Short-Term Efficacy of Enzyme Replacement Therapy in Korean Patients with Fabry Disease

Fabrazyme has been widely used for treatment of Fabry disease since its approval by the U.S. Food and Drug Administration in 2003. This study was undertaken to assess the short-term efficacy and safety of enzyme replacement therapy (ERT) for Fabry disease in Korea. Eight male patients and three female symptomatic carriers aged 13 to 48 yr were included. Fabrazyme was administered by intravenous infusion at a dose of 1 mg/kg every 2 weeks. Plasma and urine globotriaosylceramide (GL-3) levels, serum creatinine, creatinine clearance, and 24-hr urine protein levels were measured every 3 months. Kidney biopsies, ophthalmologic exams, and pure tone audiometry were performed before and 1 yr after ERT. Kidney function, including serum creatinine, creatinine clearance, and the 24-hr urine protein level, remained stable during ERT. Plasma and urine GL-3 levels were reduced within 3 to 6 months of ERT initiation. Microvascular endothelial deposits of GL-3 were decreased from renal biopsy specimens after 1 yr of treatment. The severity of sensorineural hearing loss and tinnitus did not improve after ERT. ERT is safe and effective in stabilizing renal function and clearing microvascular endothelial GL-3 from kidney biopsy specimen in Korean patients with Fabry disease

Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study

<p>Abstract</p> <p>Background</p> <p>We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system.</p> <p>Methods</p> <p>We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100^threpetitive reading, 2) rate of change, 3) average of 60–110^threading and 4) overall average of all readings.</p> <p>Results</p> <p>All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions.</p> <p>Conclusion</p> <p>The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.</p

Acute adrenal crisis after orthopedic surgery for pathologic fracture

BACKGROUND: Adrenal crisis after surgical procedure is a rare but potentially catastrophic life-threatening event. Its manifestations, such as hypotension, tachycardia, hypoxia, and fever mimic the other more common postoperative complications. Clinical outcome is dependent upon early recognition of the condition and proper management with exogenous steroid administration. CASE PRESENTATION: We report a 75-year-old man who presented with shock immediately after surgery for a femoral fracture from lung cancer metastasis. Anemia and severe hyponatremia were detected. Despite adequate fluid resuscitation, nonspecific symptoms including hypotension, tachycardia, hypoxia, fever and confusion occurred. Emergent CT revealed enlarged bilateral adrenal glands. Under the diagnosis of adrenal crisis due to metastatic infiltration of adrenal glands, the patient was treated with appropriate steroid replacement resulting in rapid improvement and recovery. CONCLUSION: We describe a case of adrenal crisis caused by the lack of adrenal reserve based on metastatic involvement and surgical stress, the first published case of adrenal crisis after surgery for a pathologic fracture from lung cancer metastasis. Surgeons treating pathologic fractures should be aware of this complication and familiar with its appropriate therapy because of increasing opportunity to care patients with metastatic bone tumors due to recent advances in cancer treatment

Effects of ocean acidification on invertebrate settlement at volcanic CO<inf>2</inf> vents

We present the first study of the effects of ocean acidification on settlement of benthic invertebrates and microfauna. Artificial collectors were placed for 1 month along pH gradients at CO2 vents off Ischia (Tyrrhenian Sea, Italy). Seventy-nine taxa were identified from six main taxonomic groups (foraminiferans, nematodes, polychaetes, molluscs, crustaceans and chaetognaths). Calcareous foraminiferans, serpulid polychaetes, gastropods and bivalves showed highly significant reductions in recruitment to the collectors as pCO2 rose from normal (336-341 ppm, pH 8.09-8.15) to high levels (886-5,148 ppm) causing acidified conditions near the vents (pH 7.08-7.79). Only the syllid polychaete Syllis prolifera had higher abundances at the most acidified station, although a wide range of polychaetes and small crustaceans was able to settle and survive under these conditions. A few taxa (Amphiglena mediterranea, Leptochelia dubia, Caprella acanthifera) were particularly abundant at stations acidified by intermediate amounts of CO2 (pH 7. 41-7.99). These results show that increased levels of CO2 can profoundly affect the settlement of a wide range of benthic organisms. © 2010 Springer-Verlag

