Development of adenocarcinoma in Barrett's oesophagus after successful antireflux surgery.
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Adenocarcinoma↗
Biomedical subjects
B Walther
Publications and source records attributed to B Walther.
[Esophageal cancer on the increase. Is Barrett esophagus the cause?].
At the Dept of Surgery, Lund University, during the 10-year period 1985-95, 54 patients with adenocarcinoma of the gastro-oesophageal junction (17 with Barrett's epithelium, and 37 without) underwent oesophageal resection: oesophagectomy and gastric pull-up (n = 10), extended total gastrectomy (n = 37), or oesophageal resection and interposition of colon (n = 2) or jejunum (n = 5). Hospital mortality was 3.7% (2/54), and the mean duration of hospitalisation 13 days (range, 9-42). Long-term survival was significantly better in the Barrett's oesophagus subgroup than in the carcinoma of the cardia (non-Barrett's oesophagus) subgroup, the respective rates being 50% vs. 10% (p = 0.0052; Log rank test). The better survival in the Barrett's oesophagus subgroup is probably to be explained by the earlier stage of disease among these patients, in turn due to a history of gastro-oesophageal reflux, whereas the predominant symptom in the cardia carcinoma subgroup was dysphagia.
Adenocarcinoma↗
Adenocarcinoma in the distal esophagus with and without Barrett esophagus. Differences in symptoms and survival rates.
OBJECTIVE: To evaluate differences in clinical appearance and survival rates in patients operated on for adenocarcinoma in the distal esophagus with and without Barrett epithelium. DESIGN: Prospective clinical study. SETTING: University hospital, Sweden. PATIENTS: Fifty-four patients with adenocarcinoma in the distal esophagus with (n = 17) or without (n = 37) Barrett epithelium. INTERVENTION: Esophagectomy or total gastrectomy. MAIN OUTCOME MEASURES: Preoperative symptoms, endoscopic results, and histological findings; postoperative morbidity, mortality, and survival rates. RESULTS: The main indication for the endoscopic examination that revealed tumor in the group with Barrett esophagus was reflex-related symptoms in 6 patients (routine Barrett examination, n = 4; symptoms of reflux, n = 2), symptoms related to upper gastrointestinal tract bleeding in 6, and malignant symptoms in 5 (dysphagia, n = 4; weight loss, n = 1). In contrast, most patients in the cardia cancer group were admitted because of malignant symptoms (dysphagia, n = 26; epigastric pain, n = 9; and anemia, n = 2). Ten of 17 patients in the Barrett esophagus cancer group had tumors limited to the mucosa and submucosa only. In 1 patient the tumor grew into the muscular layer but not through it. In the remaining 6 patients the tumor did grow through the muscular layer and lymph node metastases were found. Wall penetration was found in 30 patients and metastases to lymph nodes in 29 patients in the cardia cancer group. The hospital mortality rate was 0 of 17 patients in the Barrett cancer group and 2 of 37 patients in the cardia cancer group. In the patients operated on for adenocarcinoma in the distal esophagus, a better long-term survival rate was seen in those with Barrett epithelium (50%) than in those without this metaplasia (10%) (log rank P = .005; X2 = 7.80). CONCLUSIONS: Concomitant Barrett epithelium improved the prognosis for patients with adenocarcinoma in the distal esophagus. Probably the reason for this was a higher rate of early-stage disease, because symptoms of gastroesophageal reflux and other benign disorders, not dysphagia, were most common in patients with adenocarcinoma without Barrett epithelium in the distal esophagus.
Adenocarcinoma↗
Detection of adenocarcinoma in Barrett's oesophagus by means of laser induced fluorescence.
PATIENTS: Seven patients with Barrett's metaplastic epithelium and oesophageal adenocarcinoma were investigated by means of laser induced fluorescence after low dose intravenous injection (0.35 mg/kg bw) of Photofrin (QLT, Vancouver, Canada). Laser induced fluorescence measurements were performed immediately after resection of the oesophagus. METHODS: Laser induced fluorescence spectra were recorded from 15-30 locations in each surgical specimen from normal mucosa, Barrett's epithelium, and tumour tissue. Histological examination was performed on each location to correlate the fluorescence spectral characteristics with histological status of the epithelium (normal, metaplastic or malignant). Measurements were also performed during endoscopy in five patients to test the applicability of the method in a clinical setting. Fluorescence spectra were recorded and evaluated at characteristic wavelengths, and biopsy specimens were collected. Fluorescence ratios were calculated as the quotient of Photofrin fluorescence divided by autofluorescence. RESULTS: The mean (SD) fluorescence ratio values were 0.10 (0.058) for normal oesophageal mucosa, 0.16 (0.073) for normal gastric mucosa, 0.205 (0.17) for Barrett's epithelium with moderate dysplasia, 0.79 (0.54) for severe dysplasia, and 0.78 (0.56) for adenocarcinoma. The highest fluorescence ratios were obtained for adenocarcinoma tissue, which could generally be distinguished from all nonmalignant tissue. Metaplastic Barrett's epithelium also yielded higher fluorescence ratios than did normal mucosa. CONCLUSIONS: The results suggest that the technique can be used during endoscopy for real time tissue characterisation in the oesophagus, as an aid in detecting malignant transformation not macroscopically apparent at endoscopy.
Adenocarcinoma↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Convenient method for the analysis of nicotinic acid as a metabolite of nicotinate esters in various tissue homogenates.
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Animals↗