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Biomedical subjects

R Vogel

Publications and source records attributed to R Vogel.

At least 19 recordsLinked to original sources
PubMed1992

Topically administered norfloxacin compared with topically administered gentamicin for the treatment of external ocular bacterial infections. The Worldwide Norfloxacin Ophthalmic Study Group.

In this double-masked study, we randomly assigned 488 patients with clinical signs of acute bacterial conjunctivitis or blepharitis, or both, to treatment with either norfloxacin ophthalmic solution 0.3% (245) or gentamicin ophthalmic solution 0.3% (243) for one week. Of the patients with positive cultures, 71% (85 of 120) of the norfloxacin-treated patients and 65% (86 of 133) of the gentamicin-treated patients were clinically cured. An additional 25% (30 of 120) of norfloxacin-treated patients and 32% (43 of 133) of gentamicin-treated patients were clinically improved. On the basis of posttreatment cultures, 89% of all cultured bacteria were eradicated (146 of 179 organisms) or suppressed (14 of 179 organisms) after treatment with norfloxacin. The condition of five norfloxacin-treated patients did not clinically improve, compared with the condition of eight gentamicin-treated patients. Both antibiotics had similar efficacy against gram-positive and against gram-negative organisms. One norfloxacin-treated patient and two gentamicin-treated patients withdrew from the study because of local intolerance. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the eyelids or conjunctiva, or both. In this study, norfloxacin was clinically and microbiologically similar in activity to gentamicin.

Administration, Topical↗
PubMed1992

A prospective randomized study of 4.1 French catheters utilizing the percutaneous right brachial approach for the diagnosis of coronary artery disease.

To determine the utility of 4.1 French (F) catheters in diagnosing coronary artery disease, 50 patients were randomized to 4.1F Multipurpose or Judkins catheters utilizing the percutaneous right brachial approach. The randomized 4.1F tip shape catheter completed the procedure in 40% of the patients, and overall the 4.1F catheters completed the catheterization in 72% of the cases. With excessive or prolonged manipulation, the catheters were noted to kink and soften and required replacement for a catheter of similar or larger size. In 28% of the cases, larger F sizes (5F and 6F) were used to complete the procedure. There was 1 (2%) procedural complication. The total procedural success (accounting for all F sizes) without clinical complication was 98%. There was no difference between the 4.1F Judkins or Multipurpose catheter shapes for coronary arteriography by either qualitative or quantitative angiographic analysis. Left ventricular opacification was improved with the 4.1F Pigtail vs. the 4.1 Multipurpose by qualitative angiographic analysis. When the 4.1F angiograms were compared by quantitative angiography in blinded, but not randomized fashion to angiograms performed with 6F Judkins catheters, there was improved opacification of the LAD and diastolic frame of the left ventriculogram with the larger catheter. This difference was not noted with qualitative angiography. This study indicates that 4.1F catheters can be utilized from the right brachial approach for the diagnosis of coronary artery disease, thus avoiding the need for supine bedrest associated with routine femoral artery catheterization while maintaining diagnostic accuracy.

Brachial Artery↗
PubMed1992

Effect of animal species and age on plate-induced vascular damage in cortical bone.

Plates used for fracture fixation produce vascular injury to the underlying cortical bone. During the recovery of the blood supply, temporary osteoporosis is observed as a result of Haversian remodeling of the necrotic bone. This process temporarily reduces the strength of the bone. We tackled the postulate that quantitative differences exist between animal species, and in different bones within the same species, due to variations in the relative importance of the endosteal and periosteal blood supplies. Using implants scaled to the size of the bone, we found comparable cortical vascular damage in the sheep and in the dog, and in the tibia and femur of each animal. We observed a significant reduction in cortical vascular damage using plates that had a smaller contact area with the underlying bone. No significant difference in cortical vascular damage was noted in animals of different ages.

Age Factors↗
PubMed1992

Effect of viscosity and iodine concentration of nonionic radiographic contrast media on coronary arteriography in patients.

