Pharmacokinetics, metabolism and biliary and urinary excretion of oral ramipril in man.

In order to evaluate the pharmacokinetics and excretion of ramipril in man, 8 cholecystectomy patients aged between 53 and 68 years received 5 mg ramipril orally as a single dose. All patients had a T-drain inserted to permit bile collection; all gave their informed consent to participate in the trial. Serum samples were collected half-hourly until 2 hours, then hourly until 6 hours, then at 8, 10, 24 and 25 hours after intake. Urine was collected in 2-hour fractions until 8 hours, followed by a 4- and a 12-hour fraction. Bile was collected hourly until 6 hours, followed by a 6- and a 12-hour collecting fraction. Concentrations of ramipril and ramiprilat in serum, and determinations in urine and bile of ramipril, ramiprilat, ramipril glucuronide, ramiprilat glucuronide, diketopiperazine and diketopiperazine acid were made; total amounts excreted were calculated. Peak concentrations of ramiprilat in plasma (8.7 +/- 1.6 ng/ml) were reached after about 8 hours. AUC0-8 and AUC0-24-values were 36.5 and 111.9 ng.h/ml, respectively. Ramiprilat Cmax-concentrations were about 300-fold higher in bile than in plasma, the corresponding difference for ramipril between bile and plasma was about 4-fold. The main fractions excreted in the urine were diketopiperazine acid and ramiprilat amounting to 13.2 +/- 5.6 and 4.4 +/- 2.4%, respectively, of the dose administered. Only a very small fraction of the dose was excreted with urine as unchanged ramipril, on average 0.9 +/- 1.0%. The main fractions excreted in the bile were diketopiperazine acid, ramiprilat glucuronide and diketopiperazine, 9.0 +/- 5.3, 3.4 +/- 4.2 and 2.0 +/- 1.2% in 24 hours, respectively, of the dose administered. Only a negligible fraction of the dose (average 0.1 +/- 0.1%) was excreted with bile as unchanged ramipril. In conclusion, there is strong evidence that circulating ramipril and ramiprilat are eliminated by both the liver and the kidneys. For the patients studied it can be estimated from late collection periods that some 2/3 of circulating ramipril and ramiprilat are eliminated by the kidneys and 1/3 eliminated by the liver.

[Trachea reconstruction in inflammatory stenosis and tumors]. / Trachea-Rekonstruktionen bei entzündlichen Stenosen und Tumoren.

Primary resection of the trachea and direct anastomosis is indicated whenever inflammatory stenoses and tumors of the trachea are present. In our own series of 27 patients operated upon there were 17 stenoses by scars, two malacias of the trachea, six adenoid-cystic carcinomas, one adenoma of the bronchus and one chondroma. One patient died on the 16th postoperative day from stress-ulcer bleeding. Another patient died three months after the resection of the trachea following reoperation from a recurrence of the stenosis. There was bleeding out of the tracheostoma with aspiration. One patient had a stenosis of the cricoid three years after the tracheal resection had been performed. The stenosis could be treated successfully by reconstructive surgery. None of the other 24 patients had complications. Data on the late results are given. New reports in the literature and our own experience indicate that a tracheal resection with a direct anastomosis seems to be a standardized procedure. Using the right indication for the operation good early and late results can be achieved.

[Aneurysm of the abdominal aorta. Results of surgical therapy]. / Bauchaortenaneurysma. Ergebnisse der chirurgischen Therapie.

According to experiences in treating more than 400 patients with abdominal aortic aneurysms (AAA) following statements can be made: 1. Diagnosis of an AAA is identical with indication for surgical treatment. Only in cases of extremely high operative risk (aggravating organ deficiencies especially of heart and lungs) an expectant attitude is justified. 2. Preoperative angiography is considered to be desirable. 3. Rupture of the aneurysm depends on size and form, but small sized aneurysms can rupture as well. 4. It is of advantage to have the patients prepared preoperatively for several days for minimizing the operative risk. 5. Long follow-up results are good, the operation is able to prolong life expectancy of these patients.

Endovascular treatment of an aortic aneurysm ruptured into the inferior vena cava.

PURPOSE: To report the endovascular repair of a rare abdominal aortic aneurysm (AAA) rupture into the inferior vena cava. METHODS AND RESULTS: A 74-year-old man with a 6.0-cm saccular aortic aneurysm and a previously undiagnosed aortocaval fistula of more than 2 weeks' duration was treated successfully with a Vanguard bifurcated stent-graft. The aneurysm was excluded and no endoleak or communication between the aorta and inferior vena cava was seen on computed tomographic imaging at the 6-month evaluation. CONCLUSIONS: Aortic endografting in this life-threatening complication is an effective treatment option that avoids the significant blood loss encountered in conventional repair.

