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Biomedical subjects

M Volz

Publications and source records attributed to M Volz.

At least 19 recordsLinked to original sources

FIV-infected cats respond to short-term rHuG-CSF treatment which results in anti-G-CSF neutralizing antibody production that inactivates drug activity.

The hematological and virological effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) were evaluated in feline immunodeficiency virus (FIV)-infected cats. Six age-matched, FIV-infected cats used in this cross-over study were injected subcutaneously with 5 microg/kg of rHuG-CSF daily for 3 weeks, while six control cats received a placebo. Five of six rHuG-CSF-treated cats had significant increases in neutrophil counts that peaked on days 11-21 of treatment. All rHuG-CSF-treated cats exhibited an increase in myeloid:erythroid ratios of the bone marrow cells without significant changes in lymphocyte, CD4 counts, CD4/CD8 ratios, RBC counts, FIV antibody titers, and FIV loads in peripheral blood, and without clinical and hematological toxicities. Five of six rHuG-CSF-treated cats developed antibodies to rHuG-CSF by 14-21 days of treatment, which correlated with decreasing neutrophil counts and increasing neutralizing antibodies to rHuG-CSF. Three cats re-treated with rHuG-CSF rapidly developed neutralizing antibodies to rHuG-CSF, while one cat also developed neutralizing antibodies to recombinant feline G-CSF (rFeG-CSF). Overall, rHuG-CSF treatment increased neutrophil counts in FIV-infected cats without affecting the infection status of cats. However, long-term use of rHuG-CSF is not recommended in cats because of the neutralizing antibody production to rHuG-CSF that affects the drug activity. In addition, a preliminary finding suggests that repeated treatment cycle can also induce cross-neutralizing antibodies to rFeG-CSF, which may potentially affect the homeostasis of endogenous FeG-CSF.

Animals↗

[Suicide attempt with high-dose ecstasy].

The case of a 16-year-old female patient is reported, who has taken in 30 tablets of Ecstasy in a suicide attempt. Initially were seen a tachycardia,hyperdynamic circulation, dehydration, leg-myocloni in the awake excited female patient. For prophylaxis of aspiration general anaesthesia and intubation with following gastric lavage were performed. During the intensive care treatment the high blood pressure persisted, although general anaesthesia and anti-hypertensive therapy was continued. After extubation the neurologic status of the patient was normal. Emergency physicians see more and more often Ecstasy-intoxications. Signs of an acute intoxication with Ecstasy are a sympathomimetic reaction with tachycardia,hypertonic blood pressure and cardiac arrhythmia as well as fever, respiratory and renal insufficiency, rhabdomyolysis, cerebral edema and convulsion. A specific antidote does not exist; the symptomatic therapy consists of airway management, hemodynamic stabilisation, primary drug-elimination and, in case of need, application of betablockers and relaxants.

Adolescent↗

Effects of electrical stimulation of the Gasserian ganglion on regional cerebral blood flow after induced subarachnoid hemorrhage in pigs evaluated by 99mTc-HMPAO-SPECT.

It could be demonstrated that cervical spinal cord stimulation increases cerebral blood flow. The effects of electrical stimulation of the trigeminal ganglion in the acute phase of SAH in pigs were investigated. The experiments were carried out on 11 domestic pigs divided in two groups (group I: SAH [n = 5]; group II: SAH and trigeminal stimulation [n = 6]). In all animals a native SPECT was performed. The Gasserian ganglion was exposed for inserting the stimulation electrode. SAH was induced by injecting 10 ml autologous blood through a catheter placed in the suprasellar cistern. 30 minutes after SAH-induction electrical stimulation was started for two hours in group II (2.8-4.5 V, 50 Hz, 300 microseconds). 99mTc-HMPAO (400-540 MBq) was injected intravenously 110 minutes later. In group I 99mTc-HMPAO was applied after the same time interval. 80 minutes later SPECT was performed. Data were processed to calculate the uptake of radioactivity (%/kg tissue weight). The mean values were calculated for the different groups: native animal examination (%/kg tissue weight): 0.6343; group I: 0.468; group II: 0.6533. Comparing the mean values a highly significant difference between group I and group II (p < 0.01) and between native examination and group I (p < 0.01) could be found. No statistical significance could be detected on comparing the left/right-ratio in any ROI. The electrical stimulation of the Gasserian ganglion leads to a significantly increased uptake of 99mTc-HMPAO after induced SAH. Maybe the stimulation of the Gasserian ganglion constitutes a new therapeutic modality treating disturbed rCBF after SAH.