To assess the influence of viscosity and iodine concentration, three matched and standardized left coronary arteriograms were obtained in 20 patients using iopamidol (Isovue-370), ioversol (Optiray-320), and iohexol (Omnipaque-350). The order of contrast media was randomized and the administration of contrast was double-blinded. Quantitative densitometric angiographic evaluation of the coronary angiograms was performed in addition to independent operator qualitative assessment. The injection volume of iopamidol (5.4 +/- 1.0 ml) was slightly but significantly less than that of ioversol and iohexol (5.6 +/- 1.0 ml, 5.7 +/- 1.0 ml, both p less than 0.05). The calculated iodine concentration was also lower for ioversol (1.7 +/- 0.32 gm) than for iopamidol (1.98 +/- 0.35 gm) and iohexhol (1.9 +/- 0.35 gm, both p less than 0.05). There were significantly lower contrast syringe injection pressures for ioversol (6.6 +/- 0.8 atm) than for iopamidol (7.5 +/- 0.9 atm) and iohexol (7.2 +/- 1.1 atm, both p less than 0.05). The quantitative densitometric analysis failed to demonstrate significant differences among the contrast media with respect to image density parameters for any individual agent. All coronary angiograms were deemed of diagnostic quality. The data in this study indicated that although differences in iodine concentration exist among the three agents, operator compensation with more rapid contrast delivery (higher volume) and lower viscosity (lower injection pressure) produced equivalent image opacification during coronary angiography. Given the same incidence of adverse hemodynamic and clinical effects, selection of a low viscosity media theoretically provides an advantage during procedures using small diameter catheters or interventional procedures requiring contrast visualization through reduced catheter lumina.

Contrast Media↗
PubMed1992

Islet hormone pulse intervals are dependent upon sampling frequency.

Pulsatile insulin secretion has been reported from a variety of in vivo and in vitro systems. While it is agreed that insulin pulses exist, there is little agreement concerning the basal frequency or interpulse interval either within the same species in vivo, as both long and short term pulses have been reported, or between in vivo and in vitro preparations. We propose that the frequency of sampling may have profound effects upon the calculated pulse interval. Three systems were used to test this hypothesis: 1) artificial test data were designed to produce regular pulses with an exact 11 min period, 2) perfusate insulin concentration from isolated canine pancreata sampled at 1 min intervals and 3) peripheral blood insulin concentrations from human volunteers sampled every 2 and 5 min. Pulse parameters were determined at 1, 2, 5, 20, 15, 30 and 60 min sampling intervals for each data set by the use of the computer algorithms Pulsar and Cycle Detector. The results indicate that for insulin secretory pulses, sampling frequencies longer than 2 min may result in the production of spurious pulse trains with multiple longer term pulse periods. It is concluded that islet hormone secretory pulse period calculations are dependent upon the sampling frequency.

Analysis of Variance↗
PubMed1992

Genotoxic and embryotoxic effects of gonadotropin-hyperstimulated ovulation of murine oocytes, preimplantation embryos, and term fetuses.

Compared to spontaneous ovulation, gonadotropin-hyperstimulated ovulation (superovulation) in mice resulted in a fourfold increase in the number of preimplantation embryos 3 days post coitum, 50% of which died before term. Both in vitro development of embryos during the preimplantation period and transfer of morulae from superovulated females to pseudopregnant untreated foster mothers indicate that the prenatal loss occurring shortly before implantation up to term is due to maternal factors rather than to direct hormonal effects on oocytes or early embryos. Indeed, no genotoxic events could be observed in 4-cell to blastocyst stage embryos from superovulated female mice as revealed by the chromosomal aberration test and the sister chromatid exchange assay. Chromosome analysis of the pronuclei from mouse zygotes showed an increased rate of aberrations in oocyte-derived nuclei after superovulation in comparison to spontaneous ovulation. The present data suggest that aberrant murine oocytes may be fertilized, but they do not survive the first cleavage stages. The result is discussed with respect to the high incidence of chromosomal abnormalities found in human oocytes after gonadotropin-hyperstimulated ovulation.

Animals↗
PubMed1992

Effect of timolol versus pilocarpine on visual field progression in patients with primary open-angle glaucoma.

BACKGROUND: Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long-term effect of two ocular hypotensive agents on preservation of visual field. METHODS: In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32. RESULTS: Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily. CONCLUSION: Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine.

