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Biomedical subjects

M Wolzt

Publications and source records attributed to M Wolzt.

At least 91 records · Page 5Linked to original sources

A randomized, placebo-controlled, double-blind crossover study of the effect of pentoxifylline on ocular fundus pulsations.

PURPOSE: To estimate the short-term effects of pentoxifylline on ocular blood flow in healthy volunteers. METHODS: In ten healthy subjects, either 200 or 400 mg of pentoxifylline or placebo was administered intravenously over 90 minutes in a randomized, double-blind, placebo-controlled, three-way crossover study design. Noninvasive measurements of blood pressure, pulse rate, flow variables in the radial artery, ocular fundus pulsations, and whole blood viscosity and filterability were performed at baseline and at 30-minute intervals until four hours after the start of drug infusion. Ocular fundus pulsation amplitude, which has been shown to estimate the pulsatile component of the ocular blood flow, was recorded with a laser interferometer in the macula, the optic disk, and a peripheral region. RESULTS: Fundus pulsation amplitude significantly increased after infusion of pentoxifylline, with maximum effect 150 to 180 minutes after the start of the infusion. This effect was dose-dependent and more pronounced in the macula (+17%, P < .001 vs baseline, after 200 mg; and +27%, P < .001 vs baseline, after 400 mg of pentoxifylline) and the peripheral region (+14%, P < .001; and +26%, P < .001) than in the optic disk (+11%, P < .002; and +13%, P < .001). Viscosity but not filterability of whole blood dose-dependently decreased. Peak systolic flow velocity in the radial artery decreased after infusion of 400 mg of pentoxifylline. Blood pressure and pulse rate were unchanged during the observation period. CONCLUSIONS: These findings demonstrate that pentoxifylline increases pulsatile ocular blood flow in healthy volunteers. Our results support the possibility that pentoxifylline could be used therapeutically in several eye diseases, such as diabetic retinopathy.

Adult↗

Cerebral and ocular hemodynamic effects of sumatriptan in the nitroglycerin headache model.

BACKGROUND AND PURPOSE: Sumatriptan is a selective 5-hydroxytryptamine1d (5-HT1d)-receptor agonist, highly effective in the short-term treatment of migraine headaches. However, the mechanism underlying the action of sumatriptan is not yet completely understood. To further characterize the vascular effects of sumatriptan, we studied the effects on cerebral and ocular circulation in the well-established nitroglycerin headache model. METHODS: In a double-blind, placebo-controlled, randomized, two-way crossover study in 10 healthy male subjects, we administered either placebo plus nitroglycerin or sumatriptan plus nitroglycerin. Blood flow velocity in the middle cerebral artery and the ophthalmic artery, as well as ocular fundus pulsations and systemic hemodynamic parameters, were measured after sumatriptan and placebo and during the following infusion of nitroglycerin. RESULTS: After infusion of nitroglycerin, blood flow velocity in the middle cerebral decreased by -13.3% versus baseline after placebo pretreatment, but by only -2.2% after sumatriptan (treatment effect, +10.8%; p < 0.05). In contrast, sumatriptan had no effect in the ophthalmic artery. Ocular fundus pulsations, which estimate local pulsatile ocular blood flow, were slightly reduced after sumatriptan. Moreover, sumatriptan partially prevented the increase in fundus pulsations during nitroglycerin infusion (treatment effect, -5.4%; p < 0.05). CONCLUSIONS: Sumatriptan prevents the effect of nitroglycerin-induced vasodilation in the middle cerebral artery but not in the ophthalmic artery, which strongly supports the concept that sumatriptan directly vasoconstricts distended basal cerebral arteries. Measurement of ocular fundus pulsations indicates that sumatriptan also has a small vasoconstrictor action on resistance vessels.

Adult↗

Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in healthy volunteers.

