The Belfast approach to managing complex lower limb vascular injuries.

INTRODUCTION: Complex lower limb vascular injuries (CLVIs) in high-energy penetrating or blunt trauma are associated with an unacceptably high incidence of complications including amputation. Traumatic ischaemia and ischaemia-reperfusion injury (IRI) of skeletal muscle often lead to limb loss, the systemic inflammatory response syndrome (SIRS) which affects remote organs and even the potentially fatal multiple organ dysfunction syndrome (MODS). Surgical care of CLVIs everywhere, including Northern Ireland until 1978, was governed by an anxiety to restore arterial flow quickly often using expedient and flawed repair techniques while a damaged major vein was frequently ligated. MATERIALS AND METHODS: A new policy centred on early intraluminal shunting of both artery and vein, restoring arterial inflow and venous outflow, respectively, was introduced at the Regional Vascular Surgery Unit of The Royal Victoria Hospital, Belfast in 1979. It imposed a disciplined one-stage comprehensive approach to treatment involving a sequence of operative manoeuvres in which all damaged anatomical elements receive meticulous and optimal attention unshackled by time constraints. RESULTS: Comparisons drawn between the pre-shunt period of unplanned treatment (1969-1978) and the post-shunt period centred on the use of shunts (1979-2000) showed that early shunting of both artery and vein in both penetrating (P) and blunt (B) injuries significantly reduced the necessity for fasciotomy (P: p=0.016, B: p=0.02) and caused a significant fall in the incidence of contracture (P: p=0.018, B: p=0.02) and of amputation (P: p=0.009, P: p=0.012). CONCLUSIONS: The policy of early shunting of artery and vein in CLVIs has proved to be of great benefit in terms of significantly improved outcomes, better operative discipline and harmonious collaboration among the specialists involved.

Bilateral inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome: a comparison with other diagnostic tests.

To compare bilateral inferior petrosal sinus sampling (IPSS) with high dose dexamethasone (HDD) and CRH testing (using recently proposed stringent response criteria) in the differential diagnosis of ACTH-dependent Cushing's syndrome, we reviewed 53 consecutive cases. The main analysis was limited to 45 cases with confirmed diagnosis: 44 with pituitary dependency, proven by confirmatory histology and/or significant biochemical improvement after pituitary surgery, and 1 with ectopic ACTH syndrome. After HDD (2 mg every 6 h for 48 h), 21 of the 44 pituitary cases met the stringent more than 90% suppression criterion. Twenty-three of the 44 pituitary cases also underwent CRH testing; 16 of 23 met a stringent response criterion of a more than 50% serum cortisol rise. For HDD and CRH testing combined, 8 of 23 fulfilled both stringent criteria, 10 of 23 had discordant results, and 5 of 23 failed to fulfil either of the stringent criteria for pituitary dependency. IPSS was performed in all 44 of the proven pituitary cases; 36 had petrosal/peripheral ACTH ratios of 2.0 or more without CRH stimulation. Thus, in patients with proven pituitary disease, stringent response criteria to HDD and CRH testing were fulfilled by only 48% and 70%, respectively. IPSS, which gave direct evidence of pituitary ACTH secretion in 82% of the cases, is therefore considered necessary in a significant proportion of cases.

Accuracy of CT scanning and adrenal vein sampling in the pre-operative localization of aldosterone-secreting adrenal adenomas.

In primary hyperaldosteronism, it is important to distinguish between unilateral and bilateral disease, as management strategies differ. In the period 1983-95, we identified 34 patients with primary hyperaldosteronism. Following further investigations, a diagnosis of aldosterone-secreting adenoma was made in 17 patients, and surgery was performed. Computed tomography clearly localized an apparent adenoma (discrete adenoma=1 cm diameter; normal contralateral gland) in only 10 of these patients (59%); two of these 'adenomas' were subsequently shown to be hyperplastic glands without adenomas. Histological examination showed adrenal adenomas in the remaining 15 patients. An 'adenoma' also appeared to be clearly localized in 3/17 patients later classified as having bilateral adrenal hyperplasia by adrenal vein sampling. CT scanning, therefore clearly localizes adenomas in only 50% of histologically proven cases, and can also produce misleading results. Adrenal vein sampling results altered our management approach in one third of cases. On the basis of our detailed results we would recommend surgery if there is clear evidence of unilateral aldosterone secretion along with CT findings which may not be strictly localizing but are in keeping with the dominant side on adrenal vein sampling. The decision to refer for surgery in primary hyperaldosteronism can be difficult, and we would caution against too heavy a reliance on CT results when recommending adrenalectomy, and suggest that adrenal vein sampling should remain a routine part of the investigation of patients with primary hyperaldosteronism.

