Late Symptoms Research Articles

The Pathophysiology of Concussion

Abstract Concussion is defined as a biomechanically induced brain injury characterized by the absence of gross anatomic lesions. Early and late clinical symptoms, including impairments of memory and attention, headache, and alteration of mental status, are the result of neuronal dysfunction mostly caused by functional rather than structural abnormalities. The mechanical insult initiates a complex cascade of metabolic events leading to perturbation of delicate neuronal homeostatic balances. Starting from neurotoxicity, energetic metabolism disturbance caused by the initial mitochondrial dysfunction seems to be the main biochemical explanation for most postconcussive signs and symptoms. Furthermore, concussed cells enter a peculiar state of vulnerability, and if a second concussion is sustained while they are in this state, they may be irreversibly damaged by the occurrence of swelling. This condition of concussion-induced brain vulnerability is the basic pathophysiology of the second impact syndrome. N-acetylaspartate, a brain-specific compound representative of neuronal metabolic wellness, is proving a valid surrogate marker of the post-traumatic biochemical damage, and its utility in monitoring the recovery of the aforementioned “functional” disturbance as a concussion marker is emerging, because it is easily detectable through proton magnetic resonance spectroscopy.

Surgical closure of nasal septal perforation. Early and long term observations

Results of surgical treatment of nasal septal perforation are usually evaluated using closure of the perforation as criterion of success. Patients, however, may still have symptoms. To assess the long-term results of surgical treatment of nasal septal perforation with bilateral, posterior based mucoperichondrial septal flaps using a four-point symptom score to ultimately improve treatment and selection criteria. Patients were seen 6 months postoperatively. Questionnaires were sent to 116 surviving patients in 2008-2009. The response was 104. Patients reporting moderate or severe symptoms were seen as outpatients. Between 1987 and 2004, 126 patients were surgically treated using posterior based bilateral mucoperichondrial septal flaps. Sixteen patients had a reperforation during the first 3 months, and another 3 several years later. There was no correlation between early outcome and diagnosis, preoperative size of the perforation, gender or severity of preoperative crusting. There was an increased rate of reperforation with increasing age. Complications seen at the 6 months` follow-up of patients with closed perforations were lachrymal duct stenosis, partial vestibular stenosis, hypoesthesia, crusting and septal deviation, most of which were treatable. Long-term observation mean 10 years) of the same patients showed the following moderate or severe symptoms: crusting, obstruction and bleeding, mainly in men. Obstruction was often due to various forms of perennial rhinitis, sometimes to crusting and more rarely to septal deviation. Crusting was the only independent symptom. There was no correlation between crusting and diagnosis, preoperative size of the perforation, age or severity of preoperative crusting. Results of the surgical technique using posterior based bilateral mucoperichondrial septal flaps for treatment of nasal septal perforations were good, but depend on surgical expertise and age of the patient. Long-term results from other studies will be a guide to choose the proper surgical procedure to minimize the number of late symptoms. Prosthetic treatment cans be an alternative. Patients with return of symptoms should seek further advice.

Surgical closure of nasal septal perforation. Early and long term observations

Background: Results of surgical treatment of nasal septal perforation are usually evaluated using closure of the perforation as criterion of success. Patients, however, may still have symptoms. Aim: To assess the long-term results of surgical treatment of nasal septal perforation with bilateral, posterior based mucoperichondrial septal flaps using a four-point symptom score to ultimately improve treatment and selection criteria. Methodology: Patients were seen 6 months postoperatively. Questionnaires were sent to 116 surviving patients in 2008-2009. The response was 104. Patients reporting moderate or severe symptoms were seen as outpatients. Results: Between 1987 and 2004, 126 patients were surgically treated using posterior based bilateral mucoperichondrial septal flaps. Sixteen patients had a reperforation during the first 3 months, and another 3 several years later. There was no correlation between early outcome and diagnosis, preoperative size of the perforation, gender or severity of preoperative crusting. There was an increased rate of reperforation with increasing age. Complications seen at the 6 months` follow-up of patients with closed perforations were lachrymal duct stenosis, partial vestibular stenosis, hypoesthesia, crusting and septal deviation, most of which were treatable. Long-term observation mean 10 years) of the same patients showed the following moderate or severe symptoms: crusting, obstruction and bleeding, mainly in men. Obstruction was often due to various forms of perennial rhinitis, sometimes to crusting and more rarely to septal deviation. Crusting was the only independent symptom. There was no correlation between crusting and diagnosis, preoperative size of the perforation, age or severity of preoperative crusting. Conclusions: Results of the surgical technique using posterior based bilateral mucoperichondrial septal flaps for treatment of nasal septal perforations were good, but depend on surgical expertise and age of the patient. Long-term results from other studies will be a guide to choose the proper surgical procedure to minimize the number of late symptoms. Prosthetic treatment cans be an alternative. Patients with return of symptoms should seek further advice.

