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Background: A newly available, laparoscopic 5-mm bipolar vessel sealing device promises substantial advantages over the 10-mm instrument. This study compared the safety as well as the technical and surgical aspects of these different tools., Methods: For this study, 30 consecutive patients undergoing laparoscopic left-sided colectomy were prospectively randomized for the 5-mm LigaSure or The 10-mm LigaSure. The patients' demographics were analyzed together with their intraoperative and postoperative parameters, and the instruments were assessed by the surgeons with a standardized questionnaire., Results: The two groups were comparable and demonstrated similar mean operation times, blood losses, and hospital stays. The 5-mm LigaSure was applied in more operation steps and resulted in fewer bleeding episodes and less lens cleaning. Monopolar scissors were used less frequently in the 5-mm group, thus minimizing cauteric lesions and their complications (0 in the 5-mm group vs 2 in the 10-mm group). Overall satisfaction with the 5-mm LigaSure was significantly higher (8.4 +/- 0.18 vs 6.9 +/- 0.41 out of 10; p = 0.002), with significant advantages in terms of dissection capacity, visibility, and handling., Conclusion: The 5-mm LigaSure is as secure and fast as the larger 10-mm device and compares favorably in terms of finer dissection as well as trocar flexibility and handling. Therefore, it can be used safely in laparoscopic colorectal surgery.

Background: In laparoscopic Roux-en-Y gastric bypass (LRYGBP) surgery, the anastomosis between the gastric pouch and the jejunum can be performed using a circular stapler, as described in the original publication by Wittgrove in 1994. The introduction of the circular stapler through the thick abdominal wall in morbidly obese patients can be challenging. To overcome the difficulties of this task, a new device was developed and its use is presented., Method: The new device has the shape of a trocar tip which can be mounted on the circular stapler, giving it the properties of a trocar. Therefore, easier introduction into the abdominal cavity is feasible. The use of the device was assessed analyzing the data of a prospective database, comparing patient groups operated without the device (n=301) and patients operated with the device (n=100)., Results: The groups were comparable in age, sex, BMI and number of previous abdominal operations. The wound infection rate at the site of stapler introduction decreased from 6.6% to 1% (P=0.035). The overall operating time, hospital stay and complication rate were unchanged., Conclusion: The new device proved to be useful in daily practice and enabled an easier stapler introduction with fewer wound infections.

Hallmarks of the adaptive immune system are antigen-specific cellular and humoral immune responses. Secondary lymphoid organs serve as sites of contact between antigen-presenting cells (APCs) and immune effector T and B lymphocytes. The gut-associated lymphatic system (GALT) as the intestinal branch of the immune system provides different mechanisms to protect organisms against pathogens. Simultaneously, immune activation secondary to genetic factors and/or environmental signals can induce detrimental autoimmunity. The effector pathways in host defense and autoimmunity use similar cytokines and chemokines. Unlike few other cytokines, lymphotoxin (LT) alpha/beta regulates the development of intestinal lymphoid organs, including Peyer's patches (PPs) and mesenteric lymph nodes (MLNs). In addition, intestinal inflammation is suppressed by inhibition of LTbeta signalling, an observation which has initiated clinical studies using this treatment principle. Conversely, the course of Citrobacter rodentium-induced infectious colitis is more severe in mice with impaired LTbeta-receptor-mediated signalling. This report provides an overview on the role of the different organs of the GALT in intestinal inflammation. Moreover, it describes the role of the LTbeta-receptor-mediated signalling in intestinal inflammation as encountered in autoimmune and infectious pathology. The contribution of LT to the delicate balance of immune effector functions in host defense and autoimmunity is discussed.

The rapid increase of morbid obesity has become an important task in the Western world in recent years. Since conservative treatments have failed to prove sufficient efficacy, surgery has turned out to be the most powerful option in treating morbid obesity. In this paper, the different surgical techniques with their advantages and drawbacks are presented. In general, there are restrictive, malabsorptive and combinations of both procedures available. The adjustable gastric banding (Figure 1) represents a purely restrictive operation. It is useful for patients with a relatively low body mass index (BMI) and a good understanding and control of their eating habits. By contrast, the duodenal switch (Figure 2) stands for a mainly malabsorptive procedure that might be indicated in patients with a very high BMI. The Roux-en-Y gastric bypass (Figure 3) is the most widely used bariatric procedure worldwide. It combines restriction and malabsorption. Today, almost two thirds of all bariatric procedures are performed laparoscopically, which has further enhanced the use of surgery in the treatment of morbid obesity. In conclusion, the treatment of morbid obesity represents a significant challenge in the Western world, and bariatric surgery plays a paramount role in the fight against overweight.

