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Background: Gallbladder cancer (GBC) is an aggressive, uncommon malignancy, with variation in operative approaches adopted across centres and few large-scale studies to guide practice. We aimed to identify the extent of heterogeneity in GBC internationally to better inform the need for future multicentre studies. Methods: A 34-question online survey was disseminated to members of the European-African Hepatopancreatobiliary Association (EAHPBA), American Hepatopancreatobiliary Association (AHPBA) and Asia–Pacific Hepatopancreatobiliary Association (A-PHPBA) regarding practices around diagnostic workup, operative approach, utilization of neoadjuvant and adjuvant therapies and surveillance strategies. Results: Two hundred and three surgeons responded from 51 countries. High liver resection volume units (>50 resections/year) organised HPB multidisciplinary team discussion of GBCs more commonly than those with low volumes (p < 0.0001). Management practices exhibited areas of heterogeneity, particularly around operative extent. Contrary to consensus guidelines, anatomical liver resections were favoured over non-anatomical resections for T3 tumours and above, lymphadenectomy extent was lower than recommended, and a minority of respondents still routinely excised the common bile duct or port sites. Conclusion: Our findings suggest some similarities in the management of GBC internationally, but also specific areas of practice which differed from published guidelines. Transcontinental collaborative studies on GBC are necessary to establish evidence-based practice to minimise variation and optimise outcomes.

Background Information is scarce regarding effects of antihypertensive medication on blood pressure variability ( BPV ) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long‐term mortality in an elderly hypertensive population. Methods and Results We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24‐hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow‐up). Weighted day‐night systolic BPV was calculated for both baseline and follow‐up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV , stable: high BPV , decline: high to low , and increase: low to high . We observed an annual decline (mean± SD : −0.37±1.95; 95% CI, −0.54 to −0.19; P BPV between baseline and follow‐up. Having constant stable: high BPV was associated with an increase in all‐cause mortality (hazard ratio: 3.03; 95% CI, 1.67–5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62–8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow‐up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Conclusions Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow‐up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long‐term mortality.

Background:Oesophageal disorders and osteonecrosis of the jaw are recognised complications of the commonly prescribed medication bisphosphonate. Despite these diagnoses being seen comparatively frequently within the ENT clinic, osteonecrosis of the external ear is a less well reported complication.Methods:The current literature is reviewed and our experience with six cases of bisphosphonate-related ear canal osteonecrosis is presented.Results:Six cases were identified as suffering from ear canal osteonecrosis as a result of bisphosphonate treatment. One of our cases suffered bilateral ear canal osteonecrosis after only 20 months of oral alendronic acid treatment. Management ranged from bisphosphonate cessation and topical treatment, to surgical debridement in the operating theatre.Conclusion:Bisphosphonate-related ear canal osteonecrosis is undoubtedly under-diagnosed. For such a commonly prescribed medication, the risks and side effects of bisphosphonate should be better known and long-term treatment should be avoided if possible.

BACKGROUND Peaches (Prunus persica (L.) Stokes) are grown in several regions throughout the USA, are eaten fresh, and used as ingredients in value-added processed products. An Internet survey was conducted to investigate Mid-Atlantic consumers' fresh and processed peach purchasing behaviors, and whether packaging certain numbers of peaches together, providing information about nutritional content, and other factors would increase purchases. Additionally, laboratory-based sensory testing was used to better understand peel color, texture, sweetness, sourness, and flavor preferences for cultivars commonly grown in the Mid-Atlantic region. RESULTS Irrespective of fresh peach consumption frequency, certain value-added products were of interest. For some products, interest in purchasing was higher than reported purchasing behavior. Preference for certain fresh peach characteristics, such as peel color, differed between less frequent fresh peach consumers and those who consumed fresh peaches more often. Of the four peach cultivars included in the sensory test, most were liked; however, there were some cultivar differences pertaining to color, texture, sweetness, tartness, and flavor liking. CONCLUSION Potential marketing strategies can be developed based on frequency of fresh peach consumption and household demographics. Data can be used to select peaches that best appeal to consumers. © 2015 Society of Chemical Industry