[Diagnosis and treatment of acute injuries to the heart and intrathoracic vessels (author's transl)]. / Erkennung und Behandlung akuter intrathorakaler Gefäss- und Herzverletzungen.

The massive blood loss that accompanies penetrating chest wounds involving the heart or intrathoracic vessels generally leaves no option but to act immediately. Blunt chest trauma in combination with other injuries makes particularly stringent demands on diagnostic and therapeutic skills. Most injuries to the intrathoracic aorta are in the form of intiially closed tears of the descending part; but rupture is an ever-present threat. The symptoms are: enlargement of the mediastinum in the chest roentgenogram, differences in blood pressure between the upper and lower half of the body and haemothorax. Whenever possible aortography should be performed to locate the site of the rupture. The therapeutic measures are determined by the extent and severity of the various injuries.

[Thoracic surgical interventions]. / Thoraxchirurgische Eingriffe.

Thoracic surgery necessitates more intensive care postoperatively than general surgery. For elective lung resections mortality was significantly higher in patients older than 70 years. Operative risk has to be considered very thoroughly versus natural history of the diseases involved. Vascular reconstructions in the chest, however, were performed mainly in symptomatic patients, when increased operative risk must be accepted because of an increased threat by symptomatic disease. For surgery of the trachea or esophagus techniques are preferred which avoid thoracotomy.

Time-related alterations in shape, position, and structure of self-expanding, modular aortic stent-grafts: a 4-year single-center follow-up.

PURPOSE: To report the nature and ramifications of structural and positional changes over time in tube and modular bifurcated aortic stent-grafts. METHODS: Two hundred ninety-one patients received endovascular aortic grafts (primarily Stentor/Vanguard) between August 1994 and August 1998. Follow-up surveillance (clinical and laboratory examination, biplanar noncontrast radiography, and contrast-enhanced computed tomography) has been maintained on all patients for 4 years. Changes in the configuration and position of endografts have been noted and their sequelae charted. RESULTS: Three types of endograft shape changes have been documented: mild -- slight distortions visible on plain radiographs (n = 90, 31.0%), significant -- angulations reaching 60 degrees to 90 degrees (n = 65, 22.3%), and severe -- angulations > or = 90 degrees (n = 10, 3.4%). Changes in position never gave rise to late migration at the proximal attachment site, whereas at the distal ends, the endograft easily retracted from the iliac arteries (n = 8). Structural alterations (rupture of the stent frame, sutures, or fabric, and total graft disintegration) were more common in the original Stentor model. Shape, position, and structural alterations were mutually dependent and led to secondary endoleaks (n = 26) and graft limb thrombosis (n = 37). Late surgical conversion was necessary in 3 (1.0%) patients. CONCLUSIONS: Tortuosity of the native vessels is a source of complication in long-term follow-up just as it is during implantation. Given the late appearance of complications in this patient cohort, it would seem that the durability of an endograft cannot be evaluated with < 3 years of follow-up.

[Laparoscopic cholecystectomy: a prospective study of 1,775 unselected patients]. / Laparoskopische Cholezystektomie: eine prospektive Studie an 1775 unselektierten Patienten.

1775 patients with symptomatic cholecystolithiasis were treated by laparoscopic cholecystectomy without selection or contraindications. Complications should be compared with those of conventional cholecystectomy. 73.5% of our patients were female, the median age was 62 years (min. 9, max. 91 years). They presented uncomplicated cholecystolithiasis in 85%, acute cholecystitis in 11% and cirrhotic gallbladder in 4.5%. The rate of conversion to laparotomy was 2.9% for uncomplicated cholecystolithiasis and 11% for each cholecystitis and cirrhotic gallbladders. In general 4.4% were converted. These conversions were due to complications in 0.9% (bile duct lesions 0.7%, bowel perforation 0.2%), due to adhesions or inflammatory alterations in 3%. Perioperative letality was 0.3%, but only 0.15% were related directly to the operation. Other complications were bile duct strictures 0.3%, postoperative hemorrhage 0.3%, ileus 0.2%, perforation of diaphragm/pneumothorax 0.1%. Suspected bile duct stones were proved and treated by preoperative ERCP in 5.6%. Routinely performed intraoperative cholangiography detected unsuspected stones in 4%. These were removed mostly by postoperative ERCP. We consider laparoscopic cholecystectomy a safe method for the treatment of every stage of symptomatic cholecystolithiasis. There are no contraindications, if the operation is performed by an experienced team. Intraoperative cholangiography should remain standard. Complications in unselected patients are comparable to those of conventional cholecystectomy. The rate of bile duct lesions is equal (0.7%), a further decrease is expected (learning curve). According to this data, it is no longer justified, to perform cholecystectomy primarily by laparotomy, if there is experience with the laparoscopic method. Laparotomy by itself is no complication, it should be applied only, if the surgeon considers the operation inadequate to be continued laparoscopically.

