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Biomedical subjects

J Raymond

Publications and source records attributed to J Raymond.

At least 19 recordsLinked to original sources

Cytosolic Ca2+ and protein kinase Calpha couple cellular metabolism to membrane K+ permeability in a human biliary cell line.

Cholangiocytes represent an important target of injury during the ischemia and metabolic stress that accompanies liver preservation. Since K+ efflux serves to minimize injury during ATP depletion in certain other cell types, the purpose of these studies was to evaluate the effects of ATP depletion on plasma membrane K+ permeability of Mz-ChA-1 cells, a model human biliary cell line. Cells were exposed to dinitrophenol (50 microM) and 2-deoxyglucose (10 mM) as the standard model of metabolic injury. Whole-cell and single K+ channel currents were measured using patch clamp techniques; and intracellular [Ca2+] ([Ca2+]i) was estimated by calcium green-1 fluorescence. Metabolic stress increased [Ca2+]i, and stimulated translocation of the alpha isoform of protein kinase C (PKCalpha) from cytosolic to particulate cell fractions. The same maneuver increased membrane K+ permeability 40-70-fold as detected by (a) activation of K+selective whole cell currents of 2,176+/-218 pA (n = 34), and (b) opening of apamin-sensitive K+ channels with a unitary conductance of 17.0+/-0.2 pS. PKCalpha translocation and channel opening appear to be related since stress-induced K+ efflux is inhibited by chelation of cytosolic Ca2+, exposure to the PKC inhibitor chelerythrine (25 microM) and downregulation of PKC by phorbol esters. Moreover, K+ currents were activated by intracellular perfusion with recombinant PKCalpha in the absence of metabolic inhibitors. These findings indicate that in biliary cells apamin-sensitive K+ channels are functionally coupled to cell metabolism and suggest that cytosolic Ca2+ and PKCalpha are selectively involved in the response.

2,4-Dinitrophenol

Progression of borderline increases in albuminuria in adolescents with insulin-dependent diabetes mellitus.

We aimed to determine the natural history of borderline increases in albuminuria in adolescents with insulin-dependent (Type 1) diabetes mellitus (IDDM) and factors which are associated with progression to persistent microalbuminura. Fifty-five normotensive adolescents with IDDM and intermittent microalbuminura (overnight albumin excretion ratte of 20-200 micrograms min-1 on one of three consecutive timed collections, n = 29) or borderline albuminura (mean overnight albumin excretion rate of 7.2-20 micrograms min-1 on one of three consecutive timed collections, n = 30) were followed prospectively at 3 monthly intervals. The endpoint was persistent microalbuminuria defined as a minimum of three of four consecutive overnight albumin excretion rates of greater than 20 micrograms min-1. One hundred and forty-two adolescents with IDDM and normoalbuminura were also followed prospectively. Fifteen of the 59 patients (25.4%) with intermittent (9/29) or borderline (6/30) albuminura progressed to persistent microalbuminura (progressors) over 28 (15-50) months [median (range)] in comparison with two of the 142 patients with normoalbuminuria at entry (relative risk = 12.6; p = 0.001). Progressors to persistent microalbuminura were pubertal and had higher systolic (p = 0.02) and diastolic (p = 0.02) blood pressure, and HbA1c (p = 0.004) than non-progressors. All patients remained normotensive. Glomerular filtration rate, apolipoproteins, dietary phosphorus, protein and sodium intakes, and prevalence of smoking did not differ between progressors and non-progressors. Total renin was higher in the diabetic patients without a difference between progressors and non-progressors. In conclusion there is a relatively high rate of progression to persistent microalbuminuria in pubertal adolescents with borderline increases in albuminura and duration greater than 3 years. These patients require attention to minimize associated factors of poor metabolic control and higher blood pressure in the development of incipient nephropathy.

Adolescent

Etiology and response to antibiotic therapy of community-acquired pneumonia in French children.

