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Biomedical subjects

R Vogel

Publications and source records attributed to R Vogel.

At least 73 records · Page 4Linked to original sources
PubMed1996

A six-week dose-response study of the ocular hypotensive effect of dorzolamide with a one-year extension. Dorzolamide Dose-Response Study Group.

PURPOSE: To investigate the efficacy and dose-response relationship of three concentrations (0.2%, 0.7%, and 2.0%) of dorzolamide hydrochloride in lowering elevated intraocular pressure (IOP) in patients during a six-week period and to evaluate the efficacy of 0.7% and 2.0% dorzolamide administered for an additional year. METHODS: This prospective, double-masked, randomized, placebo-controlled, multinational study enrolled 333 adults with open-angle glaucoma or ocular hypertension. During the six-week dose-response phase, patients were randomized to thrice-daily dosing of four treatments: 0.2%, 0.7%, or 2.0% dorzolamide or placebo (vehicle of dorzolamide). During a one-year extension, patients received 0.7% or 2.0% dorzolamide, and, if needed, 0.5% timolol twice daily for elevated IOP. RESULTS: In the dose-response phase, mean percent reduction of IOP (peak) was 16% to 18% for 2.0% and 0.7% dorzolamide and 4% to 7% for the placebo group, for a net reduction of IOP by dorzolamide of 11% to 14%. The 0.2% concentration of dorzolamide was not sufficiently active for further consideration. During the extension, dorzolamide maintained an adequate reduction of IOP in 55% (174 of 316) of patients. Throughout the study, the reduction in IOP was numerically greater for patients receiving 2.0% vs 0.7% dorzolamide. After 12 months of receiving dorzolamide, 20% to 28% of total carbonic anhydrase activity was observed. CONCLUSIONS: Topical dorzolamide used three times daily in concentrations of 0.7% or 2.0% lowered IOP and was generally well tolerated as monotherapy or in combination with 0.5% timolol.

Administration, Topical↗
PubMed1996

The use of dorzolamide and pilocarpine as adjunctive therapy to timolol in patients with elevated intraocular pressure. The Dorzolamide Additivity Study Group.

PURPOSE: To report the results of two studies on the use of dorzolamide as adjunctive therapy to timolol in patients with elevated intraocular pressure (IOP). In the larger study, the additive effect of dorzolamide administered twice daily also was compared with 2% pilocarpine. METHODS: Both studies were parallel, randomized, double-masked, placebo-controlled comparisons. In the pilot study, 32 patients received 0.5% timolol twice daily plus either 2% dorzolamide twice daily or placebo twice daily for 8 days. In the Pilocarpine Comparison Study, 261 patients received 0.5% timolol twice daily plus 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, 2% pilocarpine four times daily, or placebo (twice daily or 4 times daily) for 2 weeks. Patients then entered a 6-month extension period and received 0.5% timolol twice daily plus either 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, or 2% pilocarpine four times daily. RESULTS: In the pilot study, after 8 days, additional mean percent reductions in IOP for 2% dorzolamide and placebo were 17% and 3% at morning trough and 19% and 2% at peak, respectively. In the Pilocarpine Comparison Study, after 6 months, additional mean percent reductions in IOP (morning trough) were 9%, 13%, and 10% for 0.7% dorzolamide, 2% dorzolamide, and 2% pilocarpine, respectively. Patients receiving 2% pilocarpine had the highest rate of discontinuation due to a clinical adverse experience, and the use of dorzolamide was not associated with systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors. CONCLUSION: Dorzolamide twice daily was effective and well tolerated by the patients in these studies as adjunctive therapy to timolol. The larger study demonstrated that both concentrations of dorzolamide produce similar IOP-lowering effects to 2% pilocarpine.

Adrenergic beta-Antagonists↗
PubMed1996

Influence of etiology on the course and outcome of acute pancreatitis.

