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Biomedical subjects

J Kastner

Publications and source records attributed to J Kastner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Nitric oxide synthase inhibition in the histamine headache model.

Histamine has been widely used experimentally to induce headache in healthy subjects and migraine in migraineurs. There is evidence that the vascular effects of histamine are at least partially mediated by nitric oxide (NO). Hence we hypothesized that subjective symptoms and hemodynamic effects of histamine could be reduced by systemic NO-synthase inhibition. We therefore studied the effect of pretreatment with N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO-synthase, or placebo on headache, flush and discomfort scores during histamine infusion. Additionally, blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured. Whereas L-NMMA blunted the effect of histamine in the ophthalmic artery and the ocular circulation, NO-synthase inhibition did not mitigate subjective symptoms. Histamine did not affect mean blood flow velocities in the middle cerebral artery. Hence, we conclude that NO-synthase inhibition reduces the histamine-induced vascular effects in the ocular circulation, but is not sufficient to attenuate or abort the subjective symptoms provoked by histamine infusion.

Adult↗
PubMed1997

Exhaled NO during graded changes in inhaled oxygen in man.

BACKGROUND: Nitric oxide (NO) is present in the exhaled air of animals and humans. In isolated animal lungs the amount of exhaled NO is decreased during hypoxia. A study was undertaken to determine whether changes in arterial oxygen tension affect levels of exhaled NO in humans. METHODS: Sixteen healthy subjects were randomised to inhale different gas mixtures of oxygen and nitrogen in a double blind crossover study. Eight gas mixtures of oxygen and nitrogen (fractional inspired oxygen concentration (FiO2) 0.1 to 1.0) were administered. Exhaled NO was measured with a chemiluminescence detector from end expiratory single breath exhalation. RESULTS: A dose-dependent change in exhaled NO during graded oxygen breathing was observed (p = 0.0012). The mean (SE) exhaled NO concentration was 31 (3) ppb at baseline, 39 (4) ppb at an FiO2 of 1.0, and 26 (3) ppb at an FiO2 of 0.1. CONCLUSIONS: The NO concentration in exhaled air in healthy humans is dependent on oxygen tension. Hyperoxia increases the level of exhaled NO, which indicates increased NO production. The mechanism behind this phenomenon remains to be elucidated.

Administration, Inhalation↗
PubMed1997

Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans.

It is well known that changes in PCO2 or PO2 strongly influence cerebral and ocular blood flow. However, the mediators of these changes have not yet been completely identified. There is evidence from animal studies that NO may play a role in hypercapnia-induced vasodilation and that NO synthase inhibition modulates the response to hyperoxia in the choroid. Hence we have studied the effect of NO synthase inhibition by NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg over 5 min as a bolus followed by a continuous infusion of 30 micrograms.kg-1.min-1) on the changes of cerebral and ocular hemodynamic parameters elicited by hypercapnia and hyperoxia in healthy young subjects. Mean flow velocities in the middle cerebral artery and the ophthalmic artery were measured with Doppler ultrasound, and ocular fundus pulsation amplitude, which estimates pulsatile choroidal blood flow, was measured with laser interferometry Administration of L-NMMA reduced ocular fundus pulsation. (-19%, P < 0.005) but only slightly reduced mean flow velocities in the larger arteries. Hypercapnia (PCO2 = 48 mmHg) significantly increased mean flow velocities in the middle cerebral artery (+26%, P < 0.01) and fundus pulsation amplitude (+16%, P < 0.005) but did not change mean flow velocity in the ophthalmic artery. The response to hypercapnia in the middle cerebral artery (P < 0.05) and in the choroid (P < 0.05) was significantly blunted by L-NMMA. On the contrary, L-NMMA did not affect hyperoxia-induced (PO2 = 530 mmHg) hemodynamic changes. The hemodynamic effects of L-NMMA (at baseline and during hypercapnia) were reversed by coadministration of L-arginine. The present study supports the concept that NO has a role in hypercapnia induced vasodilation in humans.

Adult↗
PubMed1996

Sex differences in concentrations of exhaled nitric oxide and plasma nitrate.