Background: Morbidly obese patients show high somatic and psychiatric co-morbidity. Bariatric surgery is accepted as the obesity treatment with the greatest long-term success. There is growing evidence that follow-up studies should address somatic as well as psychosocial conditions of patients undergoing bariatric surgery and non-operatively treated patients. This study investigates the physical and psychosocial outcomes of patients with and without bariatric surgery., Methods: A sample of 131 morbidly obese patients applying for bariatric surgery underwent somatic and psychological assessment (T0). A first follow-up study (T1) was conducted 2 years after T0 in 119 patients. The present second follow-up (T2) was carried out 4 1/2 years after T0 and 3.2 years after potential bariatric surgery. Psychological/psychosocial measures were collected in the 93 patients, 63 of whom were treated surgically, via the Psychosocial Stress and Symptom Questionnaire (PSSQ) and a telephone interview covering BMI, employability, medication, doctor consultations, eating behavior, and physical/psychological well-being., Results: Patients with and without bariatric surgery showed a BMI reduction, which was significantly greater in those who underwent surgery (P<.001). The average percentage of excess weight loss (%EWL) between T0 and T2 was 11.5% in patients with no bariatric surgery, 36.0% in patients with laparoscopic gastric banding, and 52.8% in patients with laparoscopic gastric bypass (%EWL between T0 and T2 in patients of all groups significant, P<.001). Patients with and without surgical treatment showed significant improvement with regard to depressive symptoms and binge-eating behavior. Three-quarters of the surgically-treated and two-thirds of the non-treated patients rated their physical, psychological, and psychosocial well-being as "good" at T2., Conclusion: After 3 to 4 years, all of the patients have adapted well to their weight and body appearance, regardless of whether they have undergone surgery. Weight loss is, however, greater for operated patients, which strongly decreases the risk of developing obesity-related co-morbidities.

Gastric acid secretion is activated by two distinct pathways: a neuronal pathway via the vagus nerve and release of acetylcholine and an endocrine pathway involving gastrin and histamine. Recently, we demonstrated that activation of H(+)-K(+)-ATPase activity in parietal cells in freshly isolated rat gastric glands is modulated by the calcium-sensing receptor (CaSR). Here, we investigated if the CaSR is functionally expressed in freshly isolated gastric glands from human patients undergoing surgery and if the CaSR is influencing histamine-induced activation of H(+)-K(+)-ATPase activity. In tissue samples obtained from patients, immunohistochemistry demonstrated the expression in parietal cells of both subunits of gastric H(+)-K(+)-ATPase and the CaSR. Functional experiments using the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein and measurement of intracellular pH changes allowed us to estimate the activity of H(+)-K(+)-ATPase in single freshly isolated human gastric glands. Under control conditions, H(+)-K(+)-ATPase activity was stimulated by histamine (100 microM) and inhibited by omeprazole (100 microM). Reduction of the extracellular divalent cation concentration (0 Mg(2+), 100 microM Ca(2+)) inactivated the CaSR and reduced histamine-induced activation of H(+)-K(+)-ATPase activity. In contrast, activation of the CaSR with the trivalent cation Gd(3+) caused activation of omeprazole-sensitive H(+)-K(+)-ATPase activity even in the absence of histamine and under conditions of low extracellular divalent cations. This stimulation was not due to release of histamine from neighbouring enterochromaffin-like cells as the stimulation persisted in the presence of the H(2) receptor antagonist cimetidine (100 microM). Furthermore, intracellular calcium measurements with fura-2 and fluo-4 showed that activation of the CaSR by Gd(3+) led to a sustained increase in intracellular Ca(2+) even under conditions of low extracellular divalent cations. These experiments demonstrate the presence of a functional CaSR in the human stomach and show that this receptor may modulate the activity of acid-secreting H(+)-K(+)-ATPase in parietal cells. Furthermore, our results show the viability of freshly isolated human gastric glands and may allow the use of this preparation for experiments investigating the physiological regulation and properties of human gastric glands in vitro.

Background: With a dramatically increasing number of bariatric operations performed world-wide in the recent years, more late complications have been noticed. Proximal gastric pouch dilatation is a known late complication after laparoscopic or open restrictive surgery for morbid obesity. In the present paper, we report our experience with laparoscopic re-operation of enlarged gastric pouches after laparoscopic gastric bypass, with emphasis on technique and outcome., Methods: Data were retrieved from a prospective database of 334 patients who underwent a laparoscopic gastric bypass operation at the University Hospital of Zurich from July 2000 to December 2004. Five laparoscopic revisions for pouch dilatation after primary bypass were performed., Results: 3 female and 2 male patients with median age 40 years (range 32-55) underwent a laparoscopic pouch resizing. At the time of the re-operation, the median BMI was 32.0 kg/m(2) (range 28.4-48.4). All procedures were performed laparoscopically with no conversion to open surgery. The median operating-time was 110 minutes (95-120). The median hospital stay was 6 days (range 5-14). The median BMI in the follow-up of 12 months (9-14) was 28.0 kg/m(2) (25.5-45.8). Diabetes mellitus improved in 4 cases during follow-up., Conclusion: Laparoscopic pouch resizing with redo of the gastro-jejunal anastomosis was feasible, safe and effective in this small series. It led to further weight loss and improved symptoms of poor pouch emptying.

Bariatric surgery is currently considered the best treatment option for morbid obesity. With the rapid development of laparoscopic techniques, a significant increase in the number bariatric procedures in recent years can be observed. Various surgical techniques to treat morbid obesity have been described, but only few prospective studies compare the different procedures, leading to a lack of evidence for their use. However, from the available literature some general recommendations can be given: (a) preoperative workup in an interdisciplinary team is mandatory, (b) primary bariatric procedures should be performed laparoscopically, and (c) the combination of restrictive and malabsorptive techniques is more efficient than a purely restrictive method, which is also true for the treatment of comorbid diabetes and arterial hypertension. In this paper, we present recent developments in bariatric surgery, with special emphasis on the available evidence for the best treatment of morbidly obese patients.

