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Biomedical subjects

M Krause

Publications and source records attributed to M Krause.

At least 145 records · Page 8Linked to original sources
PubMed1997

Nonoperative therapy for postcatheterization femoral artery pseudoaneurysms.

Since November 1992, 160 patients were referred to the Vascular Surgery Laboratory for duplex scanning to assess whether a femoral artery pseudoaneurysm was present. Of these patients, 33 per cent (n = 53) had femoral artery pseudoaneurysms with maximal diameters ranging from 1.5 to 8.1 cm. Most pseudoaneurysms (79%; 42 of 53) followed diagnostic or therapeutic cardiac catheterization procedures. Pseudoaneurysms were treated by external compression using an ultrasound probe in 33 of these 53 patients, and thrombosis of the aneurysm was successfully induced in 76 per cent (n = 25) of those in whom nonoperative external compression therapy was attempted. Of the eight patients in whom compression was unsuccessful, three had severe pain that required cessation of compression, and femoral nerve involvement by the pseudoaneurysm was noted at surgery in two of the three. One additional patient refused a second attempt at compression due to discomfort. Of the other four failures of compression, four (50% overall) received anticoagulants during or prior to compression. In 25 patients with successful pseudoaneurysm thrombosis after external compression, none had severe pain from compression, and 40 per cent (n = 10) were on anticoagulants until or during compression. Four of the 53 (7.5%) pseudoaneurysms diagnosed in the vascular laboratory subsequently thrombosed spontaneously, and two patients (3.8%) experienced pseudoaneurysm rupture. Thrombosis of postcatheterization pseudoaneurysms can be achieved by nonoperative compression therapy in most patients. Severe pain during external compression suggests possible femoral nerve involvement by the pseudoaneurysm and is an indication for surgical therapy.

Aged↗
PubMed1997

Bioavailability, antinociceptive and antiinflammatory properties of BP 2-94, a histamine H3 receptor agonist prodrug.

(R)alpha-Methylhistamine [(R)alpha-MeHA], a potent and selective histamine H3 receptor agonist in vitro and in vivo in rodents, was found to display comparatively low plasma level in healthy human volunteers, attributable to an extensive methylation of the drug's imidazole ring by histamine-N-methyltransferase. To limit this inactivation process, BP 2-94, ie., (R)-(-)-2-[[N-[1-(1H-imidazol-4-yl)-2-propyl]imino]phenylmethyl] phenol, was selected as a prodrug. A sensitive radioimmunoassay was developed to study the generation of (R)alpha-MeHA slowly released from BP 2-94 in vitro and in vivo by chemical hydrolysis. In mice after oral administration of BP 2-94 high levels of both prodrug and (R)alpha-MeHA were detected in plasma and various tissues except in the brain. In humans receiving 0.1 mmol BP 2-94 orally, plasma levels of (R)alpha-MeHA-like immunoreactivity decayed with a t(1/2) more than 24 hr, the area under the curve being two orders of magnitude higher than after oral administration of (R)alpha-MeHA. BP 2-94 displayed antiinflammatory and antinociceptive properties in rodents, related to the H3 receptor stimulation. It dose-dependently inhibited capsaicin-induced plasma protein extravasation in many rat tissues with ED50s of 0.6 to 14 micromol/kg p.o., and maximal reductions by 35 to 87%. BP 2-94 also reduced zymosan-induced paw swelling in mice with an ED50 of 1 micromol/kg p.o. and showed marked activity in the phenylbenzoquinone-induced writhing (ED50 = 0.03 micromol/kg, p.o.) or formalin tests in mice, but not in the hot plate jump test. From its pharmacokinetics and pharmacological profile BP 2-94 appears to be a promising novel therapeutic agent in disorders such as asthma, migraine or a variety of inflammatory diseases and pain associated with these disorders.

Adult↗
PubMed1997

[Deciding criteria for vaginal delivery from breech presentation--effect on neonatal early and late morbidity].

