Dysgnathia, orthognathic surgery and spinal posture.

The aim of this study was to evaluate the spine by video rasterstereography before and after orthognathic surgery. Twenty-nine patients (17 patients with a skeletal class III, 7 patients with a skeletal class II, and 5 patients with mandibular asymmetry) were evaluated preoperatively and 1 year postoperatively. Video rasterstereography is a method of back surface measurement and shape analysis using the moire topography. Orthognathic surgery in cases of class III and asymmetry did not lead to significant changes in body posture. In class II patients it led to some changes in body posture, but without orthopaedic consequences. It is concluded that orthognathic surgery causes minimal or no change in body posture.

Verification of a canine model of transient exercise induced myocardial dysfunction: antianginal effects of flestolol, an ultra short acting beta adrenoceptor antagonist.

STUDY OBJECTIVE - The aim of the study was to verify the reproducibility of a canine model of treadmill exercise induced regional myocardial dysfunction designed to mimic exertional angina pectoris in man. DESIGN - Dogs trained to run on a treadmill were chronically instrumented with a microtip manometer in the left ventricle, a hydraulic occluder around the circumflex branch of the left coronary artery, two pairs of crystals for sonomicrometry, and arterial and venous catheters. Experiments were started 10 d after surgery, when the animals were submitted to seven treadmill exercise cycles, each of 3 min, with a 7 min recovery period. Ischaemia was adjusted so as not to impair regional function at rest but to produce progressive dysfunction with increasing work load. Flestolol (1 microgram.kg-1.min-1) was infused intravenously during the third and fourth exercise cycle. SUBJECTS - Six mongrel dogs, 13.5-29.5 kg, were used. MEASUREMENTS and RESULTS - Flestolol caused a marked reduction in the exercise induced increase in left ventricular positive dP/dtmax, and minor reductions in heart rate and systolic blood pressure, resulting in a decrease in myocardial oxygen demand and an improvement in regional function in the circumflex area of the left coronary artery. The functional improvement was transient and disappeared entirely after termination of flestolol infusion. CONCLUSIONS - The results show that flestolol is beneficial in conditions of limited coronary reserve and exercise induced myocardial dysfunction. The fact that the extent of regional myocardial dysfunction was comparable before and after flestolol infusion confirms the stability and usefulness of this experimental model in the evaluation of antianginal drugs.

The effects of nitroglycerin on regional myocardial contractile dysfunction produced by treadmill exercise or isoprenaline stimulation in dogs.

1. To compare different methods of cardiac stress testing that are clinically applied in the management of coronary heart disease, 2 groups of dogs each were chronically instrumented and subjected to treadmill exercise or isoprenaline infusion in the presence of coronary stenosis. 2. It was of interest to determine differences in haemodynamic and regional myocardial contractile parameters, the response to antianginal therapy (nitroglycerin 15 micrograms kg-1 15 min-1, i.v.), and, in particular, whether this response differed according to the mode of cardiac stimulation, i.e. treadmill exercise or isoprenaline infusion. 3. After stenosis of the circumflex branch of the left coronary artery which affected resting myocardial function only minimally, treadmill exercise or isoprenaline infusion induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular end-diastolic pressure and left ventricular dp/dtmax were registered and myocardial oxygen demand was calculated. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4. Treadmill exercise led to an increase in systolic arterial and left ventricular end-diastolic pressure. In contrast, isoprenaline-induced stimulation led to a decrease in diastolic arterial and left ventricular end-diastolic pressure. Regional contractile function in the critically underperfused area showed a deterioration during both modes of stress. Nitroglycerin completely abolished stress-induced contractile dysfunction only in the group where treadmill exercise was employed for stimulation. 5. The inability of nitroglycerin to prevent myocardial dysfunction in the isoprenaline group may be due to exhaustion of the arterial and/or venous vasodilator potency of nitroglycerin in the presence of adrenoceptor vasodilatation induced by isoprenaline. 6. These findings indicate that clinical antianginal drug testing and the evaluation of the course of disease in patients with coronary heart disease may be highly dependent on the test method chosen.

Serum antibodies against the heat shock protein 60 are elevated in patients with osteosarcoma.

