Presence and prevalence of UV related genetic mutations in uveal melanoma: similarities with cutaneous melanoma.

Ultraviolet (UV) radiation is an accepted etiological factor in cutaneous melanoma (CM), however its role in uveal melanoma (UM) is controversial. Partly as a consequence, CM and UM are often considered to be separate conditions, and advances in the treatment of CM have not led to joint clinical trials or parallel improvements in survival of UM. This study hypothesized that a subset of UM tumors displays evidence of genetic changes consistent with UV-related damage similar to that shown in CM. Analysis of the Broad Institute's Firebrowse depository of 80 UM samples and 343 CM samples, together with the Sanger Institute's Catalogue of Somatic Mutations in Cancer depository of 995 UM and 12,447 CM samples was undertaken to identify the most frequently mutated genes, mutation types, and specific nucleotide variants (SNVs) in each condition. Somatic mutation data were cross-correlated and shared mutations assessed against known effects of UV radiation. The proportion of samples with C>T substitutions (a classic genetic marker of UV-related damage) was higher in UM than CM on both DNA strands (17.0% vs 13.1%, p=0.038). The most frequently encountered cross-correlated mutated genes between UM and CM were, in order, BRAF, NRAS, TP53, CDKN2A, TERT, PTEN, ARID2, and KMT2C, with multiple common BRAF point mutations. Each cross-correlated mutation, and each common point mutation in BRAF, was associated with UV-related mechanistic changes. These findings support the hypothesis that the etiology of a substantial minority of UMs may be more UV dependent than previously recognized.

Outbreaks of Smut Caused by Tilletia maclaganii on Switchgrass in New York and Pennsylvania.

Switchgrass (Panicum virgatum L.) is a native perennial grass with potential as a biofuel crop. The smut fungus, Tilletia maclaganii (Berk.) Clint., is associated with significant biomass reduction in switchgrass in the Midwest (4), but has not been reported in the northeast United States in more than 60 years (New York in 1890 and Pennsylvania in 1946) (2,3). From 2007 to 2010, smutted panicles were observed on the majority of plants in stands of several switchgrass cultivars at the USDA-NRCS Plant Materials Center in Big Flats (Chemung County), NY; in production fields of several switchgrass cultivars near Meadville (Crawford County), PA; and in an ornamental bed of switchgrass in Ithaca (Tompkins County), NY. Smutted panicles emerged 3 to 4 weeks prior to healthy panicles, had a compact, club-shaped appearance, and enlarged florets with swollen ovaries that readily released a powdery mass of odorless, rusty orange-to-dark brown teliospores when pinched. The entire caryopsis of every floret within a panicle was smutted and the infected plants appeared stunted, indicative of systemic infection. The fungus from each location was identified as T. maclaganii based on host, habit, and teliospore morphology (3). Teliospores were pale yellowish brown to reddish brown, varied from globose to slightly irregular in shape, and averaged 21 µm (18 to 25 µm) in diameter. The exospore was thick (2 to 3 µm), finely verrucose, and no sheath was present. True sterile cells, pale yellow and 10 to 18 µm in diameter, were sparsely present. Teliospores germinated and formed large (40 to 60 × 3 to 6 µm), nonconjugating basidiospores within 20 h on 2% water agar (WA). Occasionally, we also found the floret-infecting species T. pulcherrima (1) on switchgrass at very low incidence in Big Flats, NY, but it was easily distinguished from T. maclaganii. Stratified seeds (3 g) of 'Shelter', washed and found to be free of teliospores, were dusted with 0.04 g of teliospores of T. maclaganii isolate Tm001NY09 (Cornell Plant Pathology Herbarium Accession CUP-67931) harvested from infected 'Shelter' in Big Flats, NY in 2009. Inoculated and noninoculated seeds were sown in seedling trays, transplanted, and evaluated at panicle emergence. There were no symptoms on plants from noninoculated seeds. Symptoms on inoculated plants were consistent with field observations and teliospores were reisolated from infected panicles and cultured on 2% WA. Teliospores harvested from a single panicle infected with Tm001NY09 were used for culturing and DNA extraction. The fully annotated sequence of the rDNA internal transcribed spacer and 5.8S regions of this isolate were deposited in GenBank (Accession No. JF745116). Smut outbreaks in New York and Pennsylvania suggest that T. maclaganii must be managed effectively if switchgrass production is to be sustainable in the Northeast. References: (1) L. M. Carris et al. Plant Dis. 92:1707, 2008. (2) R. Durán and G. W. Fischer. The Genus Tilletia. Washington State University, Pullman, WA, 1961. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , May 3, 2011 (4) P. M. Thomsen et al. Online publication. doi:10.1094/PHP-2008-0317-01-RS. Plant Health Progress, 2008.

