Evaluation of outcome after cardiomyotomy for achalasia using the Chicago classification.

BACKGROUND: Achalasia can be subdivided into manometric subtypes according to the Chicago classification. These subtypes are proposed to predict outcome after treatment. This hypothesis was tested using a database of patients who underwent laparoscopic Heller's cardiomyotomy with anterior fundoplication. METHODS: All patients who underwent Heller's cardiomyotomy for achalasia between June 1993 and March 2015 were identified from an institutional database. Manometry tracings were retrieved and re-reported according the Chicago classification. Outcome was assessed by a postal questionnaire, and designated a success if the modified Eckardt score was 3 or less, and the patient had not undergone subsequent surgery or pneumatic dilatation. Difference in outcome after cardiomyotomy was analysed with a mixed-effects logistic regression model. RESULTS: Sixty, 111 and 24 patients had type I, II and II achalasia respectively. Patients with type III achalasia were more likely to be older than those with type I or II (mean age 63 versus 50 and 49 years respectively; P = 0·001). Some 176 of 195 patients returned questionnaires after surgery. Type III achalasia was less likely to have a successful outcome than type II (odds ratio (OR) 0·38, 95 per cent c.i. 0·15 to 0·94; P = 0·035). There was no significant difference in outcome between types I and II achalasia (II versus I: OR 0·87, 0·47 to 1·60; P 0·663). The success rate at 3-year follow-up was 69 per cent (22 of 32) for type I, 66 per cent (33 of 50) for type II and 31 per cent (4 of 13) for type III. CONCLUSION: Type III achalasia is a predictor of poor outcome after cardiomyotomy. There was no difference in outcome between types I and II achalasia.

The clinical spectrum of omega-5-gliadin allergy.

BACKGROUND: IgE-mediated allergy to the wheat protein omega-5-gliadin (O5G) is associated with wheat-dependent exercise-induced anaphylaxis (WDEIA), where exercise acts as a cofactor, triggering anaphylaxis after wheat ingestion. The wider application of O5G-specific IgE (sIgE) testing has revealed that the manifestations of O5G allergy extend beyond WDEIA. AIMS: This study documents clinical manifestations in a large series of patients with sIgE to O5G. METHODS: A retrospective clinical audit was performed on adult patients with a positive O5G sIgE (>0.35kU/L) between 2007 and 2013 compared with a group who had negative O5G sIgE. Clinical characteristics and skin prick test (SPT) results were examined. RESULTS: Sixty-seven patients were characterised, 26 of whom presented with food-dependent exercise-induced allergy, whilst others presented with exercise-induced symptoms without apparent food association (16/67), idiopathic anaphylaxis (10/67), food-induced allergic symptoms without exercise (10/67) or recurrent acute urticaria (5/67). Specific IgE to O5G had 91% sensitivity and 92% specificity for wheat-related allergic symptoms. SPT had sensitivity of 92% and specificity of 84%. CONCLUSION: WDEIA is the most common manifestation of O5G allergy, but patients may present with a variety of allergic manifestations, and wheat allergy is not always obvious on history. Non-exercise cofactors or a lack of cofactors were identified in many patients. A distinctive feature of this allergy is that despite regular wheat ingestion, allergic reactions to wheat occur infrequently. Testing for sIgE to O5G should be considered in patients presenting with exercise-induced urticaria/anaphylaxis, idiopathic anaphylaxis and recurrent acute (but not chronic) urticaria.

Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies.

BACKGROUND: Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE-mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated allergic disease in their children. METHODS: Follow-up of children (n = 706) at hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomized controlled trial. The intervention group (n = 368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338) received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. RESULTS: No differences were seen in the overall percentage of children with IgE-mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78; 95% CI 0.58-1.06; P = 0.11). Eczema was the most common allergic disease; 13.8% of children in the n-3 LCPUFA group had eczema with sensitization compared with 19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53-1.05; P = 0.10). CONCLUSIONS: Overall, n-3 LCPUFA supplementation during pregnancy did not significantly reduce IgE-associated allergic disease in the first 3 years of life. Further studies should examine whether the nonsignificant reductions in IgE-associated allergies are of clinical and public health significance.