Osteosarcoma is the most frequent malignant bone tumor, mainly occurring in the second and third decade of life. Diagnosis is limited to clinical symptoms, radiology and histology, but so far no diagnostic laboratory tests are available. Heat shock proteins (hsp), highly conserved proteins performing vital intracellular chaperoning functions and preventing cells from death, have been shown to be involved in tumor immunity. We analyzed 75 sera from 23 patients with high-grade osteosarcoma, 8 patients with chondrosarcoma, 10 patients with Ewing's sarcoma, 5 patients with soft tissue sarcoma, 11 patients with benign bone tumors at the time of diagnosis and from 18 healthy controls with an indirect one-site enzyme linked immunosorbent assay (ELISA) for the presence of anti-hsp60 and 70 antibodies. In these assays 10/23 osteosarcoma patients (43%) had anti-hsp60 antibodies with a mean +/- S.D. titer of 0.382 +/- 0.243 U/ml. Only one of the 18 healthy controls (1/18, 5.6%; titer 0.22 U/ml), two of the Ewing's sarcoma patients (2/10, 20%; titer 0.2 +/- 0.09 U/ml), two of the patients with a benign bone tumor (2/11, 18%; titer 0.22 +/- 0.16 U/ml) and one of the chondrosarcoma patients (1/8, 12.5%; titer 0.14 U/ml) were positive, whereas all others, including all soft tissue sarcomas were negative throughout. Anti-hsp60 antibodies in patients with osteosarcoma are therefore significantly increased (p < 0.05). 19/23 (83%) of osteosarcoma biopsy specimens expressed hsp60 immunohistochemically and all specimens from patients with a positive anti-hsp60 serum titer expressed hsp60. The level of the anti-hsp60 antibodies did not correlate with clinical parameters such as response to preoperative chemotherapy, duration of symptoms, age, gender, tumor size, serum alkaline-phosphatase levels and metastases. Although no difference in anti-hsp70 antibodies could be observed between sera from patients and healthy controls, a positive correlation was found for the presence of anti-hsp70 serum antibodies and lung metastases at the time of diagnosis in osteosarcoma patients. These data suggest an increase of anti-hsp60 antibodies at the time of first diagnosis of osteosarcoma. These findings should therefore give rise to further investigations on a group of new markers for the diagnosis of osteosarcoma.

Cardiovascular and side effects of flesinoxan in conscious hypertensive dogs. Modulation by prazosin.

Previous studies on anaesthetized animals indicate that flesinoxan exerts hypotensive effects via stimulation of central 5-HT1A receptors. The purpose of the present study was to investigate the cardiovascular and side effects of flesinoxan in conscious, renal hypertensive dogs at rest and during exercise. Animals were pretreated with prazosin (2.5 or 7.5 nmol/kg) to verify a reduction of dose-dependent side effects, as occurred in normotensive dogs. A decrease in blood pressure without reflex tachycardia was observed only with the lower dose of flesinoxan (0.1 mumol/kg). The higher dose (0.2 mumol/kg) led to an increase in blood pressure and heart rate. The increase in heart rate during exercise was diminished by 0.2 mumol/kg flesinoxan. Pretreatment with prazosin resulted in an additive hypotensive effect at rest. Side effects, occurring primarily after the higher dose of flesinoxan, were not influenced by prazosin. It is concluded that flesinoxan is not likely to be efficacious in antihypertensive therapy.

Cardiac and hemodynamic effects of the selective bradycardic agent KC 8857 during exercise-induced myocardial ischemia.

The effects of an in vitro bradycardic agent without negative inotropism, KC 8857 (3,7-di-(cyclopropylmethyl)-9,9-tetramethylene-3,7-diazabicyclo-[3.3.1]- nonane dihydrochloride), were tested in chronically instrumented dogs in a model of exercise-induced myocardial ischemia. KC 8857 was i.v. infused during critical stenosis of the circumflex branch of the left coronary artery which led to exercise-induced myocardial dysfunction. KC 8857 caused a decrease in heart rate, left ventricular dp/dtmax and calculated myocardial oxygen demand at rest and during exercise. Since positive dp/dtmax values at a given heart rate were not altered by KC 8857 it may be assumed that myocardial function was restored mainly by the decrease in heart rate.

Haemodynamic and metabolic effects of xamoterol in exercising dogs.