A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized by global developmental delays, deficits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory deficits in Shank3-deficient rats, there have been no trials in individuals with PMS. The purpose of this study is to assess the efficacy and safety of intranasal oxytocin as a treatment for the core symptoms of ASD in a cohort of children with PMS. METHODS: Eighteen children aged 5-17 with PMS were enrolled. Participants were randomized to receive intranasal oxytocin or placebo (intranasal saline) and underwent treatment during a 12-week double-blind, parallel group phase, followed by a 12-week open-label extension phase during which all participants received oxytocin. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as a number of secondary outcome measures related to the core symptoms of ASD. Safety was monitored throughout the study period. RESULTS: There was no statistically significant improvement with oxytocin as compared to placebo on the ABC-SW (Mann-Whitney U = 50, p = 0.055), or on any secondary outcome measures, during either the double-blind or open-label phases. Oxytocin was generally well tolerated, and there were no serious adverse events. LIMITATIONS: The small sample size, potential challenges with drug administration, and expectancy bias due to relying on parent reported outcome measures may all contribute to limitations in interpreting results. CONCLUSION: Our results suggest that intranasal oxytocin is not efficacious in improving the core symptoms of ASD in children with PMS. Trial registration NCT02710084.

Current Evidence for the Prevention of Endophthalmitis in Anti-VEGF Intravitreal Injections.

Intravitreal injection of a therapeutic substance is the most common procedure performed in ophthalmology. It has a low incidence of serious complications but is associated with a small chance of endophthalmitis. Although the rate of endophthalmitis is between 0.019% and 0.09%, the associated visual morbidity is often devastating. Procedural changes have evolved over the years to improve patient comfort and reduce injection-related injury and infection. Despite the availability of published evidence, there remains considerable variations and lack of consensus in practical clinical settings. In addition, emerging literature concerning the use of speculums, the use of prophylactic topical antibiotics, and the setting of injections continues to impact the ophthalmologist's injection practice. This article provides an up to date assessment of various aspects of the procedure such as the setting, ventilation, type of anaesthetic, and control of sterility during the procedure; including discussions on performing bilateral eye same-day injections and the use of antibiotics.

Significance of "reciprocal" ST segment depression: left ventriculographic observations during left anterior descending coronary angioplasty.

To evaluate the significance of "reciprocal" ST segment depression resulting from coronary occlusion, 27 patients with single vessel coronary disease were studied with intravenous digital subtraction left ventriculography before and during angioplasty of the left anterior descending coronary artery. During balloon inflation, 13 patients developed inferior lead ST depression in addition to anterior lead ST elevation (Group 1), whereas the remaining 14 patients did not (Group 2). The degree of anterior lead ST elevation in Group 1 (5 mm) was greater than that in Group 2 (1.5 mm, p less than 0.001) as was the reduction in left ventricular ejection fraction (24% versus 13%, respectively; p less than 0.02). Anterior and apical regional shortening decreased in both groups similarly, but an additional decrease in anterobasal shortening was confined to Group 1 (from 38% to 21%; p less than 0.002). Despite the presence of inferior lead ST depression in Group 1, inferior regional shortening did not change and inferobasal contraction was enhanced (from 4% to 29%; p less than 0.01). Inferior lead ST segment depression during anterior descending coronary angioplasty reflects a greater degree of anterior wall ischemia. The concurrent preservation of inferior wall contraction and the augmentation of infero-basal shortening confirm that this electrocardiographic feature is a "reciprocal" phenomenon rather than a manifestation of remote ischemia.

Irregular coronary lesion morphology after thrombolysis predicts early clinical instability.

