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Accumulating research has linked Mediterranean diet (MeDi) adherence with slower cognitive decline and reduced Alzheimer’s disease (AD) risk. However, no study to-date has examined the relationship between MeDi adherence and accumulation of cerebral Aβ-amyloid (Aβ; a pathological hallmark of AD) in older adults. Cognitively normal healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing completed the Cancer Council of Victoria Food Frequency Questionnaire at baseline, which was used to construct a MeDi score for each participant (score range 0–9; higher score indicating higher adherence). Cerebral Aβ load was quantified by Pittsburgh Compound B positron emission tomography at baseline, 18 and 36 months: Only individuals categorised as “Aβ accumulators”, and thus considered to be on the AD pathway, were included in the analysis (N = 77). The relationship between MeDi adherence, MeDi components, and change in cerebral Aβ load (baseline to 36 months) was evaluated using Generalised Linear Modelling, accounting for age, gender, education, Apolipoprotein E ε4 allele status, body mass index and total energy intake. Higher MeDi score was associated with less Aβ accumulation in our cohort (β = −0.01 ± 0.004, p = 0.0070). Of the individual MeDi score components, a high intake of fruit was associated with less accumulation of Aβ (β = −0.04 ± 0.01, p = 0.00036). Our results suggest MeDi adherence is associated with reduced cerebral AD pathology accumulation over time. When our results are considered collectively with previous data linking the MeDi to slower cognitive decline, it is apparent that MeDi adherence warrants further investigation in the quest to delay AD onset. © 2018, The Author(s).

Keratoacanthoma (KA) is a benign keratinocytic neoplasm that usually presents as a solitary nodule on sun-exposed areas, develops within 6–8 weeks and spontaneously regresses after 3–6 months. KAs share features such as infiltration and cytological atypia with squamous cell carcinomas (SCCs). Furthermore, there are reports of KAs that have metastasized, invoking the question of whether or not KA is a variant of SCC. To date no reported criteria are sensitive enough to discriminate reliably between KA and SCC, and consequently there is a clinical need for discriminating markers. We screened fresh frozen material from 132 KAs and 37 SCCs for gross chromosomal aberrations by using comparative genomic hybridization (CGH). Forty-nine KAs (37.1%) and 31 SCCs (83.7%) showed genomic aberrations, indicating a higher degree of chromosomal instability in SCCs. Gains of chromosomal material from 1p, 14q, 16q, 20q, and losses from 4p were seen significantly more frequently in SCCs compared with KAs (P-values 0.0033, 0.0198, 0.0301, 0.0017, and 0.0070), whereas loss from 9p was seen significantly more frequently in KAs (P-value 0.0434). The patterns of recurrent aberrations were also different in the two types of neoplasms, pointing to different genetic mechanisms involved in their developments.

ST7 is a candidate tumour suppressor gene at human chromosome locus 7q31.1. We have performed mutational analysis of ST7 in a wide-range of cell lines and primary epithelial cancers and detected only one missense change in a breast cancer cell line. Other mutations previously found in cell lines and primary tumours were not evident in our analysis. These results imply that another tumour suppressor gene at this locus may be more important than ST7 in carcinogenesis. British Journal of Cancer (2002) 37, 208–211. doi:10.1038/sj.bjc.6600418 www.bjcancer.com © 2002 Cancer Research UK

Objective To assess the factors that can predict the success of external needle revision of failing blebs. Design Retrospective, nonrandomized, comparative case series. Participants Forty-nine eyes of 43 patients who underwent a needle revision of a filtration bleb with 5-fluourouracil (5-FU) by one physician (SVLB) between August 1993 and December 1994. Intervention Needle revision of a failing filtration bleb using 5-FU. Main outcomes The intraocular pressure, glaucoma medications, and any complications. Results The risk ratio of fornix-based trabeculectomies compared with limbus-based trabeculectomies was 3.781; P = 0.047. The risk ratios for gender, race, type of glaucoma, lens status, previous surgery, antimetabolite used for the initial trabeculectomy, and preoperative bleb characteristics were not statistically different for any one group. Conclusions Fornix-based trabeculectomies were more likely to fail the needle revisions compared with limbus-based trabeculectomies. None of the five preneedling bleb characteristics showed a propensity toward success or failure. Other demographics such as gender, race, type of glaucoma, previous surgery, antimetabolite used for the initial trabeculectomy, and lens status were also not predictive for success.