The aim of this study was to determine the etiologic agents associated with community-acquired pneumonia in 104 French children ages 18 months to 13 years. Potential respiratory pathogens were identified in 87 (85%) cases; these included respiratory syncytial virus in ten, other viruses in 20, Streptococcus pneumoniae in 14 and Mycoplasma pneumoniae (diagnosed by serologic procedures) in 43. Of 32 patients with Mycoplasma pneumoniae infection who were initially treated with beta-lactam antibiotics, 30 failed treatment. Recovery from mycoplasma infection occurred rapidly in patients treated with macrolide antibiotics (which included spiramycin in 31 patients, josamycin in 7, and erythromycin in 3); however, cough persisted in 12 patients for one month. The high frequency of Mycoplasma pneumoniae in children over 18 months of age must be considered when selecting an antibiotic for initial therapy.

Adolescent

Staphylococcal scalded skin syndrome in a neonate.

A case of staphylococcal scalded skin syndrome in a neonate caused by mother-to-child transmission through breast-feeding is reported. Staphylococcus aureus isolates from mother and child were identified using random-amplified polymorphic DNA analysis, which is a simple and rapid method for comparing strains. This study confirms the need to avoid breast-feeding in cases of breast abscess.

DNA, Bacterial

[Role of group B streptococcus serotype V in materno-fetal infections].

BACKGROUND: The classification of serogroup B streptococci in serotype is based on the structural differences of capsular polysaccharides and on presence or absence of a protein c antigen. They are classified as Ia, Ia/c, Ib/c, II, II/c, III, IV and V. The serotype V, unknown in 1970, seems emerging, and is placed in third position of frequency in some American studies. We have therefore decided to evaluate its frequency in Paris. POPULATION AND METHODS: In a population of 137 pregnant women and 60 neonates carrying streptococcus of serogroup B, the serotype was systematically determined using the test "Group B streptococcus serotyping test" (Dako, Danemark). RESULTS: In the pregnant women population, 12% of the isolated strains were of serotype V, 26% of serotype III, 15% of serotype II, 14% of serotype Ia, and 21% could not be typed. In neonates, it represented 15% of the isolates and took place after the serotype Ia (20%), the serotype III (18%) and the serotype II (15%). None of the neonates had early- or late-onset disease. They were only colonized. Only one mother exhibited, during the per-partum, a positive blood culture with a streptococcus group B of serotype V. CONCLUSION: These results confirm, in Paris, the importance of this serotype previously observed in foreign studies. It represents 11 to 15% of the isolated streptococcus group B in the neonates and can cause early or late-onset disease. However, larger studies are needed to evaluate the exact risk of pathology for the serotype V and its significance in neonatal infectious disease.

Female

Proteasome and myogenesis.

In this report, we examine the involvement of the ubiquitin-proteasome pathway during fusion and differentiation of myoblast primary cell cultures. Up-regulation of proteasome was observed at the maximum fusion rate and was preceded by an increase of unidentified ubiquitin-conjugates. Cell permeable proteasome inhibitors prevent fusion as do antisense oligodesoxyribonucleotides targetted to three proteasome subunits. Identical results were obtained using E3 ubiquitin-ligases dipeptide inhibitor. Involvement of the ubiquitin-proteasome pathway in the regulation of myogenic factors was hypothesized.

Animals

Donor work-up and transport of bone marrow--recommendations and requirements for a standardized practice throughout the world from the Donor Registries and Quality Assurance Working Groups of the World Marrow Donor Association (WMDA).

In October 1995 the World Marrow Donor Association (WMDA) was restructured in order to facilitate its primary function of establishing guidelines in relation to international bone marrow and blood stem cell transplants -- transplants in which the donor is in one country and the patient is in another country. Five new working groups were established -- Donor Registries, Ethics, Quality Assurance, Finances, and Stem Cells. This paper, prepared by members of the Donor Registries Working Group, in consultation with the Quality Assurance Working Group, provides recommendations for the 'donor work-up'. This term covers events that start when the definitive donor has been identified, includes the harvesting (collection) and transportation of the stem cell product and ends when the product reaches the transplant centre. The paper includes examples of the documentation intended to ensure compliance with the recommendations at all key points in the sequence.