Animals↗

High cervical spinal cord stimulation (CSCS) increases regional cerebral blood flow after induced subarachnoid haemorrhage in rats.

The effects of high cervical spinal cord stimulation (cSCS) on regional cerebral blood flow (rCBF) were investigated after experimentally induced subarachnoid haemorrhage (SAH) in rats by the means of (99m)Tc-HMPAO. The experiments were carried out on a total of 24 Wistar rats, divided in three groups [group I: control without SAH, group II: SAH, group III: SAH and cSCS]. (99m)Tc-HMPAO was administered intravenously (group II/group III) 48 hours after induction of SAH. In group III, (99m)Tc-HMPAO was given after 3 hours of cSCS. All animals were sacrificed 30 minutes after application on (99m)Tc-HMPAO. Radioactivities were determined in blood, cerebrum and cerebellum. The ratio cerebrum/blood and cerebellum/blood was calculated to ascertain "extraction rate" in the sample differentially. The following mean values were calculated for the cerebellum/blood ratio: Group I: 1.06, SD: 0.21; Group II: 0.66, SD: 0.21; Group III: 1.00, SD: 0.37. Comparing the mean values a highly significant difference could be found between group II and III (p = 0.007) and between group I and II (p = 0.0019), respectively. Calculations of the cerebrum/blood ratio revealed similar results. After SAH cSCS enhances cerebral and cerebellar blood flow in rats. Possibly, cSCD constitutes a new therapeutic approach in the treatment of disturbed regional cerebral blood flow after SAH.

Animals↗

Gastric versus duodenal feeding in patients with neurological disease: a pilot study.

Both gastric and duodenal feeding tubes are used to provide enteral nutrition. Most studies comparing the two methods have focused primarily on rates of complications, rather than on nutritional outcomes, and show no difference in complications between the two methods. It is not clear which feeding route provides the best nutritional outcomes. The primary purpose of this randomized clinical pilot study was to compare the percentage of recommended calories and protein received by patients with neurological disease being fed enterally via gastric or duodenal feeding tubes. Secondary aims were to compare the following between groups: physiological effects of feeding, reasons for delay in feeding, volume of feeding residual, number of feeding tubes replaced, cost of feeding, and number and types of complications. A convenience sample of 25 neuro intensive care unit patients was randomly assigned to gastric or duodenal feeding. Enteral feeding was ordered by using a standardized prescription formula and provided by the nursing staff. Serum albumin and prealbumin levels were measured at baseline, day 3, and day 10. Nitrogen balance was measured on day 10. Enteral feeding data were collected daily. No significant differences were found between gastric and duodenal groups in nutritional outcomes, including percentage of recommended calories and protein received, physiological effects of feeding, reasons for delay in feeding, feeding residual, number of feeding tubes replaced, cost of feeding, and number and types of complications. Neither group achieved mean recommended caloric or protein intake during the 10 days of the study. Further research is needed to address how recommended nutrients can be provided enterally in a more timely and complete manner in critically ill NICU patients.

Adult↗

[The sacral perineural system--are there radiological criteria for an indication for surgery? First results and literature survey].

PURPOSE: To establish recommendations for diagnostic imaging of cystic lesions of the sacral region and to evaluate for potential predictors of therapeutic outcome. METHODS: Conventional imaging of the lumbar spine, conventional CT, myelography, post myelo-CT and MRI were performed in 7 symptomatic [corrected] patients. All patients underwent operative decompression and histological examination. The radiographic examinations were reevaluated retrospectively and correlated with the postoperative outcome. RESULTS: In one patient the differential diagnosis of a neurinoma could not be excluded with CT and CT-myelography alone. In all 7 patients MRI provided a definite diagnosis and a precise presentation of the cyst extension. A complete postoperative remission of symptoms was noticed in 4, a partial remission in three cases. The correlation of cyst extension, cyst shape, and the communication with the subarachnoid space did not provide predictive information concerning operative outcome. CONCLUSION: MR can be used as the sole imaging tool for demonstration of cystic lesions. Relevant disadvantages in comparison to myelography and myelo-CT were not evident. No imaging modality could predict the value of surgical intervention.

