Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold.

This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 µg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration-thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two- and three-compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady-state (L/kg), clearance (mL·min/kg), and terminal half-life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half-life was 23.7 ± 9.1 min, and terminal half-life was 8.9 ± 4.9 h. An effect-compartment model with a simple effect maximum model best predicted the time-course of the effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were 0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002-0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal).

Impact of the blood sampling site on time-concentration drug profiles following intravenous or buccal drug administration.

The aim of this study was to examine the effect of the sampling site on the drug concentration-time profile, following intravenous or buccal (often called 'oral transmucosal') drug administration. Buprenorphine (20 µg/kg) was administered IV or buccally to six cats. Blood samples were collected from the carotid artery and the jugular and medial saphenous veins for 24 h following buprenorphine administration. Buprenorphine concentration-time data were examined using noncompartmental analysis. Pharmacokinetic parameters were compared using the Wilcoxon signed rank test, applying the Bonferroni correction. Significance was set at P < 0.05. Following IV administration, no difference among the sampling sites was found. Following buccal administration, maximum concentration [jugular: 6.3 (2.9-9.8), carotid: 3.4 (1.9-4.9), medial saphenous: 2.5 (1.7-4.1) ng/mL], area under the curve [jugular: 395 (335-747), carotid: 278 (214-693), medial saphenous: 255 (188-608) ng·min/mL], and bioavailability [jugular: 47 (34-67), carotid: 32 (20-52), medial saphenous: 23 (16-55)%] were higher in the jugular vein than in the carotid artery and medial saphenous vein. Jugular venous blood sampling is not an acceptable substitute for arterial blood sampling following buccal drug administration.

The National Stroke Strategy - is it achievable?

INTRODUCTION: Timing of intervention in symptomatic carotid disease is critical. The UK Department of Health's National Stroke Strategy published in December 2007 recommends urgent carotid intervention within 48 h, in appropriate patients, who have suffered a transient ischaemic attack (TIA), amaurosis fugax or minor stroke. Despite the running of a rapid-access clinic for patients with symptoms of TIA, the time from symptom to surgery is rarely less than 2 weeks. To date, there has been little published research on the UK public response to the symptoms of TIA, and no study at all of the response of primary care to such patients. The aim of this study was to ascertain both these responses to see whether a 48-h target is achievable. PATIENTS AND METHODS: A total of 402 men attending our aortic aneurysm screening sessions were asked to complete a questionnaire requesting their most likely response to an episode of amaurosis fugax or TIA. All 45 GP practices in the hospital catchment area were asked how they would respond to patients requesting to be seen with the symptoms used in the questionnaire. RESULTS: Nearly one in six patients would ignore the symptom unless it recurred, approximately half would request a GP appointment and a third would see an optician if they had amaurosis fugax. The mean waiting time to see a GP was 2 days for a routine appointment and within 24 h for an emergency appointment. CONCLUSIONS: It is clear that a significant number of people would ignore the first symptom of carotid ischaemia; for those with amaurosis fugax, nearly a third would initially seek help from their optician. Those given a routine GP appointment would have to wait a minimum of 2 days. If the Department of Health is serious about reducing the incidence of stroke and introducing a target of 48 h from symptom to treatment, then there needs to be a wide-spread public and healthcare education programme, in particular alerting opticians and GP receptionists that these symptoms constitute a medical emergency.

Influence of presentation on outcome in abdominal aortic aneurysm repair.

