Natural history of Becker muscular dystrophy: a multicenter study of 225 patients.

OBJECTIVE: Becker muscular dystrophy (BMD) is a milder variant of Duchenne muscular dystrophy (DMD), a lethal X-linked muscular disorder. Here, we aim to investigat the clinical involvement of skeletal, respiratory, cardiac, and central nervous systems in patients with BMD, as well as genotype-phenotype relationships. METHODS: This nationwide cohort study investigated the clinical manifestations and genotype-phenotype relationships in 225 patients with BMD having in-frame deletion from 22 medical centers. The primary outcome was to elucidate the association of genotype with skeletal muscle, respiratory, cardiac, and central nervous system disorders. Descriptive statistics were used to analyze the data. RESULTS: The average age of the subjects was 31.5 (range, 1-81) years. Initial symptoms of BMD were muscular (60%), followed by asymptomatic hypercreatine kinasemia (32.4%) and central nervous system disorders (5.3%). Gait disturbance was observed in 53.8% of patients and the average age at wheelchair introduction was 36.5 years. The ventilator introduction rate was 6.7% at an average age of 36.6 years. More than 30% of patients had an abnormal electrocardiogram and approximately 15% had heart failure symptoms. Cardiac function on echocardiography varied significantly among the patients. The frequencies of seizures and intellectual/developmental disability were 8.0% and 16.9%, respectively. Exon 45-47deletion (del) was the most common (22.6%), followed by exon 45-48del (13.1%). Patients with exon 45-49del patients demonstrated severe skeletal muscle damage. Patients with exon 45-47del and exon 45-55del patients did not require ventilator use. INTERPRETATION: The study provides important prognostic information for patients and clinicians to establish therapy plans and to implement preventative medicine.

Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

Case report: Evolution of catatonic mutism and psychotic symptoms in an adolescent with Down syndrome: transition from Down syndrome disintegrative disorder to anti-N-methyl-D-aspartate receptor encephalitis.

During her first year of junior high school, a 12-year-old Japanese girl with Down syndrome experienced dizziness, gait disruption, paroxysmal weakness in her hands, and sluggish speaking. Regular blood tests and a brain MRI revealed no abnormalities, and she was tentatively diagnosed with adjustment disorder. Nine months later, the patient experienced a subacute sickness of chest pain, nausea, sleep problem with night terrors, and delusion of observation. Rapid deterioration then developed with simultaneous fever, akinetic mutism, loss of facial expression, and urine incontinence. These catatonic symptoms improved after a few weeks after admission and treatment with lorazepam, escitalopram, and aripiprazole. After discharge, nonetheless, daytime slumber, empty eyes, paradoxical laughter, and declined verbal communication persisted. Upon confirmation of the cerebrospinal N-methyl-D-aspartate (NMDA) receptor autoantibody, methylprednisolone pulse therapy was tried, but it had little effect. Visual hallucinations and cenesthopathy, as well as suicidal thoughts and delusions of death, have predominated in the following years. Cerebrospinal IL-1ra, IL-5, IL-15, CCL5, G-CSF, PDGFbb, and VFGF were raised in the early stage of initial medical attention with nonspecific complaints, but were less prominent in the later stages of catatonic mutism and psychotic symptoms. We suggest a disease concept of progression from Down syndrome disintegrative disorder to NMDA receptor encephalitis, based on this experience.

Rescue computed tomography-guided drainage of a giant mediastinal mature teratoma causing airway obstruction prior to surgical resection: a case report.

BACKGROUND: Giant mediastinal mature teratomas may cause airway obstruction or decreased venous return due to the mass effect. Preoperative stabilization of the respiratory and circulatory systems is important for perioperative management to safely perform surgery, including general anesthesia. However, to the best of our knowledge, there are only a few reports regarding the preoperative computed tomography (CT)-guided drainage of mediastinal tumors. CASE PRESENTATION: A 30-year-old woman was admitted to the emergency room with sudden dyspnea. CT findings revealed a giant cystic mass in the anterior mediastinum compressing the trachea and the right main bronchus. The patient was intubated and CT-guided drainage of the fluid content of the cyst was performed to decompress the airway obstruction. Thereafter, the mediastinal tumor was resected during elective surgery and pathologically diagnosed as a mature teratoma. CONCLUSIONS: Rescue preoperative CT-guided drainage of a giant mediastinal mature teratoma allowed safe general anesthesia and surgery by releasing the airway obstruction.

