In vivo Doppler optical coherence tomography of mucocutaneous telangiectases in hereditary hemorrhagic telangiectasia

BACKGROUND: Hereditary hemorrhagic telangiectasia is characterized by mucocutaneous telangiectases and visceral arteriovenous malformations. Knowledge is limited concerning the development hemodynamics of mucocutaneous telangiectases. Doppler optical coherence tomography can demonstrate microvascular blood flow at flow rates as low as 20 microm/second, which is up to approximately 100 times more sensitive than Doppler US. The aims of this study were to collect in vivo Doppler optical coherence tomography images of mucocutaneous telangiectases and normal surrounding mucosa and skin, and to gain experience for an in vivo GI endoscopic study. It was hypothesized that visibly normal areas may have occult telangiectases and that mucocutaneous telangiectases that have bled may have a higher rate of blood flow than mucocutaneous telangiectases with no history of bleeding. METHODS: Twelve patients with hereditary hemorrhagic telangiectasia and mucocutaneous telangiectases were studied. Two to 3 visible mucocutaneous telangiectases on the digits, lips, and tongue were imaged with Doppler optical coherence tomography, along with visually normal surrounding areas at each site. The Doppler optical coherence tomography images were obtained in 0.5 second by using 1310 nm light. RESULTS: A total of 67 mucocutaneous telangiectases from the 12 patients were imaged (38 digit, 16 lip, 13 tongue). Blood flow was demonstrated within every mucocutaneous telangiectasis imaged. Doppler optical coherence tomography did not identify any abnormal vasculature within visually normal areas. Mucocutaneous telangiectases with a history of bleeding (n = 18) were situated closer to the surface, compared with mucocutaneous telangiectases with no bleeding history (n = 49), but there was no difference in the Doppler flow appearance. CONCLUSIONS: Visually normal areas in patients with hereditary hemorrhagic telangiectasia did not appear to have abnormal vasculature. Mucocutaneous telangiectases with a history of bleeding were more superficial but were otherwise similar to mucocutaneous telangiectases with no bleeding history.     

Timing of coronary stent thrombosis in patients treated with ticlopidine and aspirin

In patients receiving coronary stents treated with aspirin and coumadin, the peak incidence of stent thrombosis occurs on the fifth and sixth days following the implantation procedure. Little is known about the timing of stent thrombosis in patients treated with aspirin and ticlopidine. We compared the timing of coronary stent thrombosis in patients treated with ticlopidine and aspirin with the timing in those receiving coumadin and aspirin. A retrospective databank analysis was performed and 39 patients were identified who experienced stent thrombosis after successful coronary stent implantation. Of these, 21 had been treated with ticlopidine and aspirin and 18 with coumadin and aspirin therapy. The median time from stent implantation to stent thrombosis in the ticlopidine and aspirin group was 12 hours (interquartile range 6 to 72 hours) compared with 4 days in the coumadin and aspirin group (interquartile range 21 to 68 hours) (p <0.0001). There was no significant difference between the timing of stent thrombosis in patients treated with abciximab in addition to ticlopidine and aspirin (median 17 hours, interquartile range 6 to 29) versus ticlopidine and aspirin patients who did not receive abciximab (median 11 hours, interquartile range 9 to 12, p = 0.57). Thus, in patients who receive coronary stents, stent thrombosis occurs much earlier after the procedure in patients treated with ticlopidine and aspirin than in patients treated with anticoagulation therapy.     

Exploring new drugs for heart failure: the case of urocortin.

Over the past decade, clinical development of natriuretic peptideanalogues as drug therapy for acute heart failure has sparkeda wide range of interests to seek other endogenous vasoactivepeptide systems that are operative as adaptive responders inhuman heart failure. With rapid advances in the molecular understandingof heart failure pathogenesis, several novel neurohormonal systemshave been identified and more are under study. Bringing a potentialtherapeutic concept from bench to bedside today often involvesa prerequisite set of animal and human studies. However, muchof the attention in recent years has focused on identifyingwhat the     

Aerobic Reduction of Cytochrome b566 in Pigeon-Heart Mitochondria

In anaerobic, uncoupled pigeon-heart mitochondria treated with oxidizable substrate, the cytochrome b(566) remains largely oxidized. In the presence of antimycin A, addition of oxygen induces a reduction of this cytochrome. The rate of cytochrome b(566) reduction is comparable to and dependent on the rate of cytochrome c(1) oxidation. Kinetic data suggest that either ubiquinone or another donor of similar potential provides electrons for the reduction of cytochrome b(566). It is postulated that the aerobic reduction of cytochrome b(566) is directly related to the energy conservation at site II.     

5 alpha-reduced androgens in the human fetal testis

The androgen content was measured in testes from 34 male and in ovaries from 30 female embryos that varied in age from less than 12 to approximately 20 weeks. The 5 alpha-reduced androgens dihydrotestosterone and 3 alpha-androstanediol were found in testes at a level of about a 30th of that of testosterone at all ages examined, whereas very little or no testosterone, androstenedione, or either of the 5 alpha-reduced androgens were detected in the ovaries. Whether dihydrotestosterone plays a role in the development of the testes is unknown.     