Utility of peripheral blood B cell subsets analysis in common variable immunodeficiency.

Abnormalities in peripheral blood B cell subsets have been identified in common variable immunodeficiency (CVID) patients and classification systems based upon their numbers have been proposed to predict the clinical features. We analysed B lymphocyte subsets by multi-colour flow cytometry (MFC) in a cohort of well-characterized CVID patients to look at their clinical relevance and validate the published association of different classification criteria (Freiburg, Paris and Euroclass) with clinical manifestations. CVID patients had a reduced proportion of total and switched memory B cells (MBC, swMBC) compared to normal controls (P < 0·0006). Patients classified in Freiburg Ia had a higher prevalence of granulomatous diseases (P = 0·0034). The previously published associations with autoimmune diseases could not be confirmed. The Euroclass classification was not predictive of clinical phenotypes. The absolute numbers of all B cell subsets were reduced in CVID patients compared to controls. There was a significant linear correlation between low absolute total B cells and MBC with granulomatous disease (P < 0·05) and a trend towards lower B cells in patients with autoimmune diseases (P = 0·07). Absolute number of different B cell subsets may be more meaningful than their relative percentages in assessing the risk of granulomatous diseases and possibly autoimmunity.

Oral drug challenges in non-steroidal anti-inflammatory drug-induced urticaria, angioedema and anaphylaxis.

BACKGROUND: Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). AIM: To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. METHODS: Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. RESULTS: Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. CONCLUSION: In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs.

Pharmacokinetics and safety of Intragam 10 NF, the next generation 10% liquid intravenous immunoglobulin, in patients with primary antibody deficiencies.

BACKGROUND AND AIMS: Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross-over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability. METHODS: Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2-0.8 g/kg 3-4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability. RESULTS: There was no significant within-patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996-1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P < 0.05). Headache was the most frequent treatment-related event following both products. There were no study withdrawals, deaths, or notable changes in laboratory values or vital signs. CONCLUSION: Intragam 10 NF was well tolerated and exhibited similar PK to Intragam P, with the advantage of a 45 min shorter infusion time.

Is esophageal dysphagia in the extreme elderly (>or=80 years) different to dysphagia younger adults? A clinical motility service audit.

Dysphagia in elderly patients has major effects on nutrition and quality of life. Although aging itself is associated with changes in esophageal motility, the impact of this on symptoms such as dysphagia is unclear. Data in the extreme elderly are also limited. Symptoms and manometric diagnoses from 23 consecutive older patients (older dysphagia [OD]) >or=80 reporting esophageal dysphagia (12 female, mean age 83 (range 80-93) were compared with those from 23 gender matched younger patients (young dysphagia [YD]) also with dysphagia (mean age 35, range [17-46]). More older patients reported dysphagia as their primary symptom (OD 22/23 vs YD 14/23, P = 0.005). Overall, dysphagia was most common for solids only (OD 16/23 vs YD 15/23) and rare for liquids only (OD 1/23 vs YD 3/23). Dysphagia for both liquids and solids was more frequent in older patients (OD 6/23 vs YD 1/23, P < 0.05). Fewer older patients reported heartburn (OD 3/23 vs YD 14/23, P = 0.001). Manometric diagnoses were generally similar between OD and YD patients with the most common diagnoses being 'nonspecific esophageal motility disorder' (nine each) and 'ineffective peristalsis' (OD = 6, YD = 7). There was a trend for diagnoses related to lower esophageal sphincter failure to be more frequent in younger subjects (OD 1 vs YD 7, P = 0.053). Despite differences in symptom patterns, broad manometric diagnoses in the extreme elderly with dysphagia are similar to younger dysphagia patients. Further studies are required to determine whether this relates to insensitivity in recording or reporting of esophageal manometry (or perceptual differences associated with aging).

Maximum upper esophageal sphincter (UES) admittance: a non-specific marker of UES dysfunction.

BACKGROUND: Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. METHODS: Sixty-six healthy subjects (n = 50 controls 20-80 years; n = 16 elderly >80 years), 11 patients with CPB (51-83 years) and 16 with MND (58-91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. KEY RESULTS: In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. CONCLUSIONS & INFERENCES: The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction.