In the past 20 years, breech presentation obstetrics has been characterised mainly by the work of Kubli (1975): "The safest and most simple way to prevent the foetal obstetric risk of breech presentation is the systematic Caesarean section." In the past, this resulted in judicial decisions in which due to vaginal delivery a child has been damaged and the doctor has been reproached for not performing a Caesarean section. In the report of the "Standardkommission BEL" (1983) as well as in the Guidelines for the Management of Breech Delivery (FIGO 1993), subtile criteria of decision were demanded for the vaginal delivery method. To an increasing extent clinics lack the necessary training for vaginal-operative delivery for breech presentation, followed by economic obligations and, as a result, in 1994 the frequency of Caesarean sections in cases of breech presentation was 86.9% in Bavaria. Investigations should be made as to whether it is actually necessary, for the benefit of the child, to subject a mother of a breech baby to such high-risk operations. From 1988 to 1995, 1116 breech babies were born in the Gynaecological Clinic Nürnberg, Dept. of Obstetrics. The case history of 650 children with a period of gestation > 32 weeks of pregnancy were evaluated: parity, period of gestation, method of delivery, condition after Caesarean section, premature rupture of the foetal membranes, position of legs, weight of child, Apgar score, umbilical artery pH, base excess in umbilical artery mval/l, transfer ratio to paediatric clinic, reason of transfer to paediatric clinic, rate and duration of intubation, cranial sonogram and electroencephalogram.

Acid-Base Equilibrium↗
PubMed1996

[Infectious diarrhea].

Infectious diarrhea is a very common, usually self-limited disease. Among travellers to developing countries, diarrhea is by far the most common medical problem. The intake of sufficient glucose-electrolyte solutions is the most important step to prevent dehydration. Loperamide may be prescribed as a valuable antimotility agent: however, this drug should not be used in patients with high fevers, bloody diarrhea and severe abdominal cramps. Stool cultures are recommended in cases without improvement, when clostridium difficile is suspected and when multiple cases occur. Antibiotics are indicated for treatment of certain microorganisms, for patients with immunosuppression and in dysenteric syndromes. They are not recommended for prophylaxis on a routine basis.

Anti-Bacterial Agents↗
PubMed1996

[A case of acute sarcoidosis].

Upper respiratory tract involvement occurs in 1 to 6% of all patients with sarcoidosis. Dry cough, hoarseness, dyspnea and dysphagia are the main symptoms. The diagnosis is established by biopsy demonstrating granulomatous lesions. We report the case of a 22-year-old woman who presented with erythema nodosum, arthralgias and granulomatous lesions of the trachea, larynx and bronchi. Although the biopsies of the lesions were nondiagnostic, the diagnosis of acute sarcoidosis was made, and a steroid therapy was initiated. The patient recovered rapidly, and the lesions disappeared. The features and differential diagnosis of upper respiratory tract sarcoidosis are discussed.

Acute Disease↗
PubMed1996

[Visceral and neurological complications in Varicella infections of adults].

Primary varicella-zoster virus (VZV) infections in adults generally follow a more severe course than in children and are more often associated with life-threatening complications. In the years 1992 to 1995 we observed 7 immunocompetent adults with a severe course of primary VZV infection. All 7 patients presented initially with a characteristic rash. In 6 patients the diagnosis of VZV was confirmed by ELISA on material taken from the lesions, and in all of them it was confirmed by serology. The following complications were observed: pneumonia (5x), elevated liver enzymes (4x), myocarditis (1x), encephalitis (1x) and myelitis (1x). Pulmonary lesions were characterized by bilateral interstitial infiltrates on chest-x-ray and required mechanical ventilation in 2 patients. The liver enzymes were only slightly elevated and clinically not significant. Myocarditis in one case was postulated in view of elevated creatine kinase levels, ECG-repolarization changes and AV-block III which required the insertion of a transitory pacemaker. Encephalitis presented as abnormal behaviour at work followed by seizures. Myelitis was suspected due to ascending sensory motor tetraparesis and confirmed by MRI. All patients were treated with high doses of parenteral acyclovir (3 x 10 mg/kg body weight i.v. per day) for 5-12 days. 6 patients recovered completely and only the patient with myelitis has residual neurological deficits 3 months after discharge. Although we cannot exclude the possibility that supportive therapy without acyclovir would have had the same outcome, we recommend high-dose parenteral acyclovir for treatment of visceral and neurological complications in primary VZV infections in adults.

