Practice patterns in flexor tendon repair.

BACKGROUND: There is a considerable volume of literature describing new and supposedly superior methods of flexor tendon repair. AIM: The purpose of this study was to assess the flexor tendon techniques currently used in the Republic of Ireland. METHODS: A postal survey was conducted of all consultant plastic surgeons and consultant orthopaedic surgeons who were members of the Irish Hand Surgery Society. RESULTS: The response rate was 90% (27/30). A simple running peripheral suture was used by 73% (P = 0.03) and the Kessler was the core suture of choice for 68% (P = 0.06). A significant number of respondents use non-absorbable suture materials for core (P = 0.0028) and peripheral suture (P < 0.0001). Seventy-seven percent sutured the flexor sheath where possible (P = 0.009). CONCLUSIONS: Notwithstanding the proposed advantages of newer techniques, it is evident from this study that the two-stranded Kessler core and simple running peripheral suture remains the most popular flexor tendon repair, with sheath closure preferred by the majority of respondents.

The evolution of trauma services at Beaumont Hospital.

OBJECTIVE: To review and examine the epidemiology, severity and management of trauma admissions at the national neurosurgical teaching hospital. METHODS: An extensive audit of volume, type and severity of injury and the management requirements of the trauma population admitted to the hospital. RESULTS: The vast majority of severely injured patients were referred from outside the catchment area of the hospital with only 26% being admitted directly through the Emergency Department. As a consequence, 73% of patients arrived out of normal working hours, which posed problems in providing skilled trauma specialists. CONCLUSIONS: The management of patients with serious injury is complex. The large proportion of patients with critical injuries, some of whom were paediatric, highlighted the need for 24 h cover by senior trauma personnel and the provision of radiology and operating facilities to meet their needs. The inclusion of indicators of alterations in innate or adaptive immune responses may improve the predictive power of severity of injury scores.

Co-immunotherapy with interleukin-2 and taurolidine for progressive metastatic melanoma.

BACKGROUND: Recombinant interleukin-2(rIL-2) therapy in metastatic melanoma is limited by toxicities, particularly vascular leak syndrome(VLS). Taurolidine potentiates the anti-neoplastic effects of IL-2 while reducing its associated endothelial cell dysfunction in experimental settings. We hypothesized that co-administration of rIL-2 with taurolidine could enhance tolerability without weakening effectiveness. METHODS: Eleven patients with progressive metastatic melanoma received high-dose rIL-2 with co-infusion of taurolidine. Patients were monitored for the development of toxicities and evidence of response. RESULTS: Ten patients tolerated twenty-nine courses of high-dose rIL-2 without dose-reduction. Most toxicities were low-grade. No patient developed VLS. Seven patients died from disease progression. Two had complete clinical and radiological responses to treatment. Two patients remain alive despite evidence of disease progression a mean of 17.5 months after diagnosing metastatic disease. CONCLUSION: Co-administration of taurolidine with high-dose rIL-2 in stage IV melanoma patients appears to greatly enhance the tolerability of this regime without diminishing its therapeutic value.

Taurine and vitamin C modify monocyte and endothelial dysfunction in young smokers.

BACKGROUND: Endothelial dysfunction initiated by monocyte-endothelial interactions has previously been observed in many vasculopathies, including chronic cigarette smoking. Taurine, a semiessential amino acid, and vitamin C, a naturally occurring antioxidant, have previously been shown to have endothelial protective effects when exposed to proinflammatory insults. Therefore, we hypothesized that taurine and vitamin C would restore endothelial function in young smokers by modifying monocyte-endothelial interactions. METHODS AND RESULTS: Endothelial-dependent vasodilatation was assessed in vivo using duplex ultrasonography, and monocyte-endothelial interactions were assessed in vitro using endothelial cell culture (human umbilical vein endothelial cells [HUVECs]) with monocyte-conditioned medium (MCM). Endothelial-dependent vasodilatation was significantly impaired in young smokers compared with nonsmokers. Pretreatment of young smokers for 5 days with 2 g/d vitamin C and, more significantly, with 1.5 g/d taurine attenuated this response. MCM taken from smokers impaired the release of nitric oxide and increased the levels of endothelin-1 release from HUVECs. When HUVECs were cultured with MCM from smokers who had been treated with taurine, the levels of nitric oxide and endothelin-1 returned toward control levels. This was attributed to an upregulation in endothelial nitric oxide synthase expression. CONCLUSIONS: These observations suggest that taurine supplementation has a beneficial impact on macrovascular endothelial function, and an investigation of its effect on altered endothelial function in dyslipidemic states is warranted.

