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Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 145 records · Page 8Linked to original sources

Effect of MTHFR 677C>T on plasma total homocysteine levels in renal graft recipients.

BACKGROUND: Hyperhomocysteinemia is an established, independent risk factor for vascular disease morbidity and mortality. The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T has been shown to result in increased total homocysteine concentrations on the basis of low folate levels caused by a decreased enzyme activity. The effect of this polymorphism on total homocysteine and folate plasma levels in renal transplant patients is unknown. METHODS: We screened 636 kidney graft recipients for the presence of the MTHFR C677T gene polymorphism. The major determinants of total homocysteine and folate plasma concentrations of 63 patients, who were identified to be homozygous for this gene polymorphism compared with heterozygotes (N = 63), and patients with wild-type alleles (N = 63), who were matched for sex, age, glomerular filtration rate (GFR), and body mass index, were identified by analysis of covariance. The variables included sex, age, GFR, body mass index, time since transplantation, folate and vitamin B12 levels, the use of azathioprine, and the MTHFR genotype. To investigate the impact of the kidney donor MTHFR genotype on total homocysteine and folate plasma concentrations, a similar model was applied in 111 kidney graft recipients with stable graft function, in whom the kidney donor C677T MTHFR gene polymorphism was determined. RESULTS: The allele frequency of the C677T polymorphism in the MTHFR gene was 0.313 in the whole study population [wild-type (CC), 301; heterozygous (CT), 272; and homozygous mutant (TT), 63 patients, respectively] and showed no difference in the patient subgroups with various renal diseases. The MTHFR C677T gene polymorphism significantly influenced total homocysteine and folate plasma concentrations in renal transplant recipients (P = 0.0009 and P = 0.0002, respectively). Furthermore, a significant influence of the GFR (P = 0.0001), folate levels (P = 0.0001), age (P = 0.0001), body mass index (P = 0.0001), gender (P = 0.0005), and vitamin B12 levels (P = 0.004) on total homocysteine concentrations was observed. The donor MTHFR gene polymorphism had no influence on total homocysteine and folate levels. Geometric mean total homocysteine levels in patients homozygous for the mutant MTHFR allele were 18.6 micromol/liter compared with 14.6 micromol/liter and 14.9 micromol/liter in patients heterozygous for the MTHFR gene polymorphism and those with wild-type alleles (P < 0.05 for TT vs. CT and CC). Geometric mean folate levels were lower in CT and TT patients (11.2 and 10.2 nmol/liter) compared with CC patients (13.6 nmol/liter, P < 0.05 vs. CT and TT). CONCLUSIONS: This study demonstrates that homozygosity for the C677T polymorphism in the MTHFR gene significantly increases total homocysteine concentrations and lowers folate levels in kidney graft recipients, even in patients with excellent renal function (GFR more than median). These findings have important implications for risk evaluation and vitamin intervention therapy in these patients who carry an increased risk for the development of cardiovascular disease.

Adult↗

Transcatheter closure of secundum atrial septal defects with the new self-centering Amplatzer Septal Occluder.

AIMS: The study was set up to find out whether a new self-centering prosthesis for transcatheter closure of secundum atrial septal defects could overcome the disadvantages of previously described devices. METHODS AND RESULTS: Fifty-two consecutive patients with a significant atrial septal defect were considered for transcatheter closure with the Amplatzer Septal Occluder. The device, made of a Nitinol and polyester fabric mesh, provides a different approach to defect occlusion by stenting the atrial septal defect up to a stretched diameter of 26 mm. Three infants whose large defects were demonstrated on a transthoracic echocardiogram were excluded from transcatheter treatment. On transoesophageal echocardiography, 49 defects ranged from 6-26 mm, in one adult the defect measured 28 mm and this patient was excluded from attempted transcatheter closure. At cardiac catheterization in five further patients, devices were not implanted, in two because the stretched diameter exceeded 26 mm and in three the device was withdrawn because it was unstable or compromised the mitral valve. Thus, device closure was performed in 43 patients. At follow-up after 3 months the complete closure rate was 97%. CONCLUSION: The self-centering Amplatzer Septal Occluder is very efficient and user-friendly and offers interventional closure in 83% of an unselected group of patients presented with an atrial septal defect.