Impaired bolus clearance in asymptomatic older adults during high-resolution impedance manometry.

BACKGROUND: Dysphagia becomes more common in old age. We performed high-resolution impedance manometry (HRIM) in asymptomatic healthy adults (including an older cohort >80 years) to assess HRIM findings in relation to bolus clearance. METHODS: Esophageal HRIM was performed in a sitting posture in 45 healthy volunteers (n = 30 young control, mean age 37 ± 11 years and n = 15 older subjects aged 85 ± 4 years) using a 3.2-mm solid-state catheter (Solar GI system; MMS, Enschede, The Netherlands) with 25 pressure (1-cm spacing) and 12 impedance segments (2-cm intervals). Five swallows each of 5- and 10-mL liquid and viscous bolus were performed and analyzed using esophageal pressure topography metrics and Chicago classification criteria as well as pressure-flow parameters. Bolus transit was determined using standard impedance criteria. A p-value <0.05 was considered significant. KEY RESULTS: Impaired bolus clearance occurred more frequently in asymptomatic older subjects compared with young controls (YC) during liquid (40 vs 18%, χ2  = 4.935; p < 0.05) and viscous (60 vs 17%; χ2  = 39.08; p < 0.001) swallowing. Longer peristaltic breaks (p < 0.05) and more rapid peristalsis (L: p < 0.004, V: p = 0.003) occurred in the older cohort, with reduced impedance-based clearance for both bolus consistencies (L: p < 0.05, V: p < 0.001). Decreased peristaltic vigor (distal contractile integral <450 mmHg/s/cm) was associated with reduced liquid clearance in both age groups (p < 0.001) and of viscous swallows in the older group (p < 0.001). Impedance ratio, a marker of bolus retention, was increased in older subjects during liquid (p = 0.002) and viscous (p < 0.001) swallowing. CONCLUSIONS & INFERENCES: Impaired liquid and viscous bolus clearance, esophageal pressure topography, and pressure-flow changes were seen in asymptomatic older subjects.

Increased intestinal permeability in atopic eczema.

We have investigated gastrointestinal permeability in children with atopic eczema by measuring the relative urinary excretion rates of the inert di- and monosaccharides lactulose and rhamnose following their oral administration. The median lactulose/rhamnose ratio was greater in 26 children with atopic eczema than in a control group of 29 children which included both healthy individuals and others with various noneczematous dermatoses. This increased permeability may be a primary abnormality of the gut or may reflect intestinal mucosal damage caused by local hypersensitivity reactions to food antigens.

Small cell lung carcinoma and Bowen's disease 40 years after arsenic ingestion.

A non-smoking woman presented with ectopic ACTH syndrome associated with disseminated small cell carcinoma of lung. The patient had Bowen's disease and had taken oral arsenic for psoriasis 40 years ago. It is postulated that the previous therapeutic arsenic ingestion caused both her arsenical dermatosis and her small cell carcinoma of lung.

Dietary compliance in the short bowel syndrome.

Psychologic problems associated with the short bowel syndrome have received limited recognition. The literature has previously considered these problems as due to the underlying condition or its treatment. We present a case illustrating these as well as addressing the problem of compliance to treatment that has been previously neglected. The occurrence of metabolic acidosis in this patient whenever there was not strict dietary adherence to diet provide a ready marker to her noncompliance.

An alternative method of bowel preparation for barium enemas.

A double blind trial is described comparing two methods of bowel preparation prior to barium enema. In 40 randomly selected patients a significant improvement was obtained by the use of an intestinal perfusion method.

Intralesional interferon for the treatment of metastatic carcinoid tumours.

We report the first documented case of intralesional interferon administration for the palliation of carcinoid tumour metastases. This was performed under ultrasound guidance and gave a good clinical response, which correlated with tumour necrosis demonstrated by serial CT scanning.

Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation.

