Queen Mary's Hospital

OBJECTIVES: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field (peak value) in ≥1 biopsy specimens are considered a minimum threshold for a diagnosis of EoE. The disease is restricted to the esophagus, and other causes of esophageal eosinophilia should be excluded, specifically proton pump inhibitor-responsive esophageal eosinophilia. This position paper aims at providing practical guidelines for the management of children and adolescents with EoE. METHODS: Relevant literature from searches of PubMed, CINAHL, and recent guidelines was reviewed. In the absence of an evidence base, recommendations reflect the expert opinion of the authors. Final consensus was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference. RESULTS: The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid-based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved for severe symptoms requiring rapid relief or where other treatments have failed. Esophageal dilatation is an option in children with EoE who have esophageal stenosis unresponsive to drug therapy. Maintenance treatment may be required in case of frequent relapse, although an optimal regimen still needs to be determined. CONCLUSIONS: EoE is a chronic, relapsing inflammatory disease with largely unquantified long-term consequences. Investigations and treatment are tailored to the individual and must not create more morbidity for the patient and family than the disease itself. Better maintenance treatment as well as biomarkers for assessing treatment response and predicting long-term complications is urgently needed.

Thalidomide: a brief history Thalidomide (alpha-phthalimido-glutarimide) was developed by the German firm Chemie Grunenthal as an anticonvulsant drug. Early trials showed it to be unsuitable for this pur- pose but indicated that it had sedative proper- ties. Furthermore, it had one remarkable prop- erty: overdoses simply caused prolonged sleep, not death. The drug was first marketed in Germany in 1957 under the name Contergan, and in the UK in April 1958 as Distaval. Later, compound preparations which combined tha- lidomide with other drugs were marketed for a wide variety of indications: Asmaval for asthma, Tensival for hypertension, Valgraine for migraine, and so forth. The promotion of these products laid great stress on the safety of thalidomide, based on the remarkable property described above.

Seven patients are described in whom dementia developed during treatment with methotrexate for meningeal leukaemia. The patients presented with confusion, tremor, ataxia, irritability, and somnolence. There were major epileptic fits in two cases and in one case there was progression to coma and death. Necropsy findings in the latter showed infarcted areas in the temporal and parietal lobes, with no evidence of active leukaemic disease or of viral encephalitis. The condition has not responded to radiotherapy and no positive evidence of viral encephalitis has been obtained. On the other hand, when treated with folinic and folic acid the deterioration has been arrested and there has been some improvement; thus the condition appears to be due to methotrexate. The occurrence of so many cases within the past year of a condition not previously described is probably attributable to the introduction of intensive cytotoxic therapy directed against meningeal leukaemia.

Osseointegration for the trans-femoral amputee has been used in the United Kingdom since 1997. To date, 11 candidates have undergone the procedure. The rehabilitation programme for the osseointegration candidate is a long and intensive programme following two surgical operations. This paper outlines the importance of a pre-osseointegration assessment to explore candidates' suitability and expectations for the procedure. The physical and prosthetic advantages of direct skeletal attachment have led to improvements in candidates' comfort, function and quality of life. However, some aspects of this promising developmental procedure for the management of the trans-femoral amputee need to be critically evaluated before it becomes a routine clinical procedure in the United Kingdom.

A controlled double-blind study of the effect of dipyridamole was performed in 169 patients with established cerebral vascular disease. A dose of 400 mg. was used initially, given daily for an average of 14 months; the dose was then increased to 800 mg. daily for a further average period of 11 months. When the incidence of cerebral ischaemic episodes during treatment was compared in the drug-treated and placebo-treated groups no significant difference was found.

This is the first study to report on hip range of motion (ROM) among active prosthesis users, when wearing and not wearing a trans-femoral socket prosthesis and to compare with individuals rehabilitated with an osseointegrated bone-anchored prosthesis. In addition, discomfort when sitting with the prosthesis is reported in both groups. The study group all had a non-vascular amputation and were divided into those supplied with a socket prosthesis (S group) (n = 43, mean age 51 years, 74% men) or a bone-anchored prosthesis (OI group) (n = 20, mean age 46 years, 75% men). Active hip ROM was measured with a goniometer, and self-reported problems with discomfort when sitting were recorded. The hip motion decreased in all directions when wearing the socket prosthesis compared to without it (P < 0.001 for all directions), and 37% of the subjects had less than 90 degrees of hip flexion when wearing their prosthesis. Discomfort when sitting was reported among 44% (n = 19) in the S group and was more common among individuals with less than 90 degrees of hip flexion motion (P= 0.025). In the OI group, no restriction in hip motion was measured with the prosthesis, and no subject had less than 90 degrees of flexion and 5% (n = 1) reported discomfort when sitting. This study shows that a trans-femoral prosthetic socket significantly reduces the ROM of the hip and that discomfort when sitting is common among individuals wearing such prostheses. Further, the study confirms that individuals using a bone-anchored prosthesis have no restricted hip motion with the prosthesis and report very few problems with discomfort when sitting.