Anamnesis and Clinical Findings: The 47-year-old male patient was admitted to the hospital because of newly diagnosed diabetes and elevated liver function tests (gamma glutamyl transferase 303 U/l). On admission the patient reported a reduction of appetite, which had increased during the past 2 weeks, fatigue, muscular weakness, polyuria and polydypsia. On physical examination the patient was moderately overweight, the blood pressure was normal. There were leg edema, which had not responded to previous treatment. There were no additional signs of right heart failure., Investigations: On admission there were hypokalemia and increased parameters of cholestasis. Cortilsol concentration was elevated (1744 microg/l). Hypokalemia which was refractory to treatment raised the differential diagnosis of Conn's syndrome or ectopic secretion of ACTH, although these conditions are frequently associated with arterial hypertension. Cushing's syndrome was finally diagnosed despite of the lack of classical symptoms. Underlying reason was an adenocarcinoma of the pancreas with ectopic secretion of ACTH., Treatment and Course: Therapy was targeted to control the excessive secretion of cortisol. A treatment attempt with subcutaneous somatostatin and the adrenal enzyme inhibitor ketoconazole failed to control increased cortisol secretion. Bilateral surgical adrenalectomy was performed because of the patient's progressively deteriorating clinical condition. The patient developed a lethal septic shock after surgery, most likely due to the cortisol-induced immunosuppression., Conclusion: 1. In patients presenting with muscular weakness, leg oedema refractory to treatment, hypokalemia and hyperglycemia hypercortisolism should be ruled out even in the absence of typical clinical signs. 2. Massive hypercortisolism (as present in ectopic ACTH secretion) is not necessarily associated with arterial hypertension.

In the last decades surgical treatment for morbid obesity has emerged from being the interest of only few surgeons to a well recognized surgical specialty. This development was promoted by the dramatic increase of prevalence of obesity and the development of laparoscopic surgical techniques. In 1996 the NIH consensus conference stated that bariatric surgery is the most effective therapy to treat obesity and type 2 diabetes, whereas conservative treatment strategies failed in the long-term. Only few studies have compared the different operative strategies. It has been shown that the bypass procedure is better than gastric banding with respect to weight loss and the decrease of comorbidities, but suffers from more short-term morbidity. In recent years, randomized trials have been published comparing laparoscopic with open procedures. These studies show an advantage for the laparoscopic techniques. This paper gives a critical overview on bariatric surgery and summarizes the current literature in this speciality.

Objective: To define whether laparoscopic gastric banding or laparoscopic Roux-en-Y gastric bypass represents the better approach to treat patients with morbid obesity., Summary Background Data: Two techniques, laparoscopic gastric bypass or gastric banding, are currently widely used to treat morbid obesity. Since both procedures offer certain advantages, a strong controversy exists as to which operation should be proposed to these patients. Therefore, data are urgently needed to identify the best therapy., Methods: Since randomized trials are most likely not feasible because of the highly different invasiveness and irreversibility of these procedures, a matched-pair design of a large prospectively collected database appears to be the best method. Therefore, we used our prospective database including 678 bariatric procedures performed at our institution since 1995. A total of 103 consecutive patients with laparoscopic gastric bypass were randomly matched to 103 patients with laparoscopic gastric banding according to age, body mass index, and gender., Results: Both groups were comparable regarding age, gender, body mass index, excessive weight, fat mass, and comorbidites such as diabetes, heart disease, and hypertension. Feasibility and safety: All gastric banding procedures were performed laparoscopically, and one gastric bypass operation had to be converted to an open procedure. Mean operating time was 145 minutes for gastric banding and 190 minutes for gastric bypass (P < 0.001). Hospital stay was 3.3 days for gastric banding and 8.4 days for gastric bypass. The incidence of early postoperative complications was not significantly different, but late complications were significantly more frequent in the gastric banding group (pouch dilatation). There was no mortality in both groups. Efficiency: Body mass index decreased from 48.0 to 36.8 kg/m in the gastric banding group and from 47.8 to 31.9 kg/m in the gastric bypass group within 2 years of surgery. These differences became significant from the first postoperative month until the end of the follow-up (24 months). The gastric bypass procedure achieved a significantly better reduction of comorbidities., Conclusions: Laparoscopic gastric banding and laparoscopic gastric bypass are feasible and safe. Pouch dilatations after gastric banding are responsible for more late complications compared with the gastric bypass. Laparoscopic gastric bypass offers a significant advantage regarding weight loss and reduction of comorbidities after surgery. Therefore, in our hands, laparoscopic Roux-en-Y gastric bypass appears to be the therapy of choice.

