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Biomedical subjects

M Stephan

Publications and source records attributed to M Stephan.

At least 19 recordsLinked to original sources

[Prevalence and description of treatment with intraocular pressure-lowering topical medications in continental France].

PURPOSE: The first objective of the present study was to estimate the prevalence of patients treated for glaucoma or ocular hypertension (OHT) with an IOP (intraocular pressure) -lowering topical medication. Subjects were 40 years old and living in continental France. The second objective was to describe the type of therapy, compliance, and the quality of life of the subjects treated. METHODS: This study was a telephone survey conducted in a general population on a representative sample of 5726 subjects in 2004. Subjects treated for glaucoma or OHT were defined as those declaring use of eye drops for more than 1 month and mentioning one of the 52 registered IOP-lowering topical medications and/or stating that they were taking eye drops for glaucoma or OHT. Quality of life was measured using the GlauQOL-17 questionnaire. RESULTS: 237 subjects (4.1%) corresponded to this definition. The prevalence increased with age, from 0.7% in subjects aged 40-44 years to 10.6% in those aged 80 years or more. The age-standardized prevalence was higher in the Paris area (5.3%), the Mediterranean (4.5%), and the Southwest (4.7%), and lower in rural areas (3.2%), and in subjects with less than high school education (2.9%). Beta-blockers (49.5%) and prostaglandins (37.4%) were the most frequent treatments, followed by carbonic anhydrase inhibitors (15.3%), sympathomimetics (5.7%), and myotics (1.3%). Compliance was not total in 39% of the patients (22% of those treated with once-a-day dosage). DISCUSSION: The results of the present study are in line with French health authority data and with the results of the French "Glaucoma and intraocular high pressure, one day" study results. Moreover, the lower prevalence in regions with low medical density, low socioeconomic level, and rural areas, suggest that glaucoma or OHT might be underdiagnosed. CONCLUSION: On the basis of this first nationwide study, it can be estimated that the prevalence of subjects treated with IOP-lowering topical medications is about 1.2 million in France. The number of daily doses appears to influence compliance.

Adult↗

Comparison of non-invasive measures of cholinergic and allergic airway responsiveness in rats.

AIM: Non-invasive analysis of tidal expiratory flow parameters such as Tme/TE (time needed to reach peak expiratory flow divided by total expiratory time) or midexpiratory tidal flow (EF50) has been shown useful for phenotypic characterization of lung function in humans and animal models. In this study, we aimed to compare the utility of two non-invasive measures, EF50 and Tme/TE, to monitor bronchoconstriction to inhaled cholinergic and allergic challenges in Brown-Norway rats. METHODS: Non-invasive measurements of Tme/TE and EF50 were paralleled by invasive recordings of Tme/TE, EF50 and pulmonary conductance (GL). RESULTS: First, dose-response studies with acetylcholine were performed in naive rats, showing that EF50 better than Tme/TE reflected the dose-related changes as observed with the classical invasive outcome parameter GL. The subsequent determination of allergen-specific early airway responsiveness (EAR) showed that ovalbumin-sensitized and -challenged rats exhibited airway inflammation and allergen-specific EAR. Again, EF50 was more sensitive than Tme/TE in detecting the allergen-specific EAR recorded with invasive and non-invasive lung function methods and agreed well with classical GL measurements. CONCLUSION: We conclude that non-invasive assessment of EF50 is significantly superior to Tme/TE and serves as a suitable and valid tool for phenotypic screening of cholinergic and allergic airway responsiveness in rats.

Acetylcholine↗

Biofilm population dynamics in a trickle-bed bioreactor used for the biodegradation of aromatic hydrocarbons from waste gas under transient conditions.

