Biomedical subjects
Publications and source records attributed to G Jacobson.
During a five-year-period 9 cases of duodenal carcinoma were treated. Eight of the patients were resected and 7 of them survived more than 5 years without signs of recurrent disease. Aggressive therapy, including radiotherapy and chemotherapy in cases with lymph node metastases, might in some way explain the good results. The importance of visualizing the infrapapillary region of the duodenum when performing upper endoscopy is stressed.
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In a population-based case-control study carried out in Sweden in 1982-1984, the authors examined the association of pancreatic cancer with several dietary factors, coffee, alcohol, and tobacco. Analyses were based on 99 cases, 138 population controls, and 163 hospital controls. The cases were persons aged 40-79 years diagnosed with cancer of the exocrine pancreas at three surgical departments in Stockholm and Uppsala. The risk increased with higher consumption frequency of fried and grilled meat in the comparison with each series of controls (e.g., relative risk (RR) = 1.7 (90% confidence interval (CI) = 1.1-2.7) for weekly intake and RR = 13.4 (90% CI = 2.4-74.7) for almost daily intake, in the comparison with population controls). Furthermore, associations were found with other fried or grilled foods, but not with meat other than fried or grilled. The risk also increased with the intake of margarine (e.g., RR = 9.7 (90% CI = 3.1-30.2) for 15+ g of margarine on a slice of bread, in the comparison with population controls). In contrast, no excess risk was associated with high intake of butter. A low risk was associated with frequent consumption of fruits and vegetables, particularly carrots (RR = 0.3 (90% CI = 0.2-0.7)) and citrus fruits (RR = 0.5 (90% CI = 0.3-0.9)) for almost daily intake. No consistent associations were found with coffee, artificial sweeteners or alcohol consumption, but a threefold increase in risk was associated with smoking at least one pack of cigarettes per day.
The relation between occupational factors and pancreatic cancer has been studied by two different approaches: a population based case-control study with two series of controls and a retrospective cohort study based on register data. With both approaches, some support was found for an association with occupational exposure to petroleum products. Associations were also indicated with exposure to paint thinner (case-control study) and work in painting and in paint and varnish factories (cohort study), for exposure to detergents, floor cleaning agents, or polish (case-control study) and with floor polishing or window cleaning (cohort study), and for exposure to refuse (case-control study) and work in refuse disposal plants (cohort study).
Biliary obstruction was treated with endoprosthetic drainage in 30 patients with pancreatic, 10 with gallbladder and 27 with biliary duct cancer, and 13 of the patients received more than one endoprosthesis. The median survival time in the respective cancer groups was 12, 10 and 9 weeks, including 6, 3 and 4 weeks spent in the patients' own homes. The patients with multiple endoprostheses had 24 weeks median survival with 22 weeks at home. Another patient, with a medically treated malignant endocrine tumour of the pancreas, lived for more than 3 years after biliary tract stenting. Complications associated with insertion of endoprosthesis were few, and clinical cholangitis occurred in seven cases. For individual patients it is difficult to predict the benefit of endoprosthetic drainage, but the procedure seems questionable if the predrainage bilirubin level is very high.
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The retention (k') for various biomolecules was studied as a function of the mobile phase composition in reversed-phase chromatography (RPC) and ion-exchange chromatography (IEC). The "elution window" (EW) for a molecule is defined as the mobile phase composition in which 1 less than k' less than 10. The following relations were verified: (i) EW(RPC) less than EW(IEC), and (ii) EW(large Mr) less than EW(small Mr). The results support the theory that in both RPC and IEC larger molecules interact with the stationary phase by multiple-site binding. The results are used to explain why, in both RPC and IEC, larger molecules are best separated on short columns using gradient elution while smaller molecules often require longer columns and isocratic conditions.
A women, 52 years, old, with Crohn's disease of the colon treated with colectomy 9 years earlier, got a blunt abdominal trauma in a car accident. At laparotomy two weeks after the accident an isolated transverse rupture of the common hepatic duct was found just below the confluence of the hepatic ducts. The rupture was successfully repaired by a direct anastomosis. Four years later the patient developed attacks of fever and jaundice. A cholangiogram now showed typical signs of sclerosing cholangitis and re-checking of cholangiograms taken after the primary repair revealed that the disease existed already at that time. The cholangitis is supposed to be a contributing factor to the rupture.
