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ABSTRACTVascular endothelial growth factor (VEGF) is an angiogenic cytokine that regulates tumour angiogenesis. The prognostic significance of VEGF expression remains incompletely investigated for patients with oesophagogastric cancer. This study assesses the significance of tumour VEGF (T-VEGF) and circulating VEGF (C-VEGF) expression in a 10-year follow-up of patients with oesophagogastric cancer. Patients undergoing surgical resection were prospectively recruited between February 1999 and August 2000. Circulating VEGF, derived both from plasma (P-VEGF) and serum (S-VEGF), and T-VEGF were assessed using a commercial enzyme-linked immunosorbent assay (ELISA). As platelet count may contribute to C-VEGF, pre-operative platelet levels were also recorded to exclude a confounding effect. Patients were followed up over a 10-year period using the Northern Ireland Cancer Registry. Sixty-one patients were recruited (men=45) with a mean age of 65.7 years. The 10-year survival was 19.7% (n= 12) with a median follow-up of 808 days (inter-quartile range [IQR]: 349.5-2358.5). Union for International Cancer Control (UICC) tumour staging was Stage I=9 (14.8%), Stage II=15 (24.6%), Stage III=33 (54.1%) and Stage IV=4 (6.6%). The only significant relationship between clinicopathological features and the study variables was for S-VEGF, which was elevated in patients with advanced T-stage (P=0.05). Circulating VEGF did not correlate with platelet count. Although a trend towards decreased survival was observed for patients who had positive lymph nodes (P=0.08) and advanced UICC stage (P=0.09) on univariate analysis, only lymphovascular invasion significantly predicted poor prognosis in this cohort (P=0.05). Therefore, ELISA quantification of circulatory or tumour VEGF does not appear to be a significant predictor of mortality in patients with oesophagogastric cancer.

This study compares the posterior auscultatory triangle thoracotomy incision (muscle sparing) with full posterolateral thoracotomy (where latissimus dorsi muscle is always cut across its full width), with particular attention to the difference between latissimus dorsi muscle strength, post operative pain and chronic wound related symptoms.

Learning hand-eye coordination is a crucial part of the training programme for junior laparoscopic surgeons. This study compares laparoscopic psychomotor performance from traditional standard abdominal box-training and virtual-reality training. Twenty-four right-hand dominant subjects with no experience in laparoscopy were required to complete a novel laparoscopic task. Eight subjects completed all six tasks on the Minimally Invasive Surgical Trainer Virtual Reality (MIST VR) training program. Another 16 subjects were case-matched to these subjects for gender, sight-corrected status and age (± 2 years). Eight of these subjects spent the same amount of time as their yoked MIST VR counterpart training on a traditional laparoscopic cutting task. The other eight subjects, the control group, received no training. Individuals who trained on the MIST VR program made significantly more correct incisions than their case-matched counterparts in the standard trained group (p < 0.05) and control group (p < 0.0001) and were also significantly more likely to use both hands to perform the task (p < 0.02). Virtual reality appears to offer potential as a laparoscopic laboratory-training tool for the acquisition of psychomotor skills that transfer to novel laparoscopic tasks.

Anastomotic recurrence is a major cause of late mortality following oesophago-gastrectomy (OG) for carcinoma of the oesophagus and oesophago-gastric junction using either the Ivor Lewis or left thoraco-abdominal approach with intra-thoracic anastomosis. The aim of this study was to determine whether the more extensive total thoracic oesophagectomy (TTO) with cervical anastomosis would reduce the anastomotic recurrence rate while maintaining acceptable operative morbidity and mortality.

