Content and gel filtration profiles of glucagon-like and somatostatin-like immunoreactivity in human fundic mucosa.

Biopsies from the fundic gastric mucosa of eight human subjects were extracted with acid-ethanol and analyzed for somatostatin- and glucagon-like immunoreactivity using region-specific RIAs. Five extracts were studied by gel filtration. The glucagon content was close to the detection limit in all extracts, and none of the known glucagon components could be identified by gel filtration. The concentration of somatostatin-like immunoreactivity was 17.4 +/- 2.0 pmol/g wet wt, and the immunoreactivity was distributed among four well defined peaks, two of which corresponded to somatostatin 1-14 and 1-28, respectively.

Morning or evening dosage of omeprazole for gastro-oesophageal reflux disease?

BACKGROUND AND AIMS: When routinely checking patients receiving omeprazole treatment for gastro-oesophageal reflux, we have been finding patients with surprisingly low nocturnal gastric pH. The aim of this study was to evaluate the impact of timing of the 40 mg omeprazole once daily regimen. METHODS: We evaluated the difference in effect of 40 mg omeprazole, given as a morning or evening dose, in 17 patients with gastro-oesophageal reflux disease. Gastric and oesophageal pH was recorded by portable 24-h two-channel pH-metry in a cross-over design of 14 days of morning and 14 days of evening administration. RESULTS: In five patients pathological reflux was abolished by both regimens, four only during morning dosage, and three only during evening dosage. In the remaining five patients abolition of pathological reflux was not achieved. The therapeutic outcome and patient preference for morning or evening administration were closely related to the individual oesophageal pH curves. Patients with reflux induced by physical activity had a clear preference for morning dosage, patients with nocturnal reflux showed a clear preference for evening dosage. Gastric pH profiles showed a high inter-individual variation; paired statistics, however, revealed a significant impact of dosage timing on the gastric pH profile. After morning dosage the work-day part (the first 7 h) of the gastric pH profile is 0.72 +/- 0.91 (mean difference of pairs +/- s.d.) higher than after evening dosage (P < 0.01). After evening dosage the gastric pH during the supine period is 0.64 +/- 0.83 (mean difference of pairs +/- s.d.) higher than after morning dosage (P = 0.02). CONCLUSION: The timing of a 40 mg omeprazole dosage regimen has a clinically significant impact on the 24-h pH profile, and that--by relating to the patient 24-hour oesophageal pH-metry in combination with the patient symptomatology--the timing of this dosage is highly important for therapeutic efficacy.

Does achalasia predispose to cancer of the esophagus?

In a follow-up study of 147 patients with achalasia of the esophagus treated by myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83 years [median, 46 years]). The living persons were contacted in writing or by telephone. The mean follow-up time after the operation was 23.2 years (range, 6 to 41 years). The cause of death was established for 71 patients. There were three postoperative deaths and two deaths following recurrence. In comparison with the Danish population, the 66 remaining patients were found to have a relatively higher cancer mortality (33.8 percent). Contrary to the expected less than one, ten of 23 patients who died of cancer had a malignant tumor in the esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of the deaths caused by esophageal cancer. It is concluded that there is a connection between achalasia and cancer of the esophagus that ought to be considered in the treatment and follow-up of patients with achalasia.

Arterial line filtration protects brain microcirculation during cardiopulmonary bypass in the pig.

Microemboli in the brain may inhibit brain function during cardiopulmonary bypass, and in a previous study in pigs of normothermic nonpulsatile bypass we reported a significant decrease in cerebral glucose consumption secondary to interruption of the capillary flow, possibly caused by microemboli. In the present study we measured the regional cerebral glucose consumption and the regional capillary diffusion capacity (that is, the number of perfused capillaries) in 10 different brain regions in two separate groups of animals with and without an arterial filter during normothermic cardiopulmonary bypass. Inclusion of a 40 micron arterial filter in the bypass circuit increased the regional brain glucose consumption 27% (median; range -12% to 145%) and regional capillary diffusion capacity increased 123% (median; range 36% to 829%). No change in brain histologic features, the cerebrovascular permeability to serum proteins, or cerebral water content was observed. The arterial filter probably protects the cerebral microcirculation and prevents the decrease in cerebral glucose consumption otherwise seen during bypass.