Carbon monoxide combined with artificial blood cells acts as an antioxidant for tissues thermally-damaged by dye laser irradiation.

Artificial red blood cells [i.e., hemoglobin vesicles (HbVs)] can be used as photosensitizers in pulsed-dye laser (PDL) treatment for port wine stains in animal models. Small HbVs are distributed in the vicinity of the endothelial cells of the blood vessels. In our previous in vivo experiments, both HbVs and red blood cells absorbed photons of the laser and generated heat, contributing to removal of very small blood vessels and large deeper subcutaneous blood vessels with PDL irradiation. Herein, we tested carbon monoxide-bound HbVs (CO-HbVs) that would produce heat energy while releasing CO in vessels after dye laser irradiation in a rabbit auricle model. We conducted this experiment to confirm secondary progression of thermal injury being reduced with the antioxidative property of CO. We histopathologically evaluated the damages to the large vessels and surrounding dermal tissue following PDL irradiation alone or subsequent to the intravenous injection of the qualified HbVs. The soft tissue damages were graded on a five-point scale and compared statistically. Intravenous CO-HbVs significantly reduced damage to the surrounding tissue after subsequent PDL irradiation; however, the degree of damage to the larger vessel wall resulted in a variety of changes, including a slight increase in our histopathological grades. This beneficial effect in dye laser treatment for port wine stains may be the result of the antioxidative property of CO against free radicals in the zone of stasis that may still be theoretically viable in burns. This effect of CO protecting tissues from thermal damage is consistent with previous reports of CO as a reducing agent. If the reducing agent can be delivered directly to the affected area immediately after the burn injury, even in a small amount, the complex inflammatory cascade may be reduced and unnecessary inflammation after laser treatment that lowers the patient's quality of life can be avoided.

Retrograde in situ branched stent grafting for a patient with type V thoracoabdominal aortic aneurysm.

We have presented the case of a 76-year-old patient with a type V thoracoabdominal aortic aneurysm treated by retrograde in situ branched stent grafting to the superior mesenteric artery (SMA). Via a 9-cm, median laparotomy, a percutaneous transhepatic gallbladder drainage needle was inserted from the distal part of the first jejunal artery to the origin of the SMA. After stent graft placement into the aorta, the graft was retrogradely punctured using the percutaneous transhepatic gallbladder drainage needle. The SMA ischemic time was 6 minutes. The puncture site was dilated, and a small, covered stent was deployed. Postoperative computed tomography scanning showed no endoleak with sac regression.

Amplatzer Vascular Plug With Endologix AFX Lining for Visceral Re-Entry Closure in a Patient With Chronic Type B Aortic Dissection.

PURPOSE: To demonstrate the efficacy of a combination of Amplatzer vascular plug (AVP2) and Endologix AFX for a visceral entry closure. CASE REPORT: A 70-year-old woman with treated chronic type B aortic dissection was seen to have sac enlargement. An isolated residual tear was observed at the origin of the celiac artery. A 12 mm AVP2 was successfully deployed for the entry closure. Angiography after the plug deployment still demonstrated residual flow to the false lumen. Hence, an Endologix AFX VELA proximal endograft was deployed, covering the AVP membrane and leaving no endoleak. CONCLUSION: Deployment of a vascular plug with Endologix AFX lining was efficacious for securing complete closure of an entry tear at the origin of the celiac artery in our patient. CLINICAL IMPACT: Vascular plugs are reported to be effective for closing small entries, although their effectiveness is limited when the entry site is not located on the flat intima, or in a high-flow situation. In the presented case, an isolated entry tear at the origin of the celiac artery was successfully closed with a vascular plug following Endologix AFX stent-graft lining of the true lumen.

Fully Automated 3D Segmentation and Diffeomorphic Medial Modeling of the Left Ventricle Mitral Valve Complex in Ischemic Mitral Regurgitation.