Abstract Background Resection is the treatment of choice for lung cancer, but may cause impaired cardiopulmonary function with an adverse effect on quality of life. Few studies have considered the effects of thoracotomy alone on lung function, and whether the operation itself can impair subsequent exercise capacity. Methods Patients being considered for lung resection (n = 106) underwent full static and dynamic pulmonary function testing which was repeated 3–6 months after surgery (n = 53). Results Thoracotomy alone (n = 13) produced a reduction in forced expiratory volume in one second (FEV ₁; mean (SE) 2.10 (0.16) versus 1.87 (0.15) l; p&lt;0.05). Wedge resection (n = 13) produced a non-significant reduction in total lung capacity (TLC) only. Lobectomy (n = 14) reduced forced vital capacity (FVC), TLC, and carbon monoxide transfer factor but exercise capacity was unchanged. Only pneumonectomy (n = 13) reduced exercise capacity by 28% (P|$$|APVo ₂ 23.9 (1.5) versus 17.2 (1.7) ml/min/kg; difference (95% CI) 6.72 (3.15 to 10.28); p&lt;0.01) and three patients changed from a cardiac limitation to exercise before pneumonectomy to pulmonary limitation afterwards. Conclusions Neither thoracotomy alone nor limited lung resection has a significant effect on exercise capacity. Only pneumonectomy is associated with impaired exercise performance, and then perhaps not as much as might be expected.

1.The effect of [K]0 on the current-voltage relationship is described. In the negative potential range the curves cross over as [K]0 is increased. At positive potentials the curves re-cross so that in low [K]0 there is more outward current than in high [K]02.Chord conductance has been calculated from the current-voltage relationship and this is taken as a measure ofgK. It is shown thatgK is a function of both the potassium driving force (EM-EK) and [K]0.3.Current-voltage relationships obtained by the voltage clamp technique have been compared to net current-voltage relationships obtained by phase plane analysis of the action potential. [K]0 is shown to have similar effects on both.4.The effect of [K]0 at positive potentials suggests that delayed outward current during large depolarizing voltage clamp steps is due to an activation of a time-dependent outward current and not to potassium accumulation. An analysis of current tails also suggests the presence of a time-dependent outward current.5.In contrast delayed outward current changes during small depolarizing voltage clamp steps are probably due to potassium accumulation.6.Evidence is presented which indicates that inward current tails following depolarizing voltage clamp steps are due to potassium accumulation.

The parasite fauna of cultured and wild fish in an eutrophic lowland freshwater loch in the west of Scotland was studied and compared in order to assess the impact of 4 years' fish culture activity on the natural fauna. Strigeid metacercariae dominated the fauna but infection was lower in caged trout than in feral trout and wild fish. Important protozoan pathogens were present and were probably introduced with stocked fish. Intensity of protozoa was low, probably due to therapeutic chemical treatments, with the exception ofTrichodina sp. which was a persistent problem. Endoparasitic helminths typical of salmonids were absent. The introduction of a new host species had little effect at this stage on the diversity of the parasitic helminth fauna but probably influenced the relative abundance of certain species.

The issue of performing simultaneous pulmonary resection and cardiac surgery in patients with coexisting lung carcinoma and ischaemic heart disease remains controversial. We report our experience and review the literature.

In sheep and calf ventricular bundles, increasing the internal calcium by increasing the frequency of voltage‐clamping to plateau range potentials increased the time‐independent outward current. This effect was more marked with higher [Ca]o, and was reduced if the Ca current blockers Verapamil or D 600 were used. 2. If the internal Ca was increased by the addition of cyanide and reduction of external sodium the outward current was also increased. The frequency‐dependent increase in outward current also occurred in this Na‐poor (12 mM) solution. 3. Tension measurement on the ventricular bundles showed that a Na‐free solution with cyanide did not cause a contracture. On changing from Tyrode to a Na‐free solution containing cyanide, and on changing back to Tyrode there was a potentiation of the twitch. 4. In Na‐poor solution with cyanide, although no contracture was found, ECa was less positive, suggesting that under these circumstances Ca accumulates at the inner side of the membrane, but not around the myofibrils. 5. The prolongation of the action potential in Cl‐free solution is frequency‐dependent. A greater prolongation is seen at lower frequencies suggesting that Cl current is relatively more important for repolarization at lower frequencies of stimulation. 6. It is suggested that calcium at the inner side of the membrane sets the level of the background outward current. A feed‐back mechanism on this basis is proposed for the control of the action potential duration. Various factors that could influence this basic mechanism are discussed.

