Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses.

Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membrane SCC, thus supporting a recessive risk factor for the development of cancer at both ocular locations. Analysis of genotype data from Haflinger horses with and without nictitating membrane SCC revealed that the same region on ECA12 associated with limbal SCC was also associated with nictitating membrane SCC (P < 2.04 × 10-5 ). Fine mapping of this locus using 25 cases and 49 controls supported the hypothesis that DDB2:c.1013C>T, p.Thr338Met, is a risk factor for nictitating membrane SCC, as 88% of our cases were homozygous for this variant and no other polymorphism was more strongly associated (P = 4.13 × 10-14 ). These data indicate that the genetic risk is the same for the development of both limbal and nictitating membrane SCC in Haflinger horses and validates utilization of genetic testing of the DDB2 variant for both clinical management and the guidance of mating decisions.

Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism.

Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by gonadotropin-releasing hormone deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5 months showed low testosterone (0.3 nmol/L) and undetectable gonadotropins (luteinizing hormone and follicle-stimulating hormone both <0.5 U/L), suggestive of CHH. Genetic testing identified a de novo, heterozygous mutation in fibroblast growth factor receptor 1 (FGFR1 p.L630P). L630 resides on the ATP binding cleft of the FGFR1 tyrosine kinase domain, and L630P is predicted to cause a complete loss of receptor function. Cell-based assays confirmed that L630P abolishes FGF8 signaling activity. Identification of a loss-of-function de novo FGFR1 mutation in this patient confirms the diagnosis of CHH, allowing for a timely hormonal treatment to induce pubertal development. Therefore, genetic testing can complement clinical and hormonal assessment for a timely diagnosis of CHH in childhood.

A review of 145 234 ophthalmic patient episodes lost to follow-up.

PurposeLost to follow-up and delays in follow-up care are a major problem in chronic diseases, particularly when irreversible progression precedes symptoms. The NPSA Glaucoma Safety Alert in 2009 highlighted the risk and requirements for consistent robust review systems in ophthalmology. In response, Moorfields Eye Hospital reviewed the records of all patients in all subspecialties without review appointments booked. The purpose of this study was to determine whether ophthalmic patients lost to follow-up had come to harm and develop investigation techniques to optimise safety, which do not put excessive demands on clinical staff time.MethodsThe health records of all patients lost to follow-up (LTFU) between July 2007 and November 2012 were reviewed for evidence of clinical harm using a risk-based strategy involving an initial administrative review, then a clinician led electronic patient record review, followed by a review of paper records by clinicians. The final stage was a clinical outpatient review where required determined by clinical risk.ResultsPatients identified as lost to follow-up were 145 234; 79 562 episodes were closed following administrative review; 50 519 were discharged following clinician examination of paper records; 12 316 patients required clinical review; and 16 serious incidents were identified, of which 14 patients had glaucoma, 1 a medical retinal condition with secondary glaucoma, and 1 an oculoplastic condition. A number of actions implemented hospital wide are described which minimise future risk.ConclusionRisk from delays or lost to follow-up care continue and require better capacity and more accurate data nationally.

Mindfulness-based cognitive therapy for psycho-oncology patients: an exploratory study.

OBJECTIVES: Mindfulness-based cognitive therapy (MBCT) is a group-based intervention similar to mindfulness-based stress reduction, but which includes cognitive therapy techniques. This study investigates its usefulness in the treatment of depressive, anxiety and stress/distress symptoms in cancer patients referred to a psycho-oncology service. It also examines whether effect on depression is mediated by self-compassion. METHOD: In phase 1 of this study, 16 cancer patients with mild/moderate psychological distress were randomised to MBCT (n=8) or treatment as usual (TAU; n=8), and assessed pre- and post-treatment. Analysis of variance was performed to examine the effect of treatment on anxiety and depression. In phase 2, the TAU group received the intervention, and results of pre- and post-MBCT assessments were combined with those receiving MBCT in phase 1. Finally, both groups were followed up at 3 months. RESULTS: In phase 1, the MBCT group had a significant improvement in mindfulness and a decrease in anxiety. Statistically significant improvements in both depression and anxiety were found at 3 month follow-up. Self-compassion appeared to mediate the effect on anxiety/depression. CONCLUSION: This small pilot study suggests that MBCT may have a beneficial effect on psychological variables often adversely affected in cancer in a heterogeneous cancer population.

Adaptation of the chronic disease self-management program for cancer survivors: feasibility, acceptability, and lessons for implementation.

