Histamine, mast cell tryptase and post-exercise hypotension in healthy and collapsed marathon runners.

PURPOSE: Heat stress exacerbates post-exercise hypotension (PEH) and cardiovascular disturbances from elevated body temperature may contribute to exertion-related incapacity. Mast cell degranulation and muscle mass are possible modifiers, though these hypotheses lack practical evidence. This study had three aims: (1) to characterise pre-post-responses in histamine and mast cell tryptase (MCT), (2) to investigate relationships between whole body muscle mass (WBMM) and changes in blood pressure post-marathon, (3) to identify any differences in incapacitated runners. METHODS: 24 recreational runners were recruited and successfully completed the 2019 Brighton Marathon (COMPLETION). WBMM was measured at baseline. A further eight participants were recruited from incapacitated runners (COLLAPSE). Histamine, MCT, blood pressure, heart rate, body temperature and echocardiographic measures were taken before and after exercise (COMPLETION) and upon incapacitation (COLLAPSE). RESULTS: In completion, MCT increased by nearly 50% from baseline (p = 0.0049), whereas histamine and body temperature did not vary (p > 0.946). Systolic (SBP), diastolic (DBP) and mean (MAP) arterial blood pressures and systemic vascular resistance (SVR) declined (p < 0.019). WBMM negatively correlated with Δ SBP (r = - 0.43, p = 0.046). For collapse versus completion, there were significant elevations in MCT (1.77 ± 0.25 µg/L vs 1.18 ± 0.43 µg/L, p = 0.001) and body temperature (39.8 ± 1.3 °C vs 36.2 ± 0.8 °C, p < 0.0001) with a non-significant rise in histamine (9.6 ± 17.9 µg/L vs 13.7 ± 33.9 µg/L, p = 0.107) and significantly lower MAP, DBP and SVR (p < 0.033). CONCLUSION: These data support the hypothesis that mast cell degranulation is a vasodilatory mechanism underlying PEH and exercise associated collapse. The magnitude of PEH is inversely proportional to the muscle mass and enhanced by concomitant body heating.

Developments in understanding and applying prebiotics in research and practice-an ISAPP conference paper.

AIMS: The concept of using specific dietary components to selectively modulate the gut microbiota to confer a health benefit, defined as prebiotics, originated in 1995. In 2018, a group of scientists met at the International Scientific Association for Probiotics and Prebiotics annual meeting in Singapore to discuss advances in the prebiotic field, focussing on issues affecting functionality, research methodology and geographical differences. METHODS AND RESULTS: The discussion ranged from examining scientific literature supporting the efficacy of established prebiotics, to the prospects for establishing health benefits associated with novel compounds, isolated from different sources. CONCLUSIONS: While many promising candidate prebiotics from across the globe have been highlighted in preliminary research, there are a limited number with both demonstrated mechanism of action and defined health benefits as required to meet the prebiotic definition. Prebiotics are part of a food industry with increasing market sales, yet there are great disparities in regulations in different countries. Identification and commercialization of new prebiotics with unique health benefits means that regulation must improve and remain up-to-date so as not to risk stifling research with potential health benefits for humans and other animals. SIGNIFICANCE AND IMPACT OF STUDY: This summary of the workshop discussions indicates potential avenues for expanding the range of prebiotic substrates, delivery methods to enhance health benefits for the end consumer and guidance to better elucidate their activities in human studies.

Post marathon cardiac troponin T is associated with relative exercise intensity.

