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Biomedical subjects

M Vogel

Publications and source records attributed to M Vogel.

At least 163 records · Page 9Linked to original sources
PubMed1998

Overexpression of a Hu-bcl-2 transgene in Lurcher mutant mice delays Purkinje cell death.

Cerebellar Purkinje cells in the heterozygous Lurcher mutant undergo cell autonomous degeneration beginning in the second week of postnatal development and becoming almost total around 30-45 days. The Lurcher mutation was recently identified as gain-of-function defect in the delta 2 glutamate receptor causing a constitutive current leak, suggesting that +/Lc Purkinje cells die by an excitotoxic mechanism. In previous studies we have shown that overexpression of bcl-2, a key regulator of cell death, in the heterozygous Lurcher mutant does not prevent +/Lc Purkinje cell death. To investigate further the mechanisms of +/Lc Purkinje cell death, we have crossed +/Lc mutants with a second line of Hu-bcl-2 transgenics (NSE73a) that shows an earlier onset of transgene expression and higher expression levels. Analysis of eight +/Lc-NSE73a mutants (4 at 2 months and 4 at 5-6 months) showed that Hu-bcl-2 overexpression delayed, but ultimately could not prevent +/Lc Purkinje cell death.

Animals↗
PubMed1998

Recombinant human natural autoantibodies against GPIIb/IIIa inhibit binding of autoantibodies from patients with AITP.

Autoimmune thrombocytopenic purpura (AITP) is caused by autoantibodies predominantly against platelet membrane glycoproteins (GP) IIb/IIIa and GPIb/IX. Naturally occurring autoantibodies have been described against a variety of autoantigens; it has been suggested that perturbation of their regulation may be associated with autoimmune diseases. Using a combinatorial Fab phagemid library from an individual immunized with human RhD+ red blood cells, we evaluated the presence of natural anti-GPIIb/IIIa autoantibodies as well as their relation to AITP-associated anti-GPIIb/IIIa autoantibodies. Selection on native GPIIb/IIIa and characterization of positive clones by inhibition studies against murine monoclonal anti-GPIIb/IIIa antibodies and by DNA analysis revealed the presence of two distinct recombinant anti-GPIIb/IIIa autoantibodies, which partially inhibited binding of affinity-purified platelet-associated autoantibodies from 8/12 AITP patients. Our results demonstrated that GPIIb/IIIa-specific Fab directed against conformational epitopes within the GPIIb/IIIa complex may be cloned from the genome of an individual immunized with RhD+ red blood cells, who was not affected by AITP. The partial inhibition of binding of platelet-associated autoantibodies from AITP patients to GPIIb/IIIa by the recombinant anti-GPIIb/IIIa phage clones suggests recognition of closely related antigenic epitopes. These phage clones may represent down-regulated, potentially pathological autoantibodies and could be used as new tools for investigation of AITP.

Amino Acid Sequence↗
PubMed1998

[Cardiac MR flowmetry: experimental validation and results in patients with operated heart defects].

PURPOSE: A flow-sensitive MR sequence (phase-contrast technique) was evaluated in phantom studies with regard to factors influencing measurements and correctness of results. The sequence was additionally used for functional evaluation of operated congenital heart disease. METHODS: Pulsatile and constant flow were produced with the help of a phantom. Influence of angulation, range and vessel bending was evaluated. An examination protocol was developed from the results. 35 patients with surgically repaired congenital heart disease or without repair were examined. RESULTS: A range preset below the actual flow velocity as well as angulation of more than 20 degrees were isolated as main pitfalls in MR flowmetry. In addition to morphological MR findings flow measurements were possible in 11 patients at vessel sites which were not or not completely suited for examination by Doppler ultrasound. CONCLUSION: The evaluated phase-contrast technique allows for fast and reliable flow quantification if the influences identified in phantom studies are considered.

Blood Flow Velocity↗
PubMed1998

Functional food science and substrate metabolism.

