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Biomedical subjects

H Hirche

Publications and source records attributed to H Hirche.

At least 73 records · Page 4Linked to original sources

[Ambulatory prevention of thrombosis with low molecular weight heparin in plaster immobilization of the lower extremity].

Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled, randomized and prospective study on patients with minor injuries incidence of DVT in conservatively treated out-patients with plaster cast immobilisation of the leg was 3.9% in the control group (n = 126) without prophylaxis. By s.c. self-application of LMV heparin once daily the number of DVT in the prophylaxis group (n = 115) was reduced to 0. No severe side effects of NMH were observed. We conclude that thromboprophylaxis with LMW heparin once daily up to now conspiciously reduced the risk of DVT in outpatients with plaster cast immobilisation of the leg.

Adolescent↗

Novel generation of hormone receptor specificity by amino terminal processing of peptide YY.

The physiological significance of multiple Y receptors has not been determined since until recently only one form of endogenous agonists was known, namely PYY1-36 and NPY1-36. Recently, a new molecular form of PYY was characterized as des(Tyr-Pro)PYY (PYY3-36 or PYY-II). Its ability to interact at various Y receptors was not characterized. Analytical chromatography of fresh canine colon extracts shows two peaks of immunoreactivity eluting in the positions of PYY-II and PYY1-36 (PYY). PYY-II was about 40% of the total PYY immunoreactivity indicating that it is one of the major forms of PYY expressing its biological activity. It is shown that PYY-II will not displace label from the Y1 receptors found on a human neuroblastoma cell line. It is further shown that PYY-II is as potent as PYY for the inhibition of pancreatic secretion, which must occur through Y2 receptors. The enzymatic removal of Tyr-Pro from PYY to form PYY-II must therefore regulate the relative expression of a non-selective agonist (PYY) to a highly selective Y2 agonist (PYY-II). Amino terminal processing of PYY represents a novel type of regulation of peptide hormone specificity. It has important biological implications for PYY and potential relevance for other peptide hormone receptor systems.

Animals↗

Characteristics at entry of children with severe primary vesicoureteral reflux recruited for a multicenter, international therapeutic trial comparing medical and surgical management. The International Reflux Study in Children.

A total of 532 children, 401 from Europe and 131 from the United States, was recruited into an international multicenter study comparing the results of medical and surgical treatment of children with international grade III or IV vesicoureteral reflux and urinary tract infection. Patient age was less than 11 years, glomerular filtration rate was greater than 70 ml. per minute per 1.73 m.2 and there was no obstruction, renal malformation, previous urinary tract surgery or neuropathic bladder. A total of 80 children had less than grade III vesicoureteral reflux on a second pre-entry cystourethrogram required by the European protocol, and they were followed separately as a sideline group. At entry the age distribution, history of urinary tract infection and proportion of children with grade IV vesicoureteral reflux were similar in Europe and the United States. Of the European and United States children 48% and 54% had renal scarring, and 17% and 14% had parenchymal thinning, respectively. In each group renal length and planimetric area were normal in two-thirds and 5% had small kidneys (<2 standard deviations from normal). Differences included sex distribution (24% boys in Europe and 11% in the United States group), the proportion of children in whom vesicoureteral reflux was previously known (18% Europe and 69% United States) and the proportion of children with bilateral reflux (77% Europe and 57% United States). Randomization and stratification for treatment were successful.

Child↗

A prospective randomized comparison of single-agent interferon (IFN)-alpha with the combination of IFN-alpha and low-dose IFN-gamma in chronic myelogenous leukaemia.

In patients with previously untreated chronic myelogenous leukaemia (CML) the efficacy of single-agent interferon (IFN)-alpha at an initial dose of 4 x 10(6) U/m2 (arm A) was compared with the combined administration of the identical dose IFN-alpha plus a total dose of 50 micrograms IFN-gamma (arm B). 51 patients entered this study between April 1987 and October 1989; the analysis was performed in March 1991 and was focused on response rates and toxicity. 54% of patients on arm A and 56% of arm B patients attained haematologic remission. 29% of patients on arm A and 24% of arm B patients had partial haematologic remission. A decrease in Philadelphia chromosome (Ph)-positive metaphases of more than 10% was only seen in patients who had achieved complete haematologic normalization. In 21% of patients on arm A and 20% of arm B patients, the percentage of Ph-positive cells declined to less than 35%. Toxicity was different between the two study groups with more pronounced hepatotoxicity observed in patients treated with IFN-alpha alone. Among the patients receiving both IFNs, alpha and gamma, there were 2 fatal infectious complications. This serious toxicity in conjunction with lack of a clinically meaningful difference between the two treatment schedules has led us to terminate the study. In conclusion, the addition of low-dose IFN-gamma failed to improve the efficacy of IFN-alpha in this study.