Double-Blind Method↗
PubMed1992

The safety and efficacy of topical norfloxacin compared with chloramphenicol for the treatment of external ocular bacterial infections. The Norfloxacin-Chloramphenicol Ophthalmic Study Group.

Two hundred and forty-six patients with signs of acute bacterial conjunctivitis and/or blepharitis were randomised to receive either norfloxacin or chloramphenicol for one week in this double-masked parallel group study. Ninety-two per cent of the norfloxacin-treated patients and 93% of the chloramphenicol-treated patients were rated as either clinically improved or cured at the end of the treatment period. Based upon pre-treatment bacteriological cultures, 31.3% of the patients had significant bacterial infection of the lids and/or conjunctiva. All of these culture-positive patients were rated as either clinically improved or cured. Based upon post-treatment cultures, 72 of 82 strains of Gram-positive and Gram-negative bacteria were eradicated or suppressed following treatment with either norfloxacin or chloramphenicol. However six of 41 strains persisted for norfloxacin and four of 41 for chloramphenicol. Two norfloxacin-treated patients and three chloramphenicol-treated patients had adverse experiences, predominantly ocular discomfort, which required cessation of drug therapy. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the lids and/or conjunctiva. In this study, norfloxacin was clinically and microbiologically similar in activity to chloramphenicol.

Acute Disease↗
PubMed1992

Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids.

We have identified a novel member of the steroid hormone receptor superfamily by cDNA cloning from a human osteosarcoma SAOS-2/B10 cell library. Sequence analysis predicts a protein of 441 amino acids, which includes the conserved amino acid residues characteristic of the DNA- and ligand-binding domains of nuclear receptors. Amino acid sequence alignment and transcriptional activation experiments revealed that the new protein is closely related to the mouse peroxisome proliferator activated receptor. The overall homology is 62%, and the highest similarity is seen in the DNA- and ligand-binding domains, 86% and 71%, respectively. Northern blot analysis showed that in mature rats, the receptor is highly expressed in heart, kidney, and lung as a transcript of approximately 3500 nucleotides. In human cells, the size of the mRNA is approximately 4000 nucleotides. Transcription assays using hybrid receptors consisting of the ligand-binding domain of the new protein and the DNA-binding domain of the glucocorticoid receptor showed weak stimulation by the peroxisome proliferator activator WY14643, suggesting a relationship to that receptor. Similar stimulation was observed with arachidonic and oleic acid (100-250 microM).

Amino Acid Sequence↗
PubMed1992

[Selenium poisoning in fattening swine].

A case of selenium toxicosis was observed in fattening pigs. Intoxication was caused by high levels of selenium in a commercial mineral premix. Instead of the recommended dose of 16 ppm Se, the mineral feed contained selenium at concentrations of 657 and 1059 ppm. The ration in use was found to contain more than 14 ppm selenium. Clinical symptoms were observed 5 to 6 weeks after the pigs began consuming the contaminated feed mixture. Feed intake was markedly reduced and animals showed severe lameness due to separation and necrosis of the hoof wall at the coronary band. Some pigs were reluctant to stand. In some cases alopecia was detected. At histopathological examination one animal with paralysis of the hind limbs revealed a focal bilaterally symmetric poliomyelomalacia in the lumbar segment of the spinal cord. Diagnosis was confirmed by high selenium contents of liver, kidneys and blood. After removing the incriminated feed no further pigs developed signs of intoxication. New horn growth was present and lame animals recovered slowly.

Alopecia↗
PubMed1991

In vitro studies on genotoxicity and cytotoxicity of the anticancer drugs cisplatin and cofplaton, a caffeine-8-ether plus cisplatinum compound.

The cytotoxic and genotoxic properties of the newly designed anticancer drug 'cofplaton' were investigated. Since cofplaton is a cisplatin (CDDP) plus caffeine compound, the widely applied anticancer drug CDDP alone or in combination with caffeine was studied in parallel. As measured by the MTT test the cytotoxicity of the two drugs was comparable, but cofplaton exhibited significantly fewer genotoxic side effects than CDDP in the chromosome aberration test as well as in the SCE assay. First results from animal studies indicate that cofplaton exerts antitumor activity comparable to CDDP. Because of its relatively low genotoxicity, cofplaton seems to be a promising drug in human anticancer therapy.