AIMS/BACKGROUND: Recently a laser interferometric method for topical measurement of fundus pulsations has been developed. Fundus pulsations in the macular region are caused by the inflow and outflow of blood into the choroid. The purpose of this work was to study the influence of a peripheral vasoconstricting (the alpha 1 adrenoceptor agonist phenylephrine), a predominantly positive inotropic (the non-specific beta adrenoceptor agonist isoproterenol), and a non-specific vasodilating (sodium nitroprusside) model drug on ocular fundus pulsations to determine reproducibility and sensitivity of the method. METHODS: In a double masked randomised crossover study the drugs were administered in stepwise increasing doses to 10 male and nine female healthy volunteers. Systemic haemodynamic variables and fundus pulsations were measured at all infusion steps. RESULTS: Fundus pulsation increased during infusion of isoproterenol with statistical significance versus baseline at the lowest dose of 0.1 microgram/min. Neither peripheral vasoconstriction nor peripheral vasodilatation affected the ocular fundus pulsations. CONCLUSIONS: Measurements of fundus pulsations is a highly reproducible method in healthy subjects with low ametropy. Changes of local pulsatile ocular blood flow were detectable with our method following the infusion of isoproterenol. As systemic pharmacological vasodilatation or vasoconstriction did not change fundus pulsations, further experimental work has to be done to evaluate the sensitivity of the laser interferometric fundus pulsation measurement in various eye diseases.

Adrenergic beta-Agonists↗

Influence of angiotensin II on circulating adhesion molecules and blood leukocyte count in vivo.

The mechanism of the beneficial effect of angiotensin converting enzyme inhibitors in patients with myocardial infarction is not clear. Recent in vitro data indicate that angiotensin II (AII) stimulates the expression of adhesion molecules and thus activates leukocyte endothelial interactions. In eight healthy volunteers we investigated the influence of exogenous AII on circulating adhesion molecules and on the blood leukocyte count. A systemically effective and a systemically ineffective dose of AII were administered intravenously over 4 h in a single blind crossover design. Examination of the time course of circulating intercellular and vascular adhesion molecules and E-selectin (cICAM-1, cVCAM-1, cE-selectin-1) in response to the AII infusion revealed increases of up to 11% (especially in cVCAM-1 levels) at single time points, but no significant sustained elevation or trend that can be interpreted as a drug-induced effect. The systemically effective dose, which induced an increase in mean arterial blood pressure from 80 to 108 mmHg (1 mmHg = 133.3 Pa), resulted in a significant increase in blood leukocytes, from 4.8 +/- 0.3 to 5.5 +/- 0.3 g/L (p < 0.05); the systemically ineffective AII dose did not alter blood leukocyte count significantly. Although we did not find an influence of AII on circulating adhesion molecules in vivo, we observed an increase in the blood leukocyte count; thus it may be intriguing to assess whether renin-angiotensin system modulating drugs might exert their favorable effect in ischemic diseases at least in part via an influence on leukocytes.

Adult↗

The effect of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region in healthy young men.

The purpose of this study was to investigate the influence of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region and determine a potential autoregulative capacity of the choroid under these conditions. In a randomized cross-over study 100% O2 and a mixture of 5% CO2 with air was inhaled for 10 min by ten healthy male volunteers on different study days. Fundus pulsations were measured with a recently described laser interferometer. These results were compared to changes in systemic haemodynamics and Doppler-sonographic measurements of the radial artery. The fundus pulsation amplitude significantly decreased during hyperoxia and significantly increased during hypercapnia. These effects on fundus pulsations were stronger in the optic disc region than in the macular region. The systemic parameters showed only minor changes. Hence the amplitudes of fundus pulsations measured during hyperoxia and hypercapnia are assumed to be a consequence of metabolic autoregulative mechanisms. This autoregulative capacity is greater in the optic disc region than in the macular region, implying that the fundus pulsation amplitude in the papilla is influenced by both the choroidal and the retinal circulation.

Adult↗

Is the ECG measure RSh a promising technique for detecting class I antiarrhythmic drug action in men?

Previous animal experiments suggest that the increase in the amplitude from the R-wave to the S-wave (RSh) may be more sensitive than other ECG measures to sodium channel blocking drug actions. We measured RSh of three orthogonal leads at baseline and during intravenous pharmacologic stimulation with adenosine, ajmaline, atropine, disopyramide, isoproterenol, lidocaine, norepinephrine (NE), propranolol, and verapamil in an observer-blinded placebo-controlled study in healthy young men. The short-term reproducibility of RSh was high. Ajmaline increased RSh in the anteroposterior lead, disopyramide in the anteroposterior and vertical lead, and lidocaine in the vertical and horizontal lead, respectively. Isoproterenol increased RSh in the anteroposterior lead; atropine decreased RSh in the vertical lead. The other drugs did not affect RSh significantly. Our data do not support the concept that RSh measure is a more sensitive technique for assessing class I antiarrhythmic drug action in humans, at least in healthy subjects. In addition, our results indicate that changes in autonomic tone may influence RSh measurements.