Nitric oxide (NO) is generally considered as an endogenous vasoprotective agent. Various studies indicate that the female sex hormone estradiol, that contributes to the well known gender differences in cardiovascular disease, may enhance NO-production. Thus we studied sex differences in NO-generation by measuring single breath NO-exhalation and plasma levels of nitrate (NO3), the stable endmetabolite of NO. In this observational trial 22 male and 21 female volunteers, 19 to 38 years of age, were studied on 3 days at weekly intervals. Median concentrations of NO were 20 parts per billion (95% CI: 16 to 32 ppb) in women and 34 ppb (95% CI: 31 to 58 ppb) in men. The median plasma concentrations of NO3 were 14 microM/L (95% CI: 11 to 23 microM/L) in women and 27 microM/L (95% CI: 24 to 47 microM/L) in men. Thus, men exhaled 59% more NO (p < 0.001) and had 99% higher NO3 levels than women (p < 0.0001). Even when exhaled NO concentrations were corrected for body weight, men exhaled 50% more NO than women (p = 0.024). No significant changes in measured endpoints were seen during the menstrual cycle (p > 0.05) in women. In view of the diversity of NO-actions, the finding of marked sex differences in NO-production is basic to the elucidation of gender differences in a number of (patho)-physiologic conditions.

Adult↗
PubMed1996

Adolescents with mental retardation: perceptions of sexual abuse.

Reactions of nonretarded female undergraduates to sexually coercive situations in which neither, one, or both protagonists had mental retardation were examined. Results indicated that retardation affected perceptions of both responsibility and harm. Implications for the education of mental health professionals about the emotional needs of individuals with retardation are discussed.

Adolescent↗
PubMed1995

Phase I/II trial of dexverapamil, epirubicin and granulocyte/macrophage-colony-stimulating factor in patients with advanced pancreatic adenocarcinoma.

A group of 28 previously untreated patients with locally advanced or metastatic adenocarcinoma of the pancreas were entered in this phase I/II study. Treatment consisted of oral dexverapamil 1000-1200 mg/day for 3 days, epirubicin given as an intravenous bolus injection on day 2 with a starting dose of 90 mg/m2, and 400 micrograms granulocyte/macrophage-colony-stimulating factor (GM-CSF) administered subcutaneously from day 5 through 14. Epirubicin dose escalation levels were 90, 105, 120 and 135 mg/m2. Consecutive cohorts of 4-8 patients were planned at each dose level. Treatment cycles were repeated every 3 weeks. Haematological toxicity, specifically granulocytopenia constituted the dose-limiting toxicity with a maximum tolerated dose of 120 mg/m2 for epirubicin. Despite routine supportive therapy with GM-CSF, 4, 2, and 5 patients experienced grade 4 granulocytopenia during their first two treatment courses at levels of 105, 120, and 135 mg/m2 respectively. Non-haematological toxicity was uncommon, generally modest, and did not demonstrate a clear relationship with the anthracycline dose. Dexverapamil-related cardiovascular symptoms occurred frequently, but they never resulted in serious toxicity requiring active medical intervention or permanent discontinuation of therapy. Of the 28 patients, 9 achieved partial reponses to this therapy. The recommended dose of epirubicin for this regimen with dexverapamil and GM-CSF is 120 mg/m2 every 3 weeks. Therapeutic results suggest this regimen to be an effective and tolerable treatment strategy in pancreatic cancer, which should be evaluated further.

Adenocarcinoma↗
PubMed1995

Role of nitric oxide in hemostatic system activation in vivo in humans.

NO is a potent inhibitor of in vitro platelet aggregation and adhesion. In view of possible future widespread use of NO in pulmonary and cardiovascular diseases, we investigated the role of NO in hemostatic system activation in vivo in humans. Sixteen healthy male volunteers (age range, 22 to 33 years) received either NO by inhalation (50 ppm over 30 minutes; n = 8) or the NO synthase inhibitor NG-monomethyl L-arginine (L-NMMA 3mg/kg body weight i.v. over 5 minutes; n = 8), beta-Thromboglobulin (beta-TG), an indicator of platelet activity; prothrombin fragment 1 + 2 (F 1 + 2), an index of coagulation activation; and thromboxane B2 (TxB2), a measure of platelet prostaglandin synthesis, were determined in blood samples obtained from bleeding-time incisions ("shed blood") at baseline and after administration of the respective drug. In addition, beta-TG and F 1 + 2 were also determined in venous blood. To verify the systemic effects of the drugs, methemoglobin and plasma nitrites/nitrates were measured in the NO group, and cardiac output and exhaled NO were measured in the L-NMMA group. Compared with baseline, methemoglobin and plasma nitrates increased by 73 +/- 12% (P= .006) and 60 +/- 9% (P< .001), respectively, following NO inhalation. L-NMMA infusion resulted in decreases in both cardiac output by 16 +/- 2%; P< .001) and exhaled NO (by 54 +/- 7%; P< .001). NO inhalation or L-NMMA infusion had no significant effect on beta-TG, F 1 + 2, and TxB2 levels in shed blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1995

Short-term drug effects on the signal-averaged electrocardiogram in healthy men: assessment of intra- and interindividual variability of spectral temporal mapping and time-domain analysis.