Adolescent↗

[Pulleys of the tendon sheath of the flexor pollicis longus muscle].

The fibrous wall of the flexor tendon sheath of the thumb is reinforced by pulleys similar to those in the fingers. As cited in the literature, there are two annular pulleys A 1 and A 2 and one oblique pulley. On the basis of our investigations, this distribution was found only in 10%. In 90%, the proximal (A 1) and the distal pulley (A 2) can be seen. However, between these two annular pulleys a Y-shaped fiber complex can be dissected at the level of the base and the shaft of the proximal phalanx. This complex can be further divided into an annular part (proximal) and an oblique part (distal). The annular part is associated with the tendon insertion of the adductor pollicis muscle. The oblique part arises distal from the annular part from the ulnar side of the tendon sheath, running to the radial side of the proximal phalanx interwoven with the interphalangeal joint capsule and the palmar plate. Some fiber strands continually pass into the cutaneous ligaments of Cleland. Thin accessory pulley fibers were found between the annular pulley A 1 and the annular part of the Y-shaped fiber complex in 9.5% and in 20.6% between the oblique part and the annular pulley A 2.

Adult↗

Is the function of the serratus anterior muscle disturbed following division during a standard thoracotomy?

In a prospective study the functional results after dissection or preservation of the serratus anterior muscle in the postero-lateral standard thoracotomy were evaluated. In 14 patients of our clinic with dissection and suture and in 14 patients with preservation of the serratus muscle the muscle function was assessed and compared preoperatively, within the first two post-operative weeks, and three months after the operation by the same physiotherapists. The two groups were blinded in regard to age, original disease, and mode of intervention. We compared the wing position of the scapula in the sitting position and the positioning of the scapula at fixation of the shoulder joint in the sitting and in the supine position. Using a four-grade function assessment scheme, both groups obtained the same functional results. There was no seroma in either group. After 2.8 (2.5 to 3.0) years all the surviving patients described symmetric functional conditions. We therefore conclude that in order to achieve a better view of the operative field the serratus muscle may be dissected close to the origin if it is then readapted.

Adult↗

Gross and fine motor development is impaired in children with cyanotic congenital heart disease.

Many factors may intervene with the motor development of children with congenital heart disease (CHD). Children aged 5 to 14 years with various CHD were examined for disturbances of gross and fine motor development using motometric tests and compared with 30 healthy controls. The results of the Körperkoordinationstest für Kinder (KTK) (a body coordination test for children) for gross motor development were significantly lower in patients with uncorrected cyanotic CHD (motor quotient MQ 74.8 +/- 11.7, mean +/- 1 standard deviation, n = 16) and after corrective surgery (MQ 81.2 +/- 16.6, n = 25) than in controls (MQ 102.8 +/- 11.8, n = 30). No relationship between these results and the cardiopulmonary exercise capacity was found. In patients with cyanotic CHD, significant deficits in fine motor development were present before corrective surgery (e.g. Zielpunktiertest [dotting] MQ 87.7 +/- 9.9 vs. 106.5 +/- 10.8), but already two years afterwards the results reached nearly normal values (MQ 97.1 +/- 17.0). In contrast, children with acyanotic CHD demonstrated normal gross and fine motor development. These results indicate that long-standing hypoxemia in infancy must be considered as an important cause of the pronounced motor disturbances. Early neurological evaluation of these children and a specialized motor physiotherapy are recommended.

Adolescent↗

Extracranial cephalic schwannomas: a series of 15 patients.