Bone Marrow Transplantation

Oxygen uptake and heart rate responses during arm vs combined arm/electrically stimulated leg exercise in people with paraplegia.

The purpose of this study was to compare the oxygen uptake and heart rate responses during submaximal arm cranking to combined arm cranking + electrical stimulation (ES)-induced leg cycling in individuals with spinal cord injury (SCI). Seven subjects with paraplegia (T4-T12) performed combined arm and leg cycling exercise for 5 min, followed by arm cranking alone at the same power output for a further 5 min. During both exercise conditions, steady state oxygen consumption (VO2), carbon dioxide output (VCO2), expired ventilation (VE) and heart rate (HR) were determined. The respiratory exchange ratio (RER) and oxygen pulse were calculated from the measured variables. During combined arm + electrical stimulation-induced leg cycling exercise, the VO2 was 25% higher (1.58 l min-1 vs 1.26 l min-1), but the HR was 13% lower (132 b min-1 vs 149 b min-1), than during arm cranking exercise alone. Oxygen pulse and VCO2 were also significantly higher (by 42% and 25%, respectively) during combined arm + ES-induced leg exercise, but there were no differences between the two exercise conditions for VE or RER. These data suggest that the absence of the leg 'muscle pump' and a reduced venous return of blood to the heart elevate exercise heart rates during submaximal arm cranking. Conversely, combined arm cranking + ES-induced leg cycling exercise provides the body with a greater metabolic stress than arm cranking alone, while reducing the cardiac stress. The mechanism explaining the heart rate response, however, remains unclear, but may have been influenced by the blood pressure variations across the range of lesions. The findings from this study may have implications for the relative benefit of combined arm + ES-induced leg cycling training for people with paraplegia.

Adult

A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma.

In a sequential nonrandomized study, 204 consecutive unselected patients aged < 70 years received induction chemotherapy with infusional vincristine and adriamycin with oral methyl prednisolone (VAMP: n = 75) or with additional cyclophosphamide, C-VAMP (n = 129). 38/129 C-VAMP patients also received verapamil during induction as part of a controlled trial with the aim to overcome drug resistance. A median of five courses (range 1-11) of chemotherapy were required before maximal response was attained and this was similar in both groups. An over-all response rate of 71% was noted at the end of induction. The complete remission (CR) rate with C-VAMP was 24%, which was significantly higher (P = 0.04) than the CR rate with VAMP alone (8%). The addition of verapamil did not alter the response rate of C-VAMP. Compliance to VAMP was overall 83% and not affected by the addition of cyclophosphamide. The proportion of patients going on to receive high-dose chemotherapy and an autograft was the same for VAMP and C-VAMP treated patients (71%). The median overall survival (OS) and progression-free survival (PFS) for the whole group were 4.4 years and 2.0 years and no difference in outcome was observed between the different treatment groups. Therefore the addition of weekly cyclophosphamide to VAMP induction therapy has significantly improved the response rates of previously untreated myeloma patients. C-VAMP was not more toxic and did not compromise the chances of receiving an autograft. Verapamil was without influence on any parameters in this study.

Adult

Measurement of procalcitonin levels in children with bacterial or viral meningitis.

We measured the plasma procalcitonin levels in 59 children who were admitted to the hospital because of bacterial or viral meningitis. Eighteen children with acute bacterial meningitis had elevated procalcitonin levels (mean level, 54.5 micrograms/L; range, 4.8-110 micrograms/L). The procalcitonin levels in 41 children with viral meningitis were low (mean level, 0.32 micrograms/L; range, 0-1.7 micrograms/L; P < .0001). Assay of cerebrospinal fluid (CSF) cells and proteins and serum C-reactive protein showed a zone of overlapping values between the two groups. Procalcitonin was not produced in CSF. Plasma procalcitonin levels decreased rapidly during antibiotic therapy. These data suggest that the measurement of plasma procalcitonin might be of value in the differential diagnosis of meningitis due to either bacteria or viruses.