It has been supposed that there are differences with regard to clinical course and outcome due to the underlying etiological factor in acute pancreatitis. Therefore, the objective of this study was to analyze the severity of the disease, serum enzymes, indicators of necrosis, systemic complications, and mortality in acute pancreatitis with regard to the etiology. One hundred ninety patients with acute pancreatitis (127 male, 63 female) were studied prospectively and subdivided into three etiological groups: (i) alcohol, (ii) gallstones, and (iii) other causes and idiopathic acute pancreatitis. Severity scores (Ranson and Bank) and findings by contrast-enhanced computed tomography were similar in all three groups. Analysis of serum enzymes [lipase, aspartate aminotransferase (ASAT)] and indicators of necrosis (C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, and lactate dehydrogenase) showed only for ASAT within 24 h significantly higher levels in biliary acute pancreatitis in comparison with the other groups. There were no differences in the rate of infected pancreatic necrosis and mortality in alcohol-related acute pancreatitis (31 and 5.3%), biliary acute pancreatitis (38 and 10%) and acute pancreatitis due to other etiological factors (43 and 5.5%). In conclusion, this study clearly showed that once the pathogenetic mechanisms have initiated the disease, the course and outcome of acute pancreatitis are not influenced by the underlying etiological factor.

Acute Disease↗
PubMed1996

The effect of ketoprofen creams on periodontal disease in rhesus monkeys.

Ketoprofen creams were evaluated for the treatment of periodontal disease in a placebo-controlled, double-blind study in the rhesus monkeys, Macaca mulatta. Two formulations containing ketoprofen (1%), with or without vitamin E, were evaluated against appropriate controls (8 monkeys per group). Two weeks prior to treatment, the animals received prophylaxis on only the left side of the mouth (spontaneous model). Selected teeth on the right side of the mouth were ligated (ligature model). The creams were administered to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months. Clinical assessments were made 2 wk before initiation, at baseline and 1, 2, 3 and 6 months post-treatment. The clinical parameters included plaque formation, gingival redness, edema, bleeding on probing and Ramfjord Attachment Level measurements (RAL). Radiographs were taken at 2 wk before initiation, baseline and at 3 and 6 months post-treatment. Digital, subtraction radiography was used to measure vertical linear bone loss along the interproximal root surfaces of the left and right mandibular first molars. Gingival crevicular fluid (GCF) was collected for biochemical assays on PGE2, TxB2, LTB4, IL-1 beta and TNF alpha. There were no significant differences among groups with respect to gingival indices. Radiographic data demonstrated significant positive effects on bone activity in both groups treated with ketoprofen formulations with improvement over time in the ligature model (0.01 < or = p < or = 0.04). The placebo group exhibited bone loss of 1.96 +/- 0.48 and 1.40 +/- 0.56 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream showed an apparent bone gain of 0.28 +/- 0.41 and 0.78 +/- 0.47 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream containing vitamin E showed a mean bone loss of 0.41-0.48 mm per site at 3 months with improvement to an apparent bone gain of 0.31 +/- 0.44 mm per site at 6 months. The biochemical data demonstrated early and significant suppression of GCF-LTB4 by both ketoprofen formulations at 1 month, which preceded the significant suppression of GCF-PGE2 at 2 and 3 months in the ligature model (p < 0.003) and at 2 to 6 months in the spontaneous model (p < 0.02). We conclude that ketoprofen at 1% level in suitable topical vehicles can effectively inhibit GCF-LTB4 and GCF-PGE2 and positively alter alveolar bone activity in the ligature-induced model of periodontitis in the monkey.

Administration, Topical↗
PubMed1995

A double-masked, randomized 1-year study comparing dorzolamide (Trusopt), timolol, and betaxolol. International Dorzolamide Study Group.