OBJECTIVES: In the absence of formal screening abdominal aortic aneurysms (AAA) are detected in an opportunistic manner. Many remain asymptomatic and undetected until they rupture. Incidentally discovered small AAAs are entered into a surveillance programme until they reach a suitable size for repair. The aim of this study was to examine trends in the management of AAA and whether the method of presentation had an effect on subsequent mortality. DESIGN: Observational study in UK district general hospital. MATERIALS/METHODS: This study reports a single surgeon case series identified using a prospectively maintained database. Data on mode of presentation, management and mortality were retrieved from case notes, PIMS hospital database and the Office of National Statistics. RESULTS: Two hundred and five patients were referred with AAAs between 1992 and 2004, 78% presenting in elective circumstances. The surveillance programme fed 33% of the operated cases. Two aneurysms ruptured whilst under surveillance. Overall elective operative mortality was 11.8% and has progressively decreased over time. Thirty-day operated mortality was significantly lower in patients having a period of surveillance than those having immediate elective repair (2.3 vs. 16.3%, p=0.018). A slight reduction in emergency AAA repairs was noted over the study period (r2=0.6) although registered aneurysm deaths continue to increase (r2=0.83). CONCLUSIONS: Elective mortality following AAA surgery decreased over the study period. Outcome was better in those patients who had surgery for aneurysms that had been under surveillance. Despite opportunistic screening the population adjusted mortality rate of aortic aneurysms showed a progressive increase. A reduction in deaths from aneurysms is unlikely without a formal screening programme.

Horner's syndrome following excision of a vagal paraganglionoma.

We report a case of excision of a vagal paraganglionoma resulting in Horner's syndrome. The case was initially misdiagnosed as a carotid body tumour and demonstrates the need for adequate preoperative imaging and patient counselling for likely complications of surgery.

Severe panniculitis caused by homozygous ZZ alpha1-antitrypsin deficiency treated successfully with human purified enzyme (Prolastin).

Severe panniculitis caused by alpha1-antitrypsin deficiency is very rare even though the ZZ phenotype occurs in 1 : 3500 of the population of northern Europe. We describe a 33-year-old woman with rapidly progressing panniculitis and extensive skin necrosis with multiple life-threatening complications. Initial treatment followed by maintenance therapy with human purified enzyme (Prolastin, Bayer, Bridgend, U.K.) has been life-saving.

Axillary artery pseudoaneurysm.

Axillary artery aneurysms are extremely rare. We report a case of an axillary artery aneurysm in a keen rugby player who had previous internal fixation of the shoulder for recurrent dislocation.

Mortality from ruptured abdominal aortic aneurysm in Wales.

BACKGROUND: The aim of this study was to identify the incidence of, and mortality in, patients with a ruptured abdominal aortic aneurysm (AAA) reaching hospital alive in Wales. METHODS: Patients who presented with a ruptured AAA between September 1996 and August 1997 were analysed. Data were collected prospectively by an independent body, observing strict confidentiality. RESULTS: Some 233 patients with a confirmed ruptured AAA were identified, giving an incidence of eight per 100 000 total population. Some 133 patients (57 per cent) underwent attempted operative repair; 85 (64 per cent) of these died within 30 days. Of the 233 patients, 92 were admitted under the care of a vascular surgeon and 141 under a non-vascular surgeon. Vascular surgeons operated on 82 patients (89 per cent), of whom 50 (61 per cent) died, whereas non-vascular surgeons operated on 51 patients (36 per cent), of whom 35 (69 per cent) died. DISCUSSION: This study is unique as it is an independent prospective study of mortality in patients with a ruptured AAA who reached hospital alive. Mortality was independent of the operating surgeon, but vascular surgeons turned down significantly fewer patients than non-vascular surgeons (11 versus 64 per cent, P < 0.001).

Ideal pain relief following laparoscopic cholecystectomy.

In a previous report the effectiveness of intraperitoneal bupivacaine in reducing pain following laparoscopic cholecystectomy was demonstrated. Other methods of pain relief are commonly used but none has been compared following laparoscopic cholecystectomy. In two further studies we have compared the analgesic effect of intraperitoneal bupivacaine against wound infiltration with bupivacaine, and against intraperitoneal bupivacaine with the addition of a non-steroidal anti-inflammatory drug (NSAID) in patients undergoing laparoscopic cholecystectomy. Two consecutive studies were performed. In the first, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine injected into the trocar wounds. In the second study, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity and a diclofenac suppository (100 mg) one hour before surgery. Postoperative pain was assessed with a visual analogue pain scale. There was no difference in pain scores in the two groups in either study. Intraperitoneal bupivacaine is as effective as wound infiltration. The addition of an NSAID makes no difference in the reduction of postoperative pain following laparoscopic cholecystectomy.

