Classification of endonasal HHT lesions using digital microscopy.

BACKGROUND: Recurrent spontaneous epistaxis is the most common clinical manifestation and the most debilitating symptom in hereditary haemorrhagic telangiectasia (HHT) patients. To this date, there exist only a classification of HHT patients by different genetic mutations. There is no standard classification for the mucocutaneous endonasal manifestations of HHT. The aim of the present study was to document the variety of endonasal HHT lesions using digital microscopy and to propose a clinical classification. METHODS: We recorded the endonasal HHT lesions of 28 patients using a digital microscope. We reconstructed the 3D images und videos recorded by digital microscope afterwards and classified the endonasal lesions of HHT in two classes: Grade A, presence of only flat telangiectasias in the mucosa level and Grade B, (additional) presence of raised berry or wart-like telangiectasia spots. We investigated also Haemoglobin level by routine laboratory procedures, plasma VEGF level by ELISA, Severity of epistaxis by epistaxis severity score (ESS) and quality of life by a linear visual analogue scale (VAS). RESULTS: We found a higher quality of life and a lower severity of epistaxis in Grade A patients in comparison to Grade B patients. No difference in plasma VEGF level and in Haemoglobin between Grad A patients and Grade B patients could be detected. Plasma VEGF levels showed no gender specific differences. It could also not be correlated to the extranasal manifestation. CONCLUSION: The classification for endonasal manifestation of HHT proposed in this study indicates severity of epistaxis und quality of life. Digital microscopy with the ability of 3D reconstruction of images presents a useful tool for such classifications. The classification of endonasal HHT lesions using digital microscopy allows to evaluate the dynamic of HHT lesions in the course of time independent of examiner. This allows also to evaluate the efficacy of the different treatment modalities by dynamic of HHT lesions. Moreover digital microscopy is very beneficial in academic teaching of rare diseases.

Pruritic arthropod bite-like papules in T-cell large granular lymphocytic leukaemia and chronic myelomonocytic leukaemia.

T-cell large granular lymphocytic leukaemia (T-LGLL) is a clinically indolent mature T-cell neoplasm characterized by a monoclonal population of CD3+ CD8+ cytotoxic T cells, which usually presents as neutropenia, anaemia and thrombocytopenia. Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic disorder with features of both a myeloproliferative neoplasm and myelodysplastic syndrome (MDS). Patients with CMML exhibit a persistent peripheral blood monocytosis in addition to myelodysplastic features. Because of the rarity of T-LGLL, its cutaneous manifestations are poorly documented, but include vasculitis, vasculopathy, persistent ulcerations, generalized pruritus and disseminated granuloma annulare. Various types of skin lesions have been observed in patients with CMML and reportedly occur in approximately 10% of cases. We report the extraordinary case of a patient with MDS who developed T-LGLL, and subsequently the MDS progressed to CMML. The patient then developed diffuse arthropod bite-like papules and intractable pruritus.

Model Development of Illness Perception and Consequences in Breast Cancer Patients.

Breast cancer is the first or second malignancy among women worldwide. Illness perception (IP) and quality of life (QoL) are major issues considering breast cancer management. An attempt was here made to inspect the predictive variables influencing IP and their impact on QoL in cancer patients. The key predictors adapted from previous studies including life satisfaction, perceived social support, self-esteem, hope, optimism, and spiritual well being were taken into account. Our sample included 200 female volunteers suffering from breast cancer applying exclusion criteria. The data were collected using various questionnaires and statistically analyzed by means of path analysis and structural equation modeling. The results revealed that of the six predictors, spiritual well being and social support had direct effects on QoL and IP. The only path with significant indirect correlation with IP was social support. Spiritual well being had the second significant direct effect on IP. Self-esteem occupied the third rank in direct effects on both QoL and IP. In conclusion, here in Iran and most likely in other strongly religious communities, spiritual intervention is an effective strategy to raise QoL. Also social support helps women suffering from breast cancer to experience better conception and coping strategies.

Posterior tension band wiring and instrumentation for thoracolumbar flexion-distraction injuries.