Microbicides are being actively researched and developed as woman-initiated means to prevent HIV transmission during unprotected coitus. Along with safety and efficacy, assessing and improving compliance is a major area of research in microbicide development. We have developed carrageenan-based semisoft vaginal suppositories and have previously evaluated how physical properties such as firmness, size and shape influence women's willingness to try them. Firmness has previously been quantified in terms of small-strain storage modulus, G', however large-strain properties of the gels may also play a role in the firmness perception. In the current study we prepared two sets of suppositories with the same G' but different elongation properties at four different G' values (250, 2500, 12,500, 25,000 Pa): For convenience we refer to these as "brittle" and "elastic", although these terms were never provided to study participants. In the first of two tests conducted to assess preference, women compared pairs of brittle and elastic suppositories and indicated their preference. We observed an interaction, as women preferred brittle suppositories at lower G' (250, 2500 Pa) and elastic ones at a higher G' (25,000 Pa). In the second test, women evaluated samples across different G', rated the ease-of-insertion and willingness-to-try and ranked the samples in order of preference. Brittle suppositories at G' of 12,500 Pa were most preferred. In vitro studies were also conducted to measure the softening of the suppositories in contact with vaginal simulant fluid (VSF). Release of antiretroviral drug tenofovir in VSF was quantified for the brittle and elastic suppositories at G' of 12,500 Pa to determine the effect of suppository type on release. The initial rate of release was 20% slower with elastic suppositories as compared to brittle suppositories. Understanding how different physical properties simultaneously affect women's preferences and pharmacological efficacy in terms of drug release is required for the optimization of highly acceptable and efficacious microbicides.

The electrospray (ES) ionization method is widely used in the analysis of biological molecules. The stable cone regime spray is usually obtained by adding methanol or ethanol to the electrosprayed dipolar fluid, with the role of reducing fluid surface tension. We investigate the spray onset voltages of water–ethanol mixtures starting from distilled water to pure ethanol. Positive or negative DC is applied separately in our measurements. The experimental setup allows for the study of nozzle-counter electrode gaps of up to 50 cm. Significant variations in the spray onset are observed and analyzed. The onset voltage and the surface tension of water–ethanol binary mixtures appear to be in line with Smith’s formula. The largest variations of onset values are observed for surface tensions of 20 mN/m–40 mN/m in the mixtures. The results of the study may be instrumental to electrospray electrode design and spray control.

Descending necrotising mediastinitis can complicate oropharyngeal infection and has a high associated mortality. We present three cases treated in our department and propose a treatment algorithm based on our experience and literature review. The primary oropharyngeal infection was peritonsillar abscess in two cases and odontogenic abscess in one. Two patients underwent cervicotomy and later thoracotomy. The third underwent cervicotomy with transcervical mediastinal drainage and later required pericardial drainage via a subxiphoid incision. All recovered fully and were discharged within 6 weeks. To enable successful treatment, diagnosis needs to be prompt and surgical drainage adequate. Thoracic management of the chest is essential.

Pharyngo-laryngo-oesophagectomy and gastric pull-up (PLOGP) is a complex and relatively uncommon procedure. The aim of this study is to analyse the results of PLOGP in patients with post-cricoid and cervical oesophageal squamous cell carcinomas.This study was a retrospective review of 26 patients (11 males + 15 females, mean age 63.5 years) who underwent PLOGP from 1988 to 1997. Eighteen (69 per cent) patients were staged as T3 and eight (31 per cent) T4. Eighteen (69 per cent) patients had N0, seven (27 per cent) N1 and one (four per cent) N2 disease. Multiple primary tumours were recorded in three (11.5 per cent) patients. Four (15 per cent) patients had pre-operative radiotherapy with poor response and two (eight per cent) required emergency tracheotomy prior to surgery. Feeding jejunostomy was performed on 19 (73 per cent) and neck lymph node dissection in eight (31 per cent) patients.The mean duration of surgery was five hours (range 3.5 to 7.5) with a mean blood loss of 840 ml (range 160 to 1800), a mean stay in ICU of 4.2 days and hospital stay ranged from nine to 84 days (mean 34). Three (11.5 per cent) patients died (pneumonia – one, congestive heart failure – one pulmonary embolus – one) in the early post-operative period. Eight (31 per cent) patients remain alive from 30 to 136 months (mean 58 months). Two (eight per cent) patients died with no evidence of disease. Thirteen (50 per cent) patients died of their disease between two to 51 months (mean 17.3 months) post-operatively. Kaplan-Meier survival estimates for one year was 65 per cent, for three years 35 per cent and for five years 26 per cent (see Figure 1). Median survival in the whole series was 18 months.Post-operative speech was with an electrolarynx in 16 (62 per cent). One patient (four per cent) used gastric speech and one patient (four per cent) used a Blom-Singer valve effectively. Five (19 per cent) patients had no speech post-operatively. All patients maintained oral feeding. Gastric transposition constitutes a safe and reliable method of restoring the continuity of the upper digestive tract following pharyngo-laryngo-oesophagectomy.

