Challenges and successes in the treatment of hemophilia: the story of a patient with severe hemophilia A and high-titer inhibitors.

In the past, patients with severe hemophilia have suffered a substantially reduced quality of life with frequent bleeding episodes, disabling arthropathy, and shorter life expectancy. In addition, methods of treatment and management have been costly and time-consuming, and have placed a considerable burden on patients' physical and psychological well-being. With the advent of the on-demand therapy and prophylactic treatment paradigm, patients have been able to receive care with less interruption of daily activities.

ASM LabCap's contributions to disease surveillance and the International Health Regulations (2005).

The revised International Health Regulations [IHR(2005)], which requires the Member States of the World Health Organization (WHO) to develop core capacities to detect, assess, report, and respond to public health threats, is bringing new challenges for national and international surveillance systems. As more countries move toward implementation and/or strengthening of their infectious disease surveillance programs, the strengthening of clinical microbiology laboratories becomes increasingly important because they serve as the first line responders to detect new and emerging microbial threats, re-emerging infectious diseases, the spread of antibiotic resistance, and the possibility of bioterrorism. In fact, IHR(2005) Core Capacity #8, "Laboratory", requires that laboratory services be a part of every phase of alert and response.

Roscovitine inhibits differentiation and invasion in a three-dimensional skin reconstruction model of metastatic melanoma.

The aim of this study was to investigate the therapeutic potential of a cyclin-dependent kinase inhibitor, roscovitine, in cultured melanoma cells and a three-dimensional skin reconstruction model of metastatic melanoma. The modulatory effects of roscovitine on the growth and survival of normal melanocytes and cultured melanoma cell lines were tested. Additionally, we investigated the potential of roscovitine to regulate the growth and differentiation of a metastatic melanoma cell line (A375) in a three-dimensional skin reconstruction culture consisting of A375 cells admixed with normal human keratinocytes embedded within a collagen-constricted fibroblast matrix.

Accumulation of p53 and reductions in XIAP abundance promote the apoptosis of prostate cancer cells.

Toward the goal of developing effective treatments for prostate cancers, we examined the effects of cyclin-dependent kinase inhibitors on the survival of prostate cancer cells. We show that roscovitine, R-roscovitine, and CGP74514A (collectively referred to as CKIs) induce the apoptosis of LNCaP and LNCaP-Rf cells, both of which express wild-type p53. Apoptosis required caspase-9 and caspase-3 activity, and cytochrome c accumulated in the cytosol of CKI-treated cells.

Persistent respiratory changes following intermittent hypoxic stimulation in cats and human beings.

Repeated intermittent hypoxia or other stimulation of carotid chemoreceptors produces a consistent long-term increase in respiratory nerve activity in vagotomized, artificially ventilated anesthetized or decerebrate animals, but variable results have been reported in more intact preparations. We sought additional variables that could be measured to help gain an understanding of persistent respiratory responses to intermittent hypoxia. The variance of respiratory phases decreased in 10 of 11 recordings from vagotomized anesthetized cats during long-term facilitation induced by carotid chemoreceptor stimulation.

Barrett esophagus: endoscopic findings and what to biopsy.

Barrett esophagus (BE) is considered the precursor for nearly all cases of esophageal adenocarcinoma. The potential sequence from intestinal metaplasia to dysplasia to cancer can best be monitored by careful endoscopic observation and surveillance biopsies. The ability to diagnose BE, biopsy accurately, and appropriately monitor are requisites for all who care for patients with this disorder.

Respiratory neural activity during long-term facilitation.

Intermittent hypoxia results in a long-term facilitation (LTF) of respiratory efferent activity. The studies reviewed here presented data from both anesthetized and decerebrate, paralyzed, vagotomized, artificially ventilated adult cats. Multiple arrays of tungsten microelectrodes were used to record the concurrent responses of brain stem neurons that contribute to respiratory motor pattern generation.

Inspiratory drive and phase duration during carotid chemoreceptor stimulation in the cat: medullary neurone correlations.

1. This study addressed the hypothesis that there is a parallel processing of input from carotid chemoreceptors to brainstem neurones involved in inspiratory phase timing and control of inspiratory motor output amplitude. Data were from fifteen anaesthetized, bilaterally vagotomized, paralysed, artificially ventilated cats.

Long-term facilitation of phrenic nerve activity in cats: responses and short time scale correlations of medullary neurones.

1. Stimulation of either peripheral chemoreceptors or nucleus raphe obscurus results in long-term facilitation of phrenic motoneurone activity. The first objective of this work was to measure the concurrent responses of neurones in the nucleus raphe obscurus, the nucleus tractus solitarii, and the regions of the retrofacial nucleus, nucleus ambiguus and nucleus retroambigualis during induction of long-term facilitation.

Distributed actions and dynamic associations in respiratory-related neuronal assemblies of the ventrolateral medulla and brain stem midline: evidence from spike train analysis.

1. Considerable evidence indicates that neurons in the brain stem midline and ventrolateral medulla participate in the control of breathing. This work was undertaken to detect and evaluate evidence for functional links that coordinate the parallel operations of neurons distributed in these two domains.

Simulations of a ventrolateral medullary neural network for respiratory rhythmogenesis inferred from spike train cross-correlation.