Acyclovir↗
PubMed1996

New potent azomethine prodrugs of the histamine H3-receptor agonist (R)-alpha-methylhistamine containing a heteroarylphenyl partial structure.

The therapeutic value of histamine H3-receptor ligands is under current investigation. On the basis of recently described diary limine prodrugs of the histamine H3-receptor agonist (R)-alpha-methylhistamine (1) as a series of new azomethine prodrugs containing five- and six-membered heterocycles were synthesized and tested for their in vitro hydrolysis rates and in vivo activity after oral application. It was found that electron-deficient six-membered heterocycles drastically destabilized the imine double bond so that these prodrugs decomposed unsuitably fast. On the contrary, prodrugs containing five-membered heterocycles appeared to be highly effective for the CNS delivery of 1, and a remarkable correlation between chemical structure and pharmacokinetic profile was observed. Particularly (R)-4-fluoro-2-[[N-[1-(1H-imidazol-4-yl)-2-propyl]imino] (1H-pyrrol-2-yl)methyl]phenol (8c), the 2-furanyl analogue 8d, and its 3-furanyl isomer 8e proved to be equipotent to the most potent of recently described halogenated diaryl imine prodrugs of 1. However, in contrast to any other azomethine prodrug, 8c exhibited an incomparably long lasting delivery of 1 in the CNS and can thus be regarded as a 'retard' prodrug. Assuming that a therapeutic indication of histamine H3-receptor agonists will soon be established, these highly potent heteroarylphenyl azomethine prodrugs, which already serve as valuable pharmacological tools, may also become potential drugs in clinical use.

Animals↗
PubMed1996

Diagnostic accuracy in remote expert consultation using standard video-conference technology.

An international multicenter study (Germany, Sweden, and Switzerland) was performed to investigate the feasibility and diagnostic reliability of standard video-conferencing (VC) technology for remote expert consultation in radiology. Three high-spatial-resolution films (hand-bone, mammography, chest) and two low-spatial-resolution image sets (liver CT and MRI) were studied (total 446 images taken from different examinations). The images were recorded by a video camera, transmitted via public broadband networks, and displayed on a video monitor. The resolution of the recorded images varied from 2.4 lp/mm to 4.8 lp/mm at maximum zoom. After 3-4 months, the images were reexamined using conventional light-box reading. Diagnostic reliability was evaluated by receiver operating characteristics (ROC) analysis. With video conferencing, there was a noticeable loss of diagnostic accuracy for the high-spatial-resolution films, whereas for liver CT and liver MRI images VC reading seemed to be satisfactory (average area value difference < 0.02).

Feasibility Studies↗
PubMed1996

A common pathway for p10 and calyx proteins in progressive stages of polyhedron envelope assembly in AcMNPV-infected Spodoptera frugiperda larvae.

The assembly of the polyhedron envelope in baculovirus-infected cells has been the subject of several studies, yet it is still poorly understood. We have used immunogold-labelled antibodies to two baculovirus proteins, p10 and calyx (also referred to as polyhedron envelope protein or PEP), to follow envelope assembly in AcMNPV-infected tissues of Spodoptera frugiperda larvae. We show that, in wild type virus, both proteins colocalize in fibrillar structures and associated electron-dense spacers which progress to encircle the polyhedra, as well as in completed polyhedron envelopes. In cells infected with polyhedrin-negative (PH-) viruses, an unusual proliferation of these spacers was observed suggesting a deregulatory event in the envelope assembly process. Results of Northern and Western blot analysis revealed that synthesis of P10 and calyx mRNA and proteins in PH- AcMNPV is unaffected as compared to wild type virus. Taken together, the observed physical and compositional connection between fibrillar structures, spacers and polyhedron envelopes, as well as the abnormal appearance of the spacers in PH- mutants, provide further evidence in support of a cooperative role of these structures in the assembly of the polyhedron envelope.

Animals↗
PubMed1996

A portable absorption-fluorometer for detection of organic substances in fluids.