The aim of this study was to report a series of extracranial cephalic schwannomas. Fifteen patients with extracranial schwannomas treated between 1981 and 1999 are presented, and their clinical course during a median follow-up of 4.1 years is discussed. There is a female predominance. No specific factors have been identified. Their diagnosis is often delayed (median, 2.6 years). There is no predominant side. The orbit represents the most frequent location of schwannomas (26%). The trigeminal nerve is the most often affected (53%). Computed tomography and magnetic resonance imaging contribute to the diagnosis. Macroscopically, the schwannoma is a well-defined tumor of ovoid form and brownish color. It is formed of soft tissues and is fragmented easily. Diagnosis is often evident on microscopic examination. The only treatment is surgery. It consists of enucleation after opening the epineurium using an operating microscope, without interruption of the continuity of the nerve. The authors have observed only two relapses (the first two patients operated without a microscope). Total excision allows recovery. Nerve injuries have variable prognosis. It is necessary in juvenile populations to search for neurofibromatosis. All schwannomas required surgical treatment using an operating microscope to obtain total recovery.

Adolescent↗

Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock.

OBJECTIVE: To investigate the impact of exogenous beta-adrenergic receptor stimulation on splanchnic blood flow, oxygen kinetics, glucose-precursor flux, and liver metabolism in septic shock. DESIGN: Prospective trial. SETTING: University hospital intensive care unit. PATIENTS: Six patients with hyperdynamic (cardiac index >4.0 L/min/m2) septic shock, all requiring norepinephrine to maintain blood pressure >65 mm Hg. INTERVENTIONS: We compared norepinephrine and phenylephrine titrated to achieve similar systemic hemodynamics and gas exchange. Splanchnic hemodynamics, oxygen kinetics, and metabolic parameters were measured before, during, and after replacing norepinephrine with phenylephrine. MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow and oxygen kinetics were derived from the steady-state indocyanine-green clearance based on hepatic dye extraction and arterial and hepatic venous blood gases. Endogenous glucose production rate was derived from the plasma appearance rate of stable-isotope-labeled glucose using a primed-constant infusion. Splanchnic lactate, alanine (high-performance liquid chromatography) uptake, and hepatic monoethylglycinexylidide (MEGX) (fluorescence polarization immunoassay) formation rates were calculated from splanchnic blood flow and arterial-hepatic venous concentration differences. Replacing norepinephrine with phenylephrine induced no change in systemic hemodynamics or gas exchange. While splanchnic oxygen consumption and alanine uptake rate remained unaffected, splanchnic blood flow, oxygen delivery, and lactate uptake rate were significantly decreased. Glucose production rate also decreased significantly. A return to norepinephrine restored splanchnic blood flow, oxygen delivery, and lactate uptake rate to baseline values, while glucose production rate remained depressed. Hepatic MEGX formation rate was not influenced during the investigation. CONCLUSIONS: Exogenous beta-adrenergic receptor stimulation determines splanchnic blood flow, oxygen delivery, and glucose precursor flux but not splanchnic oxygen utilization in septic shock. Gluconeogenesis is not directly affiliated to hepatosplanchnic oxygen kinetics. The different response of glucose and MEGX production rates, metabolic pathways of the periportal and perivenous region, may document intrahepatic heterogeneity associated with hepatocellular metabolic compartmentation.

Aged↗

Folding of barstar C40A/C82A/P27A and catalysis of the peptidyl-prolyl cis/trans isomerization by human cytosolic cyclophilin (Cyp18).

Refolding of b*C40A/C82A/P27A is comprised of several kinetically detectable folding phases. The slowest phase in refolding originates from trans-->cis isomerization of the Tyr47-Pro48 peptide bond being in cis conformation in the native state. This refolding phase can be accelerated by the peptidyl-prolyl cis/trans isomerase human cytosolic cyclophilin (Cyp18) with a kcat/K(M) of 254,000 M(-1) s(-1). The fast refolding phase is not influenced by the enzyme.

