Paroxysmal atrial fibrillation with high vs. low arrhythmia burden: atrial remodelling and ablation outcome.

AIMS: The relation between atrial tachyarrhythmia (ATA) burden in paroxysmal atrial fibrillation (AF), atrial remodelling, and efficacy of catheter ablation (CA) is unknown. We investigated whether high vs. low-burden paroxysmal AF patients have distinct clinical characteristics or electro-mechanical properties of the left atrium (LA) and whether burden impacts outcome of CA. METHODS AND RESULTS: Atrial tachyarrhythmia burden, defined as the percentage of time spent in ATA, was assessed by insertable cardiac monitors in 105 patients before and after CA. Clinical characteristics and electro-mechanical properties of LA were compared between patients with high vs. low ATA burden. Catheter ablation efficacy was assessed by reduction in ATA burden and 1-year freedom from any ATA. Median ATA burden was 2.7% (highest tertile 9.3%). Clinical characteristics and electrical properties of LA (refractoriness, conduction velocity, low voltage) did not differ between high (≥9.3%) vs. low ATA burden (<9.3%) patients. High ATA burden patients had larger LA diameter (46.5 ± 6 vs. 42.5 ± 6mm, P < 0.01), volume (93.8 ± 22 vs. 80.4 ± 21mL, P = 0.01), and lower LA reservoir and contractile strain (19.7 ± 6 vs. 24.7 ± 6%, P < 0.01; 10.3 ± 3 vs. 12.8 ± 4%, P = 0.01). Catheter ablation reduced ATA burden by 100% (100-100) in both groups (P = 1.0). Freedom from ATA after CA was equally high (83% vs. 89%, P = 0.38). CONCLUSION: Paroxysmal AF patients with high ATA burden have altered LA mechanical properties, reflected by larger size and impaired function. Despite mechanical remodelling of the atria, they are excellent responders to CA. Most likely the lack of fibrosis and/or advanced electrical remodelling explain why pulmonary veins remain the dominant trigger for AF in this patient cohort.

IMRT for breast. a planning study.

BACKGROUND AND PURPOSE: To evaluate the performance of ten different treatment-planning systems when intensity modulated (IMRT) plans are designed for breast treatments that include the irradiation of the internal mammary chain. PATIENTS AND METHODS: A dataset of five patients (CT images and volumes of interest) was distributed to design IMRT plans on the ten systems. To minimise biases, the same geometry and clinical planning aims were imposed on the individual plans. Results were analysed in terms of dose distributions and dose volume histograms. RESULTS AND CONCLUSIONS: For target coverage, the volume receiving more than 95% of the prescribed dose ranged from 77% (OTP) to 91% (Eclipse and Pinnacle), the volume receiving more than 107% ranged from 3.3% (Hyperion) to 23.2% (OTP). The mean dose to ipsilateral lung ranged from 13 Gy (Eclipse) to 18 Gy (OTP). The volume of the contralateral breast receiving more than 10 Gy ranged from 3% (Pinnacle) to 26% (Precise). The volume of heart receiving more than 20 Gy ranged from 7% (Eclipse) to 47% (Precise), the maximum significant dose to heart ranged from approximately 27 Gy (XiO) to approximately 49 Gy (Precise). The maximum significant dose to healthy tissue ranged from approximately 51 Gy (Eclipse) to approximately 62 Gy (OTP). It was also possible to show that the treatment geometry proposed here enables to minimise contralateral breast irradiation while keeping minimal ipsilateral lung (or heart) involvement and satisfactory target coverage.

Hypofractionated Simultaneous Integrated Boost (SIB) versus Conventional Fractionation in Localized Prostate Cancer: A Randomized Pilot Study.