[Laparoscopic selective vagotomy (posterior truncal vagotomy and anterior linear stomach resection) in complicated duodenal ulcer]. / Laparoskopische selektive Vagotomie (hintere trunkuläre Vagotomie und vordere lineare Magenresektion) beim komplizierten Ulcus Duodeni.

32 patients with complicated duodenal ulcer (bleeding, recurrence, perforation) were treated by laparoscopic posterior truncal vagotomy and anterior linear gastric resection in our modification (access to the posterior vagus via the omental bursa) of the method of Gomez-Ferrer/Taylor. Instead of the seromyotomy along the lesser curve we resect a 1 cm broad strip out of the anterior gastric wall. In one patient with additional hiatus hernia the anterior vagal trunc was cut accidentally. Converted to laparotomy this case was completed as truncal vagotomy and pyloroplasty. No disorders of postoperative gastric emptying were found. 17 patients were followed up 6 weeks postoperatively. 14 showed complete healing of the ulcer, 2 patients showed healing in progress. A follow up after 12 months obtained information about 18 patients: 7 were free of symptoms, 11 complained about intermittent pains or fullness. 8 of these 11 patients were controlled by gastroscopy, not any ulcer or gastritis or disorder of gastric emptying could be found. We see advantages of our method over Kathkouda's modification of Taylor's procedure in the simplicity of the method, the primary hemostasis and a short operating time by using the stapler. We consider our procedure a minimal invasive, quick, safe treatment for duodenal ulcer disease with lasting effect at reasonable cost, especially in complicated cases like recurrent ulcer, bleeding or penetrating ulcer and in noncompliant patients that are not suitable for medical treatment.

[Difficulties and complications in transfemoral implantation of stent prostheses in infrarenal abdominal aortic aneurysms]. / Schwierigkeiten und Komplikationen der transfemoralen Implantation von Stent-Prothesen beim infrarenalen Bauchaortenaneurysma (BAA).

Between August 31st, 1994 and January 31st 1996, 69 patients received transfemoral application of stentgrafts for treatment of AAA. Only 10 patients received tube grafts in contrast to 59 bifurcated grafts, which were assembled within the aortic lumen. All aneurysms were symptomatic, growing or sacciform. Risk factors seemed to be aggravated in comparison to conventional operations. 59 operations were technically successful, three were converted to open laparotomy, because of technical malfunction twice and misplacement once. 5 postoperative deaths occurred from multiorgan failure. 7 patients were discharged with primary persisting leakage. All patients exhibited reactions to the stentgraft deployment, which mainly referred to the clotting system and/or arterial pressure. Postoperatively nearly all patients presented a "post-implantation syndrome" over days up to 4 weeks. The observed difficulties and complications can be attributed in part to a "learning curve", in part to difficult anatomic situations, which we included in our series. During follow up at 3, 6 and 12 months 7 secondary leakages were observed, three times because of a documented desintegration, once because of suspected beginning desintegration at a stent-graft junction, and three times because of possible failure of graft material. The leakages could be repaired by interventional procedures.

[Intermediate-term complications and problems after endovascular aortic stent prostheses]. / Mittelfristige Komplikationen und Probleme nach endovaskulären Aortenstentprothesen.

From August 1994 to December 1998 321 patients were treated with endovascular stentgrafts for aortic aneurysm exclusion in our hospital. Primary exclusion rate was 91% (primary leakage 8.7%) and hospital mortality was 3.7%. 6 different types of grafts were used, 5 of them commercially available. Midterm complications are due to configuration changes of the grafts, material deterioration, side branch reperfusion and changes in aortic morphology. The common pattern of clinical expression of these complications is secondary leakage (60 cases) and graft limb occlusion (37 occurrences in 30 patients). 50% of the secondary endoleaks have been treated up to now leaving the remaining patients under a thorough follow-up. Graft limb thrombosis was treated in all but three, well compensated, patients. Midterm results of the first commercially available endografts are not yet satisfying in contrast to conventional aortic repair. The recently available grafts are promising as they have a better kink resistance, no graft sutures and fewer modular components.

[Organ blood flow in graduated, controlled hypotension induced with sodium nitroprusside]. / Organdurchblutung bei graduierter, kontrollierter Hypotension mittels Natriumnitroprussid (NNP).

Metabolic acidosis is a characteristic feature of SNP-induced hypotension; this acidosis is of hepatic origin and is not due to underperfusion of the organ but to cyanide-induced anaerobic metabolism. For SNP doses higher than 3 mg/kg body weight, lactate is produced in the myocardium, brain, and skeletal muscles. The observed changes were reversible after hypotension of 20 min duration.