After successful thrombolytic treatment for acute myocardial infarction, recurrent ischemia and infarction may occur with little warning. Coronary lesion morphology was analyzed from angiograms performed in 72 consecutive patients at 1 to 8 days after streptokinase treatment for acute myocardial infarction and the data were evaluated in relation to the subsequent clinical course. All patients were clinically stable at the time of angiography and continued to receive heparin infusion for greater than or equal to 4 days after thrombolysis. The infarct-related artery was patent in 55 patients (76%). In the 10 days after angiography, 15 patients developed prolonged episodes of angina at rest; the condition of 4 stabilized with medical treatment, but 11 required urgent medical intervention (coronary angioplasty in 8 and bypass surgery in 3). There were no differences in age, gender, left ventricular function or extent of coronary artery disease between those patients who developed unstable angina and those who had a stable in-hospital course. However, the median plaque ulceration index of the infarct-related lesion was 6.7 (95% confidence limits 6.3, 10) in the 15 patients with an unstable course versus 3.3 (2, 4.4) in those with a stable course (p less than 0.001). There were no differences between the two patient groups in the severity of stenosis, length of diseased segment, symmetry/eccentricity, presence of a shoulder, location at branch point or bend, presence of globular or linear filling defects, contrast staining or collateral supply. These data show that after thrombolysis, the degree of irregularity of the infarct-related artery is a critical determinant of early clinical instability.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary lesion morphology in acute myocardial infarction: demonstration of early remodeling after streptokinase treatment.

Coronary lesion morphology was analyzed in 72 patients 1 to 8 days after streptokinase treatment for acute myocardial infarction and compared with lesion morphology in a control group of 24 patients with stable angina. In the streptokinase group the infarct-related artery was patent in 55 patients (76%). Compared with stenoses in the stable angina group, there were no differences in the stenosis length, severity, calcification or in the proportion located at an acute bend or at a branch point. However, lesions in the streptokinase group were more often irregular (p less than 0.005) and eccentric (p less than 0.01), had a shoulder (p less than 0.0001), globular filling defects (p less than 0.01), linear filling defects (p less than 0.00005) and contrast staining (p less than 0.05). Plaque ulceration index was higher in the streptokinase than in the stable angina group (6.2 +/- 7.9 versus 3.5 +/- 3.4, p less than 0.001). Of the 72 streptokinase-treated patients, 35 were maintained on heparin infusion until angioplasty 2 to 10 days later. At repeat angiography before angioplasty, globular lesion filling defects seen in eight patients had disappeared, whereas linear filling defects persisted in 7 of 14 cases. Fewer lesions were irregular (p less than 0.0001) and the ulceration index decreased from 7.4 +/- 10.4 to 3.0 +/- 1.6 (p less than 0.001). These data show that the lesion in the infarct-related artery after streptokinase treatment is irregular and often associated with filling defects, perhaps corresponding to plaque fissuring and intraluminal thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Analog computer assisted beat-by-beat measurement of stroke volume and related variables in man.

A technique for the beat-by-beat measurement of stroke volume is described. Aortic blood velocity signals are obtained from a catheter-mounted electromagnetic velocity transducer and analysed by a purpose-built analog computer. The stroke volume is computed by integration of each period of systolic forward flow using the velocity signal as its sole input. Automatic compensation of flowmeter drift is incorporated and inappropriate triggering of integration by diastolic artefact is prevented by applying both amplitude and duration criteria for the recognition of systolic forward flow. Early diastolic reverse flow is excluded from integration. The cardiac output, mean aortic flow per beat, and interbeat interval are also computed from the velocity signal. With aortic pressure as an additional input signal the mean arterial pressure per beat and systemic vascular resistance can be computed. The computer outputs are calibrated by a manual method. Preliminary studies comparing values for the cardiac output measured by this system and the direct Fick technique have indicated an excellent correlation between the two methods.

A comparison of pathological methods of measuring lung cancer volume.

AIM: To determine which of several pathological methods of measuring lung cancer volume compared most favourably with the gold standard. METHODS: Three pathological methods were used on 54 resected lung cancers: (1) measuring the maximum dimension and assuming a spherical shape; (2) measuring three dimensions and assuming an ellipsoidal shape; and (3) deriving the volume from the area of tumour on sequential 1 cm slices using a photocopier and an image analysis system. The gold standard was obtained from the area of whole mount tumour sections on sequential 0.1 cm slices of eight cancers. RESULTS: Volumes derived from 1 cm lung slices gave results closest to our gold standard but assuming tumours were ellipsoidal was only a slightly less accurate and less time consuming method. Assuming cancers were spherical resulted in gross overestimation of the tumour volumes. CONCLUSIONS: For practical purposes, it is reasonable to measure three dimensions of a lung tumour at sectioning and calculate the volume using the formula for an ellipsoid (V = 4/3 pi d.e.f, where d, e and f are the semi-axes).

