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Current practice is to report and manage likely pathogenic/pathogenic variants in a given cancer susceptibility gene as though having equivalent penetrance, despite increasing evidence of intervariant variability in risk associations. Using existing variant interpretation approaches, largely based on full-penetrance models, variants in which reduced penetrance is suspected may be classified inconsistently and/or as variants of uncertain significance. We aimed to develop a national consensus approach for such variants within the Cancer Variant Interpretation Group UK (CanVIG-UK) multidisciplinary network.

Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice.

The importance of appropriate equipment to manage the difficult airway has been highlighted by the publication of the Australian and New Zealand College of Anaesthetists (ANZCA) guidelines in 2012. We set out to audit compliance with these guidelines in all public and private sites providing general anaesthesia in metropolitan Perth. Public and private healthcare websites identified 39 sites of which 37 were studied. Institutional and ethics approval was obtained. A tick-box design audit tool, based on the ANZCA guidelines, was used to collect information regarding the dedicated difficult airway container (DDAC) at each site. As recommended in the guidelines, only equipment within the DDAC was considered. Further data about each site, including the number of theatre suites, satellite anaesthetic areas, use of capnography and categories of patients treated (adult, obstetric and paediatric) were collected. An adult DDAC was found at 92% of all sites, but none of the sites had all the essential equipment listed in the ANZCA guidelines. There was limited provision of adult difficult airway equipment within private sites compared to public, and less provision of paediatric difficult airway equipment across all sites treating paediatric patients in metropolitan Perth. Capnography was available in 76% of post anaesthesia care units and used regularly in 27%. Adherence to the ANZCA guidelines regarding the DDAC could be improved. Standardised equipment across a metropolitan region would be of value in the management of the difficult airway.

Children undergoing anaesthesia are prone to hypothermia. Perioperative monitoring of patient temperature is, therefore, standard practice. Postoperative temperature is regarded as a key anaesthetic performance indicator in Australian hospitals. Many different methods and sites of temperature measurement are used perioperatively. It is unclear to what degree these methods might be interchangeable. The aim of this study was to determine the relationships between temperatures measured at different sites in anaesthetised children. Two hundred children, 0 to 17 years, undergoing general anaesthesia for elective non-cardiac surgery, were prospectively recruited. Temperature measurements were taken in the operating theatre concurrently at the nasopharynx, tympanic membranes, temporal artery, axilla and skin (chest). Patient age and weight were documented. Temperatures varied according to site of measurement. The mean difference from nasopharyngeal temperature to temperatures at left and right tympanic, temporal, axillary and cutaneous sites were +0.24°C, +0.24°C, +0.35°C, −0.38°C and −1.70°C, respectively. Levels of agreement to nasopharyngeal temperature were similar at tympanic, temporal and axillary sites. Tympanic and temporal temperatures were superior to axillary temperatures for detection of mild hypothermia (<36°C). Skin temperature showed a large variation from nasopharyngeal measurements. Our findings indicate that measured temperatures vary between sites. Understanding these variations is important for interpreting temperature readings.

One hundred and eighty-one patients with carcinoma of the upper thoracic oesophagus were intubated perorally using a Procter Livingstone tube. The mortality was 16·6 per cent but, in the patients who survived, the palliation achieved, as judged by improved swallowing, was considered satisfactory. Factors influencing the success of intubation are also considered.

The pressure profile of the gastro-oesophageal junctional zone was studied at rest and during abdominal compression in 26 duodenal ulcer patients after subdiaphragmatic truncal vagotomy with a drainage procedure. An ‘early’ group of 9 patients was investigated 10–14 days after surgery and a ‘late’ group of 17 patients more than 1 year after operation. Comparisons were made with 25 control subjects.The resting lower oesophageal sphincter pressures after vagotomy in both the early and late groups were similar to the levels of sphincter pressure in the controls. However, the increase in sphincter pressure always observed during abdominal compression in normal subjects was significantly decreased by complete vagotomy, and the normal increase in the gastrosphincteric pressure gradient was not produced.All 26 patients were tested for completeness of vagotomy using the insulin/pentagastrin test. In 19 patients the vagotomy was complete and in 7 patients it was judged to be incomplete. A decrease in the gastro-sphincteric pressure gradient on manometric study of the lower oesophageal sphincter was interpreted as indicating complete vagotomy. Accurate correlation between secretory response and compression response was achieved in all patients with complete vagotomy and in 5 of the 7 patients with incomplete vagotomy.

