Solitary lucent epiphyseal lesions in children

We evaluated retrospectively the varying radiographic appearances of 15 solitary lucent epiphyseal lesions occurring in children. Imaging modalities used included plain films, conventional tomography, nuclear scintigraphy, and computed tomography. Forty percent of the lesions (6) were due to osteomyelitis. The remaining lesions included tuberculosis (1), foreign body granuloma (1), chondroblastoma (2), chondromyxoid fibroma (1), enchondroma (1), osteoid osteoma (2), and eosinophilic granuloma (1). Although the radiographic appearances of such lesions may be particularly characteristic, pathologic correlation is frequently necessary. The high incidence of osteomyelitis in our cases emphasizes its importance as a cause for a lucent epiphyseal lesion.     

Principles and clinical applications of positron emission tomography.

The basics of positron emission tomography (PET) are presented, including the physics, instrumentation, and radiopharmaceuticals involved; the clinical and research applications; and the cost. In PET, organic molecules labeled with positron-emitting radionuclides are injected or inhaled, and the high-energy photons produced by annihilation events are detected by paired, integrated crystal detectors. A computer uses the lines of origin of these photons to reconstruct a three-dimensional map of a functioning organ system. The positron-emitting radionuclides most often used are carbon 11, oxygen 15, nitrogen 13, fluorine 18, and rubidium 82. PET imaging centers usually consist of a cyclotron facility, a radiochemistry facility, a PET scanner, and computers for image reconstruction. Radiopharmaceuticals used in PET may be divided into blood flow-imaging agents, metabolic imaging agents, and drug receptor-imaging agents. Although PET is still primarily a research tool, it has shown diagnostic potential in neurology, cardiology, and oncology. It has also shown promise as a tool for pharmacologic assessment, as in studies of the effects of the fluorinated quinolones on cerebral blood flow and glucose metabolism. PET may become important in drug development because it yields specific information relatively noninvasively. A single study carries an average break-even price tag of $1500-$2000; rigorous cost-benefit analyses should be conducted before society is asked to subsidize such costs. Positron emission tomography is a frontier technology for which valuable clinical applications are being discovered. Pharmacists can contribute enormously to PET applications and at the same time establish a unique subspecialty for the profession.     

Delta 9-tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex

Acute administration of 1.0-2.0 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) increased presynaptic dopamine (DA) efflux in the medial prefrontal cortex of rats, as measured by intracerebral microdialysis in awake, behaving rats. These data are congruent with suggestions that (1) marijuana's euphorigenic effects and abuse potential may be related to augmentation of presynaptic DA mechanisms, and (2) the medial prefrontal cortex may be an important site of action for drugs of abuse in general and for delta 9-THC in particular.     

Severe cerebral edema in a patient with anasarca and hypernatremia.

We describe a woman whose fatal post-liver transplantation cerebral edema was unexpected and of unusual pathogenesis. Her severe cerebral edema is of considerable pathophysiologic interest: 1) it developed in the setting of marked anasarca and persistent hypernatremia, and 2) although hepatic function was poor, it was not considered sufficiently deranged to induce cerebral edema. Furthermore, there was no histologic evidence of hepatic rejection or antemortem hepatic necrosis. We postulate that an impairment of the blood brain barrier in association with a degree of hepatic dysfunction insufficient by itself to cause cerebral edema permitted the brain interstitial fluid volume to increase pari passu with ECF expansion. Cytotoxic cerebral edema and vascular engorgement may also have contributed to a life-threatening increase in intracranial pressure.     

The hevein domain of the major latex-glove allergen Hev b 6.01 contains dominant T cell reactive sites

