Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients.

BACKGROUND: Bevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab continuation beyond initial progression among recurrent glioblastoma patients as it is a common, yet unsupported practice in some countries. METHODS: We analysed outcome among all patients (n=99) who received subsequent therapy after progression on one of five consecutive, single-arm, phase II clinical trials evaluating bevacizumab regimens for recurrent glioblastoma. Of note, the five trials contained similar eligibility, treatment and assessment criteria, and achieved comparable outcome. RESULTS: The median overall survival (OS) and OS at 6 months for patients who continued bevacizumab therapy (n=55) were 5.9 months (95% confidence interval (CI): 4.4, 7.6) and 49.2% (95% CI: 35.2, 61.8), compared with 4.0 months (95% CI: 2.1, 5.4) and 29.5% (95% CI: 17.0, 43.2) for patients treated with a non-bevacizumab regimen (n=44; P=0.014). Bevacizumab continuation was an independent predictor of improved OS (hazard ratio=0.64; P=0.04). CONCLUSION: The results of our retrospective pooled analysis suggest that bevacizumab continuation beyond initial progression modestly improves survival compared with available non-bevacizumab therapy for recurrent glioblastoma patients require evaluation in an appropriately randomised, prospective trial.

Evaluation of enrichment media for improved PCR-based detection of V. cholerae and V. vulnificus from estuarine water and plankton.

AIMS: Pathogenic Vibrio spp., including V. cholerae and V. vulnificus, are commonly found along the estuaries of the south-east United States; however, it is often difficult to recover these species directly from environmental samples. Pre-enrichment assays are commonly used to improve the detection of pathogenic vibrios from environmental sources. Here, we evaluated a novel enrichment procedure using freshly collected and autoclaved natural estuarine water amended with 1% peptone (designated as estuarine peptone water, EPW) and compared it to traditional alkaline peptone water (APW) for detection by PCR of V. cholerae and V. vulnificus. METHODS AND RESULTS: Of the 50 samples collected in total, V. cholerae DNA was detected in APW 10% of the time and in EPW 40% of the time. Likewise, the cholera toxin gene (ctxA) was detected in 4 vs 18% of the samples using APW and EPW, respectively. Conversely, APW showed improved recovery for V. vulnificus relative to EPW with respective detection frequencies of 46 and 20%. Results showed similar patterns across different sample types (water and plankton). CONCLUSIONS: While enrichment in traditional APW was adequate for the recovery of Vibrio vulnificius, use of sterile estuarine water amended with peptone significantly improved the detection of V. cholerae and the virulence gene ctxA from estuarine sources.

[Pancytopenia and hemolysis--diagnosis, differential diagnosis and therapy of pernicious anemia]. / Panzytopenie und Hämolyse--Diagnose, Differenzialdiagnose und Therapie der perniziösen Anämie.

Pernicious anemia and Vitamin B12 deficiency have a wide range of symptoms and are a common finding in the elderly. A 73 year old female is admitted to the hospital because of dyspnea, fatigue and loss of appetite and weight. While previous medical history and physical examination are inconspicuous, laboratory findings show severe pancytopenia with macrocytosis, low reticulocyte count and marked signs of hemolysis. A very low serum level of vitamin B12 and chronic atrophic type A gastritis upon endoscopy with presence of parietal cell antibodies in the serum lead to the diagnosis of pernicious anemia. Complete restitution is achieved by parenteral vitamin B12 substitution. Nowadays, severe pernicious anemia is only rarely seen. The differential diagnosis of pancytopenia (with macrocytic anemia) combined with hemolysis and the essential hints to the diagnosis of pernicious anemia are discussed, and thereby practical aspects including therapy actualized.

Regional left ventricular function during transient coronary occlusion: relation with coronary collateral flow.

OBJECTIVE: To test the hypothesis that regional left ventricular (LV) function during balloon angioplasty is related to the amount of collateral flow to the ischaemic region. DESIGN: Prospective study. SETTING: Tertiary referral centre. METHODS: In 50 patients with coronary artery disease and without myocardial infarction, regional systolic and diastolic LV function was determined using tissue Doppler ultrasound (TD) before and at the end of a 60 second occlusion of a stenotic lesion undergoing percutaneous transluminal coronary angioplasty (PTCA) through a pressure guidewire. The study population was subdivided into a group with collaterals insufficient (n = 33) and one with collaterals sufficient (n = 17) to prevent ECG ST shifts suggestive of myocardial ischaemia during PTCA. Pulsed TD was performed from an apical window in the myocardial region supplied by the vessel being treated by PTCA. Pressure derived collateral flow index (CFI) was determined by simultaneous measurement of mean aortic (P(ao)) and distal intracoronary occlusive pressures (P(occl)), where CFI = (P(occl) - 8)/(P(ao) - 8). RESULTS: At 60 seconds of occlusion, several parameters of systolic and diastolic TD derived LV long axis function were significantly different between the groups. Also, there was a significant correlation between regional systolic excursion velocity, early diastolic excursion velocity, regional isovolumetric relaxation time, and CFI. CONCLUSION: During brief coronary artery occlusions, regional systolic and diastolic LV function is directly related to the amount of collateral flow to this territory.