The effect of cardiovascular drugs on the results of the signal-averaged electrocardiogram (SA-ECG) was studied in healthy young subjects. Cardiovascular drugs may confound the analysis of SA-ECG, but the effect of drugs on time-domain analysis and on spectral temporal mapping (STM) in healthy subjects has not been investigated under standardized conditions. Also, the reproducibility of the various spectral area measurements of STM has not been assessed simultaneously. Short-term drug effects on the SA-ECG were studied in 20 healthy young men (age 23.5 +/- 2.5 years) in an observer-blinded, crossover design on separate days. Each subject was randomly assigned to four drugs. The SA-ECG was recorded at baseline and during i.v. administration of stepwise increased doses of adenosine, atropine, isoproterenol, lidocaine, norepinephrine, propranolol, verapamil and placebo. Low amplitude signal duration was significantly and dose-dependently shortened by isoproterenol, whereas no consistent effect on the filtered QRS duration or on the root mean square voltage in the terminal 40 ms of time-domain analysis was noted for any of the other drugs. Only lidocaine significantly and dose-dependently decreased the parameters of STM at QRS offset and +20 ms, even though short-term reproducibility and day-to-day reproducibility of spectral area measurements were low. Interpretation of "normal" results from SA-ECG is not relevantly influenced by the studied drugs at clinical doses. STM may prove a useful technique for detection of the actions of sodium channel-blocking drugs. Reproducibility of STM measurements is substantially lower than that of time-domain parameters.

Adenosine↗
PubMed1994

Mental retardation and adult women's perceptions of adolescent sexual abuse.

This study examined the effect of mental retardation and an adolescent girl's behavior on adult women's perceptions of sexual abuse and the girl's responsibility. Subjects were 288 women, age 18 to 33, who were randomly assigned a vignette describing a sexual encounter between an adolescent girl and boy. Girl's diagnosis (mentally retarded or nonretarded), boy's diagnosis (mentally retarded or nonretarded) and girl's behavior (encouraging, passive, or resisting) were experimentally manipulated. Factor analysis of responses yielded three factors: girl's responsibility, boy's abusiveness, and parents' responsibility. Results indicate that subjects perceive the girl's responsibility differently among girls with and without mental retardation. Regardless of her behavior, subjects perceive the girl as bearing little responsibility when she is retarded. However, when she is nonretarded, she bears more responsibility when she is encouraging than when she is passive or resisting, and she bears greater responsibility when she is passive than when she is resisting. Also, when the girl is encouraging, the boy's perceived sexual abusiveness is less when he is mentally retarded than when he is nonretarded. Finally, parents are assigned greatest responsibility when the girl is passive, regardless of her diagnosis.

Adolescent↗
PubMed1993

Motion measurement with high-speed video.

A new kinematic measurement system based on a high-speed video system, combined with a computer-assisted evaluation for the analysis of gait patterns, is described. The system allows both a reviewable visual assessment in slow motion (up to 1000 frames s-1 as well as automatic measurement of the kinematics of body segments. Specially developed software, which uses a pattern search algorithm and an additional subpixel correction, results in a deviation of less than 0.1% (without considering the lens nonlinearity). For most cases the recognition and tracking of temporarily concealed markers is also achieved. The results of the computer-assisted high-speed video analysis are being applied in rehabilitation programmes to increase the objectivity of standard movements, e.g. gait analysis of people with artificial limbs.

Algorithms↗
PubMed1993

Quantification of hind limb lameness in the horse.

The three-dimensional optoelectronic locomotion analysis system SELSPOT II was used for kinematic studies of hind limb locomotion patterns. Two groups, 11 sound horses and 15 horses suffering from hind limb lameness, were examined at the trot. Both graphical and quantitative analyses were compared in sound and lame horses. The parameter hip acceleration quotient (HAQ), using the different peaks of vertical acceleration of one hip during one stride, proved to be a suitable value for quantitative analysis of hind limb lameness. In sound horses the HAQ ranged from 1.03 to 1.54, lame horses showed values between 1.32 and 2.96. Checking and documentation of diagnostic anesthesias or therapies are possible applications.

Acceleration↗