Lipofuscin: resolution of discrepant fluorescence data.

Lipofuscin granules (age pigments) emit yellow light under ultraviolet excitation in the fluorescence microscope. The reported blue emission maximum of extracts of lipofuscin-laden cells may result from instrumental bias. The major fluorescent components that accumulate with age in these lysosomal residual bodies of human retinal pigment epithelium are yellow-emitting fluorophores. Different age-related fluorophores, which do emit blue light, are derived from other intracellular sources. A reevaluation of the connection between blue-emitting lipid peroxidation products and the age-related lipofuscin granules of classical pathology is necessary.

Elevated titers of serum agglutinators. A serologic indicator of infection.

Elevated titers of serum agglutinators (anti-FabIgG) are associated with significant and severe suppurative infection. Immunosuppression and long-term antibiotic therapy, however, may lead to negative tests.

Relaparoscopy for the detection and treatment of complications of laparoscopic cholecystectomy.

BACKGROUND: Laparotomy remains the commonest intervention in patients with abdominal complications of laparoscopic surgery. Our own policy is to employ relaparoscopy to avoid diagnostic delay and unnecessary laparotomy. The results of using this policy in patients with suspected intra-abdominal complications following laparoscopic cholecystectomy are reviewed. METHODS: Data were collected from laparoscopic cholecystectomies carried out by five consultant surgeons in one center. Details of relaparoscopy for complications were analyzed. RESULTS: Thirteen patients underwent relaparoscopy within 7 days of laparoscopic cholecystectomy for intra-abdominal bleeding (2 patients) or abdominal pain (11 patients). The causes of pain were subhepatic haematoma (1), acute pancreatitis (1), small bowel injury (1), and minor bile leakage (6). In 2 patients no cause was identified. Twelve patients were managed laparoscopically and 1 patient required laparotomy. Median stay after relaparoscopy was 7 days (range 2 to 19). CONCLUSIONS: Exploratory laparotomy can be avoided by prompt relaparoscopy in the majority of patients with abdominal complications of laparoscopic cholecystectomy.

'Surgical' peritonitis in the CAPD patient.

Peritonitis is the most frequent cause for emergency hospital admission in continuous ambulatory peritoneal dialysis (CAPD) patients. Patients may present with 'surgical' peritonitis from other intra-abdominal pathology, but are treated initially as CAPD-related peritonitis. We present nine such cases, each failing to respond to standard conservative treatment, and ultimately coming to laparotomy. Of the nine patients, six survived, five transferring to long-term haemodialysis and one patient returning to CAPD. Failure to respond to standard measures should alert the physician to the possibility of an intra-abdominal emergency. The presence of enteric organisms, particularly E. coli, is an additional suspicious feature. The diagnosis may be difficult and we recommend early surgical referral and appropriate surgical measures (laparotomy rather than simple catheter removal) in order to decrease morbidity and mortality.

Morbidity of varicose vein surgery: auditing the benefit of changing clinical practice.

During two consecutive study periods (24 months and 16 months), 997 patients (1322 legs) with varicose veins underwent surgical treatment in Huddersfield Royal Infirmary, using a variety of surgical techniques. The average length of stay was 1.5 days, and 95.5% of patients had a hospital stay of less than 2 days. Complications occurred in seven inpatients. A further 16 patients developed complications requiring readmission to hospital (10 minor and intermediate; 6 major). The complication rate appeared to be operator-dependent: an increased complication rate (particularly major complications) occurred after surgery by junior surgeons. Major complications included femoral vein injury (1 patient), postoperative deep venous thrombosis (4 patients), pulmonary embolism (1 patient) and groin lymphatic fistula requiring reoperation (1 patient). Between the first and second study period, a change in policy regarding the type of bandaging used and the use of postoperative antiembolic stockings occurred and appears to have reduced the incidence of thromboembolic complications from 0.7% to 0.2%. Varicose vein surgery is not without major complications though, fortunately, there was no mortality in this series. These complications can be minimised with good surgical technique and better supervision of surgical trainees. Modification of postoperative management can further enhance the safety of this procedure.