This guideline offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of Chlamydia trachomatis genital infection. It covers the management of the initial presentation, as well the prevention of transmission and future infection. The guideline is aimed at individuals aged 16 years and older presenting to healthcare professionals working in departments offering Level 3 care in sexually transmitted infections management within the UK. However, the principles of the recommendations should be adopted across all levels, using local care pathways where appropriate.

Group A Streptococci Resistant to Lincomycin SIR,-We have isolated group A strepto- cocci resistant to lincomycin, erythromycin, and oleandomycin from patients under treat- ment with lincomycin.

In a multicentre study the effect of ranitidine on healing non-steroidal anti-inflammatory drug (NSAID) associated peptic ulcers was compared in a group of patients who had stopped NSAID treatment with another group who continued with NSAID treatment. A total of 190 patients with confirmed ulcers were randomised to continue or stop NSAID treatment. All patients in addition received ranitidine 150 mg twice daily. Patients were endoscopically monitored at four, eight, and 12 weeks. Gastric ulcers at eight weeks had healed in 63% of those taking NSAIDs compared with 95% of those who had stopped NSAID treatment. For duodenal ulcer the healing rates at eight weeks were 84% in the group continuing NSAIDs compared with 100% in those who stopped NSAIDs. The differences in healing rates were statistically significant for both gastric ulcer (p = 0.001) and for duodenal ulcer (p = 0.006). At 12 weeks, 79% of gastric ulcers and 92% of duodenal ulcers were healed in the group continuing with NSAIDs. All patients with gastric and duodenal ulcers who stopped taking NSAIDs were healed at 12 weeks. The study shows that ranitidine 150 mg twice daily effectively heals NSAID associated peptic ulcers. Healing is more successful when NSAID treatment stops but even if these drugs are continued, substantial healing rates are achievable.

Journal Article MEASUREMENT OF SPINAL POSTURE AND RANGE OF SPINAL MOVEMENT Get access W. Y. LOEBL W. Y. LOEBL Westminster Hospital and Queen Mary's HospitalRoehampton, London Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, Volume 9, Issue 3, August 1967, Pages 103–110, https://doi.org/10.1093/rheumatology/9.3.103 Published: 01 August 1967

BACKGROUND: Long-term benefits of newborn screening (NBS) for cystic fibrosis (CF) have been established with respect to nutritional status, but effects on pulmonary health remain unclear. HYPOTHESIS: With early diagnosis and commencement of standardised treatment, lung function at ∼3 months of age is normal in NBS infants with CF. METHODS: Lung clearance index (LCI) and functional residual capacity (FRC) using multiple breath washout (MBW), plethysmographic (pleth) FRC and forced expirations from raised lung volumes were measured in 71 infants with CF (participants in the London CF Collaboration) and 54 contemporaneous healthy controls age ∼3 months. RESULTS: Compared with controls, and after adjustment for body size and age, LCI, FRC(MBW) and FRC(pleth) were significantly higher in infants with CF (mean difference (95% CI): 0.5 (0.1 to 0.9), p=0.02; 0.4 (0.1 to 0.7), p=0.02 and 0.9 (0.4 to 1.3), p<0.001, z-scores, respectively), while forced expiratory volume (FEV(0.5)) and flows (FEF(25-75)) were significantly lower (-0.9 (-1.3 to -0.6), p<0.001 and -0.7 (-1.1 to -0.2), p=0.004, z-scores, respectively). 21% (15/70) of infants with CF had an elevated LCI (>1.96 z-scores) and 25% (17/68) an abnormally low FEV(0.5) (below -1.96 z-scores). While only eight infants with CF had abnormalities of LCI and FEV(0.5), using both techniques identified abnormalities in 35% (24/68). Hyperinflation (FRC(pleth) >1.96 z-scores) was identified in 18% (10/56) of infants with CF and was significantly correlated with diminished FEF(25-75) (r=-0.43, p<0.001) but not with LCI or FEV(0.5). CONCLUSION: Despite early diagnosis of CF by NBS and protocol-driven treatment in specialist centres, abnormal lung function, with increased ventilation inhomogeneity and hyperinflation and diminished airway function, is evident in many infants with CF diagnosed through NBS by 3 months of age.

