Date of birth and the incidence of acute ischemic stroke in Hungary. / Fecha de nacimiento e incidencia del ictus isquémico agudo en Hungría.

INTRODUCTION: The effect of the date of birth on the incidence of cardiovascular disease was confirmed in earlier studies. We aimed to determine whether the season of birth may be associated with a higher incidence of stroke in later life by analyzing thrombolysis numbers according over a ten-year period in Hungary. PATIENTS AND METHODS: We analyzed daily thrombolysis numbers between 2007 and 2016 according to the patients' date of birth based on seasons. The correlation between cumulative thrombolysis numbers between 2007 and 2016 per month and birth numbers per month based on data of the 1949 census were also examined. RESULTS: Our results indicate that being born in the spring and summer in the northern hemisphere may be associated with a higher frequency of ischemic stroke necessitating thrombolytic treatment. This equates to a higher risk when conception and early pregnancy occur in the summer and autumn months. CONCLUSIONS: This, however, cannot be defined as a causal relationship if we consider the number of live births in 1949, as both measures change similarly during the year, as indicated by the strong positive correlation between thrombolysis frequency according to date of birth between 2007 and 2016 and the number of births in the 1949 census by month.

TITLE: Fecha de nacimiento e incidencia del ictus isquémico agudo en Hungría.Introducción. El efecto de la fecha de nacimiento sobre la incidencia de enfermedad cardiovascular se ha confirmado en estudios anteriores. Nuestro objetivo fue determinar si la temporada de nacimiento puede estar asociada con una mayor incidencia de accidente cerebrovascular en etapas posteriores de la vida mediante el análisis de las cifras de trombólisis durante un período de 10 años en Hungría. Pacientes y métodos. Analizamos las cifras diarias de trombólisis entre 2007 y 2016 según la fecha de nacimiento de los pacientes según las estaciones. También se examinó la correlación entre las cifras de trombólisis acumuladas entre 2007 y 2016 por mes, y las cifras de nacimientos por mes según los datos del censo de 1949. Resultados. Nuestros resultados indican que nacer en primavera y verano en el hemisferio norte puede estar asociado con una mayor frecuencia de accidentes cerebrovasculares isquémicos que requieren tratamiento trombolítico. Esto equivale a un mayor riesgo cuando la concepción y el embarazo temprano ocurren en los meses de verano y otoño. Conclusión. Esto, sin embargo, no puede definirse como una relación causal si consideramos el número de nacidos vivos en 1949, ya que ambas medidas cambian de manera similar durante el año, como lo indica la fuerte correlación positiva entre la frecuencia de trombólisis según la fecha de nacimiento entre 2007 y 2016, y el número de nacimientos en el censo de 1949 por mes.

Fecha de nacimiento e incidencia del ictus isquémico agudo en Hungría / Date of birth and the incidence of acute ischemic stroke in Hungary

Introducción: El efecto de la fecha de nacimiento sobre la incidencia de enfermedad cardiovascular se ha confirmado en estudios anteriores. Nuestro objetivo fue determinar si la temporada de nacimiento puede estar asociada con una mayor incidencia de accidente cerebrovascular en etapas posteriores de la vida mediante el análisis de las cifras de trombólisis durante un período de 10 años en Hungría. Pacientes y métodos: Analizamos las cifras diarias de trombólisis entre 2007 y 2016 según la fecha de nacimiento de los pacientes según las estaciones. También se examinó la correlación entre las cifras de trombólisis acumuladas entre 2007 y 2016 por mes, y las cifras de nacimientos por mes según los datos del censo de 1949. Resultados: Nuestros resultados indican que nacer en primavera y verano en el hemisferio norte puede estar asociado con una mayor frecuencia de accidentes cerebrovasculares isquémicos que requieren tratamiento trombolítico. Esto equivale a un mayor riesgo cuando la concepción y el embarazo temprano ocurren en los meses de verano y otoño. Conclusión: Esto, sin embargo, no puede definirse como una relación causal si consideramos el número de nacidos vivos en 1949, ya que ambas medidas cambian de manera similar durante el año, como lo indica la fuerte correlación positiva entre la frecuencia de trombólisis según la fecha de nacimiento entre 2007 y 2016, y el número de nacimientos en el censo de 1949 por mes.(AU)

