Internal mammary vein to coronary artery anastomotic fistula

Two patients are presented where internal mammary artery grafting was performed for the relief of symptomatic coronary artery disease. At follow-up the internal mammary artery was occluded and a communication between the internal mammary vein and the native coronary artery was demonstrated. These patients were characterised by the early recurrence of angina or the appearance of a continuous murmur. Both patients were treated by re-operation with ligation of the arterio-venous fistula and saphenous vein grafting. © 1996 Wiley-Liss, Inc.     

Brugada-type patterns are easily observed in high precordial lead ECGs in collegiate athletes

Background

Displacement of ECG leads can result in unwarranted findings. We assessed the frequency of Brugada-type patterns in athletes when precordial leads were purposely placed upward.

Methods

Four hundred ninety-one collegiate athletes underwent two ECGs: one with standard leads, one with V1 and V2 along the 2nd intercostal space. A positive Brugada-type pattern was defined as ST elevation in V1 or V2 consistent with a Type 1, 2, or 3 pattern in the high-lead ECG. A control group was comprised of 181 outpatients.

Results

No Type 1 patterns were seen. In 58 athletes (11.8%), a Brugada-type 2 or 3 pattern was observed. Those with Brugada-type 2 or 3 patterns were more likely male, taller, and heavier. In the control group, 18 (9.9%) had Brugada-type 2 or 3 patterns and were more likely male.

Conclusions

Proper lead positioning is essential to avoid unwarranted diagnosis of a Brugada-type ECG, especially in taller, heavier male athletes.     

Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity

With the development of targeted therapeutics, especially for small-molecule inhibitors, it is important to understand whether the observed in vivo efficacy correlates with the modulation of desired/intended target in vivo. We have developed a small-molecule inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR), platelet-derived growth factor receptor, and c-Kit tyrosine kinases, pazopanib (GW786034), which selectively inhibits VEGF-induced endothelial cell proliferation. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Because bolus administration of the compound results in large differences in C(max) and C(trough), we investigated the effect of continuous infusion of a VEGFR inhibitor on tumor growth and angiogenesis. GW771806, which has similar enzyme and cellular profiles to GW786034, was used for these studies due to higher solubility requirements for infusion studies. Comparing the pharmacokinetics by two different routes of administration (bolus p.o. dosing and continuous infusion), we showed that the antitumor and antiangiogenic activity of VEGFR inhibitors is dependent on steady-state concentration of the compound above a threshold. The steady-state concentration required for these effects is consistent with the concentration required for the inhibition of VEGF-induced VEGFR2 phosphorylation in mouse lungs. Furthermore, the steady-state concentration of pazopanib determined from preclinical activity showed a strong correlation with the pharmacodynamic effects and antitumor activity in the phase I clinical trial.     

Female striated urogenital sphincter contraction measured by shear wave elastography during pelvic floor muscle activation: Proof of concept and validation

Aims

Investigation of the function of the striated urogenital sphincter (SUS) is challenging because it is difficult to access and requires invasive measures. Ultrasound shear wave elastography (SWE) is a non‐invasive real‐time technique used to estimate tissue stiffness. As muscle stiffness can be used as an estimate of muscle force, SWE provides an opportunity to study contraction of the peri‐urethral musculature. Validation of SWE to study SUS during functional tasks, such as pelvic floor muscle contractions, is required prior to application in clinical populations.

Methods

Ten healthy females (34[5] years) participated. Stiffness in a region expected to contain the SUS was quantified using SWE at rest and during a pelvic floor muscle contractions performed at 10%, 25%, and 50% of maximal voluntary contraction (MVC). Two repetitions were performed for 10 s.

Results

During contraction, stiffness increased in the region of the SUS in all participants and at all contraction intensities. Multiple regions of increased stiffness were detected, with 95.8% of regions situated ventral to the mid‐urethra within the anatomical area of the SUS. The increase in stiffness was greater for 50% MVC than both 10% and 25% MVC contraction intensities (P < 0.01).

Conclusions

Stiffness increased within the anatomical region of the SUS during voluntary pelvic floor muscle contractions with predictable response to changes in contraction intensity. These observations support the potential for ultrasound SWE to study SUS function non‐invasively.     

Borrelia burgdorferi in an urban environment: white-tailed deer with infected ticks and antibodies.

Ticks and blood samples were collected from white-tailed deer (Odocoileus virginianus) in forests located in an insular, urban area of Bridgeport, Conn., and in rural south central Connecticut during 1992 and 1993. Immature and adult Ixodes scapularis ticks were tested for Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, by indirect fluorescent-antibody staining methods. Deer sera were analyzed for antibodies to this bacterium by an enzyme-linked immunosorbent assay. Infected ticks parasitized deer in Bridgeport from May through December; the prevalence of infection varied from 1.1% of 93 larvae to 28.1% of 114 adult females. The percentages of infected males (10.5% of 380 ticks) and females (13.7% of 328 ticks) were relatively lower in south central Connecticut. In antibody tests, the prevalence of seropositive specimens collected in Bridgeport (61% of 146 serum specimens) was more than twofold greater than that of specimens obtained in south central Connecticut (26.7% of 116 serum specimens). Foci for Lyme borreliosis can occur in forested, urban settings as well as in rural areas if there are ticks, rodents, birds, and large mammals present. Human exposure to ticks in such sites should be considered as a possible source of B. burgdorferi infection.     

Cytogenetic abnormalities in the myelodysplastic syndromes and occupational or environmental exposure

Patients with myelodysplastic syndromes (MDS) have high frequencies of cytogenetic abnormalities and evidence is accumulating of associations between exposure history and primary MDS. The objective of this article is to examine the relationship between histories of occupational or environmental exposure and presence of cytogenetic abnormalities. A case control study of MDS patients estimated lifetime exposure to more than 90 potential hazards in 400 age, sex, and area of residence matched patient and control pairs. A parallel cytogenetics study undertaken at time of diagnosis, independently of any knowledge of exposure history, identified 75 cytogenetically abnormal and 139 normal (186 not studied). Odds ratios of MDS patients and their matched controls were compared for 3 groups: cytogenetically abnormal, normal, and not known. The odds ratios for all exposures combined were possibly higher among cytogenetically abnormal 2.0 (95% confidence interval 0.8-5.9) than among normal 1.0 (0.6-1.8). This pattern was observed for exposure to semimetals, abnormal 4.0 (0.4-195.1) and normal 0.5 (0.1-1.0) and inorganic dusts, 1.6 (0. 6-3.8) and 0.4 (0.1-1.4) respectively. The pattern was principally in abnormalities in chromosomes 5 and 7. For organic chemicals and radiation, the odds ratios for both cytogenetically abnormal and normal were marginally raised: organic 1.8 (0.6-6.0) and 1.3 (0.6-2.9), respectively, and radiation 1.7 (0.5-5.6) and 1.3 (0.4-4.7) respectively. For radiation, abnormalities were mostly in chromosome 8. This study of association between exposures and cytogenetics in primary MDS complements those previously reported in secondary MDS and may provide some insight into pathogenetic mechanisms that lead to development of MDS. (Blood. 2000;95:2093-2097)