The dynamics of a multispecies biofilm population in a laboratory-scale trickle-bed bioreactor for the treatment of waste gas was examined. The model pollutant was a VOC-mixture of polyalkylated benzenes called Solvesso 100. Fluorescence in-situ hybridization (FISH) was applied in order to characterise the population composition. The bioreactor was operated under transient conditions by applying pollutant concentration shifts and a starvation phase. Only about 10% of the biofilm mass were cells, the rest consisted of extracellular polymeric substances (EPS). The average fraction of Solvesso 100-degrading cells during pollutant supply periods was less than 10%. About 60% of the cells were saprophytes and about 30% were inactive cells. During pollutant concentration shift experiments, the bioreactor performance adapted within a few hours. The biofilm population exhibited a dependency upon the direction of the shifts. The population reacted within days after a shift-down and within weeks after a shift-up. The pollutant-degraders reacted significantly faster compared to the other cells. During the long-term starvation phase, a shift of the population composition took place. However, this change of composition as well as the degree of metabolic activity was completely reversible. A direct correlation between the biodegradation rate of the bioreactor and the number of pollutant-degrading cells present in the biofilm could not be obtained due to insufficient experimental evidence.

Biodegradation, Environmental↗

Elimination of linezolid by an in vitro extracorporeal circuit model.

Linezolid is an oxazolidinone antibiotic with activity against important grampositive aerobic bacteria, including nosocomial pathogens. It is not known whether dosage adjustments are necessary in patients treated with continuous renal replacement therapies. This in vitro study was conducted to investigate the elimination of linezolid in an in vitro continuous hemo(dia)filtration model using different filter materials (polysulfone, polyacrylonitrile, polyamide), surface areas, and different modes of renal replacement therapies. Linezolid was measured using HPLC with UV-detection. No adsorption of linezolid to any of the tested membranes was detected. Recovery of linezolid in the ultrafiltrate was 98.2 +/- 10.5% in the filtration mode. During dialysis, recovery was significantly less (87.6 +/- 16.1%; p = 0.02). Linezolid elimination was not altered by filter size, when polysulfone filters with surface areas of 0.7 m2 and 1.3 m2 were tested. In conclusion, the dosage recommendations for linezolid are independent of the filter materials. However, the elimination is significantly higher during hemofiltration compared to dialysis.

Acetamides↗

Operative procedure and volumetry in experimental biomechanical hearts.

BACKGROUND: To date, skeletal muscle ventricles (SMVs) have been integrated into the circulation by a second operation following construction, vascular delay and several weeks of electrical conditioning. Recently, intra-thoracic SMVs around a mock system contracted against a pressure of 70 mmHg for several months immediately after construction in the presence of clenbuterol. This indicates that the two-step procedure may be exchanged for a clinically favorable one-step operation. The stroke volume is tested intra-operatively. METHODS: In twelve Boer goats, the latissimus dorsi muscle was folded in a double layer around a polyurethane chamber, which was integrated into descending thoracic aorta. This muscular flow-through chamber containing a stabilizing inner layer denoted "Biomechanical Heart" (BMH) showed immediate activity against systemic pressure. The conductance catheter method was applied for analysis of intra-operative stroke volume. RESULTS: The one-step operative procedure employed was practicable in all 12 goats. Operative complications were eliminated without difficulty. Intraoperative application of the conductance catheter resulted in BMH with a stroke volume of 55 +/- 14 ml. In the best BMH on postoperative day 132, a continuous pumping capacity of 1.4 l/min was measured. This BMH functioned up to day 414 postoperatively, and failed due to a rupture of the pumping chamber. CONCLUSION: This operative procedure and dynamic volumetry of experimental Biomechanical Hearts might be relevant for clinical use.

Animals↗

Fetal valproate syndrome and autism: additional evidence of an association.

Autism has been described in association with a variety of medical and genetic conditions. We previously reported on a patient whose clinical phenotype was compatible with both fetal valproate syndrome (FVS) and autism. Here we present five additional patients with FVS and autism. In all five of our patients, there was evidence of cognitive deficits, manifestations of autism, and typical phenotypic characteristics of FVS. The association between this known teratogen and autism has both clinical and research implications.

Autistic Disorder↗

Clenbuterol-supported dynamic training of skeletal muscle ventricles against systemic load: a key for powerful circulatory assist?

