Plasma secretin in response to pure bile salts and endogenous bile in man

The effect of exogenous bile salts on plasma concentrations of secretin was studied by infusion of chenodeoxycholate, cholate, glycocholate, and taurocholate into the duodenum of normal subjects. The effect of endogenous bile on plasma secretin was studied by ingestion of a liquid test meal, by reinfusion of postprandial duodenal aspirates with known contents of bile salts, and by stimulation of gallbladder contraction by cholecystokinin. Each experiment was performed in groups of seven subjects. The relative secretin-releasing potencies of glycocholate, cholate, taurocholate and chenodeoxycholate (2.25 mmol) were 1.01.31.93.2. Hydrochloric acid (0.5 mmol) was, on a molar basis, approximately ten times more potent than sodium cholate. The effect of taurocholate was diminished when a liquid meal was used as vehicle instead of saline. Endogenous bile did, in no circumstance, elicit release of secretin. It is concluded that although bile salts have the ability to stimulate secretin release, endogenous secretin release is of minor, if any, importance for secretin release when physiological conditions are approached.This study was supported by grants from the Danish Hospital Foundation for Medical Research, Region of Copenhagen, The Faroe Islands and Greenland (J.nr. 78/45 and 79/48) and Borgen Legatet.     

Short-termin vivo stability of endothelial-lined polyester elastomer and polytetrafluoroethylene grafts

A fibronectin substrate will significantly enhance the strength of endothelial cell attachment on grafts constructed of polyester elastomer (PE) and polytetrafluoroethylene (e-PTFE). This experiment was undertaken to determine the short-termin vivo stability of endothellum on these fibronectin coated surfaces. Eight mongrel dogs underwent bilateral carotid artery replacement with both graft materlals. All grafts were inoculated with 2,000 cells/mm² using cultured autogenous venous endothelium labelled with Indium-111-oxine. The Indium-111 label in the grafts was measured immediately prior to implantation, after 1 hour ofin vivo perfusion, and at explantation after 24 hours. The percentage of inoculated cells attached to the grafts before perfusion was simillar for both materials, 93.3±3.0% versus 92.2±7.2%, for PE and e-PTFE respectively. All grafts were patent at one hour after implantation. PE grafts were found to have 93.8±3.9 % of the attached cells present at one hour while e-PTFE grafts had only 54.5 ± 10.8 % remaining, p<.001. After 24 hours, 5/8 (62.5%) e-PTFE grafts and 2/8 (25.0 %) PE grafts remained patent, p=.13. Of the patent grafts however, endothelial cell retention was still superior on the PE grafts with 78.0±0.6% of the attached cells remaining compared to only 24.5±6.1% on e-PTFE, p<.001. Occluded PE grafts had fewer cells remaining at 24 hours than patent ones, 78.0±0.6% versus 31.1±32.8%, respectively, p=.13. Histologically, patent PE grafts demonstrated nearly confluent endothelial monolayers while e-PTFE had patches of endothelial cells surrounded by, a platelet-fibrin carpet. We conclude that short-term patency appears to be determined by the extent of endothelial retention on PE but not e-PTFE.     

Anastomotic false aneurysms with aortic Dacron graft after twenty-five years

One of the early diamond crimped knitted polyester (Dacron) grafts was surgically excised after implantation for 25 years in the aorto-billiac position because of false aneurysm formation at the three anastomotic sites. The sutures were no longer visible. While the areas around the false aneurysm were poorly incorporated, the graft limbs were well encapsulated with some endothelial-like cells on the luminal surface. The integrity of the graft was well preserved despite mild fraying and the disruption of one stitch.     

Traumatic aneurysms of the descending thoracic aorta

From July 1979 to December 1985 we observed 51 patients with traumatic lesions of the descending thoracic aorta. Twenty-nine had acute ruptures, mostly accompanied by multiple injuries, and 27 had to be operated upon immediately. Twenty-two patients (19 males, 3 females) had chronic traumatic aneurysms of the descending thoracic aorta (more than six weeks after trauma). Mean age at the time of trauma was 24 years. Mean age at time of surgery was 36.5 years. Twelve patients were symptomatic. All were treated surgically. At surgery, complete aortic disruption was found in 15 patients and partial rupture in seven. We did not use aortic shunting of any kind, only aortic cross-clamping. Hypertension was controlled by intravenous drug infusion. The ruptured aortic segment was replaced in all cases by prosthetic Dacron graft. There were no operative deaths. One patient (age 77) died 11 weeks after surgery from multiple organ failure. One case of postoperative paraplegia was observed. This patient recovered almost completely from his neurological deficit.     