Doppler tissue imaging for assessing left ventricular diastolic dysfunction in heart transplant rejection.

OBJECTIVE: To test the hypothesis that diastolic mitral annular motion velocity, as determined by Doppler tissue imaging and left ventricular diastolic flow propagation velocity, is related to the histological degree of heart transplant rejection according to the International Society of Heart and Lung Transplantation (ISHLT). METHODS: In 41 heart transplant recipients undergoing 151 myocardial biopsies, the following Doppler echocardiographic measurements were performed within one hour of biopsy: transmitral and pulmonary vein flow indices; mitral annular motion velocity indices; left ventricular diastolic flow propagation velocity. RESULTS: Late diastolic mitral annular motion velocity (A(DTI)) and mitral annular systolic contraction velocity (SC(DTI)) were higher in patients with ISHLT < IIIA than in those with ISHLT >/= IIIA (A(DTI), 8.8 cm/s v 7.7 cm/s (p = 0.03); SC(DTI), 19.3 cm/s v 9.3 cm/s (p < 0.05)). Sensitivity and specificity of A(DTI) < 8.7 cm/s (the best cut off value) in predicting significant heart transplant rejection were 82% and 53%, respectively. Early diastolic mitral annular motion velocity (E(DTI)) and flow propagation velocity were not related to the histological degree of heart transplant rejection. CONCLUSIONS: Doppler tissue imaging of the mitral annulus is useful in diagnosing heart transplant rejection because a high late diastolic mitral annular motion velocity can reliably exclude severe rejection. However, a reduced late diastolic mitral annular motion velocity cannot predict severe rejection reliably because it is not specific enough.

Assessment and impact of microbial fecal pollution and human enteric pathogens in a coastal community.

The goals of this study were to assess watersheds impacted by high densities of OSDS (onsite sewage disposal systems) for evidence of fecal contamination and evaluate the occurrence of human pathogens in coastal waters off west Florida. Eleven stations (representing six watersheds) were intensively sampled for microbial indicators of fecal pollution (fecal coliform bacteria, enterococci, Clostridium perfringens and coliphage) and the human enteric pathogens, Cryptosporidium, Giardia, and enteroviruses during the summer rainy season (May-September 1996). Levels of all indicators ranged between < 5 and > 4000 CFU/100 ml. Cryptosporidium and Giardia were detected infrequently (6.8% and 2.3% of samples tested positive, respectively). Conversely, infectious enteroviruses were detected at low levels in 5 of the 6 watersheds sampled. Using cluster analysis, sites were grouped into two categories, high and low risks, based on combined levels of indicators. These results suggest that stations of highest pollution risk were located within areas of high OSDS densities. Furthermore, data indicate a subsurface transport of contaminated water to surface waters. The high prevalence of enteroviruses throughout the study area suggests a chronic pollution problem and potential risk to recreational swimmers in and around Sarasota Bay.

Climate variability and change in the United States: potential impacts on water- and foodborne diseases caused by microbiologic agents.

Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments.

Relation between directly detected patent foramen ovale and ischemic brain lesions in sport divers.

BACKGROUND: In divers, the significance of a patent foramen ovale and its potential relation to paradoxical gas emboli remain uncertain. OBJECTIVE: To assess the prevalence of symptoms of decompression illness and ischemic brain lesions in divers with regard to the presence of a patent foramen ovale. DESIGN: Retrospective cohort study. SETTING: University hospital and three diving clubs in Switzerland. PARTICIPANTS: 52 sport divers and 52 nondiving controls. MEASUREMENTS: Prevalence of self-reported decompression events, patent foramen ovale on contrast transesophageal echocardiography, and ischemic brain lesions on magnetic resonance imaging. RESULTS: The risk for decompression illness events was 4.5-fold greater in divers with patent foramen ovale than in divers without patent foramen ovale (risk ratio, 4.5 [95% CI, 1.2 to 18.0]; P = 0.03). Among divers, 1.23 +/- 2.0 and 0.64 +/- 1.22 ischemic brain lesions per person (mean +/- SD) were detected in those with and those without patent foramen ovale, respectively. Among controls, 0.22 +/- 0.44 and 0.12 +/- 0.63 lesion per person were detected (P < 0.001 for all groups). CONCLUSIONS: Regardless of whether a diver has a patent foramen ovale, diving is associated with ischemic brain lesions.