Antineoplastic Combined Chemotherapy Protocols↗

Anoxia induces time-independent K+ current through KATP channels in isolated heart cells of the guinea-pig.

1. Isolated ventricular heart cells of the guinea-pig were exposed to anoxia (PO2 < 0.1 Torr) which induced a time-independent K+ current. This current was studied with the patch clamp technique in the whole-cell and cell-attached configuration. 2. The latency until anoxia-induced changes of whole-cell current developed was distributed exponentially (mean 10.5 min; n = 41). The current was abolished within 2-4 s of reoxygenation. 3. The reversal potential of the anoxia-induced change of whole-cell current at 5.4 and 15 mM [K+]o was -82 and -61 mV, respectively. 4. Analysis of current noise in whole-cell current during the phase of the slow development of the anoxia-induced current yielded a slope conductance of unitary currents of 8.1 pS (5.4 mM [K+]o) which is far below the 30 pS of KATP channels in inside-out patches with no Na+ and Mg2+ in the bath. 5. Reduced unitary current induced by anoxia was recorded in single-channel measurements with 10.4 mM-K+ in the pipette. 6. Using 150 mM-K+ in the pipette, anoxia caused unitary inward currents with a slope conductance of 83 pS. The open probability of the channels (P(o)) reached maximum values between 0.6 and 0.95. The channels closed within 1-3 s of reoxygenation. 7. At voltages between -85 and -45 mV and maximum P(o), open time histograms were dominated by a fast exponential (tau 01 = 0.55 +/- 0.21 ms, mean +/- S.D.) and one or two slow exponentials. 8. Voltage ramp experiments showed that single-channel currents were slightly rectifying in the inward direction. 9. Glibenclamide (1 microM) reversibly blocked the anoxia-induced whole-cell and single-channel currents. 10. It is concluded that during anoxia it is only KATP channels which open by a sufficient decrease of submembrane ATP levels.

Action Potentials↗

[Randomized double-blind study of therapy of sudden deafness. Low molecular weight dextran + naftidrofuryl vs. low molecular weight dextran + placebo].

Eighty patients with idiopathic sudden deafness existing no longer than 10 days were included in a prospective randomized double-blind study. Patients were treated for 10 days with infusions of either 10% low-molecular weight dextran or the combination of low-molecular weight dextran with naftidrofuryl. Before treatment and after 10 days hearing loss in the affected ear was determined at 0.5, 1, 2, 3, 4 and 6 kHz. The mean hearing loss was then calculated as the average from these values. During monotherapy with low-molecular weight dextran the mean hearing loss decreased from 40 to 27 dB compared to 38 to 17 dB when naftidrofuryl treatment was added (p < 0.01 between groups). A significant benefit of naftidrofuryl on hearing loss was also found at frequencies between 0.5 and 3 kHz. Furthermore, patients reported better improvement of tinnitus when naftidrofuryl was combined with dextran. Two patients receiving dextran alone developed side effects: one had an allergic reaction causing withdrawal of treatment, which the other case had vertigo, nausea and headache with spontaneous recovery. The results of the study showed that treatment with naftidrofuryl in addition to hemodilution with low-molecular weight dextran was of therapeutic benefit in the therapy of sudden deafness without increasing the rate of side effects.

Administration, Oral↗

[The concentration of atrial natriuretic peptides (ANP). ANP in different sections of the circulation during atrial volume load with and without anesthesia].

