Hot Tub Research Articles

The Warner Archive and DVD Collecting in the New Home Video Market

The Warner Archive and DVD Collecting in the New Home Video Market Bradley Schauer (bio) In November 2010 Metro-Goldwyn-Mayer, once known as the “Tiffany of Studios,” filed for Chapter 11 bankruptcy protection after failing to find a buyer willing to assume its nearly four-billion-dollar debt (Spector). While an investment consortium led by Sony Corporation had purchased the studio for $4.9 billion in 2004, six years later the highest bid received for MGM was $1.5 billion from Time Warner (Chakravorty and Adegoke). Rather than accept a lowball offer, MGM’s creditors voted for bankruptcy reorganization, which allowed them to retain ownership of the studio (Spector). MGM’s precipitous loss in value was tied to its chief asset: its 4,100-title film library, which includes all post-1986 MGM films as well as the films of United Artists and Orion Pictures, among other studios. MGM’s value as a producer and distributor was negligible; its only theatrical release in 2010 was the modestly budgeted comedy Hot Tub Time Machine. In contrast, its library held such lucrative properties as the James Bond franchise, itself worth as much as $1 billion, and the distribution rights to J. R. R. Tolkien’s The Hobbit (Schuker and Spector). However, by 2010 the value of the MGM library had depreciated due in large part to an industry-wide decline in home video revenue—a 14 percent drop since 2004 (White).1 At the time of the sale to the Sony consortium, MGM was earning over $500 million annually from its library; by 2009 this had plummeted to $228 million (Spector and Schuker, “MGM Drama”). Revenue from the sale of MGM DVDs dropped from $140 million in 2007 to only $30 million in 2010 (Epstein, “MGM Follies”). Sony’s purchase of MGM’s library helped its Blu-ray high-definition system defeat HD-DVD in a format war, but this was little consolation to the Wall Street investors who had gambled on the durability of the home video market and lost approximately a billion dollars in the deal (Epstein, “The MGM Follies”). The fate of MGM vividly illustrates the threat posed to the major studios by the current decline in home video revenue as consumers begin to abandon the purchase of physical discs in favor of a less expensive rental model. One of the most prominent strategies through which studios have attempted to retain the value of their libraries is through the online sale of “manufacture-on-demand” (MOD) discs of catalog titles. This distribution method, characterized by relatively low production costs and relatively high retail prices, allows studios to expedite the release of their large libraries onto DVD and to maximize the revenue generated from their less popular library product. MOD therefore represents a last-ditch effort for studios to monetize the more obscure corners of their libraries via a sell-through, physical distribution model before the predicted supplanting of that model by digital streaming, rental-based services. The MOD system is presently the primary method of retail for older (pre-1990) films that have not seen a previous home video release; at the time of writing, there are well over a thousand discs available for purchase online. Focusing on the Warner Archive, the first and largest of the studio MOD programs, this article offers a detailed look into the economics of MOD, a topic previously unexplored in academic media industry studies. After first establishing the industrial context for the rise of MOD programs, namely, the decline in the traditional DVD market since 2007, I position MOD as a key example of “Long Tail” retailing, in which a wide variety of commodities with narrow appeal are cheaply marketed and sold to niche audiences via the Internet. Yet while MOD exploits some of the efficiencies of digital convergence, it also retains the inefficiencies of physical distribution and compares unfavorably to conventional DVDs in terms of [End Page 35] consumer value. Based on the reduction of production costs and the elimination of inventory costs, the economic principles of MOD programs lead them to ignore many of the characteristics of the traditional DVD sell-through model that proved so lucrative for studios from...

Outbreak of Hot-Foot Syndrome – Caused by Pseudomonas Aeruginosa

Infections with Pseudomonas aeruginosa can cause the hot-foot syndrome, presenting with painful plantar erythematous nodules. Particularly, the mechanically stressed areas of the foot are affected after contact with contaminated water from saunas, swimming pools, hot tubs, etc. We report an outbreak of hot-foot syndrome caused by Pseudomonas in 10 patients. The therapeutic regimens applied reached from local antiseptic therapy to systemic antibiotics.