Bacterial Proteins↗

A molecular modeling study of B-DNA-intercalation complexes with amsacrine and related 9-anilino-acridines.

Computer molecular modeling studies of some complexes of amsacrine-derivatives with B-DNA-hexanucleotides were performed to shed new light on the DNA-binding mode of these drugs. The studies are based on routine methods, as are the semiempirical calculations, conformational analyses of the ligands, interaction field analyses, force field and molecular dynamics simulations of ligand/base paired DNA-complexes. The predictions suggest that the tested 9-anilino-acridines 1, 3 and 4 bind by intercalation to the base-paired oligonucleotides. Depending on the substitution pattern of the tested 9-anilino-acridine-series compounds, some distinct binding modes and base sequence selectivities were observed.

Acridines↗

The Tridimensional Personality Questionnaire as a predictor of relapse in detoxified alcohol dependents. The European Fluvoxamine in Alcoholism Study Group.

Personality traits have been found as strong predictors for treatment response in different psychiatric disorders. We administered the Tridimensional Personality Questionnaire, which measures the three personality dimensions: novelty seeking, harm avoidance (HA), and reward dependence, as introduced by Cloninger in a multicenter study (11 centers in the United Kingdom, Eire, Switzerland, and Austria) with detoxified alcohol-dependent patients (n = 521). The objective of this study was to evaluate a possible predictive value of these three dimensions on relapse over 1 -year follow up. A logistic regression analysis showed that novelty seeking is a strong predictor for relapse in detoxified male alcoholics (p = 0.0007; p values adjusted for treatment), but not in females. In both sexes, HA and reward dependence were of no predictive value. However, we found a trend for significance of HA for predicting "early" relapse (4 weeks) in females (p = 0.074). Our results show that Tridimensional Personality Questionnaire personality traits have direct clinical applications for prediction of relapse in detoxified alcohol dependents and indicate the necessity of additional therapeutic treatment in risk groups.

Adult↗

[Interdisciplinary therapeutic approaches with substance abusers taking into consideration gender differences].

Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction includes behavioral and social-context aspects that are important parts of the disorder itself. Therefore, the most effective treatment approaches will include biological, behavioral and social-context components. Whereas the basic treatment approach in substance dependence involves the medical field, psychosocial support is the second main area which has to be included in order to gain a successful treatment outcome. In addition, psychotherapy presents a third useful area in the field of the treatment of drug addiction, but only under the consideration that the addict shows a continuing motivation to change. Recognizing addiction as a chronic, relapsing brain disorder characterized by compulsive drug seeking and use can impinge on society's overall health and social policy strategies and help diminish the health and social costs associated with drug abuse and addiction. Treatment of substance dependence in men differs from treatment of substance dependence in women; drug addiction in females requires special attention when the woman is pregnant.

Adult↗

[Intracranial cavernoma. Surgical results of 47 cases].

We report the surgical results in a series of 47 patients with cerebral cavernous malformation who had undergone surgery between 1973 and 1994, with a follow up ranging from 12 months to 24 years (mean: 4 years). They were divided in there groups according to their initial clinical presentation: epilepsy (31 cases), hemorrhage (11 cases) and neurological deficit (5 cases). Surgery consisted of cavernoma resection only (11 cases) or its extension to surrounding gliotic tissue (36 cases). Results are satisfactory: no surgical mortality, low morbidity (4 cases), no recurrent hemorrhage, seizures disappearance with anticonvulsant therapy stop (4 cases) or alleviation (20 cases). Only one patient died far from surgery (6 months) consequently to his initial bleeding, while all the others lead a normal active life. The therapeutic management, compared to the literature, pleads in favour of intentionally surgical attitude and gliotic tissue removal as often as reasonably possible.

Adolescent↗

[Epidermoid cyst of the lateral ventricles].