Sir, In response to the report of Le Mire et al.1 on the incidence of malignant melanoma in Oxford renal transplant recipients (RTRs), we detail our experience of melanoma in a series of RTRs at Bart’s and the London NHS Trust. Although incidence rates in our population were similar to those documented in the Oxford study, metastatic disease was more common, and we suspect that RTRs with melanoma may have a worse prognosis than their immunocompetent counterparts, although larger, multicentre studies are now required to confirm this. A retrospective clinical and histological review of melanomas diagnosed in patients attending a dedicated RTR dermatology clinic between 1990 and 2005 was performed. All specimens were resectioned and were assessed by an experienced dermatopathologist (R.C.). In a total population of 861 RTRs with a follow-up period of 8557 patient-years, there were seven cases of de novo melanoma (five invasive and two in situ) in three men and four women. All diagnoses were made in the RTR dermatology clinic. Clinicopathological data are presented in Table 1 and are illustrated in Figure 1. All patients were on prednisolone and azathioprine, with or without ciclosporin. The mean age at diagnosis was older than in Oxford [57·7 years (range 44-68) vs. 41] and the mean time from transplantation was shorter [102 months (range 10-247) vs. 132]. All patients had skin types I-III (although 20% of our RTR cohort have skin type V or VI). None had a family history of melanoma or fulfilled criteria for atypical mole syndrome, although two patients had several atypical naevi. A high proportion of patients had a history of other invasive skin tumours (five of seven vs. four of 10 in Oxford); in all but one patient (patient 1) these tumours arose prior to the diagnosis of melanoma. Melanomas were more commonly located on the head and neck in our series, with four of seven tumours occurring at this site, in contrast to the Oxford tumours which all occurred at extracephalic sites. Ten of 12 tumours in the Oxford series were superficial spreading melanomas, whereas this subtype accounted for two of our seven cases. As in the Oxford series, Breslow thickness in the majority of cases (five of seven) was < 1 mm, and an inflammatory response was either minimal or absent in all melanomas, as has previously been documented.2 A contiguous pre-existing naevus was present in only one case, and, similarly, was detected in only a minority (three of 12) of the Oxford cases, in contrast to a previous proposal that over half of all transplant melanomas arise in pre-existing naevi.2 All melanomas in our series were treated by complete surgical excision; sentinel lymph node biopsy was not available at the time these tumours were diagnosed. In most cases immunosuppression was reduced, but not stopped. Fig 1 Clinical and histological examples of melanoma in renal transplant recipients. (a) Patient 6: lentigo maligna melanoma on right side of nose, Breslow thickness 0·4 mm. (b) Patient 2: lentigo maligna on cheek. (c) Photomicrograph of histology, ... Table 1 Clinicopathological data This series represents an elevated incidence of melanoma in our London RTR cohort: the rate in 2003 for the general population in North East Thames was 6·5 and 8·1 per 100 000 population for men and women, respectively, and we would therefore have expected approximately 0·9 cases of melanoma to have arisen in our cohort (in which 64% are male). If in situ tumours are included, these 7 cases represent an approximately 7·8-fold increased incidence compared with the general population. This is remarkably similar to the eightfold increased rate found in Oxford, and is of the same order as that reported by Moloney et al.3 who reported a 6·6-fold increase in males with melanoma in an Irish transplant population. These more recent studies report rates higher than previous estimates.4-6 Three patients in our series, but only one patient in Oxford, died from metastatic melanoma. Two deaths occurred in RTRs with melanomas exceeding 2 mm Breslow thickness. In accordance with American Joint Committee on Cancer staging, the predicted 5-year survival for patient 3 was 67% and that for patient 4 was 63%,7 yet both died within approximately 2 years. Even more unexpectedly, patient 6 developed metastases from a lentigo maligna melanoma of Breslow thickness 0·4 mm, for which the expected 5-year survival is 95% or greater. Our series of patients is too small to give statistical confirmation of a poorer prognosis in RTRs and previous studies have also not had sufficient power to examine this, although a compromised outcome from melanoma has similarly been observed in individuals with human immunodeficiency virus infection or AIDS.8 The incidence of melanoma is rising faster than for any other major cancer and will continue to do so over at least the next 30 years.9 In conjunction with the steadily improving long-term survival from organ transplantation, it is likely that post-transplant melanoma will emerge as an increasing clinical problem in coming years. Many important questions have yet to be answered in this respect: whether prognosis is, indeed, worse for post-transplant melanoma, whether more aggressive management strategies are therefore required, and how reduction in immunosuppression should be approached. Although consensus statements such as those recently reported in this Journal are a useful guideline to management of post-transplant skin cancer,10 a firmer evidence base is now required. This is a particular priority for management of post-transplant melanoma, and sufficient power to reach meaningful conclusions is only likely to be achieved in the context of a multicentre study. Such a study is currently being coordinated within the SCOPE network (Skin Care in Organ transplant Patients, Europe: http://www.scopnetwork.org) by our centre, and we invite clinicians who are interested in participating to contact us.