Effect of regulatory polypeptides on the substance P stimulated lower esophageal sphincter pressure in pigs.

The effect of graded doses of vasoactive intestinal polypeptide (VIP), enkephalin, neuropeptide Y (NPY), gastrin-17, pentagastrin, cholecystokinin (CCK)-4, CCK-8, neurotensin, somatostatin, and thyrotropin-releasing hormone (TRH) on the substance P (SP)-stimulated lower esophageal sphincter pressure (LESP) in anaesthetized pigs was studied by direct infusion of the peptides into the arterial supply of the lower esophageal sphincter (LES). Infusion of SP in a dose of 20 pmol/kg per min for 3 min significantly increased the LESP (P less than 0.01). Simultaneous VIP infusion at 5--40 pmol/kg per min showed a dose-dependent inhibition of the effect of SP on the LESP. None of the other peptides had any effect on the LESP during simultaneous infusion of SP. Pharmacological blockade by atropine (250 mu/kg) or guanethidine (1 mg/kg) had no effect on the SP-stimulated LESP. In conclusion, the SP-induced stimulation of the LESP is abolished by VIP, and both peptides seem to play a role in the complex regulation of the LESP.

Effects of regulatory peptides on the porcine lower oesophageal sphincter.

Studies were performed to investigate the effects of neurotransmitters and neurotransmitter candidates (substance P, VIP, somatostatin, Met-enkephalin, gastrin-17, CCK-4 and -8, neurotensin and TRH) of the newly discovered peptidergic nervous system on lower oesophageal sphincter pressure in anaesthetized pigs. All neuropeptides were infused over 2 min periods in 6 different doses, separated by resting periods of at least 1 min, directly into the arterial supply of the lower oesophageal sphincter. Substance P caused a dose-dependent increase in lower oesophageal shpincter pressure; the threshold dose was 9 pmol . kg-1 . min-1 and half maximal response occurred at 72 pmol . kg-1 . min-1. None of the other polypeptides, however, influenced the resting lower oesophageal sphincter. These studies show that substance P is a potent stimulant of smooth muscle in the lower oesophageal sphincter, suggesting that this peptide may be an important regulator of lower oesophageal sphincter pressure.

Regulatory peptides in the lower esophageal sphincter of man.

Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.

Monitoring of omeprazole treatment in gastro-oesophageal reflux disease.

OBJECTIVE: To test our standard dosing regimen in omeprazole treatment of gastro-oesophageal reflux disease (GORD) and to determine whether 'non-responders' could be pinpointed. DESIGN: A reverse dose-response examination using increasing doses of omeprazole. The study was conducted as an open consecutive clinical study. Response was measured by 24-h pH-metry, symptoms, endoscopy and histopathology. SETTING: All patients had been referred to one of the partaking departments for evaluation of oesophageal reflux symptoms. PATIENTS: A total of 62 patients were included, 29 with systemic sclerosis and 33 consecutively included patients suffering from idiopathic oesophageal reflux. RESULTS: Approximately one-third of the patients required doses higher than 40 mg of omeprazole/day (up to 140 mg/day) to abolish GOR. No cases of tachyphylaxia or bile-induced oesophagitis were seen in this study. In all patients subjected to dose titration we were able to achieve healing of oesophagitis assessed by symptom scoring, endoscopy and histopathology. No prediction of final dose of omeprazole could be made. CONCLUSION: Four weeks after reaching a dose level of omeprazole that ensured the abolition of GOR, healing of oesophagitis according to endoscopic/histological evaluation was obtained in all patients. Persistent oesophagitis, i.e. bile induced, was not found.

The impact of delayed diagnosis of lung cancer on the stage at the time of operation.