Objective: To define whether laparoscopic rebanding or Roux-en-Y gastric bypass represents the best approach for failed laparoscopic gastric banding in patients with morbid obesity., Summary Background Data: Countless laparoscopic gastric bandings have been implanted during the recent years worldwide. Despite excellent short-term results, long-term failures and complications have been reported in more than 20% of patients. Which rescue procedures should be used remains controversial. Therefore, we analyzed our experience with the use of laparoscopic rebanding versus laparoscopic Roux-en-Y gastric bypass after failed gastric banding., Methods: Using a prospectively collected database, we analyzed the feasibility, safety, and effectiveness of laparoscopic rebanding versus laparoscopic conversion to Roux-en-Y gastric bypass after failed laparoscopic gastric banding. RESULTS A total of 62 consecutive patients were treated in our institution between May 1995 and December 2002 for failed primary laparoscopic gastric banding, including 30 laparoscopic rebandings and 32 laparoscopic conversions to Roux-en-Y gastric bypass. Rebandings were preferably done during the initial period of the study and Roux-en-Y gastric bypass in the last period. Both groups were comparable before the initial banding procedures. At the time of redo surgery, patients receiving a gastric bypass had more esophageal dysmotility (47% vs. 7%, P = 0.002) and higher body mass index (BMI) than those elected for rebanding procedures (BMI 42.0 vs. 38.4 kg/m2, P = 0.015). Feasibility and safety: Each procedure was performed laparoscopically. Mean operating time was 215 minutes for gastric bypass and 173 minutes for rebanding (P = 0.03). Early complications occurred in one case in the rebanding group and in 2 cases in the bypass group; all underwent a laparoscopic reexploration without the need for open surgery. There was no mortality in this series. Effectiveness: BMI in the gastric bypass group decreased from 42.0 to 31.8 kg/m2 (P = 0.02) within 1 year of surgery, while it remained unchanged in the rebanding group., Conclusions: Laparoscopic conversion to a gastric bypass as well as laparoscopic rebanding are feasible and safe. Conversion to gastric bypass offers a significant advantage in terms of further weight loss after surgery. Therefore, this procedure should be considered as the rescue therapy of choice after a failed laparoscopic gastric banding.

Objective: The immediate hemodynamic effects of contrast agents are well documented. Less is known about their longer-lasting effects. We investigated the later effect of iopromide on the neurovascular coupling mechanism after the performance of cerebral or coronary angiography. Neurovascular coupling is a fine-tuned and reliable mechanism adapting cerebral blood flow to cortical activity. When performing a visual stimulation and measuring the resultant flow velocity change in the posterior cerebral artery transcranial Doppler has been used to determine vascular integrity., Methods: The visually evoked blood flow velocity response in the posterior cerebral artery was measured with transcranial Doppler before, 1-2 h after and the day after angiography. The overshoot of the flow velocity response and the stable flow velocity level at the end of the stimulation phase were used to compare the different conditions., Results: A significantly diminished overshoot was found 1-2 h after angiography only in patients undergoing cerebral angiography. The stable blood flow velocity levels at the end of the stimulation phase remained unchanged in all cases., Conclusions: Our finding demonstrates effects of contrast media on dynamic blood flow regulation of the cerebral vasculature 1-2 h after application of direct contrast agent suggesting a possible concentration effect of the contrast agent. However, since the relative blood flow velocity increase under stable blood flow conditions remained constant, this dynamic alteration does not cause a reduction in cerebral blood flow., (Copyright 2003 S. Karger AG, Basel)

History and Clinical Findings: A 56-year-old man presented himself at our polyclinic with the symptoms of dyspnoea at rest and exhaustion. The case history revealed an alcoholic liver cirrhosis (Child B) and recurrent heart burn as a sign of a gastro-esophageal reflux disease. The examination showed jaundice and enlargement of the liver as pathological features., Investigations: At gastroscopy multiple openings of pseudodiverticula and a high-grade inflammatory reaction of the esophageal mucosa was found, indicating pseudodiverticulosis of the esophagus. After staining with lugol-solution and directed biopsy of unstained areas there was no sign of malignancy in the histopathological report., Treatment: The candida esophagitis and gastroesophageal reflux disease were treated with antimycotic and proton-pump-inhibiting drugs after which the patient had no more complains. Regular gastroscopic controls are planned., Conclusion: Pseudodiverticulosis of the esophagus is a very rare disease which arises from ductal dilatation of the mucosal glands during chronic inflammation of the esophagus. In most cases the pseudodiverticulosis is an accidental finding without symptoms. Risks can arise from the most frequent complications like development of inflammatory strictures, motility disorders and transformation to malignancy. Therefore it is necessary to perform regular inspection of the esophagus by endoscopy.

Familial amyloidotic polyneuropathy (FAP) caused by amyloidogenic transthyretin (ATTR) mutations is the most common form of hereditary amyloidosis. We investigated the diagnostic value of the bone scanning agent technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in this disease. Eight patients (four males, four females; age 54.4+/-8.3 years, range 43-67 years) with ATTR-FAP proven by immunohistochemistry and molecular analysis and a control group comprising ten oncological out-patients (five males, five females; age 53.4+/-8.5 years, range 34-66 years) without evidence of bony metastases were studied using 99mTc-DPD. Whole body tracer retention was 80.1%+/-10.3% (range 65.1%-94.8%) in FAP patients and 55.7%+/-8.1% (range 40.2%-66.7%) in controls at 3 h p.i. (P<0.001), and cardiac uptake was 7.3%+/-2.2% (range 4.2%-10.1%) in FAP patients and 3.1%+/-0.5% (range 2.3%-4.0%) in controls (P<0.001). The heart/whole body uptake ratio was 8.9%+/-1.7% (range 6.5%-11.0%) in FAP patients and 5.6%+/-0.5% (range 5.1%-6.8%) in controls (P<0.001). The three FAP patients with the highest cardiac tracer uptake had cardiomyopathy or arrhythmia. 99mTc-DPD scintigraphy is proposed as a simple and valuable diagnostic aid to evaluate the severity of the disease and the risk of concomitant heart problems.

More than 75% of all types of cancer are due to environmental factors. These latter include nutrition. A diet rich in fruit and vegetables, carotenoids, and vitamin C has a protective effect against cancer. A high-calorie, high-fat diet, and the consumption of alcohol have the opposite effect. New data appear to show that the daily consumption of up to 20 g alcohol in women, and 40 g in men, previously considered innocuous, must be considered a risk for certain types of cancer. A particularly close association with alcohol is found in the case of cancer of the breast, and tumours of the mouth, pharynx and esophagus.