OBJECTIVES: This study aimed to investigate whether measures of cardiopulmonary fitness and relative exercise intensity were associated with high sensitivity cardiac troponin T (cTnT) rise after a road marathon. METHODS: Fifty-two marathon runners (age 39±11 years, body mass 76.2±12.9kg, height 1.74±0.09m) attended the laboratory between 2 and 3 weeks prior to attempting the Brighton Marathon, UK. Running economy at 10kmh-1 (RE10) and race pace (RERP), ventilatory threshold (VT) and VO2max tests were completed. CTnT was measured within 48h prior to the marathon and within 10min of completing the marathon, using a high sensitivity assay. Heart rates (HR) were recorded throughout the marathon. RESULTS: Runners demonstrated a significant increase in cTnT over the marathon (pre-race 5.60±3.27ngL-1, post-race 74.52±30.39ngL-1, p<0.001). Markers of endurance performance such as running economy (10kmh-1 223±18mlkg-1km-1; race pace 225±22mlkg-1km-1), VT (38.5±6.4mlkg-1min-1) and V˙O2max (50.9±7.7mlkg-1min-1) were not associated with post-race cTnT. Runners exercise intensity correlated with post-race cTnT (mean HR %VT 104±5%, r=0.50; peak HR %VT 118±8%, r=0.68; peak HR %V˙O2max 96±6, r=0.60, p<0.05) and was different between the low, medium and high cTnT groups (p<0.05). CONCLUSIONS: CTnT increases above reference limits during a marathon. Magnitude of cTnT rise is related to exercise intensity relative to ventilatory threshold and V˙O2max, but not individuals' absolute cardiopulmonary fitness, training state or running history.

Effects of lipid sources in the diet of laying hens on the fatty acid profiles of egg yolks.

The effects of different dietary lipids on the fatty acid profiles of eggs produced by 20- and 54-wk-old Dekalb laying hens were investigated. The 4 treatments were based on the lipid source added to the diet: soybean oil, sunflower oil, linseed oil, or control (no added oil). The experimental design was a simple random-sample design using a 4 × 2 factorial arrangement (4 treatments and 2 ages). The fatty acid composition of the yolks of eggs produced by the laying hens was analyzed. The fatty acid profiles found in the egg yolks were the same as those provided in each diet. Eggs laid by hens fed the diet containing soybean oil had a large amount of n-6 polyunsaturated fatty acids (PUFA), whereas eggs laid by hens fed the diet containing linseed oil had the highest percentage of n-3 PUFA. A decrease in PUFA deposition in egg yolks was observed as the laying hens got older. Eggs of hens fed the diet containing linseed oil presented an n-6:n-3 ratio of 2.01 in younger chickens and 2.17 in older ones. The trans fat percentages found in the egg yolks of all treatments were very low. It was concluded that the quantity of fatty acids present in the egg yolk may be altered according to the source of lipids in the diets; the addition of linseed oil to the ration of laying hens resulted in the production of n-3-enriched eggs and excellent n-6:n-3 ratios, and the egg yolks had insignificant amounts of trans fat, irrespective of the different lipid sources added to the diets or the age of the chickens.

[Importance of physical activity for prevention of chronic diseases]. / L'importanza dell'attività fisica nella prevenzione delle malattie cronico degenerative.

A lot of epidemiological studies have shown that physical activity can prevent the development of chronic diseases such as obesity, diabetes, osteoporosis, cardiovascular diseases and cancer Physical activity can be classified by rate of energy expenditure: light intensity 1-3 METs, moderate 3-6 MET's, vigorous 6-9 MET's, very vigorous >9 MET's. Although it is evident that an active lifestyle has many health benefits and sedentary habits are associated with an increased risk of chronic diseases, the debate still continues as to how much, what type, how often, at what intensity physical activity should be performed to have a positive effect on the health. Reduction of cardiovascular risk is observed already with a moderate intensity physical activity (3-6METs); whilst to improve physical fitness training must be more vigorous (6-9 METs). In conclusion good goals are achieved when moderate levels of physical activity are performed on a regular basis (at least 3- 5 days a week for 30 minutes). But to reach also countable results on body weight control the frequency should be 5-7 days a week for 60 minutes.

First administration to humans of a monoclonal antibody cocktail against rabies virus: safety, tolerability, and neutralizing activity.

Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies. The studies included healthy adult subjects in the USA and India and involved two parts. First, subjects received a single intramuscular dose of CL184 or placebo in a double blind, randomized, dose-escalation trial. Second, open-label CL184 (20IU/kg) was co-administered with rabies vaccine. Safety was the primary objective and rabies virus neutralizing activity (RVNA) was investigated as efficacy parameter. Pain at the CL184 injection site was reported by less than 40% of subjects; no fever or local induration, redness or swelling was observed. RVNA was detectable from day 1 to day 21 after a single dose of CL184 20 or 40IU/kg. All subjects had adequate (>0.5IU/mL) RVNA levels from day 14 onwards when combined with rabies vaccine. CL184 appears promising as an alternative to RIG in PEP.

Telecardiogram: still of matter in the modern cardiac imaging era?

The modern cardiovascular imaging era has seen the introduction in clinical practice of highly innovative and performing diagnostic features. The negative side of this outstanding evolution risks to be an under-assessment of well-established classical diagnostic techniques. Thereby, to support the actual relevance of a properly executed chest X-ray, this article describes two paradigmatic cases of exceptional cardiac abnormalities, in which X-rays played a key diagnostic role.

[Pendrin: physiology, molecular biology and clinical importance]. / La pendrina: fisiologia, biologia molecolare ed importanza clinica.

Pendrin, first identified in 1997, belongs to a superfamily of anion transporters localized in the thyroid gland, inner ear and kidney. Immunohistochemical studies have shown that pendrin is expressed at the apical surface of follicular thyroid cells, where it acts as a Cl-/I- exchanger regulating the chloride transport from the cytoplasm to the colloid space. In the inner ear, pendrin has been found in the stria vascularis of the cochlea and in the endolymphatic duct and sac, where it functions as a Cl- /HCO-3 exchanger. Finally, pendrin is expressed in the kidney, where it is localized in the apical membrane of type-B intercalated cells and non-A, non-B intercalated cells of the cortical collecting ducts and connecting tubules, where it again acts as a Cl /HCO-3 exchanger regulating the acid-base status and chloride homeostasis. Pendrin is encoded by the PDS gene, which is mapped on chromosome 7 (7q22-31.1). Mutations of PDS lead to the Pendred syndrome, a genetic disorder transmitted as an autosomal recessive trait characterized by sensorineural deafness and goiter. It is reasonable to hypothesize that patients affected by Pendred's syndrome may have disturbances of renal function, especially in the regulation of electrolytes and acid-base balance in stress conditions.

Coronary stenting and abciximab in primary angioplasty for ST-segment-elevation myocardial infarction.

Advances in anti-platelet therapy and improvement of stent deployment techniques have improved the safety and efficacy of stenting in the setting of ST-segment-elevation myocardial infarction (STEMI). However, in randomized trials, routine coronary stenting does not reduce mortality and re-infarction, compared to balloon angioplasty. Further, the benefits in target vessel revascularization seem to be reduced when applied to unselected patients with STEMI. Direct stenting represents an attractive strategy with potential benefits in terms of myocardial perfusion. Future large randomized trials are needed to evaluate whether this strategy has a significant impact on outcome, and to provide a cost-benefit analysis of the unrestricted use of drug-eluting stents in this high-risk subset of patients. The additional use of abciximab reduces mortality in primary angioplasty. Since the feasibility of long-distance transportation has been shown in several randomized trials, early pharmacological pre-treatment may confer further advantages by early recanalization and shorter ischaemic time, particularly in high-risk patients. Further randomized trials are needed to clarify the potential benefits from early abciximab administration and the potential role of small molecules in primary angioplasty for STEMI.

[Transient erythroblastopenia in children: assessment of a hospital caseload]. / Eritroblastopenia transitoria del bambino: valutazione di una casistica ospedaliera.