Connections among ventrolateral medullary respiratory neurons inferred from spike train analysis were incorporated into a model and simulated with the program SYSTM11 (MacGregor 1987). Inspiratory (I) and expiratory (E) neurons with augmenting (AUG) and decrementing (DEC) discharge patterns and rostral I-E/I neurons exhibited varying degrees of adaptation, but no endogenous bursting properties. Simulation parameters were adjusted so that respiratory phase durations, neuronal discharge patterns, and short-time scale correlations were similar to corresponding measurements from anesthetized, vagotomized, adult cats.

Physical growth in Brachmann-de Lange syndrome.

Growth in 30 patients with Brachmann-de Lange syndrome (BDLS) was evaluated and found to be deficient in 27/30, with 17/27 having intrauterine growth retardation (IUGR). In 12/27 patients, endocrine evaluations have been completed. Seven of 12 were normal and 4/12, one with empty sella, had "classical" growth hormone deficiency with extreme short stature, markedly delayed skeletal maturation and subnormal growth hormone secretion in response to provocative stimuli.

Dynamic reconfiguration of brain stem neural assemblies: respiratory phase-dependent synchrony versus modulation of firing rates.

1. The objective of this work was to determine whether configurations of midline brain stem neural assemblies change during the respiratory cycle. 2.

Respiratory-related neural assemblies in the brain stem midline.

1. The initial objective of this study was to determine whether respiratory-related neural assemblies exist in the brain stem midline. A second goal was to seek evidence for concurrent relationships among the neurons that could generate the detected synchrony.

Functional connectivity between brain stem midline neurons with respiratory-modulated firing rates.

1. Recent evidence supports the idea that neurons distributed along the midline of the brain stem contribute to the regulation of breathing. This study sought evidence for functional connections between midline neurons with respiratory-modulated firing rates.

Ankyloblepharon filiforme adnatum.

We treated 4 infants with ankyloblepharon filiforme adnatum (AFA), an uncommon anomaly in which the apposing eyelid margins are connected by abnormal tissue strands. One infant had AFA alone, one had Hay-Wells syndrome, characterized by ectodermal dysplasia, and the other 2 had chromosome abnormalities, trisomy 18, and complex chromosome rearrangement, with visceral malformations. Despite heterogeneity and phenotypic variability, these developmental abnormalities shared (1) involvement of tissues growing in apposition and (2) temporal overlap of their occurrence.

Simple microphthalmos.

Simple microphthalmos was diagnosed in 22 patients on the basis of a normal-appearing eye and a total axial length at least 2 SDs below the mean for age. Anterior segment length was normal in most patients while posterior segment length was at least 2 SDs below the mean in all patients, indicating that disproportionate reduction in posterior segment length accounted for the microphthalmos. The normal values for total axial length, anterior segment length, and posterior segment length were determined from the analysis of axial length measurements obtained from age-similar controls.

Complex microphthalmos.

Forty patients were diagnosed as having complex microphthalmos on the basis of a malformed globe with a total axial length measurement at least 2 SDs below the mean for age-similar controls. Three had anterior segment dysgenesis; 4, congenital lens abnormalities; 14, chorioretinal colobomas; 12, persistent hyperplastic primary vitreous; 4, retinal dysplasia; and 3, complex malformations due to ipsilateral facial malformations. Measurements of total axial length indicated that complex microphthalmos was congenital and that postnatal growth of the malformed eye was similar to that of normal eyes.

Cross-tolerance between systemic and epidural morphine in cancer patients.

Cross-tolerance to epidural morphine after prior systemic morphine therapy was studied in 26 cancer patients treated for relief of pain secondary to metastatic disease. A 'tolerance index' was calculated for each patient by multiplying the duration of previous morphine therapy with the daily dose just prior to the study and then compared with changes in the following variables measured after epidural morphine administration: with pain scores on a scale from 0 (no pain) to 10 (maximal pain), heart rate, blood pressure, respiratory rate and minute volume, arterial blood gas tensions of oxygen and carbon dioxide and arterial pH. There was no significant analgesic cross-tolerance to epidural morphine, but clear evidence for cross-tolerance regarding morphine's respiratory depressant action.

Blue cone monochromatism.

Blue cone monochromatism (BCM) is a subtype of achromatopsia in which the blue cone mechanism predominates. Each of the four patients in this study had BCM proven by their having peak spectral sensitivities in the blue region of the visible spectrum (near 440 nm). Clinically, the diagnosis was suspected because of x-linked inheritance, the presence of acuities better than 20/200 in two patients and myopia ranging from -1.

Ozone-induced alterations of lamellar body lipid and protein during alveolar injury and repair.

Alveolar Type II cells in the rat respond to severe, acute ozone injury (3 ppm ozone for eight hours) by increasing their intracellular pool of surfactant; however, the newly stored surfactant is abnormal in composition. Lamellar bodies isolated between 24 and 96 hours after ozone exposure contained significantly more cholesterol in relation to phosphatidylcholine than did controls. By contrast, the cholesterol content of surfactant isolated from alveolar lavage remained unchanged throughout an 8-day post-ozone period.

Adrenal suppression after corticosteroid injection of periocular hemangiomas.

Two infants with symptomatic periocular hemangiomas received 1-ml intralesional injections of a 50:50 mixture of triamcinolone acetonide (40 mg/ml) and betamethasone (8 mg/ml). Both developed adrenal suppression as evidenced by the immediate depression of their serum cortisol and adrenocorticotrophic hormone levels. One patient remained adrenal suppressed for five months and, concurrently, her growth rate and weight dropped from normal to below the fifth percentile.