Background: Multimodal therapeutic strategies gain importance in locally advanced squamous cell carcinoma of the head and neck. Quantitative regression grading can be traced as an independent prognostic parameter in the histological examination in many neoadjuvantly treated cancers. Various regression systems have been suggested. We propose an easy to apply and economical score that seems to have a significant prognostic value in squamous cell carcinoma of the head and neck., Patients and Methods: 43 patients with Stage IV squamous cell carcinoma of the head and neck have been treated neoadjuvantly with two cycles chemotherapy (ifosfamide 1.5 g/m2 day 1-5 with mesna [300 mg/m2], cisplatin 60 mg/m2 day 5, second cycle day 22). Hyperfractionated accelerated radiotherapy (30 Gy) was given from day 29 on. We divided the resected tumors histologically as follows: Grade I--no tumor cells to be identified, Grade II--necrosis, Grade III--partial destruction of the carcinoma, Grade IV--vital carcinoma., Results: After 1 year the overall survival amounted to 79%, after 2 years 56%. A significant correlation could be established between qualitative tumor regression and survival. The 1-year survival depended on the regression of the primary as follows: 94% in Grade I, 80% in Grade II, 60% in Grade III and 56% in Grade IV. For the 2-year survival: 76%, 40%, 40%, 11% (p < 0.01). The results were similar regarding the neck dissections., Conclusions: After radiochemotherapy the histological regression is a significant prognostic factor of survival. A simple system with four subgroups is suggested which seems to be of a high prognostic value. We discuss to intensify the treatment for patients with good regression after neoadjuvant therapy for a further reduction of recurrence.

Purpose: Hemoglobin levels are currently the focus of interest as prognostic factors in patients with head and neck cancer. Most published clinical trials have confirmed hemoglobin to possess a significant influence on survival in patients treated with radiotherapy. In our study we have investigated the prognostic value of hemoglobin in a combined modality schedule., Patients and Methods: Forty-three patients with advanced head and neck tumors were treated with combined radio-chemotherapy. The therapy comprised 2 courses of induction chemotherapy with ifosfamide (1,500 mg/m2, day 1 to 5) and cisplatin (60 mg/m2, day 5) followed by hyperfractionated accelerated radiotherapy with a total dose of only 30 Gy. Surgery involved tumor resection and neck dissection., Results: The 1-year overall survival rate and the 2-year survival rate were 79% and 56%, respectively. The 1- and 2-year recurrence-free survival rates were 68% and 49%, respectively. Prognostic factors with an impact on survival were seen in tumor size (T3 vs T4, p = 0.0088), response to radio-chemotherapy at the primary site (no vital tumor rest vs vital tumor rest, p = 0.045), response to lymph node radio-chemotherapy (no vital tumor cells vs vital tumor cells, p = 0.013) and level of hemoglobin after radio-chemotherapy (Hb > or = 11.5 g/dl vs < 11.5 g/dl, p = 0.0084)., Conclusion: In our study hemoglobin level after radio-chemotherapy was identified for the first time to be also a significant prognostic factor (univariate analysis) in head and neck cancer patients who underwent combined radio-chemotherapy. Besides chemotherapy plus low-dose irradiation achieved similar results in comparison with radical resection and high-dose radiotherapy at least for the first 2 years after therapy. Relapsing disease could be treated with 1 additional course of radiotherapy which is supposed to be well tolerated.

Objective: Mortality in diabetic patients with acute myocardial infarction (MI) is high. The significance of the pretreatment coronary status in type 2 diabetic patients with acute MI, as well as the effect of mechanical revascularization using percutaneous transluminal coronary angioplasty (PTCA), has not been established., Research Design and Methods: All patients with type 2 diabetes and acute MI (n = 54) were prospectively enrolled into a study of immediate coronary angiography to guide PTCA of the occluded infarct vessel. Hospital and long-term course were assessed and compared with an unselected control group of nondiabetic patients (n = 358) who were enrolled in the same study., Results: Angiography showed that sites of occlusion and acute coronary flow were similar in both groups. Multivessel disease and shock were more common in type 2 diabetic versus nondiabetic patients: 69 vs. 51% and 21 vs. 10% (P < 0.02), respectively. Direct PTCA was successful in > 90% in both groups. Mortality after 30 days was 13% in type 2 diabetic patients versus 5% in patients without diabetes (P < 0.04). Left ventricular (LV) ejection fraction before discharge was lower in diabetic patients (48 +/- 17 vs. 55 +/- 15%, P < 0.05). Mortality 1 year after discharge was 11 vs. 4% in diabetic versus nondiabetic patients (P < 0.02). Multivariate analysis identified type 2 diabetes as an independent risk factor for acute, but not for late, mortality., Conclusions: Direct PTCA is safe and effective in type 2 diabetic patients with acute MI. Mortality after 30 days in unselected diabetic patients is < 15% with this approach. Advanced disease and shock contribute to an increased mortality in type 2 diabetic patients with acute MI versus nondiabetic patients.