Thrombomodulin: tumour biology and prognostic implications.

BACKGROUND: Thrombomodulin (TM) is an endothelial receptor that exerts anti-coagulant, anti-fibrinolytic, and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. There is growing evidence that TM plays a role in tumour behaviour. METHODS: The electronic literature (1966-2004) was reviewed with a specific focus on tumour biology. RESULTS: TM is expressed on both the endothelium and tumour cells in several cancers. Loss of expression denotes a more malignant profile with poorer prognosis. Loss of TM is mediated by hypoxia, endotoxin, and various cytokines, while up-regulation can be achieved by pharmacological manipulation (e.g. pentoxyfylline and statins). CONCLUSION: Originally described as an endothelial anticoagulant, TM plays a key role in tumour biology and prognostics, and provides a potential therapeutic target in impeding cancer spread.

Thermotolerance attenuates ischemia-reperfusion induced renal injury and increased expression of ICAM-1.

Thermotolerance describes the process in which hyperthermia induces a transient resistance of the stressed cells to subsequent episodes of oxidative stress. The aims of this study were first, to assess the effect of ischemia-reperfusion (IR) injury on renal function and the expression of the ICAM-1 receptor and MHC antigens, and second, to evaluate the protective effects of thermotolerance on IR induced renal injury and its potential for decreasing allograft rejection, by decreasing alloantigen expression. Sprague-Dawley rats were randomized into three groups: control, IR, and hyperthermia + IR (HIR) (n=8 per group). Thermotolerance was induced 18 hr prior to IR by increasing the core body temperature to 41 degrees C+/-0.5 degrees C for 15 min. After left uninephrectomy, IR was induced by clamping the right renal pedicle for 45 min, followed by 2 hr reperfusion. Myeloperoxidase (MPO) activity was used as an indicator of renal neutrophil influx. Kidney edema was assessed using the weight difference between left and right kidneys. Renal function was evaluated by measuring serum creatinine and urea 2 hr following clamp removal. Immunocytochemistry was used to measure expression of ICAM-1 and MHC antigen. Renal function was significantly impaired by IR with serum creatinine and urea levels of 131.5+/-5.01 microM and 11.2+/-0.71 mM, respectively, compared with controls of 67.9+/-5.11 microM and 8.1+/-0.36 mM, P<0.005 in both cases. Renal function was preserved in the HIR group, serum creatinine (84.8+/-8.58 microM) and urea (9.0+/-0.52 mM) were comparable to that of controls. Renal endothelium was activated in the IR group compared with controls, with increased ICAM-1, and tubular epithelium showed increased class II MHC expression. This up-regulation was prevented by prior induction of thermotolerance. Endothelial permeability was increased in the IR group with MPO activity of 0.8+/-0.08 units/g tissue--twice that of control levels P<0.05--and a marked increase in organ edema. Thermotolerance preserved endothelial barrier function. Thermotolerance may prevent IR injury by preventing endothelium activation and has the potential to modify allograft rejection by decreasing expression of ICAM-1, an important T cell receptor, and class II MHC.

The effect of laparotomy and laparoscopy on the establishment of spontaneous tumor metastases.