Adenosine↗

Comparison of non-invasive methods for the assessment of haemodynamic drug effects in healthy male and female volunteers: sex differences in cardiovascular responsiveness.

1. The study was performed to determine the sensitivity and short-term and day-to-day variability of a novel technique based on laser interferometry of ocular fundus pulsations and of non-invasive methods for the quantification of haemodynamic drug effects. An additional aim was to assess sex differences in haemodynamic responsiveness to cardiovascular drugs in male and female healthy volunteers. 2. Ten males and nine females (age range 20-33 years) were studied in a double-blind, randomized, cross-over trial. Simultaneous measurements from systemic haemodynamics, laser interferometry of ocular fundus pulsations, systolic time intervals from mechanocardiography, a/b ratio from oxymetric fingerplethysmography and Doppler sonography of the radial artery were used to describe the haemodynamic effects of cumulative, stepwise increasing intravenous doses of phenylephrine, isoprenaline, sodium nitroprusside and of placebo. 3. Laser interferometry detected the isoprenaline-effects at the lowest dose level of 0.1 micrograms min-1 with a high signal-to-noise ratio. The reproducibility of measurements under baseline was high, no changes were observed after systemically effective doses of phenylephrine or sodium nitroprusside. Systolic time intervals were sensitive and specific for isoprenaline-induced effects, PEP and QS2c-measurements had high reproducibility. Fingerplethysmography proved a sensitive measurement for the detection of the vasodilating effects of sodium nitroprusside, but was not specific, and showed low reproducibility. Measurements from Doppler sonography had lower reproducibility and sensitivity compared with the other applied methods. 4. There was a significant sex difference for several of the haemodynamic parameters under baseline conditions; however, the responsiveness to the drugs under study was not different, when drug effects were expressed as %-change from the baseline. 5. Laser interferometry is a valuable non-invasive, highly sensitive and specific approach for the detection of pulse pressure changes. A battery of non-invasive tests appears useful for the characterization of cardiovascular drugs. Gender differences may not pose a relevant problem for the study of acute haemodynamic effects of cardiovascular drugs.

Adult↗

Effects of recombinant hirudin (r-hirudin, HBW 023) on coagulation and platelet activation in vivo. Comparison with unfractionated heparin and a low-molecular-weight heparin preparation (fragmin).

In a double-blind, randomized, crossover study, we investigated in 15 healthy male volunteers the effects of recombinant (r-) hirudin (HBW 023, 0.35 mg/kg body wt SC), unfractionated heparin (UFH, HeparinNovo; 150 IU/kg body wt SC), and a low-molecular-weight heparin preparation (LMWH, Fragmin; 75 IU/kg body wt SC) on coagulation and platelet activation in vivo by measuring specific coagulation-activation peptides (prothrombin fragment 1 + 2 [F1 + 2], thrombin-antithrombin-III complex [TAT], and beta-thromboglobulin [beta-TG]) in bleeding-time blood (activated state) and venous blood (basal state). In bleeding-time blood, r-hirudin and the heparin preparations significantly inhibited formation of both TAT and F1 + 2. However, the inhibitory effect of r-hirudin on F1 + 2 generation was short-lived and weaker compared with that of UFH and LMWH, and the TAT-to-F1 + 2 ratio was significantly lower after r-hirudin than after UFH or LMWH. Thus, in vivo, when the coagulation system is in an activated state, r-hirudin exerts its anticoagulant effects predominantly by inhibiting thrombin (factor IIa), whereas UFH and LMWH are directed against both factors Xa and IIa. A different mode of action for UFH and LMWH was not detectable. In venous blood, r-hirudin caused a moderate reduction in TAT formation and an increase (at 1 hour) rather than a decrease in F1 + 2 generation. Formation of TAT and F1 + 2 was suppressed at various time points following both UFH and LMWH. There was no difference in the TAT-to-F1 + 2 ratio after r-hirudin and heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myocardial m-[123I]iodobenzylguanidine scintigraphy for the assessment of adrenergic cardiac innervation in patients with IDDM. Comparison with cardiovascular reflex tests and relationship to left ventricular function.