OBJECTIVE: To investigate the safety profile and efficacy of 2.0% dorzolamide hydrochloride, when administered three times daily for up to 1 year, compared with that of 0.5% timolol maleate and 0.5% betaxolol hydrochloride, each administered twice daily. In addition, the effect of adding dorzolamide to the regimen of patients with inadequate ocular hypotensive efficacy while they were receiving one of the two beta-adrenoceptor antagonists and the effect of adding timolol to the regimen of patients receiving dorzolamide were also evaluated. DESIGN: A double-masked, randomized, parallel comparison. SETTING: Multinational study at 34 international sites. PATIENTS: Five hundred twenty-three patients with open-angle glaucoma or ocular hypertension, 17 to 85 years of age. Patients currently using ocular hypotensive medications were required to undergo a washout. INTERVENTION: Two percent dorzolamide three times a day, 0.5% timolol (Timoptic, Merck, Whitehouse Station, NJ) twice daily, and 0.5% betaxolol solution (Betoptic, Alcon, Fort Worth, Tex) twice daily. RESULTS: At 1 year, the mean percent reduction in intraocular pressure at peak of 2% dorzolamide, 0.5% timolol, and 0.5% betaxolol was approximately 23%, 25%, and 21%, respectively. At afternoon trough, the mean percent reduction in intraocular pressure was 17%, 20%, and 15% for dorzolamide, timolol, and betaxolol, respectively. CONCLUSIONS: The ocular hypotensive efficacy of 2.0% dorzolamide, given three times a day, is comparable with that of 0.5% betaxolol, given twice daily, for up to 1 year. In addition, long-term use of dorzolamide was not associated with clinically meaningful electrolyte disturbances or systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors.

Administration, Topical↗
PubMed1995

Cloning and stable expression of the human mitochondrial cytochrome P45011B1 cDNA in V79 Chinese hamster cells and their application for testing of potential inhibitors.

V79 Chinese hamster cells are being genetically engineered to express human mitochondrial cytochromes P450 as an analytical tool for studying adrenal steroid synthesis. Here, a V79 derived cell line is presented expressing the enzymatically active human cytochrome P45011B1 (CYP11B1) in a stable and constitutive manner. Full length CYP11B1 cDNA was obtained from surgically removed normal adrenal gland by polymerase chain reaction. The cDNA was recombined with a SV40 early promoter containing plasmid for stable integration and expression in V79 cells upon gene transfer. The presence of the human CYP11B1 cDNA in the genome of the transfected cells was confirmed by Southern analysis. CYP11B1 cDNA directed expression was detected by Northern analysis. CYP11B1 dependent hydroxylation of deoxycorticosterone and 11-deoxycortisol was measured by HPLC analysis. Interestingly, the nonsteroidogenic lung fibroblast derived V79 Chinese hamster cell line was able to support human CYP11B1 mediated steroid hydroxylation without simultaneous heterologous expression of the human electron transfer system, adrenodoxin, and adrenodoxin reductase. CYP11B1 inhibitory potency of metyrapone, spironolactone, and the azole derivatives ketoconazole, clotrimazole, miconazole, and fluconazole was measured using the newly established V79MZh11B1 cell line. Thus, beside steroid metabolism studies in general, this cell line may also serve as an in vitro tool for monitoring the interference of drugs with 11 beta-hydroxylase activity.

Adrenal Glands↗
PubMed1995

Facial sensory evoked muscle potentials during labour. A continuous objective monitor of adequacy of analgesia?

We prospectively studied the relationship between upper facial sensory-evoked muscle potential amplitude, uterine contraction amplitude and heart rate in 20 healthy parturients during the first stage of labour. Monitoring began when minimal pain was reported and continued until severe pain occurred and extradural analgesia was established. Pain intensity was assessed by each patient using a 10 cm visual analogue score. Heart rate was recorded using a pulse oximeter. Sensory evoked muscle potential was derived from frontalis biopotentials that were rectified, integrated and digitised by an Anaesthesia and Brain activity Monitor (Datex, Helsinki, Finland). An additional signal filter was included in the pre-amplifier to improve the signal-to-noise ratio. The rms amplitude of successive 10s samples of sensory evoked muscle potential, as well as heart rate and the output from an external tocotransducer, were then graphically displayed to allow assessment of temporal relationships. The data were assessed using correlation analysis and hypergeometric probability distribution. Before extradural analgesia (mean pain score 7.5 cm, SD 1.5 cm) a significant relationship was demonstrated between sensory evoked muscle potential and uterine contraction, p < 0.001). No constant relationship was seen between heart rate and uterine contraction. Following extradural analgesia (mean pain scores of 2.1 cm, SD 1.3 cm) a variable relationship between sensory evoked muscle potential and uterine contraction amplitude, and heart rate and uterine contraction, was recorded. A continuous display of the relationship between filtered sensory evoked muscle potentials of the frontalis muscle and uterine contraction may, in the future, permit an objective assessment of the adequacy of analgesia following extradural analgesia for the pain of labour.

