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Biomedical subjects

C Schnyder

Publications and source records attributed to C Schnyder.

At least 19 recordsLinked to original sources

Blood-brain barrier disruption associated with topiramate-induced angle-closure glaucoma of acute onset.

BACKGROUND: Topiramate (Topamax(R)) is an anti-epileptic drug of the sulfamate group used secondarily for bipolar disease. HISTORY AND SIGNS: One week after initiation of topiramate treatment for a bipolar disorder, a 57-year-old man presented with blurred vision. Clinical examination revealed a bilateral conjunctivitis, areflexic mydriasis, severe anterior chamber shallowing, with a myopic shift and vitritis. THERAPY AND OUTCOME: A spinal tap revealed an increased protein content of 1581 mg/L on cerebrospinal fluid (CSF) analysis, being compatible with a rupture of the blood-brain barrier (BBB). UBM exposed bilateral ciliochoroidal effusions with secondary angle-closure. Topiramate was promptly discontinued, whereas visual acuity, intraocular pressure (IOP), and anterior and posterior segments anatomy normalized within 1 week. One month later, bilateral iris atrophy was present. CONCLUSION: The presence of BBB disruption with increased protein content in CSF with simultaneous blood ocular barrier breakdown may suggest a common inflammatory mechanism.

Acute Disease↗

Comparative study between deep sclerectomy with and without collagen implant: long term follow up.

AIM: To identify the value of using collagen implant in deep sclerectomy. METHODS: A prospective randomised trial of 104 eyes (104 patients) with medically uncontrolled primary and secondary open angle glaucoma. All patients had deep sclerectomy (DS), half of them with and the other half without a collagen implant (CI) sutured in the scleral bed. The main outcome measures were intraocular pressure (IOP), visual acuity, number of treatments preoperative and postoperative, and Nd:YAG goniopunctures. RESULTS: Mean follow up period was 44.5 (SD 21) months for the DS group and 43.9 (SD 14) months for the deep sclerectomy with a collagen implant (DSCI) group. The mean preoperative IOP was 23.3 (SD 7.2) mm Hg for the DS group and 25.6 (SD 4.9) mm Hg for the DSCI group. The mean IOP at the first postoperative day was 6.1 (SD 4.21) mm Hg for the DS group and 5.1 (SD 3.3) mm Hg for the DSCI group. At 48 months IOP was reduced by 40% (14 versus 23.3 mm Hg) for the DS group and by 50% (12.7 versus 25.6 mm Hg) for the DSCI group. Complete success rate, defined as IOP lower than 21 mm Hg without medication, was 34.6% (18/52 patients) at 48 months for the DS group, and 63.4% (33/52 patients) for the DSCI group. Qualified success rate; patients who achieved IOP below 21 mm Hg with or without medication, was 78.8% (41/52 patients) at 48 months and 94% (49/52 patients) for the DSCI group. The mean number of medications was reduced from 2.1 (SD 0.8) to 1.0 (SD 1) after DS, and was reduced from 2.2 (SD 0.7) to 0.4 (SD 0.6) in the DSCI group (p = 0.001) CONCLUSION: The use of a collagen implant in DS enhances the success rates and lowers the need for postoperative medication.

Aged↗

Ultra-rapid opiate detoxification using deep sedation and prior oral buprenorphine preparation: long-term results.

