Elevated plasma glycocalicin levels and decreased ristocetin-induced platelet agglutination in hemodialysis patients

A bleeding diathesis caused by platelet dysfunction is a major cause of morbidity and mortality in patients with uremia. Platelet adhesion to vascular subendothelium is defective in uremia and depends on the interactions of the platelet glycoprotein (GP) Ib/IX complex with the vascular wall. We measured levels of platelet surface GPIb, platelet surface GPIX, plasma glycocalicin (a product of enzymatic cleavage of GPIb), and ristocetin-induced platelet agglutination (RIPA) in patients undergoing chronic hemodialysis compared with patients undergoing peritoneal dialysis and healthy controls. Patients undergoing chronic maintenance hemodialysis have higher levels of platelet surface expression of GPIb (187+/-10 fluorescent units; P < 0.001) than either healthy controls (120+/-4 fluorescent units; P < 0.001) or patients undergoing peritoneal dialysis (127+/-5 fluorescent units; P < 0.001). Similar changes were observed in platelet surface GPIX. Plasma glycocalicin levels were elevated in chronic hemodialysis patients (71+/-5 nmol/L) compared with healthy controls (36+/-3 nmol/L; P < 0.001). Plasma glycocalicin levels also increased progressively throughout the hemodialysis procedure. The slope of RIPA was significantly lower in chronic hemodialysis patients (46+/-3) than in either healthy controls (67+/-4; P < 0.05) or peritoneal dialysis patients (62+/-2; P < 0.05). In conclusion, patients undergoing chronic maintenance hemodialysis have increased plasma glycocalicin levels and decreased RIPA, which may contribute to diminished platelet adhesion to vascular subendothelium and increased bleeding associated with uremia.     

Bony fish neurophysins Identification of MSEL- and VLDV-neurophysins of the pollack (Pollachius virens)

The two types of neurophysins known in vertebrate species, namely MSEL-neurophysin (vasopressin-like hormone-associated neurophysin) and VLDV-neurophysin (oxytocin-like hormone-associated neurophysin) have been purified from the pollack (Pollachius virens) pituitary through a combination of molecular sieving and high-pressure liquid chromatography (HPLC). Homogeneity has been checked by gel electrophoresis and rerun in HPLC. The apparent molecular masses measured by SDS-electrophoresis are near 12 kDa, significantly higher than those found for their mammalian homologues (10 kDa). The two types of neurophysins have been recognized through their N-terminal amino acid sequences. The primary structure of MSEL-neurophysin has been partially determined using automated Edman degradation applied on native and reduced-alkylated protein, as well as peptides derived by trypsin or staphylococcal proteinase hydrolyses. Comparison of pollack MSEL-neurophysin with ox, goose and frog counterparts reveals that particular positions in the polypeptide chain are subjected to substitutions and that the numbers of substitutions do not seem closely related to the paleontological times of divergence between the different vertebrate classes.     

A gene transfer strategy for making bone marrow cells resistant to trimetrexate

Trimetrexate (TMTX) is an anticancer drug with potential advantages over the more commonly used antifolate, methotrexate (MTX); however, its use has been limited by severe myelosuppression. Retroviral vectors containing mutant dihydrofolate reductase (DHFR) genes have been used to protect bone marrow cells from MTX, suggesting a similar approach could be used for TMTX. We first screened six variants of human DHFR to determine which allowed maximal TMTX resistance in fibroblasts. A variant enzyme containing a Leu-to-Tyr mutation in the 22nd codon (L22Y) was best, allowing a 100-fold increase in resistance over controls. Murine hematopoietic progenitor cells transduced with an L22Y- containing retroviral vector also showed high-level TMTX resistance in vitro. Mice reconstituted with L22Y-transduced bone marrow cells were challenged with a 5-day course of TMTX to determine whether hematopoiesis could be protected in vivo. Transfer of the L22Y vector resulted in consistent protection from TMTX-induced neutropenia and reticulocytopenia at levels that correlated with the proviral copy number in circulating leukocytes. We conclude that the L22Y vector is highly effective in protecting hematopoiesis from TMTX toxicity and may provide a means for increasing the therapeutic utility of TMTX in certain cancers.     

Bone scanning with 99mtechnetium phosphate to assess condylar hyperplasia. Report of two cases

Condylar hyperplasia poses a problem in planning treatment because it is a self-limiting process for some but not all patients. Continued growth creates a progressive deformity that requires condylectomy, whereas an enlarged condyle can be left in place after hyperplastic growth ceases, even if ramus surgery is needed to correct asymmetry. Bone scan with 99mtechnetium phosphate can be used to assist in making the differential diagnosis. In the two patients reported here, abnormal metabolic activity revealed by bone scans supported clinical and historical evidence that the condylar hyperplasia was active and required surgical correction, including condylectomy. The two cases demonstrate different approaches to postsurgical orthodontic treatment, depending on the amount of normal growth expected.     

Pulmonary arteriovenous malformations: techniques and long-term outcome of embolotherapy

Over a 10-year period, 276 pulmonary arteriovenous malformations (PAVMs) were occluded with balloon embolotherapy in 76 patients, 67 (88%) of whom had hereditary hemorrhagic telangiectasia. Eleven patients (14%) were discovered by means of family screening with measurement of arterial blood gases and chest radiography. Epistaxis, dyspnea, hemoptysis, and hemothorax occurred in 79%, 71%, 13%, and 9% of patients, respectively. Clinical histories of strokes and transient ischemic attacks were present in 18% and 37% of patients, respectively. Computed tomographic scans of 59 patients showed stroke in 36%. Sixty-five percent of PAVMs were located in the lower lobes, which correlated with the finding of more pronounced hypoxemia in the upright position. After embolotherapy, symptomatic hypoxemia was corrected, and serial values have remained constant for 5 years. Complications were minimal, and no patient required surgery. Balloon embolotherapy is effective long-term therapy for PAVMs, and family screening should be pursued because of the possibility of a higher frequency of paradoxical embolization (stroke) than previously recognized.     

Evaluation of condylar position from temporomandibular joint radiographs

This investigation evaluated the accuracy of three different transcranial TMJ radiographic records of condylar position and joint space dimension. In addition, the study evaluated how reliably observers determined condylar position and joint space dimensions from the radiographs. The results of this investigation support the following conclusions. The classification of condylar position is not the same at different sagittal locations within a TMJ. Skull position and radiographic projection must be identical if joint space measurements from serial radiographs are to be compared. The actual joint space dimensions and the anatomic anterior/posterior position of the condyles in the glenoid fossae cannot be accurately recorded by the radiographic techniques used in this investigation. Condyle/fossa relationships cannot be classified reliably by subjective evaluation of TMJ radiographs.