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Biomedical subjects

M K Müller

Publications and source records attributed to M K Müller.

At least 19 recordsLinked to original sources

[Diabetes mellitus and massive lower leg edema without heart failure].

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.

Adenocarcinoma↗

[Evidential basis in bariatric surgery].

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.

Bariatric Surgery↗

[Minimally invasive surgery for morbid obesity--evidence or fashion?].

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.

Bariatrics↗

[Esophageal pseudodivertikulosis].

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.

Biopsy↗

[Cancer-inducing alcohol. "Reasonable" drinking also causes damage].

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.

Alcohol Drinking↗

[The value of qualitative regression grading as a prognostic factor for survival after preoperative radiochemotherapy in patients with advanced head and neck cancer].

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.

Adult↗

Prognostic value of hemoglobin concentrations in patients with advanced head and neck cancer treated with combined radio-chemotherapy and surgery.

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.

Adult↗

["Purple glove syndrome." Severe soft tissue reaction following phenytoin infusion].

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.

Adult↗

Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity.

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.

Amylases↗

[Sclerosing cholangitis after burn injury].

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.

Bile Ducts, Intrahepatic↗

Endocrine and exocrine pancreatic function after camostate-induced growth of the organ.

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.

Animals↗

Peptide YY inhibits exocrine pancreatic secretion in isolated perfused rat pancreas by Y1 receptors.

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.

Amylases↗

Rat pancreas after long-term treatment with the somatostatin analogue octreotide.

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.

Animals↗

The islet-acinar axis of the pancreas: is there a role for glucagon or a glucagon-like peptide?

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.

Amylases↗