Molecular interaction between two cassava geminiviruses exhibiting cross-protection

There are increasing reports of geminivirus mixed infections of field plant hosts. These mixed infections have been suggested to result in recombinations, emergence of new viruses and new disease epidemics. We previously reported the occurrence of mixed infection between African cassava mosaic virus (ACMV) and East African cassava mosaic Cameroon virus (EACMCV) resulting in severe symptoms in cassava fields in Cameroon. Here, we show that reassortment of DNA-A and DNA-B components of ACMV and EACMCV does not form viable recombinants. However, in the presence of both components of either virus, the DNA-A component of the other virus replicated and spread in the absence of its DNA-B component. This result suggests that failure of ACMV and EACMCV to form viable recombinants is due to the inability of each DNA-A component to trans-replicate the heterologous DNA-B component. This study also shows that ACMV DNA-A induces a resistance to ACMV and EACMCV as indicated by absence or late symptom development. Moreover, this resistance enabled plants to recover from severe symptoms caused by EACMCV in Nicotiana benthamiana, suggesting that the resistance induced is not specific to ACMV and is consistent with the phenomenon of cross-protection between related viruses.

Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study

Background:We surveyed the occurrence of physical symptoms among long-term gynaecological cancer survivors after pelvic radiation therapy, and compared with population-based control women.Methods:We identified a cohort of 789 eligible gynaecological cancer survivors treated with pelvic radiation therapy alone or combined with surgery in Stockholm or Gothenburg, Sweden. A control group of 478 women was randomly sampled from the Swedish Population Registry. Data were collected through a study-specific validated postal questionnaire with 351 questions concerning gastrointestinal and urinary tract function, lymph oedema, pelvic bones and sexuality. Clinical characteristics and treatment details were retrieved from medical records.Results:Participation rate was 78% for gynaecological cancer survivors and 72% for control women. Median follow-up time after treatment was 74 months. Cancer survivors reported a higher occurrence of symptoms from all organs studied. The highest age-adjusted relative risk (RR) was found for emptying of all stools into clothing without forewarning (RR 12.7), defaecation urgency (RR 5.7), difficulty feeling the need to empty the bladder (RR 2.8), protracted genital pain (RR 5.0), pubic pain when walking indoors (RR 4.9) and erysipelas on abdomen or legs at least once during the past 6 months (RR 3.6). Survivors treated with radiation therapy alone showed in general higher rates of symptoms.Conclusion:Gynaecological cancer survivors previously treated with pelvic radiation report a higher occurrence of symptoms from the urinary and gastrointestinal tract as well as lymph oedema, sexual dysfunction and pelvic pain compared with non-irradiated control women. Health-care providers need to actively ask patients about specific symptoms in order to provide proper diagnostic investigations and management.

Outgrowth inhibition of Clostridium beijerinckii spores by a bacteriocin-producing lactic culture in ovine milk cheese

In the manufacture of model cheeses, ovine milk was deliberately contaminated with spores of Clostridium beijerinckii INIA 63, a wild isolate from Manchego cheese with late blowing defect, and inoculated with nisin- and lacticin 481-producing Lactococcus lactis subsp. lactis INIA 415 as starter, to test its potential to prevent the late blowing defect, or with L. lactis subsp. lactis INIA 415-2, a spontaneous mutant not producing bacteriocins. Cheeses made individually with the lactococcal strains, without clostridial spores, served as controls. Cheese made with clostridial spores and L. lactis subsp. lactis INIA 415-2 showed late blowing defect after 120days of ripening. Spoilt cheese also showed lower concentrations of lactic acid, and higher levels of acetic, propionic and butyric acids, and of other volatile compounds such as 2-propanol and 1-butanol, than control cheese. In addition, cheese made with the bacteriocin producer did not show any late blowing symptoms, despite its spore counts similar to those of blown cheese, pointing to outgrowth inhibition of C. beijerinckii spores by bacteriocins. Besides, cheese made with the bacteriocin producer showed similar concentrations of lactic acid and volatile compounds than control cheese. Inclusion of L. lactis subsp. lactis INIA 415 in starter cultures seems a feasible method to prevent late blowing defect in cheese without altering its sensory characteristics.

