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Biomedical subjects

B Walther

Publications and source records attributed to B Walther.

At least 37 records · Page 2Linked to original sources
PubMed1996

Simplified percutaneous gastrostomy.

PURPOSE: The aim of this study was to develop a simple radiological method for the creation of percutaneous gastrostomy. MATERIAL AND METHODS: Percutaneous gastrostomy was created in 15 patients. After a blunt dissection of the abdominal wall under local anesthesia, puncture of the stomach was performed. A 6-mm peel-off introducer sheath was used to place the permanent catheter. Immediate use of the catheter was allowed. RESULTS: The procedure was successful in all cases and no procedural complications were seen. CONCLUSION: The method is simple, cost-saving, and may be recommended as an alternative to other methods.

Adult↗
PubMed1996

Identification of trimetazidine metabolites in human urine and plasma.

1. The objective was to use modern mass spectrometric techniques to update current information on the metabolism of trimetazidine in human subjects found by previous studies. 2. Urine and plasma samples were taken from four healthy human volunteers taking part in a larger kinetic study. Each subject received an oral dose of 80-mg trimetazidine daily for 4 days. 3. Identification and quantitation of trimetazidine and its metabolites in urine and plasma were achieved using modern liquid chromatography-mass spectrometric methods. 4. The major drug-related component observed in urine and plasma was unchanged trimetazidine. In addition to the parent drug, 10 metabolites were detected in urine in concentrations ranging from 0.008 (0.01% dose) to 1.094 micrograms.ml-1 (1.4% dose). Metabolic profiles following acute and chronic doses of trimetazidine were qualitatively similar.

Adult↗
PubMed1996

Synthesis of putative metabolites and investigation of the metabolic fate of gliclazide, [1-(3-azabicyclo(3,3,0)oct-3-yl)-3-(4-methylphenylsulfonyl) urea], in diabetic patients.

Synthesis of postulated hydroxylated metabolites of gliclazide is described together with their detailed structural analysis using 1H-NMR, two-dimensional 1H-NMR, and MS to characterize the products. Metabolism of gliclazide has been investigated in the urine of nine patients of different ethnic origins receiving gliclazide therapy for the treatment of diabetes. Urine extracts were analyzed by GC/MS to quantify and identify the metabolites excreted in urine and the metabolites compared with the synthesized products. Metabolic profiles in all diabetic patients were very similar and comparable with those reported for healthy human volunteers. In addition to the expected metabolites arising from oxidation of the 4-methylphenyl ring, four isomeric hydroxylated products of the azabicyclooctyl ring were identified and the structure of a fifth isomer postulated.

Adult↗
PubMed1994

Methods for the analysis of the new vinca alkaloid derivative, S 12363, in plasma by high-performance liquid chromatography with fluorescence detection.

Two sensitive analytical methods for the analysis of S 12363 in plasma are described. A highly sensitive procedure for human and dog plasma using cyanopropyl solid-phase extraction with ion pairing chromatography and fluorescence detection, has a limit of quantification of 0.1 ng ml-1. The technique has an overall precision and accuracy of 4.8 and 5.4% respectively over the concentration range 0.1-20 ng ml-1. A second, less sensitive, assay specifically adapted for rodent plasma, uses benzene sulphonyl cation-exchange solid-phase extraction followed by reversed-phase chromatography, with post-column fluorescence enhancement. This method has a limit of quantitation of 1.0 ng ml-1, with overall accuracy and precision of 7.2 and 11.6% respectively, over the concentration range 1.0-20.0 ng ml-1. Both assays have been successfully applied to dog and mouse toxicokinetic studies.

Animals↗
PubMed1994

The application of electrospray and neutral-loss mass spectrometry to the identification of the metabolites of S12813 in rat liver slices.

The metabolism of S12813, (3-(2-[4-phenyl piperazin-1-yl] ethyl)-2-oxo-2,3-dihydro oxazolo [4,5-b] pyridine chlorohydrate), in rat liver slice incubates was examined by high performance liquid chromatography combined with mass spectrometry. Electrospray ionization was used together with tandem mass spectrometric techniques of analysis (MS/MS). Polar phase I and phase II metabolites were identified as C-oxidation products, which were then conjugated to form either sulphate or glucuronide metabolites. On the basis of the identifications made, a metabolic pathway of S12813 in rat liver slices has been proposed.