The present review addresses the role of food constituents in the aetiology of metabolic conditions and chronic diseases, mostly related to energy metabolism and substrate regulation, such as obesity and non-insulin-dependent diabetes mellitus. Second, attention is paid to malnutrition, a major cause of mortality and morbidity in developing countries, which may be a cause of concern in Europe because of the increasing number of elderly people in the population. Finally, the role of diet during exercise, a condition of enormous substrate demands, is evaluated. Based on a critical evaluation of the existing knowledge in the literature, implications for future research in relation to functional foods are discussed.

Adolescent↗
PubMed1998

Efficacy and safety of teicoplanin plus rifampicin in the treatment of bacteraemic infections caused by Staphylococcus aureus.

An open study was carried out on 16 patients with hospital-acquired, bacteraemic Staphylococcus aureus infections to evaluate the safety and efficacy of teicoplanin plus rifampicin. Patients received teicoplanin 400 mg bd for the first 24 h followed by 400 mg od thereafter, and rifampicin 600 mg bd. Both agents were given intravenously. Serum samples were collected to determine trough and peak antibiotic concentrations. The MIC of teicoplanin and rifampicin and the MBC of teicoplanin were determined for all S. aureus isolates. Time-kill curves were performed for the drugs individually and in combination. Clinical efficacy was assessed by the APACHE II scoring system. Bacteriological success was evaluated by elimination, persistence or recurrence of S. aureus. Safety was carefully monitored by regular biochemical and haematological testing and recording of adverse events. Fifteen patients were evaluable, of whom 13 (86.7%) were clinically cured with elimination of S. aureus. One patient died, but death was not attributed to the study drugs. Treatment failed in another patient who relapsed with a high fever. S. aureus was recovered from blood cultures from this patient, and resistance to rifampicin had developed. Time-kill curves all showed adequate killing of S. aureus at the drug concentrations measured in vivo. Neither synergy nor antagonism between teicoplanin and rifampicin was demonstrated. The combination of teicoplanin and rifampicin is an effective and well-tolerated treatment for bacteraemic S. aureus infections, but in deep-seated foci of infection resistance to rifampicin may develop.

Adolescent↗
PubMed1998

Influence of polarity reversal on defibrillation success with biphasic shocks and a transvenous/subcutaneous defibrillator system in a porcine animal model.

Clinical studies show that polarity reversal affects defibrillation success in transvenous monophasic defibrillators. Current devices use biphasic shocks for defibrillation. We investigated in a porcine animal model whether polarity reversal influences defibrillation success with biphasic shocks. In nine anesthetized, ventilated pigs, the defibrillation efficacy of biphasic shocks (14.3 ms and 10.8 ms pulse duration) with "initial polarity" (IP, distal electrode = cathode) and "reversed polarity" (RP, distal electrode = anode) delivered via a transvenous/subcutaneous lead system was compared. Voltage and current of each defibrillating pulse were recorded on an oscilloscope and impedance calculated as voltage divided by current. Cumulative defibrillation success was significantly higher for RP than for IP for both pulse durations (55% vs 44%, P = 0.019) for 14.3 ms (57% vs 45%, P < 0.05) and insignificantly higher for 10.8 ms (52% vs 42%, P = ns). Impedance was significantly lower with RP at the trailing edge of pulse 1 (IP: 44 +/- 8.4 vs RP: 37 +/- 9.3 with 14.3 ms, P < 0.001 and IP: 44 +/- 6.2 vs RP: 41 +/- 7.6 omega with 10.8 ms, P < 0.001) and the leading edge of pulse 2 (IP: 37 +/- 5 vs RP: 35 +/- 4.2 omega with 14.3 ms, P = 0.05 and IP: 37.5 +/- 3.7 vs RP: 36 +/- 5 omega with 10.8 ms, P = 0.02). In conclusion, in this animal model, internal defibrillation using the distal coil as anode results in higher defibrillation efficacy than using the distal coil as cathode. Calculated impedances show different courses throughout the shock pulses suggesting differences in current flow during the shock.

Animals↗
PubMed1998

Hyperinsulinism, neonatal obesity and placental immaturity in infants born to women with one abnormal glucose tolerance test value.