Is an outpatient appointment required for patients referred for a minor operation under local anaesthetic?

The necessity of an outpatient (OP) consultation for patients referred for minor surgery under local anaesthetic (LA) was examined. Two separate prospective studies were performed. The first comprised 107 patients referred for minor surgery, who were assessed in the outpatient department (OPD), before being booked for minor operations. The second study comprised 106 patients whose names were placed directly on a minor operations list on the basis of the GP referral letter alone. In the first study, 97 (91 per cent) patients went on to undergo minor surgery. Five were not suitable for LA and in five an operation was considered unnecessary. Patients not suitable for LA included children, neck swellings, pre-auricular swellings and swellings described as lymph nodes. In the second study, the GP referral letters were screened to exclude the above and of 106 referrals 93 (88 per cent) underwent a minor operation. The benefit of the second study was twofold. First, 106 OP slots were available for other referrals and secondly, patients avoided the OP waiting list and did not lose time from work as a result of the OP visit. There were no adverse effects demonstrated during the second study. We believe the OP consultation can be avoided if the referral letters are carefully screened.

Provision of a vascular service in a district general hospital.

The effect of the appointment of a vascular interest surgeon (VIS) on the provision of a local vascular service has been analysed with regard to change in workload, over the 2.5 years before and after appointment. During the period analysed (1989-1994), there was an increase in elective vascular surgery: aorto/iliac reconstructions (11 v 58) and femoro-distal reconstructions (5 v 34). Carotid/subclavian, femorocrural and endoscopic cervical sympathectomy were introduced. There was a reduction in tertiary referrals (14 v 34). An associated increase in arteriography (196 v 280), angioplasty (38 v 74) and chemical sympathectomies (12 v 27) was observed. Major amputations, however, decreased (64 v 49). There was a decrease in emergency vascular operations performed; ruptured aneurysms (23 v 15), embolectomy (17 v 10). 50 per cent of these operations were performed by the VIS. The appointment of a vascular surgeon increases surgical, radiological and anaesthetic workload but there are still problems in the provision of a local vascular service.

Intraperitoneal bupivacaine for effective pain relief after laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is now widely practised. There are various methods of pain relief used but none has been assessed or compared following this procedure. We have assessed the analgesic effect of intraperitoneal bupivacaine in laparoscopic cholecystectomy. Sixty consecutive patients were randomly assigned to one of two groups. Patients in group 1 were given 20 ml of saline injected under vision into the region of the gallbladder bed. Patients in group 2 were given 20 ml of 0.25% bupivacaine in a similar fashion. Postoperative pain was assessed with a visual analogue pain scale and the site of pain was recorded. Patients in the bupivacaine group had less pain in the early postoperative period and a lower incidence of pain in the right hypochondrium. Intraperitoneal bupivacaine is a simple and effective treatment for postoperative pain after laparoscopic cholecystectomy.

Deep vein thrombosis after elective knee surgery. An incidence study in 312 patients.

The incidence of venous thromboembolism after elective knee surgery has previously been studied almost exclusively in patients receiving total knee replacements, in whom the risk of a deep vein thrombosis is approximately 60%. We report the results of ipsilateral ascending venography in 312 patients undergoing a wide variety of elective knee operations under tourniquet ischaemia, none of whom received any specific prophylaxis against thromboembolism. Total knee replacement was confirmed to carry a high risk with ipsilateral deep vein thrombosis in 56.4% and symptomatic pulmonary embolism in 1.9%. By contrast, arthroscopy was associated with a low incidence of venous thrombosis (4.2%). Meniscectomy, arthrotomy, patellectomy, synovectomy and arthrodesis were all high-risk procedures, particularly in patients over 40 years of age, and were associated with deep vein thrombosis rates of 25% to 67%. On the basis of these findings, we advise prophylaxis against venous thromboembolism in all patients over 40 years of age undergoing elective knee surgery other than arthroscopy.