Decompression, Surgical↗

Augmentative treatment of chronic deafferentation pain syndromes after peripheral nerve lesions.

Deafferentation pain syndromes developing after peripheral nerve lesions are difficult to treat. According to the follow-up (mean: 39.5 months) of 6 patients suffering from causalgic pain we will present our method of augmentative therapy in chronic neuropathic pain caused by peripheral nerve lesions, i.e., peripheral nerve stimulation (PNS), spinal cord stimulation (SCS) and chronic intrathecal opioid infusion. None of the patients showed intraoperative or follow-up complications. Evaluated by visual analogue scales all patients reported a good to excellent pain relief (75-100%). (1) Regarding the favourable long-term results of PNS, this method should be considered in cases of mononeuropathic pain syndromes. (2) Neuropathic pain syndromes which are not assignable to a singular nerve lesion, can often be managed effectively by SCS. (3) In contrast to the widespread opinion, deafferentation pain syndromes of central or peripheral origin can be treated satisfactorily by intrathecal opiate administration.

Adult↗

Steady-state plasma kinetics of slow-release propafenone, its two isomers and its main metabolites.

Steady-state plasma kinetics of propafenone (CAS 54063-53-5), the S- and R-enantiomers, and the two main metabolites were investigated in a double-blind, placebo-controlled dose-finding study using a slow-release formulation of propafenone at three different dose regimens (2 x 225 mg, 2 x 325 mg, and 2 x 425 mg). The study included a total of 24 patients (18 m, 6 f) with symptomatic ventricular arrhythmia. Since statistically valuable data was limited by a considerable portion of undetectable plasma concentrations among patients having received verum, kinetics could be followed up only in a group of 14 patients (10 m, 4 f) over a period of 12 h under steady state conditions. All patients were phenotyped prior to the study by measuring the ratio of sparteine/dehydrosparteine and three poor metabolizers were identified. A detailed description of the analytical methods used is given. With the low dose, a mean plasma level of 87 +/- 16 ng propafenone per ml plasma was obtained, with the medium dose a level of 243 +/- 34 ng/ml and with the higher dose 334 +/- 71 ng/ml were reached. All three doses of the slow-release preparation resulted in a smoothened and thus therapeutically favorable plasma concentration curve, independently from phenotype. With regard to the two propafenone enantiomers, a preferential clearance of the R-form (S/R = 2.08 +/- 0.19) could be confirmed without observing a change in the S/R ratio with time.

Acetylation↗

Interference in clinical laboratory tests, with special regard to the bilirubin assay: effects of a metabolite of the new prolyl 4-hydroxylase inhibitor, Lufironil.

During the toxicological examination of the fibrosuppressive agent, Lufironil (INN), in rats a dose-dependent positive reaction for urinary bilirubin was observed. This positive reaction was found in quantitative assays, and when using test strips. The positive reaction for bilirubin in these assay systems was caused by a metabolite of Lufironil. It was not due to drug toxicity, and it was not caused by any endogenous substrate produced under the influence of Lufironil. The compound responsible for this reaction was isolated by HPLC and its structure determined by spectroscopic methods. The structure was confirmed by synthesis, starting from pyridine-2,4-dicarboxylate. The synthesized compound and the compound in urine gave an identical reaction with the test reagent for bilirubin.

Administration, Oral↗

Steady-state plasma concentrations of propafenone--chirality and metabolism.

In a selected group of 86 patients (60 males, 26 females) with symptomatic ventricular arrhythmias, possible interactions between metabolic and chiral effects at steady-state were investigated by comparing the plasma levels of propafenone, its major metabolites and the 2 structural isomers. The antiarrhythmic drug propafenone is metabolized--besides a minor dealkylation pathway--mainly via 5-hydroxylation. It is a well-known phenomenon that this oxidative pathway is not shared by all individuals to the same extent. We were able to verify among our subjects the portion of so-called poor metabolizers reported in the literature for the total population. Propafenone was administered as a slow release formulation at 3 different dose regimens (2 x 225 mg, 2 x 325 mg and 2 x 425 mg). The crude drug is a racemic mixture of equal amounts of R- and S-forms. During treatment, the plasma S and R ratio was shifted towards the S-isomer due to preferential clearance of the R-form. It was further found that neither a genetic disposition (gender, metabolic phenotype) nor age or the dose applied had any influence on the measured plasma isomer ratio.