Preoperatively determinable factors predictive of diabetes mellitus remission following Roux-en-Y gastric bypass: a review of the literature.

It is well established that weight loss in general and bariatric surgery in particular can improve glycaemic control in diabetics. Current NICE guidelines recommend that those patients with type 2 diabetes mellitus and a BMI of 35 kg/m(2) or more should be considered for bariatric surgery in order to optimise their glycaemic control and minimise their risk of long-term complications. The commonest bariatric procedure in the UK is the Roux-en-Y gastric bypass that has been shown to result in long-standing type 2 diabetes resolution in 83 % of patients. Since such surgery carries a small but significant risk of mortality, as well as posing considerable lifestyle implications for the patient, numerous studies have been performed with a view to identifying which patients and which procedures are most likely to result in these desired benefits. This paper summarises the existing literature on this topic.

Recurrent recurrent gallstone ileus.

We describe the second reported case of three consecutive episodes of gallstone ileus and ask the question whether recurrent gallstone ileus justifies definitive surgery to the fistula itself or can be safely managed by repeated enterotomies.

Omission of concurrent chemoradiation after a response to neoadjuvant chemotherapy in locally advanced rectal cancer with a synchronous liver metastasis: a note of caution.

There is clear evidence to support the use of pre-operative concurrent chemo-radiotherapy (CRT) in locally advanced rectal cancer. In the UK, most patients are selected for treatment if the resection margin is predicted to be involved. The selection criteria used includes primary tumours that threaten the resection margins on high-resolution pelvic MRI and low tumours requiring abdominoperineal excision. There is no consensus, however, to guide the treatment of patients who present with advanced rectal disease and synchronous, potentially resectable, metastatic disease. This case illustrates the potential risk of omitting radiation following a good response to neoadjuvant systemic chemotherapy.

Ethnicity and the experience of work: job stress and satisfaction of minority ethnic teachers in the UK.

This paper presents the findings of a nationwide investigation into the mental well-being and job satisfaction of minority ethnic teachers in the UK. Data were collected via a questionnaire containing both open and closed questions. The sample, totalling 208 participants was derived from the National Union of Teachers (NUT) database of minority ethnic teachers and an advertisement in the NUT's Teacher magazine. Univariate analysis of the results revealed that this group of teachers, as compared with other groups were experiencing poorer mental health and lower job satisfaction. Multivariate analysis revealed four reliable factors regarding the 'sources of stress' these minority ethnic teachers perceived they were experiencing. They are the 'hierarchy and culture of the school', workload', 'cultural barriers', and the 'lack of status and promotion'. Some minority ethnic teachers reported that ethnic discrimination on a daily basis or at least several times per week was a contributory factor in their experience of stress. Many of the teachers believed they worked within an institutionally racist environment. Multiple regression analysis discovered that 'total stress', 'total self-esteem', 'working conditions job satisfaction' and 'total discrimination' were the major predictors of mental ill-health in the minority ethnic teachers. Job dissatisfaction was predicted by 'total discrimination', 'workload', 'total general health', 'resolution strategy', and the 'lack of status and promotion'.

Flap advancement and core fistulectomy for complex rectal fistula.

BACKGROUND: The treatment of low fistula in ano is well accepted but controversy surrounds the management of high trans-sphincteric fistulas and more complex fistulas. This study assesses the clinical results of advancement flap techniques in association with core fistulectomy for complex fistula in ano. METHODS: A retrospective analysis of the use of advancement flap techniques together with core fistulectomy in 25 patients (26 fistulas) was performed. Clinical outcome was assessed in terms of fistula healing, continence, failure and technical problems. RESULTS: Successful healing of 20 of the 26 complex fistulas was achieved using this technique with no disturbance of continence and minimal (technical) complications. CONCLUSION: Flap advancement and core fistulectomy is a safe, effective procedure for complex rectal fistulas with good functional results and minimal or no disturbance of continence, and should be considered for the treatment of complex perianal fistulas.