BACKGROUND: New methods of ultra-rapid opiate detoxification (URD) under intravenous sedation have been criticized because of limited data on safety and long-term follow-up. Premedication with buprenorphine has been advocated to improve safety by decreasing vomiting. Prior research has not explored URD in socially impaired patients. METHOD: Sixteen patients were detoxified with URD and prospectively evaluated over at least 30 months. Data of this procedure were compared with those of our previous study without buprenorphine preparation (Drug Alcohol Depend. 52(3) (1998) 243). The 16 patients were followed up by a general practitioner (GP) before and after URD. The GPs also supervised the 7-day course of buprenorphine treatment prescribed for the 16 patients prior to URD. RESULTS: During the procedure, only one episode of vomiting occurred instead of 13 out of 20 in our previous study. Post-procedure, only two patients experienced moderate withdrawal symptoms, such as persistent nausea, abdominal cramps and vomiting lasting from 24 to 48 h, in comparison with most patients in the previous study without buprenorphine. After a period of at least 30 months (36.0+/-6.38), the 16 patients were still alive and were regularly monitored by their GP. Only two of the 16 never relapsed after URD and reported total opiate abstinence. Fourteen patients relapsed; 12 of these were prescribed a licensed methadone substitution program and two were still using heroin. CONCLUSION: In this small sample, the data indicated that URD with buprenorphine preparation was safe and that it markedly decreased post-procedure morbidity. No patient died over a minimum 30-month follow-up period. Furthermore, the procedure was employed with socially impaired patients. In the long term, a few patients were still free of opiates, while the majority opted for a methadone maintenance program, showing that URD can serve as one possible step in a long-term treatment program.

Adult↗

Five year results of viscocanalostomy.

AIM: To prospectively study the success rate and complications of viscocanalostomy, a non-penetrating glaucoma surgery. METHODS: Prospective non-randomised consecutive case series of 57 eyes (57 patients) with medically uncontrolled primary and secondary open angle glaucoma. Viscocanalostomy was performed on all participants with injection of viscoelastic in the surgically created ostia of Schlemm's canal as well as in the scleral bed, the superficial scleral flap was loosely sutured. Intraocular pressure, visual acuity, and number of goniopunctures were measured. RESULTS: The mean follow up period was 34.1 months. The mean preoperative intraocular pressure (IOP) was 24.6 mm Hg; while the mean postoperative IOP was 5.6 mm Hg at day 1 and 13.9 mm Hg at 36 month. Patients who achieved IOP below 21 mm Hg with or without medication were 90% at 60 months, complete success rate (IOP<21 mm Hg without medication) was 60% at 60 months. 21 patients (37%) needed Nd:YAG goniopuncture postoperatively to control raised IOP, mean time for goniopuncture application was 9.4 months, mean pre-goniopuncture IOP was 20.4 mm Hg and mean postgoniopuncture IOP was 12.6 mm Hg (p <0.0001). CONCLUSION: Viscocanalostomy appears to be a promising modification of filtering surgery.

Aged↗

Descemet membrane detachment after nonpenetrating filtering surgery.

PURPOSE: To make surgeons performing nonpenetrating filtering surgery aware of an unusual complication namely Descemet membrane detachment. METHODS: We retrospectively reviewed nine eyes of nine patients seen in our hospital with Descemet membrane detachment occurring after nonpenetrating filtering surgery from January 1994 to December 2000. RESULTS: Both planar and nonplanar detachments were reported. Neither scrolls nor tears in the Descemet membrane were observed in any patient. After viscocanalostomy (four patients), the detachment was generally noticed shortly after the procedure and the cornea maintained its clarity. After deep sclerectomy with a collagen implant (five patients), it developed weeks to months postoperatively with adjacent corneal edema. Four patients had descemetopexy. None required more than one procedure. However, at the last visit, two detachments persisted although they had diminished in size: one after viscocanalostomy and conservative treatment and one after descemetopexy after deep sclerectomy with a collagen implant. To date otherwise, no signs of significant corneal damage could be observed clinically nor by specular microscopy and pachymetry. CONCLUSIONS: The diagnosis of Descemet membrane detachment can be easily overlooked or misdiagnosed. The clinical presentation, clinical course, and pathogenesis depend on the type of nonpenetrating filtering surgery performed. Ophthalmologists should be aware of this unusual complication, which is likely to be more common after nonpenetrating filtering surgery than after trabeculectomy. A period of observation before attempting descemetopexy is recommended.