We describe the use of a new instrument designed to create a simultaneous goniopuncture with diathermy using an ab-interno technique. The goniodiathermy ab-interno procedure was first performed on three eyes of three cynomolgus monkeys. Intraocular pressure (IOP) assessment and histologic examination were performed over a 10-day period. A functioning filtration bleb with a patent sclerostomy was achieved in all of the experimental eyes. A pilot study involving four eyes of four glaucoma patients also was performed. Of these four, successful long-term functioning filtration areas with adequate lowering of IOP were achieved in only two. The remaining two required further surgical intervention. Although combining goniopuncture and diathermy into a one-step ab-interno procedure proved successful in the primates studied, the preliminary use of this new instrument as a method of creating a filter in humans raises questions regarding its clinical usefulness.

Nonbullous congenital ichthyosiform erythroderma (NBCIE) is one of the autosomal recessive inherited non-syndromic ichthyoses and is currently diagnosed on clinical grounds alone. Skin cancer is not a recognized complication of NBCIE. We report here two NBCIE patients who have developed multiple aggressive nonmelanoma skin cancers, predominantly cutaneous squamous cell carcinoma. NBCIE may be a risk factor for skin cancer development.

Objective To evaluate the safety and efficacy of 5% imiquimod cream for cutaneous dysplasia in high-risk renal transplant recipients. Design A randomized, blinded, placebo-controlled study comparing treated with control skin. Setting A specialist organ transplant dermatology clinic. Patients Twenty-one high-risk patients with skin cancer with comparable areas of clinically atypical skin on dorsal hands or forearms. Interventions Imiquimod or placebo (randomly assigned) applied 3 times a week for 16 weeks to 1 dorsal hand or forearm, with 8 months of follow-up. At week 16, biopsy samples were collected from preassigned sites in the treatment and control areas and were examined for dysplasia. Main Outcome Measures The proportion of patients showing reduced numbers of viral and keratotic lesions and reduced histological severity of dysplasia in the treatment vs control areas at week 16, serum creatinine levels, and tumors developing in the study sites. Results Fourteen patients receiving imiquimod and 6 receiving placebo completed the study. Seven patients using imiquimod (1 taking placebo) had reduced skin atypia, 7 using imiquimod (none taking placebo) had reduced viral warts, and 5 using imiquimod (1 taking placebo) showed less dysplasia histologically. In 1 year, fewer squamous skin tumors arose in imiquimod-treated skin than in control areas. Renal function was not adversely affected. Conclusions Topical 5% imiquimod cream seems to be safe on skin areas up to 60 cm2 in renal transplant recipients. It may be effective in reducing cutaneous dysplasia and the frequency of squamous tumors developing in high-risk patients. Larger studies are required to confirm these results. Author Affiliations: Centre for Cutaneous Research and Department of Dermatology, Barts and The London School of Medicine & Dentistry, Queen Mary, University of London (Drs Brown, Cerio, Harwood, and Proby and Ms Atkins), and Cancer Research UK Skin Tumour Laboratory (Drs Ghali, Harwood, and Proby), London, England.