BACKGROUND: The profound loss of power that occurs in skeletal muscle after electrical conditioning has been the major limiting factor in its clinical application. This study investigates a 3-fold approach for chronic conditioning of skeletal muscle ventricles (SMVs) combining electrical transformation, dynamic training against systemic load, and pharmacological support with clenbuterol. METHODS AND RESULTS: In 10 adult male goats, SMVs were constructed from latissimus dorsi muscle wrapped around an intrathoracic training device with windkessel characteristics. SMVs were stimulated electrically and trained dynamically by shifting volume against systemic load. Group 1 goats were controls (n=5), and group 2 goats (n=5) were supported with clenbuterol (150 microg 3 times a week). SMV dynamics were recorded weekly over 5 to 8 months: peak pressure (P(max)), stroke volume (SV), volume displacement per minute (VD), stroke work per day (SW/d), and maximum rates of pressure generation, +dP/dt(max), and decay, -dP/dt(max). In group 1, after 149.5+/-2.7 days (n=4), data were P(max)=70.8+/-4.7 mm Hg, SV=3.2+/-1.2 mL, VD=62.3+/-21.1 mL/min, SW/d=0.8+/-0.4 kJ, +dP/dt(max)=64+/-13 mm Hg/s, and -dP/dt(max)=156+/-32 mm Hg/s. These parameters were significantly improved (P<0.007) in the clenbuterol-treated group 2 after 151+/-2.7 days: P(max)=176.2+/-43.8 mm Hg, SV=23.3+/-6.1 mL, VD=568.2+/-186.1 mL/min, SW/d=9.1+/-2.2 kJ, +dP/dt(max)=1134+/-267 mm Hg/s, and -dP/dt(max)=1028+/-92 mm Hg/s. In 2 SMVs of group 2, VD increased to 1090 and 1235 mL/min after 202 and 246 days of training, respectively. At termination, myosin heavy chains were totally transformed into myosin heavy chain-1 in all SMVs. CONCLUSIONS: This clenbuterol-supported dynamic training provides powerful SMVs that may have important clinical implications for the treatment of end-stage heart failure by muscular blood pumps.

Animals↗

Use of cryostat sections from snap-frozen nervous tissue for combining stereological estimates with histological, cellular, or molecular analyses on adjacent sections.

Adequate tissue preparation is essential for both modern stereological and immunohistochemical investigations. However, combining these methodologies in a single study presents a number of obstacles pertaining to optimal histological preparation. Tissue shrinkage and loss of nuclei/nucleoli from the unprotected section surfaces of unembedded tissue used for immunohistochemistry may be problematic with regard to adequate stereological design. In this study, frozen cryostat sections from hippocampal and cerebellar regions of two rat strains and cerebellar and cerebral regions from a human brain were analyzed to determine the potential impact of these factors on estimates of neuron number obtained using the optical disector. Neuronal nuclei and nucleoli were clearly present in thin sections of snap-frozen rat (3 microm) and human (6 microm) tissue, indicating that neuronal nuclei/nucleoli are not unavoidably lost from unprotected section surfaces of unembedded tissue. In order to quantify the potential impact of any nuclear loss, optical fractionator estimates of rat hippocampal pyramidal cells in areas CA1-3 and cerebellar granule and Purkinje cells were made using minimal (1 microm) upper guard zones. Estimates did not differ from data reported previously in the literature. This data indicates that cryostat sections of snap-frozen nervous tissue may successfully be used for estimating total neuronal numbers using optical disectors.

Animals↗

[Bilateral inferior hemianopsia as an early symptom of Heidenhain type Creutzfeldt-Jakob disease].