PURPOSE: To evaluate treatment outcome of tension band wiring followed by posterior spinal fusion and instrumentation for thoracolumbar flexiondistraction injury (FDI). METHODS: 36 men and 12 women aged 21 to 56 (mean, 36) years underwent tension band wiring followed by posterior spinal fusion and instrumentation using pedicular screws for FDI of the thoracolumbar spine. The injured vertebral levels were T11 (n=2), T12 (n=12), T11-T12 (n=1), T12-L1 (n=1), L1 (n=28), and L2 (n=4). Anterior vertebral body height and kyphosis were measured before and after surgery. Neurologic status was assessed using the American Spinal Injury Association (ASIA) scale. The Oswestry Disability Index questionnaire and visual analogue scale for pain were also used. RESULTS: The mean follow-up was 38 (range, 26-72) months. At final follow-up, the mean visual analogue scale for pain was 1.7, and the median Oswestry Disability Index was 4% (range, 0-32%). The mean anterior vertebral body height improved from 20.5 to 38.8 mm (p<0.001). The mean kyphosis improved from 20.4º to 1.5º (p<0.001). Four patients had persistent neurologic deficit: ASIA scale C (n=2) and D (n=2); their ASIA scales improved by one grade. All patients returned to their original work at 6 months. There were no intra-operative complications or implant failures. CONCLUSION: Posterior tension band wiring followed by posterior spinal fusion and instrumentation for thoracolumbar FDIs achieved good outcome.

Influencing factors on the functional level of haemophilic patients assessed by FISH.

Joint destruction in early adulthood brings the patients to the orthopaedic clinics. If a haemophilic patient becomes disabled, it shows a number of factors such as timely diagnosis, availability of appropriate treatment depending on the country, access and affordability to treatments and equally importantly the responsibility of the patient in managing self care by remaining compliant by prescribed treatment regimen. We assessed the functional level by functional independence score in haemophilia (FISH). Overall, 104 patients with haemophilia A and 29 with haemophilia B were evaluated. We assessed the function of the patients by FISH. We divided the sum scores into weak (FISH score 8-16), moderate (17-24), and good (25-32). For evaluating the level of functional deficit in a 2 × 2 table, we categorized the weak and moderate levels into Disordered Group and the good level into Not-Disordered Group. The average age was 26.9 ± 14.24. Each 1 year increase in age can increase 1.07 fold the possibility of being placed in Disordered Function Group. Severe haemophilia can increase 7.34 fold, presence of inhibitor can increase 9.75 fold and home self-care increases 3.89 fold the possibility of being placed in Disordered Function Group. To decrease the burden of the cost on patient, family and the government, education plays the most important role. We suggest that we send a trained team of physician and nurses to the deprived villages and cities instead of waiting for the patient to refer to our Care Center.

Does percutaneous kyphoplasty have better functional outcome than vertebroplasty in single level osteoporotic compression fractures? A comparative prospective study.

Purpose. To evaluate the relative differences in surgical outcome of kyphoplasty (KP) versus vertebroplasty (VP) in the patients with single level refractory osteoporotic compression fractures (OCFs). Method. From August 2008 to May 2012, we intermittently treated 57 patients with single level OCF by PV and KP (Groups A and B, resp.). We used visual analogue scale (VAS) and short form 36 (SF36) questionnaire to measure functional recovery and followed them for six months. Independent samples t- and Kendall's tau-b tests were for statistics. Results. In terms of age, number, and bone mineral density of the patients, there were no significant differences between the two groups. In both groups, VAS and SF-36 scores improved significantly and remained relatively stable throughout the follow-up period. We had 9 and 6 asymptomatic cement extravasations and 5 and 8 new vertebral fractures in Group A and B, respectively. In comparing the two groups, the results indicated that KP almost failed to show any significant higher effect relative to VP during this period. Conclusions. In considering the high cost of KP relative to VP in the developing countries like Iran, there is no logical reason to use KP in a single level refractory OCF in these regions.