We studied the effect of a volume load induced by a 45 degrees Trendelenburg position on atrial natriuretic peptide (ANP) secretion in awake and anaesthetized patients with coronary artery disease undergoing aortocoronary bypass surgery. ANP was measured in different parts of the circulation before and after induction of high dose fentanyl anaesthesia at fixed times prior to and after extracorporeal circulation. METHOD. In eight patients with coronary artery disease (NYHA classification II-III), who received neither diuretic nor positive inotropic therapy, ANP was measured in the various parts of the circulation: in a peripheral vein, a radial artery, in the pulmonary artery and in the coronary sinus. The measurements were made in the supine and 45 degrees Trendelenburg position. Measurements of mean arterial pressure (MAP), central venous pressure (RAP), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI) and heart rate (HR) were taken simultaneously. The measurements were taken in the awake patient, during steady-state high-dose fentanyl anaesthesia with 50% O2 in N2O and after extracorporeal circulation. RESULTS. Compared to measurements in a control group, ANP levels were significantly higher in all parts of the circulation in patients with coronary artery disease, although clinical symptoms of heart failure were absent. After extracorporeal circulation, significantly higher levels of ANP were found at all measurement sites; however the concentration gradient of ANP between coronary sinus and arterial or venous blood was reduced. In awake and anaesthetized patients a change in body position, causing a significant increase in filling pressures, did not produce an increase in ANP levels at all measurement sites. The induction of high-dose fentanyl anaesthesia did not have an influence on plasmatic ANP levels. CONCLUSION. The results of this study lead to the following conclusions: 1. ANP levels in patients with CAD are increased, even if clinical heart failure symptoms are absent. 2. ANP is secreted in the coronary vessels. Following dilution in the atrial blood, it is metabolized to inactive compounds in the periphery. 3. Basic ANP levels are not changed by high-dose fentanyl anaesthesia. Marked increases of the filling pressures do not correlate with atrial ANP levels either before or after induction of anaesthesia. 4. After extracorporeal circulation ANP levels are significantly increased in all parts of the circulation. The concentration gradient between coronary sinus blood, on the one hand, and arterial and venous blood on the other hand is reduced. This phenomenon is probably caused by an alteration in the metabolism of ANP during hypothermic extracorporeal circulation.

Aged↗

Alterations of ionic currents after reoxygenation in isolated cardiocytes of guinea-pigs.

Single myocytes were isolated from ventricles of adult guinea-pig hearts. The patch-clamp technique in the whole-cell configuration was used to study ionic currents. Experiments were performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure to cause metabolic inhibition after 4-35 min (mean 14.1 min, n = 20), which was indicated by the appearance of a large time-independent K current. Reoxygenation about 1 min after the first extra outward current was observed caused this current to vanish completely within 2-6 s if the calcium inside the pipette was buffered to negligible values with 20 mmol/l EGTA. With only 10 microM EGTA in the pipette, reoxygenation was followed by an arrhythmogenic period of 10-150 s duration, which was dominated by three types of event: (a) transient inward currents (Iti) developed during the first 5-10 s (26 cells); (b) the net current was increased by a factor of 1.9 +/- 0.4 (mean +/- SD, n = 17) yielding a reversal potential for the increased component of -77 +/- 4 mV (mean +/- SD, n = 4); and (c) the Ca current decreased by 20%-100% within the first 5-10 s. At the end of the arrhythmogenic period, Iti vanished, the net current recovered completely, and the Ca current recovered partially. At -45 mV, increasing preceding depolarization enlarged the amplitude of both the Iti and the net current, Iti being about four times more increased than the net current. The suppression of the Ca current was independent of the phase of the preceding Iti. We conclude that in isolated cardiocytes, after the induction of an anoxia-induced K current, reoxygenation causes a period of up to 150 s of cytosolic Ca overload, during which Iti is triggered, the net current is enhanced, and the Ca current is suppressed.

Animals↗

Reoxygenation-induced arrhythmogenic transient inward currents in isolated cells of the guinea-pig heart.