History and Admission Findings: A 37-year-old woman, known since childhood to suffer from generalized seizures, was sent to the intensive care unit in status epilepticus. On admission tonic-clonic seizures persisted even after intravenously administration of clonazepam, 2 x 1 mg. She was unconscious and reacted unfocused to painful stimuli., Treatment and Course: Further seizures occurred with vomiting and respiratory failure threatened. After intubation phenytoin was given intravenously (initially 250 mg over 10 min, then 750 mg over 24 h) into a vein on the dorsum of the hand. The seizures stopped. Within a few hours a livid swelling developed at the site of the needle puncture on the right hand, which spread to the lower arm (purple glove syndrome) and the patients could no longer move her arm because of pain. The condition improved with anti-inflammatory treatment and antibiotics as well as local measures. On discharge she was able to make a first without pain. However, she was re-admitted 3 weeks later because of renewed painful impairment of right hand movement and the picture of early Sudeck's atrophy. Under regional anaesthesia complete mobility and freedom from pain was achieved within 2 weeks., Conclusion: Administration of phenytoin into a peripheral vein, especially of the hand, can cause soft tissue damage and should be avoided. Primarily the oral route is to be preferred.

Silymarin can be extracted from the milk thistle, and silibinin is the main component of the plant extract. Possibly due to their antioxidant and membrane-stabilizing properties, the compounds have been shown to protect different organs and cells against a number of insults. Thus liver, kidney, erythrocytes and platelets have been protected from the toxic effects of ethanol, carbon tetrachloride, cold ischemia and drugs, respectively. The effect of silibinin on endocrine and exocrine pancreas, however, has not been studied. We therefore investigated whether silibinin treatment attenuates cyclosporin A (CiA) toxicity on rat endocrine and exocrine pancreas. Groups of 15 male Wistar rats were treated for 8 days with CiA and/or silibinin. On day 9, endocrine and exocrine pancreatic functions were tested in vitro. At the end of the treatment period, blood glucose levels in vivo were significantly higher in rats treated with CiA while silibinin did not affect glucose levels. In vitro, insulin secretion was inhibited after treatment with silibinin, but amylase secretion was not affected. After treatment with CiA both insulin and amylase secretion were reduced. Silibinin and CiA had an additive inhibitory effect on insulin secretion, but silibinin attenuated CiA-induced inhibition of amylase secretion. Despite CiA treatment, amylase secretion was in fact restored to normal with the highest dose of silibinin. Thus silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. This combination of effects could be useful in the treatment of non-insulin-dependent diabetes mellitus. Furthermore, silibinin protects the exocrine pancreas from CiA toxicity. As this inhibitory effect is probably unspecific, silibinin may also protect the exocrine pancreas against other insult principles, such as alcohol.

We present the case of a 57-year-old woman who developed persistent jaundice and cholestasis four weeks after a severe burn injury (34% of the body surface, 19% second degree, 15% third degree). In the endoscopic retrograde cholangiography four months later the characteristic picture of sclerosing cholangitis was found. A causal relation between the thermal injury and the development of sclerosing cholangitis is likely because of this coincidence and the absence of any preexisting disease, especially of the hepatobiliary system. Other cholestatic liver disease could be excluded. Possible pathogenetic mechanisms are discussed, especially the increased permeability of the gut mucosa after burn injuries with consecutive translocation of bacteria and toxins and their transport into the biliary tract.

Somatostatin is a potent inhibitor of endocrine and exocrine pancreatic secretion. However, it is not clear whether it also inhibits pancreatic growth. Therefore we treated male Wistar rats with a somatostatin analogue, octreotide (12-192 micrograms/(kg body wt.day)), over a period of 14 days. In a dose-dependent manner, this potent and long-acting analogue caused a reduction in weight of the pancreas and a reduction in pancreatic content of protein, DNA, trypsin, chymotrypsin, amylase and lipase, as well as pancreatic content of insulin-, glucagon- and somatostatin-like immunoreactivities. When growth of rat pancreas was induced by oral administration of camostate (200 mg/(kg body wt. day) or by subcutaneous administration of cholecystokinin (2 x 10 micrograms/(kg body wt. day)) over a period of 14 days, octreotide (12-192 micrograms/(kg body wt.day)) had the same effects, but these were even more pronounced. We conclude that somatostatin is an important regulator of pancreatic growth.

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment. In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.

Peptide YY (PYY) inhibits exocrine pancreatic secretion in several species. Two receptors, Y1 and Y2, are known to mediate PYY actions. While PYY 1-36 binds equally to both receptor subtypes, a second endogenous form of PYY, PYY 3-36, selectively activates Y2 receptors. The importance of Y receptor subtypes for inhibition of exocrine pancreatic secretion by PYY is unknown. We studied the effects of PYY 1-36 on cholecystokinin octapeptide (CCK-8)-stimulated amylase secretion in an isolated perfused rat pancreas model. To characterize functionally the receptors involved we determined the effects of a Y1-selective agonist, [Pro34]PYY; a Y2 selective agonist, PYY 3-36; and neuropeptide Y (NPY) in this model. PYY 1-36 significantly inhibited stimulated amylase secretion in the denervated rat pancreas. [Pro34]PYY and NPY both inhibited exocrine pancreatic secretion as potently as PYY 1-36. Contrary to that, the Y2 selective agonist, PYY 3-36, was inactive. We conclude that PYY inhibits exocrine pancreatic secretion in this extrinsically denervated rat pancreas model by Y1 receptors.