There is an urgent unmet need to develop a fully-automated image-based left ventricle mitral valve analysis tool to support surgical decision making for ischemic mitral regurgitation patients. This requires an automated tool for segmentation and modeling of the left ventricle and mitral valve from immediate pre-operative 3D transesophageal echocardiography. Previous works have presented methods for semi-automatically segmenting and modeling the mitral valve, but do not include the left ventricle and do not avoid self-intersection of the mitral valve leaflets during shape modeling. In this study, we develop and validate a fully automated algorithm for segmentation and shape modeling of the left ventricular mitral valve complex from pre-operative 3D transesophageal echocardiography. We performed a 3-fold nested cross validation study on two datasets from separate institutions to evaluate automated segmentations generated by nnU-net with the expert manual segmentation which yielded average overall Dice scores of 0.82±0.03 (set A), 0.87±0.08 (set B) respectively. A deformable medial template was subsequently fitted to the segmentation to generate shape models. Comparison of shape models to the manual and automatically generated segmentations resulted in an average Dice score of 0.93-0.94 and 0.75-0.81 for the left ventricle and mitral valve, respectively. This is a substantial step towards automatically analyzing the left ventricle mitral valve complex in the operating room.

Rapeseed (canola) oil aggravates metabolic syndrome-like conditions in male but not in female stroke-prone spontaneously hypertensive rats (SHRSP).

This study was conducted to investigate whether or not there are sex differences in canola oil (CAN)-induced adverse events in the rat and to understand the involvement and the role of testosterone in those events, including life-shortening. Stroke-prone spontaneously hypertensive rats (SHRSP) of both sexes were fed a diet containing 10 wt/wt% soybean oil (SOY, control) or CAN as the sole dietary fat. The survival of the males fed the CAN diet was significantly shorter than that of those fed the SOY diet. In contrast, the survival of the females was not affected by CAN. The males fed the CAN diet showed elevated blood pressure, thrombopenia and insulin-tolerance, which are major symptoms of metabolic syndrome, whereas such changes by the CAN diet were not found in the females. Plasma testosterone was significantly lower in animals of both sexes fed the CAN diet than in those fed the SOY diet, but interestingly, the lowered testosterone was accompanied by a marked increase in plasma aldosterone only in the males. These results demonstrate significant sex differences in CAN-toxicity and suggest that those sex differences may be attributable to the increased aldosterone level, which triggers aggravation of the genetic diseases specific to SHRSP, that is, metabolic syndrome-like conditions, but only in the males. The present results also suggest that testosterone may negatively regulate aldosterone production in the physiology of the males, and the inhibition of that negative regulation caused by the CAN diet is one of the possible causes of the adverse events.

Directing a dispersion cannula tip toward the aortic root during thoracic aortic arch surgery does not adversely affect cardiac function.

INTRODUCTION: Neurologic complications of open thoracic aortic surgery are devastating problems in patients with severely diseased aortas. This study aimed to clarify whether directing the aortic cannula tip toward the aortic root affects the postoperative cardiac function in patients undergoing open thoracic aortic surgery. METHODS: A total of 16 patients who underwent total or partial arch replacement between January 2014 and April 2019 were enrolled and divided into two groups. Ascending aorta perfusion was performed by placing the cannula tip toward the aortic root (reversed direction group, seven patients) or toward the aortic arch (standard direction group, nine patients). Intraoperative and perioperative data, including mortality, morbidity, and postoperative cardiac function, were compared between the groups. RESULTS: There were no hospital deaths or stroke events in either group. The aortic cross-clamping time was 102.4 ± 20.3 minutes in the reversed direction group and 87.1 ± 9.9 minutes in the standard direction group (p = 0.049). Furthermore, the intubation time was 28.4 ± 12.9 hours in the reversed direction group and 12.4 ± 6.8 hours in the standard direction group (p = 0.022). Both times were significantly longer in the reverse direction group. Postoperative serum creatine kinase-MB levels were significantly lower in the reversed direction group (6.2 ± 3.3 U/L vs 13.3 ± 4.8 U/L, respectively, p = 0.006). The cardiac output and cardiac index did not significantly differ. CONCLUSIONS: Directing the aortic cannula tip toward the aortic root does not adversely affect the postoperative cardiac function after aortic arch surgery.