Summary Background Viral warts may cause significant morbidity in individuals unable to mount an adequate T-helper 1 cell-mediated immune response to human papillomavirus. Imiquimod is a potent inducer of antiviral cytokine activity which has shown significant efficacy in the treatment of genital warts. Similar efficacy in cutaneous warts is not yet established. Objectives To assess the response of persistent cutaneous warts to 5% imiquimod cream in immunosuppressed individuals. Methods Fifteen immunosuppressed patients with warts on the hands and/or feet present for more than 18 months, which had failed to respond to a minimum of 12 weeks of topical salicylic acid and four cycles of cryotherapy, were recruited. Imiquimod 5% cream was applied in an open label, right vs. left comparison study for 24 weeks (three times weekly for 8 weeks, daily for 8 weeks, then daily with occlusion for 8 weeks). Results Twelve (80%) patients completed the study protocol. Benefit was seen in five patients [36% in the intent-to-treat analysis (14 patients)], including more than 30% clearance of warts in three patients and reduction in overall size of warts in two further cases. Local skin reactions occurred in four (29%) patients and were usually mild. A transient rise in creatinine (11–29% above baseline) was measured in three renal transplant recipients, but we did not consider that this was related to imiquimod exposure. Conclusions This is the first controlled study to assess therapeutic efficacy of topical 5% imiquimod cream in persistent warts associated with immunosuppression. It provides preliminary evidence that topical imiquimod may benefit a subgroup of immunosuppressed patients with recalcitrant cutaneous warts.

Purpose: The authors compared the effectiveness of limbus- and fornix-based conjunctival flaps in patients undergoing combined phacoemulsification, intraocular lens implantation, and mitomycin C trabeculectomy. Methods: The authors conducted a retrospective review of the records of 52 consecutive eyes of 45 patients who underwent combined surgery with limbus- and fornix-based conjunctival flaps. All surgery was by done by one surgeon on predominantly white patients in a suburban glaucoma subspecialty practice. Seven patients had both limbusand fornix-based surgery, permitting fellow eye comparisons in these patients. All patients had at least 6 months and a median of 17 months follow-up. None of the eyes that were operated on had undergone intraocular surgery previously. Results: No clinically significant difference in postoperative pressure reduction, bleb survival, or visual acuity was seen between the fornix- and limbus-based groups. Results in the fellow eye comparison subgroups were similar. The mean intraocular pressure decreased from 20.4 mmHg before surgery to a mean of 12.4 mmHg at the last followup visit. Forty-seven (90.3%) of 52 eyes had a final best-corrected visual acuity of 201 40 or better. Forty eyes (76.9%) no longer needed antiglaucoma medications at the end of follow-up. Five eyes had intraoperative posterior capsule rupture; all of these occurred in the limbus-based group. Shallow serous choroidal effusions were more common in the fornix-based group, but none were clinically significant. No difference in postoperative astigmatism between the limbus- or fornix-based group was seen. Intraoperative pupilloplasty, synechialysis, or postoperative neodymium:YAG capsulotomy had no appreciable effect on final intraocular pressure or bleb survival. Endophthalmitis, aqueous misdirection, or hypotony maculopathy did not develop in any patient. Conclusion: The effectiveness of limbus- and fornix-based conjunctival flaps appears to be similar. The limbus-based technique may result in a higher incidence of posterior capsular rupture, but the safety of limbus- and fornix-based flaps is otherwise similar. Combined phacoemulsification and mitomycin C trabeculectomy appears to be safe and effective for treating selected patients with coexisting glaucoma and cataract.