The effects of xamoterol on the haemodynamic adaptation to graded treadmill exercise were evaluated during five subsequent cycles in chronically instrumented dogs. At rest xamoterol, 0.2 mg/kg i.v., preferentially showed a positive inotropic effect, whereas 1 mg/kg i.v. also exhibited a marked chronotropic effect. The cardiac output and left ventricular power increased dose dependently. The mean left atrial pressure and total peripheral resistance decreased concomitantly. Xamoterol did not produce a noteworthy decrease in heart rate or positive dp/dtmax during exercise, even at a dosage of 1 mg/kg. A beta-adrenoceptor blocking effect could only be seen from the diminution of the exercise-induced changes in heart rate, dp/dtmax, cardiac output, left ventricular power and total peripheral resistance. Determination of the blood glucose, lactate and pyruvate levels before the start of each exercise cycle revealed that the drug induced a decrease in blood glucose and an increase in blood pyruvate. Thus, xamoterol exerted a dose-dependent sympathomimetic effect in dogs at rest. However, there was little evidence for a beta-adrenoceptor blocking action even at higher work loads, although preliminary experiments in conscious dogs showed that xamoterol shifted the isoprenaline dose-response curve to the right by a factor of 1.31 (0.2 mg/kg) and 3.05 (1 mg/kg).

Cardiovascular effects of flesinoxan in anaesthetized and conscious dogs.

Stimulation of 5-HT1A receptors is known to decrease the arterial blood pressure in anaesthetized rats, cats and dogs. We investigated the hypotensive activity of flesinoxan (0.1 + 0.2 + 0.7 mumol/kg), a 5-HT1A-receptor agonist, in dogs anaesthetized with either morphine and pentobarbital or enflurane and also in the conscious state. Flesinoxan led to a decrease in arterial blood pressure in anaesthetized, but not in conscious dogs. In the conscious state the marked increase in heart rate, which can be taken as an indicator of sympathetic tone, may have masked the consequences of vasodilatation. These different haemodynamic responses to flesinoxan may be dependent on side effects of the drug in the conscious dogs, in particular hyperventilation and salivation combined with anxiety, and on the magnitude of the decrease in baroreceptor reflex activity during anaesthesia with morphine and pentobarbital on the one hand and enflurane on the other hand.

Simultaneous assessment of cardiac output with pulsed Doppler and electromagnetic flowmeters during cardiac stimulation.

The aim of this study was to test the accuracy of cardiac output assessment by Doppler and electromagnetic flowmetry in dogs during states of (1) marked enhancement in cardiac output, which was obtained by means of either isoprenaline infusion or treadmill exercise, or (2) reduction in cardiac output obtained by administration of phenylephrine. Additionally, in vitro comparisons were undertaken between Doppler and electromagnetic flow-probes and assessment of flow by direct volumetric measurement. These in vitro experiments showed a good correlation between timed volume collections and electromagnetic flow assessment up to high flow velocities. Doppler flow measurements underestimated the flow at high velocities. In both the resting dog and after phenylephrine, that is, at states with low heart rate and cardiac output, the waveforms of electromagnetic flow and Doppler velocity were similar for both phasic and mean flow, respectively. During states of cardiac stimulation Doppler flow showed a decrease in maximum velocity in the ascending aorta. Due to this decrease in peak flow velocity, mean Doppler blood flow did not increase despite of increased heart rate. This result cannot be explained on the basis of the deviation of Doppler measurements at high velocities in the in vitro experiments. Although our results are in contradiction with earlier studies, electromagnetic assessment seems to be more reliable in blood flow measurements in the ascending aorta. Hence, Doppler flow measurements should not be used uncritically for such quantitative flow assessment in large vessels as determination of cardiac output.

Detection of orthopaedic prostheses at airport security checks.

We studied the detection of joint replacements at airport security checks in relation to their weight, using two types of detector arch. A single-source, unilateral detector showed different sensitivities for implants on different sides of a test subject. All implants weighing more than 145 g were detected by one of the arches. The degree of detection was directly related to the logarithm of the weight of the prosthesis in patients, with a linear correlation (r2 = 0.61). A bilateral arch detected all prostheses weighing over 195 g. With their usual sensitivity settings many joint replacements were detectable; an identification pass containing the site and weight of such prostheses would help to avoid the need for body-search procedures.

[Cardiovascular pharmacology. An example of the need of clinically relevant pharmacological research]. / Herz- und Kreislaufpharmakologie. Ein Beispiel der Notwendigkeit kliniknaher pharmakologischer Forschung.

Like all other scientific disciplines, preclinical pharmacological research is subject to permanent changes. New measuring devices and the possibility of continuous on line data acquisition have markedly influenced basic research in this field. Another aim of modern cardiovascular pharmacology is the testing of promising drugs in clinically relevant animal models of disease, particularly under conditions, referring to the everyday situation in patients, e.g. physical activity. Investigations carried out in this way allow an exact assessment of the clinical efficacy of new drugs, and are, thus, clearly indispensable, also from the ethical point of view, before primary evaluation of the drug in man.

Age predicts outcome of high-tibial osteotomy.