OBJECTIVE: The purpose of this investigation was to study the correlation between diagnostic delay and the stage of the lung cancer at the time of operation. A second objective was to study differences in symptoms between the patients grouped according to stage. METHODS: A total of 172 patients consecutively admitted for surgery between 1 January 1994 and 1 June 1995 at the Department of Thoracic and Cardiovascular Surgery of Rigshospitalet National Hospital of Denmark were included in the retrospective study. Two groups of patients were compared, one group with good prognosis (patients in Stages I and II) and one group with poor prognosis (patients in Stages III and IV). The time-spans studied were: (1) interval from the patient's perception of the first symptom to operation; and (2) the time from first contact with the healthcare-system to operation. The median delay between the patient-groups was compared using the Mann-Whitney U-test. To compare the symptoms which brought the patients in contact with the healthcare-system, the chi2-test was used. RESULTS: In the time interval between appearance of the first symptom and operation, a significantly shorter median delay was found for patients with Stages I and II compared to Stages III and IV (P = 0.037). Concerning the interval from first contact with the healthcare system to operation a significantly shorter median delay was found for the group of patients in Stage I and II compared to the patients-group in Stage III and IV (P = 0.017). It was found that the cancer was an accidental finding, significantly more often in patients in Stages I or II compared to patients in Stages III or IV (P = 0.0002). CONCLUSIONS: A few months delay before final treatment of a non-small-cell lung cancer seems to have an impact on the perioperative stage of the cancer, and thereby on the patients prognosis. A screening of asymptomatic risk-group patients will result in recognition of early lung cancer.

Brain damage following low flow cardiopulmonary bypass in pigs.

Reduction of pump flow during cardiopulmonary bypass (CPB) reduces the formation of microemboli and trauma to the blood components, reduces both rewarming of the heart and the noncoronary collateral flow, and improves surgical exposure. Recent studies indicate that a reduction in pump flow, even at normothermia, does not increase the incidence of postoperative cerebral dysfunction. We examined the cerebral consequences of 2 h of normothermic CPB in pigs carried out at pump flows of either 70 ml/kg per min or 50 ml/kg per min, and compared the results with those of a nonperfused control group. We measured the regional cerebral glucose metabolism and the regional capillary diffusion capacity simultaneously in ten different brain regions. Brain morphology, the blood-brain barrier permeability to serum proteins and the regional cerebral water content were also determined in the same animals. Glucose metabolism decreased significantly in both CPB groups (P < 0.001), and significant differences were found between the capillary diffusion capacities of the three groups (P < 0.05), with decreases in eight out of ten brain regions examined in the 50 ml/kg per min group. The results indicate that a reduction of pump flows from 70 ml/kg per min to 50 ml/kg per min is deleterious to the brain, and that a pump flow of 70 ml/kg per min itself has an injurious effect, when normothermic CPB is carried out for 2 h without the use of vasoactive drugs to maintain the blood pressure. Mean arterial blood pressure (MAP) rather than pump flow seemed to determine the adequacy of the cerebral perfusion.

Early experience of double-lung transplantation with bronchial artery revascularization using mammary artery.

En-bloc double-lung transplantation with tracheal and bronchial revascularization using the left internal mammary artery has been performed in 14 Danish patients. Primary healing of the tracheal anastomosis was observed in 12 patients, in 10 of whom a successful revascularization has been verified by angiography. Two patients have been operated recently and not yet examined by angiography. Mucosal necrosis and subsequent development of bronchial stenosis had to be treated by left-sided pneumonectomy in two patients with failed revascularization. All patients were early survivors (1-14 months). We conclude that bronchial revascularization with the internal mammary artery is possible with an acceptable success rate and is associated with primary healing of the tracheal anastomosis. The impact on long-term results remains to be seen.

Cardiovascular and respiratory effects of terbutaline in patients after open-heart surgery.