A method for mounting and rapidly perfusing small ventricular trabeculae (diameter around 250 micron) from either ferret or guinea‐pig is described. Tension, membrane potential (Em) and intracellular Na activity (aiNa) were measured. aiNa was measured using Na‐sensitive micro‐electrodes. At room temperature (22‐26 degrees C), [Na]o 155 mmol/l and [Ca]o 5.4 mmol/l, aiNa was 10.9 mmol/l +/‐ S.D. 4.2 mmol/l (n = 148). When [Na]o was reduced from 155 to 1.5 mmol/l contractures developed. These were about twitch height in guinea‐pig but less than the twitch height in ferret. Associated with the development of the contracture there was a decrease in aiNa. The aiNa halved within 30 s. The decrease in aiNa was not influenced by changing pHo from 7.4 to 9.5, K‐free solution or strophanthidin 50 mumol/l and was not passive since, even when the [Na]o was 1.5 mmol/l, the driving force for Na ions remained inward. The aiNa decreased if [Ca]o was increased and [Na]o decreased or vice versa. On the basis of these findings it is concluded that the decrease in aiNa is mainly due to Na/Ca exchange. Despite the large decrease in aiNa the [Ca]i, as monitored by tension changes, hardly increased. Since Ca uptake does occur in Na‐free conditions in heart muscle it is proposed that the mitochondria take up Ca ions and so prevent an excessive rise in cytoplasmic Ca. Strophanthidin increased both aiNa and the withdrawal contracture, but collected results from a number of experiments showed no clear correlation between the initial aiNa and contracture amplitude. Strophanthidin may, therefore, have actions additional to increasing aiNa.

Gastrin conjugated to bovine serum albumin was administered to New Zealand white rabbits by repeated injections at a standard immunizing dose of 2 mg BSA-gastrin conjugate, as well as at 0.2 mg (10%) and 0.02 (1%) of BSA-gastrin conjugate. The intermediate dose of immunogen (0.2 mg) was also given by multiple simultaneous intradermal injections, with one later booster immunization. Resultant antisera from footpad injected rabbits were found to be of comparable high affinity, which was uninfluenced by the size of the administered dose of antigen conjugate. Antibody binding sites concentrations in these antisera, however, were found to be proportional to immunizing dose. Antibodies to gastrin produced after intradermal injection, although of comparable serum antibody concentrations, were of significantly lower affinity than after footpad immunization. It is concluded that high affinity antisera suitable for use in radioimmunoassay of gastrin can be produced by footpad immunization utilizing a small fraction of the standard immunizing dose of gastrin-bovine serum albumin conjugate.

The present study was performed to test the effect of oral bethanechol (B) on endogenous gastrin release, both basally and in association with the physiologic stimulus of a protein meal. Serum gastrin levels were obtained from 10 normal subjects following: (1) an oral placebo; (2) an oral dose of 25 mg of B; (3) a 100-g protein meal plus placebo; and (4) a 100-g protein meal plus 25 mg of B. Following B or placebo there were no significant changes in basal serum gastrin levels of 98.7±29.3 (±se) pg/ml and 82.4±12.3 pg/ml, respectively. Significant increases of serum gastrin occurred after the protein meal (P<0.01) and after the protein meal combined with B. The gastrin levels thus obtained were significantly greater than basal values but not different from each other. It is proposed that LES pressure increases following B are not due to the release of endogenous gastrin as shown by the absence of increases in basal serum gastrin levels and failure to augment the gastrin release of a physiologic stimulus.

A retrospective study was performed to assess the advantages and disadvantages of a video-assisted thoracoscopic approach (VTS) to the surgical management of primary spontaneous pneumothorax compared with the standard posterolateral thoracotomy (PLT) or posterior muscle sparing (PMS) approaches. It was possible to make comparisons between 12 VTS, nine PLT and six PMS patients who underwent unilateral apical bullectomy/stapling with apical pleurectomy/abrasion for primary spontaneous pneumothorax. The groups were evenly matched with regards age, sex and incidence of pneumothorax. The operative time for VTS was significantly greater than for PLT (P = 0.014) but not for PMS (P = 0.297) procedures. VTS procedures resulted in significant decreases in the overall period of pleural drainage compared with PLT (P = 0.031) and PMS (P < 0.001) procedures. Patients having a VTS procedure had a median hospital stay of 3 days, significantly shorter than that associated with the other approaches (PLT, P < 0.001; PMS, P < 0.001). The daily in-hospital analgesic requirements were similar for all groups. Using VTS an identical operation can be performed with smaller incisions and shorter hospital stay. Long-term recurrence rates and length of time off work will eventually determine whether VTS is a more economic approach to pleurectomy.