BACKGROUND: Surgical extirpation of solid tumors may be entirely possible, and the consequence of surgical excision is invariably the release of tumor cells into the systemic circulation. The aim of this study was to determine whether laparotomy affects the establishment of spontaneous pulmonary metastases after excision of the primary tumor in a murine flank tumor model and to determine possible underlying immune abnormalities. METHODS: An initial experiment was carried out to compare the development of gross spontaneous pulmonary metastases in the presence of a primary flank tumor and after excision of the tumor in C57/BL6 female mice. Another group of mice had flank tumors excised and were simultaneously randomized to undergo anesthetic only (control), laparoscopy, or laparotomy, after which the subsequent development of pulmonary metastases was determined. Finally, a third experiment entailed determination of natural killer cell (NK) cytotoxicity and the effect of splenic macrophages on NK cytotoxicity at days 1,7, and 14 after tumor excision. RESULTS: Excision of the primary tumor resulted in a significant increase in the number of pulmonary metastases in mice compared with mice that did not have tumors excised (P = .01). Both laparotomy and laparoscopy significantly increased the number of spontaneous pulmonary metastases after tumor excision compared with controls (P < or = .01), and there was also a significant difference between laparotomy and laparoscopy groups (P = .00). NK cytotoxicity was significantly suppressed at all time points after operation in the laparotomy group compared with both the laparoscopy group and the controls (P < or = .01). Suppression occurred after laparoscopy at 24 hours after the procedure compared with controls (P = .00); by day 7 this difference was not significant, but as day 14 there was again a significant suppression (P < or = .03). Splenic macrophages appeared to be a suppressor to natural killer cell cytotoxicity (NKCC) in the corresponding groups and at the corresponding time points. CONCLUSIONS: The differential establishment of spontaneous metastases after tumor excision and laparotomy and, to a lesser extent, laparoscopy results in lowered host antitumor surveillance and may be mediated at least in part by the generation of splenic suppressor cells in the early postoperative period, causing a more marked and prolonged effect after laparotomy than after laparoscopy.

Hemodynamic studies of the audiofrequency analysis of carotid bruits.

The contribution of carotid audiofrequency analysis to the noninvasive diagnosis of carotid arterial lesions requires clarification. Carotid arterial stenoses were simulated in the dog and the following measurements were made: proximal and distal arterial pressure, blood flow, percent area reduction, and carotid audiofrequency analysis. A 40% area reduction produced a systolic bruit but no interference with flow or pressure. A 60% area reduction produced a pansystolic bruit and a reduction in peak systolic flow (precritical stenosis). A 70% area reduction produced a systolic bruit that extended into diastole, a reduction in mean blood flow, and an increased pressure gradient (critical stenosis). At total occlusion, there was no recordable heart sound or bruit. Carotid audiofrequency analysis can establish the hemodynamic importance of a carotid artery lesion and it is an essential component of any noninvasive examination.

Genetic evaluation of lipoprotein(a) in intracranial aneurysm disease.

OBJECTIVE: Elevations in serum lipoprotein(a) [Lp(a)] levels have been reported in intracranial aneurysm (IA) disease. Our aim was to investigate a genetic basis for this observation. METHODS: We performed a comparative analysis of size polymorphisms at two loci (kringle 4 [K4] and TTTTA pentanucleotide [PN] repeats) within the apolipoprotein(a) gene on Chromosome 6q26-27 among patients with sporadic IAs (n = 50), members of three IA families (n = 50), and control subjects (n = 50). RESULTS: There was no significant difference in mean Lp(a) levels between patients with sporadic IAs and control subjects, but IA family members exhibited a more than twofold elevation in mean Lp(a) levels, compared with control subjects (29.2 versus 12.9 mg %). Inverse relationships between K4/PN numbers and serum Lp(a) levels were demonstrated; genotype frequencies did not differ significantly from a Hardy-Weinberg equilibrium or from published frequencies for other Caucasian populations. We detected no difference in mean K4 and PN genotypic indices between patients with IAs and control subjects (9.3 and 16.92 versus 9.0 and 16.92, respectively), but IA families did exhibit a lower mean K4 genotypic index (7.7), compared with control subjects. Superficial analysis of family pedigrees revealed no suggestion of linkage between K4/PN genotypes and IA disease. CONCLUSION: The previously described elevation in Lp(a) levels among patients with sporadic IAs might be explained by an acute-phase response. Crude Lp(a) measurements might provide a useful predictive test for familial IA disease, but with the disadvantage of low specificity. The possibility of linkage of familial IA disease to a particular apolipoprotein(a) isoform size range has not been eliminated.

Tumour micrometastases: the influence of angiogenesis.

