Recombinant factor VIIa in the treatment of intractable bleeding in vascular surgery.

Intractable bleeding unresponsive to conventional haemostatic measures is an uncommon but potentially life threatening surgical complication. Several studies have suggested that recombinant factor VIIa (rVIIa), a genetically engineered substitute for endogenous factor VIIa may have therapeutic application in patients with uncontrollable haemorrhage not previously diagnosed with coagulopathy. We report our experience of rVIIa use in eight such vascular surgery patients who developed life-threatening non-surgical haemorrhage either intra-operative or post-operatively. In all but one patient a marked clinical improvement was noted following treatment with rVIIa with significantly less transfusion, and obvious haemostasis associated with haemodynamic stability without adverse thrombotic complications.

A YAC-based physical map of the mouse genome.

A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.

Analgesia following appendicectomy--the value of peritoneal bupivacaine.

PURPOSE: Peritoneal inflammation is an important feature in many patients presenting with appendicitis. The contribution of peritoneal nerve fibres to pain experienced after appendicectomy has received little attention. METHOD: In this prospective double blind randomized study a consecutive series of 60 patients undergoing appendicectomy for suspected appendicitis were enrolled. A dose of 1.5 mg.kg-1 bupivacaine 0.5% was used. Group one patients received the entire dose of bupivacaine subcutaneously. Group two patients received half the dose subcutaneously (s.c.) and half the dose to the peritoneum. Pain scores were assessed pre-operatively and at 30 min, 12 and 24 hr post-operatively using a visual analogue scale. Time to first analgesia and total analgesia requirements in the first 24 hr were recorded. RESULTS: The patients receiving the s.c. combined with peritoneal bupivacaine had a lower pain score 30 min post-operatively (32 +/- 2 vs 54 +/- 4; P < 0.0001), a longer time to first analgesia (248 +/- 20 vs 164 +/- 17 min; P = 0.002) as well as lower opioid (68 +/- 5 vs 100 +/- 7 mg; P = 0.0002) and non steroidal analgesic requirements (65 +/- 6 vs 96 +/- 6 mg; P = 0.007) in the first 24 hr post-operatively. CONCLUSION: A combination of s.c. and peritoneal infiltration with bupivacaine is superior to skin infiltration alone in the relief of pain post appendicectomy.

An STS-based map of the human genome.

A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

Descending thoracic aorto-bifemoral bypass graft: a safe alternative in the high risk patients.

A fifty-nine year old male presented with disabling intermittent claudication. A Translumbar Aortogram was performed showing ".....total occlusion of the abdominal aorta just distal to the level of the renal arteries". As a direct result of this invasive radiological procedure, he subsequently developed acute pancreatitis and a pancreatic abscess necessitating open surgical drainage. Re-vascularisation of his aortic occlusion was deferred for fifteen months when a Descending Thoracic Aorta Bifemoral (DTAB) bypass was performed--thus avoiding the insertion of foreign, sterile, arterial prosthesis in a previously infect abdominal cavity.

Continuous versus intermittent infusion of fat emulsions during total parenteral nutrition: clinical trial.

It is now generally accepted that fat emulsions are an efficient energy source during total parenteral nutrition (TPN). However, there is debate about how this fat should be prescribed. Some authorities prescribe fat as an intermittent infusion, alternating fat and carbohydrate, whereas others prefer a continuous infusion, giving fat simultaneously with carbohydrate. This 6-day crossover study examined the substrate-hormonal profiles of 10 patients in response to two isocaloric and isonitrogenous TPN regimens. In regimen A (intermittent), equicaloric volumes of 25% glucose and 10% Intralipid as energy sources were alternated every 12 h. During regimen B (continuous), the total nonprotein calories given each day was the same as in regimen A, but glucose and fat were infused simultaneously over every 24-h period. Amino acids were infused continuously throughout the study period in all patients. Blood samples were taken every 12 h. Wide fluctuations in insulin and all substrates occurred during regimen A. Persistent hyperinsulinemia throughout regimen A may have impaired the oxidation of exogenous fat. The substrate-hormonal profiles observed during regimen B approximated the normal postabsorptive state and were stable throughout the infusion period. The results of this study suggest that exogenous fat should be administered as a continuous infusion.

The effect of distal arterial anatomy on the success of popliteal aneurysm repair.