Transient erythroblastopenia of childhood (TEC) is an acquired, self-limiting, uncommon disease, characterized by the temporary arrest of red cell production, resulting in moderate to several anemia. We retrospectively evaluated four cases of TEC, identified during an 8-year period of time in our Department of Pediatrics, including one patient, who developed TEC during the course of Kawasaki's syndrome. Clinical and hematological presentations of patients were analyzed and the most recent data of literature were reviewed. In conclusion, we suggest that a better knowledge of this rare and unique hematologic disorder of childhood may help make a correct diagnosis, avoiding unnecessary laboratory tests (e.g. bone marrow aspirate) and inappropriate therapeutic modalities.

The Parkinson's disease symptom inventory (PDSI): a comprehensive and sensitive instrument to measure disease symptoms and treatment side-effects.

Parkinson's disease (PD) is associated with an array of signs and symptoms and motor fluctuations. In addition, treatments such as levodopa and dopamine agonists are associated with side-effects that impact the same health domains as disease symptomatology. To comprehensively and sensitively assess drug therapies in respect of disease symptoms and side-effects, we designed the Parkinson's disease symptom inventory (PDSI). The PDSI consists of 51 symptoms items identified through expert opinion, patient interviews, and the medical literature. Items represent a detailed array of motor, postural, muscular, gastro-intestinal, emotional, and cognitive domains. Subjects are asked to report the frequency with which each symptom is experienced, as well as the associated subjective distress. After initial elimination of 8 items that did not meet retention criteria, psychometric analysis showed excellent internal consistency (alpha=0.92-0.95) and acceptable reproducibility (ICC=0.72-0.79) of items. Comparison of results with the Unified Parkinson's disease rating scale (UPDRS) and the Parkinson's impact scale (PIMS) revealed correlation with the PDSI, with Pearson's r values of roughly 0.5 and 0.7, respectively. The PDSI demonstrated power to discriminate mean scores of patients comprising the highest and lowest tertiles of the UPDRS and PIMS instruments. In summary, the PDSI demonstrated good psychometric performance characteristics, and may yield valuable data regarding the comparative effectiveness of PD therapies.

Multicenter study of Abbott AxSYM Digoxin II assay and comparison with 6 methods for susceptibility to digoxin-like immunoreactive factors.

Performance characteristics of the Abbott nonpretreatment AxSYM Digoxin II assay were evaluated for quantification of digoxin at four independent sites. Correlation of digoxin measurements with the Abbott pretreatment AxSYM, Baxter Stratus II, Abbott TDx/ TDxFLx II, Abbott IMx, Emit 2000, and Beckman Synchron CX digoxin assays showed acceptable agreement, as indicated by: slope values > 0.84, r > 0.90, y-intercepts for all comparisons at or below the assay detection limit, and Sy/x ranging between 7.5% and 15.4% of the average digoxin value. Susceptibility to interference from digoxin-like immunoreactive factors (DLIFs) was examined in 233 samples from renal patients, liver disease patients, cord blood, and third-trimester pregnancies; the AxSYM Digoxin II assay demonstrated the least DLIFs interference. DLIF susceptibility for four of the methods was significantly greater (P < 0.05) than in the AxSYM Digoxin II assay; susceptibilities of the Stratus II and Emit 2000 methods were similar to the AxSYM Digoxin II assay.

Short- and long-term changes in striatal neurons and astroglia after transient forebrain ischemia in rats.