Treatment of acute radiation cystitis: reply by the authors

Dear Editor, We highly appreciate the comments by Drs. Wang, Horng and Lee regarding our feasibility study on prevention of radiation cystitis by intravesical instillations with chondroitin sulphate [1]. We fully agree that more pre-clinical studies may help to elucidate the mechanisms and treatment of radiation cystitis, and that several clinical studies are needed to assess the efficacy of intravesical instillations with chondroitin sulphate. In fact, we hope soon to start a double-blind study in patients undergoing primary or adjuvant radiotherapy for gynaecological malignancies. In that trial, a wider range of early and late clinical symptoms will be evaluated, as also suggested by Wang et al.

First Report of Phytophthora infestans Causing Late Blight on Solanum viarum in Colombia.

Solanum viarum Dunal (tropical soda apple) belongs to the section Acanthophora in the genus Solanum, which includes nearly 20 neotropical species of herbs and small shrubs (2). The species in this section are sometimes called the 'spiny Solanums' (2) and are adapted mainly to highly disturbed habitats and open secondary forests. The center of diversity is eastern Brazil (3). Since the early 1990s, S. viarum has been a problematic weed in Florida where it was listed as a noxious weed in 1993, followed in 1994 by its addition to the Federal Noxious Weed List of the USDA. On 17 April 2010, 12 plants of S. viarum located close to a S. betaceum crop (tree tomato) in the province of Caldas (Department of Antioquia, central northwestern Colombia) were found with symptoms similar to late blight caused by Phytophthora infestans on S. tuberosum (potato). Fifteen leaves from 12 plants with blackish, water-soaked lesions showing a white sporulation on the abaxial side were collected and processed within 3 days. The leaves were placed in a humid chamber and incubated in darkness at room temperature (18°C mean temperature) until sporulation was observed. Microscopic characteristics were consistent with Phytophthora spp. Only one axenic culture was obtained by successive subcultures in rye B agar plates. After an incubation period of 8 days, plates were washed with distilled water and ovoid, semipapillate caduceus sporangia ranging from 38 to 41 μm long (average 39; N = 86) and 23 to 29 μm wide (average 26; N = 86) were observed. To fulfill Koch's postulates and test the isolate for the ability to infect potato as well as Solanum spp. associated with potato crops in Colombia, triplicate pathogenicity tests were carried out on three detached leaves of S. viarum, S. tuberosum, and S. americanum (American nightshade). A 1 × 104 sporangia/ml suspension of the Phytophthora isolate, estimated using a haemocytometer, was obtained from 8-day-old cultures grown on rye B agar. The suspension was incubated at 4°C for 2 h to induce zoospore release. The leaves were then inoculated by spraying them until runoff. After an incubation period of 5 days at 18°C in a humidity chamber, mycelia, sporangia, and brownish lesions, similar to those described above, were observed in the leaves of all three hosts, indicating pathogenicity. DNA extraction was performed from the P. infestans isolate (4). Four nuclear loci, ITS, β-tubulin, Ras, and Avr3a, as well as one mitochondrial gene, cytochrome c oxidase 1 (Cox1), were amplified and sequenced. Sequences were compared with GenBank databases using Blastn. In all cases, the best hits corresponded to P. infestans (GenBank Accession No. HQ639930 for Avr3A, HQ639931 for β-tubulin, HQ639932 for Cox1, HQ639933 for iRas, HQ639934 for Ras, and JF419363 for ITS). Reports of P. infestans causing typical late blight symptoms on wild solanaceous plants are becoming more frequent and have been made from other countries such as Peru (1). To our knowledge, this is the first time that P. infestans has been observed and isolated from S. viarum in Colombia, introducing the possibility of this wild solanaceous weed as another late blight host.