Detection of stenoses in the internal carotid artery by waveform analysis of continuous wave ultrasound signals (II)

Analysis of the morphological aspects of continuous-wave Doppler examination is a reliable means of detecting carotid stenosis involving 50% or more of the diameter of the arterial lumen. This study was undertaken to evaluate the indexes likely to increase the diagnostic accuracy of this noninvasive investigation method. The indexes studied were the variations of the maximal frequency and the systolic peak frequencies, measured proximal to and at the level of stenosis, and the ratio of the systolic peak frequency measured in the internal carotid artery and in the common carotid artery. After obtaining data on an experimental model, the study was conducted in healthy volunteers (n = 24) and in patients with carotid atherosclerotic disease (n = 23). The experimental study confirmed that stenosis greater than 50% leads to a reduction of blood flow and that there is a mathematical relationship between the frequency measured proximal to and at the level of the stenosis and the degree of stenosis. Clinical data showed that there was a significant decrease in the frequency of the systolic peak in elderly "healthy" subjects as compared with younger subjects. However there was no difference between patients with and without stenosis. The index was 0.8 in young subjects, 1.3 in healthy elderly subjects, and greater than 1.3 in subjects who had a stenosis. There was no statistically significant difference between these two last groups. At the threshold value of 2.3, the sensitivity of the FI index was 22% and the specificity was 94% in the detection of carotid artery stenosis. In the assessment of the tight stenosis, sensitivity was 44%.     

Preoperative transhepatic biliary decompression in pancreatic and periampullary cancer

Pancreatic resection for pancreatic and periampullary cancer between 1969 and 1975 at The Ohio State University Hospitals had an associated operative mortality rate of 30% and a morbidity rate of 80%. Transhepatic biliary decompression (THD) has been accepted as a method of preoperative risk reduction in the deeply jaundiced patient and an alternative to surgical biliary decompression. The use of preoperative THD in pancreatic and periampullary cancer was examined. Of 44 patients with bilirubin greater than 10 mg/100 ml, 17 had radical resection (THD=7, no THD=10), and 27 had palliative operation (THD=17, no THD=10). Preoperative serum bilirubin in the THD group was 7.3±1.0 compared to 16.3 ±1.5 in the no THD group (p < 0.05). Operative morbidity rate was: radical surgery: THD (40%), no THD (70%); palliative surgery: THD (18%), no THD (20%). Operative mortality rate was: radical surgery: THD (28%), no THD (60%); palliative surgery: THD (6%), no THD (0%). Catheter-related complications were minimal. Preoperative THD tends to reduce the risk of curative resection for pancreatic and periampullary cancer, but does not alter the outcome of palliative surgery. Long-term THD may be an alternative if palliative surgical biliary decompression either fails or is not technically possible in the patient with unresectable cancer.

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Resumen Se ha agudizado el debate relativo al papel de la resección curativa en el tratamiento del carcinoma pancreático y periampular. Mucha de la discusión se deriva de la excesiva morbilidad y mortalidad de la pancreatoduodenectomía y de la pancreatectomía total. Las cifras sobrepasan el porcentaje de supervivencia a 5 anos en todas las series mayores, y en algunos reportes la mortalidad operatoria es igual o mayor que el porcentaje de pacientes que sobreviven un año.La resección pancreática para cáncer pancreático y periampular entre los años 1969 y 1975 en los Hospitales de la Universidad del Estado de Ohio estuvo asociada con una mortalidad de 30% y una morbilidad de 80%. La descompresión biliar transhepática (DBT) ha sido aceptada como un método de reducción preoperatoria del riesgo quirúrgico en los pacientes intensamente ictéricos y como una alternativa a la descompresión biliar quirúrgica. El uso de la DBT preoperatoria en el cancer pancreático y periampular fué analizado. De 44 pacientes con bilirrubina mayor de 10 mg/100 ml, 17 fueron sometidos a resección radical (DBT = 7, no DBT = 10), y 27 tuvieron una operación paliativa (DBT = 17, no DBT = 10). La bilirrubina sérica en el grupo con DBT fué de 7.3±1.0, comparada con 16.3±1.5 en el grupo sin DBT (p < 0.05). La siguiente fué la morbilidad operatoria: cirugía radical: DBT 40%, no DBT 70%; cirugía paliativa: DBT 18%, no DBT 20%. La siguiente fué la mortalidad operatoria: cirugía radical: DPT 28%, no DPT 60%; cirugía paliativa: DBT 6%, no DBT 0. La DBT preoperatoria tiende a reducir el riesgo de la resección curativa para cáncer pancreático y periampular, pero no modiflca el resultado de la cirugía paliativa. La DBT prolongada puede ser una alternativa si la descompresión biliar quirúrgica falla o no es técnicamente posible en el paciente con cáncer no resecable.