BACKGROUND: Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS). METHODS: Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS: The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

OBJECTIVE: To assess the frequency and phenotype of hexanucleotide repeat expansions in C9ORF72 in a large cohort of patients of Dutch descent with familial (fALS) and sporadic (sALS) amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS). METHODS: Included were 78 patients with fALS, 1,422 with sALS, 246 with PMA, and 110 with PLS, and 768 control subjects. Repeat expansions were determined by a repeat primed PCR. Familial aggregation of dementia and Parkinson disease (PD) was examined among patients with ALS who carried the repeat expansion. RESULTS: The expanded repeat was found in 33 (37%) of all patients with fALS, in 87 (6.1%) patients with sALS, in 4 (1.6%) patients with PMA, and in 1 (0.9%) patient with PLS. None of the controls carried the mutation. Patients with ALS with the repeat expansion had an earlier age at onset (median 59.3 vs 61.9 years, hazard ratio 1.55, p = 5 × 10(-5)) and shorter survival (median 2.5 vs 2.7 years, hazard ratio 1.46, p = 8 × 10(-4)). Dementia, but not PD, occurred nearly twice as often in relatives of patients with the expansion compared to all patients with ALS or controls (p = 9 × 10(-4)). CONCLUSIONS: The hexanucleotide repeat expansion in C9ORF72 is a major cause of fALS and apparently sporadic ALS in the Netherlands. Patients who carry the repeat expansion have an earlier onset, shorter survival, and familial aggregation of dementia. These results challenge the classic definition of fALS and may justify genetic testing in patients with sALS.

range= 40-100 IU/1) respectively.Tests for hepatitis B surface antigen were negative.Ultrasonography of liver and gall bladder was normal.Anaphylactoid purpura was diagnosed and treatment with intravenous hydrocortisone 100 mg four times daily started.Respiratory and abdominal symptoms resolved completely within 18 hours.The patient was discharged home nine days later taking a gradually decreasing dose of prednisolone.He remained well six weeks later and steroid treatment was stopped.All haematological and biochemical indices were within normal limits.

Endoscopy is a central tool for the evaluation and management of inflammatory bowel disease (IBD). In the last few decades, gastrointestinal (GI) endoscopy has undergone significant technological developments including availability of pediatric-size equipment, enabling comprehensive investigation of the GI tract in children. Simultaneously, professional organization of GI experts have developed guidelines and training programs in pediatric GI endoscopy. This prompted the Porto Group on Pediatric IBD of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition to develop updated guidelines on the role of GI endoscopy in pediatric IBD, specifically taking into considerations of recent advances in the diagnosis, disease stratification, and novel therapeutic targets in these patients.

BACKGROUND: We aim to investigate the effect of exercise training on endothelial function and exercise capacity in patients with coronary artery disease. METHODS AND RESULTS: A randomized, controlled trial was conducted to determine the effects of an 8-week exercise training programme (n = 32) vs. controls (n = 32) on brachial flow-mediated dilation (FMD) in patients with stable CAD. After 8 weeks, patients received exercise training had significant improvements in FMD (1.84%, p = 0.002) and exercise capacity (2.04 metabolic equivalents, p < 0.001) compared with controls. The change in FMD correlated inversely with baseline FMD (r = -0.41, p = 0.001) and positively with the increase in exercise capacity (r = 0.35, p = 0.005). After adjusting for confounders, every 1 metabolic equivalent increase in exercise capacity was associated with 0.55% increase in FMD. Furthermore, patients received exercise training had significantly increased high-density lipoprotein cholesterol and decreased diastolic blood pressure and resting heart rate compared with controls. However, exercise training did not alter high-sensitivity C-reactive protein, oxidative stress measured as superoxide dismutase and 8-isoprostane, and CD34/KDR + endothelial progenitor cell count. Subgroup analysis showed that FMD was significantly improved only in CAD patients with baseline low exercise capacity (<median value of 7.65 metabolic equivalents, p = 0.004) but not in those with normal exercise capacity. CONCLUSION: Exercise training improved FMD and exercise capacity in stable CAD patients independent of the changes in inflammation, oxidative stress, or endothelial progenitor cells. The beneficial effects of exercise training on FMD and exercise capacity are inter-related, and more pronounced in those with baseline impaired exercise capacity.