OBJECTIVE: The aim of the present study was to evaluate the long-term success of endoscopic stapling as a primary procedure for the treatment of pharyngeal pouches.METHODS: This study is a retrospective case review of 25 patients with pharyngeal pouches treated by endoscopic stapling (23 stapled, 2 abandoned) over a 4-year period (1994 to 1998) at a University teaching hospital in the United Kingdom. Outcomemeasures used were relief of symptoms over a long-term follow-up of 2 to 5 years.RESULTS: Of the 25 patients analyzed, 12 patients (48%) have remained asymptomatic after their initial stapling. Eight patients (32%) were relieved of their symptoms after revision stapling. The overall long-term success rate for endoscopic stapling was 80% (20 of 25 patients)CONCLUSION: Reduced morbidity and few complications in the elderly make endoscopic stapling a favored primary technique of treating pharyngeal pouches. Open surgery is recommended only in healthy patients with very large pouches.

Objectives We describe a rare cause of posterior triangle cervical lymphadenopathy in a third decade female, outline the clinical and histopathological features and discuss excision biopsy as the investigation of choice in this age group, with lymphoma as the diagnosis of exclusion. Case report A thirty-four year old female was referred to our Head and Neck clinic with a one-month history of left posterior triangle lymphadenopathy. She reported no other symptoms and haematological investigations were normal. She was “Red Flagged” as a possible lymphoma. Excision biopsy revealed extensive histiocytic necrotising lymphadenitis providing a diagnosis of Kikuchi-Fujimoto disease. Conclusions Persistent posterior triangle lymphadenopathy in the 16-40 year old age group warrants “Red Flag” referral to rule out serious pathology such as HIV, metastatic cancer or lymphoma. When the ENT examination and haematological work up is negative, we advocate proceeding straight to excision biopsy as the quickest way to obtain a diagnosis, which sometimes comes up with the unexpected as in this rare case of Kikuchi-Fujimoto disease.

This open-label, non-randomized, parallel-group trial investigated the pharmacokinetics of raltitrexed (Tomudex, formerly ZD1694) after a single intravenous dose of 3.0 mg m(-2), comparing eight cancer patients with mild to moderate renal impairment (creatinine clearance 25-65 ml min(-1)) with eight cancer patients with normal renal function (creatinine clearance >65 ml min(-1)). The primary end points were area under the plasma raltitrexed concentration-time curve from the start of the infusion to the last determined concentration (AUC(0-tldc)) and AUC to infinity (AUC(0-infinity)); secondary end points were peak concentrations of raltitrexed (Cmax) and elimination half-life (t(1/2gamma)). The groups were compared statistically using analysis of covariance. The AUCs were greater for patients with renal impairment than for patients with normal renal function (2452.2 compared with 1247.3 ng h ml(-1) for AUC(0-tldc) (ratio 1.97; 95% CI 1.36-2.84); 2961.5 compared with 1457.0 ng h ml(-1) for AUC(0-infinity) (ratio 2.03; 1.25-3.29). These differences were statistically significant (P = 0.002 and P = 0.008 for AUC(0-tldc) and AUC(0-infinity) respectively. Terminal half-life was longer for the renally impaired patients (271.2 compared with 143.3; P = 0.030). There was no significant statistical difference between the groups for Cmax (652.9 compared with 564.7 ng ml(-1) for patients with impaired and normal renal function respectively: ratio 1.16; 0.91-1.46; P = 0.204). There was a clear relationship between raltitrexed clearance and creatinine clearance. Adverse events, severe (WHO grade 3 or 4) toxicity and hospitalization due to adverse events were more frequent in the group with renal impairment. Therefore, a reduction in raltitrexed dose and increased interval between doses is recommended for patients with mild to moderate renal impairment.