Gender differences in coronary artery size per 100 g of left ventricular mass in a population without cardiac disease.

OBJECTIVES: To determine whether there is a gender difference in coronary artery size normalised for left ventricular (LV) mass. BACKGROUND: Small coronary artery caliber may play a role as a risk factor for coronary artery disease in women. However, the existence of a gender difference in coronary artery size is controversial. Furthermore, coronary artery size ought to be normalised for LV mass, since there is a theoretical relation of coronary artery size to LV mass according to the law of minimum viscous energy loss for the transport of blood in the coronary circulation. METHODS: In 200 individuals (100 women) without cardiac disease and with normal Doppler echocardiography, left main (LCA) and right coronary artery (RCA) size were determined using transoesophageal echocardiography. LV mass was assessed by transgastric M-mode echocardiography. RESULTS: Age (44 +/- 15 years in women; 41 +/- 16 years in men), the presence of non-cardiac diseases, cardiovascular risk factors and medication were similar in women and men. LV mass in women was lower than in men (148 +/- 36 g, 189 +/- 45 g; p < 0.0001). LCA and RCA cross-sectional areas in women were smaller than those in men (LCA: 10 +/- 3 and 16 +/- 5 mm2, p < 0.0001; RCA: 4 +/- 2 and 7 +/- 3 mm2, p < 0.0001, respectively). LCA and RCA cross-sectional areas of women were smaller even after normalisation for LV mass (LCA: 7 +/- 3 and 9 +/- 3 mm2/100 g LV mass, p < 0.0001; RCA: 3 +/- 1 and 4 +/- 1 mm2/100 g LV mass, p = 0.002, respectively). LCA caliber of women ranged below the theoretically expected size according to the law of minimum viscous energy loss for the transport of blood in the coronary circulation, whereas those of men tended to be above it. CONCLUSIONS: In a population without cardiac disease, women have smaller coronary artery size even after normalisation for left ventricular mass.

Detection of viral pathogens by reverse transcriptase PCR and of microbial indicators by standard methods in the canals of the Florida Keys.

In order to assess the microbial water quality in canal waters throughout the Florida Keys, a survey was conducted to determine the concentration of microbial fecal indicators and the presence of human pathogenic microorganisms. A total of 19 sites, including 17 canal sites and 2 nearshore water sites, were assayed for total coliforms, fecal coliforms, Escherichia coli, Clostridium perfringens, enterococci, coliphages, F-specific (F(+)) RNA coliphages, Giardia lamblia, Cryptosporidium parvum, and human enteric viruses (polioviruses, coxsackie A and B viruses, echoviruses, hepatitis A viruses, Norwalk viruses, and small round-structured viruses). Numbers of coliforms ranged from <1 to 1, 410, E. coli organisms from <1 to 130, Clostridium spp. from <1 to 520, and enterococci from <1 to 800 CFU/100 ml of sample. Two sites were positive for coliphages, but no F(+) phages were identified. The sites were ranked according to microbial water quality and compared to various water quality standards and guidelines. Seventy-nine percent of the sites were positive for the presence of enteroviruses by reverse transcriptase PCR (polioviruses, coxsackie A and B viruses, and echoviruses). Sixty-three percent of the sites were positive for the presence of hepatitis A viruses. Ten percent of the sites were positive for the presence of Norwalk viruses. Ninety-five percent of the sites were positive for at least one of the virus groups. These results indicate that the canals and nearshore waters throughout the Florida Keys are being impacted by human fecal material carrying human enteric viruses through current wastewater treatment strategies such as septic tanks. Exposure to canal waters through recreation and work may be contributing to human health risks.

Emerging marine diseases--climate links and anthropogenic factors.

Mass mortalities due to disease outbreaks have recently affected major taxa in the oceans. For closely monitored groups like corals and marine mammals, reports of the frequency of epidemics and the number of new diseases have increased recently. A dramatic global increase in the severity of coral bleaching in 1997-98 is coincident with high El Niño temperatures. Such climate-mediated, physiological stresses may compromise host resistance and increase frequency of opportunistic diseases. Where documented, new diseases typically have emerged through host or range shifts of known pathogens. Both climate and human activities may have also accelerated global transport of species, bringing together pathogens and previously unexposed host populations.

Antibodies against platelet glycoproteins and antiphospholipid antibodies in autoimmune thrombocytopenia.