INTRODUCTION: The effect of the date of birth on the incidence of cardiovascular disease was confirmed in earlier studies. We aimed to determine whether the season of birth may be associated with a higher incidence of stroke in later life by analyzing thrombolysis numbers according over a ten-year period in Hungary. PATIENTS AND METHODS: We analyzed daily thrombolysis numbers between 2007 and 2016 according to the patients’ date of birth based on seasons. The correlation between cumulative thrombolysis numbers between 2007 and 2016 per month and birth numbers per month based on data of the 1949 census were also examined. RESULTS: Our results indicate that being born in the spring and summer in the northern hemisphere may be associated with a higher frequency of ischemic stroke necessitating thrombolytic treatment. This equates to a higher risk when conception and early pregnancy occur in the summer and autumn months. CONCLUSIONS: This, however, cannot be defined as a causal relationship if we consider the number of live births in 1949, as both measures change similarly during the year, as indicated by the strong positive correlation between thrombolysis frequency according to date of birth between 2007 and 2016 and the number of births in the 1949 census by month.(AU)

Calculated versus measured pure tone bone conduction 3 kHz thresholds in sudden sensorineural hearing loss.

OBJECTIVE: To compare the measured bone conduction threshold at 3 kHz with the calculated threshold in newly diagnosed sudden sensorineural hearing loss. METHODS: A retrospective chart review was conducted of pure tone audiograms in confirmed sudden sensorineural hearing loss cases. RESULTS: Of 157 patients with sudden sensorineural hearing loss, 144 had idiopathic hearing loss, 8 had vestibular schwannoma and 5 had Ménière's disease. The r value for the correlation between the two methods of 3 kHz assessment for all patients was 0.887 (p < 0.001). The mean difference between the measured and calculated 3 kHz thresholds was 0.76 ± 7.96 dB, 0.4 ± 8.08 dB and 1.5 ± 1.8 dB in the sudden sensorineural hearing loss, idiopathic and Ménière's disease groups, respectively. The mean difference between the measured and calculated 3 kHz thresholds was significantly greater in the vestibular schwannoma group (6.86 ± 4.38 dB) than in the idiopathic group (p = 0.013). CONCLUSION: The 3 kHz frequency may encompass important audiometric information. A discrepancy between the measured and calculated bone conduction 3 kHz thresholds raises suspicion of an underlying vestibular schwannoma as an aetiology for sudden sensorineural hearing loss, and these thresholds should therefore be measured independently and routinely.

Daylight saving time and the incidence of thrombolysis to treat acute ischemic stroke.

BACKGROUND: Twenty-five percent of the global population lives in one of the more than 70 countries that observe daylight saving time (DST). These people are exposed to 1hour of time transition twice a year, influencing the circulatory system. We aimed to analyze the incidence of thrombolysis to treat acute ischemic stroke in relation to clock changes in Hungary over a 10-year period. METHODS: The number of thrombolytic treatments performed within the period between 2006 and 2015 was analyzed. Anonymized nationwide data on the dates and exact daily numbers of thrombolysis interventions were provided by the National Health Insurance Fund. We compared the mean number of thrombolytic treatments on the day before with that on the day after each transition, and also between the preceding and following one week and month. RESULTS: Our data including the last days of each month suggested a significant increase in thrombolysis numbers both in spring and in autumn on the day and the week after the clock change. However, when the last days of each month were excluded from analysis (as this in itself was associated with a 7-fold increase in stroke incidence in our earlier study), no significant difference in the number of thrombolysis treatments between the days and weeks before and after the clock change was detectable. The long-term, monthly analysis also did not reveal a significant difference. CONCLUSIONS: Our findings reflect that psychosocial factors, such as the approach of the last day of the month override the intrinsic effect of disturbances of the circadian rhythm on stroke incidence.

