A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold {odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6}. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.     

Failure of Ixodes ticks to inherit Borrelia afzelii infection

To define conditions promoting inherited infection by Lyme disease spirochetes in Ixodes ticks, we variously infected ticks with Borrelia afzelii and examined their progenies by dark-field microscopy, immunofluorescence, PCR, and serial passage. No episode of inherited infection was evident, regardless of instar or gender infected or frequency of exposure. We suggest that these spirochetes rarely, if ever, are inherited by vector ticks.     

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Simulation of the condition of plane sections in the finite element method

An approach making it possible to simulate the condition of plane sections in solution of two-dimensional elastoplastic problems by the finite-element method is proposed.Translated from Problemy Prochnosti, No. 5, pp. 35–38, May, 1992.     

Influence of strain rate on the nature of failure under prolonged static and cyclical loads. 2. Examples of calculation

Based on a physicomechanical model of intercrystallite failure in materials, such as presented in the previous communication, we have proposed a computational algorithm for the endurance of polycrystalline material under cyclical load. We have provided examples for the calculation of the cyclical strength in austenitic steel under various strain rates. Comparison of the theoretical results against the experimental data demonstrated the possibility of using the model developed here to describe the quantitative relationships governing intercrystallite failure of the material over a broad range of load regimes.Translated from Problemy Prochnosti, No. 8, pp. 42–47, August, 1991.     

Stress-strain curves of polycrystals: Analysis of hardening and softening

The stress-plastic strain curve is regarded as a result of the simultaneous action of two processes: hardening occurring during instantaneous loading and softening which depends on temporal parameters. A physical interpretation of the piecewise-parabolic dependence for the stress—plastic strain curve is given. It was established experimentally that the instantaneous stress-plastic strain curve of a number of annealed polycrystals (copper, brass, duralumin, steel) regardless of the degree of plastic strain or type of deformation substructure can be described by a single parabolic function called the astructural stress-strain curve. The formation of the substructure provides realization of softening processes, the rate of which depends on the type of substructure. A criterion of transition from one parabolic segment of the stress-strain curve to another and, accordingly, change of the deformation substructures is formulated as the condition of maximum stress relaxation during deformation.Translated from Problemy Prochnosti, No. 10, pp. 18–33, October, 1995.     

Accurate localization of cortical convolutions in MR brain images

Analysis of brain images often requires accurate localization of cortical convolutions. Although magnetic resonance (MR) brain images offer sufficient resolution for identifying convolutions in theory, the nature of tomographic imaging prevents clear definition of convolutions in individual slices. Existing methods for solving this problem rely on heuristic adaptation of brain atlases created from a small number of individuals. These methods do not usually provide high accuracy because of large biological variations among individuals. The authors propose to localize convolutions by linking realistic visualizations of the cortical surface with the original image volume. They have developed a system so that a user can quickly localize key convolutions in several visualizations of an entire brain surface. Because of the links between the visualizations and the original volume, these convolutions are simultaneously localized in the original image slices. In the process of the authors' development, they have implemented a fast and easy method for visualizing cortical surfaces in MR images, thereby making their scheme usable in practical applications.     

Obturation of a C-shaped canal using an improved method of warm lateral condensation

Pilot studies conducted by the authors seem to indicate that obturation of a root canal system by the lateral condensation of gutta-percha using an electrically heated spreader results in a more homogeneous mass of gutta-percha than standard lateral condensation. This article describes an improved variation which prevents inadvertent dislodgement of the mass of gutta-percha during the obturation. The authors refer to this technique as "zap and tap" and a case report describes its use to obturate a C-shaped canal system of a mandibular second molar.