A prospective randomized controlled trial has compared single dose systemic cefuroxime (n = 27) or intra-incisional cefuroxime (n = 26) with a control group (n = 28) in 81 patients undergoing gastric resection, revision gastric surgery or operation for gastro-oesophageal malignancy. In the controls the incidence of sepsis was: 35 per cent wound infection, 29 per cent abscess, 21 per cent septicaemia. After intra-incisional cefuroxime the incidence was: 4 per cent wound sepsis, 19 per cent abscess and 4 per cent septicaemia. After systemic cefuroxime only 2 patients developed wound sepsis (7 per cent) with no cases of abscess or septicaemia. Excluded from this high risk group were 36 patients who had a vagotomy with or without drainage during the trial where antibiotics were not given, 4 of whom developed wound sepsis only (11 per cent). There was a poor correlation between the individual species isolated from the gastric aspirate and the organisms responsible for postoperative infection in the controls, but there was a good correlation between fasting gastric pH and the risk of sepsis in the controls.

A series of 58 cases of traumatic diaphragmatic hernia following blunt and penetrating injury is reviewed. The problems of radiodiagnosis are outlined and the need for barium contrast studies of the entire gastrointestinal tract to ensure recognition of isolated small bowel herniation is emphasized. Surgical access via laparotomy is recommended in the immediate post-traumatic presentation, whereas thoracotomy is preferable in cases diagnosed after a latent interval. Penetrating injury resulted in smaller diaphragmatic defects, greater morbidity and higher mortality due mainly to infective complications.

Stimulated neutrophils (PMNs) produce large quantities of superoxide anion, which is the precursor for hydrogen peroxide (H2O2). We developed a new fluorimetric assay to measure the H2O2 released by zymosan A-activated PMNs utilizing the oxidation ofp-hydroxyphenylacetic acid by H2O2 to its fluorescent dimer in the presence of horseradish peroxidase. Zymosan-activated PMNs isolated from nine healthy volunteers and 20 patients with acute hypoxemic respiratory failure (AHRF) released after 90 min 2.3±0.3 and 2.4±1.3 nmol H2O2/106 PMNs, respectively. Inhibition of the heme enzymes by 1.0 mM sodium azide (NaN3) increased the H2O2 production to 21.6±4.4 nmol H2O2/106 PMNs in the control group (P<0.001), and to 22.5±14.7 nmol H2O2/106 PMNs in patients with AHRF (P<0.001). Incubation temperature, room temperature or 37‡C, did not change the total amount of H2O2 produced after 90 min by zymosan-activated PMN. Addition of NaN3 improved both the sensitivity and reproducibility of the measurement of H2O2 and allowed detection of H2O2 released by PMNs with coefficients of variation of less than 5% at PMN concentrations as low as 0.1×106 cells/ml. The amount of H2O2 released by activated PMNs did not distinguish healthy controls from patients with AHRF.

Readers′ comprehension and eye-fixations are monitored as they read descriptions of simple machines, pulley systems. The comprehension data indicate that readers′ comprehension depends on both the medium of instruction and the ability of the reader. The conjunction of text and diagrams particularly facilitated the understanding of how the pulley system moved, whereas either medium alone was sufficient for conveying the system configuration. The eye-fixation data indicate that subjects integrate the information in the text and diagram at the level of individual pulley-system components or groups of connected components. They read the text in increments, often rereading the information about a component or group of components before constructing a spatial mental model of these components with the aid of the diagram. Subjects′ diagram inspections vary from local inspections concerned with encoding the relations between two or three components to global inspections concerned with integrating the relations between many components.