INTRODUCTION: Many cancer patients have undetected micrometastatic disease at first presentation which ultimately progresses. Angiogenesis-the development of an independent blood supply-is a key event in the growth of metastases. Improved understanding of the influence of angiogenesis on micrometastatic growth may lead to new therapeutic intervention. METHODS: This study examines current concepts of the significance of micrometastases and the role of angiogenesis in their development and destruction. A comprehensive review of the literature on micrometastasis and angiogenesis was performed using the Medline database between 1966 and 1999. CONCLUSIONS: Advances in technology have improved our ability to diagnose metastatic disease, but micrometastases in loco-regional lymph nodes and at distant sites can only be detected by sophisticated histological techniques. While the significance of micrometastases remains controversial, there is increasing evidence that micrometastatic status provides useful prognostic information and should be part of standard staging techniques. Anti-angiogenic therapy has the potential to favourably influence management of certain cancers by manipulating a number of key events in the metastatic process.

Tamoxifen inhibits endothelial cell proliferation and attenuates VEGF-mediated angiogenesis and migration in vivo.

INTRODUCTION: Angiogenesis is fundamental to tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic cytokines known. We have previously demonstrated that tamoxifen reduces serum VEGF in certain cancer patients. We hypothesized that tamoxifen may attenuate the angiogenetic response to VEGF. METHODS: Human dermal microvessel endothelial primary cell cultures (HMEC) were incubated with tamoxifen (1.25-5.0 microg) or vehicle. Cell proliferation was quantified using 5-bromo-2'-deoxyuridine (BrdU) labelling endothelial cell proliferation assay. The effect of oral tamoxifen (20 mg/day) on VEGF-mediated angiogenesis in vivo was assessed using a Matrigel angiogenesis assay in the Sprague-Dawley rat. RESULTS: Tamoxifen (5.0 microg/ml) significantly reduced HMEC proliferation over 24 h when compared with cells treated with vehicle alone. Oral administration of tamoxifen in the rat (20 mg/day) significantly reduced endothelial cell proliferation and migration in response to VEGF. CONCLUSION: Tamoxifen (5.0 microg/ml) reduces proliferation of a VEGF-dependent endothelial cell line in vitro. In vivo, orally administered tamoxifen reduces VEGF-mediated angiogenesis in the rat. These findings indicate that tamoxifen may directly inhibit the effect of VEGF on the endothelial cell, in addition to its previously described effect of reducing serum VEGF levels. This data supports a role for tamoxifen in modulation of the VEGF-dependent angiogenic response to surgical trauma, particularly as an adjuvant therapy for VEGF-dependent tumours.

Taurine and human nutrition.

Taurine (2-aminoethane sulphonic acid), a ubiquitous beta-amino acid not incorporated into proteins but found either free or in some simple peptides is considered as a conditionally semi-essential amino acid in man. Once thought of as no more than an innocuous end product of cysteine metabolism, taurine has in recent years generated much interest due to research findings indicating a role in numerous physiological processes. These roles are varied and include membrane stabilization, detoxification, antioxidation, osmoregulation, maintenance of calcium homeostasis, and stimulation of glycolysis and glycogenesis. Intracellular and plasma taurine levels are high and although cellular taurine is tightly regulated, plasma levels are known to decrease in response to surgical injury and numerous pathological conditions including cancer, trauma and sepsis. Decreased plasma concentrations can be restored with supplementary taurine. Although the importance of taurine as a physiological agent with pharmacological properties is now recognised, the potential advantages of dietary supplementation with taurine have not as yet been fully exploited and this is an area which could prove to be of benefit to the patient.

Host defense--a role for the amino acid taurine?

