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Biomedical subjects

G Wegener

Publications and source records attributed to G Wegener.

At least 37 records · Page 2Linked to original sources

Completion thyroidectomy in 131 patients with differentiated thyroid carcinoma.

OBJECTIVE: To evaluate the prognostic factors that influence survival and recurrence after "completion" thyroidectomy (removal of the total thyroid remnant after diagnosis of carcinoma has been made in a specimen that was incompletely excised for a benign condition). DESIGN: Open study. SETTING: Teaching hospital, Germany. SUBJECTS: 131 Patients (65 with papillary and 66 with follicular thyroid cancer) who underwent completion thyroidectomy after primary subtotal resection. INTERVENTIONS: Indications for further operation were: tumour stage worse than pT1 ( n = 116), tumour stage pT1 and the suspicion of persistence of the tumour (n = 13), and incompletely resected tumour (n = 2). Multivariate analysis by Cox's proportional hazards model. MAIN OUTCOME MEASURES: Recurrence, development of metastases, and length of survival. RESULTS: Patients who underwent their completion thyroidectomies within six months of the primary operation had significantly fewer recurrences, fewer lymph node metastases, fewer haematogenous metastases and survived significantly longer than those in whom the second operation was delayed for longer than six months. The age at the time of diagnosis and the stage of the tumour influenced survival, whereas sex and type of tumour did not. CONCLUSION: Completion thyroidectomy as soon as possible after incomplete resection of the tumour may improve prognosis in differentiated thyroid cancers the stage of which is worse than pT1 or in patients whose recurrent tumour is diagnosed at follow-up.

Adenocarcinoma, Follicular↗

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from frog skeletal muscle: purification, kinetics and immunological properties.

Fructose 2,6-bisphosphate is the most potent activator of 6-phosphofructo-1-kinase, a key regulatory enzyme of glycolysis in animal tissues. This study was prompted by the finding that the content of fructose 2,6-bisphosphate in frog skeletal muscle was dramatically increased at the initiation of exercise and was closely correlated with the glycolytic flux during exercise. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, the enzyme system catalyzing the synthesis and degradation of fructose 2,6-bisphosphate, was purified from frog (Rana esculenta) skeletal muscle and its properties were compared with those of the rat muscle type enzyme expressed in Escherichia coli using recombinant DNA techniques. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from frog muscle was purified 5600-fold. 6-Phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities could not be separated, indicating that the frog muscle enzyme is bifunctional. The enzyme preparation from frog muscle showed two bands on sodium dodecylsulphate polyacrylamide gel electrophoresis. The minor band had a relative molecular mass of 55,800 and was identified as a liver (L-type) isoenzyme. It was recognized by an antiserum raised against a specific amino-terminal amino acid sequence of the L-type isoenzyme and was phosphorylated by the cyclic AMP-dependent protein kinase. The major band in the preparations from frog muscle (relative molecular mass = 53,900) was slightly larger than the recombinant rat muscle (M-type) isoenzyme (relative molecular mass = 53,300). The pH profiles of the frog muscle enzyme were similar to those of the rat M-type isoenzyme, 6-phosphofructo-2-kinase activity was optimal at pH 9.3, whereas fructose-2,6-bisphosphatase activity was optimal at pH 5.5. However, the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from frog muscle differed from other M-type isoenzymes in that, at physiological pH, the maximum activity of 6-phosphofructo-2-kinase exceeded that of fructose-2,6-bisphosphatase, the activity ratio being 1.7 (at pH 7.2) compared to 0.2 in the rat M-type isoenzyme. 6-Phosphofructo-2-kinase activity from the frog and rat muscle enzymes was strongly inhibited by citrate and by phosphoenolpyruvate whereas glycerol 3-phosphate had no effect. Fructose-2,6-bisphosphatase activity from frog muscle was very sensitive to the non-competitive inhibitor fructose 6-phosphate (inhibitor concentration causing 50% decrease in activity = 2 mumol.l-1).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of insulin-like growth factor I on the rates of glucose transport and utilization in rat skeletal muscle in vitro.