PURPOSE: Radical prostatectomy or radiotherapy has comparable results in the treatment of localized prostate cancer. High dose external irradiation entails a prolonged 7-8 weeks of treatment with significant inconvenience to elderly patients. Hypofractionated regimen in prostate cancer depends on the distinctive radiobiological properties of prostate cancer cells; their relative low alpha beta ratio compared to that for late-reacting rectal tissue allows for significant dose escalation per fraction without expected increase in late normal tissue reaction. PATIENTS AND MATERIALS: Between July 2012 and December 2013, twenty patients were blindly randomized into two groups. The planning target volume in the study group received 65Gy to 67.5Gy/25 fractions over 5 weeks. The patients in the control arm received 74Gy to 78Gy in 2Gy/fraction. Cost-benefit was evaluated for both regimens. RESULTS: Both groups were comparable regarding risk factors, with no significant statistical differences. Four patients in the study group developed grade 2 urinary toxicity and one patient had grade 3 during treatment. At six months no patient had urinary symptoms. In the control arm 4 patients have grade 2 toxicity during treatment which disappeared at six months. The two groups showed no statistical difference in the mean quality of life. Serum PSA reached a nadir value of 0.02 and 0.04 in the study and control groups respectively at 3 month post-treatment. The cost of treatment for the study group was 25000 L.E. per patient compared to 40000 L.E. in the control group. The hypofractionated group consumed 31138 MU compared to 45611 MU for the control group with a p-value of 0.015. CONCLUSION: Hypofractionated IMRT with concomitant boost for localized cancer prostate is a feasible option with lesser cost and comparable toxicities. Longer followup is required to assess the late effects before recommending it as a standard of care.

The anus in the newborn.

The size of the anus is defined in newborns of varying weights. A plea is made for proper examination of the anus at birth.

In utero development of fetal thirst and appetite: potential for programming.

Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to programming of adulthood hyperphagia and obesity. Further research is needed to delineate the mechanistic relationship between the intrauterine environment and the development of the setpoints of adult appetite and thirst.

Determination of inorganic cations and anions by ion-exchange chromatography with evaporative light-scattering detection.

Evaporative light-scattering detection (ELSD) was investigated for the direct determination of alkali and alkaline-earth cations by cation-exchange chromatography. Successful single run analysis of Na+, K+, Mg2+ and Ca2+ was achieved in 11 min on the Hamilton PRP-X200 column using an aqueous solution of ammonium formate as mobile phase under a salt concentration step gradient mode (20 mM and 100 mM). Surprisingly the use of ELSD reveals a weak retention of inorganic anions (Cl-, NO3-, SO4(2-)) onto the polymeric cation exchanger, which enables the simultaneous determination of inorganic anions (C1- and NO3-) associated with the cations analysed (Na+ and K+).

Unopposed appetite (orexigenic) mechanisms in the near-term ovine fetus: central leptin does not inhibit sucrose ingestion.

OBJECTIVE: Leptin is produced in adipocytes and is present in the term fetus. In the adult, leptin acts centrally to inhibit neuropeptide Y-induced carbohydrate intake. We sought to examine if central leptin alters fetal ingestion of oral sucrose in the near-term ovine fetus. METHODS: Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual and intracerebroventricular (ICV) catheters and esophageal electromyogram electrodes, and studied at 132 +/- 1 days' gestation (term 145-150 days). Following a 2-h baseline period, 10% sucrose was infused sublingually (0.25 ml/min) for the duration of the study. At time 4 h, leptin (0.075 mg/kg) was administered ICV and fetal swallowing was monitored for an additional 6 h. RESULTS: During the basal period, fetal swallowing averaged 0.7 +/- 0.1 swallows/min. Fetal swallowing increased significantly in response to 10% sucrose (1.2 +/- 0.1 swallows/min; p < 0.05). In response to ICV leptin, fetal swallowing remained significantly elevated at 2, 4 and 6 h (1.3 +/- 0.4, 1.4 +/- 0.3 and 1.5 +/- 0.2 swallows/min, respectively; p < 0.05 vs. control). CONCLUSIONS: These results indicate that central leptin inhibition of sucrose ingestion is not functional in the near-term fetus. We speculate that a leptin-mediated anorexigenic response is not present at birth, such that unopposed appetite stimulatory mechanisms in the newborn may facilitate rapid newborn weight gain despite high body fat levels.

[Polypoidal choroidal vasculopathy in a patient with a melanocytoma of the optic nerve]. / Vasculopatía coroidal polipoidea en paciente con melanocitoma del nervio óptico.

PURPOSE/METHOD: The choroidal neovascularization (CNV) may be associated with several types of choroidal tumors. The polypoidal choroidal vasculopathy (PVC) is a variant of the choroidal neovascularization. We present a case of PCV associated with melanocytoma of the optic nerve. RESULTS/CONCLUSIONS: Although we cannot rule out that these two entities are independent of each other, the reported cases of choroidal tumors with CNV, the publication of a similar case and the epidemiological similarity between melanocytoma and PCV leads us to think that they may be related. We confirm the efficacy of laser argon treatment (Arch Soc Esp Oftalmol 2002; 77: 455-458).