Taurine (2-aminoethane sulphonic acid), a ubiquitous beta-amino acid is conditionally essential in man. It is not utilized in protein synthesis but found free or in some simple peptides. Derived from methionine and cysteine metabolism, taurine is known to play a pivotal role in numerous physiological functions. Some of the roles with which taurine has been associated include osmoregulation, antioxidation, detoxification and stimulation of glycolysis and glycogenesis. Intracellular taurine is maintained at high concentrations in a variety of cell types and alteration of cell taurine levels is difficult. The role of taurine within the cell appears to be determined by the cell type. Recent research has determined a regulatory role for taurinechloramine, the product formed by the reaction between taurine and neutrophil derived hypochlorous acid on macrophage function. Plasma taurine levels are also high, although decreases are observed in response to surgical injury and numerous pathological conditions including cancer and sepsis. Supplementary taurine replenishes decreased plasma taurine. Although commonly used as a dietary supplement in the Far East, the potential advantages of dietary taurine supplementation have not as yet been fully recognized in the Western World; this is an area which could prove to be beneficial in the clinical arena.

Myeloperoxidase (MPO) may mediate neutrophil adherence to the endothelium through upregulation of CD11B expression--an effect downregulated by taurine.

Extracellular myeloperoxidase (MPO) is a macrophage modulator which stimulates release of the pro-inflammatory cytokine TNF alpha in addition to reactive oxygen species (ROS) generated by these cells. MPO-induced macrophage secretion of pro-inflammatory mediators indirectly upregulates neutrophil pro-inflammatory capacity through contributing to neutrophil priming for respiratory burst activity. However, to date the question concerning a direct influence on the neutrophil by MPO or the MPO-derived product hypochlorous acid (HOCl) remains to be elucidated. Taurine, the most abundant free amino acid in human neutrophils acts as an antioxidant through the formation of taurine-chloramine by sequestering HOCl. Zinc also has antioxidant properties and taurine-zinc complexes have been shown to have greater efficacy than either agent alone in protection against ROS-mediated tissue damage. The aims of this study were: (a) to determine if extracellular MPO modulates the inflammatory response through autocrine feedback on the neutrophil and to investigate if taurine either directly or indirectly through taurine-chloramine formation may further influence this pathway and (b) to evaluate the efficacy of a taurine-zinc combination in modulating MPO-induced CD11b receptor expression.

Upper limb emboli. A review of 55 patients managed surgically.

During an eleven years period 1976-1986, 55 patients with emboli to the upper limb were managed at St. Laurence's Hospital. The presentation was classical for acute limb ischaemia in the majority while 27% presented 48 hours or more after the onset of symptoms. Four patients presented with gangrene. In 41 patients a source of embolus was readily identified: atrial fibrillation (33), recent myocardial infarct (5), subclavian artery aneurysm (2), left atrial myxoma (1). In the remaining 14 patients the source of the embolus was not initially apparent but investigation by echocardiography, 24 hour Holter monitoring and coagulation studies suggested a source in eight. Embolectomy was performed in 51 patients and amputation as a primary procedure in two. The patients with subclavian artery aneurysms were not treated surgically. A normal circulation was restored both clinically and angiographically in 43 patients, four of whom later died from myocardial infarction. Four of the remaining eight patients had residual arm claudication, three required amputation and one had an ischaemic contracture. The failure to restore a normal circulation was uniformly associated with delayed presentation or failure to adequately anticoagulate the patient with heparin.

Is compliance mismatch the major cause of anastomotic arterial aneurysms? Analysis of 42 cases.

In 1,348 anastomoses carried out prior to 1976 at St. Laurence's Hospital, Dublin, 36 anastomotic aneurysms developed for an incidence of 2.7%. Six further anastomotic aneurysms occurred following repair of anastomotic false aneurysms. Suture material failure, infection or lymphatic leakage were not associated with aneurysm formation. Twenty three aneurysms occurred in eight hundred and sixty Dacron to artery anastomoses while 6 occurred in 420 vein to artery anastomoses. Anastomotic false aneurysms were found only with the Dacron to artery anastomoses. Only 9 of 590 anastomoses performed for abdominal aortic aneurysm developed false aneurysms while 14 occurred in 270 for occlusive atherosclerosis. We have concluded that compliance mismatch producing anastomotic shear stress damages the arterial wall. This structural impairment permits tearing out of sutures from the vessel wall. The process is facilitated by prior loss of structural integrity of the vessel wall.

Post-cholecystectomy symptoms after laparoscopic cholecystectomy.