Is whole-lung CT scanning still necessary in all cases of ACTH-dependent Cushing's syndrome in the era of petrosal sinus sampling?

We reviewed 31 patients in whom both bilateral inferior petrosal sinus sampling without CRH stimulation, and a CT scan of the lungs were done. Twenty-five had normal lung CT scans, of whom 23 had a higher inferior petrosal sinus: peripheral ACTH ratio > or = 1.5. After careful follow-up, none was subsequently shown to have ectopic ACTH syndrome. Six had abnormal lung CT scans, of whom two had ratios > or = 1.5. In these two patients, other investigations suggested pituitary disease, and pituitary surgery led to apparent cure. Of the remaining four patients, who had ratios < 1.5, two had incidental lung findings, and pituitary abnormalities were demonstrated at pituitary surgery. The third underwent bilateral adrenalectomy, and no evidence of ectopic ACTH syndrome has emerged as yet after 4 years follow-up. The fourth had a small-cell carcinoma of the lung, confirmed histologically. Our series suggests that whole-lung CT scanning is only necessary in cases of ACTH-dependent Cushing's syndrome where bilateral inferior petrosal sinus sampling has not demonstrated a significant increase in petrosal sinus ACTH levels as compared with the peripheral level. Thus, in our experience the test is now only necessary in those patients (approximately 25%) where the ratio is < or = 1.5.

Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging.

A wide variety of neuroendocrine tumours express somatostatin receptors, and can be visualized by radiolabelled somatostatin analogue scintigraphy. To investigate the value of [111In]-octreotide scintigraphy (Octreoscan), 48 patients (37 with proven carcinoid, pancreatic endocrine and medullary carcinoma of thyroid tumours, 11 with neuroendocrine syndromes multiple endocrine neoplasia (MEN-I) and Zollinger-Ellison syndrome (ZES) were examined with 111In-DTPA-D-Phe1-octreotide. Scintigrams were obtained at 24 and 48 h, and the results were compared with CT and magnetic resonance imaging (MRI). Thirty-five of 48 patients had positive [111In]-octreotide scintigraphy (23/25 (92%) carcinoids, 8/9 (89%) PETs, 4/11 (36%) MEN-I & ZES). Of the 42 lesions located by conventional imaging techniques, 37 (88%) were also identified by Octreoscan. Unexpected lesions (40 sites), not detected by CT or MR imaging were found in 24/48 (50%) patients. [111In]-octreotide scintigraphy has a higher sensitivity for tumour detection, and is superior to MR imaging and CT scanning in the identification of previously unsuspected extraliver and lymph node metastases. It may also be helpful for the localization of clinically suspected tumours in patients with MEN-I and ZES.

A comparison of intra-arterial digital subtraction angiography with Doppler sonography in the assessment of carotid arterial stenosis.

A comparison is made of the use of selective intra-arterial subtraction angiography and doppler sonography in the assessment of disease in 206 carotid arteries. Maximal stenoses in each of the internal, external and common carotid arteries were recorded and compared using both modalities. In 93% of cases, arteries reported as normal ultrasonically were also found to be normal on angiography. However, agreement between the modalities in the assessment of severe stenoses was rather less at 79%. Overall agreement between the two modalities was good using statistical analysis (weighted Kappa). It is our view that ultrasound is reliable in normal vessels, but where significant disease is present the rate of error between the two modalities is too high to warrant omission of angiography.

Diagnosis of common bile duct stones by intravenous cholangiography: prediction by ultrasound and liver function tests compared with endoscopic retrograde cholangiography.