Adult↗

Five-year results of deep sclerectomy with collagen implant.

PURPOSE: To study prospectively the success rate and complications of deep sclerectomy with collagen implant (DSCI), a nonpenetrating filtration procedure. SETTING: Glaucoma Unit, Department of Ophthalmology, Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland. METHODS: This nonrandomized prospective trial comprised 105 eyes of 105 patients with medically uncontrolled primary or secondary open-angle glaucoma. Visual acuity, intraocular pressure (IOP), and slitlamp examinations were performed before and after surgery at 1 and 7 days and 1, 3, 6, 9, 12, 18, 24, 30, 36, 48, 54, 60, and 66 months. Visual field examinations were repeated every 6 months. A qualified success was defined as IOP below 21 mm Hg with or without medication. A complete success was defined as IOP lower than 21 mm Hg without medication. RESULTS: The mean follow-up was 43.2 months +/- 14.3 (SD). The mean IOP was 26.8 +/- 7 mm Hg preoperatively, 5.1 +/- 3 mm Hg 1 day postoperatively, and 11.8 +/- 3 mm Hg 60 months postoperatively. At 60 months, the qualified success rate was 94.8% and the complete success rate, 61.9%. The IOP was lower than 21 mm Hg with medication in 32.1% of patients at 60 months; 48 patients (45.7%) had an IOP of 15 mm Hg or lower without medication. No patient developed a shallow or flat anterior chamber, endophthalmitis, or surgery-induced cataract. However, 23 (21.9%) had progression of a preexisting senile cataract. Injections of 5-fluorouracil were given to 25 patients (23.8%) who had DSCI to salvage encysted blebs. The mean number of medications per patient was reduced from 2.30 +/- 0.76 to 0.49 +/- 0.72. CONCLUSION: Deep sclerectomy with collagen implant provided reasonable IOP over a long-term follow-up with few immediate postoperative complications.

Aged↗

Haplotype analysis in determination of the heredity of erythropoietic protoporphyria among Swiss families.

Defects in the human ferrochelatase gene lead to the hereditary disorder of erythropoietic protoporphyria. The clinical expression of this autosomal dominant disorder requires an allelic combination of a disabled mutant allele and a low-expressed nonmutant allele. Unlike most other erythropoietic protoporphyria populations, mutations identified among Swiss erythropoietic protoporphyria families to date have been relatively homogeneous. In this study, genotype analysis was conducted in seven Swiss erythropoietic protoporphyria families, three carrying mutation Q59X, two carrying mutation insT213, and two carrying mutation delTACAG(580-584). Three different haplotypes of five known intragenic single nucleotide polymorphisms, namely -251 A/G, IVS1-23C/T, 798 G/C, 921 A/G, and 1520C/T, were identified. Each haplotype was shared by families carrying an identical mutation in the ferrochelatase gene indicating a single mutation event for each of the three mutations. These mutations have been present in the Swiss erythropoietic protoporphyria population for a relatively long time as no common haplotypes of microsatellite markers flanking the ferrochelatase gene were found, except of two conserved regions, telomeric of the insT213 allele and centromeric of the delTACAG(580-584)allele, each with a size > 3 cM. Among the nonmutant ferrochelatase alleles, patients from six erythropoietic protoporphyria families shared a common haplotype [-251G; IVS1-23T] of the first two single nucleotide polymorphisms. An exception was the haplotype [-251 A; IVS1-23C] identified in the index patient of one erythropoietic protoporphyria family. These results supported the recent findings that the low expressed allele is tightly linked to a haplotype [-251G; IVS1-23T] of two intragenic single nucleotide polymorphisms in the ferrochelatase gene.

Family Health↗

Influence of age and gender on the clinical expression of acute intermittent porphyria based on molecular study of porphobilinogen deaminase gene among Swiss patients.

BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disorder in the heme biosynthetic pathway caused by a partial deficiency of porphobilinogen (PBG) deaminase. Clinically, AIP is characterized as acute neurovisceral attacks that are often precipitated by exogenous factors such as drugs, hormones, and alcohol. An early detection of mutation carriers is essential for prevention of acute attacks by avoiding precipitating factors. This study was aimed at analyzing genetic defects causing AIP among Swiss families to further investigate aspects concerning the clinical expression of the disease. MATERIALS AND METHODS: The PBGD gene of index patients from 21 Swiss AIP families was systematically analyzed by denaturing gradient gel electrophoresis of polymerase chain reaction (PCR) amplified DNA fragments and direct sequencing. RESULTS: Five new mutations insA503, del L170, T190I, P241S, and R321H, as well as three known mutations (R26H, R173Q and W283X) were detected. Twelve of the 21 index patients (57%) carried the prevalent mutation W283X previously found among the Swiss AIP population. Family-specific mutations were then screened among relatives of the index patients. Among the 107 studied individuals, 58 carried a PBGD gene mutation--30 were overt AIP patients and 28 were asymptomatic carriers. The apparent rate of overt disease in the study cohort was 52%, which is significantly higher than the previously reported penetrance of 10-20%. To further examine the clinical expression of AIP, the cumulative life-time risk was calculated among 58 mutation-positive individuals after stratifying for age. The result shows a linear increase of the percentage of the symptomatic patients with age, reaching up to 75% among carriers aged over 60. Moreover, statistical analysis of the gender distribution among patients and asymptomatic carriers indicated that the disease was more frequently expressed among females than males (Fisher's exact test two sided, p= (0.001). CONCLUSIONS: This comprehensive search for genetic defects in the PBGD gene confirmed the existence of a prevalent mutation W283X among Swiss AIP patients, as well as a number of family-private mutations. Genetic analysis laid a groundwork for further studies such as the effects of gender and age on the clinical expression of AIP.

Adolescent↗

Frequency doubling technique in patients with ocular hypertension and glaucoma: correlation with octopus perimeter indices.

PURPOSE: To ascertain whether frequency doubling technique (FDT) (Welch-Allyn, Skaneateles, NY; Zeiss-Humphrey, San Leandro, CA) indices provide results comparable with those of standard Octopus threshold perimeters (Interzeag AG, CH-8952 Schlieren, CH) in patients with glaucoma and in patients suspected of having ocular hypertension, glaucoma, or both. DESIGN: A comparative, consecutive, case series. PARTICIPANTS: Thirty-nine glaucomatous patients and 41 patients with ocular hypertension or suspected glaucoma were recruited consecutively. METHODS: The visual field of the study participants were assessed by FDT program C-20 full threshold and Octopus program dG1X. Only one eye of each participant was selected randomly. Pearson's r correlation coefficient was calculated among the FDT and Octopus indices. MAIN OUTCOME MEASURES: Using Octopus perimeter, mean defect (MD), mean sensitivity (MS), loss variance (LV), and corrected loss variance (CLV) were calculated and used for correlation. For the FDT, mean deviation (FDT-MD) and pattern standard deviation (FDT-PSD) were calculated and used for correlation. Also, the time required to perform the visual field test was considered. RESULTS: In the entire population, a statistically significant correlation (Pearson's r, P<0.001) was found between FDT-MD and both MS (0.77) and MD (-0.80) and between FDT-PSD and both LV (0.50) and CLV (0.45). When the glaucoma group was considered alone, similar significant correlation was found between the indices. In the suspected ocular hypertension and glaucoma suspect group, no significant correlation was found. A significant (P<0.001) difference was found between FDT and Octopus for the time needed to perform the visual field test. CONCLUSIONS: This new technique could be used both to screen populations and to observe glaucomatous visual field progression in early and moderate stages. The FDT is a faster way to analyze the visual field and captures threshold values for each point, but it is important to remember that this is a new technique and its limits are still unknown.