Functional Outcomes of Surgery in Cervical Spondylotic Radiculopathy versus Myelopathy: A Comparative Study.

Background. Cervical spondylosis can cause three different categories of symptoms and signs with possible overlap in the affected patients. Aim. We aim to compare functional outcome of surgery in the patients with cervical spondylotic radiculopathy and myelopathy, regardless of their surgical type and approach. Materials and Methods. We retrospectively reviewed 140 patients with cervical spondylotic radiculopathy and myelopathy who had been operated from August 2006 to January 2011, as Group A (68 cases) and Group B (72 cases), respectively. The mean age was 48.2 and 55.7 years, while the mean followup was 38.9 and 37.3 months, respectively. Functional outcome of the patients was assessed by neck disability index (NDI) and patient satisfaction with surgery. Results. Only in Group A, the longer delay caused a worse surgical outcome (NDI). In addition, in Group B, there was no significant relationship between imaging signal change of the spinal cord and our surgical outcomes. Improvement in NDI and final satisfaction rate in both groups are comparable. Conclusions. Surgery was associated with an improvement in NDI in both groups (P < 0.001). The functional results in both groups were similar and comparable, regarding this index and patient's satisfaction score.

Strong optical interaction of two adjacent rectangular nanoholes in a gold film.

The strong near-field optical interaction between two adjacent nanoholes milled in a gold film is investigated. A single nanohole is modeled as a magnetic dipole described by the simple relation between the magnetic- and electric-polarization in electromagnetic theory. To elucidate the role of the electric and magnetic fields in near-field characteristics of a nanohole illuminated by an optical plane-wave, the normalized electric and magnetic power amplitudes are accordingly introduced. This is extended to model the strong optical interaction of the two adjacent nanoholes in the near-field regime, leading to the magnetic coupled-dipole approximation (MCDA). It is shown that the optical transmission spectrum of the nanostructure may exhibit hybridized resonant peaks, depending on the configuration or the polarization. Compared to the known effects in the optical properties of a pair of metal nanoparticles for which the electric-field of the incident light is crucial, here it is illustrated that the magnetic-field of the incident light plays the dominant role in defining the optical properties of the complement structure. Thus, the strength of the interaction of the two adjacent nanoholes and the resulting hybridized plasmon resonances are strongly depends on the magnetic-field orientation in respect to the pair axis as well as on the separating distance of the nanoholes. The theoretical findings are supported by the electromagnetic computations.

Magnetic Resonance Imaging versus Electrophysiologic Tests in Clinical Diagnosis of Lower Extremity Radicular Pain.

Introduction. Radicular low back pain is one of the most common medical problems. The aim of this study was to evaluate the diagnostic accuracy of MRI and electrodiagnosis in lower extremity radicular pain in relation to history and clinical findings. Methods. In this cross-sectional study, we studied 165 sciatalgic subjects. A comprehensive history and physical examinations were taken from the subjects and recorded, and then MRI scanning and electrodiagnostic (nerve conduction velocity and electromyography) tests were performed. Results. From 152 subjects who remained in the study, 67 cases (44.1%) had radicular pain in left lower limb, 46 (30.3%) in right, and 39 (25.6%) in both lower limbs. 104 cases (68.4%) had shown some type of abnormalities in both MRI and electrodiagnosis, 30 (19.7%) had shown this abnormality only in MRI, and 21 (13.8%) only in electrodiagnosis, while 10 cases (6.5%) had both normal MRI and electrodiagnostic studies. Coordination rates of MRI and electrodiagnosis with clinical findings were 58.6% and 89.5%, respectively. Conclusion. In many MRI negative but symptomatic subjects, electrodiagnosis has an important diagnostic value.

Sexuality after breast cancer: need for guideline.