Self-management in chronic disease has been shown to improve patient-reported and health care-related outcomes. However, relatively little information about its utility in cancer survivorship is known. We evaluated the feasibility and acceptability of the delivery of an adaptation of the evidence-based Chronic Disease Self-management Program (Stanford) called Cancer Thriving and Surviving (CTS). Triangulated mixed methods were used to capture baseline characteristics and post-program experiences using a combination of closed- and open-ended survey items; emergent coding and simple descriptive statistics were used to summarize the data. Twenty-seven workshops were delivered by 22 CTS leaders to 244 participants between August 2011 and January 2013 in a variety of settings (48 % community, 30 % health care, 22 % regional/community cancer center). Representing a variety of cancer types, about half the participants were 1-3 years post-diagnosis and 45 % were 4 or more years from diagnosis. Program attendance was high with 84 % of participants attending four or more of the six sessions in the workshop. Overall, 95 % of the participants were satisfied with the program content and leaders, and would recommend the program to friends and family. These results confirm the feasibility and acceptability of delivery of a high-fidelity, peer-led model for self-management support for cancer survivors. Expansion of the CTS represents a powerful tool toward improving health-related outcomes in this at-risk population.

Factitious disorder as a differential diagnosis for recurrent skin graft failure.

This case report presents the history of a 43-year-old man who sustained a relatively minor burn to his face but who subsequently suffered significant morbidity. Although the wound was grafted on a number of occasions, it failed to heal. Multiple investigations were carried out to determine the cause of recurrent wound breakdown. It had been suspected that the patient was interfering with the wound but this could not be proven initially. He was eventually diagnosed with factitious disorder and it was only when this was managed in the multi-disciplinary setting that his wound finally healed.

Complications after posterior dislocation of the hip.

Thirty-five consecutive patients with unilateral posterior dislocation of the hip were studied for complications at an average follow-up of 4.6 years (range 2-10 years). Thompson-Epstein type IV dislocation was most frequent (10/35), reflecting an increase in high-speed motor vehicles in the developing countries. It is also a severe injury that leads to a maximum number of complications, which include avascular necrosis, osteoarthosis, sciatic nerve injury and heterotrophic ossification. Avascular necrosis and osteoarthritis of the hip were observed maximally in type IV patients, even when reduction was achieved in less than twelve hours and may reflect the severity of initial injury. Heterotrophic ossification was observed in five of the ten patients with type IV dislocation and was associated with multiple attempts at reduction. Sciatic nerve injury did not recover completely in all cases, especially when reduction was delayed over twelve hours. Observing that the greatest numbers of complications were seen among patients with type IV dislocations, it may be prudent to warn such individuals about the likely prognosis at the outset, especially in today's world when the demands and expectations are high.

Psychiatric morbidity in a regional plastic surgery centre--one-year review with a proposed categorisation.

Few studies describe the incidence and nature of psychiatric morbidity in plastic surgery patients. We undertook a review of all referrals from the Plastic Surgery Service to the Psychological Medicine Service over a 1-year period (January-December 2001). Standardised socio-demographic information, nature and cause of injury/defect, surgical intervention, surgical outcome, psychiatric diagnosis and psychiatric follow-up were determined. The majority of patients referred had a significant existing psychiatric illness, had made a suicide/parasuicide attempt, or were burns patients. There was a high rate of referral of plastic surgery inpatients. Liaison with plastic surgery staff to allow rapid identification and early management of psychiatric morbidity is an important role for psychological medicine. We outline a defined categorisation of common contexts in which psychiatric morbidity may present to plastic surgery services.

Lymphangioleiomyomatosis: CT of diurnal variation of lymphangioleiomyomas.

PURPOSE: To evaluate the imaging and clinical features of lymphangioleiomyomas and to describe the phenomenon of diurnal variation in the size of lymphangioleiomyomas in patients with lymphangioleiomyomatosis. MATERIALS AND METHODS: One hundred twenty-eight patients with lymphangioleiomyomatosis underwent chest and abdominopelvic computed tomography (CT). Thirteen patients underwent CT in the morning and afternoon of the same day to assess diurnal variation in lymphangioleiomyoma size. RESULTS: Twenty-seven of 128 patients (21%) had 54 lymphangioleiomyomas. The vast majority (96%) of these masses contained material of low attenuation at CT. Associated CT findings included enlarged abdominal lymph nodes, pleural effusions, ascites, and dilatation of the thoracic duct. The prevalence of lymphangioleiomyomas was 15% in patients who had mild pulmonary disease, 19% in patients who had moderate disease, and 26% in patients who had severe disease. Diurnal variation in size of masses was demonstrated in 12 of 13 patients. Seven of the 27 patients who had masses underwent biopsy; all seven were confirmed to have lymphangioleiomyomas. The most common symptoms associated with lymphangioleiomyomas were bloating, abdominal pain, and edema of the lower extremities. The majority of the patients reported worsening of symptoms as the day progressed. CONCLUSION: Lymphangioleiomyomas are common in patients with lymphangioleiomyomatosis. Diurnal variation in size may explain worsening of symptoms during the day.