A case of epidermoid cyst of the lateral ventricles is reported. The patient presented with a weakness of the left lower limb and neuropsychological disorders. The diagnosis was assessed by CT scan and MRI, and confirmed at the operation. The lesion has been largely removed through a transcallosal approach though incompletely. However the long term follow-up was uneventful. Twenty-nine cases of the literature have been reviewed.

Adult↗

[Frontal sinus approach to olfactory groove meningiomas].

We report on our experience of the frontal sinus approach for removing olfactory groove meningiomas. Five tumors were operated on, one unilateral, four bilateral. Osteotomy of the anterior wall of the frontal sinus was performed with an oscillating saw without any burr hole. The posterior wall of the sinus was resected and the tumor was attacked along the plane of the anterior skull base. Ethmoidal blood supply was controlled at the initial stage of the operation, allowing avascular tumor debulking. Olfactory nerves, invaded by the tumor, usually cannot be spared. Tumor extensions towards the sella and the optic canals were removed without any brain retraction, nor opening of the sylvian fissure, nor dissection of the carotid arteries. The frontal sinus approach is technically easy to achieve. Osteotomy and reconstruction of the anterior wall of the frontal sinus are rapidly performed. When the frontal sinus is small, image guided surgery allows to delineate precisely its limits and the flap includes the calvarial outer layer, tangenitally cut from one supra-orbital canal to the other. Cosmetic result is perfect. The frontal sinus approach gives access to the medial part of the orbital roofs and to the central anterior skull base from the crista galli to the tuberculum sellae and the anterior clinoids. The frontal sinus approach represents an alternative to conventional craniotomies for tumors developed in the central anterior skull base, especially for olfactory groove meningiomas.

Frontal Sinus↗

[Mycotoxins as exposure parameters in bioaerosols of composting sites].

The potential to produce mycotoxins was investigated for freshly isolated strains of airborne fungi. The spectra of metabolites in conidial extracts and culture extracts were compared for some relevant species. Furthermore, their potential to produce mycotoxins on semi-natural media (compost extract agar) supplemented with sucrose, yeast extract, and carboxymethylcellulose in different combinations was investigated. In native bioaerosols in a compost facility (plant 2), tryptoquivaline, a compound with tremorgenic properties, and trypacidin, for which no toxic properties are described, were found. The highly toxic metabolites gliotoxin and verruculogen were not found in the bioaerosols, although they were produced by some strains in pure culture. An inventory of microbial metabolites in addition of fungal propagules has led to a more detailed identification of potential health hazards at the working place. In addition to the pathogenic and allergological relevance, airborne fungi are thus of toxicological concern.

Aerosols↗

[MVOC of fungi--use as an indicator for exposure level].

The production of microbial volatile organic compounds (MVOC) by fungi derived from biowaste was studied on synthetic agar (YES), compost-extract media (CEA VAR 1-3) and compost. Exposure assessment was carried out in composting facilities and the occurrence of VOC/MVOC was related to the presence of airborne fungi. A number of non-specific MVOC was found at all sampling sites or in each season, some of which showed preferences for certain sampling sites (3-methyl-1-butanol, 3-octanone). They seemed to be correlated with a certain species composition or with microbial activity, and may thus be used to describe a certain state of decomposition. Correlations between single volatiles and certain fungi were found in situ, but these findings did not match with the species-specific volatiles obtained from pure cultures.

Air Pollutants, Occupational↗

["Microbial air pollutants--methods for detection of endotoxins, mycotoxins and MVOC"].

In the context of microbial emissions from composting facilities the methods for the detection and identification of the groups of substances released, i.e. endotoxins, mycotoxins and Microbial Volatile Compounds (MVOC) are discussed. With the aid of an overview of the different methods employed for the investigation of the single groups of compounds the current state of the art in this field is presented. In conclusion the enormous research needs, especially with regard to the mycotoxins and MVOC, are pointed out.

Air Microbiology↗