Intraoperative cone-beam CT spatial priors for diffuse optical fluorescence tomography.

A hybrid system for intraoperative cone-beam CT (CBCT) imaging and continuous-wave fluorescence tomography (FT) has been developed using an image-guidance framework. Intraoperative CBCT images with sub-millimeter spatial resolution are acquired with a flat-panel C-Arm. Tetrahedral meshes are generated from CBCT for finite element method implementation of diffuse optical tomography (NIRFAST). Structural data from CBCT is incorporated directly into the optical reconstruction process using Laplacian-type regularization ('soft spatial priors'). Experiments were performed using an in-house optical system designed for indocyanine green (ICG) fluorescence. A dynamic non-contact geometry was achieved using a stereoscopic optical tracker for real-time localization of a laser diode and CCD camera. Source and detector positions were projected onto the boundary elements of the tissue mesh using algorithms for ray-triangle intersection and camera lens calibration. Simulation studies showed the capabilities of a soft-prior approach, even in the presence of segmentation uncertainties. Experiments with ICG targets embedded in liquid phantoms determined the improvements in the quantification of the fluorophore yield, with errors of 85% and <20% for no priors and spatial priors, respectively. Similar results were observed with the ICG target embedded in ex vivo porcine loin, with errors of 52% and 12%, respectively. A proof-of-principal animal study was performed in a VX2-tumor in vivo rabbit model using liposomal nanoparticles co-encapsulating contrast for CT (iohexol) and fluorescence (ICG) imaging. Fusion of CBCT and FT reconstructions demonstrated concurrent anatomical and functional delineations of contrast enhancement around the periphery of the buccal tumor. These developments motivate future clinical translation of the FT system into an ongoing CBCT-guided head and neck surgery trial.

Indicators of Renal Glomerular and Tubular Functions in Patients with Beta-Thalassaemia Major: A cross sectional study at the Royal Hospital, Oman.

OBJECTIVES: There are limited data concerning the assessment of renal function in beta-thalassaemia major, with no study of such involvement in Omani patients. The objective of this study was to establish the pattern of renal glomerular and tubular function using traditional and specific laboratory tests in patients with beta-thalassaemia major. METHODS: This cross-sectional study, from January-July 2008, included 30 patients of the Thalassaemia Clinic at the Royal Hospital, Oman, with transfusion-dependent homozygous beta-thalassaemia major. They included 15 males and 15 females, aged 16-32 years with mean ± standard deviation of 21.23 ± 3.42 years. The medical records were reviewed and renal function states assessed as follows: serum creatinine, estimated glomerular filtration rate (eGFR); urea; phosphate, fractional excretion of filtered sodium (FENa); urine albumin: creatinine index; urine ß2-microglobulin:creatinine index; tubular reabsorption of phosphate (TRP), and tubular maximum phosphate reabsorption (TmP)/GFR. RESULTS: All patients had eGFR >90 ml/min/1.73m(2); serum creatinine <90 µmol/L; serum urea <6.0 mmol/L, and urine albumin:creatinine <2.5 mg/mmol. Only 2 (6.7%) patients had FENa >1% and 3 (10.0%) patients had urine ß2-microglobulin: creatinine >22 µg/mmol. All patients had TRP >0.85, of whom seven (23.3%) patients had values within the range of 0.85-0.95 and 23 (76.7%) had values >0.95. Also, all patients had TmP/GFR >1.0 mmol/L, of whom only one (3.3%) patient had TmP/GFR of 1.0-1.5, and 29 (96.7%) patients had TmP/GFR >1.5 mmol/L. Finally, 24 (80%) patients had serum phosphate >1.4 mmol/L. Linear regression revealed a highly significant correlation between serum phosphate and TmP/GFR (r = 0.904, P < 0.001). CONCLUSION: Renal function, glomerular and tubular, appears to be well preserved in beta-thalassaemia major. Almost all renal function indicators were within the recommended ranges. Raised TmP/GFR and TRP were noted in the majority of patients, reflecting an up-trend in serum phosphate and therefore increasing renal phosphate reabsorption.