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.

We report a case of giant cell tumour of the temporal bone arising in a 31-year-old man. The presenting symptoms were unusual, being rotational vertigo, unilateral tinnitus, and hearing loss. A computed tomography (CT) scan showed a large mass within the right temporal bone and the infratemporal fossa. The radiological appearance was suggestive of an aggressive primary neoplasm arising within bone. Biopsy and subsequent resection showed a giant cell tumour of bone. The tumour was histological grade 1. At two-year follow-up, there was no evidence of tumour recurrence or metastasis.

PURPOSE To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) with recombinant human interferon alfa-2a (Roferon-A; Hoffman La-Roche AG, Basel, Switzerland) versus the combination of 5-FU with leucovorin (LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 496 previously untreated colorectal cancer patients were randomized to receive either Roferon-A (9 MIU) subcutaneously three times per week, with 5-FU (750 mg/m2/d) by continuous intravenous (i.v.) infusion (CIV) on days 1 to 5, then, after a 9-day hiatus, as a weekly i.v. bolus at the same dose (IFN/5-FU); or LV (200 mg/m2/d) by i.v. infusion plus 5-FU (370 mg/m2/d) by i.v. bolus on days 1 to 5, repeated every 4 weeks (LV/5-FU). RESULTS There were no significant differences between IFN/5-FU and LV/5-FU in the overall response rate (21% v 18%), duration of response (7.3 v 6.2 months), or survival time (median, 11.0 v 11.3 months). Toxicity profiles differed; constitutional symptoms and myelosuppression were more frequent and more severe with IFN/5-FU, and gastrointestinal symptoms with LV/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/5-FU than with LV/5-FU. Five treatment-related deaths occurred with each regimen. CONCLUSION The combination IFN/5-FU produced response rates, response durations, and survival times similar to those with LV/5-FU. Biochemical modulation of 5-FU by either IFN or LV appears to result in equivalent efficacy; however, fewer patients were able to tolerate the specified IFN/5-FU combination used in this study.

SummaryThe aim of this study was to determine the effects of the surgical treatment of morbid obesity on some aspects of haemostatic and fibrinolytic function. Measurement of haemostatic and fibrinolytic factors was performed before and again 6 and 12 months after operation in 19 patients suffering from morbid obesity. Surgical treatment resulted in a mean decrease in body weight of 50 kg at 6 months and 64 kg at 12 months. Weight loss was accompanied at 12 months by significant reductions in median (interquartile range) concentrations of serum cholesterol from 5.3 (4.5–6.2) mmol/1 to 3.6 (2.9–4.6) mmol/1; factor VII from 113 (92–145)% of normal to 99 (85–107)%; of fibrinogen from 3.5 (3–9.3) g/1 to 2.8 (2.4–3.8) g/1; and of plasminogen activator inhibitor-1 (PAI-1) activity from 21 (11–30) IU/ml to 6.3 (5–10) IU/ml. The decrease in PAI-1 activity probably accounted for a significant reduction in euglobulin clot lysis time. Tissue plasminogen activator activity was undetectable in most patients pre-operatively but increased slightly after 1 year to 110 (100–204) mIU/ml. There were no significant changes in plasma levels of KCCT, factor VIII, von Willebrand factor antigen, alpha-2-antiplasmin, antithrombin III, protein C antigen, beta thromboglobulin, platelet factor 4, fibrinopeptide A or platelet count. These findings provide support for the hypothesis that the surgical treatment of morbid obesity may have a long-term beneficial effect on mortality from cardiovascular and thromboembolic disease.