Adult↗

Ureaplasma urealyticum chronic osteomyelitis in a patient with hypogammaglobulinemia.

Mycoplasma species are recognized as important pathogens in patients with hypogammaglobulinemia. In this article we describe, for the first time, a patient with hypogammaglobulinemia who developed osteomyelitis of the hip caused by Ureaplasma urealyticum. This article emphasizes the need for considering infection with Mycoplasma species in patients with antibody deficiency.

Adult↗

Pharmacokinetics and metabolism of HOE 077. Preclinical studies.

The studies were performed in healthy male rats and in one male dog after oral and intravenous administration of [2-carbamoyl-14C]HOE 077. HOE 077 wa rapidly and completely absorbed after oral administration. In blood, tmax was at about 0.5 h and cmax 2.63 +/- 0.92 micrograms equivalents/g in rats (5 mg/kg), and 18.1 micrograms equivalents/g in the dog (15 mg/kg). The predominant half-lives for total radioactivity were in the range of 1 h in the rats and 2 h in the dog, independent of the route of administration. The radioactivity was distributed throughout the body. The highest concentrations were detected in kidneys and liver. Urine (75% of dose) was the main route of excretion after oral and intravenous administration. The radioactivity was almost entirely eliminated 2 days after administration. The compound was intensively metabolized by rat and dog. While the parent compound was the major component in plasma at early time after dosage, more than ten metabolites, accompanied by only small amounts of original substance, were detected in the urine of the first study day. In faeces only metabolites were found. The known metabolites are assumed to be formed by oxidative degradation of the alkylic side chains of the molecule, preferably that in the 2-position of the pyridine ring. The main metabolite in the dog urine was a 2-hydroxyethyl derivative (M4), and in the rat a hippuric acid analogue of HOE 077 (M6). The pyridine carboxylic acid in 2-position of the side chain of HOE 077 (M2) was the predominant metabolite in faeces of rat and dog. In both animal species, more than 80% of the administered radioactivity had been identified. In rats with liver damage caused by treatment with CCl4 the amount of parent compound increased and the rates of formation of metabolites were lower than in normal rats. This can be interpreted as a consequence of the diminished number of hepatocytes able to metabolize HOE 077.

Animals↗

Pharmacokinetics of amlodipine in renal impairment.

Amlodipine was administered as 14 single 5-mg oral daily doses to 27 male subjects with renal function ranging from normal to haemodialysis-dependent. Blood specimens were obtained for measurement of plasma amlodipine concentrations for 24 h following the first dose, for 168 h following the final dose and during daily administration of amlodipine. Amlodipine was well tolerated. Renal impairment had little effect on the pharmacokinetics of amlodipine. The elimination half-life was of the order of 50 h, similar to previously reported values and did not vary with renal function. Steady-state pre-dose concentrations were observed after the ninth dose. Accumulation of amlodipine was not significantly different from that expected on theoretical grounds and did not significantly change with renal function. These results suggest that once daily administration of amlodipine is suitable for all degrees of renal function and that dosage adjustment is not necessary in renal impairment.

Adult↗

The vasopressor system in patients with heart failure due to idiopathic dilated cardiomyopathy--influence of the clinical stage of disease and of chronic drug treatment.

Alterations in the vasopressor system found in cardiac failure are part of compensatory measures that may modify pharmacologic-therapeutic response. Therefore, in 64 patients with dilated cardiomyopathy, we investigated its enhanced activity in different clinical stages of the disease as compared to normal controls. Patients in NYHA class II (n = 20) demonstrated increased activity of the sympathico-adrenal, renin-angiotensin-aldosterone, vasopressin, and atrial natriuretic factor systems, while maximum values were found in patients of NYHA class IV (n = 24). In these patients, noradrenaline was enhanced by a factor of 7, adrenaline by a factor of 2, plasma-renin-activity by a factor of 7, angiotensin II by a factor of 2.5, aldosterone by a factor of 5, vasopressin by a factor of 1.5, and ANF by a factor of 4 as compared to normal controls. Clinical NYHA classes correlated to a certain degree with the various plasma hormones. Patients treated with an aldosterone inhibitor in addition to digitalis and diuretics revealed significantly higher values for aldosterone, vasopressin, and angiotensin II as compared to those who received digitalis and diuretics alone. The addition of ACE-inhibitor therapy resulted in a decrease of angiotensin II, aldosterone, and vasopressin. Plasma catecholamines and ANF, however, did not change under the influence of cardiac medication. Diuretic treatment in NYHA class II patients reduced plasma volumes (p less than 0.01). Plasma volume in NYHA class IV patients only was found to be higher than in normal controls. Thus, analysis of the neurohumoral system can aid both in the identification of the clinical degree of dilated cardiomyopathy and in its optimal therapy.

