Viral titers in nasal lining fluid compared to viral titers in nasal washes during experimental rhinovirus infection

BACKGROUND: The concentration of rhinovirus in nasal wash specimens from infected volunteers peaks at 48-72 h after inoculation. The volume of expelled nasal fluid peaks at the same time, raising the question of whether the viral concentration in nasal wash reflects viral replication in nasal cells or merely the production of an increased volume of nasal fluid during a cold. OBJECTIVES: To determine the amount of rhinovirus in nasal lining fluid during colds before the nasal fluid has been diluted in a nasal wash. STUDY DESIGN: Rhinovirus titers were determined in nasal wash specimens collected daily for five days from 14 subjects with type16 rhinovirus infection. The urea concentration in nasal lining fluid equals that in blood. By determining the urea concentration in a nasal wash and comparing it to the urea concentration in blood from the same subject, it was possible to determine the amount of dilution of the nasal lining fluid. The dilution factor (reciprocal of the dilution) was then used to calculate the viral concentration in undiluted nasal lining fluid. RESULTS: The dilution factor in 70 nasal washes varied from 5 to 64. The viral GMTs (+S.E.) in nasal washes were 1.79 (+0.3) TCID(50)/ml at 24 h, 3.11 (+0.15) at 48 h, and 2.61 (+0.3) at 72 h. The viral GMTs in nasal lining fluid, based on urea adjusted values, paralleled those in nasal washes but were approximately one log higher. Virus concentrations returned to near baseline values by day 5. CONCLUSIONS: The temporal pattern of rhinovirus shedding observed in nasal wash specimens, with a peak in virus concentration at 48-72 h after infection, is a true indication of virus production in nasal cells and not an artifact of the increased amount of nasal fluid produced during the early phase of a cold.     

Acoustic transmission in normal human hips: structural testing of joint symmetry

An acoustical technique has been developed for the measurement of structural symmetry of the hip joints. A mild vibratory force was applied to the sacrum and sound signals were picked up at both hips by a pair of microphones installed in two stethoscopes. These stethoscope–microphone assembles were calibrated to achieve a difference in relative sensitivity of less than 0.2 dB. The relative transmission of sound signals was analysed and compared between both hips by a dual-channel signal analyser. Twenty-seven healthy adults, 20 healthy pre-school children and 19 normal neonates were tested. Results from these three groups showed high coherence of the sound signals and that the discrepancy between both hips was smallest in the frequency range of 200–315 Hz. For normal neonates, the sound signals maintained a high coherence (γ²>0.97) and small discrepancy (D<1.25 dB) between both hips. This study has shown that the acoustical technique provides a practical structural testing for bony symmetry of the hips and the results offer a baseline for further investigation into developmental dysplasia of the hip (DDH) in neonates. Clinical screening for DDH is still problematic in developing countries.     

Thermal regulatory responses to submaximal cycling following lower-body cooling in humans

This study compared the effects of pre-exercise cooling with control water immersions on exercise-induced thermal loads derived from steady-state submaximal exercise. Eight healthy male participants [mean (SEM) age 29 (1) years, maximal oxygen uptake 3.81 (0.74) l·min^–1, and body surface area 1.85 (0.11) m²] took part in experiments that included 30 min of baseline data collection [ambient temperature 21.3 (0.2°C)], 30 min of immersion in water to the level of the supra-iliac crest [water temperatures of 35.1 (0.3)°C for thermoneutral and 17.7 (0.5)°C for precooled treatments], and 60 min of cycling exercise at 60% of maximal oxygen uptake. No significant differences were noted during exercise in net mechanical efficiency, metabolic rate, O₂ pulse, or ratings of perceived exertion between the two treatments. Precooling resulted in a significant negative body heat storage during immersion and allowed greater heat storage during exercise. However, net body heat storage for the entire protocol was no different between treatments. Cooling significantly lowered rectal, mean skin, and mean body temperatures as well as more than doubling the exercise time until a 0.5°C rectal temperature increase was observed. The cooling trial significantly delayed onset of sweating by 19.62 min and decreased sweat rate by 255 ml·h^–1 compared to control. Thermal and sweat sensation scores were lower after the cooling treatment compared to control. These data suggest that lower-body precooling is effective at decreasing body heat storage prior to exercise and decreases reliance on heat dissipation mechanisms during exercise. Therefore, this unique, well-tolerated cooling treatment should have a broader application than other precooling treatments. Electronic Publication     

Functional tyrosine kinase inhibitor profiling: a generally applicable method points to a novel role of platelet-derived growth factor receptor-beta in tuberous sclerosis