Major abdominal surgery is accompanied by intra-operative increases in factor VIII (FVIII), plasminogen activator activity (PAA) and fibrinopeptide A (FPA). Vasopressin (aVP) released during surgery mediates some of the effects but the mechanisms involved in this response are unclear. To investigate the role of the operative procedure, 20 subjects were studied during inguinal hernia operation under local anaesthesia. Venous blood samples were taken for FVIII coagulant activity (FVIII:C), euglobulin clot lysis time (ECLT), FPA, crosslinked FDPs (XL-FDP) and a VP. In six patients, aVP rose from (median) 0.5 to 38.3 pg/ml at bowel manipulation and fell to 4.1 pg/ml post-operatively. PAA rose from 33 units to 377 and 316 units (P less than 0.01), FVIII:C from 1.58 to 2.4 IU/ml (P less than 0.01) and FPA from 5.0 to 6.8 and 11.0 pmol/ml intra-operatively (P less than 0.002). XL-FDP rose from a median value of 34 ng/ml pre-operatively to 230 ng/ml post-operatively. In 14 patients plasma aVP levels remained constant and both FVIII:C and PAA remained unchanged. FPA rose from 2.6 pmol/ml to 5.9 pmol/ml intra-operatively (P less than 0.05) and XL-FDP fell from 110 to 60 ng/ml. Between groups, the changes were significantly different for FVIII:C (P less than 0.05) and PAA (P less than 0.03) with no differences in blood pressure, pulse or symptoms. These results support the hypothesis that aVP secretion during surgery mediates increases in FVIII and PAA. FPA tended to be higher in the aVP secreting group which indicates that aVP mediated activation of coagulation results in a hypercoagulable state.

We present a case of extensive recurrence of a retro-pharyngeal liposarcoma following surgical removal 18 years previously. The surgery and pathology are discussed, and management strategies of head and neck liposarcomas are reviewed.

Oesophageal ulceration is an unusual complication of doxycycline treatment (Vibramycin®) presenting to an Otorhinolaryngology department. A case report is presented with discussion of investigations and management of the patient.