BACKGROUND: Sensitization to natural rubber latex (Hevea brasiliensis) is a major cause of occupational asthma and rhinitis affecting frequent latex-glove users. Hev b 6.01, a known major latex allergen, is cleaved naturally into hevein (4.7 kDa) and a C-terminal fragment (14 kDa). Hevein is an abundant protein in latex-glove extracts. As the immune response to allergens is initiated by activation of allergen-specific CD4(+) T cells, identification of dominant T cell epitopes is crucial for the development of specific immunotherapy. OBJECTIVE: To identify dominant T cell epitopes of Hev b 6.01 in latex-allergic glove users. METHODS: Ten latex-allergic frequent glove users and six non-latex-allergic atopic control subjects were selected, based on clinical symptoms and positive latex-specific serum IgE. Serum IgE reactivity to glove extract and recombinant Hev b 6.01 (rHev b 6.01) were analysed by ELISA. Latex-specific short-term oligoclonal T cell lines were generated from peripheral blood of latex-allergic subjects. These lines were tested for proliferative responses to overlapping 20-mer peptides of the Hev b 6.01 molecule. CD4(+) T cell intracellular cytokines, IL-4 and IFN-gamma were assessed following stimulation with immobilized anti-CD3 in the presence of IL-2. RESULTS: All ten of the latex-allergic patients showed serum IgE binding to glove extract while eight of these also showed IgE binding to rHev b 6.01 by ELISA. Western blotting confirmed reactivity with rHev b 6.01 at around 20 kDa. T cell proliferation assays showed that latex-specific T cell lines from all subjects responded to one or more peptides, with greatest frequency of reactivity to peptides Hev b 6.01 p(10-29) and Hev b 6.01 p(19-38) in the hevein domain. An allergic-type cytokine profile with considerable IL-4 in addition to IFN-gamma was evident from intracellular cytokine staining. CONCLUSION: Hevein is an important T cell as well as B cell immunogen and contains dominant T cell reactive sites.     

Cystic fibrosis detection in high-risk Egyptian children and CFTR mutation analysis.

BACKGROUND: Knowledge about Cystic Fibrosis (CF) in Egypt is very limited. The objective of this study was to screen for CF in Egyptian children with suggestive clinical features and to identify causative genetic mutations. METHODS: Sixty-one patients from the Chest Unit, Cairo University Children's Hospital, Egypt, were included. Subjects presented with persistent or recurrent respiratory symptoms, failure to thrive, diarrhea and/or steatorrhea and unexplained persistent jaundice. Patients were screened using the CF Indicatortrade mark sweat test system (PolyChrome Medical, Inc., Brooklyn Center, MN). A quantitative sweat testing was conducted on 10 of the 12 positive patients. Seven probands and one sibling underwent molecular analysis by direct DNA sequencing of the coding region and of the intronic sequences adjacent to the 27 exons of the CFTR gene. RESULTS: Of 61 patients, 12 (20%) had positive sweat chloride screening. Ten of the 12 patients underwent quantitative sweat testing and were positive. Eight CFTR sequence changes were identified in seven affected probands and two were confirmed in one sibling by direct DNA sequencing. CONCLUSION: The study results suggest that CF is more common in Egypt than previously anticipated. Larger studies are warranted to identify the incidence, molecular basis and clinical pattern of CF in the Egyptian population.     

Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.     

The Hyperplantarflexion Ankle Fracture Variant

Various patterns of ankle fractures that are not accounted for by common classification systems have been the subject of case reports. The first difficulty with these variant patterns is recognizing all associated pathology, followed by the successful application of stable fixation. The purpose of this study was to describe the common morphologic features and ligamentous injuries of a unique variant fracture pattern, as well as the surgical treatment technique and the short-term functional and radiographic outcomes. Of 121 consecutive unstable ankle fractures over a 2-year period, 7 patients were found to have a similar constellation of injuries around the ankle. A vertical shear fracture of the posteromedial tibial rim was the main feature. Six of the 7 also had a fracture of the posterior malleolus. On magnetic resonance imaging, the deltoid and posterior tibiofibular ligaments were intact in all cases. Fractures were treated with open anatomic reduction of the posteromedial and posterior fragments with antiglide plate fixation. All fractures healed at 2 months without loss of reduction, fixation failure, or surgical complications. The average American Academy of Orthopaedic Surgeons lower extremity score was 79 at an average of 8 months' follow-up. The common radiographic and morphologic features associated with this posteromedial fracture indicate that it likely occurs through a common mechanism that involves hyperplantarflexion. The characteristics of this fracture pattern have not been fully described previously, but this ankle fracture variant may occur in up to 6% of cases. Unstable ankle fractures should be evaluated carefully for evidence of posteromedial involvement so appropriate treatment may proceed.