Laser Ablation Facilitates Closure of Chronic Enterocutaneous Fistulae

This report describes the use of laser ablation for treatment of chronic enterocutaneous fistulae (ECFs) after failure of conservative therapy. Three patients underwent laser ablation for treatment of 8 ECFs. Mean duration of fistula patency was 28 months with mean fistula output of 134 mL/day. The initial technical success was 100% with no major or minor complications. Three ECFs required repeat treatment. At mean follow-up of 53 days, 7 of the fistulae were occluded. One fistula showed a markedly reduced output of 10 mL/day.     

Definition of functionally important mechanistic differences among selective estrogen receptor down-regulators

One subclass of antiestrogens, the selective estrogen receptor down-regulators (SERDs), have received considerable attention of late as they competitively inhibit estrogen binding and induce a rapid, proteasome-dependent degradation of the receptor. Contained within this class of molecules is the steroidal antiestrogen ICI182,780 (faslodex), recently approved for the treatment of metastatic cancer, and GW5638/DPC974, a SERD that is currently being evaluated in the clinic. Given that mechanistic differences between different selective estrogen receptor modulators have been translated into important clinical profiles, it was of interest to determine if the SERD subclass of ligands were likewise functionally or mechanistically distinguishable. In this study, we show that although the steroidal and nonsteroidal SERDs target ERalpha for degradation, the underlying mechanism(s) are different. Of note was the identification of a specific protein-protein interaction surface presented on ERalpha in the presence of the ICI182,780-activated receptor which is required for degradation. Interestingly, this surface is also presented on ERalpha in the presence of RU58,668, a SERD that is chemically distinct from ICI182,780. This surface is not required for GW5638-mediated degradation, and thus, this SERD seems to affect ERalpha down-regulation by a different mechanism. These data suggest that sequencing of therapies using drugs of this class is likely to be possible. Finally, because of the unmet need for orally active SERDS that function similarly to ICI182,780, we have used the insights from these mechanistic studies to develop and validate a high-throughput screen for compounds of this class with improved pharmaceutical properties.     

Hormone responses to a continuous bout of rock climbing in men

Rock climbing is rapidly increasing in popularity as a recreational activity and as a competitive sport. Few studies have tested acute physiological responses to climbing, and no studies to date have tested hormone responses to a climbing-based workout. This study aimed to measure testosterone (T), growth hormone (GH), and cortisol (C) responses to continuous vertical climbing in young male rock climbers. Ten male rock climbers, aged between 21 and 30 years, climbed laps on a submaximal 55' climbing route for 30 min, or until exhaustion, whichever came first. Heart rate (HR) was recorded after every lap. Blood samples were collected by venipuncture before (Pre), immediately post (IP), and 15 min after the climbing exercise (P15) to assess blood lactate and plasma GH, T, and C. Subjects climbed 24.9 ± 1.9 min and 507.5 ± 82.5 feet. Peak HR was 182.1 ± 2.3 bpm, and lactate (Pre: 2.9 ± 0.6 mmol/dL, IP: 11.1 ± 1.0 mmol/dL) significantly (P < 0.05) increased from Pre to IP. T concentrations significantly (P < 0.05) increased from Pre (6.04 ± 0.31 ng/mL) to IP (7.39 ± 0.40 ng/mL) and returned to baseline at P15 (6.23 ± 0.33 ng/mL). Cortisol levels did not significantly change during the protocol. GH significantly (P < 0.01) increased from Pre (0.63 ± 0.17 ng/mL) to IP (19.89 ± 4.53 ng/mL) and remained elevated at P15 (15.03 ± 3.89 ng/mL). An acute, short-term bout of high-intensity continuous climbing was an effective exercise stimulus for elevating plasma testosterone and growth hormone levels in young males.     

Different Mechanisms Underlying Consecutive, Postoperative Atrial TachyArrhythmias in a Fontan Patient

Introduction: Atrial tachyarrhythmias (AT) frequently develop later after a Fontan operation and can be successfully treated by ablative therapy. However, new arrhythmias often develop.
Methods and Results: Consecutive AT emerging in a Fontan patient were ablated using three-dimensional electro-anatomical mapping. During a 6-year period, nine different AT were ablated, including intraatrial reentrant AT (N = 5), focal AT (N = 3), and focal atrial fibrillation (N = 1) originating from distinct right atrial sites.
Conclusion: In a Fontan patient, successive AT can be caused by different mechanisms. These AT are most likely the result of progressive atrial cardiomyopathy and can be treated by catheter ablation.     

Regulation of bone remodeling by vitamin K2

All living tissues require essential nutrients such as amino acids, fatty acids, carbohydrates, minerals, vitamins, and water. The skeleton requires nutrients for development, maintaining bone mass and density. If the skeletal nutritional requirements are not met, the consequences can be quite severe. In recent years, there has been growing interest in promotion of bone health and inhibition of vascular calcification by vitamin K2. This vitamin regulates bone remodeling, an important process necessary to maintain adult bone. Bone remodeling involves removal of old or damaged bone by osteoclasts and its replacement by new bone formed by osteoblasts. The remodeling process is tightly regulated, when the balance between bone resorption and bone formation shifts to a net bone loss results in the development of osteoporosis in both men and women. In this review, we focus on our current understanding of the effects of vitamin K2 on bone cells and its role in prevention and treatment of osteoporosis.     

Sources of subcortical afferents to the macaque's dorsal lateral geniculate nucleus

Background: The dorsal lateral geniculate nucleus (dLGN) is the thalamic region responsible for transmitting retina signals to cortex. Brainstem pathways to this nucleus have been described in several species and are believed to control the retinocortical pathway depending on the state of the animal (awake, asleep, drowsy, etc.). The purpose of this study was to determine all of the subcortical sources of afferents to the dLGN in a higher primate, the macaque monkey, whose visual system is similar to that of humans. Methods: Injections of horseradish peroxidase (HRP), with or without conjugation to wheat germ agglutinin, were made into the dLGNs of seven macaque monkeys, followed by perfusion, brain sectioning, and analyses of neurons in the brainstem, thalamus, and hypothalamus that contained the retrogradely transported marker. Results: The reticular nucleus of the thalamus, pedunculopontine nucleus, parabigeminal nucleus, pretectal nucleus of the optic tract, superior colliculus, dorsal raphe nucleus, and tuberomammillary region of the hypothalamus contained many retrogradely labeled neurons ipsilateral to the injections. In the contralateral brainstem, HRP-labeled cells were found only in the pedunculopontine nucleus, nucleus of the optic tract, and dorsal raphe nucleus. The number of labeled neurons on the contralateral side was about one-half of that in corresponding ipsilateral nuclei. The locus coeruleus contained no labeled neurons in four of the macaques that had injections limited to the dLGN. Conclusion: There are seven subcortical regions that send afferents to the dLGNs of macaque monkeys. Except for the locus coeruleus, these are the same as observed for other species, such as the cat and rat, and indicate the possible sources of subcortical control over the dLGNs of humans. © 1995 Wiley-Liss, Inc.     

Deep vein thrombosis: significant limitations of noninvasive tests

Impedance plethysmography (IPG) has a reputed sensitivity of 95% in the detection of proximal, clinically significant deep venous thrombosis (DVT). A review of the radiologic studies of 100 consecutive patients who underwent both venography and IPG showed venographic evidence of proximal DVT in 40 patients. The IPG was negative in 15 (38%) of these 40 cases. The specificity of the IPG was 83%. The predictive value of a negative study, with this 40% prevalence of DVT, was 77%. These disturbing results indicate a continuing role for venography in the workup of DVT.