How the hippies saved physics: science, counterculture, and the quantum revival

Today, quantum information theory is among the most exciting scientific frontiers, attracting billions of dollars in funding and thousands of talented researchers. But as MIT physicist and historian David Kaiser reveals, this cutting-edge field has a surprisingly psychedelic past. How the Hippies Saved Physics introduces us to a band of freewheeling physicists who defied the imperative to shut up and calculate and helped to rejuvenate modern physics. For physicists, the 1970s were a time of stagnation. Jobs became scarce, and conformity was encouraged, sometimes stifling exploration of the mysteries of the physical world. Dissatisfied, underemployed, and eternally curious, an eccentric group of physicists in Berkeley, California, banded together to throw off the constraints of the physics mainstream and explore the wilder side of science. Dubbing themselves the Fundamental Fysiks Group, they pursued an audacious, speculative approach to physics. They studied quantum entanglement and Bell's Theorem through the lens of Eastern mysticism and psychic mind-reading, discussing the latest research while lounging in hot tubs. Some even dabbled with LSD to enhance their creativity. Unlikely as it may seem, these iconoclasts spun modern physics in a new direction, forcing mainstream physicists to pay attention to the strange but exciting underpinnings of quantum theory. A lively, entertaining story that illuminates the relationship between creativity and scientific progress, How the Hippies Saved Physics takes us to a time when only the unlikeliest heroes could break the science world out of its rut.

Removal of Cryptosporidium and polystyrene microspheres from swimming pool water with sand, cartridge, and precoat filters

Cryptosporidium has caused the majority of waterborne disease outbreaks in treated recreational water venues in the USA for many years running. This research project evaluated some common US swimming pool filters for removing Cryptosporidium oocysts, 5-µm diameter polystyrene microspheres, and 1-µm diameter polystyrene microspheres. A 946 L hot tub with interchangeable sand, cartridge, and precoat filters was used at room temperature for this research. Simulated pool water for each experiment was created from Charlotte, NC (USA) tap water supplemented with alkalinity, hardness, chlorine, and a mixture of artificial sweat and urine. Precoat (i.e., diatomaceous earth and perlite) filters demonstrated pathogen removal efficiencies of 2.3 to 4.4 log (or 99.4-99.996%). However, sand and cartridge filters had average Cryptosporidium removals of 0.19 log (36%) or less. The combined low filter removal efficiencies of sand and cartridge filters along with the chlorine-resistant properties of Cryptosporidium oocysts could indicate a regulatory gap warranting further attention and having significant implications on the protection of public health in recreational water facilities. The 5-µm microspheres were a good surrogate for Cryptosporidium oocysts in this study and hold promise for use in future research projects, field trials, and/or product testing on swimming pool filters.

Hot Tub Lung From Mycobacterium asiaticum

INTRODUCTION: Nontuberculous mycobacteria (NTM) are ubiquitous in our environment and can cause multiple pulmonary diseases, including nodulocavitary disease, interstitial disease, and hypersensitivity pneumonitis-like granulomatous lung disease. The latter disease is often referred to as ‘hot tub lung’ in the literature due to its association with exposure to NTM present in hot water aerosols primarily during indoor hot tub use by immunocompetent hosts. Diagnostic criteria include history of hot water aerosol exposure, recurrent symptoms coinciding with exposure, radiological evidence of bilateral ground glass or poorly defined centrilobular nodular opacities, bronchoalveolar lavage lymphocytosis and histological evidence of diffuse inflammatory infiltrates along interstitium and nonnecrotizing granulomas 1.

Disposable swim diaper retention of Cryptosporidium-sized particles on human subjects in a recreational water setting

Cryptosporidium is a chlorine-resistant protozoan parasite responsible for the majority of waterborne disease outbreaks in recreational water venues in the USA. Swim diapers are commonly used by diaper-aged children participating in aquatic activities. This research was intended to evaluate disposable swim diapers for retaining 5-μm diameter polystyrene microspheres, which were used as non-infectious surrogates for Cryptosporidium oocysts. A hot tub recirculating water without a filter was used for this research. The microsphere concentration in the water was monitored at regular intervals following introduction of microspheres inside of a swim diaper while a human subject undertook normal swim/play activities. Microsphere concentrations in the bulk water showed that the majority (50-97%) of Cryptosporidium-sized particles were released from the swim diaper within 1 to 5 min regardless of the swim diaper type or configuration. After only 10 min of play, 77-100% of the microspheres had been released from all swim diapers tested. This research suggests that the swim diapers commonly used by diaper-aged children in swimming pools and other aquatic activities are of limited value in retaining Cryptosporidium-sized particles. Improved swim diaper solutions are necessary to efficiently retain pathogens and effectively safeguard public health in recreational water venues.