Aged↗

Stage of change of cigarette smoking in alcohol-dependent patients.

Despite the heavy burden of tobacco-related problems in alcohol-dependent patients, little effort has been directed toward reducing the prevalence of smoking in these patients. It seems reasonable to develop nicotine addiction treatments for alcohol-dependent patients based on the smoker's stage of change. To assess the stage of change for tobacco consumption and possible quitting barriers in alcohol-dependent patients, 88 consecutively admitted inpatients of a Swiss university-affiliated alcohol withdrawal clinic were interviewed with a semistructured schedule. More than half of the alcohol-dependent smokers (50.7%) considered the possibility of smoking cessation or had already decided to stop, although the majority (83.1%) were highly dependent smokers. Positive reinforcers were factors influencing motivation both to stop smoking as well as to continue smoking, whereas negative reinforcers had no influence. As recovering alcoholic patients are often interested in smoking cessation and the introduction of nicotine treatment interventions has been shown not to jeopardize the outcome of alcohol treatment, alcohol treatment programs should include counseling for smoking cessation. Education and training for staff is essential, as their beliefs and habits remain an important barrier.

Adult↗

[Multidisciplinary team and coordination of treatment network].

Because of the adverse consequences of alcohol dependence on somatic, psychological and social functions, treatment of alcoholics always requires a multidisciplinary approach. It is a good example of a treatment network. Despite the numerous difficulties encountered in such a multidisciplinary approach, its beneficial effect, its efficacy and even its rewards are tremendously important. The alcohol treatment network of our region should permit such multidisciplinary therapies. Two clinical presentations are used to illustrate its virtues, but also some open questions.

Alcoholism↗

Determination of chlorzoxazone and 6-hydroxychlorzoxazone in plasma by gas chromatography--mass spectrometry.

A gas chromatographic-mass spectrometric method is presented which allows the determination of chlorzoxazone and 6-hydroxychlorzoxazone after derivatization with the reagent N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamide. No interference was observed from endogenous compounds following the extraction of plasma samples from six different human subjects. The standard curves were linear over a working range of 20 to 4000 ng/ml and of 20 to 1000 ng/ml for chlorzoxazone and 6-hydroxychlorzoxazone, respectively. Recoveries ranged from 65 to 97% for the two compounds and intra- and inter-day coefficients of variation were always less than 9%. The limit of quantitation of the method was found to be 5 ng/ml for the two compounds, hence allowing its use for single low dose pharmacokinetics.

Acetamides↗

Inhibition of CYP2E1 by chlormethiazole as measured by chlorzoxazone pharmacokinetics in patients with alcoholism and in healthy volunteers.

BACKGROUND: Chlormethiazole has been shown in in vitro studies, with use of rat and human liver microsomes, to specifically inhibit cytochrome P4502E1 (CYP2E1)-mediated activity by inhibition of the rate of CYP2E1 gene transcription. It is known that CYP2E1 is involved in the activation of many low-molecular-weight toxins and carcinogens and may be involved in the development of alcohol-induced liver disease. METHODS: The pharmacokinetics of a single oral dose of 250 mg chlorzoxazone, a marker of the activity of CYP2E1, were measured in five healthy drug-free volunteers and in 16 patients with alcoholism receiving 1.2 gm or 2.4 gm chlormethiazole per day for 1, 2, or 3 days. The patients were starting an alcohol-withdrawal program and were supposed to have an induced CYP2E1 activity. RESULTS: The results suggest that chlormethiazole strongly decreased chlorzoxazone clearance in the patients with alcoholism compared with clearance in the control subjects (3.98 +/- 1.8 L/hr versus 12.7 +/- 5.6 L/hr; p < 0.005), prolonged the elimination half-life (3.91 +/- 1.23 hours versus 1.12 +/- 0.34 hours; p < 0.001), and caused a threefold increase in the area under the concentration versus time curve of chlorzoxazone (73.0 +/- 35.5 mg.hr/L versus 21.3 +/- 13.7 mg.hr/L; p < 0.005). They also suggest that chlormethiazole significantly decreased the area under the concentration versus time curve of the metabolite 6-hydroxy-chlorzoxazone (4.56 +/- 1.27 mg.hr/L versus 7.1 +/- 1.84 mg.hr/L; p < 0.05). CONCLUSION: Chlormethiazole administration seems to result in a marked reduction of CYP2E1 activity in subjects with high CYP2E1 activity and could at least partially explain the claimed hepatoprotective action of this drug.