OBJECTIVES: To assess a protocol for treatment of sting anaphylaxis. DESIGN: Prospective assessment of treatment with oxygen, intravenous infusion of adrenaline (epinephrine), and volume resuscitation with normal saline. SETTING: Sub-study of a venom immunotherapy trial. PARTICIPANTS: 21 otherwise healthy adults with systemic allergic reactions to diagnostic sting challenge. MAIN OUTCOME MEASURES: Response to treatment, total adrenaline dose and infusion duration, recurrence of symptoms after stopping the infusion, and additional volume resuscitation. RESULTS: 19 participants required intervention according to the protocol. All received adrenaline, and five received volume resuscitation. In nine cases, physical signs of anaphylaxis recurred after initial attempts at stopping adrenaline but resolved after recommencing the infusion. The median total dose and infusion duration were 590 micro g and 115 minutes respectively, but were significantly higher for eight patients who had hypotensive reactions (762 micro g and 169 minutes respectively). Hypotension was always accompanied by a relative bradycardia, which was severe and treated with atropine in two patients. Widespread T wave inversion occurred, before starting treatment with adrenaline, in one person with an otherwise mild reaction. All patients fully recovered and were fit for same day discharge, apart from the person with ECG changes who was observed overnight and discharged the following day. CONCLUSIONS: Carefully titrated intravenous adrenaline combined with volume resuscitation is an effective strategy for treating sting anaphylaxis, however severe bradycardia may benefit from additional treatment with atropine. Cardiac effects of anaphylaxis, perhaps including neurocardiogenic mechanisms, may be an important factor in some lethal reactions.

Prolene plug repair for femoral hernia.

We present the technique and our results in using a plug of Prolene mesh to repair femoral hernias. By filling the femoral canal with a Prolene plug we achieved a sound hernia repair. Our results allow us to recommend the technique to others.

Primary restorative colectomy in malignant left-sided large bowel obstruction.

A series of 18 consecutive patients who underwent primary resection and immediate anastomosis as the treatment for malignant left-sided large bowel obstruction are presented. Intraoperative mechanical preparation of the colon was omitted. There was no clinical evidence of anastomotic dehiscence or wound infection. The mean duration of hospital stay was 11 days. It is suggested that colonic continuity can be restored immediately and safely without mechanical bowel preparation, providing attention is directed to constructing an anastomosis that has a good blood supply and is free from tension.

Immunoblot analysis of IgE and IgG antibodies to honey bee venom: cross sectional and sequential studies in bee sensitive subjects.

To investigate the specific IgE and IgG immune response to honey bee venom (bv), we performed immunoblot analysis of sera from 47 bee sensitive subjects and followed the response during and after venom immunotherapy in 15 of these subjects. Fifteen venom proteins varying in molecular size from 20 to 105 kDa were identified as being antigenic and consisted of a high molecular weight (HMW) group (5 to 105 kDa, containing the previously identified allergens B and C) and a low molecular weight group (LMW) containing hyaluronidase and phospholipase A. In general for a given individual the anti-venom IgE and IgG response was qualitatively similar although some variation between individuals was apparent. Reactivity with hyaluronidase and phospholipase A appeared only in those subjects showing reactivity with HMW components. During immunotherapy specific anti-venom IgG and IgE responses tended to be linked. Increased responses being seen against all components in 4 of 12 subjects, reductions in 3 and unchanged responses in the remainder. Following immunotherapy (mean 4.0 years), spontaneous reduction of IgE and IgG was seen in 5 of 5 subjects. Loss of reactivity with the LMW components was prominent in these sera.

Bee sting anaphylaxis in an urban population of South Australia.

The clinical manifestations and circumstances of bee sting anaphylaxis have been studied retrospectively in 98 subjects. Most reactions occurred in children but the most severe reactions were seen in adult males, of whom 7 lost consciousness and 2 required cardiopulmonary resuscitation. Most stings causing anaphylaxis occurred on the unprotected feet whilst the subject was on lawn in the afternoons in December, January and February when the maximum daily temperature was between 20 and 30 degrees C. This is the temperature range when bees are particularly active in gathering pollen. However, a significantly greater frequency of anaphylactic reactions occurred at higher temperatures when bees are less active, suggesting that high environmental temperature may predispose the individual to greater exposure to bees or possibly to anaphylactic reactions per se. The presence of atopy did not appear to predispose subjects to bee venom hypersensitivity. Considerable anxiety and lifestyle alteration were identified in some subjects. The alleviation of this anxiety is considered an appropriate indication for bee venom immunotherapy.