BACKGROUND: Clinical experiences have revealed that patients with breast cancer experience various sexual problems following their treatment. Breast cancer negatively impacts the sexual life of the afflicted couples, and as a traumatic event can influence women's psychosexual functioning and intimate relationship. This review focuses on sexuality after breast cancer and on a growing need for bio-psycho-social guidelines for breast cancer treatment. METHODS: This study aims to review the literature on management, psychological outcomes and sexual dysfunction in patients with breast cancer. RESULTS: Although the benefits of the current treatment strategies are well established, many cancer survivors are at risk for developing psycho physiological symptoms including sexual dysfunction. Cancer and treatment-related factors can influence sexual functioning. We review current treatment-related side effects on sexual functioning such as desire, arousal and orgasm in breast cancer patients. Despite the impact of medical treatment on survival of patients with breast cancer, no satisfactory steps have been taken towards improving sexual functioning of these patients. CONCLUSION: Breast cancer affects many aspects of sexuality, including changes in physical functioning and in the perception of feminity. Sexual dysfunction following breast cancer should be diagnosed and managed as a systematic approach with multidisciplinary inputs. Healthcare professionals should assess the effects of medical and surgical treatment on the sexuality of breast cancer survivors.

Painful and tender toe, osteoid osteoma of the distal phalanx of toe, a diagnostic dilemma.

Osteoid osteoma rarely involves the phalanges of the toes. Basically osteoid osteoma is often a diagnostic dilemma in musculoskeletal practice especially in the foot and ankle. Its presentation is confusing and this may result in delayed diagnosis. We have reported a case of osteoid osteoma of the distal phalanx of the second toe which was treated successfully with surgical excision and reviewed the literature.

Phase I trial of i.v. administered tirapazamine plus cyclophosphamide.

Our objective was to determine the maximum tolerated doses of tirapazamine and cyclophosphamide given i.v. in combination. Eligible patients had advanced solid tumors refractory to conventional treatment. Tirapazamine (escalated from 80 to 390 mg/m(2)) was given i.v. over 2 h and followed by cyclophosphamide over 1 h. The cyclophosphamide dose was fixed at 1000 mg/m(2) until the tirapazamine dose of 390 mg/m(2) was reached. Once that dose of tirapazamine was reached, the cyclophosphamide dose was escalated to 1250 and 1500 mg/m(2). Twenty-eight patients were enrolled. The dose-limiting toxicity was granulocytopenia. One patient had transient deafness for 2 days. Four other patients had grade 1 ototoxicity. Grade 1 and 2 muscle cramps were observed at all dose levels. Other toxic effects observed included fatigue, nausea, vomiting, headache, diarrhea, drug fever, elevated transaminases and elevated creatine phosphokinase. Three patients had stable disease and the longest time to progression was 5 months. The combination of tirapazamine and cyclophosphamide is feasible, and the dose-limiting toxicity is granulocytopenia. The use of growth factors could possibly allow escalation of tirapazamine doses in future phase II trials. Without growth factor support, the recommended doses of tirapazamine and cyclophosphamide when administered in this schedule are 260 and 1000 mg/m(2), respectively.

Myelodysplasia presenting as granulocytic sarcoma of mediastinum causing superior vena cava syndrome.

Granulocytic sarcomas (GS) are extramedullary tumor masses of immature myeloid cells, most frequently associated with hematological disorders including acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS). Recent interest has centered upon the possible biologic properties that enable theses myeloid cells to adhere to tissues and establish a tumor mass. GS presenting as a mediastinal mass is relatively infrequent, and more uncommon is presentation with the superior vena cava syndrome. We present one such case and review some of the available literature.

Variations in the low levels of cyclin D1/BCL1 have prognostic value in chronic lymphocytic leukemia.