Environmental Risk Factors for Pulmonary Mycobacterium avium-intracellulare Complex Disease

Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous pathogen found in soil and water. Environmental exposure is the primary route for MAC infection. However, specific environmental risk factors have been poorly determined in immunocompetent patients with pulmonary MAC disease. A case-control study was performed with 106 patients with pulmonary MAC disease (men [women], 23 [83]; age, 64.3 ± 9.2 years) and 53 age-matched control patients with bronchiectasis but not pulmonary MAC infection (men [women], 7[46]; age, 63.0 ± 11.0 years). All participants completed a standardized questionnaire that included questions about medical history, smoking history, alcohol usage, age at menopause, and environment exposures. Environment exposures included soil exposure from farming or gardening; water exposure from bathing, showering, hot tub use, dishwashing, swimming, and drinking water; and pet exposure. No differences were identified in the patient characteristics and underlying diseases. More case patients experienced high soil exposure (≥ 2 per week) than control patients (23.6% vs 9.4%, P = .032); this remained significant after multivariate analysis (OR, 5.9; 95% CI, 1.4-24.7; P = .015). There were no significant differences in other environmental exposures. Case patients with high soil exposure were significantly older than those with low soil exposure (67.3 ± 7.3 years vs 64.3 ± 9.5 years, P = .037). Other characteristics, underlying diseases, and mycobacterial species did not differ between the two groups. Patients with pulmonary MAC disease had significantly more soil exposure than noninfected control patients, which suggests that environmental soil exposure is a likely risk factor for the development of pulmonary MAC disease.

Pseudomonas Mastitis Caused by Hot Tub Exposure

To the Editors: Mastitis most frequently occurs in relation to lactation, whereas nonlactational mastitis is rare in adolescents.1 We report a case of an 11-year-old prepubertal girl presenting with mastitis caused by Pseudomonas aeruginosa after using a hot tub. The patient presented to hospital with a 3-day history of left-sided mastalgia and breast swelling. Twenty-four hours after onset, she developed a widespread pustular, erythematous rash affecting her trunk, groin area, thighs, and upper arms, but sparing her face and neck. It first appeared on her abdomen in a single area, and then became widespread over a 24-hour period. She had no systemic symptoms. Four days before presenting to the hospital, she had shared a hot tub with several other people at a friend's house. Several children and one adult also noted a similar rash, but no one developed mastalgia or mastitis. Breast examination demonstrated a tender left breast, with overlying mild erythema. She had associated tender lymphadenopathy in the left axilla. There were no signs of a breast abscess. She also had a widespread symmetrical papulopustular rash affecting her trunk, groins, upper thighs, and upper arms. The pustules varied in size, but were not larger than 4 mm in diameter. The rash was not itchy, but several of the pustules were tender. A blood sample was obtained for assessment of a full blood count, urea and electrolytes, and C-reactive protein level. A swab was obtained from a pustule for microscopy, culture and sensitivity. The blood test results were within normal range, except for a slightly elevated C-reactive protein level of 11 mg/L (normal range, 0–10 mg/L). She was treated with oral flucloxacillin and regular analgesia for the mastitis. Clinical review after 48 hours revealed no improvement in her symptoms. A dermatology opinion was sought for the rash, and a literature search revealed an association between Pseudomonas folliculitis, the suspected clinical diagnosis for the rash, and mastitis. The results of the swab culture, reported on that day, identified P. aeruginosa. The antibiotic was changed to oral ciprofloxacin, as per sensitivity, and 24 hours later the rash had improved dramatically. There was complete resolution of the Pseudomonas folliculitis after 1 week. The mastitis had improved greatly, but there was still some mild tenderness, which settled after a few days. A swab obtained from a pustule of the patient's younger brother also identified P. aeruginosa. The other children who developed a rash did not attend hospital, and their symptoms resolved spontaneously within a few days. The association of mastitis with Pseudomonas folliculitis does not appear to be well recognized among clinicians treating either condition. In our patient, it is probable that the mastitis occurred as a direct result of infection of the mammary gland or glands of Montgomery.2,3 Her breasts were enlarging because of the influence of pubertal hormones, increasing their susceptibility to infection,4 and the high bather load and occlusion of her swimming costume made her susceptible to the development of infection with Pseudomonas.2,5 Susannah M. C. George, MRCP Department of Dermatology Brighton and Sussex University Hospitals NHS Trust Jaspal Rattan, MRCGP Department of Paediatrics Western Sussex Hospitals NHS Trust Katy Walker, MRCPCH Department of Paediatrics Brighton and Sussex University Hospitals NHS Trust Brighton, United Kingdom Anil Garg, FRCPCH, FRCPI Department of Paediatrics Western Sussex Hospitals NHS Trust Worthing, United Kingdom