Autoantibodies against platelet glycoproteins (anti-GP) are found in the majority of patients with autoimmune thrombocytopenia (AITP) as well as in thrombocytopenia associated with systemic lupus erythematosus (SLE). Some of these patients may have anti-phospholipid antibodies (anti-PL). To evaluate the pathogenetic significance of anti-PL and anti-GP antibodies in AITP and SLE patients, we investigated anti-cardiolipin (anti-CL), anti-phosphatidylserine (anti-PS) and anti-GP antibodies (anti-GPIIb-IIIa and anti-GPIb-IX) in 71 patients with AITP and 3 thrombocytopenic patients with SLE. Anti-GP antibodies were detected in 52 (70%) patients. Fifty-six (73%) patients showed anti-PL antibodies. Seven patients (6 AITP, 1 SLE) with both anti-GPIIb-IIIa and IgG anti-PL antibodies were followed during treatment with corticosteroids. Antibodies were measured before treatment and at the time of platelet-peak. Anti-GPIIb-IIIa antibodies decreased in all or became undetectable in five. In contrast, IgG anti-PS and IgG anti-CL antibodies decreased only moderately or remained positive. Adsorption experiments, using gelfiltered platelets, erythrocyte (Ec)-inside-out-vesicles and purified GPIIb-IIIa, showed that anti-GP and anti-PL antibodies have distinct specificities and do not crossreact. We conclude that anti-PL and anti-GP antibodies may be present simultaneously in some patients with immune mediated thrombocytopenia. Although anti-PS as well as anti-CL antibodies may be responsible for thrombocytopenia, we speculate that anti-GPIIb-IIIa antibodies are more related to the severity of thrombocytopenia.

Nurses' knowledge of advance directives.

BACKGROUND: The Patient Self-Determination Act offers persons the opportunity to make their end-of-life choices known by the use of advance directives. Although nurses are designated advocates for patients and are available to communicate patients' concerns and wishes to other healthcare providers, few data on nurses' knowledge of advance directives have been reported. OBJECTIVE: To describe nurses' knowledge of advanced directives. SAMPLE: A volunteer sample of 339 RNs in a 600-bed acute care teaching hospital was surveyed. The sample represents 38% of the approximately 900 nurses employed at this hospital. METHODS: Data obtained from a 44-item questionnaire that tested nurses' knowledge of advance directives were analyzed. In addition, the relationship between nurses' knowledge of advance directives and certain demographic factors was analyzed. RESULTS: The mean score for knowledge of advance directives was 78% correct answers. Fifty-five percent of the respondents indicated that they did not have a good understanding of advance directives. Only 14% had completed these end-of-life documents for themselves, and 92% indicated that further education would increase their understanding of advance directives. An analysis of variance produced only one significant finding: the relationship between ethnicity and knowledge about advance directives. CONCLUSIONS: Nurses must increase their knowledge of advance directives. Results of this survey should stimulate caregivers and hospital policy makers to take a long-range view of their responsibilities to patients regarding advance directives and their responsibilities for educating the persons who convey information about advance directives to patients.

Athletic physeal injury in children and adolescents.

Physeal injuries occur in 15% of children with fractures, and 10% of all physeal injuries are sport related. Soccer, alpine skiing, gymnastics, weight lifting and baseball are sports commonly associated with physeal injury. Swelling, hyperemia, and deformity in the physeal area are the classical signs of physeal injury. Pain may be less intense than with other fractures. Treatment usually includes immobilization. Growth disturbance depends on extent of the injury and the amount of remaining growth potential. Prevention should focus on sport participation within the parameters of ability, maturation, and use of proper equipment.

The role of seafood in foodborne diseases in the United States of America.