Comparison of once-a-day and twice-a-day theophylline in asthma

Sustained-release theophylline compounds given once (Uniphyl) or twice (Theodur) daily were compared in adult asthmatics. Following a single dose of oral medication, large and peripheral airways bronchodilation occurred; response to theophylline correlated significantly with the log plasma theophylline concentration. Cardiac output and stroke volume, measured noninvasively using the acetylene technique, also increased significantly. During maintenance therapy, both preparations caused similar improvements in pulmonary function and symptoms; however, side effects were less with once-daily therapy.     

Use of nifedipine in hypertrophic cardiomyopathy in infants. A report of two cases

Hypertrophic cardiomyopathy was diagnosed in two symptomatic neonates. Treatment with nifedipine, a calcium blocking agent, was encouraging and warrants further investigation.     

Biphasic 19-nor-deoxycorticosterone excretion after adrenal enucleation is associated with altered adrenal mitochondrial cytochrome P450 11 beta-, 18-, and 19-hydroxylase activities

After adrenal enucleation (AE) rats avidly retain sodium (early phase), but after 7-10 days they lose this sodium avidity (late phase). Although increased production of a mineralocorticoid, 19-nor-deoxycorticosterone (19-Nor-DOC), has been implicated, 19-Nor-DOC levels during the early and late phases of AE have not been systematically measured. Furthermore it is not known why 19-Nor-DOC production should increase during a time when production of 11 beta- and 18-hydroxylated corticosteroids are decreased in AE. The purpose of this study was to examine the 11 beta, 18-, and 19-hydroxylase pathways in the early and late phases of AE. The results demonstrate increased urinary 19-Nor-DOC and decreased 18-OH-DOC and corticosterone excretion in the early phase of AE at a time when adrenal mitochondrial 11 beta- and 18-hydroxylase activities were decreased but 19-hydroxylase activity was unchanged. During the late phase of AE, urinary 19-Nor-DOC had decreased and 18-OH-DOC and corticosterone had increased to levels indistinguishable from those in sham controls. This reduction in 19-Nor-DOC was associated with a decrease in 19-hydroxylase activity in AE. Since the 11 beta, 18-, and 19-hydroxylases have a common substrate (DOC), it is possible that differential flux of DOC through these pathways could account for the changes in steroid production in AE. These data suggest that the increased 19-Nor-DOC excretion in AE may be due to alterations in enzyme activity leading to a shunting of DOC into the 19-Nor-DOC pathway. In addition, the synchronicity of 19-Nor-DOC with sodium excretion suggests that it has an important role in the pathogenesis of the sodium retention in AE.     

An ambulatory ventricular function monitor: validation and preliminary clinical results

A device for the continuous measurement of left ventricular (LV) function was tested in a series of 34 subjects. The instrument consisted of 2 arrays of radiation sensitive cadmium telluride detectors held in place over the region of the left ventricle and lung by a vest-like garment (hence the name VEST). The VEST electronic instrumentation included analog-to-digital converters, a battery pack, microprocessor and gating device, which were worn in a back pack. Data generated by the VEST, including the digitized average electrocardiogram, RR interval, counts/13 ms in each radiation detector, and time since commencement of data recording, were recorded on a cassette tape recorder every 2 minutes for subsequent analysis. At the conclusion of conventional multigated blood pool imaging, the VEST was positioned and worn by the subjects while supine, standing in place and walking. The correlation of ejection fraction calculated independently from the VEST and scintillation camera data was greater than 0.95. The inter-record reproducibility of the ejection fraction measured by the VEST in sedentary subjects was less than 3%.     

Immunological distribution of one form of insulin-like growth factor (IGF)-binding protein and IGF peptides in human fetal tissues

Insulin-like growth factors (IGFs) are expressed by, and are biologically active on, human fetal cells. The mitogenic actions of IGF-I are modulated by the 21-41 kDa class of IGF-binding proteins (IGF-BPs). Using a rabbit anti-human IGF-BP antibody raised against a highly pure 26 kDa IGF-BP derived from amniotic fluid, we have compared the cellular location of IGF-BP and IGF peptides in tissue sections from prostaglandin-induced human abortuses of 14-16 weeks of gestation. The monoclonal and polyclonal antibodies used were raised against human IGF-I, but did not distinguish between IGF-I and IGF-II. Positive staining for IGF-BP was seen in every tissue except brain, spleen and thyroid. With the exception of skin, the cellular distribution of IGF-BP was similar to that of IGF peptides. Strong immunostaining was found in hepatocytes, hepatic erythropoietic cells, pulmonary epithelium, the tubular epithelium of kidney, intestinal epithelia, the fetal adrenal cortex and cardiac and skeletal muscle fibres. In skin, IGF-BP was located throughout the dermis and in the germinal layer of the epidermis. IGF peptide in skin was restricted to the deeper dermal layers. In the tibial epiphyseal growth plate both IGF-BP and IGF peptide were located in chondrocytes throughout the proliferation and hypertrophic zones. The similarity in distribution of IGF-BP and IGF peptides in fetal tissues suggests that the latter may exist predominantly complexed to IGF-BP in or on the surfaces of cells in vivo. The distribution of IGF-BP may define the sites of biological action of IGF peptides.