Fertility intelligence: what hospital employees don't know may surprise you

Hospital employees are often thought to be knowledgeable about many aspects of healthcare and are often asked by patients and the community for advice, including about reproduction. The purpose of this study was to determine the basic knowledge level of hospital employees about fertility and infertility. Anonymous questionnaire. A ten-item questionnaire was distributed to attendees of an employee health fair at a large private metropolitan hospital. Demographic information was limited to job title. Data were analyzed using descriptive and comparative statistics. 252 questionnaires were completed and returned from 85 licensed providers (LP; nurses, physicians, and physician assistants) and 167 support staff (SS). Although 67% correctly said ovulation occurs 2 wk before menses, 33% believed ovulation occurred during menses, after basal temperature rise, or during intercourse. The majority knew smoking and irregular menses are infertility risks, but only 27% identified acne and hirsutism as risk factors while 52% said oral contraceptive use for 5+ yr was a risk factor. Only 28% said male use of nutritional supplements is a potential risk. LP were more accurate than SS at identifying hirsutism, irregular menses, and male use of hot tubs as risks. As for treatment, 31% said clomiphene is the first step for infertility management, although 66% overestimated its risk of multiple pregnancy, with 22% thinking that triplets occurred in ≥ 50% of pregnancies. Alarmingly, 56% of LP and 54% of SS believed testosterone to be a successful treatment for male infertility. 58% stated that infertility treatment is elective and not covered by the majority of insurance companies. Asked when a couple should seek medical advice for infertility, 85% selected “after 1 yr” or “whenever they have concern.” Hospital employees are not well educated about infertility. Lack of general knowledge about fertility as well as inaccurate fears may impede prompt infertility evaluation and treatment.

Quantitative analyses of mycobacteria in water: Adapting methods in clinical laboratories

An outbreak of occupational hot tub lung necessitated quantitative analysis of mycobacteria in water samples. We combined procedures for cultivation of mycobacteria in urine and quantitative analyses of dialysis water. Whirlpool spa water samples were analyzed showing promising results. In conclusion, quantitative mycobacterial culture of water is possible by adapting methods routinely used in clinical laboratories.

Ten Things We Did (and Probably Shouldn't Have) (review)

Reviewed by: Ten Things We Did (and Probably Shouldn't Have) Karen Coats Mlynowski, Sarah . Ten Things We Did (and Probably Shouldn't Have). HarperTeen, 2011. [368p]. ISBN 978-0-06-170124-5 $16.99 Reviewed from galleys R Gr. 9-12. Left behind when her mother had an affair and moved to Paris, April learns that her father and his new wife want her to leave her Connecticut home and long-time boyfriend to move to Cleveland the second semester of her junior year. April freaks and hatches a plan with her friend, Vi, to live at Vi's house for the rest of the year. [End Page 531] The problem is that Vi's mother has just landed a role in a traveling production, so the girls will have the place to themselves. Knowing April's father would never agree, Vi pretends to be her own mother on the phone, and the girls set up fake email addresses so that their "parents" can communicate with each other online. The emancipated girls behave as one might imagine: hosting parties, suffering minor household disasters with confusing cleaning products, getting an unauthorized pet, skipping school, buying a hot tub, and losing their virginity. This last is a bigger deal for April, because, although she loves Noah, his behavior since she moved in with Vi has been weird and disapproving. When April tests positive for chlamydia, it's seemingly prudish Noah who has some explaining to do, and April has to face some difficult emotional issues that she's left unresolved since her parents' break-up. While this is a rather sitcommy set-up for a serious coming-of-age narrative, it offers the advantage of posing important questions about assuming adult responsibilities from a wish-fulfilling premise; April and Vi, like many teens, are thrilled to be living on their own, but, amidst the parties and freedom, they also face loneliness and the harsh truth that their parents' lives are perfectly fulfilled without them, thank you very much. Additionally, when April finds herself attracted to a new boy, she must reconcile her anger toward her mother with a fear that she is like her. Likewise, when she finds out what Noah did, she has to face her more persistent fear that she will be like her father—the one who gets cheated on and left—reminding readers that even without your parents in the next room, they're closer than you could ever imagine. Copyright © 2011 The Board of Trustees of the University of Illinois