Administration, Oral↗

Validation of the Addiction Severity Index in French-speaking alcoholic patients.

OBJECTIVE: Evaluation of a French translation of the Addiction Severity Index (ASI) in 100 (78 male) alcoholic patients. METHOD: Validity of the instrument was assessed by measuring test-retest and interrater reliability, internal consistency and convergence and discrimination between items and scales. Concurrent validity was assessed by comparing the scores from the ASI with those obtained from three other clinimetric instruments. RESULTS: Test-retest reliability of ASI scores (after a 10-day interval) was good (r = 0.63 to r = 0.95). Interrater reliability was evaluated using six video recordings of patient interviews. Severity ratings assigned by six rates were significantly different (p < .05), but 72% of the ratings assigned by those who viewed the videos were within two points of the interviewer's severity ratings. Cronbach alpha coefficient of internal consistency varied from 0.58 to 0.81 across scales. The average item-to-scale convergent validity (r value) was 0.49 (range 0.0 to 0.84) for composite scores and 0.35 (range 0.00 to 0.68) for severity ratings, whereas discriminant validity was 0.11 on average (range-0.19 to 0.46) for composite scores and 0.12 (range-0.20 to 0.52) for severity ratings. Finally, concurrent validity with the following instruments was assessed: Severity of Alcoholism Dependence Questionnaire (40% shared variance with ASI alcohol scale), Michigan Alcoholism Screening Test (2% shared variance with ASI alcohol scale) and Hamilton Depression Rating Scale (31% shared variance with ASI psychiatric scale). CONCLUSIONS: The Addiction Severity Index covers a large scope of problems encountered among alcoholics and quantifies need for treatment. This French version presents acceptable criteria of reliability and validity.

Adult↗

[Opinion and attitude of physicians regarding organization and participation on a multidisciplinary alcoholism unit].

The inaccuracy of physicians in the diagnosis, evaluation and treatment referral of alcoholic patients has prompted us to set a Multidisciplinary Alcohol Unit (Unit). Its aims are to set coordinated and individualized treatment proposals and to train medical staff in dealing with alcohol problems. After six months of activity we performed an investigation by all physicians who delt with the Unit including residents and practitioners. We sent 78 questionnaires investigating training in alcohol problems, addictive diseases and psycho-social medicine, subjective usefulness of the Unit for the patient as well as for the medical staff, subjective effectiveness of treatments for alcoholics and reasons for patients' referral. 87% of the physicians completed the questionnaire. According to groups, 12 to 20% of the physicians reported that their training in addictive problems was sufficient. Half of practitioners and 20% of hospital residents reported that their training in psychosocial medicine was satisfactory. All the physicians who answered the questionnaire considered the Unit to be usefull for themselves, mainly because of the Unit's teaching abilities and 89% considered the Unit useful for the patients. In term of effectiveness, alcoholism treatment is percieved by residents to be more efficient when mediated by a specialized unit rather than by practitioners or by themselves. Practitioners percieved that the treatment is more efficient when handled by themselves or by a specialized social unit. Principal reasons to seek help from the Unit were a main diagnosis of alcohol-related disease, the need to complete the psycho-social evaluation and subjective insufficient skills in the field. In conclusion the Unit seems to meet the need of medical doctors despite the limited number of referred cases and is said to be usefull for their patients as well as for themselves.

Adult↗