Cardiac imaging using m-[123I]iodobenzylguanidine (mIBG) reflects sympathetic myocardial innervation. In patients with insulin-dependent diabetes mellitus (IDDM), the following were studied: 1) the prevalence of derangements of cardiac autonomic innervation as detected by mIBG scintigraphy in comparison with cardiovascular reflex tests and 2) the relationship between adrenergic cardiac innervation and left ventricular (LV) function. Twenty-four patients with IDDM without overt heart disease were studied after silent coronary artery disease was excluded by 201Tl scintigraphy. Cardiac innervation was evaluated by both mIBG scintigraphy (tomographic imaging) and cardiovascular reflex tests. Systolic (ejection fraction [EF] percentage) and diastolic (peak filling rate [PFR] defined as end-diastolic volumes per second [EDV/s]) LV function were determined by equilibrium radionuclide angiography at rest and during bicycle exercise. mIBG scintigraphy was also performed in 10 control subjects. All control subjects exhibited a normal myocardial mIBG distribution. Among diabetic patients, only six had normal mIBG scans (group 1), whereas 18 had evidence of regional adrenergic denervation (group 2). Reflex tests suggested cardiac autonomic neuropathy in only seven of these patients (P < 0.01 vs. mIBG). All patients had a normal EF at rest. However, group 2 showed an impaired response to exercise as indicated by a smaller increase in EF (5 +/- 6 vs. 13 +/- 5%, P < 0.05) and a lower PFR (5.9 +/- 0.8 vs. 7.3 +/- 1.2 EDV/s, P < 0.01). Myocardial mIBG scintigraphy reveals that in patients with IDDM, sympathetic myocardial dysinnervation is much more common than previously thought. Furthermore, subclinical LV dysfunction is related to derangements of adrenergic cardiac innervation.

3-Iodobenzylguanidine↗

Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man.

In a double-blind, randomized, cross-over study the neutralizing action of protamine towards unfractionated heparin (UFH, 150 U/kg i.v.) and a low molecular weight heparin (LMWH, Fragmin, 100 anti-Xa U/kg i.v.) was investigated in 15 healthy subjects in vitro by measuring activated partial thromboplastin time (APTT), thrombin time (TT) and anti factor Xa activity (anti-Xa) in venous blood and in vivo by determination of prothrombin fragment 1.2 (f1.2) and thrombin-antithrombin III complexes (TAT) in venous blood and in shed blood. UFH and LMWH caused a prolongation of APTT and TT, an increase in anti-Xa and significantly inhibited f1.2 and TAT formation in shed blood, whereas only a minimal effect on TAT and f1.2 formation in venous blood was noted. Administration of 1 mg protamine/100 U UFH resulted in a near complete reversal of APTT, TT and anti-Xa, whereas lower doses (0.25 and 0.5 mg) were less effective. The effects of UFH on f1.2 and TAT generation in shed blood were partially (60-70%) neutralized only by the high dose (1.0 mg). Application of 1 mg protamine/100 anti-Xa U LMWH caused a near complete reversal of both APTT and TT but had only a weak effect on anti-Xa. In shed blood, the effect of LMWH on TAT and f1.2 formation was reversed by protamine only by 14% and 23% respectively. Our data do not support the concept that to reduce the incidence of protamine's potential clinical side effects, the administration of a lower dose of protamine than 1 mg protamine/100 U UFH is justified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

Effects of neuropeptide Y and vasoactive intestinal peptide on human venous smooth muscle in vivo.

The direct and noradrenaline-modulating effects of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) on venous smooth muscle were studied in healthy volunteers employing the dorsal hand vein compliance technique. Local infusions of NPY had no measurable effect on venous tone, but coinfusion of a constant high dose of NPY (242 pmol/min) with noradrenaline caused a 2.9-fold increase in the mean ED50 for noradrenaline. The dilating effect of VIP on preconstricted hand veins was weak, maximal venodilation could not be achieved, because systemic side effects occurred at submaximally venodilating doses. Coinfusion of noradrenaline with a weakly venodilating, constant dose of VIP (93.2 pmol/min) caused a 0.5-fold decrease in the sensitivity for noradrenaline. Although functional interactions between NPY or VIP and noradrenaline could be demonstrated, the dosages of the peptides required were high. Thus our results indicate that neither NPY nor VIP exert a major direct or noradrenaline-modulating effect on human veins.