Treatment of aggressive fibromatosis: the experience of a single institution.

AIMS: Aggressive fibromatosis is a locally aggressive infiltrative low-grade tumour, although pathologically benign, and it does not metastasise, yet it can cause serious local distressing symptoms by virtue of local destruction and impairment of local function. The aim of this study was to emphasise the role of radiotherapy and adequate surgery in the treatment of fibromatosis in patients presenting with newly diagnosed or recurrent disease and to analyse our treatment results over 15 years for this rare tumour type. MATERIALS AND METHODS: Fifty-four patients with confirmed diagnosis of aggressive fibromatosis treated at King Faisal Specialist Hospital between 1990 and 2006 were identified from our local cancer registry. Forty-seven patients had surgery: complete resection (R0) in 20 patients, incomplete surgery (R1/2) in 27 patients, and seven patients had biopsy only. Forty-five patients were treated with radiotherapy: 38 patients were treated with postoperative radiotherapy, three patients were treated with preoperative radiotherapy and four patients had radiotherapy as the only treatment. The radiotherapy dose ranged between 45 and 60Gy (median 50.4Gy). Three patients did not receive any form of treatment apart from biopsy, but were still included in the final analysis. RESULTS: Fifty-two per cent (28/54 patients) of our patient population had tumour recurrence when first presented to King Faisal Specialist Hospital. The median age was 29.5 years (range 2-63 years). The most common site of involvement was the extremities (28 patients). Among the 54 patients (with primary and recurrent presentation) there were 10 local recurrences, all of which were within the original primary site. The 5-year progression-free survival and overall survival rates for the whole group were 75 and 95%, respectively. Univariate and multivariate Cox regression analysis showed that the depth of invasion significantly affected progression-free survival. CONCLUSION: Aggressive fibromatosis is effectively treated with surgery and postoperative radiotherapy. Patients first presenting with tumour recurrence may still have local tumour control comparable with newly diagnosed patients.

Nursing in the United Arab Emirates: an historical background.

AIM: To gain a better understanding of some of the factors that may be contributing to the shortage of national nurses in the United Arab Emirates (UAE). BACKGROUND: Approximately 3% of the UAE nursing workforce are currently nationals, which explains the UAE dependency on transient expatriate nurses. Even though Emirati women have been recently empowered to join the national workforce, not many have joined the nursing profession. Several factors may be contributing, in varying degrees, to this predicament. METHOD: The socio-economic factors as well as the cultural and religious customs that have shaped the country and its people are examined. Hence, the historical background to the establishment of the UAE, women in Islam, the first nurse in Islam, the development of nursing in the UAE and the Emirates Nursing Association are considered. CONCLUSION: Factors contributing to the limited number of UAE nationals in the nursing profession include, but are not limited to: the low status of nursing in the UAE; the variations in basic nursing programmes in the country; the lack of Arabic educational resources; the affluent life style of UAE nationals as well as the strict cultural norms and religious values by which they live. As the need to nationalize the nursing workforce in the UAE is paramount, these issues and other perceived barriers from the perspective of Emirati nurses need to be explored and addressed.

Enantioselective synthesis of 2- and 3-substituted 2,3-dihydro[1,4]dioxino[2,3-b]pyridine derivatives and enantiomeric purity control by capillary electrophoresis.

A rapid and simple procedure for enantioselective preparation of 2- and 3-substituted 2,3-dihydro[1,4]dioxino[2,3-b]pyridine derivatives (A and B, respectively) is described. The enantiomeric purity of each isomer was determined by capillary electrophoresis using a dual-cyclodextrin system (S-beta-CD/beta-CD) dissolved in formic acid-ammonia buffer (pH 4, ionic strength 50 mM).

Impact of FDA advisory on reported vacuum-assisted delivery and morbidity.

