Functional organisation of the field-L-complex of adult male zebra finches.

Functional maps of auditory response areas were established from multiunit recordings in the caudal telencephalon of male zebra finches. The response criterion was a difference of activity from the spontaneous discharge level. Pure tones and conspecific song were used as stimuli. The auditory part of the caudal telencephalon in zebra finches can be subdivided into six functionally separated centres. The definition of separate areas is based on the existence of tonotopic gradients in each single area and on differences in neural response behaviour between areas. The anatomical area L2a is functionally subdivided into two tonotopic centres. Other areas can be identified by anatomy and function. The borders vary slightly depending on the description method.

Induction of p-glycoprotein, glutathione-s-transferase-pi, catalase, C-fos and C-erbb1 in rodent cell-lines after exposure to Doxorubicin, ethanol and caffeine.

Murine NIH-3T3 cells were exposed to doxorubicin (DOX, 1 mu g/ml), ethanol (EtOH, 0.2%) and caffeine (CAFF, 200 mu g/ml) and analyzed for the induction of resistance proteins (P-glycoprotein, glutathione S-transferase-pi, catalase) and oncoproteins (c-EOS, c-ERBB1). P-glycoprotein (P-170), glutathione S-transferase-pi (GST-pi) and catalase (CAT) levels were found to be elevated after exposure of the cells to doxorubicin. In EtOH-treated cells the P-170 level was moderately increased (12 to 36 h after exposure), whereas the GST-pi and CAT levels were greatly increased (1 to 48 h). CAFF caused a moderate increase of P-170 (12 to 36 h) and of GST-pi (6 to 72 h). The accumulation of rhodamine 123 was reduced after the level of the resistance proteins had risen. After exposure to DOX, c-FOS was expressed moderately whereas c-ERBB1 was expressed strongly. Both oncoproteins showed a significant increase after exposure to EtOH. Only a moderate increase of c-FOS was seen after exposure to CAFF. Five out of seven additionally investigated rodent cell lines showed an increase in the expression of P-170, GST-pi and c-FOS after exposure to DOX, EtOH or CAFF.

Long-term results of treatment of Cushing's disease by adrenalectomy.

Patients treated by adrenalectomy for suspected Cushing's syndrome were reviewed for the incidence to early and late complications, side effects, survival, and quality of life. Of a total of 141 patients, 109 had Cushing's disease, and were treated with subtotal (n = 15) or total (n = 94) adrenalectomy. All hospital charts were reviewed, and surviving patients were asked to fill in a questionnaire. Ten patients died in hospital. Morbidity was 13% (n = 18). Five patients required reoperation because of recurrent adrenal hyperplasia after subtotal adrenalectomy (n = 3) or incomplete adrenalectomy (n = 2). All patients received conventional corticosteroid supplementation. Ten patients developed Nelson's syndrome 3-20 years after adrenalectomy. Of the 109 patients with Cushing's disease 80 were alive 1-34 years after operation. Only four late deaths were related to Cushing's disease: 3 postoperative deaths followed reoperation and 1 was the result of an Addisonian crisis. About two thirds of the patients interviewed had satisfactory quality of life and were able to work. Total bilateral adrenalectomy has a five to seven fold higher perioperative mortality than transphenoidal operations. The prognosis of patients who survive the early postoperative period, however, is comparable to that of the general population.

Gastric lymphoma causing granulocytopenia and cold intolerance, with recovery after treatment.

A 34-year-old man was found to have granulocytopenia with a white blood count of 2.3 x 10(9) l-1, consisting of 10% segmented neutrophils, 50% monocytes and 40% lymphocytes. A bone marrow aspirate showed 20% promyelocytes and 10% blasts with monoblastic features, and a smouldering myelomonocytic leukaemia was considered to be a possible diagnosis. In cold weather the patient experienced cold intolerance with acrocyanosis and small ulcerations on the ears. The test for heparin-precipitable protein ('cryofibrinogen') was strongly positive. During the following year, these signs and symptoms persisted, and the patient also developed constant moderate pain in the epigastric region. Gastroscopy revealed a large lymphoma of the stomach, which was a high-grade malignant centroblastic type of non-Hodgkin's lymphoma. After successful removal of the tumour, and six courses of potent cytostatic combinations, the patient recovered completely, and the granulocytopenia and cold intolerance disappeared.