Amelioration of hepatic fibrosis via Padma Hepaten is associated with altered natural killer T lymphocytes.

Hepatic fibrosis is the end-stage consequence of chronic liver disease, affecting many people worldwide. Unlike the anti-fibrotic effect of natural killer (NK) cells, CD8 and NK T subsets are considered as profibrogenic subsets. Padma Hepaten is a multi-compound herbal preparation derived from Tibetan medicine and has proven efficacy in some clinical trials and tests at the cellular level. In this study, we evaluate the immune efficacy of Padma Hepaten administered intraperitoneally (i.p.) and/or orally in a mice model of hepatic fibrosis. Hepatic fibrosis was induced by 6 weeks of biweekly i.p. carbon tetrachloride (CCl4) injections in male C57Bl6 mice. There were four groups, including naive mice, non-treated fibrotic mice and fibrotic mice treated by Padma Hepaten at weeks 5-6 of fibrosis induction either orally or by i.p. injections. Padma Hepaten was prepared at 10 mg/ml in saline and 250 microl (2.5 mg) were administered four times per week. After week 6, animals were killed. To isolate a Padma Hepaten-associated effect on lymphocytes, splenocytes were harvested from either naive or Padma Hepaten-treated non-fibrotic donors. Isolated splenocytes were therefore reconstituted into two groups of irradiated recipients. Recipients were then administered the same CCl4 regimen. Hepatic fibrosis was determined by sirius red staining of liver sections and by assessment of alpha smooth muscle actin expression compared with beta-actin (both by mRNA as well as the protein liver extract western blotting). Hepatic fibrosis and alanine aminotransferase serum levels were decreased significantly in both Padma Hepaten-treated groups compared with the non-treated fibrotic group. Padma Hepaten treatment was associated with attenuation of lymphocyte subsets in both treated groups. Using a chemiluminescence technique to assess total anti-oxidant capacities (TAC), it was found that both the plasmas and livers of mice treated by CCl4 had significantly higher TAC compared with controls. However, the levels of TAC in animals treated either by CCl4 alone or CCl4 with Padma Hepaten were similar. Adoptive transfer of Padma Hepaten-treated lymphocytes was associated with fibrosis amelioration compared with recipients with naive lymphocytes. CCl4 generates higher levels of anti-oxidant capacities, probably as a response to oxidative stress. Padma Hepaten administration attenuated hepatic fibrogenesis significantly, accompanied by attenuation of lymphocyte but not anti-oxidant capacities.

Immunomodulatory effects of plasminogen activators on hepatic fibrogenesis.

Tissue-type plasminogen activators (tPA) and urokinase-type plasminogen activators (uPA) are involved in liver repair. We examined the potential immunomodulatory actions of uPA, tPA and uPA-receptor (uPAR) in carbon-tetrachloride-induced hepatic fibrosis in wild-type (WT), tPA-/-, uPA-/- and uPAR-/- mice. Carbon-tetrachloride treatment increased fibrosis in four groups but significantly less in three knock-out models. Serum cytokines and intrahepatic T cells elevated significantly following fibrosis process in WT animals but not in the knock-out groups. In culture, uPA increased lymphocyte proliferation significantly in WT and uPA-/- but not uPAR-/- animals. Following uPA exposure in vivo, there was CD8 predominance. To isolate uPA's effect on lymphocytes, WT mice were irradiated sublethally and then reconstituted with WT or uPA-/- lymphocytes. In these animals fibrosis was decreased and T cells were reduced in the uPA-/- recipients. Based on these data we postulate that plasminogen activators affect fibrosis in part by liver-specific activation of CD8 subsets that govern the fibrogenic activity of hepatic stellate cells.

