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Biomedical subjects

T Winkler

Publications and source records attributed to T Winkler.

At least 91 records · Page 5Linked to original sources
PubMed1987

Further observations on the depression of group Ia facilitation of motoneurons by vibration in man.

Stimulation of low threshold afferents in the peroneal nerve causes a short latency facilitation of individual tibialis anterior motor units considered to be due to the composite Ia EPSP. This facilitation is depressed by vibration 20 to 128 Hz applied over the tibialis anterior. The depression occurs without any change in the firing rate of the motor unit or in the facilitation from cutaneous afferents and so is unlikely to be due to postsynaptic inhibition. The depression can occur with vibration frequencies as low as 40 Hz and is therefore unlikely to be due to occlusion in Ia afferents. There is no evidence that vibration alters the electrical threshold of large afferents. A similar facilitation of soleus motor units resulting from stimulation of low threshold afferents in the tibial nerve is depressed for up to 75 ms following a 40 ms burst of 50 Hz vibration applied to the tendon of the tibialis anterior. The burst of vibration itself did not facilitate soleus motor units so there is no evidence to suggest that the vibration spread to soleus spindles. Homosynaptic depression is, therefore, unlikely. These findings provide further evidence that presynaptic inhibition of Ia afferents occurs in man.

Action Potentials↗
PubMed1986

Biotransformation of oxaprotiline: isolation and identification of metabolites in urine of rat and dog.

The biotransformation of oxaprotiline has been investigated in rat and dog after oral administration of racemic 14C-labelled oxaprotiline X HCl. Rats excreted 28% dose in urine within 120 h and dogs 32% within 96 h. The metabolites were isolated by liquid chromatography and their structures elucidated by spectroscopic methods. In both species, oxaprotiline is extensively metabolized. Principal metabolic transformations are aromatic hydroxylations and formation of aromatic hydroxy-methoxy derivatives, N-demethylation, deamination and direct O-glucuronidation. Most of the primary metabolites formed by functionalization reactions occur in both free and glucuronidated form. In the rat, diastereoisomeric 3-hydroxy metabolites and the corresponding phenolic glucuronides are predominant. Products of deamination are minor, and products of direct O-glucuronidation are not detectable. In the dog, biotransformation is more complex. Major metabolites are diastereoisomeric 2- and 3-hydroxy compounds and the corresponding phenolic glucuronides. Oxidations in the side-chain and direct O-glucuronidation are minor metabolic pathways.

Animals↗
PubMed1986

The metabolism of 14C-oxcarbazepine in man.

The disposition of the new anti-epileptic agent oxcarbazepine (10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide) has been studied in two healthy volunteers following an oral 400 mg dose of 14C-labelled drug. The dose was excreted almost completely in the urine (94.6 and 97.1%) within six days. Faecal excretion amounted to 4.3 and 1.9% of the dose in the two subjects. In the 0-6 days urine samples the biotransformation products have been isolated and identified. 10,11-Dihydro-10-hydroxycarbamazepine (GP 47,779) and its two diastereoisomeric O-glucuronides were found as main metabolites. Taken together, they accounted for 79% of urinary 14C. Unchanged oxcarbazepine, and its sulphate and glucuronide conjugates were isolated in smaller amounts only (13%). Other minor metabolites were the trans- and cis-isomers of 10,11-dihydro-10,11-dihydroxy-carbamazepine (approximately 4%), and a phenolic derivative of GP 47,779 (less than 1%). The biotransformation of oxcarbazepine proceeds mainly by reduction to GP 47,779, and subsequent conjugation with glucuronic acid. Reduction is stereospecific, favouring the S-configuration of GP 47,779. Direct conjugation of oxcarbazepine, in the enol form, is a minor pathway. Oxidative reactions are unimportant.

Biotransformation↗
PubMed1985

Indoxyl derivatives of drug metabolites.

Indoxyl derivatives were detected as minor products among the urinary metabolites of two trial drugs, a benzodiazepine (GP 55 129) and a benzophenone (CGP 11 952). Their structures were elucidated by NMR and mass spectroscopy. Presumably, metabolites containing potential aldehyde functions react spontaneously with endogenous indoxyl. Such derivatives have not hitherto been encountered in drug metabolism.

