Dnmt3a regulates T-cell development and suppresses T-ALL transformation.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm resulting from the malignant transformation of T-cell progenitors, and comprises ~15% and 25% of pediatric and adult ALL cases, respectively. It is well-established that activating NOTCH1 mutations are the major genetic lesions driving T-ALL in most patients, but efforts to develop targeted therapies against this pathway have produced limited success in decreasing leukemic burden and come with significant clinical side effects. A finer detailed understanding of the genetic and molecular mechanisms underlying T-ALL is required identify patients at increased risk for treatment failure and the development of precision medicine strategies. Generation of genetic models that more accurately reflect the normal developmental history of T-ALL are necessary to identify new avenues for treatment. The DNA methyltransferase enzyme DNMT3A is also recurrently mutated in T-ALL patients, and we show here that inactivation of Dnmt3a combined with Notch1 gain-of-function leads to an aggressive T-ALL in mouse models. Moreover, conditional inactivation of Dnmt3a in mouse hematopoietic cells leads to an accumulation of immature progenitors in the thymus, which are less apoptotic. These data demonstrate that Dnmt3a is required for normal T-cell development, and acts as a T-ALL tumor suppressor.

Lumbosacral epidural lipomatosis causing rapid onset cauda equina syndrome.

Spinal epidural lipomatosis (SEL) is a rare cause of cauda equina syndrome (CES), which must be diagnosed with MRI in conjunction with a high level of clinical suspicion. Most reported cases are associated with obesity, steroid use or are secondary to endocrinopathies, frequently present subacutely or chronically, and have been managed with both surgical decompression and non-operative measures. We describe an obese 55-year-old man with rapid onset CES secondary to idiopathic lumbosacral SEL which was managed successfully with surgical decompression. Although often thought to be a trivial radiological finding, it is important not to be dismissive of patients presenting with compressive neuropathy and MRI evidence of space-occupying SEL.

Brown tumour of the spine in a renal transplant patient.

We report a 30-year-old male who had undergone a renal transplant and suffered with secondary hyperparathyroidism. He presented with back pain and minimal neurological deterioration, caused by a thoracic brown tumour. The imaging findings, surgical treatment of the spinal lesion and outcome are discussed. We also discuss primary medical therapy and suggest a rational approach to further imaging of patients in whom brown tumour is suspected.

Acute, disruptive cough.

Preview Acute, disruptive cough is the second most common reason for which office visits are made and prescriptions written. But even when specific therapy is prescribed, a disruptive nonproductive cough may become nagging and prompt a patient to seek help again. The authors discuss the mechanism and causes of cough and describe symptomatic therapies in terms of their proposed mechanisms and indications.

Common pitfalls in the diagnosis and treatment of sexually transmitted diseases.

To facilitate proper diagnosis of STDs, they must be considered as a diagnostic possibility in all sexually active patients. Whenever possible, appropriate laboratory tests must be performed to confirm a clinical diagnosis. Once the diagnosis is established, the physician can administer specific and adequate treatment. The physician should have a comprehensive up-to-date treatment schedule to select a recommended treatment. Such treatment schedules are available upon request from most municipal and state health departments.