BACKGROUND AND PURPOSE: The striatum is one of the regions most sensitive to transient forebrain ischemia. After 30-minute ischemia, areas of massive neuronal degeneration are clearly detectable a few hours after the insult and attain their maximal extension 24 hours after the insult. However, for most cellular and neurochemical parameters it is not known whether some recovery occurs at later times. We examined certain cell populations in the caudate putamen at different times after transient ischemia. METHODS: Adult male Sprague-Dawley rats were subjected to 30-minute forebrain ischemia (four-vessel occlusion model). Six experimental groups were considered: control animals and ischemic animals killed 4 hours, 1 day, 7 days, 40 days, and 8 months after reperfusion. Three striatal cell populations were examined by means of immunocytochemistry coupled to computer-assisted image analysis: vulnerable medium spiny neurons, resistant aspiny neurons, and reactive astrocytes, labeled for their content of dopamine- and cAMP-regulated phosphoprotein mr32 (DARPP-32), somatostatin and neuropeptide Y, and glial fibrillary acidic protein, respectively. RESULTS: (1) The area containing DARPP-32 immunoreactive neurons was markedly decreased (15% to 20% of control caudate putamen area) at 1 day after reperfusion and partially recovered at the following times (40% to 50% at 7 days and 50% to 60% at 40 days and 8 months after reperfusion). (2) The appearance of reactive astrocytes was precocious (4 hours to 1 day after ischemia) in the medial caudate putamen, the region in which DARPP-32 recovered within 40 days after ischemia, and late (7 to 40 days after ischemia) in the lateral caudate putamen, where no DARPP-32 recovery was detected. (3) Neuropeptide Y/somatostatin-containing neurons resisted the ischemic insult and could be detected in areas devoid of DARPP-32 immunoreactive neurons as long as 8 months after reperfusion. CONCLUSIONS: The present results show a marked recovery of DARPP-32-positive neurons within 40 days after 30-minute forebrain ischemia in the medial, but not the lateral, caudate putamen. Medial caudate putamen also contains a high density of reactive astrocytes on the first day after ischemia, suggesting that astrocytic support has an important role in the spontaneous recovery of ischemic neurons.

Cabergoline in the treatment of early Parkinson's disease: results of the first year of treatment in a double-blind comparison of cabergoline and levodopa. The PKDS009 Collaborative Study Group.

Cabergoline is a potent D2 receptor agonist with a half-life of 65 hours that may provide continuous dopaminergic stimulation administered once daily. In this study, we randomized de novo Parkinson's disease (PD) patients to treatment with increasing doses of cabergoline (0.25 to 4 mg/d) or levodopa (100 to 600 mg/d) up to the optimal or maximum tolerated dose. Decreases of > 30% in motor disability (Unified Parkinson's Disease Rating Scale Factor III) versus baseline were considered indicative of clinical improvement. If 30% improvement was not achieved, levodopa/ carbidopa could be added on an open basis. Of the 208 patients entered in the cabergoline group, 175 remained in the study for 1 year at a mean dose of 2.8 mg/d; in the levodopa group, 176 of the 205 patients entered were still on study after 1 year at a mean dose of 468 mg/d. The proportion of patients requiring additional levodopa/carbidopa increased in the cabergoline group from 18% at 6 months to 38% at 1 year versus 10% (p = 0.05) at 6 months and 18% (p < 0.01) at 1 year in the levodopa group. The proportion of patients showing clinical improvement did not differ significantly between the two groups, or between the subgroups on monotherapy, at any endpoint. Irrespective of levodopa/carbidopa addition, 81% of patients in the cabergoline group and 87% of patients in the levodopa group were clinically improved at 1 year (p = 0.189); the corresponding figures for the subgroup on monotherapy were 79% in the cabergoline-treated patients and 86% in the levodopa-treated patients (p = 0.199). The mean difference versus baseline in Unified Parkinson's Disease Rating Scale Factor III scores in patients who remained on monotherapy up to 1 year was 12.6 (95% confidence interval [CI]: 10.8, 14.3) in the cabergoline group and 16.4 (95% CI: 14.8, 18.0) in the levodopa group. Adverse events occurred in 76% of patients on cabergoline and in 66% of patients on levodopa. The severity profile for reported events was similar for the two agents. The results of this study indicate that cabergoline treatment for up to 1 year is only marginally less effective than levodopa in the proportion of patients who can be treated in monotherapy. More than 60% of de novo PD patients could be managed on cabergoline alone up to 1 year. In the patients in whom levodopa/carbidopa was needed, the combination therapy provided efficacy similar to that obtained with levodopa alone, with a relevant sparing of levodopa.