Animals↗
PubMed1985

Isolation and identification of hydroxylated maprotiline metabolites.

Lipophilic maprotiline metabolites were extracted from human urine and animal excreta, with or without prior enzymic hydrolysis, purified by repeated t.l.c. and their structures determined by u.v., n.m.r. and mass spectrometry. Urine from patients under treatment with maprotiline contained the isomeric phenols, 2- and 3-hydroxymaprotiline, the 2,3-dihydrodiol, and an alcoholic metabolite, besides smaller quantities of the corresponding N-demethylated compounds. In dog urine and/or faeces the same products of aromatic hydroxylation were present as in human urine and in addition 3-hydroxy-2-methoxymaprotiline; alcohols were not detected. The only metabolites identified in rabbit urine and rat bile were 3-hydroxy- and 3-hydroxy-2-methoxymaprotiline.

Animals↗
PubMed1984

The metabolic fate of [14C]oxaprotiline.HCl in man. II. Isolation and identification of metabolites.

The new antidepressant agent oxaprotiline is extensively metabolized by man. Following an oral 50 mg dose of racemic [14C]oxaprotiline, most of the 14C was excreted in the urine as metabolites (greater than 98% total 14C); only 1% was excreted unchanged. Glucuronidation at the carbinol group of the molecule is the major metabolic pathway (83%). The two diastereoisomeric glucuronides were separated; the more polar O-glucuronide of S(+)-oxaprotiline predominates (44%), suggesting stereoselective disposition of the two enantiomers. Oxidative pathways are minor, and yield desmethyl oxaprotiline (10%) and 3-hydroxy R(-)-oxaprotiline (4%), both of which are conjugated with glucuronic acid. The biotransformation of oxaprotiline in man is less complex than that of other polycyclic antidepressants, which are metabolized mainly by oxidative reactions.

Anthracenes↗
PubMed1983

Synthesis and biological evaluation of neutral derivatives of 5-fluoro-2'-deoxyuridine 5'-phosphate.

5-Fluoro-5'-(2-oxo-1,3,2-oxazaphosphorinan-2-yl)-2'-deoxyuridine (1a) and 5-fluoro-5'-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-2'-deoxyuridine (1b) were prepared by reaction of 5-fluoro-2'-deoxyuridine (7a) and phosphoryl chloride with 3-amino-1-propanol and 1,3-propanediol, respectively. The thymidine analogues, 1c and 1d, were prepared similarly from thymidine. Compound 1b was synthesized in better yield from 13a and trimethylene phosphate with triphenylphosphine/diethyl azodicarboxylate as a condensing agent. Compounds 1a-d were resistant to degradation by 5'-nucleotidase, alkaline phosphatase, venom phosphodiesterase, and crude snake venom. None of these compounds were significantly biotransformed when incubated with mouse hepatic microsomal preparations in the presence of an NADPH-generating system. When administered intraperitoneally (ip) for 5 consecutive days, 1a was nearly as effective as 5-fluorouracil at prolonging the life spans of BDF1 mice implanted intraperitoneally with leukemia P-388. However, much larger dosages of 1a were required for optimal activity. Compound 1b administered similarly was only marginally effective. Neither 1a nor 1b was active against a P-388 mutant resistant to 5-fluorouracil.

5'-Nucleotidase↗
PubMed1979

Biotransformation of diclofenac sodium (Voltaren) in animals and in man. I. Isolation and identification of principal metabolites.

1. The anti-inflammatory agent diclofenac sodium (o-[(2,6-dichlorophenyl)amino]phenylacetic acid sodium salt) is extensively metabolized by rat, dog, baboon and man. The main metabolites were isolated from the urine of all species and from the bile of rat and dog and identified by spectroscopy. 2. Metabolism involves direct conjugation of the unchanged drug, or oxidation of the aromatic rings usually followed by conjugation. Sites of oxidation are either position 3' or 4' of the dichlorophenyl ring or, alternatively, position 5 of the phenyl ring attached to the acetic acid moiety. 3. In the urine of rat, baboon and man conjugates of the hydroxylated metabolites predominate, but the major metabolite in dog urine is the taurine conjugate of unchanged diclofenac. 4. In the bile of rat and dog, the main metabolite is the ester glucuroniade of unchanged diclofenac.