The success of bypass grafting for popliteal aneurysms may be compromised by the natural history of these lesions. During a 9-year period 35 patients had repair of 48 popliteal aneurysms. Elective repair was performed in 26 limbs and the remaining 22 limbs required urgent or emergent treatment after aneurysm thrombosis (16) or embolic digital ischemia (six). Retrospective review of preoperative and intraoperative arteriograms and CT or ultrasound scans was done to define the relationship of distal runoff anatomy to initial symptoms and long-term grafting success during a mean follow-up of 48 months. Only five of 48 limbs (10%) had three continuous tibial vessels and a patent pedal arch. Twenty-six limbs (55%) had one or no named calf vessels and 11 limbs had incomplete pedal arches. When thrombosis or symptomatic embolism occurred, the anatomy was significantly worse; 15 of 22 such limbs (68%) had one or no patent tibial vessels and seven had incomplete pedal arches. Nineteen of 28 aneurysms examined by CT or ultrasound scanning showed intraluminal thrombus. Eight of 13 patent aneurysms with intraluminal thrombus had one or no patent tibial vessels. The 5-year graft patency rate was 74% for the entire study group. Bypass for repair of asymptomatic aneurysms had a patency rate of 91% at 5 years vs 54% for symptomatic patients (p less than 0.05). Patients with popliteal aneurysms often have advanced tibial disease that appears worse in those with symptoms. The occurrence of a patent popliteal aneurysm with intraluminal thrombus and advanced runoff disease suggests that chronic microembolism may be an etiologic factor in the tibial disease observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Does a water soluble contrast enema assist in the management of acute large bowel obstruction: a prospective study of 117 cases.

We have performed a prospective study on 117 patients in order to assess the value of a single contrast water soluble enema in acute large bowel obstruction. In 99 cases where the plain films suggested a diagnosis of mechanical obstruction, the Diodone enema confirmed its presence in 52, and relocated its site in 11. There was free flow of contrast to the caecum in the remaining 35, 11 of whom were shown to have idiopathic pseudo-obstruction. The plain films suggested a diagnosis of pseudo-obstruction in 18 patients. The Diodone enema confirmed this diagnosis in 15, but revealed an unsuspected mechanical obstruction in two. The examination failed in two cases. We conclude that the water soluble single contrast enema is of value in the management of large bowel obstruction. It will confirm the diagnosis of mechanical obstruction and prevent unnecessary surgery in patients with pseudo-obstruction.

The penetration of latamoxef disodium (moxalactam) into the subcutaneous fat and skeletal muscle of ischaemic lower limbs with atherosclerotic disease.

After pre-operative administration of 1 g, latamoxef disodium (moxalactam) levels were measured in peripheral venous blood, skeletal muscle and subcutaneous fat sampled from 29 patients during either arterial reconstruction or amputation undertaken for arterial occlusive disease. Tissue samples were taken from both proximal and distal levels in the amputated limbs. Levels of latamoxef disodium were above the minimum inhibitory concentration required for most commonly encountered Gram-positive and Gram-negative organisms. No patients developed toxicity or superficial wound infection but there was one vascular graft infection by Candida albicans. It has been shown that latamoxef disodium penetrates rapidly into the subcutaneous fat and skeletal muscle of relatively ischaemic limbs, achieving levels inhibitory to many common pathogens.

Cholecystokinin constricts the canine cystic duct.

The effects of cholecystokinin and cholecystokinin-octapeptide on the canine cystic duct have been studied. The resistance to flow through the duct in vivo, assessed by measuring the flow rate of saline that was perfused through the duct at constant pressure, was increased by cholecystokinin in a dose-dependent manner. Cholecystokinin also produced the well-recognized, dose-dependent elevations of gallbladder intraluminal pressure. Comparison of dose-response curves prepared in each animal indicated that the sensitivity of the cystic duct was significantly lower than that of the gallbladder. Isolated strips of cystic duct and gallbladder in vitro were contracted by cholecystokinin or cholecystokinin-octapeptide; again, cystic duct muscle displayed a lower sensitivity than gallbladder to the contractile effects of these agents. It is not known whether cholecystokinin can affect cystic duct resistance under physiologic conditions.

Stimulatory and inhibitory histamine receptors in canine cystic duct.

1 The effects of histamine receptor stimulation were assessed on the resistance of the canine cystic duct in vivo and on the contractility of circular muscle preparations of canine cystic duct in vitro. 2 In anaesthetized dogs, the H1-receptor agonist, 2-pyridylethylamine (0.05 to 15 mumol, i.a.), elicited dose-dependent increases in cystic duct resistance, whereas the H2-receptor agonist, 4-methylhistamine (0.05 to 15 mumol, i.a.) decreased cystic duct resistance. These responses were antagonized by the H1-receptor antagonist, diphenhydramine, and the H2-receptor antagonist, cimetidine, respectively. 3 Histamine (0.1 to 3000 nmol, i.a.) also increased cystic duct resistance in vivo. In the presence of diphenhydramine, the stimulatory effect of histamine was antagonized and slight decreases in cystic duct resistance became apparent. Cimetidine or prazosin also antagonized the stimulatory effects of histamine. 4 Histamine (1 to 100 microM) or 2-pyridylethylamine (1 to 100 microM) contracted, whereas 4-methylhistamine (1 to 100 microM) relaxed, circular muscle preparations of cystic duct. These excitatory and inhibitory responses were antagonized by diphenhydramine and cimetidine, respectively. 5 These results indicate that the canine cystic duct possesses excitatory H1- and inhibitory H2-receptors. The predominant effect of histamine is an H1-receptor-mediated increase in cystic duct resistance. Histamine, which may be released in association with cholecystitis, may exert significant effects on the regulation of bile flow in and out of the gallbladder and may contribute to gallbladder stasis during biliary disease.