The effect of chemical sympathectomy on insulin-stimulated gastric secretion in dogs.

Administration of 6-hydroxydopamine (6-OHDA) causes selective acute degeneration of the adrenergic nerve terminals--that is, a reversible chemical sympathectomy. The effect of this drug was studied on the insulin-stimulated gastric secretion. Insulin-stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin were measured before and after 6-OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibers in the vagus nerve might have some modulating effect on the insulin-induced gastrin release.

The effect of chemical sympathectomy on insulin-stimulated gastric secretion in dogs.

Administration of 6 hydroxydopamine (6 OHDA) causes selective acute degeneration of the adrenergic nerve terminals, that is a reversible chemical sympathectomy. The effect of this drug was studied on the insulin stimulated gastric secretion. Insulin stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin was measured before and after 6 OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations, that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibres in the vagus nerve might have some moduling effect on the insulin induced gastrin release.

The lack of effect of propranolol on the intestinal phase secretion in the dog.

Four mongrel dogs were prepared with a Heidenhain pouch, a gastric fistula, and a 90-cm-long Thiry-Vella loop. After recovery, the jejunal loop was perfused for 3 h with either 5% liver extract or with 0.15 M NaCl, and measurements of gastric acid and pepsin secretion and serum gastrin levels were performed. The experiments were repeated during beta-adrenergic blockade induced by intravenous infusion of propranolol in a dose of 20 micrograms/kg/min. As control, propranolol was also given alone without intestinal perfusion. Perfusion of the jejunal loop with liver extract caused a significant acid secretion from the Heidenhain pouch and gastric fistula. In addition, significant pepsin secretion was obtained, but only from the gastric fistula. The serum gastrin levels remained unchanged during intestinal perfusion. Beta-adrenergic blockade did not influence any of these measurements. The results suggest that the intestinal-phase hormone also stimulates pepsin secretion in dogs. Furthermore, it seems that neither the release nor the action of this hormone is controlled by the beta-adrenergic nerves in the gut.

The effect of propranolol on insulin-stimulated gastric secretion in dogs.

The effect of beta-adrenergic blockade on the insulin hypoglycemia-induced gastric secretion was studied. Insulin-stimulated (0.15 IU/kg) gastric acid and pepsin output and serum gastrin were measured before and after beta-adrenergic blockade with propranolol (20 microgram/kg/min intravenous infusion) in gastric fistula and Heidenhain pouch dogs. Insulin injection caused acid and pepsin secretion from the gastric fistula, and both acid and pepsin secretion was significantly increased during beta-adrenergic blockade. Significant gastrin release was observed after insulin stimulation. However, the insulin-induced gastrin release was unaltered by intravenous infusion of propranolol. The Heidenhain pouch did not show any secretion in these experiments. It is concluded that beta-adrenergic blockade augments the hypoglycemia-induced gastric secretion in dogs. Furthermore, it seems that this effect is not dependent on vagally released gastrin.

Non-gastrin, intestinal-phase secretion. Experimental confirmation in the dog.

Four mongrel dogs were prepared with a Heidenhain pouch, a gastric fistula, and a 90-cm-long Thiry-Vella loop. After recovery, dose-response curves were obtained with different doses of pentagastrin, and the maximal acid output was determined. The jejunal loop was perfused for 3 h with either 5% liver extract or with 0.15 M NaCl at a rate of 114 ml/h. To verify that the stomach could release gastrin and that the assay could detect that change, antral perfusion with liver extract was performed. Serum gastrin levels and acid output were measured every 30 min. Perfusion of the jejunal loop with liver extract resulted in a significant increase in acid output from the Heidenhain pouch and the gastric fistula, whereas perfusion with saline solution failed to show any changes. The magnitude of acid response from the Heidenhain pouch and gastric fistula was 11% and 18%, respectively, as compared with maximal pentagastrin stimulation. The serum gastrin levels remained unchanged during both liver extract and saline perfusion of the jejunal loop, in contrast to the marked increase in serum gastrin level after antral perfusion. The results confirm the existence of the intestinal phase of gastric acid stimulation in dogs as an entity and show that the magnitude of this phase is significantly lower than has been suggested by results of earlier studies. Furthermore, the results suggest that the intestinal phase of gastric secretion in dogs is most probably elicited through a humoral agent other than gastrin.