Adult↗
PubMed1994

NER, a new member of the gene family encoding the human steroid hormone nuclear receptor.

NER, a new member of the steroid hormone nuclear receptor (NR)-encoding gene family, was isolated from a human osteosarcoma SAOS/B10 cell line cDNA library. NER codes for a polypeptide of 461 amino acids which contains the conserved sequences of the DNA-binding and ligand-binding domains of typical steroid hormone NR. It has highest homology with the retinoic acid receptors: 55% at the DNA-binding domain and 38-40% at the ligand-binding domain. A single transcript of 2.3 kb was detected in all cells and tissues tested. Although no ligand was identified for NER-I, its wide distribution may indicate that this novel steroid hormone NR may play a basic role in cell function.

Amino Acid Sequence↗
PubMed1994

Involvement of 11p15 and 3q21q26 in therapy-related myeloid leukemia (t-ML) in children. Case reports and review of the literature.

The cytogenetic findings of therapy-related myeloid leukemia (t-ML) in three children are presented. These included one male patient with acute lymphoblastic leukemia (ALL) who underwent bone marrow transplantation and developed therapy-related myeloproliferative disease (t-MPD) in the female-donor hematopoietic cells 2.5 years after receiving radiation and epipodophyllotoxin therapy for ALL testicular relapse. Bone marrow leukemic cell karyotype revealed 46,XX,add (11)(p15) and a normal female karyotype in the peripheral blood lymphocytes. The other two children, one with ALL and one with ganglioneuroblastoma, developed fatal t-MPD and therapy-related acute myeloblastic leukemia (t-AML) preceded by myelodysplastic syndrome (t-MDS), respectively, 5 years after diagnosis, following administration of alkylating agents and irradiation. Monosomy 7 was present in both, and was combined with inv(3)(q21q26) in the second patient. Our review of the cytogenetic findings in 91 previously reported pediatric patients with t-ML suggested that the involvement of 11p15 and 3q21-->23, 3q24-q26 with or without a combination of translocation 11q23 and -7/7q-, respectively, are nonrandom aberrations of t-ML in children. Comparison of the chromosomal changes in t-ML between the pediatric and an adult series revealed some differences which may result from differences in treatment modalities and which, in addition, may indicate a possible role of genetic and/or age-dependent factors in the pathogenesis of therapy-related leukemogenesis in children.

Antineoplastic Agents↗
PubMed1994

Clinical and angiographic variables affecting the progression of coronary artery disease as determined by quantitative angiography.

To assess by serial quantitative angiography, the significance of clinical and angiographic variables that affect the progression of coronary artery disease (CAD). Progression of disease by sequential angiography is unpredictable and the role of clinical risk factors controversial. Various intervention trials have demonstrated less progression and even regression in hyperlipidemic patients. Correlates of progression have included a younger age, unstable angina, and greater involvement of the coronary arteries, with few studies looking at angiographic features of individual lesions. Serial angiograms on 74 patients were analyzed by computer assisted quantitative angiography using absolute measurements. A total of 99 diseased segments were analyzed for progression defined as an absolute reduction of 20% in luminal cross-sectional area. A preliminary correlation coefficient was calculated for each of the clinical and angiographic variables to detect any association with progression, and the odds ratio determined. The presence of any of the clinical risk factors-diabetes, hypertension, serum cholesterol, smoking, and a family history of coronary disease could not predict progression. The use of beta blockers was three times less likely to be associated with progression (odds ratio 0.33). While the presence of distal disease was associated with progression of a more proximal lesion (odds ratio 2.4), eccentricity, branch point location, lesion length, calcification, thrombus, or the presence of collaterals did not influence progression of disease in an individual segment. In conclusion, the presence of any of the clinical risk factors could not predict progression of disease in an individual coronary segment as determined by serial quantitative angiography, and the use of beta blockers and the absence of coexistent distal disease was associated with less progression of disease in an individual coronary segment. This may be related to changes in wall stress, reduced platelet interactions, and the integrity and permeability of the vascular endothelium to lipids.