In the United States of America, seafood ranked third on the list of products which caused foodborne disease between 1983 and 1992. Outbreaks connected with fish vectors were caused by scombroid, ciguatoxin, bacteria and unknown agents; in shellfish, unknown agents, paralytic shellfish poisoning, Vibrio spp. and other bacteria, followed by hepatitis A virus, were responsible for the outbreaks. At least ten genera of bacterial pathogens have been implicated in seafood-borne diseases. Over the past twenty-five years, bacterial pathogens associated with faecal contamination have represented only 4% of the shellfish-associated outbreaks, while naturally-occurring bacteria accounted for 20% of shellfish-related illnesses and 99% of the deaths. Most of these indigenous bacteria fall into the family Vibrionaceae which includes the genera Vibrio, Aeromonas and Plesiomonas. In general, Vibrio spp. are not associated with faecal contamination and therefore faecal indicators do not correlate with the presence of Vibrio. Viruses are the most significant cause of shellfish-associated disease: in New York State, for example, 33% and 62% of 196 outbreaks between 1981 and 1992 were caused by Norwalk virus and gastrointestinal viruses (small round structured viruses), respectively. In addition, several illnesses are a result of toxic algal blooms, the growth of naturally occurring bacteria and diatoms causing neurotoxic shellfish poisoning, paralytic shellfish poisoning, diarrhoetic shellfish poisoning, amnesic shellfish poisoning and ciguatera. Current estimates place the annual number of ciguatera cases at 20,000 world-wide. Scombroid poisoning is the most significant cause of illness associated with seafood. Scombrotoxin is of bacterial origin and halophilic Vibrio spp. causing high histamine levels are implicated as the source. Scombroid poisoning is geographically diverse and many species have been implicated, namely: tuna, mahi-mahi, bluefish, sardines, mackerel, amberjack and abalone. Temperature abuse has been cited as a major cause of scombroid poisoning. For routine work, the use of faecal indicators to predict the relative level of faecal contamination should not be disposed of. However, the main source of seafood illness is due to species which are not predicted by these organisms. In order to protect public health, routine surveillance using new pathogen-specific techniques such as polymerase chain reaction should be used. This, in combination with risk assessment methods and hazard analysis and critical control points, will begin to address the need for improvement in the safety of seafood.

International study to compare antigen-specific methods used for the measurement of antiplatelet autoantibodies.

Platelet-associated and plasma autoantibodies against platelet glycoproteins (GP) have been demonstrated in patients with autoimmune thrombocytopenia (AITP) using various methods. Eight laboratories in seven countries participated in this international study to evaluate the interlaboratory agreement using glycoprotein-specific immunoassays for these autoantibodies. The participating laboratories received blind samples of frozen washed platelets and plasma from 22 normal donors and 22 AITP patients. Platelet-associated and plasma autoantibodies against GPIIb-IIIa and GPIb-IX were measured by MAIPA, immunobead assay or modified antigen capture assay. Of the control samples, 96.0% and 97.2% of all results for platelet-associated and plasma autoantibodies to GPIIb-IIIa/ GPIb-IX, respectively, were negative. The mean variation coefficient of the control samples of platelet-associated and plasma autoantibodies was 89.5% (range 11.1-272.9%) and 46.5% (range 21.0-78.0%), respectively. In 20/22 patient samples, platelet-associated autoantibodies to either glycoprotein were noted by at least two laboratories. The mean degree of agreement in these samples was 74.0%. There was a significant correlation in the individual antibody measurements between all laboratories (Kendall coefficient of concordance 0.60 and 0.38, P < 0.001; Spearman rank order test, range of correlation coefficient 52.3-94.0% and 42.2-85.0%, P < 0.05, for anti-GPIIb-IIIa and anti-GPIb-IX, respectively). In contrast, plasma autoantibodies to either glycoprotein were noted by at least two laboratories in only 13/22 patient samples. Moreover, the degree of agreement was poor (50.1%) and a significant correlation was noted between only six pairs of laboratories. We conclude that methods used in this study yield good interlaboratory agreement in measuring platelet-associated autoantibodies against GPIIb-IIIa and GPIb-IX. In contrast, poor agreement was found in detecting plasma autoantibodies to the same glycoproteins.

Cardiovascular disease risks in adolescent males.

Although primary prevention efforts aimed at reducing heart disease have focused on adults, there is evidence that risk factors for heart disease are likely to be present in children and adolescents. To identify the risk factors present in adolescent boys, 82 male adolescents were enrolled in a study. Blood pressure, cholesterol, percent body fat, and body mass index (BMI) were measured along with data collection pertaining to diets, substance use, stress, and family history of heart disease. A statistically significant number of adolescent male subjects had high blood pressure, high cholesterol, high percent body fat, and high BMI and used substances associated with heart disease (smoking cigarettes, smokeless tobacco, alcohol, and amino acids). Thus, interventions must begin early in life if heart disease is to be prevented.

Behavior of long-term dantrolene sodium-treated rat skeletal muscles. Histochemical and electromechanical aspects.

Histochemical and electrochemical studies were carried out on skeletal rat muscles treated with dantrolene sodium (DS) for 60 days. Histochemical experiments revealed a conversion from fast twitch (type II) to slow twitch (type I) fibers for soleus (S), gastrocnemius (GM),a dn extensor digitorum longus (EDL) muscles. However, a significant decrease of muscle contractility was not observed in these chronically treated rat muscles in opposition to both those directly exposed in vitro as the muscles obtained from only 1-h DS-treated animals.