This combined analysis investigated the effect of marimastat, a specific inhibitor of matrix metalloproteinases, on markers of tumor progression measured in patients with advanced cancer. By defining the tolerability and biological activity of the drug, it aimed to establish an appropriate dose range for use in Phase III trials. Patients with advanced, serologically progressive ovarian, prostatic, pancreatic, and colorectal cancer were recruited into six nonrandomized, dose ranging, multicenter clinical trials in North America and Europe. The biological activity of marimastat was assessed by serial measurements of the serum tumor markers carcinoembryonic antigen, CA125, CA19-9, and prostate-specific antigen. Patients were recruited with tumor markers rising by more than 25% averaged over a 4-week screening period. A biological effect was defined as a level of tumor marker at the end of treatment no greater than at study entry; a partial biological effect was defined as a rise in the level of tumor marker over the treatment period of 0-25% per 4 weeks. Pharmacokinetic and safety data were collected and assessed as the studies progressed. All patients were followed up for survival.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting side effect of neurotoxic chemotherapy for breast cancer patients. CIPN develops within weeks or months after chemotherapy is initiated and affects 30-40% of breast cancer patients. As a result of severe CIPN, about 8% of breast cancer patients require their chemotherapy dose to be reduced or discontinued, which could detrimentally impact breast cancer related outcomes. Acupuncture is a Traditional Chinese Medicine technique that involves inserting filiform stainless steel needles into pre-defined points on the skin. Previous clinical trials suggest that acupuncture may be an effective treatment to reduce CIPN symptoms with minimal interactions with chemotherapy. Methods: We are conducting a pilot, randomized, standard care and placebo controlled clinical trial (N = 60) assessing the effects of acupuncture to prevent chemotherapy dose reduction due to CIPN. Breast cancer patients receiving taxane based chemotherapy in the neoadjuvant or adjuvant setting will be screened for development of Grade 2 CIPN by completing a weekly Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-Ntx) questionnaire. If patients develop Grade 2 CIPN during chemotherapy they will be randomized to one of three groups: real acupuncture (N = 20), sham acupuncture (N = 20) or standard of care (N = 20). Patients and investigators will be blinded to the treatment assignments. All patients will complete FACT-Ntx and Neuropathy Pain Scale questionnaires weekly. Patients in the real or sham acupuncture groups will receive weekly real or sham acupuncture treatments. Use of pain medications and acupuncture-related adverse events will be self recorded daily in patient diaries. We will explore changes in serum nerve growth factor and other neurotrophic factors such: as brain-derived neurotrophic factor, neurotrophin-3, insulin-like growth factors, and vascular endothelial growth factor. Blood (4 ml) will be drawn before each real or sham acupuncture treatment, at the end of chemotherapy, and at a 4 week follow up visit. Statistics: We expect that acupuncture will significantly decrease the number of patients who require dose reduction during a course of chemotherapy, and increase chemotherapy cumulative relative dose intensity. When a sample size in each cohort is 20, a three group Chi-square test with a 0.05 Type I error will have an adequate 85% power to distinguish between these groups of patients when the proportions are characterized by effect size, of 0.187. We expect the following proportions of patients who would require dose reduction in the acupuncture, sham acupuncture and standard care arms to be 0.05, 0.2, and 0.5, respectively. Statistical analysis will be conducted on-intent-to treat basis. Our specific aims are: to determine the effect of acupuncture on chemotherapy dose reduction, to determine the effect of acupuncture on CIPN during chemotherapy and to explore the mechanisms of acupuncture in treating CIPN. Nine subjects have been consented for screening and one has been randomized. Recruitment is ongoing. Please contact rkirk@umm.edu if interested in the trial. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-09.

Desmoid tumors are slowly growing fibrous tumors highly resistant to therapy and often fatal. Here, we report hereditary desmoid disease (HDD), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene. In general, one or more members in approximately 10% of the FAP families manifest desmoid tumors. Affected individuals from the HDD kindred are characterized by multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and other congenital features were also observed. We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development.

BACKGROUND--Obstructive jaundice is associated with an increased incidence of infection and endotoxaemia, which may result from impaired host immunity. Neutrophil adhesion to vascular endothelium is a key part of the inflammatory response. AIMS--To investigate neutrophil adhesion molecule expression and activation in obstructive jaundice. PATIENTS--Nine adult patients with obstructive jaundice and 11 control subjects. METHODS--The expression of the neutrophil adhesion receptors L-selectin, CD11a, CD11b, CD11c, and CD15 was determined using flow cytometry. CD11b expression in response to stimulation with fMLP and endotoxin was measured. RESULTS--The basal expression of L-selectin, CD11a, and CD15 was significantly decreased in jaundiced patients (p < 0.05) and the expression of CD11b in response to stimulation with fMLP and endotoxin was significantly impaired in the jaundiced group. Endotoxin stimulation without plasma did not reverse the impaired response showing that it is not caused by endotoxin inactivation by plasma proteins. CONCLUSIONS--Neutrophils from patients with obstructive jaundice show decreased adhesion receptor expression and an impaired response to stimulation with bacterial products. This cellular dysfunction may be responsible for the high incidence of septic complications in these patients.

Two cases of osteomyelitis of the cervical spine complicating tracheo-oesophageal puncture are reported. There was considerable delay between onset of symptoms and diagnosis in both cases due to pre-existing cervical arthritis. Previous radiotherapy was felt to be a contributory factor in both cases.

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VIII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.

There appear to be 3 factors in the development of papilloedema - an arterial shunt to the prelaminar tissue and a raised venous pressure in the absence of a raised intraocular pressure, which are passive effects, and an overspill of pial autoregulative vasodilatation which is not passive. In addition the arterial shunt may lead to excessive local autoregulative effects. The engorgement of the fine vessels of the prelaminar tissue, the loss of the spontaneous venous pulse on the disc and the venous overfilling are thought to indicate increased supply and blood flow rather than the reverse. The other general causes of papilloedema can also be explained by the autoregulative mechanism or its breakdown as they involve hypercapnia, tissue anoxia or severe hypertension.