Animals↗
PubMed1991

Embryologic and cytogenetic effects of ethanol on preimplantation mouse embryos in vitro.

Ethanol and its primary metabolite acetaldehyde were studied in cultured preimplantation mouse embryos with respect to embryotoxicity, embryolethality, chromosome breaking activities, and ability to induce sister chromatid exchange (SCE). Analysis of differentiation and cell number of mouse morulae and blastocysts show that acetaldehyde is three orders of magnitude more toxic than ethanol, indicating that the metabolite is responsible for the embryotoxicity of ethanol in preimplantation embryos. Concentrations of ethanol that do not inhibit growth induce SCEs and chromosome aberrations. The SCE-inducing effect of ethanol disappears in the presence of 4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase (ADH). These data suggest that preimplantation embryos are able to convert ethanol to acetaldehyde and that ADH is the enzyme involved. It is, furthermore, shown histochemically that mouse oocytes as well as morulae and blastocysts are able to oxidize ethanol in the presence of NAD+.

Alcohol Dehydrogenase↗
PubMed1991

Cytotoxicity test using blastocyst-derived euploid embryonal stem cells: a new approach to in vitro teratogenesis screening.

To develop a mammalian in vitro system for teratogenicity testing, cytotoxicity of xenobiotics was evaluated in pluripotent euploid embryonal stem cells (ESC) derived from mouse blastocysts. The dimethyl-thiazol-diphenyl tetrazolium bromide (MTT) assay was the most appropriate test system for cytotoxicity determinations with ESC. Only compounds that do not require metabolic activation were selected for testing from the database for validation of in vitro teratogenesis assays by Smith et al. Results obtained with ESC were compared to corresponding data from fibroblasts from day-14 mouse embryos to detect differences in sensitivity between undifferentiated and differentiated cells. ESC showed a higher sensitivity to known teratogens than fibroblast cultures, which allows calculation of a sensitivity ratio of "adult" cells (differentiated fibroblasts) to embryonal cells (undifferentiated ESC) in a mammalian system similar to the hydra assay. Although some xenobiotics had to be classified as false negatives in our system, the ESC cytotoxicity assay holds promise as a new in vitro screening assay in teratology.

Animals↗
PubMed1991

The increase of suicides in psychiatric hospitals in southwestern Germany according to diagnostic subgroups.

In this paper, results are shown of a study on suicides committed by psychiatric inpatients in four state mental hospitals in Baden-Württemberg, Federal Republic of Germany during the 15 years from January 1, 1970 up to the end of 1984. There was a mean suicide rate of 195 per 100,000 admissions. A comparison of 5-year sequences showed a significant increase of so-called hospital suicides in two of the hospitals at the end of the seventies and the beginning of the eighties. A statistical analysis of a trend of increase using nonparametric methods (Spearman rho, Kendall tau) showed a significant increase in the number of suicides and suicide rates in all four hospitals. In a second step, the same statistical procedure testing for an increase in the fifteen years was used for the group of schizophrenic (N = 106) and depressed (N = 55) inpatients who committed suicide. An impressive and highly significant increase was found especially in schizophrenic male inpatients with the ICD-9 diagnosis 295.3 (paranoid-schizophrenia), and within that group, in inpatients with 3 or more inpatient treatments. There was also an increase in the depressed group, especially in female depressives, but only significant at the 5% level in the trend analysis.

Data Interpretation, Statistical↗
PubMed1990

Mapping of the prekallikrein-binding site of human H-kininogen by ligand screening of lambda gt11 expression libraries. Mimicking of the predicted binding site by anti-idiotypic antibodies.