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients.

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.

Lymphangioleiomyomatosis: abdominopelvic CT and US findings.

PURPOSE: To describe the abdominal computed tomographic (CT) and ultrasonographic (US) findings in patients with thoracic lymphangioleiomyomatosis (LAM) and to relate the prevalence of the findings to the severity of pulmonary disease. MATERIALS AND METHODS: Eighty patients with LAM underwent chest and abdominopelvic CT and abdominopelvic US. The images were reviewed prospectively by one radiologist, and the abdominal findings were recorded and correlated with the severity of pulmonary disease at thin-section CT. RESULTS: Sixty-one (76%) of 80 patients had positive abdominal findings. The most common abdominal findings included renal angiomyolipoma (AML) in 43 patients (54%), enlarged abdominal lymph nodes in 31 (39%), and lymphangiomyoma in 13 (16%). Less common findings included ascites in eight (10%), dilatation of the thoracic duct in seven (9%), and hepatic AML in three (4%). A significant correlation (P =.02) was observed between enlarged abdominal lymph nodes and increased severity of lung disease. CONCLUSION: There are characteristic abdominal findings in patients with LAM that, in conjunction with the classic thin-section CT finding of pulmonary cysts, are useful in establishing this diagnosis.

Utilization of oriented peptide libraries to identify substrate motifs selected by ATM.

The ataxia telangiectasia mutated (ATM) gene encodes a serine/threonine protein kinase that plays a critical role in genomic surveillance and development. Here, we use a peptide library approach to define the in vitro substrate specificity of ATM kinase activity. The peptide library analysis identified an optimal sequence with a central core motif of LSQE that is preferentially phosphorylated by ATM. The contributions of the amino acids surrounding serine in the LSQE motif were assessed by utilizing specific peptide libraries or individual peptide substrates. All amino acids comprising the LSQE sequence were critical for maximum peptide substrate suitability for ATM. The DNA-dependent protein kinase (DNA-PK), a Ser/Thr kinase related to ATM and important in DNA repair, was compared with ATM in terms of peptide substrate selectivity. DNA-PK was found to be unique in its preference of neighboring amino acids to the phosphorylated serine. Peptide library analyses defined a preferred amino acid motif for ATM that permits clear distinctions between ATM and DNA-PK kinase activity. Data base searches using the library-derived ATM sequence identified previously characterized substrates of ATM, as well as novel candidate substrate targets that may function downstream in ATM-directed signaling pathways.

Head and neck schwannomas--a 10 year review.

Schwannomas of the head and neck are uncommon tumours that arise from any peripheral, cranial or autonomic nerve. Twenty-five to 45 per cent of extracranial schwannomas occur in the head and neck region and thus are usually in the domain of the otolaryngologist. They usually present insidiously and thus are often diagnosed incorrectly or after lengthy delays, however, better imaging and cytological techniques have lessened this to some degree more recently. For benign lesions conservative surgical excision is the treatment of choice bearing in mind possible vagal or sympathetic chain injury. Malignant schwannomas are best treated with wide excision where possible. The role of adjuvant therapy remains uncertain and irrespective of treatment modality prognosis is poor with an overall survival of 15 per cent. However, recent advances in ras oncogene inhibitors may hold hope for the future.

Autoimmune lymphoproliferative syndrome: a syndrome associated with inherited genetic defects that impair lymphocytic apoptosis--CT and US features.

PURPOSE: To describe the imaging findings in patients with autoimmune lymphoproliferative syndrome (ALPS) and to relate the findings to the clinical and genetic features of this recently recognized syndrome. MATERIALS AND METHODS: Retrospective or prospective reviews of the computed tomographic (CT) and ultrasonographic (US) studies and the clinical features in 19 consecutive patients with ALPS were performed. RESULTS: Most patients presented in the 1st year of life with symptoms of adenopathy and hepatosplenomegaly. At the time of presentation to the institution, 12 patients had already undergone splenectomy, and 14 patients had developed autoimmune disorders. All patients had multifocal adenopathy, which was massive in some patients; 14 of 15 patients who underwent CT of the chest had an enlarged thymus, and all six patients who retained their spleens and who underwent imaging had splenomegaly. Ten of 18 patients who underwent liver imaging had hepatomegaly. The adenopathy at US was hyper- and/or isoechoic relative to the liver and thyroid and was enhanced at CT in some patients. All patients had defective lymphocytic apoptosis, or programmed cell death, which was due to specific Fas (APT1 [TNFRSF6]) mutations in 15 patients. CONCLUSION: Patients with ALPS demonstrate nonspecific but often dramatic imaging findings of lymphoproliferative disorders, such as adenopathy, splenomegaly, thymic enlargement, and hepatomegaly. The stability of the clinical findings over months to years and the pattern of lymph node echogenicity may suggest the diagnosis of ALPS.