Human gastrin I heptadecapeptide, infused intravenously to healthy volunteers in a dose of 0.5 µg/kg/hr, caused a prompt, significant reduction in gastric potential difference (decrease of mucosal negativity), with the peak change at 6 min. This decline in potential difference occurred at a time when the serum gastrin level was between 24 and 83 pg/ml; at the same time, scanning electron microscopic examination of fractographs of parietal cells demonstrated marked increase in canalicular membrane area. This study shows that the decrease in potential difference after gastrin occurs with serum gastrin levels which are in the physiologic range.

Summary: The present studies were directed to examine the effect of gastrin-releasing peptide (GRP) on β-adrenergic stimulated gastrin release by cultured rat antral mucosa and to assess the anatomical relationship between gastrin cells and GRP nerves in rat and human antrum. Peptide-containing cells were identified by application of an avidinbiotin-peroxidase immunocytochemical double staining method utilizing antibodies to GRP and gastrin prepared in rabbits. Rat antral mucosa was cultured for 60 min and gastrin released into the culture medium was measured by radioimmunoassay. Inclusion of antibodies to GRP in culture medium did not affect carbachol-stimulated gastrin release, whereas isoproterenol-stimulated gastrin release into the medium was inhibited significantly by addition of GRP antiserum to the culture medium. GRP-containing neurons and axonal fibers were stained immunocytochemically with diaminobenzidine (reddish-brown specific staining) and were located in the lamina propria adjacent to and surrounding the main lobules of antral glands. After double staining utilizing 4-Cl-1-Naphthol as substrate, blue stained gastrin-containing cells were identified in the middle and deeper regions of antral glands in close proximity to GRP neuronal elements. These studies suggest that β-adrenergic, but not cholinergic, stimulation of gastrin release is mediated, at least in part, through GRP. They also demonstrate intimate anatomical, as well as functional, relationships between gastrin cells and GRP-containing neurons.

Summary The modern view of the mammalian ventricular action potential is that Na-ions are responsible for depolarization, the plateau is maintained by an inward Ca current and repolarization is due to the inactivation of this inward Ca current against a background outward K current. The electrical activity spreads over the surface and T-tubules of the cell and the inflow of Ca-ions, and possibly also the electrical signal, cause, a further release of Ca from internal stores, the lateral cisternae of the sarcoplasmic reticulum (SR). This released Ca, by triggering the splitting of ATP, induces contraction. The released Ca is pumped back into the longitudinal SR and, as the Ca concentration is reduced, relaxation occurs. The Ca in the longitudinal SR is transported back to the storage site in the cisternae. This completes the cycle, release, uptake, transport back to the releasing site. On the basis of this scheme, the action of various drugs is briefly discussed.

Ventricular cells possess two Ca extrusion mechanisms, a Na/Ca exchange system and a Ca pump. Reversing the exchanger by extracellular Na removal causes [Na]ito decrease, and the cells take up mmolar quantities of calcium. Since [Ca]ishows only a marginal increase the calcium load must be buffered. The capacity of the SR is limited so the mitochondria probably buffer a large part of this load. However, when Ca uptake into the mitochondria is blocked, the gain in Ca is still mmolar and the increase in [Ca]istill marginal, suggesting an additional buffering site. Measurements of the Na/Ca stoichiometry on sarcolemmal vesicles gave a value of 3, but in ventricle values of around 2.5 or 3 are found. Reasons for this are discussed, as are the differences amongst the different methods of Ca measurement. The interaction of the sarcolemmal Ca pump and the exchanger are considered and it is suggested they could interact via [Na]i, At rest both systems could remove Ca from the cell but on a large perturbation the Na/Ca exchange would be the more important of the two.

1. The exchanges of potassium and various other substances have been measured in beating frog's ventricles, using both superfused and distended preparations. In both preparations the high fluid flow rates used (1 ml./sec) cleared the ventricular cavity with a half‐time (T½) of about 130 msec.

1. A new perfused preparation of frog's ventricle is described, whose main advantage is that there are short diffusion distances between the cells and the washing fluid.