Cyclin D1 (CyD1)/BCL1 (PRAD1) is expressed at high levels in almost all cases of mantle cell leukemia/lymphoma (MCL) and in rare cases of chronic lymphocytic leukemia (CLL). The CyD1/BCL1 protein plays an important role in the progression of cells through the G1 phase of cell cycle. Most of the CyD1/BCL1 protein expression studies are performed using immunohistochemistry. We used a sensitive solid-phase radioimmunoassay (RIA) to quantify CyD1 protein expression in 199 patients with CLL. Of these 137 patients were previously untreated with the rest having had standard chemotherapeutic regimens including alkylating agents and fludarabine before being referred to our center. Median white cell count in these patients was 49x10(3) /microl (range 3.0-438.5x10(3)/microl), hemoglobin level 13.1 g/dl (range 5.2-17.3 g/dl), platelet count 157x10(3) /microl (range 10-377x10(3) /microl), age 58 (range 26-89), and beta2-microglobulin 2.75 mg/dl (range 1.1-14.3). The median radioactivity (CPM) of mononuclear cells obtained from 56 normal individuals was assigned a value of 1. There was no significant variation in CyD1 levels among normal individuals (SD=0. 12). While most CyD1 levels in MCL varied from 6.5 to 15.6, the median CyD1/BCL1 in CLL was 1.4 with 75th percentile under 2.12. Rare CLL cases (3.5%) showed levels between 4 and 8.83. When divided into two groups at the median level, patients with higher CyD1/BCL1 expression had shorter survival (P = 0.03). This remained true when applied only to the previously untreated patients (P=0.05). Despite the relatively low expression, the CyD1/BCL1 levels in univariate analysis were as good or better predictors of survival than Binet (P = 0.03) or Rai (P = 0.05) staging. Furthermore, CyD1/BCL1 levels correlated with serum beta2-microglobulin (P = 0.001), white blood cell count (P = 0.004) and hemoglobin levels at the time of collection (P = 0.0003) but not with lymphocyte count, platelet count or age. The data demonstrate that CyD1/BCL1 is likely to play a significant role in the biology of CLL and can be used as a prognostic indicator. Further studies to clarify the role of CyD1 in the biology of CLL and its value as a prognostic indicator at the time of diagnosis are encouraged.

Cutaneous ulcers associated with hydroxyurea therapy in myeloproliferative disorders.

Hydroxyurea (HU) is an established chemotherapeutic agent in the treatment of myeloproliferative disorders (MPD) including chronic myelogenous leukemia (CML), polycythemia vera and essential thrombocythemia (ET). It is well tolerated, has minimal toxicities, and produces hematological response in most patients treated. Side effects of hydroxyurea are few and include myelosuppression, oral ulcers and skin rashes. Cutaneous toxicity is rare. This study aims to describe the occurrence of cutaneous ulcerations attributed to HU therapy in patients with MPD, and familiarize the oncology community with this unusual but disturbing toxicity of HU. Five patients with MPD receiving HU therapy at doses of 0.5 to 4 g/day who developed skin ulceration were reviewed (median age was 53 years). Three patients had Philadelphia positive CML, and two had ET. Cutaneous ulcers developed after a long period of HU therapy (median 36 months, range 7 to 96 months). The time after discontinuation of HU to the healing of the ulcers was 1 to 4 months. Ulcers developed mainly in the lower extremities particularly adjacent to the malleoli, indicating a possible relation to trauma. In conclusion, cutaneous ulceration represents a poorly recognized and rare HU-related side effect. Discontinuation of HU usually leads to slow resolution of the ulcers over several months. The etiology of this rare side effect remains poorly understood.

Fluoropyrimidines: a critical evaluation.

After nearly four decades of clinical experience with the fluoropyrimidines, 5-fluorouracil (5-FU) remains an integral part of chemotherapy for colorectal cancer. A range of 5-FU treatment regimens with or without biochemical modulation are currently used and toxicity appears to be schedule dependent. The use of oral 5-FU was abandoned because of erratic absorption caused by varying levels of dihydropyrimidine dehydrogenase (DPD) found in the gastrointestinal tract. This effect may be overcome by administering agents that are converted to 5-FU or by inhibiting or inactivating DPD. Xeloda((R)) (capecitabine) was designed as an orally administered, selectively tumoractivated(TM) cytotoxic agent which achieves higher levels of 5-FU in the primary tumor than in plasma or other tissues. The United States Food and Drug Administration (FDA) has approved Xeloda for use in patients with metastatic breast cancer resistant to paclitaxel and in whom further anthracycline therapy is contraindicated. Xeloda is also registered in Canada, Switzerland, Thailand and Argentina. In phase II clinical trials in colorectal cancer, Xeloda produced response rates of 21-24% and median time to disease progression of 127-230 days. Other oral agents in development for the treatment of colorectal cancer include tegafur/uracil plus oral leucovorin, S-1 and eniluracil plus oral 5-FU.