The carbon dioxide and neodymium:yttrium aluminum garnet lasers have well documented but characteristically different biological effects, yet little is known about their cumulative, synergistic, or paradoxical effects when used sequentially on living tissue. Using a Merrimack ML 880 laser, a series of superimposed CO2 and Nd:YAG lesions in various combinations were produced on the undersurface of dog tongues. Therapeutic time and power settings were chosen and the number of applications varied, with suitable controls. Observations and measurements were made on acute, healing, and healed lesions. All lesions were excised and submitted for routine hematoxylin and eosin histology. Acute lesions were also assessed for cell viability using rhodamine 123 as a supravital marker. The results show that, even though all the lesions eventually heal, the actual cell damage produced by the Nd:YAG laser is much more than is suggested by the size of the acute lesion. This cell damage can be reduced by the surface carbonization produced by initial application of the CO2 laser. Higher surface temperatures are reached in this combination with less fibrosis and scarring than equal energy counterparts where the Nd:YAG laser was applied first. The knowledge of these synergistic effects can be used to advantage in the clinical setting. The rhodamine 123 technique also appears to be a valid measure of acute thermal tissue injury.

We present a 20-year review of juvenile angiofibroma in the relatively static population of Northern Ireland. Seventeen cases were identified and new slides were prepared from the stored paraffin blocks of all their original biopsy material, and re-examined. Five females, a 36-year-old and an 18-year-old male had their diagnoses revised. We suggest clinical criteria, which in conjunction with radiological investigations, should be strictly applied in all cases. Such application would, in retrospect, have identified those cases excluded by pathological re-examination, thus avoiding unnecessary surgery and radiotherapy. Atypical cases which do not satisfy the clinical criteria may be subjected to repeat biopsy but routine initial biopsy is not recommended.

The 1972 AAOO committee (Alford, 1972) guidelines brought some uniformity into the evaluation of therapy for Meniere's Disease. We have adhered to its recommendations in this long-term follow-up report of 21 saccus decompressions and 29 vestibular nerve sections performed on 46 patients between 1968 and 1977. Comparisons between these and other groups have been possible with regard to: 1. control of vertigo; 2. hearing; 3. tinnitus; and 4. development of hydrops in the contralateral ear. All the vestibular nerve section group have enjoyed sustained relief from vertigo. Class D results (recurrent vertigo) account for 14 per cent of the saccus decompression group at one year and 29 per cent at eight to 10-year follow-up. Hearing levels in both groups deteriorated in parallel as time progressed but tinnitus became less noticeable. Nineteen per cent of the long-term review patients showed evidence of developing cochlear hydrops in the contralateral ear. Conservative surgical procedures should be employed whilst any useful hearing exists, though the emphasis remains on controlling vertigo. Saccus decompression, despite its controversial therapeutic basis, will remain the first-line surgical procedure for many otologists. However, in the fit young Meniere's cripple or saccus decompression failure with serviceable hearing, vestibular nerve section remains the treatment of choice.

Summary A 10-year review of acute mastoid abscess treated surgically in Belfast revealed a total of 24 cases, 12 of which were found to have an underlying cholesteatoma. The surgical management of these 12 cases is outlined but despite a desire to maintain an intact canal wall, 9 of them to date have ended up with an open cavity. The danger of conservative management and the possible association between acute mastoid abscess and cholesteatoma, especially in developed countries, is stressed.

The anterior tympanomeatal angle remains the main problem area in anterior marginal perforations with both conventional onlay and underlay techniques. Here we describe a variation of Gerlach's quilting technique to overcome the problem and this modification has proven to be both simple and effective. When the graft is prepared a small tag is fashioned anteriorly and later pulled through a small tunnel under the anterior-superior annulus. This prevents the graft falling away anteriorly without producing the blunting associated with more extensive undermining of the anterior annulus.