In 10 patients after mitral or/and aortic valve replacement, terbutaline was given intramuscularly (10 mcg/kg body wt.) to see what cardiovascular and respiratory effects were produced. A marked cardiovascular effect was seen. Increase in heart rate (20%) was of sinus or atrial origin, no ventricular arrhythmias were seen. Cardiac index rose (46%) left and right stroke work increased (18%, 31%); systemic and pulmonary vascular resistance decreased (32%, 19%); Arterial oxygen tension decreased from 134 to 102 mmHg (24%); O2-consumption remained unchanged. Except for an increase in compliance no changes in respiratory dynamics occurred in the total respiratory system. Terbutaline's cardiovascular effects, its low toxicity, lack of ventricular arrhythmias and unchanged oxygen consumption, indicate that it could be useful to patients where an increase in cardiac output and improvement in peripheral circulation is needed.

The cardiovascular and respiratory effects of fenoterol in patients after open-heart surgery.

Fenoterol (a selective beta-2-adrenergic drug) was given intravenously (2 mcg/kg body weight/15 min) to 7 normotensive patients after open-heart surgery in order to study the cardiovascular and respiratory effects. A marked cardiovascular effect was seen without changes in venous or arterial pressure. The increased heart rate (46%) was of sinus or atrial origin; no ventricular arrhythmias were seen. The cardiac index rose by 91%; left and right ventricular stroke work increased by 26% and 54% respectively; systemic and pulmonary vascular resistance decreased by 31% and 23% respectively; arterial oxygen tension decreased from 264 to 205 mm Hg; oxygen consumption rose 31%. No changes occurred in respiratory dynamics, in the total respiratory system of patient and tubes. The cardiovascular effect of fenoterol, without a corresponding increase in end-diastolic filling pressure and resistance against systolic ejection of the left ventricle, as well as the absence of ventricular arrhythmias, indicate that the drug may be useful as a supplement to other sympathomimetic compounds in normal use.

[Electric stimulation of the autonomic nervous system and vasoactive intestinal peptide and substance P release on the lower esophageal sphincter]. / Estimulación eléctrica del sistema nervioso autónomo y descarga de polipeptido intestinal vasoactivo (VIP) y sustancia P (SP) sobre el esfinter esofáfico inferior (EEI).

The effect of electrical stimulation of splanchnic and vagal nerve supply to the in vivo isolated porcine LES on the lower esophageal sphincter pressure (LESP) and the secretion of VIP and SP into the venous effluent into the venous effluent of the LES was investigated. Functional integrity of the autonomic nerve supply was assessed by the effect of nerve stimulation on heart rate. Vagal nerve stimulation increased LESP (8-Fold) as well as VIP output (3 Fold) significantly (p less than 0.01) whereas the secretion of SP was unaffected of vagal nerve stimulation. Splanchnic nerve stimulation increased heart rate significantly but was without effect on LESP, VIP, and SP outputs. Atropine partially abolished the effect of vagal nerve stimulation on LESP but the VIP secretion was completely resistant to atropine blockade. Administration of guanethidine was without effect on LESP, VIP, and SP outputs during vagal as well as splanchnic nerve stimulation. It is concluded that VIP acts as a neuro-transmitter since vagal stimulation increase the release of VIP from LESP. However, the finding of a partial atropine resistance of the LESP despite an unchanged release of VIP and SP, suggests that other transmitters participate in vagal activation of LESP.

[Does achalasia predispose to cancer of the esophagus?]. / Disponerer achalasia til esophaguscancer?

In a follow-up study of 147 patients with achalasia of the esophagus treated by myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83 years; median 46 years). The living persons were contacted in writing or by telephone. The mean follow-up time after the operation was 23.2 years (range, six to 41 years). The cause of death was established for 71 patients. There were three postoperative deaths and two deaths following recurrence. In comparison with the Danish population, the 66 remaining patients were found to have a relatively higher cancer mortality (34.9% percent). Contrary to the expected less than one, ten of 23 patients who died of cancer had a malignant tumor in the esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of the deaths caused by esophageal cancer. It is concluded that there is a connection between achalasia and cancer of the esophagus that ought to be considered in the treatment and follow-up of patients with achalasia.