Autologous transfusion: an alternative to transfusion with banked blood during surgery for cancer.

Autologous blood transfusion in surgery for cancer has been avoided because of the metastatic potential of reinfused malignant cells. This study determined whether viable tumour cells remain in the red cell concentrate after separation and whether blood transfusion filters remove these tumour cells before reinfusion. Units of banked blood were inoculated with tumour cell lines: breast cancer SKBr3; colon cancer COLO 320; lymphoma Daudi; erythroleukaemia K562. After processing with the Cell Saver, aliquots of the red cell concentrate and waste saline wash were examined for tumour cells and cultured. Tumour cells from all four cell lines were identified in the red cell concentrate but not in the waste saline wash. All the cell lines except Daudi grew from the red cell concentrate. Experiments on two of the cell lines (SKBr3 and COLO 320) were performed in which the red cell concentrate was either unfiltered (control) or filtered with SQ40S blood transfusion filter or RC100 leucocyte depletion filter. Both cell lines were present in the control samples and after filtration with SQ40S filters, and cells from these samples grew normally in culture. No tumour cells were evident after filtration with the RC100 filters and no growth of either cell line was found after 1 week in culture. The Cell Saver in combination with RC100 filters may be suitable for use during the surgical treatment of malignant disease.

Somatostatin binding in normal and malignant human gastrointestinal mucosa.

Somatostatin is a regulatory peptide implicated in the control of cellular proliferation in epithelial tissues and this regulation may occur directly via membrane bound receptor activation. The aim of this study was to investigate somatostatin binding in human gastrointestinal cancer and normal mucosa. Plasma membranes were prepared from specimens of tumour and normal mucosa from 51 patients undergoing surgical resection for malignancy (28 gastric, 23 colorectal). Using a competitive displacement assay, specific 125I-tyrosine-11-somatostatin-14 binding to plasma membranes was assessed and and characterised in terms of receptor affinity (Kd) and maximum binding capacity (Bmax) as determined by Scatchard analysis. Specific low affinity (Kd = 166 nM), high capacity (Bmax = 1.2 pmol mg-1 protein) somatostatin binding was demonstrated in 22 of the gastric cancers and 17 of the colorectal cancers (Kd = 140 nM, Bmax = 1.8 pmol mg-1 protein). Similar affinity and binding capacity was demonstrable in normal mucosal samples. High affinity receptors for somatostatin were expressed by one gastric carcinoma (Kd = 0.9 nM; Bmax = 0.23 pmol mg-1 protein). Thus, low affinity, high capacity binding is a common feature of gastrointestinal tumours and normal mucosa, and high affinity receptors may occasionally be demonstrated. The functional significance of these low affinity binding sites requires elucidation to determine whether long-acting somatostatin analogues may have therapeutic benefit in gastrointestinal malignancy.

Characterization of a bombesin/gastrin-releasing peptide receptor on a human gastric-cancer cell line.

This study examined the expression of receptors of the bombesin (BBS) family in human gastric-cancer cell lines. Of 5 cell lines screened, only one, St42, demonstrated specific binding sites for 125I-Tyr4-BBS, which have been further characterized. This binding was saturable, and temperature- and time-dependent. Scatchard analysis of displacement data performed at 37 degrees C revealed 2 binding sites: a high-affinity, low-capacity site (KD = 0.13 nM, Bmax = 1500 sites/cell) and a lower-affinity, higher-capacity site (KD = 11 nM, Bmax = 35,000 sites/cell); the latter was lost when internalization of peptide was prevented, suggesting that it may be an artefact. Displacement assays with gastrin-releasing peptide (GRP) and neuromedin B (NMB) revealed that the receptor was of the GRP-preferring sub-type (GRP IC50 = 0.35 nM; NMB IC50 = 112 nM). Co-valent cross-linking of 125I-Tyr4-BBS to the receptor demonstrated the presence of a single band corresponding to a molecular weight of 37 to 44 kDa on SDS-PAGE, similar to that of the cloned GRP receptor protein core. G-protein linkage of this receptor was demonstrated by selective inhibition of 125I-Tyr4-BBS binding by guanosine nucleotides. The binding of BBS to the receptor resulted in a rise in intracellular calcium. Three of four structurally distinct BBS antagonists bound to the receptor with high affinity, but [DPhe12, Leu14]-bombesin did not cause any displacement of 125I-Tyr4-BBS even at 10 mM. The functional significance of GRP receptors on human gastric-cancer cells is as yet unknown, but further studies may determine whether such receptors have importance in the therapy of gastric cancer.