Adolescent

The role of transvenous embolization in the treatment of intracranial dural arteriovenous fistulas.

OBJECTIVE: To evaluate the role of transvenous embolization in the treatment of intracranial dural arteriovenous fistulas (DAVFs), including its efficacy and safety. METHODS: We retrospectively studied the charts of 24 patients (21 women and 3 men) treated for an intracranial DAVF since 1990 in whom a transvenous approach was attempted either alone (16 patients) or in combination with arterial embolization (8 patients). There were 12 cavernous sinus, 9 transverse-sigmoid sinus, 2 inferior petrosal sinus, and 1 intradiploic fistulas. Three fistulas were Type I, 12 were Type IIa, and 9 were Type IIa+b, according to the revised Djindjian's classification. Transvenous embolic agents included coils (17 patients), detachable balloons (6 patients), bucrylate (2 patients), and silk sutures (1 patient). RESULTS: Anatomic cure was proven in 21 patients (87.5%). Clinical cure was obtained in 23 cases (96%), as follows: 15 patients with a single transvenous approach, 6 with a combined arteriovenous approach, and 2 with an arterial approach after failure of venous access. There was one persistent cavernous fistula despite coil packing of the cavernous sinus. Complications were as follows: five transient and one permanent sixth nerve palsies in cavernous DAVFs, two transient labyrinthic dysfunctions in transverse sinus DAVFs, and one subarachnoid hemorrhage without sequelae. CONCLUSION: Transvenous embolization is a useful and safe approach in the management of intracranial DAVFs.

Adult

Safety and efficacy of endovascular treatment of acutely ruptured aneurysms.

OBJECTIVE: To study the safety and efficacy of endovascular treatment of acutely ruptured aneurysms with Guglielmi detachable coils. METHODS: From August 1992 until December 1995, 75 patients were referred for endovascular treatment of acutely ruptured aneurysms. There were 49 women and 26 men, with a mean age of 55 years. Patients were classified according to the Hunt and Hess grading system. There were 18 Grade I patients (24%), 13 Grade II patients (17%), 30 Grade III patients (40%), 11 Grade IV patients (15%), and 3 Grade V patients (4%). Fifty patients (66%) were treated within 48 hours, and 64 (85%) were treated within 1 week of hemorrhage. The most frequently treated aneurysms were located at the basilar bifurcation (32%), anterior communicating artery (16%), posterior communicating artery (15%), and ophthalmic segment of the carotid artery (11%). Most of the aneurysms were smaller than 15 mm (77%). Fifty-six percent of the aneurysms had small (4 mm) necks, and 44% had wide (> 4 mm) necks. Clinical follow-up was performed at 6 months, and results were classified according to the Glasgow Outcome Scale (GOS). Control angiograms were performed immediately, at 6 months, and yearly thereafter. RESULTS: Immediate angiographic results were considered to be satisfactory in 58 patients (77%) (complete obliteration, 40%; residual neck and dog ear, 37%). Technical failures occurred in 5 patients (7%), and 12 patients experienced some residual opacification of their aneurysms (16%). The procedure-related mortality and morbidity rate was 8%. At 6 months, the outcomes were as follows: GOS score of 1, 50 patients (66.7%); GOS score of 2, 4 patients (5.3%); GOS score of 3, 4 patients (5.3%); and GOS score of 5, 17 patients (22.7%). The main causes of death and disability at 6 months were the direct effect of the initial hemorrhage (9%), delayed ischemia (6.7%), subsequent bleeding (4%), intraprocedural rupture (4%), open surgical complications (3%), and unrelated deaths (4%). Six-month angiographic follow-up data were available for 50 patients (67%). The morphological results were considered to be satisfactory in 44 of these 50 patients (88%) (complete occlusion, 46%; residual neck or dog ear, 42%). CONCLUSION: Endovascular treatment of acutely ruptured aneurysms was attempted without clinically significant complication in 92% of the patients. The morphological results were unsatisfactory in 23% of the patients. Complete obliteration of the sac, with or without residual neck, is essential to prevent subsequent bleeding, which occurred in 5% of the patients. The overall outcome at 6 months was similar to that of surgical series, despite a selected group of patients with negative prognostic factors.