Fixed combinations of low-molecular weight or unfractionated heparin plus dihydroergotamine in the prevention of postoperative deep vein thrombosis.

A prospective, double-blind, randomized, controlled clinical trial compared the efficacy and safety of fixed combinations of low-molecular weight heparin or standard unfractionated heparin plus dihydroergotamine mesylate in the prevention of deep vein thrombosis in high-risk patients undergoing elective major abdominal surgery. Two hundred patients, with a mean age of 66.6 years and almost half with malignancy, were allocated to receive either 5,000 IU unfractionated heparin plus 0.5 mg dihydroergotamine mesylate twice daily or 1,500 IU low-molecular weight heparin plus 0.5 mg dihydroergotamine mesylate once daily together with one placebo injection per day. Treatment was commenced 2 hours preoperatively and continued for at least 7 days. The incidence of deep vein thrombosis, determined by radiolabelled fibrinogen uptake and phlebography, was 11 percent in the unfractionated heparin plus dihydroergotamine mesylate group and 11.4 percent in the low-molecular weight heparin and dihydroergotamine mesylate group. Neither these figures nor those for major proximal thrombi proved significantly different. Of the four parameters used to assess hemorrhagic complications, only the decrease in postoperative hemoglobin levels in the low-molecular weight and dihydroergotamine mesylate group reached statistical significance. These results indicate that once-daily prophylaxis with a combination of low-molecular weight heparin and dihydroergotamine is safe, effective, and convenient in high-risk patients undergoing major abdominal surgery.

Hamartoma of Brunner's gland causing pyloric obstruction and a biliary fistula. Case report.

Hamartoma of Brunner's gland is rare. They have previously been described as a cause of gastrointestinal haemorrhage and obstruction. This is the first report of a hamartoma causing pyloric obstruction and a biliary fistula.

Diagnosis and surgical treatment of the maldescended testis.

Maldescent is a common anomaly. Treatment is recommended at two years of age. Extensive retroperitoneal mobilization may be necessary for the high testis, but treatment may be facilitated by a preoperative course of gonadotrophin injections. This article is based on our management of 405 consecutive orchidopexies.

Metabolic epidemiology of large bowel cancer: fecal bulk and constituents of high-risk North American and low-risk Finnish population.

The dietary pattern and fecal constituents of two populations with distinct risk for the development of colon cancer, a high-risk population in New York Metropolitan area and a low-risk population in rural Kuopio, were studied. The average daily intake of dietary fat and protein was the same in the two groups, but the sources of fat were different, a greater portion coming from dairy products in rural Kuopio and from meat in the New York Metropolitan area. Not only the frequency of bowel movements was higher, but also the daily total stool output as well as the fecal fiber excretion were greater in Kuopio compared with New York due to high dietary intake in rural Kuopio of cereal products rich in fiber. The concentration of fecal secondary bile acids and bacterial beta-glucuronidase activity was lower in rural Kuopio, but the total daily excretion of these constituents was the same in two populations. The daily fecal excretion of bacterial nuclear dehydrogenase activity and of neutral sterols was higher in rural Kuopio, and the concentration of these constituents was the same in the two groups. The high daily excretion of cholesterol metabolites in Kuopio might be due to high dietary intake of dairy products. The data suggest that one of the factors contributing to the low-risk of large bowel cancer in Finland, in spite of high dietary intake of fat, appears to be the fact that a high dietary fiber leads to an increase in stool bulk, thus diluting bile acids, which have promoting activity.