BACKGROUND: The Heidenhain variant is a subtype of Creutzfeldt-Jakob disease (CJD) where visual symptoms are leading. HISTORY AND SIGNS: We report on a 60-year-old woman who developed within a few weeks bilateral inferior hemianopsia. Morphological findings of the eyes were normal. Neurological examination and cerebral CT/MRI were normal too. P 100 latency of visual evoked potentials (VEP) of both eyes, however, was delayed. OUTCOME: During the course of the disease visual field narrowed progressively and 3 months after the first symptoms the patient went blind. Only at that time myoclonia, hyperkinesia, and psychiatric symptoms appeared. Changes of EEG and cerebrospinal fluid were suggestive of Creutzfeldt-Jakob disease (CJD). The patient died after 5 1/2 months and diagnosis was confirmed neuropathologically with mainly occipital spongiform encephalopathy. CONCLUSION: This case illustrates the diagnostic difficulties of the Heidenhain type of CJD and demonstrates that in patients with progressive visual field defects without morphological abnormalities of the eyes or radiological abnormalities of the brain CJD should be considered. It should be looked out for additional neurological (especially extrapyramidal) and psychiatric symptoms.

Creutzfeldt-Jakob Syndrome↗

Acute pediatric digoxin ingestion.

Although most acute pediatric ingestions of digoxin or other related cardiac glycosides result in minimal or no symptoms, occasionally a child is symptomatic. Gastrointestinal complaints or first-degree AV block are the most common presenting symptoms. Children can generally be given a single dose of activated charcoal, observed, and discharged without any subsequent problems. However, some patients will be toxic and require monitoring, medication, and possibly digoxin-specific antibody fragments. The most important role of the clinician is to recognize the clinical manifestations and institute the appropriate therapy. As in the case presented, the history of an ingestion may not always be obtained initially. Thus, the physician should maintain a high index of suspicion for acute digoxin ingestion and order the appropriate confirmatory tests (eg, a digoxin level, a potassium level, and a 12-lead ECG) when necessary.

Acute Disease↗

[Eosinophil cationic protein in a 39-year-old patient with Churg-Strauss syndrome].

HISTORY AND CLINICAL FINDINGS: A 39-year-old woman in good health suddenly developed painful paraesthesia and incomplete paresis of all four limbs. Furthermore, arterial hypertension and tachycardia were found. The patient reported a history of chronic allergic rhinitis for 10 years and asthma one year. INVESTIGATIONS: Laboratory data showed an increased leucocyte count with a substantial increase in eosinophils in peripheral blood as well as in bone marrow. Nonspecific inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein, fibrinogen as well as eosinophil cationic protein (ECP) were also increased. Histological investigations of a skin-muscle biopsy of the quadriceps revealed necrotizing vasculitis with extravascular granulomata and histiocytic giant cells. DIAGNOSIS, TREATMENT AND COURSE: Based on the diagnosis of Churg-Strauss syndrome treatment with methylprednisolone (500 mg every second day) was started, but was found to be ineffective after 10 days. Symptoms responded well to a subsequent course of 150 mg cyclophosphamide combined with 50 mg prednisolone per day. Pareses and pain were significantly reduced and all qualitative nerve functions returned to normal within two weeks of treatment. Laboratory parameters, especially the ECP, were similarly normalized. CONCLUSION: Churg-Strauss syndrome should be considered in the differential diagnosis of unexplained polyneuropathy. Determination of ECP may not only help in the diagnosis but does also facilitate monitoring of treatment and of further course of the disease.

Adult↗

An evidenced-based clinical pathway for acute appendicitis decreases hospital duration and cost.

BACKGROUND/PURPOSE: In the pediatric population, appendicitis remains the most common surgical emergency encountered. The purpose of this study was to determine the impact of an evidence-based clinical pathway for acute appendicitis on patient care as well as hospital and home care costs at the authors' pediatric institution. METHODS: A prospective evaluation was conducted of an appendicitis clinical pathway (June 1996 through November 1996) compared with historical control patients (June 1994 through November 1994) not cared for by the pathway. RESULTS: Data (average +/- SD) for 120 pathway (P) patients were compared with 122 control (C) patients. Age (11.5 +/- 3.6 years for C v 11.2 +/- 3.9 years for P), rates of negative appendectomy (12.3% for C v 9.2% for P) and perforation (26.2% for C v 18.3% for P) were similar. Pathway patients with nonperforated appendicitis were more often discharged from the hospital within 24 hours (48% for C v 67% for P; P = .014) with lower hospital costs ($4,095 +/- $1,280 for C v $3,638 +/- $1,633 for P; P = .001). Pathway patients with perforated appendicitis had shorter hospitalization (185.2 +/- 59 hours for C v 113 +/- 44 hours for P; P = .0001) and lower hospital costs ($11,175 +/- $3,893 for C v $7,823 +/- $2,366 for P; P = .0001). CONCLUSION: An evidence-based appendicitis pathway decreased duration of hospitalization and cost without adversely affecting diagnosis or therapy. Clinical pathways for surgical diagnoses may prove useful as a means to minimize costs without compromising patient care.