Several groups have reported a risk of fetal macrosomia in pregnancies with maternal glucose intolerance which is intermediate between gestational diabetes (GDM) and normal glucose tolerance. The present study was designed to determine whether these pregnancies are also at risk for fetal obesity, hyperinsulinism and placental villous immaturity. 325 women with risk factors for GDM underwent a 75 g OGTT interpreted according to the O'Sullivan criteria. All women who met the criteria for GDM were managed with diet therapy. Insulin therapy was added for women with a mean serum glucose value > 100 mg/dl on a 24 hour glucose profile. Patients not meeting the GDM criteria were managed without special intervention. Primary outcome variables were measures of neonatal weight and skinfold thickness, fetal and neonatal insulin and glucose concentration, and placental villous maturation. Outcome parameters were compared among three groups: pregnancies with normal OGTT (control, n = 95), 1 abnormal value in the OGTT (1 abnl, n = 76) and GDM (n = 154). The outcome of pregnancies with 1 abnormal value in the OGTT was different from those with normal OGTT. Regarding fetal growth, rates of LGA were approximately twice as high in groups with one abnormal value and GDM (21% and 24%) compared to women with normal OGTTs (11%: p < 0.05 vs GDM and p = 0.07 vs 1 abnormal value). The percent of infants with skinfold thickness > 90th percentile was also greater in the 1 abnormal value and GDM groups (31.1 and 31.6% respectively) compared to controls (19.2%; p < 0.05 for GDM vs control only). Regarding fetal hyperinsulinism, AFI concentrations were similar in control and GDM groups (3.1 +/- 0.4 and 3.4 +/- 0.8 microU/ml, respectively), but were higher in the group with one abnormal OGTT value (4.3 +/- 1.2 microU/ml, p < 0.05 vs controls). Cord blood insulin: glucose ratios were elevated in both the 1 abnormal value and GDM groups (0.22 +/- 0.05 and 0.20 +/- 0.02 microU/ml per mg/dl), compared to controls (0.12 +/- 0.01 microU/ml per mg/dl, p < 0.05 vs 1 abnormal value). Neonatal glycemia < 30 mg/dl was significantly more common in the one abnormal value than in the control group (49% vs 34% of infants) and intermediate in the GDM group (40%). Severe placental villous immaturity was more than twice as frequent in the 1 abnormal value group compared to controls (24% vs 9%, p < 0.05) and the most frequent in the GDM group (33%; p < 0.001 vs controls). Pregnancies with glucose intolerance below the thresholds for diagnosis of GDM have an increased risk for fetal obesity, hyperinsulinism, postpartum hypoglycemia and placental immaturity. These findings indicate the continuum of risk for fetal morbidity associated with increasing maternal glucose intolerance in pregnancy.

Adult↗
PubMed1998

Circadian reactions to nCPAP treatment.

To determine possible effects of apnea attacks on the spontaneous behavior of the circadian system (body temperature, sleeping behavior, vigilance), 11 patients with obstructive sleep apnea (OSA) were observed before therapy over a 24 h period under a special constant routine (bed-rest study) and again during therapy with nCPAP (nasal continuous positive airway pressure). Clinical indicators (polysomnographical, subjective sleep quality, etc.) indicated successful therapy. During the bed-rest study with nCPAP therapy, the 24 h amplitude of core temperature was found to be greater than the amplitude measured before therapy. Also, therapy decreased sleep disturbances at night and reduced daytime sleeping times. Consequently, the level of subjective vigilance was higher during the daytime during therapy. OSA attacks do not only impair sleep; they disturb the whole circadian system. This may also impair recuperation and sleep. Further research should test whether measurements of the spontaneous circadian system could have additional diagnostic value and whether the stabilization of the circadian system has therapeutic value.

Adult↗
PubMed1998

3874 H1 and H3, novel antifungal heptaene antibiotics produced by Streptomyces sp. HAG 003874.

New antifungal antibiotics, designated as 3874 H1 and H3, were discovered in the fermentation broth of the strain Streptomyces sp. HAG 003874. The compounds were obtained as yellow powders after sequential purification by chromatography on MCI Gel CHP20P, Fractogel HW-40 and ODS reversed phase chromatography. On the basis of the results of spectroscopic analysis, it was found that 3874 H1, C58H86N2O18, MW 1098, belongs to the p-aminoacetophenone containing family of heptaene antibiotics, while 3874 H3, C57H87NO18, MW 1073, is a non-aromatic heptaene. In addition to these, a minor component, 3874 H2, C59H88N2O18, MW 1112, a N-methyl derivative of 3874 H1 has been detected. The structures were elucidated through mass spectral analyses and 1-D and 2-D homonuclear and heteronuclear NMR data. The outstanding physico-chemical feature of 3874 H3 is its improved solubility. The new heptaenes are potent antifungal compounds with broad activity spectra, encompassing dermatophytes, yeasts and filamentous fungi.