Treatment and Outcomes of Melanoma in Acral Location in Korean Patients

PURPOSE: A retrospective study was conducted to review the treatment and outcomes of mainly melanomas in acral location in a single institution in Korea, and to evaluate the prognostic significance of anatomic locations of the tumor. MATERIALS AND METHODS: A retrospective review was completed on 40 patients between 2001 and 2006 to obtain pertinent demographic data, tumor data, treatment characteristics, and follow-up data. RESULTS: Forty melanoma patients were identified and analyzed. Of these, 18 were male and 22 were female patients and the mean age at the time of diagnosis was 55.9 years. Of the tumors, 65% were located on the hands and feet with acral lentiginous melanoma being the most common histological subtype. Univariate analysis for the overall melanoma survival revealed that the thickness of the tumor and the clinical stage have prognostic significances. The most significant factor as analyzed by a multivariate analysis was shown to be the advanced clinical stage. Acral melanomas did not show statistically significant differences in the age at diagnosis, thickness of the tumor, stage, ulceration, and survival rates compared to non-acral melanomas. There was also no significant difference in the survival rate between the patients treated by amputation versus wide local excision in acral melanomas. CONCLUSION: In Korean melanoma patients, thickness and advanced stages are significant factors for poorer prognosis. However, the location of melanoma did not have a significant prognostic value. In treating the melanomas in acral location, local wide excisions resulted in a similar prognosis compared to amputations.ope

Visual Personal Familiarity in Amnestic Mild Cognitive Impairment

BACKGROUND: Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general concept or helps to identify an object or a person. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, we investigated the neural networks associated with the perception of personal familiar faces and places in patients with amnestic mild cognitive impairment and healthy control subjects. Irrespective of stimulus type, patients compared to control subjects showed lower activity in right prefrontal brain regions when perceiving personally familiar versus unfamiliar faces and places. Both groups did not show different neural activity when perceiving faces or places irrespective of familiarity. CONCLUSIONS/SIGNIFICANCE: Our data highlight changes in a frontal cortical network associated with knowledge-based personal familiarity among patients with amnestic mild cognitive impairment. These changes could contribute to deficits in social cognition and may reduce the patients' ability to transition from basic to complex situations and tasks

Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells

<p>Abstract</p> <p>Background</p> <p>Isothiocyanates are natural compounds found in consumable cruciferous vegetables. They have been shown to inhibit chemical carcinogenesis by a wide variety of chemical carcinogens in animal models. Recent studies have also shown that isothiocyanates have antitumor activity, inhibiting the growth of several types of cultured human cancer cells. Our previous study showed that PEITC inhibited human leukemia cells growth by inducing apoptosis. However, the effect of isothiocyanates on lung cancer cell metastasis has not been studied. In the present study, we investigated the inhibitory effects of BITC and PEITC on metastatic potential of highly metastatic human lung cancer L9981 cells.</p> <p>Methods</p> <p>Cell migration and invasion were measured by wound healing assay and transwell chemotaxis assay. Expression of metastasis-related genes was assessed by quantitative RT-PCR and Western blotting. The mechanisms of action were evaluated by flow cytometry, reporter assay and Western blotting.</p> <p>Results</p> <p>Our data showed that both BITC and PEITC inhibited L9981 cell growth in a dose-dependent manner, the IC50 values were 5.0 and 9.7 μM, respectively. Cell migrations were reduced to 8.1% and 16.5% of control, respectively; and cell invasions were reduced to 2.7% and 7.3% of control, respectively. Metastasis-related genes MMP-2, Twist and β-catenin were also modulated. BITC and PEITC inhibited cell survival signaling molecules Akt and NFκB activation. Moreover, BITC and PEITC increased ROS generation and caused GSH depletion. Pretreatment with NAC blocked BITC and PEITC induced ROS elevation and NFκB inhibition.</p> <p>Conclusion</p> <p>Our results indicated that BITC and PEITC suppress lung cancer cell metastasis potential by modulation of metastasis-related gene expression, inhibition of Akt/NFκB pathway. Induction of oxidative stress may play an important role.</p