OBJECTIVE: In May 1998 the US Food and Drug Administration (FDA) issued a health advisory reporting neonatal injuries/deaths following vacuum delivery and encouraged voluntary reports of future adverse events. We compared FDA reports of vacuum delivery adverse events prior to and following the advisory. METHODS: The FDA database (MAUDE) was searched for vacuum deliveries using brand name, manufacturer name, and procedure "string searches." Cases were sorted by report date, source, and manufacturer. Neonatal morbidity was quantified as deaths and life-threatening or nonlife-threatening events. RESULTS: A total of 80 reported adverse cases were identified after duplicate cases were consolidated. Twenty-five were reported to the FDA prior to the 1998 advisory and 55 in the immediate 6-month period following the advisory. There was a 22-fold increase in reported events from five events/year prior to the advisory to an estimated 110 events/year following the advisory. The distribution of reporting sources changed significantly following the advisory with increased "manufacturer" (8-43%) and decreased "voluntary" reports (56-20%). All major brand names were represented. During the 6 months following the FDA advisory there were 10 neonatal deaths, 30 life-threatening events, 12 nonlife-threatening events, and three equipment-related reports. Infant deaths were due to intracranial or subgaleal hematomas. Injuries included skull fracture, scalp abrasions, and cephalohematomas. CONCLUSIONS: The FDA advisory was associated with a 22-fold increase in the rate of reported adverse events. This increase in reporting likely represents both enhanced awareness of complications as well as an increase in vacuum-related adverse neonatal sequelae. As vacuum delivery is associated with greater neonatal morbidity/ mortality than was previously recognized, the adage that the vacuum is "designed to come off before infant damage occurs" appears unsubstantiated. It is recommended that manufacturers quantify the suction and traction capabilities of present and new proposed vacuum cup designs.

Dynamic of antibiotic accumulation by Streptomyces aureofaciens in a laboratory fermentor.

In a laboratory fermentor, the growth of Streptomyces aureofaciens on corn meal extract and its production of antibiotic was investigated. Weak biosynthesis of the antibiotic started after 12 hours of incubation, when phosphorus depletion in the medium occurred. During the third and fourth day of fermentation about 80.4% of the antibiotic was produced. The relationship between growth, antibiotic formation, and the uptake of both sugar and nitrogen was also studied. A chromatogram, showing the types of sugar present during fermentation period is given. Improvement of antibiotic accumulation either by adding sugar at the end of the logarithmic phase of growth or by determining the rate of aeration is also discussed.

Purification and identification of Streptomyces aureofaciens lD13 antibiotic.

Complete extraction of S. aureofaciens lD13 antibiotic was achieved by adding n-butanol to the clarified culture filtrate (v/2v) at pH 8.0. Using the column chromatography technique, 85.7% of the initial amount of the antibiotic was obtained in a purified form. Data of the Rf values of the antibiotic in different organic solvents revealed that it belongs to the tetracycline group. The antibiotic was chromatographically analyzed, using the thin-layer technique. UV and IR spectra, optical rotation, melting point as well as 15 colour reactions were also determined.

Nitric oxide modulates angiotensin II-induced drinking behavior in the near-term ovine fetus.

OBJECTIVE: Human and ovine fetuses demonstrate an enhanced rate of spontaneous and angiotensin II-stimulated swallowing. Angiotensin II and nitric oxide synthase have been localized to thirst centers in the brain. This study was performed to determine whether central nitric oxide contributes to the regulation of angiotensin II-induced fetal swallowing. STUDY DESIGN: Six pregnant ewes with near-term singleton fetuses were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram and esophageal electromyogram electrodes. After a 2-hour control period, fetuses were administered serial lateral ventricle injections (1 mL) of angiotensin II (3.2 microg; time, 2 hours) and N omega-nitro-L -arginine methyl ester (3 mg; time, 3 hours) and a repeat angiotensin II injection (3.2 microg; time, 5 hours). All fetuses received an additional control study of lateral ventricle injections of artificial cerebrospinal fluid on a previous day. RESULTS: Angiotensin II injection significantly increased mean +/- SEM fetal swallowing (0.9 +/- 0.1 to 2.7 +/- 0.4 swallows/min). N omega-nitro-L -arginine methyl ester significantly decreased fetal swallowing to below the basal rate (0.4 +/- 0.1 swallows/min), and swallowing did not increase with the second angiotensin II dose (in the presence of nitric oxide blockade). CONCLUSIONS: These results demonstrate that inhibition of central nitric oxide suppresses fetal swallowing behavior in response to central angiotensin II. We speculate that tonic nitric oxide facilitates angiotensin II swallowing stimulation by maintenance of glutamate activation of hypothalamic N -methyl-D -aspartate receptors.

Nitric oxide modulates spontaneous swallowing behavior in near-term ovine fetus.