RESISTANCE EVALUATION ON POPULATIONS OF CROSSES BETWEEN TRANSGENIC POTATO KATAHDIN RB AND NON-TRANSGENIC ATLANTIC AND GRANOLA TO LATE BLIGHT (Phytophthora infestans) IN CONFINED FIELD TRIAL

Late blight resistance gene (RB gene) isolated from Solanum bulbocastanum, is a broad resistance gene against all races of Phytophthora infestans. The gene was transformed into Katah-din event SP904 and SP951 using Agrobacterium tumefaciens and these transgenic plants have been crossed with susceptible potato cultivars Atlantic and Granola. Populations of the crosses have been molecularly characterized for the integration of the RB transgene. The study aimed to evaluate the resistance of the populations of crosses between transgenic Katahdin RB and susceptible non-transgenic parents (Atlantic and Granola) to late blight in a confined field trial at Pasir Sarongge, Cianjur, West Java. A total of 84 clones originated from four popula-tions were evaluated for resistance to late blight. These included 22 clones of Atlantic x transgenic Katahdin SP904, 16 clones of Atlantic x transgenic Katahdin SP951, 19 clones of Granola x transgenic Katahdin SP904, and 27 clones of Granola x transgenic Katahdin SP951. Observations of the late blight infection were conducted when late blight symptoms were detected, i.e. at 56, 60, 63, 70, and 77 days after planting (DAP). The result showed there were high variations in the resistance level of all the 84 clones tested. Clones of crosses between susceptible parents (Atlantic or Granola) and resistant parents (transgenic Katahdin SP904 or Katahdin SP951) showed a similar pattern based on the area under disease progress curve (AUDPC) value, i.e. 377.2 greater than the AUDPC of the resistant parents (180.1), but smaller than that of the susceptible parents (670.7). Observation at 77 DAP resulted four resistant potato clones having resistance score of 7.0-7.6, higher than the transgenic parents Katahdin SP904 (4.6) and Katahdin SP951 (6.8), i.e. clone B8 (Atlantic x transgenic Katahdin SP951) with resistance score of 7.6 and clones B26 (Atlantic x transgenic Katahdin SP951), C183 (Granola x transgenic Katahdin SP904), and D89 (Granola x transgenic Katahdin SP951) with resistance score of 7. These four transgenic potato resistant clones need to be further developed as promising potato clones to late blight.<br /><br />

The Impact of Clinical Factors on the Development of Late Radiation Toxicity: Results from the Medical Research Council RT01 Trial (ISRCTN47772397)

Aims A variety of dosimetric parameters have been shown to influence the incidence of late radiation toxicity. The effect of other treatment- and patient-related factors is less well established. The aim of this study was to elucidate the influence of such factors in the development of late symptoms after radical radiotherapy to the prostate. Materials and methods Patient- and treatment-related factors that are thought to influence the development of late toxicity were analysed in 788 patients who had received radical radiotherapy to the prostate in the Medical Research Council RT01 trial. Late toxicity data were recorded using the Radiation Therapy Oncology Group, Late Effects of Normal Tissues/Subjective, Objective, Management, Analytic, Royal Marsden Hospital and the University of California, Los Angeles, Prostate Cancer Index. Acute toxicity was measured using the Radiation Therapy Oncology Group grading system. Results On multivariate analysis, acute bowel toxicity was statistically significantly associated with increased proctitis (hazard ratio = 1.63, 95% confidence interval 1.18, 2.24; P = 0.003) and increased stool frequency (hazard ratio = 1.77, 95% confidence interval 1.27, 2.46; P = 0.001). Hypertension was strongly associated with a decreased risk of poor urinary stream (hazard ratio = 0.25, 95% confidence interval 0.09, 0.71; P = 0.009). There was an increased risk of rectal bleeding with increased age (hazard ratio = 1.04 per year of age, 95% confidence interval 1.01, 1.08; P = 0.009). As expected, a higher prescribed dose increased the risk of several late toxicity end points. Although acute bladder toxicity was associated with the presence of bladder symptoms at 5 years, the effect disappeared for all symptoms except increased urinary frequency and haematuria when a change in bladder function from baseline was calculated. Patients with any pretreatment bladder symptoms were more likely to report increased urinary frequency (hazard ratio = 2.09, 95% confidence interval 1.48, 2.95; P < 0.0005), increased urinary incontinence (hazard ratio = 4.22, 95% confidence interval 2.13, 8.35; P < 0.0005) and decreased stream (hazard ratio = 2.64, 95% confidence interval 1.62, 4.31; P < 0.0005), after treatment and before the most recent follow-up assessment. Conclusions In this study, increased acute gastrointestinal and bladder symptoms and prescribed dose were associated with increased late radiation toxicity. The presence of hypertension seemed to be protective for the development of late effects. Baseline symptoms should be taken into account when radiation toxicity is analysed.

