Epidemiologic and diagnostic evaluation of a recent mumps outbreak using oral fluid samples.

OBJECTIVE: To determine the optimal strategy to investigate mumps virus infection in a partially vaccinated cohort. STUDY DESIGN: 122 oral fluid and serum samples were collected in a recent outbreak in Ireland. The largest age cohort, students aged 18-21 years old attending third level institutions, were investigated using virus isolation, detection of mumps specific IgM, IgG, RT-PCR and molecular genotyping. RESULTS: 97% of patients had both detectable serum IgM and IgG. Mumps virus RNA was detected in 17 oral fluid samples and 14 of these originated from a single geographic location. Only 6 of the IgM positive samples had detectable mumps virus RNA whereas this could be detected in 11 IgM negative samples. Genotyping studies revealed that genotypes G and J were co-circulating during this outbreak. CONCLUSIONS: The use of an oral fluid sample to detect mumps virus RNA and IgM offers a major improvement over serological diagnosis in acute infection in both non-vaccinated or partially vaccinated individuals, and has the advantage that specimens are collected non-invasively.     

Impaired Microvascular Function in Normal Children: Effects of Adiposity and Poor Glucose Handling

Clustering of cardiovascular risk factors is thought to occur early in life. The endothelium is an important regulator of microvascular function. We investigated the relationship between microvascular function and cardiovascular risk factors in 145 normal, healthy children aged 11-14 years. Skin microvascular responses, measured using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), were negatively correlated with percentage body fat ( r =−0.20, P < 0.05 and r =−0.18, P < 0.05, respectively). Subjects were stratified into quintiles based on 2-h, post-feeding glucose levels. Subjects in the upper glucose quintile (range 7.4-11.4 mmol l⁻¹) showed significantly lower vasodilatation to both ACh (   P < 0.005  ) and SNP (   P < 0.02  ) than those in the lower quintile (range 3.9-4.9 mmol l⁻¹). Waist-to-hip ratio and the fasting insulin resistance index were significantly greater in subjects in the upper quintile than those in the lower quintile ( P < 0.001 and P < 0.05, respectively). Additionally, in subjects in the upper glucose quintile, fasting triglyceride correlated with fasting insulin ( r = 0.59, P < 0.001) and with the fasting insulin resistance index ( r = 0.49, P < 0.009), and plasma levels of cholesterol and 2-h glucose were also correlated ( r = 0.40, P < 0.05). In a cross-section of normal children, microvascular function was negatively associated with adiposity. Additionally, in a subgroup of subjects, there was a clustering of high post-feeding glucose, impaired microvascular function, increased insulin resistance and higher central fat distribution. These findings suggest that risk factors for adult cardiovascular disease begin to cluster in normal children, which might have important consequences for development of atherosclerosis later in life.     

Passive hyperthermia reduces voluntary activation and isometric force production

It has been suggested that a critically high body core temperature may impair central neuromuscular activation and cause fatigue. We investigated the effects of passive hyperthermia on maximal isometric force production (MVC) and voluntary activation (VA) to determine the relative roles of skin (T_sk) and body core temperature (T_c) on these factors. Twenty-two males [O_2max=64.2 (8.9) ml kg^–1 min^–1, body fat=8.2 (3.9)%] were seated in a knee-extension myograph, then passively heated from 37.4 to 39.4°C rectal temperature (T_re) and then cooled back to 37.4^oC using a liquid conditioning garment. Voluntary strength and VA (interpolated twitch) were examined during an isometric 10-s MVC at 0.5°C intervals during both heating and cooling. Passive heating to a T_c of 39.4^oC reduced VA by 11 (11)% and MVC by 13 (18)% (P<0.05), but rapid skin cooling, with a concomitant reduction in cardiovascular strain [percentage heart rate reserve decreased from 64 (11)% to 29 (11)%] and psychophysical strain did not restore either of these measures to baseline. Only when cooling lowered T_c back to normal did VA and MVC return to baseline (P<0.05). We conclude that an elevated T_c reduces VA during isometric MVC, and neither T_sk nor cardiovascular or psychophysical strain modulates this response. Results are given as mean (SD) unless otherwise stated.     

Staphylococcal accessory regulator (sar) in conjunction with agr contributes to Staphylococcus aureus virulence in endophthalmitis.

