3D contrast-enhanced MR angiography

Safe, fast, accurate contrast arteriography can be obtained utilizing gadolinium (Gd) and 3D MR data acquisition for diagnosing vascular diseases. Optimizing contrast enhanced MRA (CE MRA), however, requires understanding the complex interplay between Gd injection timing, the Fourier mapping of 3D MR data acquisition and a multitude of parameters determining resolution, anatomic coverage, and sensitivity to motion artifacts. It is critical to time the bolus peak to coincide with central k-space data acquisition, which dominates image contrast. Oversampling the center of k-space allows reconstruction of multiple 3D acquisitions in rapid succession to time-resolve the passage of the contrast bolus. Parallel imaging increases resolution, shortens scan time and compresses the center of k-space into a shorter period of time, thereby minimizing motion and timing artifacts. Absence of ionizing radiation allows MRA to be repeated and combined with additional sequences to more fully characterize anatomy, flow, and physiology. Utilizing stepping table technology and thigh compression, whole body MRA is possible with a single contrast injection. As MR technology continues to advance, CE MRA becomes better and simpler to perform, increasing its efficacy in the diagnosis and management of vascular diseases.     

Early therapeutic response assessment by (18)FDG-positron emission tomography during chemotherapy in patients with diffuse large B-cell lymphoma: isolated residual positivity involving bone is not usually a predictor of subsequent treatment failure

Residual 2-fluoro-2-deoxyglucose (FDG) - positron emission tomography (PET) positivity during treatment of patients with diffuse large B-cell lymphoma (DLBLC) prospectively identifies a subgroup at high likelihood of subsequent treatment failure. A single institution clinical audit of FDG-PET performance for this indication was undertaken for patients with DLBCL treated with anthracycline-based chemotherapy +/- radiotherapy. Of 45 eligible patients, 14 (31%) were PET-positive after a median of three chemotherapy cycles (range 1 - 5), of which 10 (71%) progressed at a median of 6.5 months. An interim positive PET was a statistically significant adverse prognostic factor for treatment failure (P < 0.0001, log-rank analysis) with a hazard ratio for a positive interim-treatment PET of 9 (95% confidence interval = 4 - 55) and positive predictive value of 71% and negative predictive value of 90%. Notably, four patients with low-grade FDG-avidity limited to sites previously involved by biopsy-proven osseous lymphoma, remain progression-free (median follow-up 62 months). Low-grade FDG-avidity on interim restaging at sites of bone involvement by DLBCL at diagnosis, appears to be less predictive of disease progression than residual nodal or extra-nodal soft tissue abnormality by PET.     

Osteonecrosis of the jaw complicating bisphosphonate treatment for bone disease in multiple myeloma: an overview with recommendations for prevention and treatment

Osteonecrosis of the Jaw (ONJ) is a recently recognised and potentially highly morbid complication of bisphosphonate therapy in the setting of metastatic malignancy, including myeloma. Members of the Medical and Scientific Advisory Group of the Myeloma Foundation of Australia formulated guidelines for the management of bisphosphonates around the issue of ONJ, based on the best available evidence in June 2008. Prior to commencement of therapy, patients should have an oral health assessment and be educated about the risks of ONJ. Dental assessment should occur 6 monthly during therapy. If tooth extraction is required, sufficient time should be allowed for complete healing to occur prior to commencement of bisphosphonate. As the risk of ONJ increases with duration of bisphosphonate therapy, we recommend annual assessment of dose with modification to 3 monthly i.v. therapy or to oral therapy with clodronate for those with all but the highest risk of skeletal-related event. Established ONJ should be managed conservatively; a bisphosphonate "drug holiday" is usually indicated and invasive surgery should generally be avoided. These recommendations will assist with clinical decision making for myeloma patients who are at risk of bisphosphonate-associated ONJ.     

Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.     

A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2)

Progressive myoclonus epilepsy of the Lafora type or Lafora disease (EPM2; McKusick no. 254780) is an autosomal recessive disorder characterized by epilepsy, myoclonus, progressive neurological deterioration and glycogen-like intracellular inclusion bodies (Lafora bodies). A gene for EPM2 previously has been mapped to chromosome 6q23- q25 using linkage analysis and homozygosity mapping. Here we report the positional cloning of the 6q EPM2 gene. A microdeletion within the EPM2 critical region, present inhomozygosis in an affected individual, was found to disrupt a novel gene encoding a putative protein tyrosine phosphatase (PTPase). The gene, denoted EPM2, presents alternative splicing in the 5' and 3' end regions. Mutational analysis revealed that EPM2 patients are homozygous for loss-of-function mutations in EPM2. These findings suggest that Lafora disease results from the mutational inactivation of a PTPase activity that may be important in the control of glycogen metabolism.      

Preliminary evidence of disease response to the pan deacetylase inhibitor panobinostat (LBH589) in refractory Hodgkin Lymphoma

There are few treatment options for patients with Hodgkin Lymphoma (HL) who relapse after conventional therapies. Panobinostat is an orally available pan deacetylase inhibitor with evidence of activity in myeloid malignancies and cutaneous T cell lymphoma. Thirteen HL patients were treated with escalating doses of this novel agent in a phase IA/II multicentre study. A computed tomography partial response was achieved in 5/13(38%), and a metabolic response by ¹⁸F-fluoro-2-deoxy- d - glucose positron emission tomography scanning in 7/12 (58%) evaluable patients. This report describes the preliminary evidence of anti-tumour activity seen in the early phase of this study, which recently closed to accrual.     

Scarring alopecia: clinical and pathologic study of 54 African-American women

Background  Cicatricial or scarring alopecia results in the destruction of hair follicles and is a significant cosmetic concern in African-American women.
Objective  To correlate the clinical examination and histologic findings in African-American women with scarring alopecia with a history of hairstyling practices.
Methods  We reviewed retrospectively the medical records and scalp biopsy specimens of 54 women with scarring alopecia. Patients were selected from two dermatologic practices in the Detroit Metropolitan area.
Results  Alopecia commonly presents in patients who use a variety of traumatic haircare techniques, including chemical and physical straighteners, traction, braiding, hair extensions, hair gluing, and chemical curls. Histologic findings are centered around the follicular infundibulum with a lymphocytic infiltrate and perifollicular fibrosis.
Conclusion  Traumatic hairstyling techniques are common in African-American women, and all result in a similar picture of a peri-infundibular lymphocytic infiltrate and fibrosis, leading to alopecia.