Using the method of multipath-saturation fluorescence, which considers both fluorescent as well as nonfluorescent substances, the total absorption coefficient can be determined with high sensitivity. This new fluorescence method is appropriate, e.g. for in-situ applications. Thus a portable absorption-fluorometer has been constructed. The main part of the device is a multireflection cell based on a design of Herriott with a 1 cm quartz-cuvette. Two pairs of spherical dielectric mirrors are used to realize the multireflection of the excitation radiation in the UV and blue spectral range. The combination of a cylindrical and a convace mirror leads to a long pathway of the excitation radiation and, thus, to a full absorption by the fluid. A first experiment has been performed with drinking water samples defined polluted by non-fluorescent p-nitrophenol and 2-nitroaniline. Based on the method of multipath-saturation fluorescence a good correlation to the substance concentration was achieved, whereas the conventional absorption failed.

Journal Article↗
PubMed1996

Structure-activity relationships of novel azomethine prodrugs of the histamine H3-receptor agonist (R)-alpha-methylhistamine: from alkylaryl to substituted diaryl derivatives.

This study was performed on the basis of recently developed prodrugs of the histamine H3-receptor agonist (R)-alpha-methylhistamine (1) to determine structure-activity relationships of azomethine prodrugs of 1, in which the primary amine functionality is bioreversibly linked to aromatic ketones. Therefore, the pro-moiety was systematically altered from alkylaryl over benzylaryl to diaryl substitution. Those compounds that emerged to be stable enough during preparation were tested for their in vitro hydrolysis rates. Apparently, bulky alkyl residues were capable of preventing previously observed intramolecular cyclization, but the obtained azomethines 12a-c were far too unstable to serve as prodrugs. However, the benzylaryl imines 12d, e were stable compounds, but 12d decomposed too rapidly under in vitro conditions. Distinctly greater stability was provided by diaryl pro-moieties, even if strongly electron-withdrawing functionalities were introduced. Selected compounds were also tested in vivo following p.o. application to mice. Particularly the trifluoromethyl substituted imine 12i proved to be highly effective as stability and rate of conversion were well-balanced, so that brain penetration of 1 was strikingly facilitated. Thus 12i, a highly potent azomethine prodrug, may serve as an important pharmacological tool and, possibly, a therapeutic agent.

Animals↗
PubMed1996

Autologous connective tissue chamber as a tool for introducing active substances into the CNS.

A new method of introducing active substances into the CNS is described. The autologous connective tissue chambers were obtained by implantation of a silicone tube under the back skin of rats. Subsequently they were filled with fibrine and additionally with NGF or submicrosomal fractions from nonpredegenerated and predegenerated peripheral nerves. Filled chambers were implanted stereotaxically into the injured hippocampus. The neurite outgrowth was examined by means of FITC-HRP and acetylcholinesterase-method. Implanted connective tissue chambers are very useful in getting active substances into the CNS. This method allows to avoid inflammatory processes and does not hinder the histological procedures.

Acetylcholinesterase↗
PubMed1995

Comparison of mortality from acute myocardial infarction in patients receiving anistreplase with those not receiving thrombolysis.

Within 1 year, 434 patients were admitted to 14 hospitals with suspected acute myocardial infarction (AMI) < or = 4 hours after the onset of symptoms. Group A consisted of 171 patients (39%) treated with thrombolysis, and group B consisted of 263 patients (61%) with contraindications. Patients in group A more likely had a "definite AMI" (92%; group A1) than patients in group B (67%; group B1). Group B1 had 277 contraindications (1.6/per patient) with increased risk for life-threatening bleeding being the most frequently recorded at admission. The in-hospital mortality in group A1 was 7% (11 of 158) and in group B1, 27% (47 of 177) (p < 0.0001). Age and type of therapy (thrombolysis or no thrombolysis) were identified as independent predictors of increased mortality (p < 0.0001 and < 0.05, respectively). Thus, although most patients with an AMI are excluded from thrombolytic therapy because of contraindications, our data suggest that their in-hospital mortality is unexpectedly high. Further evaluation of this group of patients is warranted to define the impact of contraindications as an independent factor of mortality.

Aged↗
PubMed1995

Synthesis, X-ray crystallography, and pharmacokinetics of novel azomethine prodrugs of (R)-alpha-methylhistamine: highly potent and selective histamine H3 receptor agonists.