Anti-Bacterial Agents↗
PubMed1998

[Roentgen diagnosis without medical indications and physical injury. Verdict of the federal court 3 December 1997--2 StR 397/97].

An orthopedist had been sentenced for different offenses to two years and six months imprisonment by the Landgericht Frankfurt (superior court). One point of the ruling had been the evaluation of the use of X-ray methods without medical indication, which the Landgericht Frankfurt/Main (superior court) finally did not evaluate as bodily harm. The Bundesgerichtshof (supreme court) of Germany overruled this interpretation and referred the case back for new trial and ruling.

Germany↗
PubMed1998

Peripheral scotoma associated with chronic ethmoidal sinusitis. A case report and review of the literature.

Diseases of the paranasal sinuses may cause visual disturbances, especially diminished visual acuity and visual field defects, by affecting the optic nerve. We report the unusual case of a female patient with unilateral peripheral, quadrantic scotoma and concomitant chronic ethmoidal sinusitis. Visual acuity was not diminished. Despite extensive diagnostic examinations no other cause of the scotoma could be evaluated. As conservative therapy had been unsuccessful, endonasal pansinus operation was performed. Upon surgery, nearly all ethmoidal cells appeared to be filled with polypous mucosa. The sphenoid sinuses, however, contained air. In contrast, pre-operative CT scans had shown only a slight opacity of the ethmoid bone. Already two weeks after surgery a reduction in size of the scotoma could be noted. In addition to this case report, possible causes of visual field defects due to inflammatory diseases of the paranasal sinuses are discussed. In cases of unilateral visual field reduction associated with symptoms of chronic paranasal sinusitis, early operative exploration of the paranasal sinuses should be considered after exclusion of other possible causes, even if radiological findings do not warrant such a procedure.

Adult↗
PubMed1998

Sequence and specificity analysis of recombinant human Fab anti-Rh D isolated by phage display.

BACKGROUND AND OBJECTIVES: Hyperimmune anti-Rh D serum is worldwide in short supply. As a first step to develop an alternative source of Rh D antibodies, we describe in this study the isolation and characterization of recombinant anti-Rh D Fab fragments. MATERIALS AND METHODS: Peripheral blood mononuclear cells harvested from a hyperimmunized donor were used to construct two combinatorial Fab libraries. Phages expressing these Fab fragments were selected on whole red blood cells followed by testing of positive clones in an indirect hemagglutination assay. RESULTS: Individual Fab clones are of high affinity and competitively inhibit the binding of a registered anti-D immunoglobulin. The Fab clones are also specific against the partial D phenotypes, Rh33, DIII, DIVa, DIVb, DVa, and DVII. The 13 different but highly homologous clones express preferentially VH3 segments. CONCLUSION: These Fab fragments show potential for the development of a new generation of therapeutic anti-Rh D reagents.

Amino Acid Sequence↗
PubMed1997

NOS type-1 mRNA expression and protein localization in spinal autonomic neurons.

Autonomic neurons of the rat spinal cord show strong NADPH diaphorase activity and immunoreactivity for nitric oxide synthase (NOS). Here we show mRNA expression of NOS type-1 (neuronal or brain NOS) transcripts in cell bodies of sympathetic preganglionic neurons (SPNs) of the intermediolateral (IML) cell column by non-radioactive in situ hybridization using NOS-I riboprobes. Hybridization signals occurred only in neuronal cell bodies and not outside, in what appeared to be fibers and/or terminals. In preganglionic fibers of SPNs, however, dense axoplasmic immunogold labeling was detected with a monoclonal anti-NOS-I antibody. Expression of NOS-I mRNA in SPN cell bodies and axoplasmic immunolocalization of NOS-I protein suggest that protein translocation is involved in NO-mediated preganglionic control of peripheral targets.