Analgesics↗
PubMed1993

Method for the analysis of S9788, a drug to reverse resistance to anticancer agents, in animal plasma and human plasma and serum by high-performance liquid chromatography with ultraviolet detection.

An extraction method has been developed using benzene sulphonyl cation-exchange sample preparation cartridges and reversed-phase high-performance liquid chromatography with ultraviolet detection for the measurement of S9788, a drug to reverse resistance to anticancer agents, in plasma and serum. This includes a toxicokinetic assay which has a mean precision and accuracy of 11.7% and 7.9%, respectively, over the range 10-1000 ng ml-1 and a quantification limit of 10 ng ml-1 and a more sensitive pharmacokinetic procedure with a mean precision and accuracy of 5.0% and 7.9%, respectively, over the range 1-500 ng ml-1 and a quantification limit of 1 ng ml-1. The specificity of the procedure has been demonstrated by mass and ultraviolet spectrometry, and linearity, precision, accuracy, recovery and sensitivity have been established. The assays have been successfully applied to toxicokinetic and pharmacokinetic studies.

Animals↗
PubMed1993

Outcome 5 years after 360 degree fundoplication for gastro-oesophageal reflux disease.

Forty patients with a mean age of 45 (range 22-65) years were operated on between 1982 and 1985 for gastro-oesophageal reflux disease with a short floppy 360 degree fundoplication. The results of the operation were determined by endoscopy, oesophageal manometry, ambulatory 24-h pH recording and symptom evaluation 6 months and 5 years after operation. These results were compared with findings in healthy controls. The median pressure in the lower oesophageal high-pressure zone was 13.3 (interquartile range (i.q.r.) 11.3-21.3) mmHg after 5 years, which did not differ significantly from the value at 6 months' follow-up or from that in controls. It was, however, significantly higher than the preoperative pressure. The median intra-abdominal length of the high-pressure zone was 1.7 (i.q.r. 1.3-2.3) cm after 5 years, significantly less than at 6 months but equal to control length. Measurement of the proportion of total time at pH < 4 at 5 years (median 0.2 (i.q.r. 0.0-0.6) per cent) and 6 months after operation revealed a significant reduction in acid reflux compared with preoperative values and normal controls. There was no significant difference in acid exposure between the two postoperative investigations. Endoscopy showed that 27 patients had no oesophagitis, three had erythema and three persistent Barrett's oesophagus 5 years after operation. Normal belching was possible in 22 patients and 18 experienced increased flatulence 5 years after fundoplication. An independent gastroenterologist found that the result was excellent in 16 patients, good in 16 and fair in four; two patients had a poor overall outcome of the operation. It is concluded that a 360 degree fundoplication provides good long-term control of reflux and that slight symptoms of overcompetence are common among patients operated on without affecting the overall result.

Adult↗
PubMed1993

Local regulation of vascular tone by bradykinin and angiotensin converting enzyme inhibitors.

Part of the vasodilator response to angiotensin converting enzyme (ACE) inhibitors depends on stimulation of bradykinin receptors, but in most studies the anticipated increase in plasma kinin concentration during ACE inhibition was not detected. We investigated the role of local ACE inhibition on endothelial control of vascular tone. Rings of bovine coronary, renal and tail arteries, as well as human coronary arteries, were mounted in organ chambers so that the isometric force could be recorded. The ACE inhibitors, captopril, fosinoprilat, enalaprilat, lisinopril, and ramiprilat alone had no affect on the vascular tone of bovine coronary arteries with endothelium. However, these ACE inhibitors did potentiate relaxations to bradykinin and the slowly degradable bradykinin derivative [Hyp3-Tyr(Me)8]-bradykinin (3 x 10(-11) M). A similar response was observed in human coronary arteries. The response was not observed in rings of any vessel without endothelium, or after incubation with nitro-L-arginine (10(-4) M), or the bradykinin2-receptor antagonists Hoe 140 (10(-8) M). The sensitivity to bradykinin was higher and the potentiating effect of ACE inhibition larger in the bovine coronary artery than in the renal and tail artery. Thus, ACE inhibition causes selective coronary vasodilation by potentiating the bradykinin-induced release of nitric oxide from the endothelium. The related mechanism underlying these effects must occur at the surface or within the arterial wall and seems to be independent of the degradation of the kinins.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Aplasia of the retinal vessels combined with optic nerve hypoplasia, neonatal epileptic seizures, and lactic acidosis due to mitochondrial complex I deficiency.

