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Biomedical subjects

H Nowak

Publications and source records attributed to H Nowak.

At least 19 recordsLinked to original sources

Multichannel magnetography in unshielded environments.

Any biomagnetic instrumentation requires a very sensitive sensor. As the strength of the magnetic field of interest ranges from about 10 fT to 50 pT, the only field sensor having the required sensitivity and small sampling volume is the superconducting quantum interference device (SQUID) e.g. thin-film DC SQUIDs. For transforming the signal from the antenna to the SQUID, a thin-film coupling coil is used. The SQUID itself is shielded and therefore insensitive to external noise. In a five-channel system second-order gradiometers are used in an unshielded environment. The measuring system enables us to balance each channel by means of lead plates without removing it from liquid helium. The lead plates can be handled by a revolver system from outside the dewar. By an iterative balancing procedure inside an artificial uniform field, imbalances less than 10(-4) could be achieved. These results are confirmed by mathematical calculation of mechanical balancing. Sensitivities down to 20 fT Hz-1/2 could be achieved during 'quiet' hours. Another method for the suppression of disturbances is electronic balancing. One of the most important problems in the multichannel system is the cross talk between the single channels. With respect to the geometry of our five-channel device the cross talk coefficient was calculated to be 3.9% and measured at 3.8%.

Equipment Design

[Effect of vibration on crystalline lens transparency].

It was demonstrated experimentally that the transparency of the eye lenses diminishes under the influence of a prolonged vibration. Investigations were performed in a group of rabbits which were subjected to a long-lasting exposition to mechanical vibration of 10 Hz throughout a period of 5 months. The transparency of the extracted lenses was evaluated by spectrophotometry and compared with lenses of 2 control groups. Group 1 consisted of rabbits which in the same period of 5 months were subjected to a continuous neon illumination of 1200 lx intensity as a cataractogenous factor. A second comparative group consisted of rabbits not exposed to any external factor. The authors detected a statistically significant decrease of transparency of lenses of the examined group in reference towards the second comparative group, it was however smaller than in the 1-st group.

Absorption

[Primary liver cell carcinoma among the population of Białystok in 1975-1988 in relation to hepatitis B virus infection].

In presented study, retrospective epidemiological analysis was performed in 84 patients dead due primary hepatocellular carcinoma, selected from among 17,973 persons dead in Białystok hospitals from 1975 till 1988. In the part from among these patients was estimated prevalence of serological markers of Hepatitis B virus infection, as a potential oncogenic factor. Analysis of this carcinoma diagnosis frequency in particular years showed rising tendency: from 1975 till 1979 number of PHC diagnosis was from 0 to 5 a year, whereas in 1988 it was 13. Percentage of necropsy diagnosed PHC was similar and increased to over 1% of all necropsies in 1988. Mean age of patients dead due PHC was 65, and 71.4% were men. Serological markers of HBV infection were observed in 50% and HBsAg in 34.6% from among PHC-dead patients. These percentage values were significantly higher, than observed in control group of Białystok population, which indicate possibility of association between HBV infection and PHC development.

Adult

Long-term multicentric study with azelastine in patients with intrinsic asthma.

Efficacy and tolerance of azelastine (A 5610; CAS 58581-89-8), a new antiallergic compound with a unique structure, were investigated over up to one year of treatment in 225 male and female out-patients (age mean +/- s = 48 +/- 13 years) suffering from chronified intrinsic asthma. The trial was conducted by 24 German and Austrian consulting physicians of pneumology. Plasma levels indicated sufficient compliance in almost 90% of the patients. Tablets containing 4.4 mg azelastine HCl were administered b.i.d. in addition to the pre-existing antiasthmatic medication. Only other antiallergic agents were excluded. Adverse events, vital parameters and laboratory tests on safety were tightly assessed. Eighteen patients dropped out because of adverse events, 78 reported adverse experiences under therapy, normally mild and "vegetative" symptoms. No indicative findings regarding blood pressure, heart rate and laboratory tests were seen. The most frequent observations were taste disorders, asthenia and weight gain. No serious side effects at all were reported. The results on efficacy obtained from this non-controlled study may be predicative due to a baseline validation by an initial single blind placebo controlled run-in phase. Statistically significant improvements were seen for FEV1 and for the physicians' and the patients' rating on efficacy. To a lesser extent peak flow and airway resistance were improved, too. Thus, azelastine was safely tolerated over one year and might be effective in intrinsic asthma.

Adolescent

[Biochemical aspects of the evaluation of fixed drug combinations].