Impact of Ocean Warming and Ocean Acidification on Larval Development and Calcification in the Sea Urchin Tripneustes gratilla

Background: As the oceans simultaneously warm, acidify and increase in P-CO2, prospects for marine biota are of concern. Calcifying species may find it difficult to produce their skeleton because ocean acidification decreases calcium carbonate saturation and accompanying hypercapnia suppresses metabolism. However, this may be buffered by enhanced growth and metabolism due to warming.Methodology/Principal Findings: We examined the interactive effects of near-future ocean warming and increased acidification/P-CO2 on larval development in the tropical sea urchin Tripneustes gratilla. Larvae were reared in multifactorial experiments in flow-through conditions in all combinations of three temperature and three pH/P-CO2 treatments. Experiments were placed in the setting of projected near future conditions for SE Australia, a global change hot spot. Increased acidity/P-CO2 and decreased carbonate mineral saturation significantly reduced larval growth resulting in decreased skeletal length. Increased temperature (+3 degrees C) stimulated growth, producing significantly bigger larvae across all pH/P-CO2 treatments up to a thermal threshold (+6 degrees C). Increased acidity (-0.3-0.5 pH units) and hypercapnia significantly reduced larval calcification. A +3 degrees C warming diminished the negative effects of acidification and hypercapnia on larval growth.Conclusions and Significance: This study of the effects of ocean warming and CO2 driven acidification on development and calcification of marine invertebrate larvae reared in experimental conditions from the outset of development (fertilization) shows the positive and negative effects of these stressors. In simultaneous exposure to stressors the dwarfing effects of acidification were dominant. Reduction in size of sea urchin larvae in a high P-CO2 ocean would likely impair their performance with negative consequent effects for benthic adult populations

Food Supply and Seawater pCO2 Impact Calcification and Internal Shell Dissolution in the Blue Mussel Mytilus edulis

Progressive ocean acidification due to anthropogenic CO2 emissions will alter marine ecosytem processes. Calcifying organisms might be particularly vulnerable to these alterations in the speciation of the marine carbonate system. While previous research efforts have mainly focused on external dissolution of shells in seawater under saturated with respect to calcium carbonate, the internal shell interface might be more vulnerable to acidification. In the case of the blue mussel Mytilus edulis, high body fluid pCO2 causes low pH and low carbonate concentrations in the extrapallial fluid, which is in direct contact with the inner shell surface. In order to test whether elevated seawater pCO2 impacts calcification and inner shell surface integrity we exposed Baltic M. edulis to four different seawater pCO2 (39, 142, 240, 405 Pa) and two food algae (310–350 cells mL−1 vs. 1600–2000 cells mL−1) concentrations for a period of seven weeks during winter (5°C). We found that low food algae concentrations and high pCO2 values each significantly decreased shell length growth. Internal shell surface corrosion of nacreous ( = aragonite) layers was documented via stereomicroscopy and SEM at the two highest pCO2 treatments in the high food group, while it was found in all treatments in the low food group. Both factors, food and pCO2, significantly influenced the magnitude of inner shell surface dissolution. Our findings illustrate for the first time that integrity of inner shell surfaces is tightly coupled to the animals' energy budget under conditions of CO2 stress. It is likely that under food limited conditions, energy is allocated to more vital processes (e.g. somatic mass maintenance) instead of shell conservation. It is evident from our results that mussels exert significant biological control over the structural integrity of their inner shell surfaces