Involuntary movements as a prognostic factor for acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and white matter lesions with reduced diffusion, which are often accompanied by involuntary movements. The neurological outcomes of AESD vary from normal to mild or severe sequelae, including intellectual disability, paralysis, and epilepsy. The present study aimed to clarify the prognostic factors of AESD, including involuntary movements. METHODS: We enrolled 29 patients with AESD admitted to Tottori University Hospital from 1991 to 2020 and retrospectively analyzed their clinical data. Neurological outcomes were assessed by the Pediatric Cerebral Performance Category score and cerebral paralysis as neurological sequelae. RESULTS: Of the 29 patients, 12 had favorable outcomes and 17 had unfavorable outcomes. Univariate analysis revealed that the presence of underlying diseases, a decline in Glasgow Coma Scale (GCS) score 12-24 h after early seizures, and involuntary movements were associated with unfavorable outcomes. In multivariate analysis, a decline in GCS score and involuntary movements were associated with unfavorable outcomes. The sensitivities and specificities of underlying diseases, a decline of ≥ 3 points in GCS score 12-24 h after early seizures, and involuntary movements for unfavorable outcomes were 53% and 92%, 92% and 65%, and 59% and 92%, respectively. CONCLUSIONS: The appearance of involuntary movements may be associated with unfavorable outcomes of AESD. The prognostic factors identified herein are comparable with previously known prognostic factors of consciousness disturbances after early seizures.

Predicting the Onset of Acute Encephalopathy With Biphasic Seizures and Late Reduced Diffusion by Using Early Laboratory Data.

Background: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) often causes various neurological sequelae, necessitating early and objective differentiation of AESD from a febrile seizure (FS). Therefore, we developed a scoring system that predicts AESD onset using only early laboratory data. Methods: We selected patients with AESD or FS admitted to the Tottori University Hospital between November 2005 and September 2020 and collected laboratory data from onset to discharge in patients with FS and from onset to the second neurological events in patients with AESD. Results: We identified 18 patients with AESD and 181 patients with FS. In comparison with patients with FS, patients with AESD showed statistically significant increases in ammonia (NH3), blood sugar (BS), and serum creatinine (Cr) levels, and the white blood cell (WBC) count, and a significant decrease in pH at <3 h from onset. We set the cut-off values and adjusted the weight of each of these parameters based on data obtained <3 h from onset and proposed a scoring system for predicting AESD. This system showed 91% sensitivity and 94% specificity for distinguishing AESD from FS. These accuracies were only slightly improved by the addition of information related to consciousness and seizure duration (sensitivity, 91%; specificity, 96%). Conclusion: NH3, BS, and Cr levels, WBC count, and pH were significantly different between patients with AESD and patients with FS at <3 h from seizure onset. This scoring system using these data may enable the prediction of AESD onset for patients under sedation or without precise clinical information.

Left atrial geometry in an ovine ischemic mitral regurgitation model: implications for transcatheter mitral valve replacement devices with a left atrial anchoring mechanism.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) is a challenging, but promising minimally invasive treatment option for patients with mitral valve disease. Depending on the anchoring mechanism, complications such as mitral leaflet or chordal disruption, aortic valve disruption or left ventricular outflow tract obstruction may occur. Supra-annular devices only anchor at the left atrial (LA) level with a low risk of these complications. For development of transcatheter valves based on LA anchoring, animal feasibility studies are required. In this study we sought to describe LA systolic and diastolic geometry in an ovine ischemic mitral regurgitation (IMR) model using magnetic resonance imaging (MRI) and echocardiography in order to facilitate future research focusing on TMVR device development for (I)MR with LA anchoring mechanisms. METHODS: A group of 10 adult male Dorsett sheep underwent a left lateral thoracotomy. Posterolateral myocardial infarction was created by ligation of the left circumflex coronary artery, the obtuse marginal and diagonal branches. MRI and echocardiography were performed at baseline and 8 weeks after myocardial infarction (MI). RESULTS: Six animals survived to 8 weeks follow-up. All animals had grade 2 + or higher IMR 8 weeks post-MI. All LA geometric parameters did not change significantly 8 weeks post-MI compared to baseline. Diastolic and systolic interpapillary muscle distance increased significantly 8 weeks post-MI. CONCLUSIONS: Systolic and diastolic LA geometry do not change significantly in the presence of grade 2 + or higher IMR 8 weeks post-MI. These findings help facilitate future tailored TMVR device development with LA anchoring mechanisms.

Fully hydrogenated canola oil extends lifespan in stroke-prone spontaneously hypertensive rats.