Granulocytic sarcoma of the pancreas: a report of two cases and literature review.

Granulocytic sarcomas (GS) are extramedullary tumour masses of immature myeloid cells, also known as chloroma and extramedullary myeloid cell tumour. These neoplasms usually occur simultaneously with, or follow the onset of acute myeloid leukaemia (AML). Rarely, they are the first manifestation of AML. GS may also be the first sign of transformation to AML in patients with chronic myeloproliferative disorders and myelodysplastic syndromes. GS have been reported to occur in a variety of tissues, but presentation as an abdominal mass and, in particular, infiltration of the pancreas is rare. We report two cases of pancreatic GS, review the literature, and discuss recent insights into the basic biological properties of these rare tumours.

Thrombotic microangiopathy associated with interferon therapy for patients with chronic myelogenous leukemia: coincidence or true side effect?

BACKGROUND: Interferon-alpha (rIFN-alpha) is an established therapy for patients with myeloproliferative disorders. Unusual immune-mediated side effects have been associated with rIFN-alpha therapy. The association of rIFN-alpha therapy with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) has been reported infrequently. METHODS: Two patients with chronic myelogenous leukemia (CML) treated with rIFN-alpha-based regimens at the University of Texas M. D. Anderson Cancer Center developed thrombotic microangiopathy (HUS/TTP). The course of their disease is described. A third patient who developed renal failure while receiving rIFN-alpha therapy and had no other causative factor for his renal failure is also described. RESULTS: The patients were ages 24, 49, and 36 years, and they had received rIFN-alpha therapy for 37, 67, and 92 months, respectively, prior to the development of the disorder. One patient had discontinued rIFN-alpha 1 month before the event because of presumed rIFN-alpha-related cardiomyopathy. Two patients received hydroxyurea and cytarabine as part of their therapy. No patient was receiving any medication known to be associated with HUS/TTP. None had a history of diarrheal illness, but Escherichia coli OH157.H7 was grown from the stool of one patient. Two patients responded to plasmapheresis with normalization of counts and other indices, but both developed renal failure and became dependent on dialysis. One patient had evidence of disease progression and died of multiorgan failure. The third patient required dialysis for 18 months but is currently off dialysis; this patient has some residual renal impairment. CONCLUSIONS: Although no definitive association between rIFN-alpha therapy and thrombotic microangiopathies can be concluded from these data, these and other previously reported cases suggest that HUS/TTP is a rare side effect of rIFN-alpha therapy that should be managed in the standard fashion. Hypotheses regarding the mechanism underlying this association are discussed in this article.

Hypereosinophilia Progressing to Granulocytic Sarcoma and Acute Myelocytic Leukemia with Trisomy 8: A Case Report and Review of the Literature.

Conditions associated with increased peripheral blood and bone marrow eosinophil count may be reactive, clonal or idiopathic. Clonal eosinophilic disorders are characterized by increased production of eosinophils alongside a clone of malignant cells. In these patients, the eosinophils can either be demonstrated as being part of the malignant clone or produced as a result of cytokine production by the malignant clone. Criteria for the diagnosis of idiopathic hypereosinophilic syndrome (HES) include the exclusion of other known causes of hypereosinophilia. A few patients with the initial diagnosis of HES develop clonal disorders manifested by granulocytic sarcoma or acute leukemia. We report a patient with a nine year history of HES before progressing to chloroma and acute leukemia. Cytogenetic studies on the bone marrow specimen revealed trisomy 8. This report and others in the literature support the concept that at least some cases of HES are as yet unidentified clonal diseases. Cytogenetic studies are therefore recommended at diagnosis and during the follow up of patients with HES.