Maternal use of hot tub and major structural birth defects

Previous studies on the associations between hot tub use during early pregnancy and birth defects have found an increased risk of neural tube defects, but no increase in risk of cardiac defects. No previous studies have assessed the association between maternal hot tub use and other types of noncardiac birth defects. We included mothers of infants with birth defects (n = 10,825) and mothers of infants without birth defects (n = 6795) who participated in the multisite National Birth Defects Prevention Study between 1997 and 2005. Odds ratios were adjusted for maternal ethnicity and education. Analysis of 17 birth defects revealed that mothers of infants with gastroschisis and anencephaly were significantly more likely to report any use of a hot tub in early pregnancy: adjusted odd ratios were 1.54 (95% confidence interval [CI], 1.10-2.17) and 1.68 (95% CI, 1.05-2.70), respectively. Among the mothers who reported using a hot tub more than once in the exposure period and remaining in it for more than 30 min, we found significantly elevated odds ratios (≥2.0) for esophageal atresia, omphalocele, and gastroschisis and a nonsignificant elevation (≥2.0) for spina bifida and anencephaly. These results suggest that women who use hot tubs more than once during early pregnancy and for long periods of time have an increased risk of certain birth defect phenotypes, particularly anencephaly and gastroschisis. Because of multiple statistical tests and small sample sizes, we cannot exclude the possibility that some of these elevated associations may be due to chance.

Mysterious Foot Lesions in a Healthy Eight Year Old

Mysterious Foot Lesions in a Healthy Eight Year Old

Fatal Pseudomonas aeruginosa pneumonia in a previously healthy woman was most likely associated with a contaminated hot tub

Community-acquired pneumonia due to Pseudomonas aeruginosa in previously healthy individuals is a rare disease that is associated with high fatality. On 14 February 2010 a previously healthy 49-year-old woman presented to an emergency room with signs and symptoms of pneumonia, 2 days after returning from a spa holiday in a wellness hotel. Blood cultures and respiratory specimens grew P. aeruginosa. Despite adequate antimicrobial therapy, the patient died of septic multiorgan failure on day nine of hospitalization. On February 26, nine water samples were taken from the hotel facilities used by the patient: In the hot tub sample 37,000 colony-forming units of P. aeruginosa/100 ml were detected. Two of five individual colonies from the primary plate used for this hot tub water sample were found to be genetically closely related to the patients’ isolates. Results from PFGE, AFLP and MLST analysis allowed the two lung isolates gained at autopsy and the whirlpool bathtub isolates to be allocated into one cluster. The patient most likely acquired P. aeruginosa from the contaminated water in the hotel’s hot tub. The detection of P. aeruginosa in high numbers in a hot tub indicates massive biofilm formation in the bath circulation and severe deficiencies in hygienic maintenance. The increasing popularity of hot tubs in hotels and private homes demands increased awareness about potential health risks associated with deficient hygienic maintenance.

“Hot Tub” Folliculitis from a NonChlorinated Children’s Pool

Pseudomonas aeruginosa is common cause of folliculitis following contact with contaminated water. We report a case of pseudomonal folliculitis that occurred after swimming in a children's pool filled with water from a well.

A rapid detection method using flow cytometry to monitor the risk of Legionella in bath water