Animals↗
PubMed1979

Human urinary metabolites of 1-(tetrahydro-2-furanyl)-5-fluorouracil (ftoraful).

Two hydroxylated metabolites were isolated from the urine of a patient who had received ftorafur (5 g/sq m). These metabolites were identified by mass spectrometry and nuclear magnetic resonance spectroscopy as trans-3'- and cis-4'-hydroxyftorafur. The compounds were not converted to 4-fluorouracil when incubated in plasma, base (pH 9), or water. Because of their stability, it is unlikely that these metabolites are in vivo precursors of 5-fluorouracil. There are indications that less stable, unisolatable, hydroxylated ftorafur derivatives are intermediates in the conversion of ftorafur to 5-fluorouracil.

Chemical Phenomena↗
PubMed1977

Retrieval of an upper third molar from the infratemporal space.

A case of dislocation of a maxillary third molar into the infratemporal fossa is described. The diagnostic and therapeutic problems are discussed. The tooth was removed through an osseous window that was made in the posterior wall of the maxillary sinus. The healing was uncomplicated, without maxillary sinusitis, and the reduced ability to open the mouth returned to normal. A slight diplopia persisted.

Adult↗
PubMed1975

Direct bonding on impacted teeth.

In eighteen patients twenty-three impacted teeth were surgically exposed and provided with Cuspid-Pull Brackets by the direct-bonding technique. Light orthodontic traction was applied after 10 minutes. Only three brackets were lost during the experiment. The experiment showed that sufficient bonding could be established on impacted teeth without pumicing the tooth surface and that phosphoric acid in minimal amounts causes no harm to the adjacent tissues but assists in preventing bleeding from the surrounding tissues. This made it possible to obtain the necessary dryness of the exposed tooth surface. The reasons for bond failure are discussed.

Adolescent↗
PubMedDate not supplied

Listeria brainstem encephalitis: two own cases and literature review.

We analysed two of our own and 21 patients described in the literature with listeria brainstem encephalitis. The disease was characterised by a prodromal state with fever, nausea and headache followed by severe brainstem dysfunction with multiple cranial nerve palsies, ataxia, respiratory insufficiency and coma. The diagnosis was established by isolation of Listeria monocytogenes from CSF and/or serum. Serological tests are without diagnostic evidence. Cerebrospinal fluid examination may not initially point to a bacterial infection. Computed tomography and magnetic resonance imaging technique might supply evidence of brainstem involvement and contribute to an early diagnosis. There is a high percentage of lethal outcome without early antibiotic therapy.

Adult↗
PubMedDate not supplied

Percutaneous creation of arteriovenous hemodialysis grafts: work in progress.

PURPOSE: To develop a technique of percutaneous creation and/or revision of arteriovenous hemodialysis access grafts, and to study the feasibility of the technique in the acute setting. MATERIALS AND METHODS: Arteriovenous shunts, consisting of silicone-covered Wallstents 6 (n = 10) or 8 (n = 1) mm in diameter and 11-17 cm in length, were created in 10 mongrel dogs. All shunts were created percutaneously except one, in which the carotid artery was exposed surgically and the jugular vein accessed percutaneously to create a straight external graft. All other grafts were femoral loops (femoral artery to femoral vein). Eight were tunneled subcutaneously and three were left external. All shunts were delivered through 10-F peel-away sheaths. RESULTS: The 11 shunts were allowed to flow for a mean of 4 hours (range, 1.0-6.5 hours) before the animals were killed. Leakage around the "anastomoses" was not observed. Leaks in the silicone covering were observed, resulting in one early shunt failure. Two attempted survival experiments were aborted due to early shunt dislodgment at 1.5 and 3.5 hours. CONCLUSIONS: Percutaneous arteriovenous shunt creation is feasible through acceptably small sheaths. Peel-away sheath placement of the stent circumvents the technical problem of placing a closed device into both artery and vein. This technique may allow percutaneous revision of existing hemodialysis access grafts and possibly de novo creation of grafts in humans, but modification of the grafts will be needed to prevent dislodgment.

Animals↗