[Surgical treatment of cancer of the cardia and the esophagus]. / Kirurgisk behandling af cancer cardiae og cancer esophagi.

During the period 1977 to 1989, 379 patients with cancer cardiac and cancer esophagi were admitted. The ages ranged from 18-88 years with an average of 65 years. The treatment concept was basically unchanged during the study period. Resection as described by Ivor Lewis was employed as palliative or curative treatment when resection was considered possible. Intubation of the esophagus was employed when no other treatment was considered possible. Resection was employed in 251 patients, eight of these emergencies on account of perforation or haemorrhage. Bypass operations were employed in five patients, intubations in 63 and no surgical treatment was undertaken in 60 patients. The all over operative mortality for resections was 11.2% and for elective operations 9.9%. The operative mortality increased with the TNM stage of the tumour and was 3.2% for stages I + II, 8.2% for stage III and 24.4% for stage IV. The complication ration was 42%. 15% of the patients submitted to resection required reoperation. Anastomotic leaks were encountered in 18 patients and nine of these died. Pulmonary complications were the most frequent and resulted in ten early postoperative deaths. The mortality connected with intubations was 15%. The over all five-year survival rate after resections was 10.4%. In stages I + II this was 42% and 8% in stage III. None of the patients in stage IV survived for two years. The longest survival after intubation was less than one year.

[The connection between delayed diagnosis of lung cancer and the intraoperative stage]. / Sammenhaengen mellem forsinket diagnose af lungecancer og stadium på operationstidspunktet.

The five-year survival after surgery for non-small cell lung cancer is good with respect to Stage I and Stage II and poor with respect to higher stages. The aim of this retrospective study of 172 patients was to detect a connection between the intraoperative stage and the pre-operative delay. Concerning the intervals from first symptom to operation and from first contact with the healthcare system to operation, the delay was significantly shorter for the patients in Stage I and II compared to Stage III and IV. The fraction of lung cancers detected by coincidence was significantly higher in Stage I and II compared with Stage III and IV. In conclusion, a few months' delay before final treatment of a non small-cell lung cancer has an impact on the perioperative stage, and thereby on the patient's prognosis. Screening asymptomatic risk-group patients will result in recognition of early lung cancer.

[Lung transplantation. Indications, preoperative evaluation and postoperative treatment]. / Lungetransplantation. Indikationer, proeoperativ bedømmelse og postoperativ behandling.

Thirty-six heart-lung and lung transplantations have been performed in Denmark from January 1992 to January 1994. Heart-lung transplantations was initially carried out in patients with pulmonary vascular diseases. Single lung, double lung and heart-lung transplantation have become therapeutical alternatives and the indications have been expanded to terminal patients with pulmonary diseases. Careful selection of patients and donors, careful surgical techniques and a stringent immunosuppressive treatment have minimized the perioperative mortality. Daily lung function measurements, transbronchial biopsies and bronchoalveolar lavage have created possibilities for an early and safe diagnosis of infections and rejections. A high frequency of obliterative bronchiolitis with loss of pulmonary function is still a serious and unsolved problem. Intensive investigations with the aim of understanding, preventing and treating obliterative bronchiolitis are going on.

[Transplantation of lung lobe from a mother to a child previously transplanted with her bone marrow]. / Transplantation af lungelap fra mor til barn som tidligere var blevet transplanteret med knoglemarv fra moderen.

The lower lobe of the left lung was transplanted from a mother to her child, who previously had received a bone marrow transplant from the mother because of an immune defect. After the bone marrow transplant the child had developed progressive pulmonary fibrosis (obliterative bronchiolitis). The surgical procedure and the early postoperative period has been uncomplicated. Immunosuppression with corticosteroids was only given for a short period, after which no immunosuppressive treatment has been given. The operation and results for both donor and recipient are described. The early results are promising, but rehabilitation is progressing slowly.