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.     

Follistatin and activin A production by the male reproductive tract

Follistatin is a binding protein for the activin and inhibin family of hormones, regulating their biological activity. In the male reproductive tract, the interaction of these factors is likely to be involved in the regulation of the proliferation of several cell types. We have investigated the presence of follistatin and activin A in seminal plasma using specific immunoassays and have localized follistatin and activin/inhibin subunits in the adult human testis, prostate and seminal vesicle to establish their likely sources. High concentrations of immunoreactive follistatin were present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in peripheral plasma) and were similar in men with oligo/azoospermia and following vasectomy. Follistatin immunoreactivity was localized to both Leydig and Sertoli cells of the testis, and to epithelial cells of the prostate gland and seminal vesicle, which are likely to be the predominant sources of the hormone in seminal plasma. Activin A was also present in seminal plasma in normal men but was undetectable following vasectomy, thus deriving from the testis. Consistent with this finding, the betaA-subunit was immunolocalized in Sertoli and Leydig cells but was not present in seminal vesicle or prostate gland. The functional significance of the high concentrations of follistatin secreted into seminal plasma by the prostate gland and/or seminal vesicle is uncertain, but they may regulate the biological activity of testis-derived activin A and inhibin B.      

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Hodgkin disease: contributions of chest CT in the initial staging evaluation

Chest radiographs and chest computed tomography (CT) scans were compared in 203 patients with newly diagnosed Hodgkin disease. The incidence of positive findings was tabulated from six intrathoracic lymph node groups, lung parenchyma, pericardium, pleura, and chest wall. The discordant cases were assessed to determine impact on clinical management. The CT scans provided additional evidence of disease involvement, ranging from 0% to 15% at each of the designated anatomic sites. Treatment was altered in 9.4% of all patients (19 of 203), including 13.8% (nine of 65) of those undergoing radiation therapy alone and 8.2% (ten of 122) of those undergoing combined-modality treatment. We conclude that routine chest CT examinations are valuable in the clinical management of those patients for whom radiation therapy is planned.     

Simulated implant surgery in rabbit long bones: a descriptive study.

The objectives of this study were: (a) to observe and describe the variability of bone healing in implant receptor sites which were prepared in rabbit femurs by use of different surgical methods; and (b) to determine if the animal model which was used was suitable for the detection of differences in healing reactions in implant receptor sites which were prepared by different surgical methods. Three 3-mm-wide implant receptor sites were prepared in the right and left femurs of four large New Zealand white rabbits. The surgical parameters used in preparation of the different sites included: low speed with no irrigation (LSO); low speed with internal irrigation only (LSI); low speed with external irrigation only (LSE); high speed with no irrigation (HSO); or high speed with external irrigation only (HSE). The sites were randomized so that each animal had one of each type of site in either the right or left femur. A non-treated control site was located in each animal for comparison with experimental sites. The animals were killed at 7, 14, 21, and 28 days post-operatively. The resultant samples were fixed, embedded, sectioned, and stained with basic fuchsin and toluidine blue. The results indicated that this was probably not a suitable animal model, since no discernible differences were detected in the various healed sites.     

Recall of childhood illnesses

Recall of eight childhood communicable diseases and other illnesses was validated among 95 adults by comparison to longitudinal childhood health records. Self-reports at age 50 of several illnesses were highly accurate; however, German measles was correctly recalled by only 34% of subjects. Similar levels of accuracy were consistently found among a subset who also completed health history interviews 8 and 20 years earlier. Over-reporting of some health events was common. Past exposure to viral or bacterial agents is sometimes assessed in case-control studies by self-reports. Misclassification of prior exposure due to faulty recall may distort true associations between childhood illness and chronic disease in later life.     

Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes

We have recently isolated a cDNA encoding a novel human intracellular tyrosine kinase, termed RAFTK (for a related adhesion focal tyrosine kinase). The RAFTK cDNA, which encodes a polypeptide of 1,009 amino acids, shares 65% homology to the focal adhesion kinase (FAK), including several consensus motifs. In this report, we describe the biochemical characterization and functional analysis of the RAFTK protein. Coexpression of RAFTK and FAK proteins in megakaryocytic cells and blood platelets was observed. Using a specific antibody to RAFTK and the monoclonal antibody 2A7 to FAK, FAK and RAFTK could be distinguished antigenically. RAFTK had intrinsic tyrosine kinase and autokinase activities. It was phosphorylated on tyrosine in growing cultures of COS cells transfected with the pCDNAIII/flag-RAFTK expression vector containing the RAFTK cDNA ligated with the 8 amino acid flag peptide sequence. Similar to FAK, dephosphorylation of RAFTK was observed when adherent transfected COS cells were detached. Phosphorylation was regained upon replating of these cells on the fibronectincoated dishes. Analysis of tyrosine-phosphorylated RAFTK from adherent transfected COS cells showed that the Src homology 2 (SH2) domains of the Src and Fyn protein kinases as well as the Grb2 adaptor protein were able to specifically associate with RAFTK. Tyrosine phosphorylation of endogenous RAFTK was observed upon fibronectin-induced activation of human megakaryocytic cells. Furthermore, colocalization of RAFTK protein with vinculin, a focal adhesion protein, was observed by confocal microscopy in focal adhesion- like structures in adherent CMK cells and in transfected pCDNAIII/flag- RAFTK COS cells upon fibronectin activation. These data suggest that RAFTK is a novel member of the FAK family, that it localizes to focal adhesion-like structures in CMK megakaryocytic cells, that it participates in integrinmediated signaling pathways in megakaryocytes, and that it is able to associate with the tyrosine kinases Src and Fyn as well as the adaptor protein Grb2 via SH2-phosphotyrosine interactions.