This study compares the predictive value of age at surgery in high tibial osteotomy. Twenty-seven high-tibial osteotomies in patients who are 65 years or older (mean age at surgery 68+/-4 years, follow up 12+/-2 years) were compared to 67 osteotomies in patients younger than 65 years (mean age at surgery 56+/-6 years, follow up 13+/-3) with respect to the outcome by Cox regression analysis. Failure, i.e. endpoint, was defined as implantation of a knee endoprosthesis and assessed by Kaplan-Meier analysis. There is a significantly higher risk for failure of high tibial osteotomies in patients of 65 years or more compared to younger patients (failure rate 38.4+/-11.3% vs. 23.1+/-5.8%) resulting in a relative risk of 1.5 (P=0.0461). The hazard of failure increased 7.6% per year of age. We conclude that in regard to the increasing risk of failure per year of age and the higher failure rate in older patients, high-tibial osteotomy should not be performed on patients older than 65 years.

[Minimally invasive therapy of painful osteoporotic vertebral fractures]. / Minimal-invasive Therapie osteoporotischer Wirbelkörperfrakturen.

INTRODUCTION: Osteoporosis is the most common bone disease. Due to an increase of the older population an higher impact of osteoporosis and its treatment can be expected. BACKGROUND: Painful osteoporotic vertebral fractures result in an increased morbidity and mortality. Standard treatment of painful osteoporotic vertebral fractures comprises analgetics, bed rest and, if needed, orthotics. METHOD: By mere augmentation of the vertebra with polymethylmet acrylate (PMMA), the so called "vertebroplasty" a good pain reduction and increase in function and quality of life can be achieved. With the technique of kyphoplasty (Kyphon) it is feasible to correct a kyphotic deformity. Inflatable balloons are introduced to the vertebra to lift the endplates. The created cavity is filled with bone cement (PMMA). DISCUSSION: Kyphoplasty is able to correct osteoporosis induced kyphotic deformity. Compared to the technique of vertebroplasty, kyphoplasty is less risky but is more time consuming and more expensive. Time will show whether the expected advantage of deformity correction will result in a better outcome for the patient, e. g. in a lower incidence of refractures.

[Minimal invasive stabilization of osteoporotic vertebral compression fractures. Methods and preinterventional diagnostics]. / Minimal-invasive Stabilisierung osteoporotischer Wirbelkörpereinbrüche. Methodik und präinterventionelle Diagnostik.

PURPOSE: Minimal invasive stabilizations represent a new alternative for the treatment of osteoporotic compression fractures. Vertebroplasty and balloon kyphoplasty are two methods to enhance the strength of osteoporotic vertebral bodies by the means of cement application. MATERIAL AND METHODS: Vertebroplasty is the older and technically easier method. The balloon kyphoplasty is the newer and more expensive method which does not only improve pain but also restores the sagittal profile of the spine. RESULTS: By balloon kyphoplasty the height of 101 fractured vertebral bodies could be increased up to 90% and the wedge decreased from 12 to 7 degrees. Pain was reduced from 7.2 to 2.5 points. The Oswestry disability index decreased from 60 to 26 points. This effect persisted over a period of two years. Cement leakage occurred in only 2% of vertebral bodies. Fractures of adjacent vertebral bodies were found in 11%. CONCLUSION: Good preinterventional diagnostics and intraoperative imaging are necessary to make the balloon kyphoplasty a successful application.

Cardiac and hemodynamic effects of diltiazem during exercise-induced myocardial dysfunction in dogs.

The effects of diltiazem were tested in chronically instrumented dogs in a model of exercise-induced myocardial dysfunction. Since various bradycardiac agents have beneficial effects on myocardial function during ischemia, it was of interest to find out how a decrease in afterload, possibly combined with a decrease in myocardial oxygen demand, influences dysfunction. Therefore, diltiazem (1 mg/kg i.v.) was tested during critical stenosis of the circumflex branch of the left coronary artery, which led to exercise-induced myocardial dysfunction. At rest, diltiazem causes a reflex increase in heart rate. During exercise, a decrease in heart rate and hence in myocardial oxygen demand was neutralized by a decrease in arterial blood pressure and hence a lowered myocardial perfusion pressure. Therefore, systolic shortening in the ischemic area improved neither at rest nor during exercise after diltiazem.

Esmolol: effects on isoprenaline- and exercise-induced cardiovascular stimulation in conscious dogs.