Emergency medical services in mass gatherings: the experience of the Formula 1 Grand Prix 'San Marino' in Imola.

Mass gatherings are special situations for which mass medical care must be preplanned. Acute emergencies occur at public gatherings and medical coverage on site has proven benefit. Responsibility of general plan, management of specific problems, transport planning, communications system, guidelines and protocols, special situations management, ancillary supports, sources of extra help for unforeseen needs are the most important items to consider. In mass gatherings the whole emergency medical service (EMS) planning and management has to depend on the emergency department direction, with its authority on all aspects of patient care in the EMS system. This report concerns the planning of EMS and of medical care in a situation at risk for mass casualties at the Formula I Grand Prix-Championship Racing 'San Marino' of Imola.

Cryoprostatectomy consistently elevates serum creatine kinase-MB isoenzyme.

STUDY OBJECTIVE: To measure serum CK-MB, a market of myocardial infarction (MI), in elderly men before and after cryoprostatectomy. DESIGN: Serum CK-MB was measured on each patient before and after cryoprostatectomy. Each patient's preoperative result was used as control measurement for comparison with measurements made after cryoprostatectomy. SETTING: Inpatient operating room and postanesthetic recovery unit of a university-affiliated general hospital. PATIENTS: 38 male patients, mean (SEM) age 69.1 +/- 1.4 years, undergoing cryoprostatectomy. INTERVENTIONS: All patients had a 12-lead ECG prior to surgery, in the recovery room, and 24 hours after surgery. Serum CK-MB was measured prior to induction of anesthesia, on arrival in the recovery room, and at 8 and 24 hours after surgery. Lactate dehydrogenase (LDH) and isoenzymes also were measured in 10 patients before and after cryoprostatectomy. MEASUREMENTS AND MAIN RESULTS: All patients underwent uneventful cryoprostatectomy. No patients had new ECG changes after surgery. All patients had normal serum CK and CK-MB concentrations before surgery. Serum CK and CK-MB were significantly elevated after cryoprostatectomy (p < 0.001). Enzyme values were greatest 8 hours after surgery: total CK mean 1453 +/- 145 U/L (range 199 to 3,356 U/L); CK-MB mean 52 +/- 3 ng/ml (range 12 to 114 ng/ml) or 5.0 +/- 0.5% of total CK (range 1.6% to 12.4%). All patients had significant elevations of LDH after cryoprostatectomy but did not show an increase in the ratio of LDH1 to LDH2 isoenzymes. Finally, unlike patients with an acute MI, the activity of CK-MB isoenzyme when measured by gel electrophoresis was two to three times greater (mean, 2.6 +/- 0.7) than the concentration measured with the monoclonal antibody assay in patients after cryoprostatectomy. CONCLUSION: Serum CK-MB is an unreliable test to diagnose an MI in patients who have undergone cryoprostatectomy.

Cabergoline improves motor disability without modifying L-dopa plasma levels in fluctuating Parkinson's disease patients.

Studies on the influence of some dopamine agonists, particularly bromocriptine, on the pharmacokinetics of L-dopa have furnished contrasting results. Thus, any possible pharmacokinetic interaction should be taken into consideration when adding a new dopamine agonist to L-dopa treatment. In 12 Parkinson's disease (PD) patients with motor fluctuations, cabergoline was added in an 8-week study to their usual L-dopa/carbidopa therapy. Cabergoline was administered once a day at increasing doses of 0.5, 1, 2, and 3mg/day for a period of one week per dose, and 4mg/day for three weeks. Motor performance was assessed weekly evaluating the motor examination of the Unified Parkinson's Disease Rating Scale (UPDRS) and the patients' diaries of daily on-off time. Blood levels of both L-dopa and 3-O-methyldopa (3-OMD) were assayed by HPLC in two different days, over an 8-hour period, before initiating cabergoline and at the end of the study. The results of this study confirm that cabergoline is effective in the management of PD motor fluctuations without modifying L-dopa and 3-OMD pharmacokinetics.