A newborn male with mitochondrial complex I deficiency suffered from neonatal epileptic seizures, which later developed into infantile spasms. The infant was blind due to aplasia of the retinal vessels and hypoplasia of the optic nerve. There was congenital lactic acidosis, which persisted in later life. The boy was microcephalic and retarded. Muscular hypotonia later shifted to spasticity. Succinic acid was increased in urine. We assume that the aplasia of the retinal vessels is due to damage of the retinal ganglion cells caused by the mitochondrial disease in the first 3 to 4 months of pregnancy.

Acidosis, Lactic↗
PubMed1992

Nutrient intake and biochemical markers of nutritional status during long-term follow-up after total and partial gastrectomy.

Dietary intake and biochemical nutritional status was studied in patients who had undergone total gastrectomy (TG, n = 10) or partial gastrectomy (PG, n = 10) several years ago. The dietary intake of energy, macronutrients and micronutrients was very similar in the two groups and was also similar to the intake reported for healthy subjects in Sweden. The concentration of alpha-tocopherol in serum was subnormal in the TG group and that of carotene in both groups of patients, and the values were also significantly lower in the TG group than in the PG group. This was probably due to fat malabsorption, since dietary intake was found to be adequate. The proportions of n-6 and n-3 polyunsaturated fatty acids in serum phosphatidylcholine were not significantly different between the TG and PG groups. Iron deficiency was found in three patients in the TG group. Three patients (two TG, one PG) had elevated serum alkaline phosphatase and one patient (PG) had subnormal cobalamin concentration. For ascorbic acid, folate, calcium, phosphorus, magnesium, zinc, copper and selenium, the serum concentrations were normal or close to normal. Although the stores of some micronutrients seemed smaller after total gastrectomy, no major differences in nutritional status were found between the TG and PG groups. For the demonstration of decreased micronutrient stores during long-term follow-up after gastrectomy, an extended profile of biochemical markers of nutritional status is recommended.

Biomarkers↗
PubMed1991

Nutritional status after total and partial gastrectomy with Roux-en-Y reconstruction.

Dietary intake and nutritional status were studied in two groups of patients after total gastrectomy (n = 10) and after partial gastrectomy (n = 10). All patients were reconstructed with a Roux-en-Y loop. Investigations were carried out 4-17 years after the operation. Eight patients in the group undergoing total gastrectomy and four patients undergoing partial gastrectomy had gastric carcinoma and were without recurrent disease 5-15 years after the operation. A clinical dietician conducted an anthropometric evaluation. All patients underwent an upper gastrointestinal endoscopy, clinical examination, [14C]triolein breath test and a blood chemistry profile. The median weight loss from operation to investigation was 2.1 kg in the partial gastrectomy group and 6.7 kg in the total gastrectomy group (n.s.). After partial gastrectomy three patients had a subnormal body mass index (n.s.). This was not found in the total gastrectomy group. Energy intake was below that recommended in seven patients in the partial gastrectomy group (three of them had a subnormal body mass index) and in two in the total gastrectomy group (n.s.) [14C]triolein breath testing revealed fat malabsorption in three patients after partial gastrectomy and in five patients after total gastrectomy (n.s.).

Adult↗
PubMed1991

Structure-metabolism relationships in the hydrolysis of nicotinate esters by rat liver and brain subcellular fractions.

Rat liver and brain subcellular esterase activities toward nicotinic acid esters were studied, under varying conditions, such as pH, organic solvents, protein concentration, duration of incubation, and substrate concentration. Esterases in each subcellular fraction displayed activities that obey Michaelis-Menten kinetics, although subcellular fractions are heterogeneous. The Km values were of the same magnitude, and the Vmax values were lower in microsomes than in cytosol of the liver. Brain activities normalized to protein concentration, were much lower than liver activities, aromatic nicotinates being the best substrates in both tissues. Myelin and brain mitochondria of nerve-ending and neuroglial origin display esterase activity toward phenyl nicotinate. In contrast to brain esterases, liver esterases appear homogeneous, and esterase activities in both tissues react differently to changes in pH. Qualitative and quantitative structure-metabolism relationships are not suggestive of tissue-specific ester hydrolysis.