Adult↗

Studies on the effect of short-term oral dihydroergotamine and troxerutin in patients with varicose veins.

OBJECTIVE: To evaluate the clinical efficacy and pharmacologic effects of dihydroergotamine and troxerutin on varicose veins. METHODS: A double-blind, randomized, placebo-controlled parallel-group study was conducted in 53 patients with primary varicose veins. Patients received either a fixed combination of 3 mg dihydroergotamine and 300 mg troxerutin three times a day or placebo for 3 weeks. Symptomatic improvement was assessed by a self-assessment score, venocontracting effects on a varicose vein were quantified by the venous compliance technique (VCT), and changes in venous dysfunction were measured by digital photoplethysmography (DPPG). RESULTS: A significant reduction (p < 0.01) of subjective symptoms was observed in both groups. Results from VCT and DPPG after the therapy with dihydroergotamine and troxerutin or placebo were not significantly different (p > 0.05) from pretreatment values. Furthermore, no significant intergroup difference was observed when the before- and after-therapy differences of values of the self-assessment scores (VCT and DPPG) were compared. CONCLUSION: In our study, 3 weeks of treatment with a fixed drug combination of 3 mg dihydroergotamine plus 300 mg troxerutin three times a day had no measurable effect compared with placebo on any of the evaluated end points.

Adult↗

In vivo study of the effect of exogenous estradiol on alpha-adrenoceptor responsiveness of human veins.

Based on previous experimental and epidemiologic findings, we hypothesized that 17 beta-estradiol (E2) could decrease the alpha-adrenergic responsiveness in venous smooth muscle cells (VSMC), thereby decreasing venous tone and contributing to the pathogenesis of varicose veins. To test this hypothesis, the effect of an acute increase in E2 serum concentrations on venous alpha-adrenergic responsiveness to norepinephrine (NE) was studied in young healthy men. We conducted a double-blind, randomized, placebo-controlled cross-over study in 23 male volunteers; 96 +/- 2 h after a single intramuscular (i.m.) injection of 10 mg estradiol valerate or placebo, we quantified the pharmacologic effects of estradiol on alpha-adrenergic responsiveness of superficial hand veins by venous compliance technique (VCT) and on resting blood pressure (BP). After administration of estradiol, E2 serum levels increased 9.97 +/- 7.54-fold (mean +/- 1 SD, p < 0.001) to within the range of premenopausal preovulatory women. No significant difference was observed in mean dose of NE required for half-maximal venoconstriction (ED50, p = 0.224), however, or in the maximal effect of NE (Emax, p = 0.796) after administration of E2 as compared with placebo. A significant difference in diastolic BP (DBP) (p = 0.039) was observed after E2 administration (64.6 +/- 7.7 mm Hg) as compared with placebo (68.3 +/- 7.6 mm Hg); BP (SBP) was not affected (p = 0.786). Our findings do not support the concept that E2 reduces alpha-adrenoceptor responsiveness of SMC in superficial veins.

Adult↗

Effects of 17 beta-estradiol on circulating adhesion molecules.

The effects of 17 beta-estradiol (E2) on the serum levels of the circulating endothelial-leukocyte, intercellular, and vascular adhesion molecules [ELAM-1, ICAM-1 (CD54), and VCAM-1] were evaluated in healthy male volunteers after single im injection of 10 mg E2 valerate. In addition, a time course of the effects of E2 on circulating adhesion molecules (AMs), cortisol serum levels, differential blood counts, and surface expression of the lymphocyte function-associated antigen-1 (CD11a/CD18), CD3, CD4, CD19, and CD25 on leukocytes was studied in another group of volunteers. A 5% decrease in circulating ICAM-1 (P = 0.045 vs. placebo) was found when a single time point (96 h after E2 injection) was studied. However, this decrease was smaller than the intrasubject (day to day) variability observed, and there was no consistent and time-dependent effect of E2 on circulating AMs. Circulating neutrophils increased 2.3-fold over baseline after E2 treatment (P = 0.0008 vs. placebo). The mean coefficients of variation for the intrasubject (day to day) and intersubject variability of circulating AMs were between 5.4-7.5% and 20-29%, respectively. Our findings indicate that the effect of E2 on circulating AMs is not distinguishable from the intrasubject variability observed after placebo treatment. Thus, an effect of E2 on adhesion molecules is unlikely to contribute to the antiatherogenic-cardioprotective effect of E2. The pronounced E2-mediated increase in neutrophils deserves further studies to elucidate its (patho-)physiological implications.