Lymphocyte-hepatic stellate cell proximity suggests a direct interaction.

Recent functional research studies suggest an anti-fibrotic role for natural killer (NK) cells coupled with a profibrotic role for CD8 cells. However, the morphological cellular interplay between the different cell types is less clear. To investigate lymphocyte/hepatic stellate cell (HSC) interactions, hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) intraperitoneally (i.p.) for 4 weeks in C57Bl/6 mice. Animals were killed at 0, 1, 2, 3 and 4 weeks. Liver sections were stained for Sirius red. Confocal microscopy was used to evaluate alpha smooth-muscle actin (alphaSMA) and lymphocyte subsets in liver sections. At weeks 0 and 4, liver protein extracts were assessed for alphaSMA by Western blotting and isolated liver lymphocytes as well as HSC were analysed by fluorescence activated cell sorter (FACS). Similar to the results obtained from classical Sirius red staining and alphaSMA blotting, analysis of liver sections by confocal microscopy revealed a marked and continuous accumulation of alphaSMA staining along sequential experimental check-points after administering CCl4. Although the number of all liver lymphocyte subsets increased following fibrosis induction, FACS analysis revealed an increase in the distribution of liver CD8 subsets and a decrease of CD4 T cells. Confocal microscopy showed a significant early appearance of CD8 and NK cells, and to a lesser extent CD4 T cells, appearing only from week 2. Lymphocytes were seen in proximity only to HSC, mainly in the periportal area and along fibrotic septa, suggesting a direct interaction. Notably, lymphocyte subsets were undetectable in naive liver sections. Freshly isolated HCS show high expression of major histocompatibility complex (MHC) class II and CD11c. In the animal model of hepatic fibrosis, lymphocytes infiltrate into the liver parenchyma and it is thought that they attach directly to activated HSC. Because HSCs express CD11c/class II molecules, interactions involving them might reflect that HSCs have an antigen-presenting capacity.

[Pharmacokinetic study of percutaneous absorption of salicylic acid from baths with salicylate methyl ester and salicylic acid]. / Pharmakokinetische Untersuchung zur perkutanen Aufnahme von Salicylsäure aus Bädern mit Salicylsäuremethylester und Salicylsäure.

Percutaneous uptake of methyl salicylate was investigated by use of Leukona-Rheumabad (Dr. Atzinger) in 10 volunteers. Percutaneous uptake of salicylic acid was investigated by use of Contrheuma-Bad (Spitzner) in 15 volunteers. By use of bathing concentration of 0.03 g/l of methyl salicylate, plasma levels of 220-820 ng/ml were found 1 h after beginning, and 46-193 ng/ml after 6 h. 2.3-8.7 mg of salicyluric acid was eliminated on the first day, and 0.47 to 1.48 mg on the second day. By use of bathing concentration of 0.33 g/l of salicylic acid constant plasma levels of 10 +/- 1.27 ng/ml were found in a period of 24 h. The renal elimination of 0.92 +/- 0.14 at first day, 0.72 +/- 0.11 at second day, and 0.50 +/- 0.08 mg salicyluric acid at third day was found. Salicylic acid was eliminated 0.086 +/- 0.009 resp. 0.079 +/- 0.007 resp. 0.043 +/- 0.011 mg by those days. The half-time of elimination in urine after methyl salicylate bathing is (as with injected salicylic acid) between 2.4 to 4 h. Conversely half-time of elimination in urine by salicylic acid bathing is between 30 to 50 h, and is greater with salicylic acid bathing than with other application forms. This is in agreement with earlier examinations and results which point out the deposition of salicylic acid in skin. Any definitive deposition of salicylic acid in skin by methyl salicylate bathing was not found.(ABSTRACT TRUNCATED AT 250 WORDS)