Reassessment of the rate of fixative diffusion.

The diffusion of fixatives is slow. Early work using plasma gels and animal tissues showed the distance penetrated by a fixative to be a simple function of the fixation time but this relation has not been established in human tissues. The rates of diffusion into whole human spleens were measured for three primary fixatives over periods ranging from one to 25 days. A positive correlation was demonstrated between penetration distance (mm) and fixation time (hours). The diffusion rates were slower than those in previous studies. These results have possible implications for the handling of surgical specimens.

Successful treatment of Staphylococcus lugdunensis endocarditis complicated by multiple emboli: a case report and review of the literature.

We describe the prompt diagnosis and successful treatment of mitral valve endocarditis in a 52-year-old woman due to a recently described coagulase negative staphylococcus, Staphylococcus lugdunensis. Endocarditis due to this organism has a high mortality rate with 8 out of 12 published cases ending in fatality. Review of the literature revealed that use of commercial identification systems can lead to misidentification of Staphylococcus lugdunensis and consequently delay appropriate treatment. It is clinically important to distinguish Staphylococcus lugdunensis from other coagulase negative staphylococci by detailed microbiological testing. The awareness of this from of endocarditis and its natural history is important since it differs significantly from other coagulase negative staphylococci. It highlights the need for early surgical intervention not only for haemodynamic complications but also for recurrent emboli. Multiple emboli appears to be a frequent finding on review of the literature.

Long-term pretreatment with pentoxifylline increases random skin flap survival.

Optimizing survival of random skin flaps is essential to ensure successful rehabilitation of patients in whom flap reconstruction is necessary. This study tested the hypothesis that pentoxifylline improves random skin flap survival in porcine dorsal flank flaps when administered for at least 2 weeks preoperatively. Specific aims included establishing the mechanisms by which pentoxifylline enhanced survival. Treatment with pentoxifylline (25 mg/kg per day) for 14 days before surgery and for 7 days thereafter significantly increased mean flap survival to 73.2% +/- 4.5% compared with mean flap survival of 49.6% +/- 2.2% in untreated pigs. Increased flap survival was associated with a parallel increase in red blood cell flexibility. Plasma concentration of pentoxifylline ranged from 92.9 to 122.7 ng/mL but did not correlate directly with the improved flap survival. Likewise, pentoxifylline decreased platelet aggregation; there was a trend toward increased flap survival in those pigs with the least amount of aggregation. Thus, pentoxifylline improves random flap survival but only after a sufficient pretreatment period of at least 14 days.

Pharmacologic enhancement of random skin flap survival by prostaglandin E2.

This study evaluated the effect of prostaglandin E2 on skin flap survival in the porcine model. Dorsal random skin flaps on hypopigmented 15- to 25-kg pigs were used. Prostaglandin E2 (10 ng/kg per minute) was infused for 2 days prior to surgery and continued during the 7-day postoperative period. Mean flap survival was 52.58% +/- 3.62% for the control group and 68.51% +/- 3.34% for the experimental group (P < .05). A moderate correlation existed between prostaglandin E2 serum levels and flap viability. A strong correlation was noted between red blood cell flexibility and the amount of flap survival (r = .86). As red blood cell flexibility increased, the survival percentage also increased. Although prostaglandin E2 reduced adenosine diphosphate-induced platelet aggregation from a baseline of 86.08% +/- 8.33% to 54.61% +/- 17.21%, no correlation was noted between the amount of platelet aggregation and percent flap survival (r = .52).

Responses of neonates to parents' and others' voices.