First Report of Crown Rot on Gypsophila (Gypsophila paniculata) Caused by Fusarium proliferatum in Korea.

Gypsophilas commonly cultivated are Gypsophila elegans B. and G. paniculata L. In September of 2009 and 2010, a severe wilt symptom due to crown rot was observed on G. paniculata (cv. Bristol Fairy) in greenhouses in Yeosu, South Korea. The area of cultivation (~8 ha) in Yeosu covers 90% of production in the Jeonnam Province. Disease outbreak was 20 to 30% in affected greenhouses. Early symptoms included brown discoloration surrounding basal stems and slight wilting. Late symptoms included a sunken stem rot next to the roots, root rot, severe wilting, and dying plants. The causal fungus appeared to invade plants through the basal stem, causing a crown rot that prevented the plant from taking up water and nutrients. Crown rot occurred on young and mature plants. Ten fungal isolates were recovered from basal stems and roots of wilted plants. Microconidia were abundantly produced on potato dextrose agar (PDA), V8 juice agar (VA), carnation leaf agar (CLA), and oatmeal agar (OA). Microconidia were single celled, variable, oval-ellipsoid cylindrical, straight to curved, club-to-kidney shaped or spindle shaped on OA, more slender on VA. Macroconidia were not found on any media used. Microconidia on PDA were 5.9 to 15.1 (9.9) × 2.7 to 4.3 (3.5) μm. Germinated conidia (or false conidia) were often formed on CLA. Conidiophores as phialides were singly formed but often branched. Length of conidiophores was up to 31.1 μm on CLA. Small-sized chlamydospores were rarely found. Fusarium isolates (EML-GYP1, 2, and 3) were selected and identified. From extracted genomic DNA, the internal transcribed spacer (ITS) region including 5.8S rDNA was amplified using ITS1F (5'-CTTGGTCATTTAGAGGAAGT-3') and LR5F (5'-GCTATCCTGAGGGAAAC-3') primers. Sequence analyses by BLAST indicated that the isolates (GenBank HM560019, HM560020, and HM560021) were most similar to F. proliferatum (EF4534150) with sequence identity values of 99.3, 99.4, and 99.1%, respectively. The causal fungus was determined to be F. proliferatum based on morphological data and ITS rDNA sequences. Pathogenicity tests with the three isolates were performed on 10 plants of G. paniculata using the dipping method. Healthy roots and basal stems were soaked in a conidial suspension adjusted to ~1.2 × 106 conidia/ml (distilled water) for 15 min. Plants were potted in sterile soil, kept in a humid chamber for 72 h, and moved to a greenhouse. The experiment was carried out in duplicate and repeated two times. Similar symptoms to those observed in the greenhouses were seen 7 days after inoculation. The causal fungus was reisolated from the artificially inoculated basal stems, fulfilling Koch's postulates. Control plants whose basal stems and roots were dipped in sterile water showed no crown rot and wilt symptoms. EML-GYP2 was determined to be the most pathogenic. Ten records of disease caused by three Fusarium species (Fusarium sp., F. oxysporum, and F. udum) have been found on gypsophilas (1), but only F. oxysporum has been reported to cause wilt on G. elgans in Korea (2). To our knowledge, this is the first report of crown rot on gypsophila caused by F. proliferatum in Korea as well as the world.

Outcomes of Mesenteric Reinterventions for In-Stent Restenosis in Patients Treated for Atherosclerotic Mesenteric Artery Disease