Adrenergic beta-Antagonists↗
PubMed1993

L-arginine-derived nitric oxide: a major determinant of uveal blood flow.

The effect of inhibition of the L-arginine-nitric oxide pathway on regional ocular blood flow was studied in anaesthetized Beagle dogs. Under control conditions (mean arterial blood pressure 105 +/- 6 mmHg) trapping of 11 and 15-microns-diameter tracer microspheres revealed the following regional blood flows (ml min-1 g-1): retina 0.065 +/- 0.016, choroid 5.72 +/- 0.32, ciliary body 0.77 +/- 0.11, iris 0.18 +/- 0.04. After i.v. infusion of nitro-L-arginine methylester (20 mg kg-1), a potent inhibitor of nitric oxide production from L-arginine, mean arterial blood pressure increased from 105 +/- 6 mmHg by 19% to a new steady-state level of 125 +/- 7 mmHg. This increase of arterial blood pressure extended over 3 hr and was reversible after i.v. infusion of L-arginine (100 mg kg-1 over 10 min). Despite the increase in blood pressure following infusion of nitro-L-arginine methylester blood flow of choroid, ciliary body, and iris were significantly decreased by 40, 40 and 48%, respectively. Retinal blood flow did not change significantly (-12%). These results suggest that the L-arginine-nitric oxide pathway is of major importance for the adjustment of uveal blood flow under resting physiological conditions.

Animals↗
PubMed1993

In vitro approach to fertility research: genotoxicity tests on primordial germ cells and embryonic stem cells.

In vitro screening tests for reproductive toxicology are required by the 7th amendment of the directive 67/548 EEC and the OECD-programme on existing chemicals. Unfortunately, appropriate methods for testing developmental toxicity or impairment of fertility are not at hand. Therefore, we have tried to design test method based on mutagenic effects in germ cells that may be used as a test of fertility impairment as well. Embryonic stem cells (ESC) derived from mouse blastocysts can be kept in culture routinely. Establishment of ESC and improvement of their culture conditions are described and special properties of ESC are discussed in relation to germ cells. Because some properties of germ cells and pluripotent embryonic stem cells (ESC) are found to be comparable, permanent lines of ESC hold promise to be used as an in vitro test of impairment of fertility.

Animals↗
PubMed1993

A prospective randomized trial of Novoste right versus Judkins catheters for engagement of the right coronary artery during diagnostic catheterization.

There has been little technical advancement in catheter shape for diagnostic cardiac catheterization since the early reports of Sones and colleagues during the development of the procedure. In order to determine the utility of a new catheter that directly, without torque or rotation, engages the right coronary artery (RCA), one hundred patients were randomized between 6Fr standard RCA Judkins (6Fr R4) (Cordis Corporation, Miami, FL, USA) or 6Fr Novoste RCA catheters (Novoste Corporation, Aguadilla, Puerto Rico). Endpoints included the duration of the various aspects of the procedure and a qualitative and quantitative assessment of angiographic quality. The Novoste RCA catheters were associated with statistically decreased times of catheter insertion (42 +/- 37 vs 90 +/- 119 secs), and engagement (31 +/- 35 vs 77 +/- 117 secs), of the right coronary artery as compared to Judkins catheters. Judkins RCA catheters had a significantly higher primary success rate (96%) than the Novoste group (84%, P = 0.045). There was no difference in angiographic quality in either group and no complications occurred during the study. While taller patients (mean 68 in) had increased success with the Novoste catheter, no other clinical, demographic, or anatomical characteristics of the RCA orifice predicted successful engagement and angiography. The direct engagement Novoste RCA catheter is associated with a more expeditious procedure than Judkins catheters when they can engage the RCA orifice. However, Novoste catheters were less successful and required more frequent exchanges to complete the procedure.

Adult↗