Somatostatin binding in human gastrointestinal tissues: effect of cations and somatostatin analogues.

This study characterises the somatostatin binding site in human gastrointestinal cancer and mucosa in terms of cationic specificity and relative affinity for three somatostatin analogues. Competitive displacement assays were performed on plasma membranes from human gastric and colonic tissues using radiolabelled somatostatin-14 as ligand. Comparison was made with the somatostatin binding site in rat cerebral cortex. In gastrointestinal tissue, magnesium decreased and sodium increased specific binding. By contrast, in rat cerebral cortex, the converse cationic effect was seen. These changes resulted from alterations in receptor density, with no change in receptor affinity. Displacement studies were then performed with somatostatin-14 and somatostatin analogues RC-160, somatuline, and octreotide. RC-160 and somatuline displaced radiolabel from binding sites in gastric and colonic cancer and mucosa with 10-fold lower affinity than the native peptide. Octreotide did not displace radioligand in gastric or colonic cancer at any concentration tested. By contrast, in rat cortex, although all three analogues displaced with a lower affinity than the native peptide, there was no difference between analogues. These data suggest a distinct somatostatin receptor subtype in gastrointestinal tissues.

High-affinity binding sites for gastrin-releasing peptide on human colorectal cancer tissue but not uninvolved mucosa.

Human colorectal cancer tissue and matched uninvolved mucosa from 21 patients were examined by radioligand displacement for the presence of binding sites for bombesin-like peptides. Five cancers, but no uninvolved mucosa, expressed high-affinity, low-capacity bombesin binding sites (Kd = 6.53 nM, Bmax = 58.6 fmol mg-1 protein) of the gastrin-releasing peptide (GRP)-preferring subtype (IC50 4.8 nM). Bombesin-like peptides may have a role in the pathogenesis of colorectal cancer, and bombesin receptor antagonists may be of value in the treatment of receptor-positive tumours.

Randomized clinical trials to determine the role of topical glyceryl trinitrate in peripheral intravenous nutrition.

BACKGROUND: The contribution of glyceryl trinitrate (GTN) to prevention of peripheral vein thrombophlebitis (PVT) during peripheral intravenous nutrition delivered by fine-bore midline intravenous catheter is unclear. The aim of this study was to establish its role. METHODS: Two consecutive randomized clinical trials were conducted. In trial 1 patients were randomized to receive standard peripheral intravenous nutrition containing heparin and hydrocortisone with or without the placement of a topical GTN patch (triple therapy or dual therapy). In trial 2 patients were randomized to receive standard peripheral intravenous nutrition with either dual therapy or topical GTN alone (monotherapy). RESULTS: Dual therapy was as effective as triple therapy in preventing PVT (incidence 10 of 37 versus 11 of 39 patients respectively). Dual therapy reduced the incidence and increased the time to onset of PVT compared with monotherapy (14 of 41 versus 22 of 35 patients respectively, P = 0.012; median 17.3 (95 per cent confidence interval (c.i.) 13.4 to 21.1) versus 8.9 (95 per cent c.i. 6.7 to 11.0) days, P = 0.007). CONCLUSION: Use of a topical GTN patch confers no benefit when peripheral intravenous nutrition is delivered via a fine-bore midline intravenous catheter.