Intravenous glucagon inhibits exocrine pancreatic secretion in vivo, but exogenous glucagon does not affect exocrine secretion in vitro. Recent work, however, suggested that endogenous glucagon may be involved in the regulation of exocrine secretion even in vitro. We therefore investigated the effects of exogenous and endogenous glucagon on exocrine secretion by the isolated perfused rat pancreas in the presence of 1.8 mM glucose. Exogenous glucagon did not affect CCK-stimulated amylase output. 20 mM arginine stimulated glucagon release, but did not affect basal enzyme secretion. CCK-stimulated amylase output, however, was significantly inhibited in the presence of arginine. This inhibitory effect of arginine on exocrine pancreatic secretion could be blocked by glucagon antibodies, but not by nonspecific gammaglobulins. Thus exogenous glucagon failed to affect exocrine pancreatic secretion in vitro, but endogenously released glucagon or a glucagon-like peptide inhibited amylase release in the isolated perfused pancreas. We conclude that glucagon or a glucagon-like peptide may be a mediator in the islet-acinar axis.

Experimental pancreatic lesions can be induced by a number of different procedures, e.g. pancreatic hyperstimulation, intraductal application of bile acids, feeding choline deficient diet, obstruction of pancreatic duct, or reducing pancreatic blood flow. The pathogenetic mechanisms leading to pancreatic lesions include basolateral enzyme secretion, acinar cell polarisation defect, intracellular activation of proteases, and the production of free radicals and other active metabolites. The importance of these individual mechanisms in the production and progression of different experimentally-induced pancreatic lesions remains speculative. These pathogenetic concepts have inspired the study of a number of substances likely to protect the pancreas and prevent the pancreatic lesions. This paper gives an overview of the pathogenetic concepts of development of and protection against experimental pancreatic lesions produced in animal models. Special mention has been made of an animal model of pancreatic lesion produced by immunosuppressives.

Specific inhibitors acting upon pancreatic proteinases in the gut can cause pancreatic hypertrophy ('growth'), which is probably mediated through a feedback mechanism utilizing cholecystokinin. We have proposed the involvement of somatostatin, and here test the hypothesis that endogenous somatostatin secreted into pancreatic juice may regulate pancreatic growth. Groups of rats were given the proteinase inhibitor camostate intragastrically for either 3, 7, 14, 28, or 56 days, when they were sacrificed. In some groups the pancreata were weighed and homogenized while in other groups isolated perfused pancreatic organ preparations were performed. Somatostatin was measured in the homogenates, pancreatic juice and portal vein effluents. In camostate-fed animals, pancreatic weights increased to a maximum at 28 days, while pancreatic somatostatin content increased significantly from the third day onwards, and somatostatin secretion into pancreatic juice increased progressively until day 28. In contrast, somatostatin secretion into portal blood remained unchanged from those of untreated controls over the duration of the experiment, and its concentration was lower than in pancreatic juice. These observations provide further evidence that endogenous pancreatic somatostatin may control pancreatic growth in rats.

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and glucagon release as well as exocrine pancreatic secretion in the presence of 1.8 mM glucose. Cysteamine, 10 mM, released somatostatin, but had no effect on CCK-stimulated amylase secretion. Arginine-stimulated glucagon release, however, was significantly inhibited by cysteamine. Concomitantly we still observed stimulation of somatostatin secretion, but also a potentiation of CCK-stimulated amylase secretion. Our results are consistent with a role of somatostatin in the regulation of exocrine pancreatic secretion via its effect on pancreatic A and B cells.

Pancreastatin was isolated from porcine pancreas in 1986 and has been shown to inhibit insulin release and exocrine pancreatic secretion in vivo. In the isolated perfused rat pancreas, we investigated its effect on the exocrine pancreas and evaluated its indirect effects mediated via the islet-acinar axis. In the presence of 16.7 mmol/L glucose, 20 pmol/L, 200 pmol/L, and 2 nmol/L pancreastatin reduced insulin release but did not affect exocrine pancreatic secretion stimulated by cholecystokinin (CCK), secretin, or bombesin. Pancreastatin also failed to affect unstimulated exocrine pancreatic secretion. In the presence of 1.7 mmol/L glucose, 200 pmol/L and 2 nmol/L pancreastatin inhibited glucagon release and potentiated CCK-stimulated exocrine pancreatic secretion. Inhibition of glucagon release and augmentation of exocrine pancreatic secretion may be independent phenomena, but they could be linked by the islet-acinar axis. Thus we speculate that a pancreastatin-induced inhibition of glucagon release may indirectly have caused augmentation of exocrine pancreatic secretion.

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and insulin release as well as exocrine pancreatic secretion in the presence of 16.7 mM glucose and 180 pM CCK-8. At a concentration of 0.1 mM, cysteamine had no significant effect on pancreatic endocrine and exocrine functions. At 10 mM, however, cysteamine released somatostatin (380 +/- 70 vs 100 +/- 20 fmol/20 min), inhibited insulin output (890 +/- 120 vs 13210 +/- 3260 mu units/20 min) and reduced exocrine pancreatic secretion (volume: 12 +/- 2 vs 20 +/- 2 microliters/20 min; lipase: 31 +/- 3 vs 60 +/- 7 units/20 min). We conclude that the complex changes induced by cysteamine are consistent with a physiological role of endogenous somatostatin in the regulation of insulin release. The reduction of exocrine pancreatic secretion, however, was at least in part, if not completely, mediated via the insuloacinar axis rather than a direct effect of cysteamine-released somatostatin on pancreatic acinar cells.