Objective: Mesenteric artery stents (MAS) for chronic mesenteric ischemia (CMI) have been plagued by high restenosis and reinterventions rates. This study reviewed the outcomes of patients treated for mesenteric artery in-stent restenosis (MAISR) with open surgical (OR) or redo endovascular mesenteric revascularization (ER). Methods: The clinical data of 157 patients (190 MAS) treated for CMI were entered into a prospective database (1998-2010). Fifty-six patients (37%) developed MAISRs, defined by duplex ultrasound peak systolic velocity >350 cm/s or angiographic stenosis >60%. We reviewed the clinical data and outcomes of patients undergoing reinterventions for MAISR. End points were procedure-related mortality and morbidity, and late patient survival, symptom recurrence, reintervention, and patency rates. Results: There were 30 patients (19%) treated for MAISR, including 25 women and 5 men, with a mean age of 69 ± 14 years. Twenty-four patients presented with recurrent symptoms (27 chronic and 3 acute), and 6 had asymptomatic preocclusive lesions. Twenty-six patients (87%) had endovascular reintervention, including stent placement in 19 (15 uncovered and 4 covered) or percutaneous transluminal angioplasty (PTA) in 7. Four patients (13%) underwent OR, including one with acute ischemia. There was one death (3%) in a patient with acute ischemia treated with redo stenting. Seven patients (27%), all treated by ER, developed complications, including access site problems in four, and distal embolization with bowel ischemia, congestive heart failure or SMA reocclusion in one each. Symptom improvement was noted in 23 of the 24 symptomatic patients (96%). After a mean follow up of 29 ± 12 months, 11 patients developed a second restenosis, and 7 required treatment for recurrent symptoms. Rates of symptom recurrence, restenosis, and reinterventions were 0/4, 0/4, and 0/4 for covered stents, 2/7, 3/7, and 2/7 for PTA, 5/14, 8/14, and 5/14 for uncovered stents, and 1/4, 4/4, and 0/4 for OR. For all patients, freedom from recurrent symptoms, restenosis and reinterventions were 70% ± 10%, 50% ± 11% and 60% ± 11% at 2 years. For patients treated with ER, secondary patency rates were 73 ± 11 at the same interval. Conclusion: Nearly 40% of patients developed mesenteric in-stent restenosis, of which half required reintervention because of symptom recurrence or a preocclusive lesion. Mesenteric reinterventions were associated with low mortality (3%), a high complication rate (27%), and excellent symptom improvement (96%).

Depressive Symptoms and Amygdala Volume in Elderly with Cerebral Small Vessel Disease: The RUN DMC Study

Introduction. Late onset depressive symptoms (LODSs) frequently occur in elderly with cerebral small vessel disease (SVD). SVD cannot fully explain LODS; a contributing factor could be amygdala volume. We investigated the relation between amygdala volume and LODS, independent of SVD in 503 participants with symptomatic cerebral SVD. Methods. Patients underwent FLAIR and T1 scanning. Depressive symptoms were assessed with structured questionnaires; amygdala and WML were manually segmented. The relation between amygdala volume and LODS/EODS was investigated and adjusted for age, sex, intracranial volume, and SVD. Results. Patients with LODS had a significantly lower left amygdala volume than those without (P = 0.02), independent of SVD. Each decrease of total amygdala volume (by mL) was related to an increased risk of LODS (OR = 1.77; 95% CI 1.02–3.08; P = 0.04). Conclusion. Lower left amygdala volume is associated with LODS, independent of SVD. This may suggest differential mechanisms, in which individuals with a small amygdala might be vulnerable to develop LODS.

Low-level laser therapy (LLLT) acts as cAMP-elevating agent in acute respiratory distress syndrome

The aim of this work was to investigate if the low-level laser therapy (LLLT) on acute lung inflammation (ALI) induced by lipopolysaccharide (LPS) is linked to tumor necrosis factor (TNF) in alveolar macrophages (AM) from bronchoalveolar lavage fluid (BALF) of mice. LLLT has been reported to actuate positively for relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased TNF mRNA expression and dysfunction of cAMP generation observed in ALI can be influenced by LLLT. For in vivo studies, Balb/c mice (n = 5 for group) received LPS inhalation or TNF intra nasal instillation and 3h after LPS or TNF-α, leukocytes in BALF were analyzed. LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 660nm and a dose of 4.5J/cm(2). The mice were irradiated 15min after ALI induction. In vitro AM from mice were cultured for analyses of TNF mRNA expression and protein and adenosine3':5'-cyclic monophosphate (cAMP) levels. One hour after LPS, the TNF and cAMP levels in AM were measured by ELISA. RT-PCR was used to measure TNF mRNA in AM. The LLLT was inefficient in potentiating the rolipram effect in presence of a TNF synthesis inhibitor. LLLT attenuated the neutrophil influx and TNF in BALF. In AM, the laser increased the cAMP and reduced the TNF-α mRNA. LLLT increases indirectly the cAMP in AM by a TNF-dependent mechanism.

Does early surgical intervention improve left ventricular mass regression after mitral valve repair for leaflet prolapse?