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Résumé La résection pancréatique pour cancer périampullaire ou pour cancer du pancréas entre 1969 et 1975 à Ohio State University Hospital accuse une mortalité opératoire de 30% et une morbidité de 80%. Le drainage biliaire transhépatique (transhepatic biliary decompression: T.H.D.), en présence de ces résultats, a été employé à titre pré-opératoire pour diminuer les risques de l'intervention chez les malades très ictériques et comme alternative au drainage biliaire chirurgical.Chez 44 malades qui présentaient un taux de bilirubine supérieur à 10 mg/dl, 17 ont subi une exérèse (7 après drainage transhépatique, 10 sans drainage transhépatique), 27 ont été traités par une intervention palliative (17 après drainage, 10 sans drainage). Le taux de bilirubine pré-opératoire fut ramené à 7.3±10 chez les malades drainés alors qu'il atteignait 16.3± 1.5 chez les malades qui n'avaient pas subi de drainage préalable.La morbidité opératoire fut en cas de chirurgie radicale de 40% après drainage et de 70% en l'absence de drainage; en cas de chirurgie palliative elle fut de 18% après drainage et de 20% en l'absence de drainage. La mortalité opératoire fut en cas de chirurgie radicale de 28% après drainage et de 60% en l'absence de drainage; en cas de chirurgie palliative elle fut de 6% après drainage et de 0% en l'absence de drainage. Les complications du drainage sont très rares. En un mot le drainage biliaire pré-opératoire réduit les risques de l'exérèse des cancers pancréatiques et des cancers périampullaire mais elle est sans influence en cas d'intervention palliative. Le drainage biliaire transhépatique prolongé offre une alternative au drainage chirurgical lorsque celui-ci échoue ou quand le cancer ne peut être réséqué.

     

Penetration of teniposide (VM-26) into human intracerebral tumors

Thirty-four consenting patients received VM-26 50–100 mg/m² I.V. before surgical resection of intracerebral tumor, and drug was measured using a high pressure liquid chromatographic technique. Sufficient tumor for analysis was obtained from 29 patients. Brain metastases (13 patients) had higher concentrations of V M-26 than did gliomas (13 patients). Concentrations were comparable in brain metastases and meningiomas (3 patients). Prolonged (24 h) infusion of V M-26 did not appear to result in higher tumor drug concentrations in 5 patients than did rapid (1 h) infusion in 24 patients. Pretreatment with Amphotericin-B 10 mg/m² 12 h and 1 h before VM-26 did not appear to have any effect on VM-26 uptake into 4 intracerebral tumors, although data were limited, and VM-26 concentrations were very high in 1 metastasis. Pretreatment with oral glycerol 500 mg/kg 18 h, 12 h, 6 h, and immediately before I.V. VM-26 may have resulted in increased penetration of VM-26 into 9 tumors, although confirmation is required. Amphotericin-B, glycerol, and operative conditions did not appear to alter VM-26 plasma pharmacokinetics.VM-26 4-demethylepipodophyllotoxin 9-(4-6-O-thenylidene-B-D-glucopyranoside) - VP-16 4-demethylepipodophyllotoxin 9-(4-6-O-ethylidene-B-D-glucopyranoside) Presented in Part at the 74th Annual Meeting of the American Association for Cancer Research, San Diego, California, May 25–28, 183(1).     

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.