Previous work has shown that cyclosporin A is toxic to the endocrine and exocrine pancreas. The aim of this study was to examine whether endogenous eicosanoids play a role in controlling cyclosporin A induced toxicity. Rats were treated for eight days with indomethacin (2 mg/kg, twice daily) in addition to cyclosporin A (5 or 10 mg/kg daily). Effects of drug treatments on exocrine (as assessed by amylase and protein secretion into the pancreatic juice) and endocrine (as assessed by the glucose dependent insulin release) pancreatic functions, and pancreatic formation of prostaglandins and thromboxane were evaluated. Treatment with cyclosporin A in the doses used did not inhibit eicosanoid formation by the pancreatic tissue ex vivo. Indomethacin caused significant inhibition of pancreatic formation of prostaglandin E2, 6k prostaglandin F1 alpha and thromboxane B2. Combined treatment with indomethacin and cyclosporin A (5 or 10 mg/kg) augmented cyclosporin A induced pancreatic toxicity with further impairment of insulin release, amylase secretion, and pancreatic juice protein content, but did not result in more pronounced inhibition of pancreatic eicosanoid formation. The increased toxicity of the combined treatment was, however, associated with raised cyclosporin A whole blood concentrations. The data suggest that the potentiation of pancreatic toxicity of cyclosporin A observed during coadministration of indomethacin is not the result of suppression of endogenous pancreatic eicosanoid biosynthesis, but more likely results from altered cyclosporin A pharmacokinetic which may be caused by an interference of indomethacin with the hepatic cytochrome P-450 dependent monooxygenase involved in cyclosporin A metabolism. The possibility that coadministration of non-steroidal antiinflammatory drugs aggravates toxic effects in cyclosporin A treated patients should be considered.

When diagnosed, the greater proportion of functioning endocrine tumors have already metastasized. As a result, the primary aim of treatment--complete surgical removal of the growth--is possible in only a small number of patients. This gives considerable importance to palliative treatment. Interferons and somatostatin are the substances in the forefront of therapeutic interest today, cytostatic chemotherapy having proved largely ineffective and associated with considerable side effects. A feature common to interferons and somatostatin is the fact that they are much more likely to achieve a subjective improvement in clinical symptoms rather than objective remission. However, this is not disadvantage, since, in view of the slow growth of these tumors, quality of life is determined by controlling endocrine activity and not by debulking tumor mass.

Recently we could demonstrate that in rats with pancreatic hypertrophy, somatostatin is secreted in higher concentrations into the pancreatic juice than into the portal vein blood. For measurement of juice somatostatin and to characterize the molecular forms, we established a new reverse-phase HPLC method, which we describe herein. This HPLC method, using a linear gradient system consisting of 0.2% heptafluorbutyric acid in 10 mM sodium acetate and acetonitrile, showed a stable recovery rate of about 85%. Applying the pure juice to this gradient system, we detect somatostatin-14 to be the major form of immunoreactive somatostatin (IRSS) in the pancreatic juice of the rat (5% of total IRSS). The remaining 35% were found to be somatostatin-28. The role of somatostatin in pancreatic juice is not known. It raises the hypothesis that it possibly interacts with the influences intraluminal intestinal growth factors. This study supports the assumption for the existence of an insuloacinar portal system to regulate exocrine pancreatic functions by islet hormones.

Endocrine cells are characterized by common biochemical properties and specific cellular markers. Endocrine tumors, too, differ from other types of tumor in a number of ways. These have to do with the classification, the occurrence of functioning or nonfunctioning forms, benign and malignant courses, solitary or multiple presentation, as well as entopic and ectopic growth forms. The incidence of the gastrointestinal functioning tumors is about 0.5-1.0 per 100,000, the nonfunctioning tumors predominating many times over. The diagnosis of functioning endocrine tumors in the early phases of the disease is based on the biochemical demonstration of substances released into the blood, and the clinical picture is determined not primarily by the size or extent of the tumor, but by the biological effects of the tumor secretions. The clinical symptomatology associated with these tumors is often much more marked than the measurable tumor manifestation.

The influence of the neuropeptide galanin, present in intrapancreatic nerve endings, on the endocrine pancreas is well known. The most potent effect of galanin is inhibition of insulin release. Little is known of its effect on the exocrine pancreas. Whether galanin plays a role in the regulation of exocrine pancreatic secretion and whether this effect is mediated directly on acinar cells or indirectly via the influence on insulin secretion is not clear. In the present study, we investigated these questions using the model of the isolated and arterially perfused rat pancreas with intact exocrine and endocrine secretion. In the presence of 15.8 mM glucose in a modified Krebs-Ringer buffer and during half-maximal stimulation of enzyme secretion with 100 pmol/ml cholecystokinin octapeptide (CCK-8), a dose-response study of 0.001-100 pmol/ml porcine galanin was performed. At concentrations of 0.001 and 0.01 pmol/ml, porcine galanin significantly stimulated insulin release (p < 0.05 and < 0.01, respectively) and also significantly enhanced CCK-8-stimulated amylase secretion (p < 0.05). Doses of 0.1 and 1 pmol/ml galanin resulted in a nonsignificant inhibition of insulin release, while 10 and 100 pmol/ml strongly inhibited the endocrine response (p < 0.001). However, concentration levels of 1-100 pmol/ml galanin did not affect CCK-8-stimulated amylase secretion. Rat galanin, tested at 0.01 and 10 pmol/ml, showed no significant difference from the effects of porcine galanin at the equipotent concentrations. It is concluded that the effect of galanin on exocrine pancreas, like the effect on endocrine functions, tends to be a direct one and that it could exert a modulatory influence on the level of neuronal transmission.