BACKGROUND: Canola oil (Can) and several vegetable oils shorten the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). Although similar lifespan shortening has been reported for partially hydrogenated Can, the efficacy of fully hydrogenated oils on the lifespan remains unknown. The present study aimed to investigate the lifespan of SHRSP fed diets containing 10 % (w/w) of fully hydrogenated Can (FHCO) or other oils. METHODS: Survival test: Upon weaning, male SHRSP were fed a basal diet for rodents mixed with one of the test oils -i.e., FHCO, Can, lard (Lrd), and palm oil (Plm) throughout the experiment. The animals could freely access the diet and drinking water (water containing 1 % NaCl), and their body weight, food intake, and lifespan were recorded. Biochemical analysis test: Male SHRSP were fed a test diet with either FHCO, Can, or soybean oil (Soy) under the same condition, except to emphasize effects of fat, that no NaCl loading was applied. Soy was used as a fat source in the basal diet and was set the control group. Blood pressures was checked every 2 weeks, and serum fat levels and histological analyses of the brain and kidney were examined after 7 or 12 weeks of feeding. RESULTS: During the survival study period, the food consumption of FHCO-fed rats significantly increased (15-20 % w/w) compared with that of rats fed any other oil. However, the body weight gain in the FHCO group was significantly less (10-12 %) than that in the control group at 9-11 weeks old. The FHCO (> 180 days) intervention had the greatest effect on lifespan, followed by the Lrd (115 ± 6 days), Plm (101 ± 2 days), and Can (94 ± 3 days) diets. FHCO remarkably decreased the serum cholesterol level compared with Can and the systolic blood pressure from 12 to 16 weeks of age. In addition, while some rats in the Can group exhibited brain hemorrhaging and renal dysfunction at 16 weeks old, no symptoms were observed in the FHCO group. CONCLUSION: This current study suggests that complete hydrogenation decreases the toxicity of Can and even prolongs the lifespan in SHRSP.

The results of aortic arch replacement using antegrade cerebral perfusion in haemodialysis patients: analysis of the Japan cardiovascular surgery database.

OBJECTIVES: There have been limited data available regarding aortic arch replacement in dialysis patients. The purpose of this study was to examine real-world data and to determine the impact of preoperative dialysis status and other risks on surgical aortic arch replacement using the Japan Cardiovascular Surgery Database. METHODS: A total of 5044 patients who underwent elective, isolated aortic arch replacement using antegrade cerebral perfusion during 2014-2017 were eligible for the study. Of these, 89 patients received haemodialysis preoperatively. The patients were divided into 6 groups according to their preoperative estimated glomerular filtration rate and dialysis status for comparison. Preoperative and postoperative data were examined using a multivariable regression model. RESULTS: The overall surgical mortality rates of non-Chronic Kidney Disease (CKD) (estimated glomerular filtration rate >60 ml/min/1.73 m2), stage 3A, stage 3B, stage 4, stage 5 CKD and dialysis patients were 2.6%, 3.1%, 6.8%, 11.6%, 16.7% and 13.5%, respectively. After risk adjustment, dialysis was shown to be strongly associated with surgical mortality (odds ratio 4.39 and 95% confidence interval 2.22-8.72) and have a trend to be associated with postoperative stroke (odds ratio 2.02, 95% confidence interval 1.00-4.10, P = 0.051) when compared to the non-CKD group. As predictors of mortality, male sex, peripheral arterial disease, preoperative liver dysfunction and impaired left ventricular function were identified. CONCLUSIONS: The Japanese nationwide database revealed the outcomes of aortic arch replacement in dialysis patients. Appropriate counselling and an alternative strategy should be considered for such patients with multiple risks for mortality.

Artificial red blood cells increase large vessel wall damage and decrease surrounding dermal tissue damage in a rabbit auricle model after subsequent flashlamp-pumped pulsed-dye laser treatment.