Acute tonsillitis is a common condition and usually runs a benign course. However life-threatening complications do still occur, even in this postantibiotic era. Infection can spread downwards into the mediastinum through the anatomic cervical spaces, causing widespread cellulitis, necrosis, abscess formation and sepsis. We present a case of descending mediastinitis in an 18-year-old woman, arising from her first episode of tonsillitis and treated successfully by surgical drainage. We believe that an awareness of this complication, early diagnosis using computed tomography scanning, and prompt, adequate surgical drainage will reduce morbidity and mortality.

From 1981 to 1987 nine patients have undergone resection and reconstruction of the oesophagus as an emergency, using a two-part left-sided approach with oesophagogastric anastomosis in the neck. Five patients had oesophageal perforation with a carcinoma; one had spontancous perforation of an intrathoracic stomach: two had severe haemorrhage; and one had acute sterile mediastinitis. Following operation there was one postoperative death (11 per cent) and no major complications. Long-term survival was marred only by the development of further malignancy in four patients. Subtotal oesophagectomy has both theoretical and practical advantages over conventional oesophagogastrectomy in oesophageal emergencies and we suggest that it should be considered as the method of choice in the management of these difficult cases.

Mr and Mrs W were admitted to the regional thoracic unit with sternal fractures following a head-on road traffic accident at a combined speed greater than 70 mph. Both were wearing lap–shoulder seat-belts, but only the driver's side had an air bag, which deployed normally on impact. They were assessed and treated according to the Royal College of Surgeons Advanced Trauma and Life Support guidelines at the crash site and transferred to the regional trauma centre for further assessment and treatment. Manual extraction from the vehicle was not required.1. What further information from the paramedic team would be helpful in this situation?Both Mr and Mrs W complained of severe retrosternal pain exacerbated by inspiration. No other complaints were noted. Both patients had normal Glasgow Coma Scales and remained haemodynamically stable. ach had bruising and marked tenderness over the sternum. Mr W had further bruising and tenderness over the right supraclavicular fossa but no other abnormality. Auscultation confirmed normal heart sounds, and satisfactory air entry to both lung fields without added sounds. The rest of the clinical assessment was unremarkable. Both patients were previously well and smoked (20/day).2. What initial investigations would you request?Haematological investigations were normal with haemoglobin concentrations of 14.4 g/dl and 13.9 g/dl respectively. Serum creatinine kinase was raised as expected but the myocardial band isoform remained normal. Twelve-hour serum troponin-1 was also normal. Electrocardiograph demonstrated normal sinus rhythm with no acute changes. The sternal view radiograph revealed sternal fractures in both individuals with increased displacement of the posterior table in Mr W's X-ray. Frontal radiograph of the chest performed in both patients did not reveal any evidence of rib fractures, pneumothorax or haemothorax.3. What are the treatment options for both patients?Both patients were treated conservatively with oral analgesia, inhaled nebulisers, chest physiotherapy and monitored by cardiac telemetry for 24 hours. Throughout the admission, Mr W complained of more severe sternal tenderness than his wife, who remained comfortable. He also complained of back pain. Repeat clinical examination showed soft tissue tenderness at the level of the thoracic vertebrae. Thoracic spinal X-rays demonstrated old crush fractures with no acute injury. No active intervention was required following orthopaedic assessment.Mrs W was discharged well on day 3 and Mr W on day 4. Mr W was reviewed 2 weeks post-discharge complaining of persisting sternal pain. Clinical examination elicited sternal tenderness as before but also a firm swelling in the line of his seat belt at the right supraclavicular fossa. Ultrasound showed a resolving haematoma with no evidence of a traumatic false aneurysm. At 6-month review, Mrs W remained well but Mr W still complained of persistent sternal tenderness requiring regular oral analgesia. Check X-rays of both patients showed healing sternal fractures with no other abnormality. No other investigation or treatment was required and they were discharged.

THESE experiments were started to test the flux predictions made by Noble1from his equations used to describe the action potential of Purkinje fibres. The experiments were done on frog ventricle, as this is the most suitable tissue histologically. Although the results are in general agreement with these equations, they suggest a considerably greater diminution in the potassium permeability during the plateau of the cardiac action potential than that used for the equations.