Transient inward currents (Iti), activated by a rise in intracellular Ca concentration, are believed to trigger cardiac arrhythmias in reperfused hearts. In this report, Iti in isolated cardiocytes from the guinea-pig were evoked by reoxygenation following a period of anoxia of between 4 min and 35 min. Reoxygenation was performed 1 min after the full development of an anoxia-induced time-independent K current. This current disappeared within 2-6 s and in the following 10 s Iti developed to maximum amplitude. Iti were evoked using a constant pulse pattern (holding potential Vh = -45 mV; test potential Vt = +10; pulse duration 350 ms; frequency 1 Hz). In more than 95% of the cells, Iti at the holding potential Iti (-45 mV) declined with a time constant of tau = 670 +/- 240 ms (mean +/- SD, n = 17). In two cells, undamped oscillatory currents were observed. The amplitude of Iti (-45 mV) was proportional to the amplitude and duration of the preceding depolarizing test pulse. Test pulses of long duration (500 ms and 1000 ms, mean +/- SD) to potentials positive to +10 mV produced slowly decaying tail currents (tau = 391 +/- 51 ms, mean +/- SD), which superimposed with Iti (-45 mV). The current/voltage relationship of Iti peaked between -30 mV and -10 mV and approximated zero at the most positive potentials, i.e. no reversal of Iti was found up to +80 mV. Using double-pulse protocols (prepulse potential +40 mV), Iti were enhanced at potentials negative to -30 mV and were also present in the range of the normal resting potential of ventricular heart cells. The instantaneous current-voltage relationship was monotone between -50 mV and +40 mV. Because of the dependence of Iti on the preceding depolarization, the instantaneous current-voltage relationship provides more reliable information on the voltage dependence of Iti. The interval between two subsequent Iti (-45 mV) values was 237 +/- 35 ms (mean +/- SD, n = 27) and depended on the amplitude of Iti (-45 mV) to increase by 5.2 +/- 0.5% (mean +/- SD) per 100 pA decrease in Iti (-45 mV). A simple noise analysis showed that if one assumes that ionic channels are responsible for the generation of Iti (-45 mV), their unitary conductance cannot exceed 0.36 pS. We conclude that reoxygenation-induced Iti are triggered by a cyclic release of Ca from the sarcoplasmic reticulum and provide evidence that they are mediated by the electrogenic Na/Ca exchanger.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Anoxia opens ATP regulated K channels in isolated heart cells of the guinea pig.

We studied single channel ionic currents in cell-attached patches of guinea pig heart cells under conditions of anoxia (pO2 less than 0.1 torr) to identify the type of channels which contribute to the anoxia-induced time-independent K current in whole cells. In most experiments, K currents were recorded at negative potentials as inward currents with 150 mmol/l KCl in the pipette. After periods of 5-60 minutes of anoxia, opening events of one to four voltage-independent 83 pS channels developed whose open probability reached a steady state value between 0.6 and 0.95 (T = 35 degrees C). The reversal potential of the unitary currents, determined at 150 mmol/l and 10.8 mmol/l K+ in the pipette, showed that the channels were highly selective for K+ ions. Open time histograms were fitted by two or three exponentials of which the fast time constant (tau O1 = 0.46 +/- 0.20 ms, mean +/- SD) was bandwidth-limited by our filter and the slow components substantially varied (tau O2 = 1.5-19 ms; tau O3 = 23-200 ms). Voltage ramp experiments showed that the channels were slightly rectifying in an inward direction. The unitary conductance of anoxia-induced outward currents at reduced K+ in the pipette was smaller (11 pS at 5.4 mmol K+, 25 pS at 10.8 mmol/l K+) than in excised patches. It is concluded that in isolated cardiocytes substrate-free anoxia causes opening of ATP regulated K channels whose conductance is reduced at physiological levels of [K+]O by a fast block, most likely by intracellular Mg++ and Na+.

Adenosine Triphosphate↗

Hemostatic changes due to the venom gland extract of the red-necked keelback snake (Rhabdophis subminiatus).

After a bite by the aglyphous red-necked keelback snake Rhabdophis subminiatus a complete defibrinogenation syndrome with severe hemorrhagic diathesis developed in a 25-year-old man. In vitro studies showed that the venom gland extract of the snake contains a very active prothrombin (Factor II) activator. The thrombin generated is inhibited neither by antithrombin III nor the antithrombin-III-heparin complex. The venom gland extract stimulated also the tissue plasminogen activator; however, it did not cause direct activation of plasminogen, protein C, Factor X or direct degradation of fibrinogen.

Adult↗

[Digital luminescence radiography (DLR) for skeletal diagnosis in traumatology].

170 patients who had suffered trauma to bones or soft tissues were examined by a digital and a conventional film/screen technique. In addition to "standard" and edge-enhanced images, post-processing was carried out and compared with conventional radiographs. Four radiologists and two surgeons evaluated the compacta, spongiosa, soft tissues, fractures and osteo-synthetic materials as shown on the two systems. The "standard" digital images are inferior to film images, but edge-enhanced images showed definite advantages for demonstrating soft tissues. Evaluation of osteo-synthetic material is limited by the creation of artifacts. Recognition of detail can be significantly improved by using post-processing with optimized parameters.