I report the use of partial-thickness Tenon'sconjunctival tissue in the repair of an intraoperative scleral-flap buttonhole that developed during trabeculectomy using adjunctive mitomycin C.

The short-pulse laser may prove superior to the argon laser in producing noninvasive iridectomies. Little is known of the effects of the laser shockwave on anterior segment structures adjacent to the iris. To investigate this question, iridectomies were produced in two owl monkeys using a neodymium (Nd):YAG laser and tissues were evaluated by light microscopy and scanning and transmission electron microscopy. For purposes of comparison, one eye received an iridectomy produced by an argon laser. Results indicate that while clean iris colobomas can be produced with a well-focused Nd:YAG laser, its shock-wave affects tissues in both the trabecular meshwork and corneal endothelium if the iridectomy is located within 0.8 mm of the limbus. No damage to the trabecular meshwork or corneal endothelium was evident after the argon laser iridectomy.

A prospective study was conducted in 30 eyes of 30 patients to determine if pilocarpine would prevent increased intraocular pressure following Q-switched neodymium (Nd):YAG laser posterior capsulotomy. Fifteen eyes were given pilocarpine 4%, immediately following laser therapy and every hour until bedtime. Fifteen eyes served as untreated controls. Our results show that without prophylactic therapy, 10 of 15 eyes (67%) had a post-laser intraocular pressure (IOP) elevation of greater than 10 mmHg, while only one of 15 (6.6%) of the pilocarpine-treated eyes had a rise of that magnitude. The facility of outflow was reduced by 42% in the untreated eyes in contrast to an increase of 3% in those eyes treated with pilocarpine. Thus, pilocarpine 4% is effective in reducing the incidence and magnitude of elevated IOP following Nd:YAG posterior capsulotomy.

Thirty-nine eyes of 34 patients with open-angle glaucoma who had been treated successfully with argon laser trabeculoplasty underwent either extracapsular cataract extraction with posterior chamber intraocular lens implantation or intracapsular cataract extraction without lens implantation. Cataract surgery did not have a significant effect on the magnitude of intraocular pressure reduction obtained with laser trabeculoplasty. This study supports the view that eyes with coexisting cataract and glaucoma may benefit from laser trabeculoplasty before cataract surgery.

A surgical approach that involves paracentesis and gentle anterior chamber washout and minimal surgical trauma is presented for dealing with traumatic hyphema. This technique taught by Dr. Paul Chandler produces excellent results and is safe, simple, and without need for elaborate instrumentation.

Because of inadequate control of intraocular pressure, 26 eyes of 24 patients with primary and secondary open-angle glaucoma who had previously undergone argon laser trabeculoplasty were re-treated. Re-treatment was successful in ten eyes (38%); their average decrease in intraocular pressure was 10.2 mm Hg. After laser re-treatment, three eyes (12%) had marked increases in intraocular pressure, ranging from 10 to 37 mm Hg above baseline, necessitating urgent surgical intervention.

The Radiation Monitoring Equipment (RME) was flown on STS-11 Space Shuttle Mission for the purpose of testing a concept for in-cabin, real-time crew dosimetry, and for the purpose of obtaining time resolved gamma-ray background data and neutron/proton background data. The RME consists of two instruments, EG&G HRM-III gamma-ray counter and EG&G Pocket REM Meter (PRM) neutron/proton dosimeter. The HRM-III was operated by the astronaut crew four times during the mission with each operation lasting 52.5 minutes. The PRM was operated twice during the mission with each operation lasting a minimum of 15 hours. The results from the HRM-III operations were plotted as a function of time and as a function of ground position. The data show large increases in count rate during periods when the Orbiter was in the East Asian Anomaly. These data are consistent with the data obtained from other missions. The RPM results are displayed in tabular form. The average dose rate from these operations is . 359mrem/hr ((2.84) x 10 to the 5th rad/hr). The total mission neutron/proton dosage predicted by these readings is approximately 60.30mrem (4.77mrads).