Adult↗

Hypergranular acute lymphoblastic leukemia (ALL). Report of a case and review of the literature.

We report a case of adult acute lymphoblastic leukemia (ALL) with myeloid-like hypergranulation of blast cells. Like most of the "granular" ALLs described in the literature, the blast cells had L2 morphology and exhibited a common-ALL immunologic phenotype. The clinical findings at diagnosis were unremarkable. Cytogenetic analysis showed a 46XY karyotype. Molecular genetic analysis revealed T-cell receptor (TCR) gamma and immunoglobulin heavy chain rearrangements; no rearrangement was found at the TCR beta gene locus. The polymerase chain reaction (PCR) for the BCR-ABL translocation was negative. The clinical course of the patient was uncomplicated. On standard ALL treatment protocol he achieved complete remission (CR) within 4 weeks, and he is currently disease free 8 months after diagnosis. The case contributes well-documented data to the characterization of adult "granular" ALL, with special regard to changes at the molecular genetic level.

Adult↗

The role of iodine-123-Tyr-3-octreotide scintigraphy in the staging of small-cell lung cancer.

The purpose of this study is to investigate the role of 123I-Tyr-3-octreotide scintigraphy in staging small-cell lung cancer (SCLC), its efficacy for the discrimination of limited and extensive disease stages and its regional sensitivity for different metastatic locations. Twenty patients with histologically confirmed SCLC and 50 radiologically staged tumors sites were investigated by an imaging protocol including dynamic (0-30 min p.i.), static (30 min, 90 min, 4 hr, 24 hr p.i.) and SPECT (90 min p.i.) studies. The primary tumor site was visualized in 84%, whereas the best delineation was noted in early planar (15-30 min p.i.) and SPECT studies, due to a rapidly decreasing tumor-to-background ratio. Lymph node metastases were seen in 73%, but SPECT was needed for anatomical localization. All three adrenal metastases could be identified in sequential planar images. One clinically unsuspected brain metastasis was seen, whereas a second clinically overt metastasis was not visualized. The global and regional sensitivity for liver and bone metastases was unsatisfactory. In summary, 78% (7/9) of the patients with extensive disease were correctly identified by scintigraphy alone. We conclude that 123I-Tyr-3-octreotide scintigraphy is a substantial tool in the staging work-up of SCLC if it is performed initially to allow fast identification of patients with extensive disease stages and save additional radiological or invasive examinations. Yet, 123I-Tyr-3-octreotide scintigraphy cannot substitute liver sonography or conventional bone scanning in patients who have no scintigraphic evidence of distant tumor spread.

Carcinoma, Small Cell↗

Effects of serotonin and noradrenaline on superficial hand veins in patients with primary hypertension and in healthy volunteers.

In vitro and animal experiments suggest that a constitutional increase in vascular responsiveness to serotonin (5-HT) may play a role in the development of essential hypertension. We have studied the potential alterations in vascular responsiveness to the direct and catecholamine-potentiating effects of exogenous 5-HT in patients with essential hypertension, by comparing in vivo responsiveness of superficial hand veins to local infusions of 5-HT or to coinfusions of 5-HT and noradrenaline in unmedicated hypertensive patients and in healthy control subjects. The dorsal hand vein compliance technique was employed. There was no significant difference between patients and control subjects in the maximal 5-HT-induced venoconstriction or in the doses required for half-maximal venoconstriction (ED50) for 5-HT. Coinfusions of a constant dose of 5-HT caused a significant leftward shift in the dose response curve for noradrenaline as compared with noradrenaline alone. This was indicated by a 9.7 +/- 13.7 fold and a 10.4 +/- 13.8 fold increase in the ED50 for noradrenaline in the patient and control groups, respectively (p = 0.89 between study groups). Our results argue against a generalized increase in responsiveness to the direct or catecholamine-potentiating effect of 5-HT in vivo in vascular smooth muscle, associated with hypertension.

Adult↗