Artificial red blood cells (i.e. hemoglobin [Hb] vesicles [Hb-Vs]) function effectively as photosensitizers in flashlamp-pumped pulsed-dye laser (PDL) treatment for port-wine stains in animal models. Hb-Vs deliver more Hb to the vicinity of the endothelial cells. Both Hb-Vs and red blood cells absorb the laser energy and generate heat, supporting the removal of very small blood vessels and deeper subcutaneous blood vessels with PDL irradiation in in vivo experiments. Here, we analyzed the photosensitizing effect of Hb-Vs in PDL irradiation on large blood vessels and surrounding soft tissues. We histopathologically analyzed markers of damage to the large vessels and surrounding dermal tissue in a rabbit auricle model following PDL irradiation alone or subsequent to the addition of intravenous Hb-V injection. Markers were graded on a five-point scale and statistically compared. The changes in laser light absorption and reflection in a human skin model caused by the administration of Hb-Vs were evaluated using Monte Carlo light-scattering programs. Histological markers of damage to blood vessels were significantly greater in Hb-V-injected arteries and veins measuring 1-3 mm in diameter as compared with the controls. However, Hb-V injection significantly reduced PDL-induced necrosis and hemorrhage in the surrounding tissues. During computer simulation, photon absorption increased within the vessel layer and decreased around the layer. Intravenous Hb-Vs increase the extent of damage in larger vessel walls but significantly reduce damage to the surrounding skin after subsequent PDL irradiation. These beneficial effects are the result of improving vessel selectivity by Hb-Vs in vessels. Hb-V administration prior to PDL irradiation therapy could mechanically improve the outcomes and safety profiles of port-wine stain treatment protocols.

Multimodal image analysis and subvalvular dynamics in ischemic mitral regurgitation.

Background: The exact geometric pathogenesis of leaflet tethering in ischemic mitral regurgitation (IMR) and the relative contribution of each component of the mitral valve complex (MVC) remain largely unknown. In this study, we sought to further elucidate mitral valve (MV) leaflet remodeling and papillary muscle dynamics in an ovine model of IMR with magnetic resonance imaging (MRI) and 3-dimensional echocardiography (3DE). Methods: Multimodal imaging combining 3DE and MRI was used to analyze the MVC at baseline, 30 minutes post-myocardial infarction (MI), and 12 weeks post-MI in ovine IMR models. Advanced 3D imaging software was used to trace the MVC from each modality, and the tracings were verified against resected specimens. Results: 3DE MV remodeling was regionally heterogenous and observed primarily in the anterior leaflet, with significant increases in surface area, especially in A2 and A3. The posterior leaflet was significantly shortened in P2 and P3. Mean posteromedial papillary muscle (PMPM) volume was decreased from 1.9 ± 0.2 cm3 at baseline to 0.9 ± 0.3 cm3 at 12 weeks post-MI (P < .05). At 12 weeks post-MI, the PMPM was predominately displaced horizontally and outward along the intercommissural axis with minor apical displacement. The subvalvular contribution to tethering is a combination of unilateral movement, outward displacement, and degeneration of the PMPM. These findings have led to a proposed new framework for characterizing PMPM dynamics in IMR. Conclusions: This study provides new insights into the complex interrelated and regionally heterogenous valvular and subvalvular mechanisms involved in the geometric pathogenesis of IMR tethering.

Novel toxicity of tris(1,3-dichloro-2-propyl) phosphate in adult male rats.

The widespread use of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) as a flame retardant has led to its release to the environment. Thus, the toxicological effects of TDCIPP on humans and animals are of importance. For better understanding of its potential toxicities, TDCIPP (250, 500, or 650 mg/kg/day) or vehicle control was administrated orally to adult male Wistar-Imamichi rats for 7 days. After the final administration of compounds, organ weights, histopathology, blood biochemistry, and hematology were examined. Hepatic toxicity was observed at doses ≥ 500 mg/kg/day of TDCIPP, and renal toxicity was observed at 650 mg/kg/day. The anti-androgenic activity of TDCIPP was previously confirmed in vitro and in vivo, but weights of epididymis, an androgen-dependent organ, were not affected by TDCIPP treatment in adults. Serum alkaline phosphatase activity was significantly decreased in all TDCIPP-treated rats independent of dose. Hemoglobin concentration, hematocrit, red blood cell count, and reticulocyte count were decreased in all TDCIPP-treated rats, but mean corpuscular volume, total iron-binding capacity, and serum iron were normal, suggesting that renal anemia was caused by TDCIPP. Together with previous reports on effects of anti-androgenic substances on red blood cell indices, anemia caused by TDCIPP could be due to its anti-androgenic activity. These considerations will contribute to further assessment of the toxicity of the compound.