I. Poloxamer-formulated plasmid DNA-based human cytomegalovirus vaccine: evaluation of plasmid DNA biodistribution/persistence and integration

Preclinical studies were conducted in mice and rabbits to evaluate biodistribution/persistence and potential integration of plasmid DNA (pDNA) after intramuscular administration of a poloxamer-formulated pDNAbased vaccine, VCL-CT01, encoding gB, pp65, and IE1 human cytomegalovirus (hCMV) immunogens. Tissue distribution in mice vaccinated with VCL-CT01 was compared with that in mice vaccinated with a phosphate- buffered saline (PBS)-formulated control pDNA vaccine. Residual pDNA copy number (PCN), in selected tissues collected on days 3, 30, and 60 after vaccination, was measured by quantitative polymerase chain reaction. In VCL-CT01-vaccinated mice and in control pDNA-vaccinated mice, pDNA was below the limit of detection by day 60 in all tissues except the injection site. Clearance of pDNA from the injection site was slower in VCL-CT01-vaccinated mice compared with PBS-pDNA-vaccinated mice. An integration study was conducted in rabbits to determine whether pDNA integration into the genome of the vaccinated animal contributed to pDNA persistence. Residual pDNA in VCL-CT01-injected rabbit muscle collected 60 days after vaccination (geometric mean of 1085 PCN/microg total DNA) was comparable to that observed in VCL-CT01- injected mouse muscle (geometric mean of 1471 PCN/microg total DNA) collected at the same time point. pDNA integration was not detectable by column agarose gel electrophoresis despite the persistence of pDNA at the injection site 60 days after vaccination. Therefore the risk of genomic integration of hCMV pDNA formulated with poloxamer was considered negligible.     

A case of allergic bronchopulmonary aspergillosis leading to pneumonia with unusual organisms

We describe the case of a 50-year-old male with a history of asthma and seizure disorder who presented with a 5-month history of dyspnea. The patient had been treated with multiple courses of antibiotics for presumed community-acquired pneumonia before being determined to have allergic bronchopulmonary aspergillosis (ABPA) by serologic and radiographic criteria. Inflammation resulting from this disease had potentiated a postobstructive pneumonia caused by Nocardia asteroides and Stenotrophomonas maltophilia. Therapy with corticosteroids, trimethoprim sulfa, and voriconazole failed to prevent subsequent destruction of the right upper lobe and the patient required surgical intervention. The discussion emphasizes the diagnostic criteria for ABPA including historic, serologic, and radiographic findings; staging, and treatment. Other possible diagnoses, such as invasive pulmonary aspergillosis, chronic necrotizing aspergillosis, and hyper-IgE syndrome are also briefly reviewed.     

Pituitary adenomas in childhood

Pituitary adenomas are common tumors composed of adenohypophysial cells.Although they usually arise in the sella turcica, they may occasionally be ectopic. Pituitary adenomas are rarely diagnosed in. childhood and adolescence, but their mass effect and endocrine abnormalities can compromise both quality and length of life. Many signs or symptoms of pituitary adenoma, complained of in adulthood, not became evident during adolescence, suggesting true prevalence of this tumor in teenagers is higher than expected. Pititury adenoma occuring during adolescence are associated with features or therapeutic needs sometimes different from those occuring in adulthood. At the onset of disease, delay in growth was rarely observed in teenagers with pituitary adenomas. Many girls complain of oligoamenorrhoea and galactorrhoea, while heActache and delay in pubertal development are the most commons features in boys. Hypopituitarism is occasionally encountered in adolescence. Early diagnosis and appropriate choice of therapy are necessary to avoid permanent endocrine complications of disease and its treatment.     

Syncope and head CT scans in the emergency department

Context Patients presenting with syncope to the emergency department (ED) of a community hospital were evaluated. Aim The objective of this study is to examine the use and results of head computerized tomography (CT) scans in patients presenting with syncope to the ED of a community hospital. Settings and design A retrospective chart review of patients presenting with syncope to the emergency room was conducted. Methods and materials We reviewed the charts of patients who presented to the ED over a 6-month period with syncope. When performed, head CT scan findings were noted, and their relationship to the clinical presentation was examined. Results One hundred twenty-eight patients were identified. Forty-four patients had their head CT scans performed. In 1 patient, the CT scan showed evidence of infarction in the posterior circulation. In 19 patients, the head CT scan was normal. Twenty-four patients had abnormal findings unrelated to the ED presentation. Conclusions Head CT scans were commonly used in our series of syncope patients. Abnormal findings pertinent to the syncope were observed in only 1 patient. A prospective study examining yield in a larger series of patients may help define the utility of this neuroimaging modality in syncope.     

Dopamine transporter as target for drug development of cocaine dependence medications

Because much evidence implicates the dopamine transporter in the reinforcing effects of cocaine, development of potential medications for cocaine dependence has included the dopamine transporter as a target. The present overview covers progress in the drug development area regarding several classes of dopamine uptake inhibitors, with an emphasis on structure-activity relationships that enhance potency and selectivity at transporters for dopamine compared with those for serotonin or norepinephrine. The following categories of compounds are covered: tropane, benztropine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR), methylphenidate, mazindol, and phencyclidine analogs. Activity at transporters as well as on behavior is highlighted.