A ubiquitous herpesvirus that establishes life-long infection, the Epstein-Barr virus (EBV) has yielded little insight into how a single agent in general accord with its host can produce diverse pathologies ranging from oral hairy leukoplakia to nasopharyngeal carcinoma, from infectious mononucleosis to Hodgkin's disease (HD) and Burkitt's lymphoma. Its pathogenesis is further confounded by the less than total association of virus with histologically similar tumors. In other viral systems, defective (interfering) viral genomes are known to modulate outcome of infection, with either ameliorating or intensifying effects on disease processes initiated by prototype strains. To ascertain whether defective EBV genomes are present in HD, we examined paraffin-embedded tissue from 56 HD cases whose EBV status was first determined by cytohybridization for nonpolyadenylated EBV RNAs (EBERs). Using both standard polymerase chain reaction (PCR) and PCR in situ hybridization, we successfully amplified sequences that span abnormally juxtaposed BamHI W and Z fragments characteristic of defective heterogeneous (het) EBV DNA from 10 of 32 (31%) EBER-positive tumors. Of 24 EBER-negative HD, 8 yielded PCR products indicating presence of het EBV DNA. Two of these contained defective EBV in the apparent absence of the prototype virus. Of the 42 tumors analyzed for defective EBV by both PCR techniques, there was concordance of results in 38 (90%). Detection of defective EBV genomes with the potential to disrupt viral gene regulation suggests one mechanism for pathogenic diversity that may also account for loss of prototypic EBV from individual tumor cells.     

A critical function for type I interferons in cancer immunoediting

'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in this process, the involvement of type I interferons (IFN-alpha/beta) has not been elucidated. We now show that, like IFN-gamma, endogenously produced IFN-alpha/beta was required for the prevention of the growth of primary carcinogen-induced and transplantable tumors. Although tumor cells are important IFN-gamma targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma.     

Use of Leu M1 and antiepithelial membrane antigen monoclonal antibodies for diagnosing Hodgkin's disease

Biopsies of 82 patients diagnosed as having Hodgkin's disease were reviewed. Seventeen were reclassified histologically as non-Hodgkin's lymphoma or reactive lymphoid hyperplasia. A substantial number of cases of Hodgkin's disease were negative when stained with Leu M1. Staining for Leu M1 was not found in the cases of non-Hodgkin's lymphoma or reactive lymphoid hyperplasia. With the exception of the lymphocyte predominant nodular subtype of Hodgkin's disease, epithelial membrane antigen staining was seen in a few cases of Hodgkin's disease and non-Hodgkin's lymphomas. This was not a useful discriminating feature.     

Cat shedding of Fel d I is not reduced by washings, Allerpet-C spray, or acepromazine

Background: No published studies have compared the effectiveness of several treatments proposed to reduce cat allergenicity. Cat washing studies demonstrating efficacy involved very small sample sizes or infrequent washings. Allerpet-C (Allerpet, Inc., New York, N.Y.), a widely advertised topical spray, and acepromazine, a tranquilizer advocated as efficacious in subsedating doses, have never been scientifically studied. Objective: We compared the effects of cat washing, Allerpet-C spray, and acepromazine with that of no treatment on the shedding of the primary cat allergen, Felis domesticus I by cats. Methods: In a blinded, comparative, controlled study, we measured the amounts of Fel d I shed during an 8-week treatment period with a sample of 24 female mongrel cats randomly assigned to four groups; one group received weekly distilled water washings, one received weekly Allerpet-C spray applications, one received daily oral acepromazine, and one had no treatment (control). Thirty-minute, twice-weekly air samples were collected from each cat with a laminated plastic–acrylic chamber and air sampler. Results: One-sample, two-sided t tests comparing baseline to final-week measurements revealed no significant change in Fel d I within each group (mean change ±SD: washing; 487.6 ± 1896.4 mU per 30 minutes, p = 0.63; Allerpet-C spray, 429.2 ± 871.6 mU per 30 minutes, p = 0.46 acepromazine; −620.6 ± 1031.2, p = 0.52 per 30 minutes). Furthermore, analysis of covariance revealed no significant change in Fel d I levels between groups (p = 0.72). Conclusions: Our data do not show significant reductions in Fel d I shedding as a result of any of these treatments. Therefore we cannot recommend them to patients allergic to cats. (J ALLERGY CLIN IMMUNOL 1995;95:1164-71.)     

Mosaic tetraploidy in a two-year-old female

A 24-month-old female with severe physical and mental retardation is described. Peripheral lymphocytes demonstrated tetraploid/diploid mosaicism. That this does not represent an artifact in vitro was supported by the finding of buccal mucosal cells with two Barr bodies and tetraploid/diploid mosaicism in fibroblasts and bone marrow cells.