BMI The Princess Margaret Hospital

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD), recently downgraded from a T-cell lymphoma, is a poorly characterized histopathological entity. Presenting as a solitary lesion that often grows rapidly, it may raise suspicion for a cutaneous B-cell lymphoma. However, classically, the dermal lymphoid proliferation is predominantly CD4+ with a follicular T-helper profile and a smaller B-cell fraction. Diagnostic uncertainty may arise when B cells are present in large numbers, a B-cell clone is present, or large cell populations are seen. To meet the diagnostic criterion of PCSM-LPD, large cells should not constitute more than 30% of the infiltrate. The 2 cases presented in this article caused diagnostic uncertainty owing to the observation of high numbers of large cells and in one case the presence of a B-cell clone, on the background of otherwise typical clinicopathological features of PCSM-LPD. We review the literature specifically regarding the prevalence of large cell populations and their immunophenotypic characteristics and in light of this discuss whether a current diagnostic criterion should be reconsidered.

Otosclerosis is a common form of hearing loss which typically presents in young adults. The disease has a familial, monogenic form and a non-familial form with a more complex aetiology. A previous genome wide association study identified evidence that variants within RELN are associated with the condition. Other genes in which an association has been reported include BMP2, COL1A1, FGF2, PPP2R5B and TGFB1. However, follow up studies have often failed to replicate initial positive results. The aim of this study was to establish if an association exists between eight single nucleotide polymorphisms (SNPs) in these six previously implicated genes and otosclerosis in a British case–control cohort (n = 748). Evidence of an association between rs1800472 in TGFB1 and otosclerosis was found (p = 0.034), this association was strongest amongst non-familial cases (p = 0.011). No evidence of an association was detected with variants in COL1A1, FGF2, BMP2, and PPP2R5B. No association between variation in RELN and otosclerosis was observed in the whole cohort. However, a significant association (p = 0.0057) was detected between one RELN SNP (rs39399) and otosclerosis in familial patients. Additionally, we identify expression of one RELN transcript in 51 of 81 human stapes tested, clarifying previous conflicting data as to whether RELN is expressed in the affected tissue. Our findings strengthen the association of TGFB1 (rs1800472) with otosclerosis and support a relationship between RELN and familial otosclerosis only, which may explain previous variable replications.

Polymorphic light eruption (PLE) is the commonest photodermatosis, demonstrating intermittently appearing non-scarring pruritic, erythematous papules, vesicles or plaques on patient skin within hours of ultraviolet radiation (UVR) exposure. It depends on genetic susceptibility as well as environmental UVR exposure and is apparently a failure of normal UVR-induced immunosuppression in the presence of simultaneously produced skin photoneoantigens1,2, with a resulting increased immune response. Reduced TNF-α, IL-4 and IL-10 expression, a lack of neutrophils, reduced T-helper-1/T-helper-2 skewing and reduced Langerhans cell migration have also been demonstrated in UVB-irradiated PLE skin3. Bead-array immunoassay studies have further revealed significantly higher PLE baseline IL-1β and CCL11 (eotaxin) spring plasma levels4, while decreased TGFs1, IL-10 and receptor activator of nuclear factor kappa-B ligand (RANKL) epidermal and dermal expression, and reduced T-reg cells occur in UVA-1-irradiated patients5, as well as decreased T-reg cell function in all PLE patients, irradiated or not6. This article is protected by copyright. All rights reserved.

This review documented the range and nature of reported outcome measures in the context of adult auditory rehabilitative research. A scoping review conducted as a part of the development of a systematic review of the effect of interventions to improve hearing aid use. The authors searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials; PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP; and additional sources for published and unpublished randomized control trials. The date of the search was November 6, 2013. Outcomes were grouped using a framework suggested by the Cochrane Effective Practice and Organization of Care group. Patient outcomes included adherence to hearing aid use, daily hours of aid use, hearing handicap, hearing aid benefit, quality of life, and communication and psychological outcome. Satisfaction and speech perception were frequent secondary outcomes. There was diversity in measures used to report patient outcomes. Outcome categories other than patient health status and behavior were rarely reported. The timing of outcome measurement was often short term (<12 weeks), with a relative lack of evidence on long-term outcomes (>1 year). This review has highlighted considerable diversity in patient-reported outcome measurements in randomized control trials in the context of adult auditory rehabilitation. In addition, there are gaps in the literature with respect to measurement of other outcome types of potential interest to stakeholders, including policymakers and commissioners. Long-term outcome assessment is rare.