BACKGROUND: Routine intravenous cholangiography using the safer contrast medium, meglumine iotroxate, may be a useful investigation prior to laparoscopic cholecystectomy for the detection of suspected common bile duct stones. We compared this with endoscopic cholangiography. METHODS: Eighty-one consecutive nonjaundiced patients (mean age 62 years; range 20 to 90) with suspected common bile duct stones referred for endoscopic cholangiography to one center underwent intravenous cholangiography that was considered positive if it detected ductal stones. The ability of ultrasound scans and liver function tests to predict ductal stones was also assessed. RESULTS: Sixty patients had both endoscopic and intravenous cholangiograms performed. Thirteen out of 27 patients with ductal stones confirmed by endoscopic cholangiography had positive intravenous cholangiograms, and 29 out of 30 with no stones had negative intravenous cholangiograms. The sensitivity for intravenous cholangiography was 48%, specificity 97%, positive predictive value 93%, negative predictive value 67%, and accuracy 73%. For ultrasound scans the positive predictive value was 69%; negative predictive value was 78%. For liver function tests the positive predictive value was 68%; negative predictive value was 93%. CONCLUSIONS: Intravenous cholangiography cannot be recommended instead of endoscopic cholangiography except in situations where the latter is not readily available. Ultrasound and liver function tests are useful in predicting ductal stones.

A review of the management of iatrogenic bile duct injuries.

Injuries to the extrahepatic biliary tree occurring during cholecystectomy or other upper gastrointestinal surgical procedures are not uncommon. The consequences are often catastrophic. We report the results of a personal series of bile duct repairs from a tertiary referral centre over a twenty-one year period. A total of 33 patients were referred. Percutaneous transhepatic cholangiography was the radiological investigation of choice to outline the biliary system. Percutaneous transhepatic dilatation was performed in six patients and 22 patients had either primary surgical repair, or reconstruction of their biliary tree performed by hepaticojejunostomy with an 80 cm Roux-en-Y limb. Of these only two have required revision surgery. We recommend early referral of patients with recognised iatrogenic injuries to specialist hepatobiliary units with no attempt at repair prior to referral.

A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin.

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study.

OBJECTIVE: We aimed to study the effect of biosynthetic growth hormone (GH) replacement in growth hormone deficient adults. DESIGN: We performed a double-blind placebo-controlled cross-over study of 6 months biosynthetic GH, replacement and 6 months placebo separated by a 1-month's washout period. PATIENTS: Fourteen growth hormone deficient adults were studied. MEASUREMENTS: We measured total body weight, percentage fat mass, lean body mass, muscle volume, exercise capacity, maximum oxygen consumption, muscle strength, bone mineral content, a number of biochemical parameters, IGF-I, GH antibodies and psychological well-being. RESULTS: Total body weight remained unchanged, but lean body mass increased (before GH mean +/- SEM 49.8 +/- 5.5, after 53.4 +/- 5.6 kg; placebo before 51.2 +/- 5.4, after 50.4 +/- 5.1 kg; P less than 0.05 and fat mass decreased (before GH 21.5 +/- 4.1, after 19.3 +/- 4.3; placebo before 19.3 +/- 4.0, after 22.5 +/- 4.5 kg; P less than 0.05). Thigh muscle volume increased: (before GH 94.1 +/- 7.7, after 99.5 +/- 8.4 ml; placebo before 99.3 +/- 8.6, after 95.4 +/- 7.8 ml/0.8 mm computerized tomographic slice; P less than 0.05). Exercise capacity increased (before GH 174 +/- 15, after 199 +/- 18.9 watts; placebo before 162.5 +/- 2.3, after 154 +/- 19.8 watts; P less than 0.05), as did maximum oxygen consumption (before GH 1.93 +/- 0.2, after 2.17 +/- 0.2 l/m; placebo before 1.92 +/- 0.3, after 1.98 +/- 0.2 l/m; P less than 0.05). There was no change in quadriceps muscle strength. Alkaline phosphatase increased (before GH 87.5 (32-158), after 106.0 (49-179) U/I, placebo 99.5 (50-145), after 72.0 (40-111) U/I; P less than 0.05) without a change in the spinal bone density. IGF-I increased (before GH 62 (36-97), after 216 (62-362) micrograms/l; placebo before 59 (52-112), after 60.5 (38-94) micrograms/l; P less than 0.05). Carbohydrate tolerance remained unchanged as did fasting lipids, serum sodium, potassium, urea, calcium, phosphate and liver transaminases. Psychological well-being remained unchanged. No growth hormone antibodies were detected before or after GH treatment. CONCLUSIONS: GH alters the body composition of growth hormone deficient adults and leads to improved exercise capacity; alkaline phosphatase activity increases but without a change in spinal bone density, and carbohydrate tolerance remains unaltered.