Submental tracheal intubation is a simple, quick and effective alternative to oral and nasal tracheal intubation or tracheostomy in the surgical management of selected patients with craniomaxillofacial injuries. It has a low morbidity and it does not impede the surgical field, allowing for temporary maxillo-mandibular fixation (jaw wiring) intra-operatively, and nasal assessment, manipulation and bone grafting, either simultaneously or as an independent procedure. We report 12 cases utilizing this technique in this retrospective study, this includes 11 patients with mid-facial fractures and associated base of skull fractures, and one patient who underwent an elective Le Fort III advancement. The techniques and indications for submental tracheal intubation are described.

PURPOSE: The original Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity and the more recent Portsmouth predictor equation for mortality scoring systems were developed to provide risk-adjusted mortality rates in general surgery. The aim of this study was to compare crude and risk-adjusted operative mortality rates among four surgeons using the above scoring systems and assess their applicability for patients scored retrospectively. METHODS: A total of 505 consecutive patients undergoing major gastrointestinal surgery were analyzed; 65 percent underwent colorectal, 27.5 percent underwent upper gastrointestinal, and 7.5 percent underwent small-bowel surgery. The observed:predicted mortality ratios using the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity and Portsmouth predictor equation for mortality scoring systems were calculated for each surgeon. RESULTS: The actual overall operative mortality rate was 11.1 percent (elective was 3.9 percent, and emergency was 25.1 percent). The Portsmouth predictor equation for mortality equation predicted a mortality rate of 11.3 percent (P = 0.51). However, the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity scoring system was found to overpredict death by a factor of two: 21.5 percent (P < 0.001). Mortality rates among the four surgeons varied from 7.6 to 14.7 percent but depended on the proportion of elective vs. emergency surgery. The observed:predicted ratio for Portsmouth predictor equation for mortality was close to unity (0.905-1.067) for all surgeons, but it was 0.45 to 0.56 for Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity. CONCLUSION: The Portsmouth predictor equation for mortality equation seems to be a more accurate predictor of mortality in gastrointestinal surgery. It would seem to provide the best choice for analyzing operative mortality rates for individual surgeons, taking into account variation in case mix and fitness of patients even when scored retrospectively. This has important implications for the future assessment of surgeons' clinical standards and the assessment of quality of surgical care.

OBJECTIVE: To assess doctors' and nurses' views on the presence of relatives in the resuscitation room during cardiac arrest or major trauma. DESIGN: Questionnaires were sent to accident and emergency (A&E) nurses and doctors of all disciplines in a London teaching hospital. Recipients were asked if they would favour the presence of selected relatives in the resuscitation room and to give comments. RESULTS: 103 questionnaires were distributed and 81 returned, a response rate of 78.6%; 33% were senior house officers, 29% consultants, 16% senior registrars/registrars, 12% A&E nurses, and 10% house officers. Of the respondents, 63% were not in favour of relatives being present, and 37% were in favour. The likelihood of being in favour of allowing relatives to be present was high among A&E nurses; among doctors it increased with rising seniority. Most respondents felt that more resuscitation training would be necessary, in addition to counselling for staff and relatives. CONCLUSIONS: Staff with the least experience in dealing with resuscitations and distressed relatives were likely to be opposed to relatives being present in the resuscitation room. As there is evidence that the bereavement process is eased if a partner/relative witnesses the resuscitation, relatives should be offered the opportunity to witness resuscitation if staff training is geared towards the presence of relatives. ALS/ATLS training for all hospital doctors and nurses should include the management of distressed relatives observing a resuscitation.

The possible role of environmental stress in precipitating the onset or relapse of acute schizophrenia was investigated by Brown and Birley (1968), Birley and Brown (1970). They enquired about events which could be dated to a definite point in time and which usually involved either actual or threatened danger or important fulfilments or disappointments. They distinguished between independent events, which were outside the control of the subject, and possibly independent events, which were not so clearly out of his control but which seemed unlikely to be produced by unusual behaviour of the subject himself. In their main group of patients a significant concentration of independent events (about 60 per cent) was found in the three weeks preceding onset or relapse of schizophrenia. In examining two small sub-groups they found that 4 of 13 patients (31 per cent) who relapsed after reducing or discontinuing phenothiazine therapy had experienced a life event in the three weeks before relapse, compared with 3 of 5 patients (60 per cent) who had been taking phenothiazines regularly at the time of relapse. Although these proportions are very different, the numbers in the groups are too small for the difference to reach significance. Furthermore the groups were not matched in any way, and there may be important differences between patients who discontinue medication themselves and those who carry on taking it regularly.