1. The effects of insulin-like growth factor I (IGF-I) on the rates of glucose transport and utilization and its interaction with insulin were investigated in rat soleus muscle in vitro. IGF-I increased the rates of glucose transport, lactate formation, glycogen synthesis and the flux of glucose to hexose monophosphate, but it had no effect on the rate of glucose oxidation or glycogenolysis. 2. In the absence of insulin, low levels of IGF-I (0-30 ng/ml) increased the rate of glycolysis and the content of fructose 2,6-bisphosphate, but the content of glucose 6-phosphate remained unaltered; at higher levels of IGF-I (300-3000 ng/ml) the rate of glycolysis and the content of fructose 2,6-bisphosphate showed a further modest increase, but the content of glucose 6-phosphate doubled. Similar changes were seen when the level of insulin was increased from basal (0-0.4 ng/ml) to maximal (40 ng/ml). 3. Neither IGF-I nor insulin affected the contents of ATP, ADP, AMP, phosphocreatine or citrate. 4. Maximal concentrations of IGF-I increased the rate of lactate formation to a greater extent than did maximal concentrations of insulin. 5. In the presence of IGF-I, the rate of glucose utilization was less responsive to insulin. 6. The results suggest that, in rat skeletal muscle: (a) IGF-I increases the rates of glucose transport and utilization independently of insulin, and has a preferential effect on the rate of lactate formation; (b) the effects of IGF-I and insulin are not additive; (c) in addition to its effects on glucose transport, IGF-I increases the rate of glycogen synthesis and may stimulate glycolysis at the level of 6-phosphofructokinase; (d) changes in the content of fructose 2,6-bisphosphate may be part of the mechanism to regulate glycolytic flux in skeletal muscle in response to either IGF-I or insulin.

Animals↗

Effects of in-vivo administration of insulin-like growth factor-I on the rate of glucose utilization in the soleus muscle of the rat.

This study investigated the effects of insulin-like growth factor-I (IGF-I) administered to rats in vivo on the soleus muscle isolated from these rats. In order to study the interactions between IGF-I and insulin, the soleus muscles were incubated in the presence of various concentrations of insulin. IGF-I (190-200 micrograms) was given twice daily; the rats were killed 1 h after one injection of IGF-I (acute administration) or after treatment with IGF-I for 10 days (prolonged administration). The level of IGF-I in plasma was increased by approximately 100% after acute administration and by around 30% after 10 days of treatment with IGF-I. Acute administration of IGF-I to the rats increased the flux of glucose to hexose monophosphate and the rates of lactate formation and glycogen synthesis in the soleus muscles; however, the responsiveness of these muscles to insulin was lost: the increase in the rate of glucose utilization by IGF-I at physiological concentrations of insulin (10 or 100 mU/l) was similar to that observed at maximal concentrations of insulin (1000 mU/l). Similar results were obtained after prolonged treatment of the rats with IGF-I; however, the increase in the rate of glucose utilization was less pronounced than when IGF-I was given acutely and the muscles were still capable of responding to insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fructose 2,6-bisphosphate and glycolytic flux in skeletal muscle of swimming frog.

Glycolytic flux in skeletal muscle is controlled by 6-phosphofructokinase but how this is achieved is controversial. Brief exercise (swimming) in frogs caused a dramatic increase in the phosphofructokinase activator, fructose 2,6-bisphosphate, in working muscle. The kinetics of phosphofructokinase suggest that in resting muscle, the enzyme is inhibited by ATP plus citrate and that the increase in fructose 2,6-bisphosphate is part of the mechanism to activate phosphofructokinase when exercise begins. When exercise was sustained, fructose 2,6-bisphosphate in muscle was decreased as was the rate of lactate accumulation. Glycolytic flux and the content of fructose 2,6-bisphosphate appear to be closely correlated in working frog muscle in vivo.

Animals↗

[Radical surgical intervention with conventional radiation versus multimodality therapy protocol in undifferentiated thyroid cancer].

Out of a total of 550 patients with thyroid cancer diagnosed over the 16-year period 1972-June 1989, 44 showed undifferentiated carcinoma and were treated by thyreoidectomy and early postoperative external irradiation. In order to analyse the outcome in patients treated by primary surgery in contrast to patients treated by means of a multimodal therapy concept we compared our surgical procedures with regard to primary surgical approach, early postoperative course, operative complications and survival to the data on the multimodal therapy concept of the Karolinska Hospital reported by E. Tallroth et al. 1987. A significantly better survival was correlated with radical (n = 20) versus palliative tumour resection (n = 24) (p less than 0.001), and total thyroidectomy (n = 25) versus subtotal thyroidectomy (n = 19) (p less than 0.006). Radical surgery with early postoperative external irradiation revealed no postoperative mortality and no symptomatic cervical tumour recurrence. By contrast, palliative surgery, particularly in the case of synchronous tracheotomy, was attended by a relatively high mortality (29%) and symptomatic local recurrences. The results of this study suggest that in undifferentiated thyroid carcinoma an attempt at radical tumour resection should be undertaken, since multimodal therapy procedures revealed a significantly highly complication rate (up to 36%) and, in comparison with a radical surgical treatment policy, showed a higher rate of local recurrences (0% vs. 48%) and a lower survival (mean survival 42 vs. 15 months).

Aged↗

Bronchoscopy in severe blunt chest trauma.