The respective influences of ischemic neuronal damage and infarction on the development of abnormal blood-brain barrier (BBB) permeability and cerebral edema were evaluated in a rat model of temporary four-vessel occlusion in which ischemic neuronal damage with only infrequent infarction is produced. Survival times ranged from 40 minutes to 5 days after ischemia. Evans blue and horseradish peroxidase (HRP) were given before sacrifice. The majority of brain showed moderate ischemic neuronal damage inthe striatum. In these areas there was neither leakage of Evans blue nor extravasation of HRP. Astrocytic processes were moderately swollen. Large, grossly-visible unilateral infarcts were present in only 5 animals, and all showed abnormal BBB permeability of HRP which occurred via enchanced pinocytosis, and occasionally via diffuse leakage through necrotic vessels. Astrocytic processes were markedly swollen and their plasma membranes were disrupted. Whole brain and regional water content in a parallel series of animals were measured from 15 minutes (min) to 48 hours (h) postischemia. They showed a transient, 1% increase in whole brain water content from 15 to 60 min postischemia, but no increase in regional water content at any postischemic interval. These studies suggest that ischemia produces BBB permeability to large molecules, and sustained cerebral edema only when the process damages blood vessels and astrocytes; neuronal necrosis alone is insufficient.
Twenty-four patients with probably resectable carcinoma of the head of the pancreas were examined by means of CT, ERCP and US and supplemented with angiography to assess the resectability. Resection was possible in half of the patients. As the series consisted only of potentially resectable cases, those with obvious liver metastases at CT or US were not included. The 3 patients in whom CT or US revealed a tumour larger than 5 cm were inoperable. A distance less tan 5.5 cm between the hilum of the liver and the proximal margin of the tumour measured in the common bile duct at ERCP also meant inoperability. Invasion of the superior mesenteric or splenic vein at angiography as an indication of non-resectability was confirmed at laparotomy in 12 of 13 cases.
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Human thyroid blood flow (TBF) was studied with electromagnetic flowmetry during operation. Measurements were made of the effect on TBF of injections of bovine TSH into one inferior thyroid artery in 6 patients; 6 other patients were given human TSH, and in 10 patients measurements were made both of TBF and endogenous TSH released after administration of TRH in a peripheral vein. The TBF increased after all three types of injection. The mean of the TBF maxima after bovine TSH was 2.26 +/- 0.35 (mean +/- SEM) relative to basal TBF, after human TSH 1.97 +/- 0.28, and after TRH 1.64 +/- 0.20. In the three groups combined it was 1.92 +/- 0.16. The TBF was often increased already during the first recording period 1-10 min after TSH or TRH administration. The mean TBF was approximately doubled at 30-50 min. There were considerable inter-individual variations in the latent time and maximum response of TBF, especially after human TSH, but we found no correlation between the response and the TSH serum concentration in any group. A prompt, but inter-individually varying, increase in TBF was confirmed. This increase is suggested to be secondary to an increased intrafollicular metabolic activity and not primarily regulating thyroid function.
The alpha and beta subunits of human pituitary thyrotropin were prepared by a process developed earlier. Each subunit preparation contained four isoforms which were isolated by preparative agarose-suspension electrophoresis. The alpha subunit isoforms were homogeneous upon examination by analytical electrophoresis in polyacrylamide gel. Contrarily, the isolated beta subunit isoforms were always to some extent contaminated by the adjacent more acidic component. This was considered to show a transformation of these forms favoured by hydroxyl ions. Amino acid analysis revealed no differences between the alpha isoforms nor between the beta isoforms, and the amino acid compositions were in very good agreement with those earlier obtained for multi-alpha and multi-beta preparations. Attempts to recombine different alpha and beta isoforms were made at pH 7.0. The activities of recombined thyrotropin (in terms of MRC Research Standard A) ranged from 1.1 unit/mg (recombination of two minor components) to 3.5 units/mg (recombination of two major components). The activities of native and recombined thyrotropins as well as the subunit activities were followed by radioimmunoassays. The activity of native thyrotropin as a function of time was studied under different storage conditions. The subunit activities were also measured. All conditions resulted in a decrease in the thytrotropin activity (about 40% in 10 weeks). This decrease was not due to dissociation as the subunit activities remained approximately constant.
The potential use of a pancreatic iso-amylase test has been studied by computer simulation. This simulation was performed to assess the quality requirements on the test in different clinical situations. It was shown that, in most situations studied, an optimal discriminating level and an optimal analytical quality (imprecision and bias) could be established. In one situation studied in more detail, it was found that the influence of pre-analytical variation, duplicate determinations, reclassification of borderline cases and size of reference sample groups were of minor importance. The weighting ratio of false negatives: false positives was found to be critical for the results. It is concluded that a simulation study of this type can be recommended prior to entering the phases of analytical refinement and clinical testing on patients.
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