Animals↗
PubMed1990

Behavioural and pharmacokinetic studies on nicotine, cytisine and lobeline.

Previous work has suggested that cytisine and lobeline are of low potency in producing nicotine-like behavioural effects, despite having some nicotine-like peripheral effects and potently inhibiting the binding of tritiated nicotine to the brain of the rat. Rats were trained to discriminate nicotine from saline in a two-bar operant conditioning procedure with food reinforcement. It was confirmed that cytisine had a nicotine-like discriminative effect, but it was much less potent than nicotine itself. Lobeline failed to produce a nicotine-like discriminative effect, even at doses that greatly reduced overall rates of responding. Neither drug attenuated discriminative responses to nicotine. The concentrations of drugs in plasma and brain were determined by HPLC in rats of the same sex, strain and age as those used in the behavioural experiments. The rank order of the ratios of concentrations in brain to plasma was lobeline greater than nicotine greater than cytisine, which was directly proportional to their lipophilicity determined by reversed-phase HPLC. Based on the concentrations in brain and known affinities for high-affinity nicotine binding sites, in vivo tests should show cytisine to be slightly more potent than nicotine and lobeline to have nicotine effects in the doses used. These predictions were not fulfilled and thus, the behavioural effects of cytisine and lobeline cannot be correlated with their effects at the binding site for tritiated nicotine. Since pharmacokinetic factors do not account for this discrepancy, a pharmacodynamic explanation will be necessary.

Alkaloids↗
PubMed1989

Cerebral function monitoring in rats with a critical hepatic injury treated with pneumatic antishock garment and infusion.

Twenty-nine rats were subjected to a severe standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG inflated to 40 mm Hg, PASG and infusion of Ringer's acetate, or PASG and infusion of Ringer's acetate and Dextran 70 in combination. The aim of the infusion therapy was to stabilize the mean aortic blood pressure at 60 mm Hg. PASG significantly prolonged the survival time and the time during which a sensory evoked response could be observed. The PASG also prolonged the time before the EEG amplitude began to decrease or a burst-suppression pattern appeared in the EEG. Intravenous infusion of Ringer's acetate did not prolong these times compared to when PASG was used alone; when Dextran 70 was added to the infusion therapy these times were reduced. Changes in the EEG were recorded at a mean aortic pressure of 60 mm Hg when infusions were given, whereas the aortic pressure had to fall to 40 mm Hg before any changes could be observed when no infusions were used.

Acute Disease↗
PubMed1989

Fat malabsorption in patients before and after total gastrectomy, studied by the triolein breath test.

The feasibility of using the triolein breath test to demonstrate fat malabsorption was evaluated in a prospective study of patients before and after total gastrectomy and Roux-en-Y reconstruction. Two of 11 patients had subnormal fat absorption before the operation, but 1 and 6 months after the operation 9 of 11 patients had subnormal fat absorption. Peak expiratory 14CO2 (median (range] at the three investigations was 3.9%/h (2.1-5.9%/h), 2.1%/h (1.4-4.5%/h), and 2.0%/h (1.2-6.0%/h), respectively. Patients who underwent a Nissen fundoplication were used as controls. They had normal fat absorption both before and after operation. Serum amylase was not appreciably affected by total gastrectomy and was similar to control values. In contrast, serum albumin decreased 1 month after gastrectomy and recovered after 6 months. In control patients pre- and post-operative albumin concentrations did not differ and were comparable to preoperative albumin values in the total gastrectomy group. The lowered fat absorption may be explained by duodenal bypass with decreased pancreatic stimulation, and it may in part explain the weight loss in patients operated on with total gastrectomy.

Aged↗
PubMed1989

Reduction of secretion from a small-bowel fistula by somatostatin. Case report.

A 69-year-old man with intra-abdominal abscesses and small-bowel fistula after total gastrectomy received two 12-hour continuous i.v. infusions of somatostatin (250 micrograms/h) with a 24-hour interval. Secretion through the fistula decreased markedly during the infusion, with rebound rise after its discontinuation. The concentration of bilirubin in the secretion, but not that of amylase, also fell during somatostatin infusion.

Abdomen↗