Previous studies showed that an agr mutant strain of Staphylococcus aureus was partially attenuated in virulence compared to a parental strain in experimental endophthalmitis. The purpose of this study was to determine whether the sar locus, either alone or through interactions with agr, contributes to the regulation of virulence in S. aureus endophthalmitis. Experimental endophthalmitis was established by the midvitreous injection of approximately 30 CFU of S. aureus RN6390 or the isogenic attenuated strains RN6911 (agr mutant), ALC136 (sar mutant), and ALC135 (agr sar double mutant). Unexpectedly, the rate of reduction in electroretinographic B-wave amplitude in eyes infected with strain ALC136 (sar mutant) was not significantly different from the parental strain on postinfection day (PID) 5 (10% retention). In contrast, ALC135 (agr sar double mutant)-infected eyes retained 73% of preoperative B-wave amplitude on PID 5. Therefore, unlike agr, a mutation in the sar locus alone does not alter the overall virulence of wild-type S. aureus in experimental endophthalmitis. However, the combined effect of insertional mutations in both the sar and agr global regulators leads to near-complete attenuation of virulence.     

Inhibitory effect of adenosine on electrically evoked contractions in the rat vas deferens: pharmacological characterization

The inhibitory effects of adenosine as well as its related analogues on the contractile response of the rat vas deferens to field stimulation were compared in the absence and in the presence of nitrobenzylthioguanosine (NBTGR), a potent adenosine uptake inhibitor. In the presence of NBTGR, the order of potency was N6-cyclohexyladenosine (CHA) greater than or equal to L-N6-phenylisopropyladenosine (L-PIA) greater than 2-chloroadenosine greater than D-N6-phenylisopropyladenosine (D-PIA) greater than or equal to adenosine greater than 2'-deoxyadenosine. The inhibitory effect of adenosine but not that of clonidine, beta-endorphin and somatostatin was blocked by 1,3-diethyl-8-phenylxanthine (DPX, pA2 = 7.2), a potent P1-purinergic antagonist. The results suggest that adenosine inhibited the electrically evoked contractions of the rat vas deferens via the activation of the A1 subtype of P1-purinergic receptors.     

Frequent allelic loss of 21q11.1 approximately q21.1 region in advanced stage oral squamous cell carcinoma

A fine mapping of loss of heterozygosity (LOH) was performed in oral squamous cell carcinoma (OSCC), using 12 markers on 21q11.1 approximately q21.1. We studied 43 resected primary invasive tumors and their paired normal tissues, concurrent dysplasia or carcinoma in situ in separate areas from 8 of the specimens, and 6 local recurrent carcinomas. LOH status was compared between lesions of different phases of progression within the same patient. A high frequency of LOH was observed for D21S1410, D21S120, and D21S1433 (60% each) in the primary lesions, constituting two interstitial deleted regions encompassing eight known genes. Cases showing LOH of D21S120 were significantly associated with advanced clinical stages (III and IV; P=0.02). Consistent allelic loss was observed in 64.2% of the informative cases between the precursor lesions and their corresponding invasive tumors, and in 59.5% of those between the primary lesions and their recurrent counterparts. Fewer than half of the different lesions within a given patient showed discordant allelic loss for tested markers. Our results suggest that 21q11.1 approximately q21.1 harbors tumor suppressor genes in OSCC. Genetic divergence may develop during tumor clone evolution.     

Role of pulmonary alveolar macrophages in defense of the lung against Pseudomonas aeruginosa

Alveolar macrophages (AM) provide one of the first lines of defense against microbial invasion in the lower airways. The role of AM in the clearance of Pseudomonas aeruginosa in mice after intrapulmonary challenge was evaluated. AM were depleted by intranasal administration of liposome-encapsulated dichloromethylene diphosphonate. At 24 h following the instillation of liposomes, a sublethal dose of P. aeruginosa was inoculated intranasally. Spleen, liver, and lung tissue was then evaluated for viable bacteria and for histopathology. AM depletion of 78 to 88% did not affect the survival rate of infected mice or clearance of P. aeruginosa from the spleen, liver, or lung, compared to the control group, but the mice's susceptibility to Klebsiella pneumoniae was greatly enhanced. The recruitment of neutrophils to the lung was also not affected. Freshly explanted AM were not competent to phagocytose unopsonized P. aeruginosa but were able to phagocytose zymosan particles. Further studies were conducted to assess the in situ phagocytic activities of AM. Three hours after the intranasal instillation of P. aeruginosa or other particles, bronchoalveolar lavage was performed. AM phagocytosis of zymosan particles and latex beads exceeded that of P. aeruginosa. Neutrophils were recruited to the lung in response to a high-dose bacterial challenge. These results suggest that AM do not play an important role in defense of the lung against P. aeruginosa.