Bioethical Issues↗

Do the factors associated with successful contact tracing of patients with gonorrhoea and Chlamydia differ?

OBJECTIVE: To assess and compare factors which may be associated with successful contact tracing in patients with gonorrhoea and chlamydia. STUDY DESIGN: Prospective observational study of patients attending a genitourinary medicine clinic with a diagnosis of gonorrhoea or chlamydia. Multivariate analysis model including demographic, socioeconomic, and behavioural variables. RESULTS: The attendance of at least one sexual contact was associated with naming more contacts for patients with gonorrhoea (OR 1.44, 95% CI 1.04-2.01). A history of gonorrhoea was associated with successful contact tracing for patients with chlamydia (OR 1.46, 95% CI 1.12-1.9). Successful contact tracing, as defined by at least one confirmed contact attendance after the index case, was not associated with age, sex, sexual orientation, history of chlamydia, use of condoms, marital status, ethnicity, or socioeconomic status for either gonorrhoea or chlamydia. CONCLUSIONS: Differences in the composition of the core groups infected with gonorrhoea and chlamydia are not explained by differences in contact tracing success. In the clinic setting studied, the outcome of contact tracing was not associated with a variety of demographic, socioeconomic, and behaviour factors.

Adult↗

Occurrence of gouty tophi following acitretin therapy.

Acitretin (Ro 10-1670 or Neotigason), a free acid and the main metabolite of etretinate (Ro 10-9359 or Tigason), is the most recent of the retinoids used orally in the treatment of psoriasis and numerous other dermatoses exhibiting disorders of keratinization. In the majority of cases, its side-effects are similar to those of hypervitaminosis A.

Acitretin↗

Effect of long-term treatment with a purified micronized flavonoid fraction on pancreatic mononuclear cell infiltration in diabetic BB rats.

Bio Breeding (BB) rats develop a genetically determined insulin-dependent diabetes, because of the early destruction of pancreatic beta cells of Langerhans islets, massively infiltrated by inflammatory mononuclear cells. S 5682, registered as Daflon, 500 mg, is a purified micronized flavonoid fraction (90% diosmin, 10% hesperidin), which has been shown to possess antiinflammatory properties, including anti-free radical activity, effects on vascular permeability, venous tone, and perivenous inflammation. We studied the effect of S 5682 on the course of pancreatic insulitis in diabetic BB rats. All the diabetic BB rats were hyperglycemic, with an increase of plasma levels of fructosamine, alpha-1 acid glycoprotein, and fibrinogen, and a dramatic decrease of C-peptide level. These parameters were not modified by S 5682. Pancreas histologic studies showed that in S 5682-treated diabetic BB rats, lymphocytic infiltration of Langerhans islets was less important and frequent than in untreated diabetic BB rats. By quantitative analysis, a highly significant difference was observed for insulitis, as well as perivasculitis, between S 5682-treated and untreated diabetic BB rats. This inhibitory effect of S 5682 on pancreatic mononuclear cell infiltration may be useful for a complementary treatment to decrease the development of insulitis in human insulin-dependent diabetes mellitus.

Animals↗

Herpesvirus-like DNA sequences and Kaposi's sarcoma: relationship with epidemiology, clinical spectrum, and histologic features.

BACKGROUND: The evidence of an infectious agent other than human immunodeficiency virus (HIV) acting as a possible etiologic cause of Kaposi's sarcoma (KS) has received considerable attention in the last years. Recently, DNA sequences from a new herpesvirus (HHV-8) have been observed in several cases of KS. The discovery suggests that this virus may play a role in the pathogenesis of KS. To evaluate these results, we determined the frequency of HHV-8 DNA sequences in 78 specimens of KS according to different epidemiologic origins (sporadic KS: 6, immunosuppressive drug-associated: 11, and AIDS-associated: 61), clinical forms (cutaneous: 69, mucocutaneous: 4 and visceral; 5) and histologic variants (early-patch: 40, late-plaque or nodular: 38). METHODS: We used the hot start polymerase chain reaction amplification method with KS330 primers specific for HHV-8 DNA. Tumoral or nontumoral skins and visceral specimens free of KS, originating from patients with KS positive for HHV-8 DNA sequences or from immunosuppressed patients without KS, served as controls. Normal skin from healthy HIV seronegative patients was also included. RESULTS: HHV-8 DNA sequences were found in 3 of the 6 sporadic KS (50%), in 5 of the 11 immunosuppressive drug-associated KS (45%), in 41 of the 61 AIDS-associated KS (67%), in 32 of the 69 cutaneous KS (46%), in 3 of the 4 mucocutaneous KS (75%) in 2 of the 5 systemic KS (40%), in 23 of the 40 early or patchstage KS (58%), in 30 of the 38 late plaque or nodular stages KS (79%). These sequences were also demonstrated in one sample of skin with scabies and in a glomerulonephritis lesion from two immunosuppressed patients with KS who were also positive for herpesvirus-like in their KS lesions. None of the other skin or visceral specimens, originating from healthy, AIDS, or transplanted patients without KS, were positive. CONCLUSIONS: Our results reinforce the hypothesis that HHV-8 is incriminated in different epidemiologic, clinical and histologic stages of KS and could contribute to the pathogenesis of this tumor. However, the presence of HHV-8 DNA sequences in skin and visceral samples free of KS from KS indicates that the virus is not restricted to the tumor tissue, and thus is able to disseminate in many organs of the target individual. Absence of the virus from healthy, AIDS, or transplanted patients without KS suggests that the viral Sequences either do not spread easily or do not easily maintain themselves in the human population.

Acquired Immunodeficiency Syndrome↗

Renal and microvascular effects of an aldose reductase inhibitor in experimental diabetes. Biochemical, functional and ultrastructural studies.

Aldose reductase inhibitors, and particularly sorbinil, have been reported to prevent glomerular basement membrane thickening (GBMT) and albuminuria development in diabetic rats, but contradictory observations have been published. The aim of this study was to answer the following questions (i) is the corrective effect of sorbinil on GBMT, if confirmed, associated with an effect on collagen metabolism alterations? (ii) Is it associated with an effect on microvascular functional alterations? We therefore studied the influence of sorbinil on glucosyl-galactosyl-hydroxylysyl-glucohydrolase activity (GGHG; EC 3.2.1.107 which is involved in the catabolism of collagen disaccharide units), 3- and 4-hydroxyproline content and GBMT by ultrastructural morphometry in the kidney cortex of streptozotocin-diabetic rats after 5 months of disease. In parallel, the effects on albumin renal clearance and another functional alteration, the microvascular response to norepinephrine, were evaluated. We confirmed a corrective effect of sorbinil on both renal albumin clearance and GBMT. In the diabetic rats, sorbinil diminished the 3-hydroxyproline (but not the 4-hydroxyproline) content, whether expressed per mg protein or per total kidney cortex relative to body weight. Sorbinil reduced GGHG activity measured in the dialysed 10,000 g supernatant whether expressed per mg protein or per total kidney cortex; this activity has been shown to be increased in diabetes. Sorbinil also corrected the microvascular response to norepinephrine which is altered in diabetes.

Albuminuria↗