Acute Disease↗

Imaging of thoracic and lumbar spinal extradural arachnoid cysts: report of two cases.

Extradural arachnoid cysts are uncommon expanding lesions in the spinal canal which may communicate with the subarachnoid space. Usually in the lower thoracic spine, they may cause symptoms by compressing the spinal cord or nerve roots. We report cases of thoracic and lumbar arachnoid cysts studied by cystography, myelography, CT and MRI. These techniques showed extradural cystic lesions containing cerebrospinal fluid, with variable communication with the subarachnoid space, causing anterior displacement and flattening of the spinal cord.

Adolescent↗

Placental biogenic amine transporters: cloning and expression.

During intrauterine development, catecholamine turnover (production and clearance rates) is higher than under any other circumstances. This is mediated in large part by placental clearance of circulating catecholamines via a cocaine-sensitive, neuronal transporter-dependent mechanism. In order to confirm the molecular mechanisms for placental transport, we screened an ovine placental cDNA library for biogenic amine transporters. We report here the identification of two biogenic amine transporters with sequences very similar to their neuronal counterparts. One is an ovine serotonin transporter (oSERT) with > 90% homology to the human neuronal SERT. Expression studies confirm transport and competitive binding affinities consistent with a SERT transporter. We have also isolated a partial sequence for the ovine norepinephrine transporter (oNET). These results confirm the placental expression of plasma membrane biogenic amine transporters. We suggest the exaggerated fetal vulnerability to uptake inhibitors, like cocaine, may be due to blockade of placental biogenic amine transport.

Amino Acid Sequence↗

A randomized phase II study of BB-10010: a variant of human macrophage inflammatory protein-1alpha for patients receiving high-dose etoposide and cyclophosphamide for malignant lymphoma and breast cancer.

Macrophage inflammatory protein-1alpha (MIP-1alpha) is a chemokine that can inhibit the cell cycle progression of both primitive haemopoietic and epidermal progenitor cells. This property could potentially be exploited to attenuate both the myelosuppressive effects of chemotherapy as well as mucositis. We evaluated both the biological and clinical effects of BB-10010, a genetically engineered variant of MIP-1alpha, in patients with malignant lymphoma or breast cancer receiving high-dose etoposide (VP 3.6 g/m2) and cyclophosphamide (Cy 200 mg/kg). 52 patients were randomized to one of three cohorts. Cohort A received no BB-10010; cohorts B and C received 10 microg/kg and 100 microg/kg of BB-10010, respectively. All patients received post-chemotherapy G-CSE BB-10010 was well tolerated. There were no significant differences between groups in recovery to an ANC > 0.5 x 10(9)/l, 1 x 10(9)/l or 1.5 x 10(9)/l, the number of days with an ANC < 0.5 x 10(9)/l, days to a platelet count > 50 x 10(9)/l or 100 x 10(9)/l, or the incidence and severity of mucositis. There was no evidence of any effect of BB-10010 on colony-forming cell (CFC) or long-term culture-initiating cell (LTC-IC) mobilization, cycling activity in the marrow or on chemotherapy-induced changes in CFC or LTC-IC number both of which were in the normal range by 22 d after completion of the chemotherapy. To our knowledge this is the first report of a myelointensive regimen having no apparent long-term effect on the LTC-IC compartment. In summary, BB-10010 is safe when used in patients receiving high-dose therapy but has no effect on reducing the toxicity of such therapy.

Adolescent↗