Extended lesions of the lung parenchyma are often seen in association with blunt chest trauma. Blood aspiration, atelectasis and the formation of bronchopleural fistulae can lead to early respiratory deterioration and the development of severe post-traumatic complications (pneumonia, acute respiratory distress syndrome). Diagnostic and therapeutic bronchoscopy is essential on admission. This procedure helps to estimate the severity and extent of parenchymal lesions even before chest X-ray signs are noted. Bronchoalveolar lavage is needed for removal of aspirates. In our study bronchoalveolar lavage on admission reduced bacterial contamination and pneumonia in comparison to patients not lavaged. A new method for closure of bronchopleural fistulae is described. Fibrin instillation after balloon catheter occlusion leads to a significant reduction of tidal volume loss (greater than 50% in average).

Adult↗

Glycogen phosphorylase in fish muscle: demonstration of three interconvertible forms.

White skeletal muscle of crucian carp contains a single isoenzyme of glycogen phosphorylase, which was purified approximately 300-fold to a specific activity of approximately 13 mumol.min-1.mg protein-1 (assayed in the direction of glycogen breakdown at 25 degrees C). Tissue extracts of crucian muscle produced three distinct peaks of phosphorylase activity when separated on DEAE-Sephacel. Peaks 1 and 3 were identified, in terms of kinetic properties and by interconversion experiments, as phosphorylase b and a, respectively. Peak 2 was shown to be a phospho-dephospho hybrid. The three interconvertible forms of phosphorylase were purified and shown to be dimeric molecules at 20 degrees C. At 5 degrees C, a and the hybrid tended to form tetramers. The Mr of the subunit was estimated to be 96,400 from sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The hybrid is kinetically homogeneous, and its kinetic properties are intermediate between those of b and a forms. The b, hybrid, and a forms of phosphorylase can be isolated from rapidly frozen muscle of crucian but in different proportions, depending on whether fish were anesthetized or forced to muscular activity for 20 s. Muscle of anesthetized crucian had 36, 36, and 28% of phosphorylase b, hybrid, and a forms, respectively, whereas the corresponding values for exercised fish were 12, 37, and 51%. Results suggest that three interconvertible forms of phosphorylase exist simultaneously in crucian muscle and that hybrid phosphorylase is active in contracting muscle in vivo.

Anesthesia, General↗

[Undifferentiated thyroid cancer: improved therapeutic results following initial radical intervention and early postoperative radiotherapy].

During a 16-year period (1972-1988), 40 out of 477 thyroid cancer patients underwent thyroidectomy for undifferentiated thyroid carcinoma. To analyse the significance of "radical" versus "palliative" surgical procedures with regard to early postoperative course, operative complications and survival, all patients records were reviewed and actually followed up. A significant better survival was correlated with radical (n = 17) versus palliative tumor resection (n = 23) (p less than 0.001), and total thyroidectomy (n = 22) versus subtotal thyroidectomy (n = 18) (p less than 0.006). Radical surgery with early postoperative external irradiation revealed no postoperative mortality and only one symptomatic cervical tumor recurrence. In contrast, palliative surgery, particularly in the case of synchronous tracheotomy, was attended with a relatively high mortality (30%) and symptomatic local recurrences. The results of this study suggest that in undifferentiated thyroid carcinoma without infiltration of the esophageal or tracheal mucosa an attempt of radical tumor resection should be undertaken, since palliative surgical procedures revealed a significantly lower survival due to complications of persistent or recurrent cervical tumor infiltration and frequently were accompanied by local complications during the postoperative course.

Aged↗

Antagonistic effects of hexose 1,6-bisphosphates and fructose 2,6-bisphosphate on the activity of 6-phosphofructokinase purified from honey-bee flight muscle.

6-Phosphofructokinase purified from honey-bee flight muscle is inhibited by ATP and, unusually, by glucose 1,6-bisphosphate and fructose 1,6-bisphosphate. The inhibition by either of the bisphosphates is not relieved by AMP, but is relieved by fructose 6-phosphate and especially by fructose 2,6-bisphosphate. Lack of effect by AMP is consistent with a low activity of adenylate kinase in this muscle.

Adenosine Triphosphate↗

Effects of cold adaptation and starvation on sciatic nerve fibers in the frog.

The conditions under which frogs are kept prior to experimentation were found to have a measurable effect on peripheral nerve structure. Frogs kept for 12 weeks at 4 degree C had markedly shrunken sciatic nerve fibers compared with frogs kept at 19 degrees C. Intermediate fiber shrinkage was found for frogs kept at 19 degrees C without feeding. Counts of neurofilaments and microtubules showed that fiber shrinkage was from a preferential loss of filaments, indicating cold- or starvation-induced atrophy of the axon's cyto-skeleton. This effect, however, was superimposed with additional osmotic axonal shrinkage, causing filament densities to increase per area. There were no changes in myelin sheath thickness due to cold adaptation or fasting.

Adaptation, Physiological↗

Age affects the metabolic rate of insect brain.

Brains of adult insects can be isolated and studied in vitro. In female blowflies the oxygen uptake of the brain is age dependent. A steady increase is followed by a precipitous decrease around the middle of the little span. These changes are accompanied by alterations of mitochondrial structure and deposits of lipofuscin-like material.

Aging↗