Venous thromboembolism (VTE) risk stratification in general medical patients at an academic medical center

Journal of Thrombosis and Thrombolysis - Hospital-acquired venous thromboembolism (VTE) is still a concern for general medical patients. Pharmacologic prophylaxis can reduce VTE incidence, but...     

Use of urea kinetics in the nutritional care of the acutely ill patient

In acutely ill patients nitrogen balance is often assessed clinically from measurements of protein intake and urinary urea nitrogen. We have utilized urea kinetic modeling to measure urea generation rates, protein catabolic rates and nitrogen balance in 19 acutely ill patients with varying degrees of renal dysfunction and have studied the effect of varying caloric intake on protein balance during a period of fixed protein intake. In patients with measured creatinine clearances equal to or greater than 50 ml/min there was a highly significant correlation between nitrogen balance estimates derived from urea kinetic modeling and those obtained from urinary urea nitrogen (R = 0.939; p less than 0.001). When creatinine clearance measurements were between 20 to 50 ml/min the correlation between the two estimates was poorer (R = 0.337; p less than 0.001). In patients whose creatinine clearance was below 20 ml/min the correlation between measurements was worse still (R = 0.229; p less than 0.002). To determine the effects of increasing caloric intake on protein catabolic rate seven acutely ill patients were studied. When caloric intake was increased from 27.8 to 34.2 kcal/kg/day while on a fixed protein intake of 1.27 g/kg/day there was a significant fall in protein catabolic rate from 1.39 to 0.99 g/kg/day (p less than 0.002). As urea kinetic modeling takes into account changes in blood urea nitrogen, extrarenal losses of urea and the urinary urea pool, it is the preferred method for measuring protein balance in acutely ill patients particularly those with poor renal function. Serial monitoring of protein catabolic rates permits easy continuous assessment of the effect of increasing caloric intake on protein sparing during parenteral hyperalimentation.     

Bowel migration in the normal fetus: US detection

Ten fetuses underwent ultrasound scanning at 7-10 weeks gestational (postmenstrual) age. In all cases, an echogenic mass measuring 0.5-1.0 cm was demonstrated within the base of the umbilical cord at its insertion into the fetal abdomen. No area with echogenicity characteristic of the small bowel was identified within the lower part of the fetal abdomen. All fetuses were reexamined 4-12 weeks later, at which time the mass in the umbilical cord was no longer seen, and normal fetal bowel was visualized in the lower abdominal cavity of the fetus. This sequence of findings appears to represent the sonographic demonstration of normal fetal bowel migration early in gestation and should not be confused with defects of the abdominal wall such as omphalocele or gastroschisis.     

The characterization of α-bungarotoxin receptors on the surface of parasympathetic neurons in the frog heart

Receptors for α-bungarotoxin are found on the surface of parasympathetic neurons in the frog cardiac ganglion by light microscopic autoradiography. Competition studies suggest that these receptors are cholinergic and indicate that they are also recognized by neuronal bungarotoxin (κ-bungarotoxin). These receptors are outnumbered by those recognized exclusively by neuronal bungarotoxin. Unlike neuronal bungarotoxin receptors, α-bungarotoxin receptors are not concentrated at synaptic sites. Fluorescence techniques fail to find evidence for clusters of α-bungarotoxin receptors anywhere on the neuronal surface. The possible function of these receptors, which apparently do not play a role in fast synaptic transmission, is discussed.     

Ablepharon‐macrostomia syndrome

We report three new cases of ablepharon‐macrostomia syndrome (AMS) and give a 10‐year follow‐up on a newborn reported in an abstract. These four patients, as well as those previously reported, all had absent hair, brows, and lashes, absent or short eyelids, macrostomia, ear anomalies, redundant skin, and abnormal genitalia. Many have persistent visual problems, often related to early corneal exposure. Hearing loss, poor hair growth, finger contractures, and growth retardation were also chronic problems. Developmental impairment was present in two‐thirds of patients but was usually mild. This report contributes to our knowledge regarding the natural history of AMS and includes the first report of an adult patient. It also adds further evidence that AMS is distinct from Barber‐Say syndrome, which has similar features. © 2001 Wiley‐Liss, Inc.     

