A gap detection tactility test for sensory deficits associated with carpal tunnel syndrome

An automated gap detection tactility test was investigated for quantifying sensory deficits associated with carpal tunnel syndrome (CTS). The test, which involved sensing a tiny gap in an otherwise smooth surface by probing with the finger, had functional resemblance to many work-related tactile activities such as detecting scratches or surface defects. Gap detection thresholds were measured using the converging staircase method of limits paradigm. Sixteen normal subjects between 21 and 66 years of age were tested for studying important factors affecting gap detection thresholds. Actively probing with the index finger had a threshold almost an order of magnitude more sensitive (mean = 0.19 mm, SD = 0.11 mm) than passive touch (mean = 1.63 mm, SD = 0.62 mm), which was similar to two-point discrimination. Average thresholds decreased by 24% as contact force increased from 25 to 75 g. Performance in this tactility test quickly stabilized and showed little learning effects over the period of the test, as evidenced by the lack of significant differences between six replicates. The results were highly repeatable. No significant threshold differences were observed between test and retest trials on different days, or between dominant and non-dominant hands. A contact force of 50 g was recommended as optimal for this test since it required moderate force but resulted in a smaller threshold compared with 25 or 75 g. A companion study was conducted using eight normal subjects and ten subjects diagnosed as having CTS. Average gap detection threshold, when finger probing was allowed, was 0.20 mm (SD = 0.11 min) for the normal subjects and increased two-fold to 0.40 mm (SD = 0.19 mm) for the CTS subjects. Average gap detection threshold, when the finger probing was not allowed, was 1.71 mm (SD = 0.53 mm) for the normal subjects and increased by 48% to 2.53 mm (SD = 0.87 mm) for the CTS subjects. The results suggest that people suffering from CTS may experience similar functional deficits in daily living and work activities. The small inter-subject variability makes this test a candidate for having utility as a monitoring test for loss of cutaneous tactile sensitivity.     

Sperm immobilizing activity of a synthetic bioactive peptide 20-44 of 37-kDa cationic antimicrobial protein (CAP37) of human neutrophils

We have previously reported that human sperm coincubated with human peripheral blood neutrophils in the presence of complement (C)-fixing antisperm antibody (ASA)-positive sera are rapidly internalized and degraded within the neutrophil phagolysosome. However, the mechanism by which motile sperm are processed within the phagolysosome is unknown. Various spermicidal/antimicrobial proteins contained in azurophilic granules that can be secreted into the phagolysosome may play a role in sperm disposal. In this study, we examined the expression of a 37-kDa cationic antimicrobial protein (CAP37) during sperm phagocytosis and the effect of its synthetic bioactive fragment, Peptide 20-44 (P20-44), on sperm motility, acrosomal integrity, and mitochondrial functionality. CAP37 expression by neutrophils undergoing ASA- and C-dependent sperm phagocytosis was increased as measured by flow cytometry. Exposure of motile sperm to a cationic P20-44, the bioactive antimicrobial fragment of CAP37, resulted in the loss of sperm motility without disruption of the acrosomal membrane. The sperm immobilizing activity (SIA) of P20-44 was modulated by the length of incubation, the concentration of the peptide, and the pH of the assay medium. SIA induced by P20-44 was partially reversible and was unaffected by the presence of anionic heparin or seminal plasma. Similar to the antimicrobial activity of P20-44, the SIA was also dependent on the presence of a disulfide bond between cysteine residues at positions 26 and 42 and was inhibited by Lipid A. However, the mechanism of action of P20-44 on sperm is not totally dependent on the molecule's cationicity, because five other cationic antimicrobial peptides had no detectable effect on sperm viability. Thus, the mechanism of action of P20-44 on human sperm is different from its cationic antibactericidal effect. These findings established that motile human sperm are sensitive to CAP37 or its synthetic bioactive peptide and suggested that this protein could play a role in neutrophil-mediated immune destruction of sperm in the female genital tract. P20-44 of CAP37 may be useful in investigating the regulation of human sperm motility and to construct "hybrid peptides" with enhanced potency as a component of vaginal contraceptive that could doubly be effective by killing infectious agents and inhibiting sperm transport.     

Peripheral blood-derived CD34+ progenitor cells: CXC chemokine receptor 4 and CC chemokine receptor 5 expression and infection by HIV

The present study demonstrates cell surface expression of both CXC chemokine receptor 4 (CXCR4) and CC chemokine receptor 5 (CCR5), major coreceptors for T cell-tropic and macrophage-tropic strains of HIV, respectively, on CD34+ progenitor cells derived from the peripheral blood. CD34+ progenitor cells were susceptible to infection by diverse strains of HIV, and infection could be sustained for prolonged periods in vitro. HIV entry into CD34+ progenitor cells could be modulated by soluble CD4, HIV gp120 third variable loop neutralizing mAb and the cognate ligands for the CXCR4 and CCR5 HIV coreceptors. This study suggests that a significant proportion of the circulating progenitor cell pool may serve as a reservoir for HIV that is capable of trafficking the virus to diverse anatomic compartments. Furthermore, the infection and ultimate destruction of these progenitor cells may explain in part the defective lymphopoiesis in certain HIV-infected individuals despite effective control of virus replication during highly active antiretroviral therapy.     

Effects of curvature and stenosis-like narrowing on wall shear stress in a coronary artery model with phasic flow

To gain insight into the details of intracoronary flow we have used computational fluid dynamic techniques to determine the velocity and wall shear stress distributions in both steady- and phasic-flow models of a curved coronary artery with several degrees of stenosis. The steady-flow Reynolds number was 500 and the peak phasic flow Reynolds number was 700. Without stenosis and at 25% (area) stenosis wall shear stress and velocities are higher at the outer wall than the inner wall but retain the same direction as the superimposed flow. At higher stenoses laminar flow separation occurs and the inner wall is exposed to shear stresses that vary widely, both temporally and spatially.     

A case of interatrial communication in a dog

A 4 month old female German Shepherd was presented for the work-up of a heart murmur that has been detected by the referring veterinarian. Clinical examination and thoracic radiography showed an enlargement of the right ventricle, and an increased pulmonary perfusion. Echocardiography showed an interatrial communication (atrial septum defect), and colour Doppler allowed the confirmation of a left to right shunt. The article discusses the diagnostic possibilities of this rare congenital cardiac malformation in the dog.     

Phase II study on cisplatin and ifosfamide in recurrent high grade gliomas

27 patients with recurrent high grade glioma following surgery and radiation therapy were treated with 100 mg/m2 cisplatin and 6 g/m2 ifosfamide per cycle, administered on days 1-3 in 4 week cycles, for a maximum of six cycles. Toxicity was assessed after every cycle. Response was assessed following every second cycle, and a 50% decrease of the largest cross-sectional tumour area on contrast enhanced magnetic resonance imaging or computed tomography scan was considered a partial response (PR). A total of 95 cycles was administered; 26 patients were evaluable for response. In 5 patients (19%), a PR was obtained (median time to progression (TTP): 34 weeks). Stable disease was observed in 6 patients (23%, median TTP: 22 weeks). The most frequent toxicity was haematological: 37% of cycles were complicated by a grade 3 or 4 leucopenia. 1 patients died, probably as a consequence of increased cerebral oedema induced by the cisplatin hydration schedule. Determination of the cisplatin concentration in this patient showed a 10-fold increase in the tumour concentration as compared with that in normal brain tissue, demonstrating the absence of a blood-brain barrier in the tumour. In conclusion, generally this schedule was well tolerated, but it is of moderate activity for recurrent glioma.