Polypoid lesions of airways: early experience with computer-assisted detection by using virtual bronchoscopy and surface curvature.

PURPOSE: To test the application of a technique developed by the authors for the computer-assisted diagnosis of polypoid airway lesions from surface rendered virtual bronchoscopic reconstructions. MATERIALS AND METHODS: A computer algorithm was developed to detect polypoid airway lesions by means of segmentation of the bronchial surface with curvature classification. This method was tested with a bronchial phantom, five cadaveric lung specimens, and virtual bronchoscopic studies in 16 patients. RESULTS: For the patient studies, the sensitivity and specificity of the method were 47%-88% and 58%-89%, respectively, depending on the value of an adjustable parameter (the mean curvature threshold). The sensitivity increased (by 20% to 34%) when only lesions larger than 5 mm in diameter were considered. CONCLUSION: With this method, polypoid airway lesions can be detected automatically, although false-positive diagnoses present an important limitation.

The use of intrathecal morphine for analgesia after posterolateral lumbar fusion: a prospective, double-blind, randomized study.

STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled study was undertaken to evaluate the efficacy and safety of intrathecal morphine for postoperative analgesia after posterolateral lumbar fusion. OBJECTIVES: To compare the early postoperative analgesia in patients who receive a single dose of intrathecal morphine intraoperatively with that of patients using a patient-controlled analgesia pump only. SUMMARY OF BACKGROUND INFORMATION: Although intrathecal morphine is used as an analgesic in a variety of medical and surgical conditions, very little has been published on its use after posterior lumbar spine surgery. Because the thecal sac is readily available during these procedures, the addition of a single injection of morphine before wound closure can be done with technical ease. If its efficacy and safety can be verified, then it could serve as a useful adjuvant to the postoperative analgesia regimen. METHODS: Sixty-eight consecutive patients undergoing posterolateral lumbar fusion were randomly assigned to two groups. The experimental group was injected intrathecally with morphine 30 minutes before wound closure, and the control group was similarly injected with a placebo of normal saline solution. All patients were connected to an on-demand patient-controlled analgesia pump to provide any additional necessary analgesia. Their use of the patient-controlled analgesia pump was tabulated by counting the number of demands and the actual amount of morphine delivered. Additionally, a visual analog scale was used to assess pain levels at pre-established regular intervals. RESULTS: The visual analog scale measurements were significantly lower for the intrathecal morphine group initially, but they surpassed those of the control group after 24 hours. Likewise, the number of patient-controlled analgesia pump demands and the amount of narcotic delivered initially were significantly lower in the experimental patients, but again reversed after the first postoperative day. The late rebound in pain and patient-controlled analgesia pump use did not reach statistical significance. There were no significant complications related to the analgesia. CONCLUSIONS: Intrathecal morphine can be safe and efficacious as an early postoperative analgesic after lumbar fusion when respiratory monitoring is used.

Grey matter heterotopia: an unusual association of intractable epilepsy.

Heterotopic grey matter is an abnormality of neuronal migration that has been reported in association with refractory epilepsy. In this study we reviewed the magnetic resonance (MR) imaging records of all patients undergoing MR scanning for evaluation of intractable epilepsy and identified sixteen patients who had grey matter heterotopia. The distribution of the grey matter heterotopia was periventricular in 9 patients, laminar in 3 and was in a "band" form in 4 patients. Congenital anomalies associated with grey matter heterotopia in this study included polymicrogyria in one patient and absence of the corpus callosum in 2 patients. Grey matter heterotopia is an important MR finding in patients with intractable epilepsy.

Advantages of polytetrafluoroethylene arteriovenous loops in the thigh for hemodialysis access.

BACKGROUND: The upper thigh is an alternative but infrequently used site to the forearm for placement of subcutaneous polytetrafluoroethylene (PTFE) arteriovenous conduits in patients requiring hemodialysis for end stage renal failure. This site has the great advantage of easier accessibility for self-cannulation. METHODS: The outcome was reviewed for 74 PTFE loops placed in 61 patients between 1985 and 1991. RESULTS: Mean loop survival time was 99.8 weeks (SD 78.0) when patients with early failure (<1 week), and those patients whose loops functioned adequately until transplantation or death were excluded. Infection occurred in 12 of 74 loops. CONCLUSIONS: Thigh PTFE loops provide satisfactory medium- to long-term vascular access for hemodialysis although, like all other forms of access currently available, they fall short of the ideal for prolonged dialysis.