Adolescent↗

[Prevention of arterial and venous vascular diseases, especially the correlation between risk factors and arteriosclerosis].

In a epidemiological study 3840 clerks of state of North Rhein Westfalia were investigated concerning the frequency of atherosklerotic leasions of the carotid and femoral arteries in duplex scanning. 17% of all investigated showed independency to age, sex and risk factors alterations of the vessel walls. Men had twice as much plaques as women and male subjects with multiple risk factors had four times more plaques than those without.

Adult↗

[Imaging real-time sonography (B-scan) of peripheral veins--possibilities for use with reference to secondary prevention].

In 2400 male and 1400 female persons the proximal femoral and saphenal venous vessels have been monitored and measured with a Ultramark 4, build by ATL, by use of 7.5 megacycle/s. transducer. Moreover, we took the venous calibers at the junction of the saphenous veins into femoral veins. In patients with marked varices or less symptomatic patients as well as clinically asymptomatic persons with positive family history there could be found significantly bigger dilatation of vessel calibers in those patients laying than those standing up, in contrast to healthy persons. B-Scan ultrasound consequently in future offers a new range of diagnostic values in examination of venous vessels, that is to say a non-invasive, reproducible and haemodynamically tolerable method which helps to improve secondary prevention.

Female↗

[Duplex procedure in prevention of arteriosclerosis].

Early atherosclerosis can be easily dedected in arteries accessable to ultrasound. The main localisations are the carotid and femoral arteries, which can be deseased alone or together. The progression seems to be higher in the femoral vessels. There is the impression that the growth can be influenced by drugs which lower blood cholesterol or are partial inhibitors of serotonin receptors (S 2).

Adult↗

Oral antidiabetic combination therapy with sulphonylureas and metformin.

In a multicentre trial in general practice, a total of 1823 type 2 diabetics, not adequately controlled by diet and maximal sulphonylurea therapy, were treated with additional metformin 850--2 550 mg/d for 12 weeks. The average postprandial blood sugar decreased from 15.48 mmol/l to 10.43 mmol/l, HbA1 fell from 11.0% to 9.1%. Serum triglycerides decreased from an initial level of 2.87 mmol/l to 2.41 mmol/l an mean total cholesterol from 6.76 mmol/l to 6.16 mmol/l. In addition, body weight and blood pressure declined steadily. All the described changes were statistically significant. The metformin-sulphonylurea combination therapy was generally well tolerated. Gastrointestinal side effects occurred in about 7% of patients, but mainly in the first week of treatment, generally disappearing spontaneous as therapy was continued. Side effects led to a discontinuation of the treatment in 4.2% of patients.

Administration, Oral↗

Acromegaly and hypertension: prevalence and relationship to the renin-angiotensin-aldosterone system.

The prevalence of arterial hypertension was evaluated in a retrospective study of 158 patients with acromegaly, and results were compared to control populations, namely, the Munich Blood Pressure Study (MBPS) and the Framingham Study. The prevalence of hypertension (defined according to WHO criteria) was significantly increased in female patients but not in men; hypertensive acromegalics were older and tended to have higher body weight compared to normotensive patients. Hypertension was not related to serum concentrations of growth hormone. After successful treatment of acromegaly, growth hormone levels and systolic and diastolic blood pressure fell only in female hypertensive acromegalics; this did not occur in normotensives. The rise in plasma renin activity in response to upright posture was diminished in 57.9% of acromegalic patients. The prevalence of low-renin hypertension in our group of patients was 31.6%, which is similar to figures reported for unselected non-acromegalic subjects with essential hypertension. Orthostatic renin activity was weakly and inversely related (r = -0.3) to blood pressure. No relationship between plasma aldosterone concentration and blood pressure could be detected; however, in acromegalic women, aldosterone rose higher after ambulation than in men. In conclusion, hypertension is a common problem in acromegaly and at least in part related to similar risk factors in control populations. The association with abnormalities of the renin-angiotensin-aldosterone system is difficult to interpret and does not offer an explanation for the slight increase in the prevalence of hypertension.

Acromegaly↗