Abdominal symptoms persist in up to 40% of patients after laparotomy cholecystectomy and biliary lithotripsy. Laparoscopic cholecystectomy is now the treatment of choice for symptomatic gallstone disease. However, no data exist as to the influence of laparoscopic cholecystectomy on symptoms. We analysed 100 patients who had undergone laparoscopic cholecystectomy at a median of 12 months (range 10-19 months) previously. Pre- and postoperative symptoms were compared and patient satisfaction was graded from 1 (best) to 5 (worst). Time to resumption of full activity (mean +/- SD) was recorded. All patients had more than two symptoms preoperatively. Postoperatively, 61 patients had complete absence of symptoms, 14 patients complained of only one symptom during the postoperative period and 25 patients continued to have at least two symptoms. The mean time taken to return to full activity was 2.4 +/- 1.7 weeks. In patients without any symptoms postoperatively, time taken to return to full activity was 2.3 +/- 1.5 weeks, 2.7 +/- 1.4 weeks for patients with one symptom postoperatively, while patients with two or more symptoms returned to full activity in 2.3 +/- 1.3 weeks and 2.6 +/- 1.7 weeks, respectively. Notwithstanding that 25% of patients reported two or more symptoms postoperatively, most patients (n = 84) considered the procedure to be a complete success. A further 10 patients had significant improvement after laparoscopic cholecystectomy. Five patients considered themselves only slightly improved, while a single patient was no better off postoperatively. These data indicate that after laparoscopic cholecystectomy most patients return to full activity within 3 weeks. Thus, the incidence of post-cholecystectomy symptoms is similar after laparoscopic and laparotomy cholecystectomy and biliary lithotripsy.Patients should be advised of the risk of persistent symptoms after these procedures.

The role of CT in the management of carcinoma of the oesophagus and cardia.

The role of computed tomography in assessing tumour spread and tumour resectability was evaluated in 50 patients with oesophageal carcinoma (17 middle third, 33 lower third). CT accurately identified all patients with tumour confined to the oesophagus (Stage I or II) but was limited in its ability to assess direct organ invasion (Stage III) with an overall accuracy for evaluating middle third lesions of 82% (aorta 70%, tracheobronchial tree 94%, other mediastinal structures 82%) compared to an overall accuracy for lower third lesions of 97% (aorta 97%, pancreas 100%, diaphragm 97%). Tumours deemed resectable on CT were always resectable at operation but two of seven middle third tumours and one of twelve lower third lesions deemed unresectable underwent curative resection. Preoperative CT evaluation of oesophageal tumours is useful in that it may reliably identify tumour lesions confined to the oesophagus and reliably identify distant metastases. Because of its limitations however in the assessment of organ invasion, particularly by middle third lesions, this study suggests that patients with oesophageal tumours with no evidence of distant metastases, who are otherwise fit to undergo tumour resection, should not be denied surgery on the sole basis of positive organ invasion on CT particularly if that organ is the aorta.

The research abstract: worth getting it right.

BACKGROUND: Scientific merit and clarity are critical in evaluation of quality in research. We hypothesised that avoidable errors of presentation adversely impact on abstract selection for scientific meetings. AIM: To prospectively evaluate compliance with abstract guidelines among abstracts submitted to a national surgical scientific meeting. METHODS: Compliance of all submitted abstracts with 13 instructions to authors was compared using ANOVA and Chi-squared tests. Results are expressed as mean (standard deviation, range). RESULTS: Of 45 abstracts submitted, only 8 (17%) complied with all guidelines. Rejected abstracts were less concise than accepted abstracts (280.5 +/- 73.8 words vs. 244.2 +/- 42.5; p=0.006) and were more likely to be rejected (chi2 = 8.67, 1 df, p<0.05). There was no significant difference between the number of errors in accepted (1.6 [1.43, 0-4]) versus rejected (2.4 [1.87, 0-7], ANOVA; p=0.217) abstracts. All late submissions (30%) were rejected. Nine abstracts (20%) contained statistical errors or omissions. CONCLUSIONS: Succinct presentation may reflect clarity of focus or increased writing experience. Reviewers favour concise abstracts. Concise presentation and timely submission are easily achieved and increase the likelihood of research acceptance for scientific meetings.