Since various neuroregulatory functions of the histamine H3 receptor have been proved during the last few years, the H3 receptor is of current interest. Azomethine derivatives of the highly potent histamine H3 receptor agonist (R)-alpha-methylhistamine (1) were prepared as lipophilic prodrugs to improve the bioavailability of the hydrophilic drug, particularly its entry into the brain. Additionally, azomethine derivatization provides protection against histamine methyltransferase, the major metabolizing enzyme in man, and thus efficiently enhances the bioavailability of 1. The molecular conformations of (R)-2(-)[[N(-)[1-(1H-imidazol-4-yl)-2-propyl]- imino]phenylmethyl]phenol (9a) and (R)-4-fluoro-2(-)[[N(-)[1-(1H-imidazol-4-yl)-2-propyl[imino]- (4-chlorophenyl)methyl]phenol (9p) were determined by X-ray structure analysis. An intramolecular hydrogen bond which is essential for the stability of these azomethines was thereby confirmed. Moreover, the pharmacokinetic parameters of the prodrugs were investigated in vitro as well as in vivo. The halogenated azomethines have an effect following peroral administration in mice, and some of them seem to be highly potent for the central nervous system (CNS) delivery of 1. At present the most potent prodrug of 1 is (R)-4-chloro-2(-)[[N(-)[1-(1H-imidazol-4-yl)-2-propyl]imino](4- chlorophenyl)methyl]phenol (9q), reaching by far the highest CNS level of 1 (Cmax = 71 ng/g). Prodrugs of this type are not only valuable pharmacological tools but may also become H3 histaminergic drugs for therapeutic use.

Animals↗
PubMed1995

[Intensive care aspects in severe tropical malaria: clinical aspects, therapy and prognostic factors].

In a retrospective study we analyzed the clinical and blood chemical data of 12 patients with severe tropical malaria in the intensive care units of the University Hospital Zurich and the Stadtspital Triemli, Zurich, between 1991 and 1994. None of the 12 patients had been exposed to malaria before or had taken drugs for chemoprophylaxis. 7 patients survived, 5 died from complications of malaria. According to the criteria of severe tropical malaria defined by the WHO, the following pathological clinical and blood chemical parameters were noted on admission: cerebral coma (2/12); blood hemoglobin < 5 g/dl (0/12), < 8 g/dl (2/12); serum creatinine > 265 mumol/l (3/12); blood glucose < 2.2 mmol/l (0.12); circulatory collapse/shock (0/12); bleeding/signs of disseminated intravascular coagulation in laboratory tests (4/12); acidosis with pH < 7.25 (1/12). Further signs of severe tropical malaria were: hyperparasitemia > 5% (9/12); qualitative and quantitative disturbances of consciousness (6/12); thrombocytopenia < 30 x 10(9)/l (9/12); hyponatremia 125-135 mmol/l (9/12), < 125 mmol/l (2/12); rhabdomyolysis with creatine kinase > 1000 U/l (4/12). The basic treatment consisted of parenteral quinine hydrochloride in all patients; doxycycline was added in 8 cases, clindamycin in 3. Adjuvant therapy with desferrioxamin was given in 3 cases. 6 patients had exchange transfusions. Parasitemia cleared in all patients within 5 to 6 days. Later in the course, 5 patients developed acute respiratory distress syndrome, 6 required hemofiltration due to oliguria, and one became comatose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

MyoD and myogenesis in C. elegans.

One of the goals in developmental biology is the identification of key regulatory genes that govern the transition of embryonic cells from a pluripotent potential to a specific, committed cell fate. During vertebrate skeletal myogenesis, this transition is regulated by the MyoD family of genes. C. elegans has muscle analogous to vertebrate skeletal muscle and has a gene (hlh-1) related to the MyoD family. The molecular and genetic characterization of hlh-1 shows that it is very similar to the vertebrate MyoD family in many respects, including its expression pattern and DNA binding activity. The hlh-1 product is required for proper myogenesis, but it is not required for myogenic commitment during embryogenesis in the nematode. The role of this MyoD-related gene in nematode myogenesis is discussed and compared to those of the vertebrate MyoD family.

Animals↗