Left ventricular hypertrophy is associated with adverse cardiovascular outcomes. It is unclear whether hypertrophy caused by severe chronic mitral regurgitation regresses after mitral valve repair and, if so, which factors promote reverse remodeling and influence its prognostic significance. Between March 1995 and December 2005, 2589 patients had mitral valve repair. Five hundred thirty patients (346 of whom were male) underwent isolated repair for leaflet prolapse and had echocardiographic data available from which the left ventricular mass index could be calculated. Concomitant preoperative tricuspid valve regurgitation was more than mild in 95 (18%) patients. Those with preoperative atrial fibrillation and other cardiac pathologies necessitating intracardiac repair were not included. Significant regression of left ventricular mass index occurred during the first 3 years (-28 g/m(2), P < .001) and was maintained during follow-up for more than 3 years (-26 g/m(2), P < .001). Higher preoperative left ventricular ejection fraction and greater preoperative left ventricular mass index independently predicted improved left ventricular mass index regression at 3 years. During follow-up of greater than 3 years, greater preoperative left ventricular mass index persisted in predicting improved mass regression (P < 0.001), and greater than mild preoperative tricuspid valve regurgitation was associated with less mass regression (P < .001). Late recovery of normal left ventricular ejection fraction was impaired in those with the greatest residual left ventricular mass; however, there was no difference in late symptoms or survival. Performing mitral valve repair before a decrease in left ventricular ejection fraction and the development of significant secondary tricuspid valve regurgitation is associated with a greater likelihood of significant regression of left ventricular mass, possibly predicting improved recovery of normal left ventricular function after surgical intervention. These data provide additional support for early degenerative mitral valve repair.

Long-term follow-up after catheter ablation for atrioventricular nodal reentrant tachycardia: a comparison of cryothermal and radiofrequency energy in a large series of patients

BackgroundRadiofrequency (RF) catheter ablation for atrioventricular nodal reentrant tachycardia (AVNRT) is highly successful but carries a risk for inadvertent atrioventricular block. Cryoablation (cryo) has the potential to assess the safety of a site before the energy is applied.PurposeThe aim of this study was to evaluate the long-term efficacy and safety of cryothermal ablation in a large series of patients and compare it to RF.MethodsAll consecutive routinely performed AVNRT ablations from our centre between 1999 and 2007 were retrospectively analysed.ResultsIn total, 274 patients were elegible: 150 cryoablations and 124 RF. Overall procedural success was 96% (262/274), and equal in both groups, but nine patients were crossed to another arm. Mean fluoroscopy time was longer in the group treated with RF (27 ± 22 min vs. cryo 19 ± 15 min; p = 0.002). Mean procedure time was not different (RF 138 ± 71 min vs. cryo 146 ± 60 min). A permanent pacemaker was necessary in two RF patients. The questionnaire revealed a high incidence of late arrhythmia related symptoms (48%), similar in both groups, with improved perceived quality of life. The number of redo procedures for AVNRT over 4.3 ± 2.5-years follow-up was not statistically different (11% after cryo and 5% after RF).ConclusionsOur data confirm that cryo and RF ablation with 4-mm tip catheters for AVNRT are equally effective, even after long-term follow-up.

La radiothérapie conformationnelle associée à l’hormonothérapie du cancer de prostate localisé : l’âge est-il un facteur limitant ?

No study on side effects had showed that conformal radiation therapy for prostate cancer is more harmful in patients older than 70 years to patients younger. The aim of this study was to evaluate acute and late toxicities of conformal radiotherapy, with high dose for localized prostate cancer in patients older than 70 years and compared to patients younger than 70 years. Between 1996 and 2009, 104 patients were treated with radiation therapy and hormonal therapy for localized cancer prostate. Median follow-up was 105 months (9-300). Acute (occurred at ≤ three months) and late side effects of 55 patients older than 70 years (median age: 75 [71-92]) were graded according to the CTCAE 3.0 criteria and compared to the younger population. Median dose to the prostate was 75.6 Gy (67-80) in both groups. There were no significant differences in acute and late side effects between age groups. For patients above 70 years, the incidence of grade II or higher acute and late side effects were respectively 27 and 22% for urologic symptoms and 13 and 16% for rectal symptoms. The frequency of grade III late symptoms was low and ranged between 0 and 6% for the evaluated symptoms, irrespective of age group. Older patients had a better biochemical recurrence-free survival than younger patients (86 versus 77% at four years, P=ns). High dose 3D conformal radiotherapy for localized prostate cancer was well tolerated in patients older than 70 years. Age is not a limiting factor for conformal radiation therapy and hormonotherapy for older patients.