Various disciplines have to contribute to the general problem of the evaluation of fixed dose combination drugs, as for instance (clinical) pharmacology, biometry, scientific drug regulations and public health officials. The EC guideline 75/318/EWG and its eludications as well as the German "Arzneimittelprüfrichtlinien" of Dec. 14, 1989 (as referred to in the "Arzneimittelgesetz" of 1986) required that such issues concerning fixed dosage combination drugs must be considered and taken into account. In this framework it is the responsibility of biometry to both to guarantee the use of a valid study design to assure interpretation of the results and to quantify the reliability of pharmacological and clinical considerations. The following paper is concerned with biometrical aspects of the combination drug problem. Basic considerations from a clinical or a pharmacological point of view with respect to the question of whether fixed combination drugs are reasonable or not are not discussed. To support the use of combinations of drugs, a central argument is the improvement of the benefit risk relation compared with that of an adequate monotherapy. Beyond this the fixed combination drugs require additional arguments regarding the enhencement of the safety or the simplicity of the therapy fixing the ratio. It follows that fixed combination drugs have to be supported twice, first with respect to the combination itself, and second with respect to the fixed mixing ratio of its components. The biometrical aspects of the assessment of the gains from (fixed) drug combinations are related to the kind of benefit/risk improvement that is expected. In the first section we discuss some possible types of benefit and risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[A grenade splinter as the cause of cholangitis and icterus].

Forty five years after being injured by a grenade splinter a now 74-year old man suddenly developed colicky pain in the right upper abdomen, accompanied by colourless stools, jaundice and fever. The white cell count was 21,000/microliters, bilirubin was raised to 10.9 mg/dl, and ultrasound examination revealed a sharply circumscribed echo in the distal choledochal duct. Retrograde endoscopic cholangiography revealed a metal-dense concrement, presumably the nidus of gallstone formation. After endoscopic emptying of the bile duct the patient quickly improved so that cholecystectomy could be performed. The long symptom-free interval was most likely due to an at first peripheral position of the splinter in liver tissue. The secretory pressure of the liver cells then probably caused a slow migration into the choledochal duct.

Aged

[Studies of the effect of a protein-free diet and branched-chain amino acids (preparation Aminosteril-Hepa) on selected biochemical indicators in chronic experimental hepatic encephalopathy].

The latest observations suggest that a decreased level of serum branched-chain amino acids plays a role in the pathogenesis of liver encephalopathy. In this study we analysed the behaviour of the serum concentrations of: ammonia, phenols, alpha-amino nitrogen, tyrosine, phenylalanine and tryptophan in rats with thioacetamide-induced liver encephalopathy. The first group of rats was on protein-free diet and Aminosteril-Hepa (Fresenius FRG)--an amino acids solution with predominance of branched-chain amino acids. The second group of rats received a diet with 1 g/kg b.w. of protein daily. The levels of biochemical indices were analysed 0, 3, 5 and 7 days after liver encephalopathy development. The results of our study indicate a favourable influence of infusion a branched-chain amino acids solution (Aminosteril-Hepa) on the biochemical indices, particularly phenols and alpha-amino nitrogen in experimental liver encephalopathy.

Amino Acids

The distribution of peroxidase in phagocytizing human blood platelets, electron microscopy findings.

On the basis of a previously elaborated method for testing the phagocytic ability of human blood platelets we have undertaken studies for testing the distribution of peroxidase in phagocytizing platelets. Our findings confirmed the distribution of peroxidase in the dense tubular system and in granules in regular blood platelets. In the course of phagocytosis we noted the presence of peroxidase less evidently in both subcellular structures during the first of 5 minutes. In the next steps we observed the localization of this enzyme mainly near the phagolysosome. The change of this localization and the role of this enzyme in unspecific immunity against bacteria and neoplasia is briefly discussed.

Blood Platelets

Phagocytic activity of human blood platelets examined by electron microscopy.

On the basis of a previously elaborated system for testing the phagocytic ability of the human blood platelets we have undertaken studies of testing the interaction between platelet and bacteria during phagocytosis examined by the electron microscope. We have found that during phagocytosis platelets lose their discoid shape and demonstrate numerous pseudopods. During 2 min a complete engulfment of the bacterium could be observed. 10 min after starting phagocytosis it is possible to note partially destroyed bacteria. The role of human blood platelets in the antibacterial mechanisms is briefly discussed.

Blood Platelets

[On the existence of a myeloproliferative factor in patients with a myeloproliferative syndrome (author's transl)].

Serum of patients suffering from a chronic myeloproliferative disorder (polycythaemia, era, osteomyelofibrosis, chronic myeloid leukaemia) and serum of lethally irradiated rats injected before application of a single doses of erythropoietin did not enhance the effect of erythropoietin -- measured with the iron incorporation rate of polycythemic mice. The rationale for these experiments is to try to find a "myeloproliferative factor", which augments the number of stem cells as described in sera of patients with polycythaemia vera, osteomyelofibrosis, and lethally irradiated mice.

Adult

Clinical pharmacology in normal volunteers of praziquantel, a new drug against schistosomes and cestodes. An example of a complex study covering both tolerance and pharmacokinetics.