Comparison of gastric secretory response in man to duodenal and jejunal liver extract perfusion.

The stomachs of six healthy volunteers were intubated with a Levine tube. In addition, a thin polyethylene tube was placed in the proximal jejunum or in the proximal duodenum. After a 1-h period with no perfusion the intestine was perfused for 2 h with 7% liver extract (LE) (pH 5.5; 380 MOsm/kg water) at a rate of 100 ml/h. In control tests 200 ml of 0.9% physiologic saline solution were used as perfusate. Reflux to the stomach was determined by addition of radioactive B12 to the perfusates. Plasma gastrin, gastric acid, and pepsin levels were measured in 15-min periods. During perfusion of the proximal jejunum only pepsin outputs were increased significantly. During duodenal perfusion of LE, gastric acid and pepsin outputs were increased to 31% and 73% of maximal pentagastrin stimulation, respectively. Controls showed no changes in gastric secretion. Plasma gastrin levels were not elevated after jejunal or duodenal perfusion. These results confirm that the intestinal phase of gastric secretory stimulation does exist in humans. Furthermore, it appears that the major portion of this stimulation originates from the duodenum and is not gastrin-dependent.

Plasma gastrin and gastric secretory response to duodenal perfusion with liver extract in healthy human subjects.

The stomachs of 8 healthy volunteers were intubated with a Levine tube under radiological control. In addition, a thin polyethylene tube was placed in the proximal duodenum. After a 1-hour period with no perfusion, the duodenum was perfused for two hours with 15% liver extract (LE) (pH 4.5--5.5; 1027 mosm/kg water) at a rate of 100 ml/hour either alone or in combination with intravenous infusion of different doses of exogenous pentagastrin. All subjects were also tested with the tubes in place for 3 hours, but with no perfusion or pentagastrin. Reflux to the stomach was monitored by addition of radioactive B12 to the perfusates. Plasma gastrin, gastric acid, and pepsin were measured in 15-minute periods. During perfusion of the proximal duodenum, where reflux of the perfusates was less than 4%, only a slight and inconstant change in plasma gastrin was seen. Gastric acid and pepsin outputs were increased to approx. 18% and 25% of the maximal pentagastrin stimulation respectively. Whereas 15% LE was shown to release gastrin by antral perfusion however, such release was not found by duodenal perfusion, except where reflux to the antrum was seen. The results suggest that intestinal stimulation of gastric secretion exists, but has not been found to be gastrin dependent in the present investigation.

The intestinal phase of gastric secretion. Response to liver extract infusion into the proximal jejunum of healthy human subjects.

A Levine tube was placed under radiological control in the stomach, and a thin polyethylene tube in the proximal jejunum of 6 healthy volunteers. The stomach and proximal part of jejunum were perfused for 2 hours with 1% acetylcholine, 20% meat extract (Bovril), and 15% liver extract (LE) alone and in combination with simultaneous infusion of different doses of exogenous pentagastrin intravenously. A significant increase in serum gastrin concentration was found with antral perfusion of LE only, whereas perfusion of the proximal jejunum did not change the basal level of the serum gastrin concentration. No change from control values was observed in gastric acid, and pepsin output on perfusing proximal jejunum with LE alone, or in combination with pentagastrin. Reflux to the stomach varied between 0-1.4%, as determined by addition of radioactive B12 to the perfusates. The experiments showed that gastrin was released from the antrum of the stomach by perfusion with 15 per cent LE, but not from the jejunum under the present experimental conditions. In the present experiments Bovril and acetylcholine perfusions did not cause significant responses from the antrum or from the proximal jejunum.