Esmolol, a recently developed ultra-short acting beta-adrenoceptor blocking agent, was evaluated in 12 conscious chronically instrumented dogs with intact autonomic reflexes. The significance of its beta 1-adrenoceptor selectivity was examined at various cardiovascular activation levels established by either incremental isoprenaline infusion or graded treadmill exercise. The observed parameters were heart rate, systolic and diastolic arterial blood pressure, left ventricular dp/dtmax, and left ventricular end-diastolic pressure. Intravenous infusion of esmolol (25 and 250 micrograms.kg-1.min-1) led to a dose-dependent reduction of the isoprenaline-induced increase in positive dp/dtmax. The concomitant increase in heart rate was suppressed to a lesser extent. Characteristically of a beta 1-selective agent, esmolol had only a slight effect on the isoprenaline-induced reduction in diastolic blood pressure. The impact of esmolol on exercise-induced hemodynamic activation was much smaller. Exercise-induced increase in positive dp/dtmax was more sensitive to beta-adrenoceptor blockade than the concomitant increase in heart rate. Diastolic blood pressure was not influenced significantly. beta-Adrenoceptor blockade was virtually reversed within 20 min of discontinuation of esmolol infusion.

Effects of flestolol, an ultra-short acting beta-adrenoceptor antagonist, on hemodynamic changes produced by treadmill exercise or isoprenaline stimulation in conscious dogs.

The beta-blocking activity of flestolol was established during increasing isoprenaline infusions and during graded physical exercise in conscious, chronically instrumented dogs. After a control cycle, flestolol was infused at three doses (1, 2.67, and 10 micrograms/kg/min). Flestolol has an extremely short half-life, demonstrated by an 83% loss of effect within 25 min. Thus, flestolol allows easy titration of the effect, which might be a valuable property for its use in the treatment of critically ill patients. Due to the difference between pure beta-adrenergic stimulation and the much more complex regulation of circulation during exercise, the hemodynamic response to flestolol elicited marked differences between both set ups. Flestolol shifted the dose-response curves of isoprenaline-induced changes in heart rate, positive left ventricular dp/dtmax, and diastolic arterial pressure dose dependently to the right, while its main effect during exercise was a decrease in positive left ventricular dP/dtmax. Thus, testing of beta-adrenoceptor blockers using isoprenaline-induced tachycardia leads to an overestimation of potency and therefore is not appropriate to predict the clinical efficacy of these drugs to prevent stress- or exercise-induced increases in heart rate and hence myocardial oxygen-demand.

Influence of alpha 1-adrenoceptor blockade and/or 5-HT1A agonism on blood pressure and heart rate at rest and during exercise in hypertensive dogs.

1. Antihypertensive effects resulting from alpha 1-adrenoceptor blockade and stimulation of central nervous 5-HT1A receptors were compared with the effects arising from stimulation of 5-HT1A receptors alone during arterial hypertension. 2. Urapidil and 5-methyl-urapidil were less effective in decreasing arterial blood pressure than the lowest dose of the selective 5-HT1A receptor agonist, flesinoxan. After the higher dose of urapidil, a certain dampening of barareceptor reflex was found which was also seen with flesinoxan. 3. Flesinoxan was the only drug which did not reduce the exercise-induced increase in systolic arterial blood pressure. 4. Stimulation of 5-HT1A receptors alone, which is assumed to occur with flesinoxan, exerted antihypertensive activity only at low doses, without inducing reflex tachycardia at rest. 5. Only the combined effects of alpha 1-adrenoceptor blockade and 5-HT1A receptor stimulation, as assumed to occur with urapidil and 5-methyl-urapidil, lead to both a decrease in arterial blood pressure at rest and during exercise.

Oral N(G)-nitro-L-arginine in conscious dogs: 24 hour hypertensive response in relation to plasma levels.

Haemodynamic changes after oral administration of 30 mg/kg N(G)-nitro-L-arginine (L-NNA) were studied in conscious chronically instrumented mongrel dogs throughout a 24 h observation period in order to evaluate the long-term efficacy of L-NNA-induced inhibition of endothelium-dependent relaxation and its relation to plasma L-NNA level. Diastolic blood pressure remained elevated for the entire 24 h observation period, but systolic blood pressure was raised only up to the 6 h value. The hypertensive response was accompanied by bradycardia. The increase in blood pressure and the plasma L-NNA level both reached their maxima at 3 h. The plasma L-NNA level at the end of the observation period was diminished by only 21.7% with respect to the maximum increase, whilst the maximum increase in mean arterial blood pressure was attenuated by 72.2% at 24 h. These data show a dissociation between plasma L-NNA level and the respective blood pressure.