Human and ovine fetuses demonstrate an enhanced rate of swallowing, an activity critical for amniotic fluid regulation. Fetal swallowing may be modulated by both systemic and central factors. Nitric oxide (NO) is a central neuromodulator that has been localized to brain regions regulating thirst and swallowing. We sought to determine if NO contributes to the regulation of spontaneous ovine fetal swallowing. Six time-dated pregnant ewes with singleton fetuses (129 +/- 1 day) were chronically prepared with fetal vascular and lateral ventricle catheters and electrocorticogram (ECoG) and esophageal electromyogram electrodes. After a 2-h control period, fetuses were given lateral ventricle injection of NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) and monitored for 2 h. NO precursor L-arginine was then injected into the lateral ventricle, and fetuses were monitored for a final 2 h. All fetuses received an additional control study of fetal swallowing before and after lateral ventricle injection of artificial cerebrospinal fluid (aCSF). Data were analyzed with repeated-measures ANOVA and paired t-test (P < 0.05). Suppression of a central NO with central L-NAME significantly reduced mean (+/-SE) spontaneous fetal swallowing (1.2 +/- 0.1-0.6 +/- 0.1 swallows/min low-voltage ECoG; P < 0.01). Restoration of central NO by L-arginine significantly increased fetal swallowing to pre-L-NAME levels (1.2 +/- 0.1 swallows/min low voltage). There were no changes in fetal swallowing during the control study of aCSF. Fetal ECoG activity and blood pressure did not change during the study or control aCSF injection. We conclude that NO is an important neuromodulator of fetal swallowing activity. Central NO synthase activity may contribute to the heightened level of spontaneous fetal swallowing and thus amniotic fluid regulation.

Effects of central angiotensin II receptor antagonism on fetal swallowing and cardiovascular activity.

OBJECTIVE: Fetal plasma angiotensin II levels are 10 times the levels found in adults. Despite these high levels, central injection of angiotensin II may stimulate fetal swallowing and increase fetal arterial blood pressure. We postulated that the high rate of spontaneous fetal swallowing and normal fetal pressor regulation may be dependent, in part, on central angiotensin II. In view of the potential dipsogenic role of both type 1 and type 2 angiotensin II receptors, we examined the central effect of the nonselective angiotensin II receptor antagonist saralasin on fetal swallowing and cardiovascular responses. STUDY DESIGN: Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular catheters, electrocorticograms, and esophageal electromyogram electrodes and studied at 130 +/- 1 days' gestation. After an initial 2-hour baseline period (0 to 2 hours), saralasin (1 mL, 64 microg) was injected intracerebroventricularly (2 to 4 hours). After 4 hours the dose of saralasin was repeated together with angiotensin II (1 mL, 6.4 microg), and the fetuses were monitored for a final 2 hours. Four fetuses also underwent an identical control study (on an alternate day) in which saralasin was replaced with artificial cerebrospinal fluid. RESULTS: Blockade of central angiotensin II receptors by intracerebroventricular saralasin significantly reduced mean (+/- SEM) spontaneous fetal swallowing (1.3 +/- 0.1 to 0.4 +/- 0.1 swallows per minute; P <.001) but did not alter fetal mean blood pressure (50 +/- 5 versus 56 +/- 5 mm Hg). Intracerebroventricular angiotensin II, in the presence of saralasin, did not affect swallowing (0.6 +/- 0.1 swallows per minute) or fetal blood pressure. In the control study, intracerebroventricular artificial cerebrospinal fluid did not change fetal swallowing (0.9 +/- 0.1 versus 1.0 +/- 0.1 swallows per minute), whereas intracerebroventricular angiotensin II significantly increased swallowing activity (1.0 +/- 0.1 versus 2.0 +/- 0.1 swallows per minute; P <.001) and fetal blood pressure (51 +/- 2 to 59 +/- 3 mm Hg; P =.003). CONCLUSIONS: Tonic activity of central angiotensin II receptor stimulation contributed to the high rate of basal ovine fetal swallowing but not fetal basal blood pressure. Angiotensin II-mediated fetal dipsogenic and pressor responses are a result of specific angiotensin II receptor binding in central brain regions. These results indicate that fetal exposure to angiotensin II antagonists or angiotensin-converting enzyme inhibitors may have adverse effects on fetal and amniotic fluid homeostasis.