High molecular weight (H-)kininogen, a non-enzymatic cofactor of the contact activation system, has on the COOH-terminal part of its light chain a unique binding site which complexes prekallikrein or factor XI with high affinity and specificity. In a conventional protein fragmentation approach, the prekallikrein-binding site was mapped to positions 556-595 of the human H-kininogen sequence (Tait, J. F., and Fujikawa, K. (1986) J. Biol. Chem. 261, 15396-15401). To gain more insight into the minimum structural requirements of the prekallikrein-binding site, we have developed an alternative strategy employing the lambda gt11 expression cloning system. A ligand assay was established which probes for the binding site in H-kininogen or recombinant fusion proteins thereof by complexation with prekallikrein, followed by a specific antibody against prekallikrein and a secondary labeled antibody. A cDNA library constructed in lambda gt11 from random fragments of a cDNA clone encoding the COOH-terminal part of the kininogen light chain was screened by the ligand assay, and 17 positive clones were identified. Analysis of their inserted cDNA sequences revealed a consensus sequence of 119 nucleotides which maps to the extreme 3' end (positions 1759-1877) of the coding part of the prekininogen mRNA. The consensus sequence encodes positions 569-607 of the kininogen light chain and overlaps by 27 residues (positions 569-595) with the binding segment identified previously by the fragment approach. Analysis of successively shortened peptides revealed that the common segment of 27 residues but not truncated versions thereof contains the essential structural elements for prekallikrein binding. This conclusion was corroborated by the finding that anti-idiotypic antibodies toward a monoclonal antibody directed to the binding segment of 27 residues bear internal image(s) of the binding site of H-kininogen. It is pointed out that the methodology described in this study may prove generally useful in the cloning and mapping of high affinity binding sites of proteins.

Amino Acid Sequence↗
PubMed1990

High molecular weight kininogen-binding site of prekallikrein probed by monoclonal antibodies.

A panel of monoclonal antibodies against human prekallikrein was raised in mice and characterized with respect to the major antigenic epitopes. Of 18 antibodies, nine were directed against the light chain portion performing the proteolytic function of activated kallikrein, and nine recognized the heavy chain mediating the binding of prekallikrein to high molecular weight (H-)kininogen. Among the anti-heavy chain antibodies, one (PK6) interfered with the procoagulant activity of prekallikrein, and prolonged in a concentration-dependent manner the activated partial thromboplastin time of reconstituted prekallikrein-deficient plasma (Fletcher type). Antibody PK6 was subtyped IgG1,k and had an apparent Kass of 6.8 +/- 0.44.10(8) M-1 for prekallikrein. Functional analyses revealed that PK6 does not interfere with prekallikrein activation by activated Hageman factor (beta-F XIIa), and has no effect on the kininogenase function of activated kallikrein. Monoclonal antibody PK6 but none of the other anti-heavy chain antibodies completely prevented complex formation of prekallikrein with H-kininogen, and readily dissociated preformed complexes of prekallikrein and H-kininogen. Likewise, Fab' and F(ab')2 fragments of PK6 blocked H-kininogen binding to prekallikrein. A synthetic peptide of 31 amino acid residues encompassing the entire prekallikrein binding region of H-kininogen effectively competed with PK6 for prekallikrein binding indicating that the target epitope of PK6 is juxtaposed to, if not incorporated in the H-kininogen-binding site of prekallikrein. Extensive cross-reactivity of PK6 with another H-kininogen-binding protein of human plasma, i.e. factor XI, suggested that the structure of the target epitope of PK6 is well conserved among prekallikrein and factor XI, as would be expected for the kininogen-binding site shared by the two proteins. It is anticipated that monoclonal antibody PK6 will be an important tool for the precise mapping of the hitherto unknown kininogen-binding site of prekallikrein.

Antibodies, Monoclonal↗
PubMed1990

Synthesis and secretion of hirudin by Streptomyces lividans.

To examine the secretory production of heterologous proteins by Streptomyces lividans, we fused the DNA encoding the signal peptide of the alpha-amylase inhibitor tendamistat, derived from S. tendae with a synthetic gene encoding the thrombin inhibitor hirudin. The analysis of secretion by immunoblots revealed an efficient translocation of hirudin through the membrane, with no detectable immunoreaction among the cellular proteins. The secreted hirudin was stable in the shaking culture for about 6 days. A comparison of the hirudin secreted by S. lividans and recombinant reference hirudin from yeast by immunoblots and thrombin inhibition assays shows that hirudin from Streptomyces has a lower specific activity, which may be due to a different aminoterminal sequence or to inexact processing of the precursor.

Amino Acid Sequence↗