Animals↗
PubMed1997

Right ventricular function in patients treated with inhaled nitric oxide after cardiac surgery for congenital heart disease in newborns and children.

Measurement of right ventricular (RV) function is essential for complete assessment of the effects of inhaled nitric oxide in the postoperative cardiac patient; nitric oxide therapy can result in a decrease in pulmonary vascular resistance and improved echocardiographic RV ejection fraction without necessarily inducing a significant change in pulmonary artery pressure.

Child↗
PubMed1997

[Selective excimer laser ablation of the trabecular meshwork. Clinical results].

PURPOSE: Examination of the efficacy of pore formation in the trabecular meshwork by excimer laser to reduce intraocular pressure in glaucoma eyes. PATIENTS AND METHODS: In 27 consecutive eyes with chronic simple glaucoma and 8 eyes with low-tension glaucoma, 3 to 5 pores were ablated into the trabecular meshwork with an excimer laser (308 nm, 35-55 mJ/mm2), creating an open communication between the anterior chamber and Schlemm's canal. This was accomplished by the use of a 400-micron quartz fiber and a modified Trokel goniolens. All patients were candidates for trabeculectomy because visual fields continued to deteriorate in spite of maximum medication. RESULTS: Intraocular pressure was median reduced by 7 mmHg (range 10.5 to 1.5 mmHg) in 22 of 27 eyes with chronic simple glaucoma over a median follow-up of 7 months. In 12 eyes, further medication has to be continued, yet at a lower dose and lower level of intraocular pressure. In five eyes therapy failed. In three of these eyes, a trabeculectomy had to be performed. In eight eyes with low-tension glaucoma, a median reduction of intraocular pressure of 5 mmHg (range 10 to 0.5 mmHg) was accomplished over a median follow-up of 7 months. In five of these eyes, further medication on a lower level was continued. No further surgery was necessary. CONCLUSIONS: With the microsurgical method of pinpoint ablation of the trabecular meshwork by excimer laser, intraocular pressure was reduced in 30 of 35 eyes over a median follow-up period of 7 months. These results encourage us to continue the development of this procedure, perhaps with a microendoscope. The minimal trauma to the eye of this procedure leaves all other options of surgery open.

Follow-Up Studies↗
PubMed1997

Quantification of stromal thinning, epithelial thickness, and corneal haze after photorefractive keratectomy using in vivo confocal microscopy.

PURPOSE: The authors establish, for the first time, observer-independent quantification of stromal thinning, epithelial thickness, and corneal haze after excimer laser photorefractive keratectomy (PRK) using a unique, new form of in vivo confocal microscopy. METHODS: Rapid, continuous z-scans of high-resolution confocal images, termed confocal microscopy through focusing (CMTF), were performed in the central corneal area of 17 patients before and 1 month after PRK for low- to moderate-grade myopia (-2.88-9.13 diopters [D]). Corneal, epithelial, and stromal thickness measurements and an objective haze estimate were obtained from each CMTF scan by digital image analysis. RESULTS: Epithelial thickness averaged 51 +/- 4 microns before and 45 +/- 10 microns 1 month post-PRK (P < 0.005), whereas stromal thinning ranged from 20 to 154 microns, representing a direct estimate of the actual photoablation depth. Corneal thickness averaged 560 +/- 36 microns before PRK and 462 +/- 52 microns at 1 month. The change in corneal thickness correlated closely with the change in spherical equivalent refraction (r = 0.94, P < 0.0001); linear regression analysis revealed a value of 14.3 microns corneal thinning per diopter of correction. A significant correlation was found between the objective CMTF haze estimate and a clinical haze grading obtained by slit-lamp examination (r = 0.73, P < 0.001). CONCLUSIONS: Confocal microscopy through focusing is a new, powerful in vivo tool that enables quantitative, unbiased evaluation of PRK procedures over time by providing epithelial and stromal thickness analysis, photoablation depth assessment, and unbiased haze measurement. The method is uniquely valuable in the pre- and postoperative assessment of PRK patients and for determining the optimal treatment strategy, especially in assessing refractive and visual outcomes in individual cases.

Adult↗