The tolerance of Praziquantel (2-cyclohexylcarbonyl-1, 3, 4, 6, 7, 11b-hexahydro-2H-pyrazino-[2, 1-a]isoquinoline-4-one) in oral doses of 1 X 20 mg/kg, 1 X 50 mg/kg, 3 X 10 mg/kg and 3 X 25 mg/kg body weight (tau = 4 h) was tested in a complex study involving 36 healthy volunteers. In addition to the usual assessment of clinical chemistry, haematology, coagulation physiology, urinalysis, clinico-physiological examination including EEG, and medical examination, clinico-psychological parameters were also recorded and special neurological investigations were performed. No clinically relevant changes were found in any of the laboratory parameters, nor in the medical-neurological or clinico-physiological examinations. Based on a few clinico-psychological parameters and subjective comments, the largest daily dose tested (3 X 25 mg/kg = 75 mg/kg) produced a slight, transient disturbance in general well-being, which was barely detectable on objective clinical examination. The pharmacokinetic behaviour was dominated by rapid metabolism and pronounced first-pass metabolism of praziquantel, which greatly limits the value of results obtained by GC analysis of unchanged drug in serum. The peak concentration in serum was reached after 1--2 h, and the elimination half-life for the period 2--8 h was 1--1.5 h.

Adult

Comparative bioavailability: influence of various diets on the bioavailability of indomethacin.

After oral application of 100 mg indomethacin to eight healthy male volunteers, the concentrations in plasma and their time course were determined when the drug was given to fasting individuals or after a high-protein, a high-lipid or a high-carbohydrate meal. The study was designed as a fourfold-crossover experiement with intermissions of at least one week between applications. Indomethacin in plasma was determined by fluorimetry after a double extraction procedure. Indomethacin plasma concentrations and the truncated areas under the curves (AUC) were evaluated. Administration to fasting subjects provides higher plasma levels and a smaller tmax value than after either one of the three diets. Also the absorption rate was higher in fasting individuals. However, the absorbed amount of indomethacin after 24 hr was practically equal in all four groups. Attempts to distinguish between the effects of the various diets revealed significant differences in the time period necessary to reach the peak values. After high-protein and high-lipid diets they were reached in the 90 min sample while after high-carbohydrate 120 min were required. These values are significantly different from fasting controls (45 min) and from each other. There is no great influence of food on the other aspect of bioavailability, amount of unchanged drug reaching the systemic circulation.

Adult

[Psychodynamic aspects of paraphrenia].

Proceeding from Kraeplin's original a brief summary is given of the literature about the extensive interpretations of the term paraphrenia. Our study is based on a catamnestic examination of schizophrenic diseases first acute in 1930-1940 after 30 respectively 40 years (H. Hinterhuber) and a second group of paraphrenics who at the time being have been under our control for five years. By a simplifying scheme our own conception of paraphrenia is then defined and differentiated from the paranoid schizophrenia and the development of paranoia with special reference to the characteristic juxaposition of schizophrenic symptomatic in otherwise intact personality without a noteworthy derangement of the evironmental relations. The intact personality stands in clear contrast to the only "intact outside personality' with schizophrenic derangement of the ego. Thus the paraphrenic has the possibility to withdraw to the core of his sound personality and erect a mostly stable barrier against the partly massive hallucinations on the periphery of his personality. This corresponds to a passive attitude of avoidance in the sense of behaviour psychology. As THEREFORE the paraphrenic, similar to the phobic, tends to confine the borders of his existence by an increasingly passive avoidance attitude, he tries by a systematic desensibilisation to keep the borders of existence just in the area between psychosis and sound personality and thus render the best possible extent of personality development avoiding secondary restrictions.

Behavior Therapy

[Pharmacokinetics of pramiverine in rats, dogs, and monkeys (author's transl)].

The pharmacokinetic properties of 4,4-diphenyl-N-isopropyl-cyclohexylamine-hydrochloride (pramiverine, Sistalgin) in Wistar rats, beagles, and rhesus monkeys are described. After i.v. injection of 14C-labelled pramiverine incorporation of radioactivity from the blood into organs and tissues is rapid. The radioactivity is eliminated from the blood with a half-life of 4-7 h in rats, 17-32 in dogs, and 8-26 h in rhesus monkeys. Unmetabolized pramiverine, in contrast, is eliminated much faster, the half-lives are 2 h in dogs and 3 h in rhesus monkeys. After oral administration maximum serum concentrations are reached after 4 h in rats and dogs and 2 h in rhesus monkeys. The drug undergoes a marked first-pass effect in the liver. In all species pramiverine is absorbed rapidly from the gastro-intestinal tract. Drug and/or metabolites are eliminated in rats and dogs predominantly with feces, in monkeys with urine, independent of the route of administration. During a 6 h interval, biliary elimination was found to be 50% after i.v. and 30% after oral administration. 90% of pramiverine present in the blood plasma is reversibly bound to proteins.

Administration, Oral