Infants stimulated with 8-s recordings of speech and voices reading numbers showed a discrimination between their own mothers' and alien voices. In general, the infants' heart rates rose more in response to their mothers' than to an alien voice. However, infants tested less than 24 h after birth responded with significant heart rate deceleration to the mother's spontaneous speech and to the mother reading numbers. Response to the father's voice was also deceleration but to all alien voices was acceleration. Older infants' responses also tended to be acceleratory to most stimuli. Results support the suggestion that sounds which are repeatedly experienced before birth (especially the mother's voice) become familiar to the fetus so that the neonate responds selectively by orienting to them during the first few hours after birth.

Evaluation of cracks associated with ultrasonic root-end preparation.

The purpose of this study was to evaluate the integrity of resected root-end surfaces of extracted human teeth after using ultrasonic tips at low or high frequencies for root-end preparation. Thirty bilaterally matched pairs of single-rooted human teeth had root-end resections using a low-speed diamond saw and were examined for root-end cracks. The matched pairs of teeth were then divided into two experimental groups, with one member of each pair being placed in each group. In group 1, root-end preparations were made with an ultrasonic tip on the lowest frequency setting. The preparations in group 2 were done on the highest power setting. Two investigators again examined the resected root-ends using a stereomicroscope at x20 to x63 and recorded the numbers, types, and location of the cracks. Three types of cracks were observed: canal cracks, intradentin cracks, and cemental cracks. There were significantly more root-ends with cracks after ultrasonic root-end preparation than after root-end resection only. In root-ends that had any cracks, significantly more canal cracks per root occurred when the ultrasonic tip was used on the high-frequency setting for root-end preparation than when the ultrasonic tip was used on the low power setting.

Pasteurella multocida meningitis and septic arthritis secondary to a cat bite.

Animal bites are seen almost daily in the emergency department, and the majority heal without complication. Pasteurella multocida is frequently the causative organism of localized wound infections and cellulitis in this patient population. P. multocida infection is usually associated with close contact with pets, such as dogs and cats, that harbor this organism as normal oral flora. Meningitis and septic arthritis are very rare sequelae of P. multocida infection. This case report presents a patient with P. multocida bacteremia, meningitis, and septic arthritis developing together as a complication of a cat bite.

Comparison of french-pezzar and Malecot catheters for percutaneously placed gastrostomy tubes in cats.

Gastrostomy tubes were placed percutaneously in 28 cats by use of an endoscope. French-pezzar mushroom-tip catheters were used for 14 of the procedures, and Malecot catheters were used for the remainder. Inner flanges were not used in gastrostomy tube placement. The french-pezzar catheters remained in place and functional for 2 weeks in all 14 cats. The Malecot catheters remained in place and functional for 2 weeks in 4 cats. Malecot catheters pulled out in 10 cats, and 2 of these cats died or were euthanatized because of complications. The gastrostomy tubes were removed in 18 cats 2 weeks after placement by applying gentle, steady traction and removing the entire catheter or by cutting the tube flush with the skin and leaving the catheter tip in the cat's stomach. Neither method of removal was associated with problems.

Lymphocele in a cat.

A 21-month-old spayed domestic shorthair cat was examined to determine the cause of a chronic fluctuant swelling involving the left hind limb. A lymphocele was tentatively diagnosed on the basis of results of blood tests, radiography, and cytologic examination. Lymphangiography revealed the lymphocele and 2 tortuous collateral lymphatic channels. The lymphocele and a mass of fatty tissue were excised and 3 aberrant lymphatic vessels were ligated. Histologic examination did not reveal evidence of neoplasia. The cyst wall was composed of a layer of collagen and fibroblasts. The mass was an inflammatory nodule incorporating a lymphatic vessel. The authors believe this cat had an acquired lymphocele. The exact cause of lymphoceles is uncertain, but acquired lymphoceles have been reported secondary to tissue trauma or surgery in human beings. Treatment has included aspiration, tube drainage, open drainage and second-intention healing, surgical excision, ligation of lymphatic vessels, and chemical sclerosis of the cyst.

Levels of state anxiety for males facing redundancy and subsequently reporting to be employed or unemployed.

State anxiety scores for male adults, facing redundancy, were elevated whilst subjects awaited dismissal. Six months later, anxiety levels fell most notably for the reemployed. Simple strategies, providing some amelioration for individuals during the stressful anticipation period, were rarely provided by employers.

Relationship between years of training and judged performance in Shotokan karate black-belts.

The relation between length of training and Dan rank was significant for 110 male black-belts, although the complication of tied ranks was noted.