Changing patterns in presentation and management of the Zollinger-Ellison syndrome in Northern Ireland, 1970-1988.

The clinical features, diagnostic methods, management and survival in 16 cases of Zollinger-Ellison syndrome encountered in Northern Ireland between the years 1970 and 1988 are described. While the majority of patients in the first decade of the study period had surgical treatment, those presenting in the latter period have been managed with medical therapy in the form of H2-receptor antagonists or omeprazole. The increasing use of these agents seems to be altering the severe clinical features of this condition, reducing the indications for surgery and maintaining patients, with or without evidence of metastatic disease, in clinical remission.

A long-term dose-response study of somatostatin analogue (SMS 201-995, octreotide) in resistant acromegaly.

Ten acromegalic subjects were studied in a trial designed to ascertain the optimum dosage of the somatostatin analogue SMS 201-995 (octreotide) in active acromegaly. Twenty-four-hour growth hormone (GH) profiles were assessed monthly for 6 months and again after 1 year of continuous therapy. After basal assessment octreotide was administered subcutaneously at a dose of 100 micrograms three times a day throughout the first month. The dose was increased by 300 micrograms/day at monthly intervals to a maximum of 1500 micrograms/day, unless serum GH fell to within set criteria. Eight patients completed the trial. One patient withdrew because of intractable diarrhoea while another died of causes related to his acromegaly and we have no evidence that octreotide played any part in his death. Mean 24-h GH fell from a basal level of 34.3 +/- SEM 7.6 mU/l to 8.0 +/- 1.3 mU/l (P less than 0.05) after 6 months. At 1 month (300 micrograms/day) mean GH was 13.6 +/- 2.2 mU/l and at 2 months (600 micrograms/day) 10.8 +/- 2.2 mU/l (P less than 0.05 vs 300 micrograms/day dose), and at 5 months (1500 micrograms/day) 11.3 +/- 2.0 mU/l (all P less than 0.05 vs basal). Analysis of group means revealed no significant difference between any dose schedules above 600 micrograms/day. After 1 year the mean GH of the group (n = 8) was 7.5 +/- 1.3 mU/l (P less than 0.05 vs basal). Three patients developed a deterioration and one an improvement in their glucose tolerance and three developed asymptomatic gallstones during the year of therapy. In conclusion, octreotide lowered GH levels in acromegaly over a 1-year period. We found no evidence that routinely increasing the dose beyond 600 micrograms/day was helpful.

Development of a radioimmunoassay for neurone specific enolase (NSE) and its application in the study of patients receiving intra hepatic arterial streptozotocin and floxuridine.

A radioimmunoassay has been developed for neurone specific enolase (NSE) and used to measure serum NSE levels in patients with neuroendocrine and non-neuroendocrine tumours following intra hepatic arterial chemotherapy. Ten patients were studied, 7 receiving streptozotocin and floxuridine for neuroendocrine tumours and three receiving cisplatinum for non-neuroendocrine neoplasms. All ten patients had liver metastases. In patients with tumours of neuroendocrine origin, a significant increase in serum NSE was recorded within 24 h of therapy. Slight increases in serum NSE levels were also recorded in three patients with non neuroendocrine tumours. These increases may reflect lysis of neuroendocrine cells within the tumour. Raised levels in non-neuroendocrine tumour patients may reveal damage done to healthy neuronal and neuroendocrine cells during treatment. NSE may be a useful marker of the extent of cell death following chemotherapy.

The role of emergency venography in the diagnosis and management of deep venous thrombosis.

A retrospective study of patients who had undergone venography for suspected deep venous thrombosis during a six month period was undertaken to assess the influence of the examination on the subsequent management. Of these patients 38.6% had evidence of thrombus confirmed by the examination. This figure is comparable with other published results and did not bear out the impression that too many negative venograms were being obtained. Objective diagnosis of deep venous thrombosis is essential to ensure safe and cost-effective management. Other techniques have been advocated for the diagnosis of this condition but all have significant disadvantages compared with venography.