Although many PCL injuries are in combination with posterolateral corner (PLC) injuries, there has been little work done on combined injury reconstruction; the literature includes differing recommendations. It was hypothesised that a double-bundle PCL reconstruction would restore both posterior drawer and external rotation laxities closer to normal than an isolated single-bundle reconstruction in combined PCL plus PLC-deficient knees. However, it was also hypothesised that an isolated PCL reconstruction would still leave abnormal rotation laxity. In this controlled laboratory study, cadaver knee kinematics were measured electromagnetically with posterior drawer, external rotation, varus rotation loads applied, at sequential stages: intact; PCL-deficient; PCL plus PLC-deficient; double-bundle PCL reconstruction; single-bundle PCL reconstruction. The grafts were tensed using a posterior drawer laxity matching protocol. There was no significant difference between single- and double-bundle PCL reconstructions at any angle of flexion: both reconstructions restored posterior drawer to normal; neither reconstruction restored external rotation or varus laxity to normal. We concluded that, in combined PCL plus PLC deficiency, isolated PCL reconstruction only controls tibial posterior drawer, but is not sufficient to restore rotational laxity to normal. Double-bundle PCL reconstruction was not better than single-bundle, so the added complexity of double-bundle reconstruction does not seem to be justified by these results.

A 58 year old female attended our A&E department following a fall in the garden with swelling and bruising of the right arm and the elbow. Anteroposterior and lateral radiographs were interpreted as showing a normal elbow joint. A diagnosis of soft tissue injury to the elbow was made and the patient was discharged with advice. She returned 2 days later, did not have an x ray, and again given advice. Three weeks later she was referred back to A&E by the general practitioner with persistent swelling of the elbow. Further radiographs showed a posterolateral dislocation of the elbow. The elbow was reduced under sedation but was subsequently dislocated at follow up, and was treated by external fixator and transolecranon pin. The fixator was removed at 4 weeks and the elbow was then stable. This case highlights that recurrent elbow dislocations due to significant ligament injuries can present in joint and subsequently dislocate. A high index of suspicion is necessary and appropriate referral to the specialist must be made to avoid the morbidity associated with recurrent dislocation. It also emphasises the need to always assess the patient on his or her own merits despite previously normal investigations.

A double blind study was performed on 13 patients with food intolerance, confirmed by elimination dieting and repeated challenge. Intradermal testing was performed at 1:500, using 10 commonly reacting foods and 10 which rarely gave reactions, a total of 260 tests. As compared with the results of challenge, intradermal skin tests were assessed as 57.5% accurate. The results are compared with other studies, and whilst single strength intradermal testing cannot be put forward as a valid test for food intolerance it is suggested that apparent “false positive” responses may be due to a mechanism akin to atopy in IgE allergy.

Normal gut fermentation is the process whereby non‐starch‐soluble polysaccharides are metabolized in the large bowel to provide nutrients. It is well represented in the literature. Abnormal fermentation however can also be present. A test for this demonstrates the production of trace amounts of ethanol, measurable in blood. Beta‐alanine production, measured by urinary excretion, is associated with normal fermentation, but this study demonstrates that beta‐alanine production may be a consequence of abnormal fermentation as well as normal. We consider that it may be an independent marker of the disease. process.

Patients with abnormal gut fermentation commonly have marked craving for sugars and fermentable foods. True food allergy to sucrose is rare, and intolerance is also uncommon. It is suggested that the craving mechanism in abnormal gut fermentation may be similar to that of alcohol craving in alcoholics.A group of patients seen in 1983 who were then diagnosed as food intolerant had been given challenges with Isomaltulose, a sugar, and Thaumatin, a protein sweetener. The diagnoses were revised retrospectively into food intolerance and abnormal gut fermentation. The challenge results were then re‐interpreted to see if the two groups behaved differently.None of the intolerant group reacted to the fermentable sugar: 4 out of 10 fermenters did. Reactions to Thaumatin were similar in both groups. Fermenters were three times more likely than intolerants to crave sucrose. The craving was relieved by Isomaltulose in two‐thirds of this group, but Thaumatin had no effect on craving in either group. The results were statistically analyzed, but the numbers were probably too small to achieve significance.Subjects with apparent intolerance to sugars, starches, yeast and cheese may be affected not by intolerance, but by abnormal gut fermentation. Such patients may respond even to novel fermentable foods in a different way to intolerants, and tend to have sucrose craving. As the results of the fermentation include ethanol production the mechanism may well have biochemical unities with the addictive alcohol craving in alcoholics.

A laboratory study was performed comparing the patterns of urinary amino acid excretion in patients with chronic fatigue syndrome (CFS) with a control group of subjects without fatigue or allergy. Fifteen out of 21 patients in the CFS Group showed abnormal patterns with both reduced and increased excretion of some acids. In contrast, the control subjects showed only increased excretion of some acids, and a finding present in only four out of 20 subjects.