Suramin interference with transforming growth factor-beta inhibition of human renal cell carcinoma in culture.

Suramin is a polyanionic compound used clinically for the treatment of trypanosomiasis, which is known to inhibit the action of many protein factors in vitro. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory protein which inhibits the growth of renal cell carcinoma in culture. While suramin at 50-500 micrograms/ml had no significant effect on the growth of renal cell carcinoma in culture in our experiments, it did partially reverse the growth inhibition induced by TGF-beta in the two cell lines tested. This effect apparently is caused by suramin's direct interference with 125I-labeled TGF-beta's ability to bind to the cell, and not by any effect of suramin on the TGF-beta receptor. Furthermore, suramin dissociates TGF-beta bound to the cell with a t1/2 of less than 30 min. These results are consistent with those previously reported regarding suramin's interaction with other protein growth factors, and suggest that suramin may interact with the TGF-beta protein itself to inactivate it.     

Dose-response effects of pegylated human megakaryocyte growth and development factor on platelet production and function in nonhuman primates

Thrombopoietin (TPO) is the physiologic Mpl-ligand regulating platelet production. Pegylated human recombinant megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated polypeptide Mpl-ligand derivitized with poly-(ethylene glycol), induces megakaryocyte endoreduplication and proliferation in vitro and in vivo. In the present study, the dose-response effects of PEG-rHuMGDF on pharmacokinetics, megakaryocytopoiesis, platelet production, and platelet function were characterized for dosing 0.05, 0.10, 0.50, or 2.5 micrograms/kg/d in 22 baboons for 28 days. Daily subcutaneous injections of PEG-rHuMGDF produced linear log-dose responses in (1) steady-state trough plasma levels of PEG-HuMGDF (P < 10(-3)); (2) marrow megakaryocyte volume (P < 10(-3)), ploidy (P < 10(-4)), and number (P < .01); and (3) peripheral platelet concentrations (P < 10(- 4)) and platelet mass turnover (P < 10(-3)). Platelet morphology, life span, and recovery were normal, and peripheral leukocyte, neutrophil, and erythrocyte counts were not significantly affected by PEG-rHuMGDF (P > .1 in all cases). PEG-rHuMGDF at 0.5 micrograms/kg/d produced similar blood concentrations of Mpl-ligand and platelets as 10 times the dose of rHu-MGDF (5.0 micrograms/kg/d), reflecting the extended plasma half-life achieved through pegylation. Whereas PEG-rHuMGDF did not induce platelet aggregation in vitro, platelet aggregatory responsiveness induced by thrombin receptor agonist peptide (TRAP1-6) and collagen was transiently enhanced ex vivo during the initial few days of PEG-rHuMGDF administration. However, adenosine diphosphate (ADP)-induced platelet aggregation was not enhanced ex vivo by PEG- rHuMGDF therapy. 111In-platelet deposition on segments of homologous endarterectomized aorta (EA) and vascular graft (VG) interposed in arteriovenous femoral shunts increased in direct proportion to the circulating platelet concentration (P < 10(-4) for both EA and VG); 125l-fibrin accumulation was not affected by PEG-rHuMGDF-induced increases in peripheral platelet counts. Changes in platelet production and function produced by PEG-rHuMGDF returned to baseline within 2 weeks after discontinuing treatment. Thus, in nonhuman primates, PEG- rHuMGDF increases platelet production in a linear log-dose-dependent manner by stimulating megakaryocyte endoreduplication and new megakaryocyte formation from marrow hematopoietic progenitors. These findings suggest that appropriate dosing of PEG-rHuMGDF therapy during periods of chemotherapy-induced marrow suppression may maintain hemostatic concentrations of peripheral platelets without increasing the risk of thrombosis.