Adult↗

Hemodynamic, antiischemic, and neurohumoral effects of enoximone in patients with coronary artery disease.

To evaluate the risk of ischemia in 17 patients with significant coronary artery disease, the influence of enoximone was analyzed under the following conditions: (1) at rest (RC) and during exercise (ExC) under control conditions and (2) at rest (RE) and during exercise (ExE) after administration of enoximone (0.75 mg/kg, intravenously). During ExC all patients had ischemia (angina, and ST segment alterations); metabolic markers of ischemia (MMI) increased, as did the mean pulmonary artery pressure, from 19 to 41 mm Hg. However, during ExE ischemia was abolished (no angina, decrease in mean pulmonary artery pressure to 24 mm Hg, and improvement in MMI) and there was some improvement in left ventricular pump function, whereas pre- and afterload decreased (pulmonary artery pressure by 40%, systemic vascular resistance by 10%), and heart rate, arterial pressure, and myocardial oxygen consumption (MVO2) were all unchanged (p greater than 0.05). Comparative hemodynamics at RE vs RC showed a decrease in pulmonary artery pressure (by 25%) and pulmonary vascular resistance (by 19%) and an increase in heart rate (by 11%), whereas arterial pressure and MVO2 were unchanged (p greater than 0.05). Enoximone did not induce changes in plasma catecholamine, prostaglandin, or thromboxane levels (p greater than 0.05), whereas the atrial natriuretic factor decreased (by 15%), probably because of unloading of the atria during exercise. We concluded that enoximone induces beneficial hemodynamic effects in coronary artery disease without causing ischemia, probably by enhancing myocardial contractility, vasodilation, and improved diastolic properties.

Atrial Natriuretic Factor↗

The influence of various degrees of cardiac failure, chronic medical treatment, and acute additional enoximone application on the parameters of the vasopressor system.

The characteristics of norepinephrine and epinephrine as well as plasma renin activity, angiotensin II, aldosterone, vasopressin, and atrial natriuretic factor (ANF) were examined in 64 patients (mean age of 52 +/- 16 years) with dilated cardiomyopathy. The findings were grouped according to the NYHA classification and compared with a normal cohort of 38 patients (mean age of 42 +/- 10 years). Furthermore, the influence of different cardioactive substances used in the treatment of cardiac failure was analyzed in more detail. Patients in NYHA class II already demonstrated an increased activity of the sympathicoadrenal, renin-angiotensin-aldosterone system (RAAS), vasopressin, and ANF system. The highest values were found in patients of NYHA class IV. In these patients, norepinephrine was enhanced by a factor of 7, epinephrine by a factor of 2, plasma renin activity by a factor of 7, angiotensin II by a factor of 2.5, aldosterone by a factor of 5, vasopressin by a factor of 1.5, and ANF by a factor of 4 compared with those in normal subjects. The highest correlation coefficient was found for norepinephrine (r = 0.84). The acute application of 1-2 mg/kg of body weight of enoximone in patients with dilated cardiomyopathy (n = 15) resulted only in a significant lowering of the atrial natriuretic factor as an indicator for drug-induced unloading effects (venous pooling). All the parameters showed only a tendency; in none could statistical significance be established. Application of 0.75 mg/kg of body weight of enoximone i.v. in patients with coronary artery disease (n = 17) has no direct influence either on the sympathoadrenal, the ANF, or the prostaglandin systems. It could be demonstrated that the mode of medical treatment influences the parameters of vasoconstrictor systems in different ways.

Adult↗