Low-Level Laser Therapy Associated toN-Acetylcysteine Lowers Macrophage Inflammatory Protein-2 (MIP-2) mRNA Expression and Generation of Intracellular Reactive Oxygen Species in Alveolar Macrophages

The aim of this work was to investigate the low-level laser therapy (LLLT) effect on alveolar macrophages (AM) activated by oxidative stress and lipopolysaccharide (LPS). LLLT has been reported to actuate positively relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased MIP-2 mRNA expression and intracellular reactive oxygen species (ROS) generation observed in acute lung inflammation (ALI) can be influenced by LLLT. Rat AM cell line (AMJ2-C11) was cultured with LPS or H(2)O(2) and laser irradiated. MIP-2 mRNA and ROS production in the AM were evaluated by Real Time-PCR and the 2',7'-dichlorofluorescin diacetate (DCFH-DA) respectively. The NF-κB protein in the AM was measured by the enzyme linked immunoassay method. To investigate the antioxidant effect of laser, the AM were prebathed with N-acetylcysteine (NAC) and then irradiated with laser. LLLT was also studied in the presence of an inhibitor of NF-κB (BMS 205820). In addition, the effect of LLLT on NF-κB protein was investigated. LLLT attenuated the MIP-2 mRNA expression and intracellular ROS generation after LPS or H(2)O(2). When the AM were pretreated with NAC, the laser effect was potentiated. BMS 205820 suppresses the effect of LLLT on MIP-2 mRNA expression and ROS generation, stimulated by LPS or H(2)O(2). On NF-κB transcription factor, both the LLLT and NAC reduced this protein in the AM exposed to LPS or H(2)O(2). The synergistic effect between LLLT and NAC on the reduction the NF-κB was also evidenced. Results indicate that there is a synergistic action of LLLT with NAC on MIP-2 mRNA expression from LPS- or H(2)O(2)-stimulated AM, and that both ROS intracellular generation and NF-kB signaling seem to be involved.

Late‐life depression and the death of Queen Victoria

The objective of this study was to evaluate relationships between the death of Queen Victoria and the depressive episode she experienced during the last year of her life. The last volume of Queen Victoria's personal Journal was reviewed from a geriatrician's perspective, tracing the onset and course of depressive symptoms from entries beginning on 17 August 1900 and ending on 13 January 1901, 9 days before her death. The Queen's own words are supplemented with observations from contemporaneous secondary sources. The antecedents of Queen Victoria's late-life depression, including multiple losses, disabilities, and chronic pain, taken together with the presentation of vegetative, affective, and late cognitive symptoms, suggested the presence of a distinctively geriatric major depressive disorder. The absence of any other medical condition to explain the clinical picture seemed probable but not certain. Although historians and biographers have long been aware of Queen Victoria's final depression, the emphasis has mostly been on her earlier and prolonged mourning for her husband Prince Albert. Re-examined now, the Queen's Journal suggests that a severe late-life depressive episode occurring approximately in her last 5 months contributed meaningfully to her death.

878 Tlr2 and Tlr4 Polymorphisms in Kawasaki Disease

Kawasaki disease (KD) is a febrile acute systemic vasculitis in childhood, primarily affecting coronary arteries. Different causes are discussed including infectious agents, cofactors, and genetic predisposition. We tested the hypothesis that polymorphisms of TL-2 and TLR4, key mediators of the innate immune system influence coronary artery involvement in KD patients. 15 patients with KD in childhood were revaluated in young adulthood including the analysis of TLR2 and TLR4 regarding expression pattern, stimulation effects and polymorphisms (SNP) compared to an ageand sex related control group.Heterozygote Genotype for TLR2 SNP was found in two KD patients, one also positive for TLR4 SNP, both had no acute or late cardiac symptoms. The expression pattern on the surface of monocytes showed no difference between the KD and control group, nor in the KD patients with or without cardiac pathology. Stimulation via TLR2 and TLR4 also showed no significant influence on p38 and ERK phosphorylation and cytokine induction.We can conclude that there is no disturbance in the innate immune system of previous patients with KD, but a modest positive effect of TLR2 and TLR4 SNPs on coronary involvement can be discussed.