Acute Disease

Regulation of NMDA receptor subunit mRNA expression in the guinea pig vestibular nuclei following unilateral labyrinthectomy.

The localization of neurons expressing mRNAs for the NR1 and NR2A-D subunits of the glutamatergic NMDA receptor was examined by non-radioactive in situ hybridization throughout the guinea pig vestibular nuclei. After deafferentation of the vestibular nuclei by unilateral labyrinthectomy, modifications of the mRNA distributions were followed for 30 days. A quantitative analysis was performed in the medial vestibular nucleus by comparison of the labelled neurons in the ipsi- and contra-lateral nuclei. In vestibular nuclei, the NR1 subunit mRNA was found in various populations of neurons. The NR2A and NR2C subunit mRNAs were less widely distributed, whereas little NR2D mRNA was detected and only rare cells contained NR2B mRNA. NR1 and NR2A-D mRNAs were colocalized in some but not other neuronal types. Twenty hours after the lesion, there was a transient ipsilateral increase of NR1 mRNA level in the medial vestibular nucleus, followed by a decrease 48 h after the lesion and, at 3 days, by recovery to the control level. An ipsilateral increase in the mRNA level of NR2C subunit was detected 20 h after lesion and maintained at 48 h. No significant changes were apparent in NR2A, NR2B and NR2D mRNA levels. The distributions and the differential signal intensities of NR2A-D mRNAs suggest various subunit organizations of the NMDA receptors in different neurons of the vestibular nuclei. Neuronal plasticity reorganizations in the vestibular nuclei following unilateral labyrinthectomy appear to include only changes in NR1 and NR2C mRNA levels modifying the functional diversity of the NMDA receptor in the ipsilateral medial vestibular nucleus neurons. The transient changes in NR1 and the NR2C subunit mRNA expressions in response to sensory deprivation are consistent with an active role for NMDA receptors in the appearance and development of the vestibular compensatory process.

Animals

AMPA receptors in cultured vestibular ganglion neurons: detection and activation.

The presence and the activity of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptors were investigated in mouse cultured vestibular ganglion neurons using immunocytochemistry and measurement of intracellular calcium concentration ([Ca2+]i) by spectrofluorimetry. Cultures of dissociated vestibular ganglia from 18 gestation day mouse embryos were grown in vitro for 3-4 days. Immunocytochemical labelling of AMPA receptor subunits GluR2/R3 and GluR4 was detected in neuron cell bodies and proximal neurites and more lightly in glial cells. There was no clear selective subcellular localization of the different subunits. For the GluR1 subunit a signal was observed only in some neurons and neurites and was weak. Vestibular ganglion neurons responded to fast application of 1 mM glutamate and 10 mM aspartate through unknown receptors by a transient increase in [Ca2+]i. The mean amplitude of this rapid increase was about nine times the resting level and recovery was complete within 30-45 s after the application. If separated by an interval of at least 10 min, consecutive applications produced similar calcium responses. AMPA (1 mM) application induced the same type of responses. Five minutes prior to the AMPA exposure, the application of a specific AMPA antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX, 1.5 mM), in the external medium inhibited the response to AMPA. Chelation of external calcium by EGTA (1.5 mM) abolished the responses to drug applications, indicating that an influx of external calcium is involved in the [Ca2+]i increase. These observations suggest that heteromeric AMPA receptors are expressed in vestibular ganglion neurons in culture and play a functional role in their glutamate-induced depolarization. Experiments are in progress using specific AMPA and NMDA antagonists to characterize the participation of the two types of ionotropic glutamate receptors in the glutamate/aspartate-induced intracellular calcium response.

Animals