Thirteen patients with chronic pepticulcer disease (two with duodenal ulcer and eleven with recurrent ulceration after previous gastric surgery) were studied. In each patient plasma-gastrin was measured before and after meat-extract ('Oxo') test meal. In six patients (group A) fasting plasma-gastrin was 497±44 pg. per ml. (mean±S.D.) and in the other seven (group B) it was 185±9 pg. per ml. Peak gastrin concentration after oxo was 1304±179 pg. per ml. in group A and 405±20 pg. per ml. in group B. The integrated gastrin response was 2490±808 pg. and 601±70 pg. in groups A and B, respectively. The differences between the means for all three measurements were statistically significant. At laparotomy none of the patients had a pancreatic tumour. A hemigastrectomy was performed in each patient. The gastrin (G) cells in the resected antrum were examined by a specific immunofluorescence technique. All the patients with hypergastrinæmia (group A) had numerous G cells in their antra, whereas the patients in group B had significantly fewer G cells. Although the number of patients in each group was relatively small, these differences in the plasma-gastrin response and in the appearances of the antra under immunofluorescence were striking. It is suggested that antral-G-cell hyperplasia may be a separate clinical entity.

Two hundred successive patients with upper gastro-intestinal tract haemorrhage were admitted to a surgical unit for management. One hundred and thirty-five patients (67.5 per cent) had a chronic peptic ulcer, 33 patients (16.5 per cent) had acute lesions (either an erosive gastritis or an acute gastric ulcer), and 32 patients (16 per cent) were a mixture of other diagnoses, of which 13 (6.5 per cent) were simple conditions but 19 (9.5 per cent) were conditions with a bad prognosis, e.g., carcinoma of the stomach, oesophageal varices, aortic aneurysm. Surgery was undertaken for massive, continuing, or recurrent bleeding and was as ‘conservative’ as thought possible. In duodenal ulcer this consisted of suture of the ulcer with vagotomy and pyloroplasty, and suture of the ulcer with vagotomy where possible in cases of anastomotic ulcer. In gastric ulcer only those less than 2 cm. in diameter were treated by suture with vagotomy and pyloroplasty. Ulcers greater than 2 cm. in size requiring surgery were treated by gastrectomy.In the 181 patients whose underlying condition had a good prognosis there were 7 deaths (4 per cent). In this group 81 operations were carried out; 61 were ‘conservative’ operations for peptic ulcer, 2 were for repair of a hiatus hernia, and there were 18 gastrectomies, usually for a large gastric ulcer. There were 2 deaths among the operated patients; 1 after gastrectomy and 1 after a ‘conservative’ operation. There were 5 deaths among the 100 patients in the group which was treated non-operatively. There were 8 deaths among the 19 patients with underlying conditions of grave prognosis.The case for the admission of patients with upper gastro-intestinal tract bleeding to a surgical unit is fully discussed and it is advocated together with a selective policy for operation. Where operation is necessary this should be as conservative as possible for bleeding duodenal ulcer, chronic gastric ulcer less than 2 cm. in size (ulcers of larger size may well respond but the method was not assessed for such ulcers), solitary acute gastric ulcer, and anastomotic ulcer. Gastric resection should be retained for the few patients with diffuse erosive gastritis requiring surgery and possibly for patients with a very large chronic peptic ulcer.

Artificial skin, applied as a completely synthetic bilaminate skin evolving into a completely biologic self-skin replacement, was initially used in 1980. It has been used in 121 patients to date, at the Massachusetts General Hospital and the Boston Unit of the Shriners Burns Institute with follow-up as long as ten years. This report describes the generally gratifying long-term results with the use of artificial skin in massive burns.

Chronic active hepatitis was selectively induced in mice by the feeding of a diet containing 3-hydroxy-4-pyrone (0.5% by weight) for periods of 6 weeks and longer. This model should be of particular value in elucidating the pathogenesis of drug-induced forms of chronic active hepatitis. Maltol (3-hydroxy-2-methyl-4-pyrone) did not produce any liver lesion.

Indigofera spicata Forsk (previously I. endecaphylla Jacq.) would be a useful tropical pasture legume without its toxic properties (for review, see ref. 1). It has been shown to be hepatotoxic to sheep, cows and rabbits, and has caused abortion in pregnant animals2. Hutton et al.3,4showed that the leaf and seed were hepatotoxic to rabbits and mice and that β-nitropropionic acid, which occurs only in the leaf, did not account for these liver lesions. Britten et al.5found that β-nitropropionic acid or a compound closely associated with it in the leaf was toxic to chicks, which were not affected by the hepatotoxin(s) present in the seed.

The isolation of the title compound (I) and the X‐ray structure of its hydrochloride (space group P212121, Z=4) are described.