Legionella species are the causative agents of human legionellosis, and bathing facilities have been identified as the sources of infection in several outbreaks in Japan. Researchers in Japan have recently reported evidence of significant associations between bacterial counts and the occurrence of Legionella in bathing facilities and in a hot tub model. A convenient and quantitative bacterial enumeration method is therefore required as an indicator of Legionella contamination or disinfection to replace existing methods such as time-consuming Legionella culture and expensive Legionella-DNA amplification. In this study, we developed a rapid detection method (RDM) to monitor the risk of Legionella using an automated microbial analyzing device based on flow cytometry techniques to measure the total number of bacteria in water samples within two minutes, by detecting typical patterns of scattered light and fluorescence. We first compared the results of our RDM with plate counting results for five filtered hot spring water samples spiked with three species of bacteria, including Legionella. Inactivation of these samples by chlorine was also assessed by the RDM, a live/dead bacterial fluorescence assay and plate counting. Using the RDM, the lower limit of quantitative bacterial counts in the spiked samples was determined as 3.0×103(3.48log)countsmL−1. We then used a laboratory model of a hot tub and found that the RDM could monitor the growth curve of naturally occurring heterotrophic bacteria with 1 and 2days' delayed growth of amoeba and Legionella, respectively, and could also determine the killing curve of these bacteria by chlorination. Finally, samples with ≥3.48 or <3.48logtotal bacterial countsmL−1 were tested using the RDM from 149 different hot tubs, and were found to be significantly associated with the positive or negative detection of Legionella with 95% sensitivity and 84% specificity. These findings indicated that the RDM can be used for Legionella control at bathing facilities, especially those where the effectiveness of chlorine is reduced by the presence of Fe2+, Mn2+, NH4+, skin debris, and/or biofilms in the water.

Ethnic differences in thermoregulatory responses during resting, passive and active heating: application of Werner’s adaptation model

For the coherent understanding of heat acclimatization in tropical natives, we compared ethnic differences between tropical and temperate natives during resting, passive and active heating conditions. Experimental protocols included: (1) a resting condition (an air temperature of 28°C with 50% RH), (2) a passive heating condition (28°C with 50% RH; leg immersion in a hot tub at a water temperature of 42°C), and (3) an active heating condition (32°C with 70% RH; a bicycle exercise). Morphologically and physically matched tropical natives (ten Malaysian males, MY) and temperate natives (ten Japanese males, JP) participated in all three trials. The results saw that: tropical natives had a higher resting rectal temperature and lower hand and foot temperatures at rest, smaller rise of rectal temperature and greater temperature rise in bodily extremities, and a lower sensation of thirst during passive and active heating than the matched temperate natives. It is suggested that tropical natives' homeostasis during heating is effectively controlled with the improved stability in internal body temperature and the increased capability of vascular circulation in extremities, with a lower thirst sensation. The enhanced stability of internal body temperature and the extended thermoregulatory capability of vascular circulation in the extremities of tropical natives can be interpreted as an interactive change to accomplish a thermal dynamic equilibrium in hot environments. These heat adaptive traits were explained by Wilder's law of initial value and Werner's process and controller adaptation model.

Prevalence and Antimicrobial-Resistance of Pseudomonas aeruginosa in Swimming Pools and Hot Tubs

Pseudomonas aeruginosa is an important opportunistic pathogen in recreational waters and the primary cause of hot tub folliculitis and otitis externa. The aim of this surveillance study was to determine the background prevalence and antimicrobial resistance profile of P. aeruginosa in swimming pools and hot tubs. A convenience sample of 108 samples was obtained from three hot tubs and eight indoor swimming pools. Water and swab samples were processed using membrane filtration, followed by confirmation with polymerase chain reaction. Twenty-three samples (21%) were positive for P. aeruginosa, and 23 isolates underwent susceptibility testing using the microdilution method. Resistance was noted to several antibiotic agents, including amikacin (intermediate), aztreonam, ceftriaxone, gentamicin, imipenem, meropenem (intermediate), ticarcillin/clavulanic acid, tobramycin (intermediate), and trimethoprim/sulfamethoxazole. The results of this surveillance study indicate that 96% of P. aeruginosa isolates tested from swimming pools and hot tubs were multidrug resistant. These results may have important implications for cystic fibrosis patients and other immune-suppressed individuals, for whom infection with multidrug-resistant P. aeruginosa would have greater impact. Our results underlie the importance of rigorous facility maintenance, and provide prevalence data on the occurrence of antimicrobial resistant strains of this important recreational water-associated and nosocomial pathogen.

Mycobacterial hypersensitivity pneumonitis requires TLR9-MyD88 in lung CD11b+ CD11c+ cells

Mycobacteria are among the most common causes of hypersensitivity pneumonitis (HP), but controversy persists with regard to the involvement of the infectious potency of the organism in mycobacterial HP (hot tub lung). This study aimed to establish a mouse model of hot tub lung to clarify its pathophysiology. Mice were exposed intranasally to formalin-killed Mycobacterium avium from a patient with hot tub lung (HP strain) or chronic pulmonary infection (non-HP strain), and bronchoalveolar lavage fluids and lung tissues were evaluated for allergic inflammation. Dead M. avium HP strain, but not non-HP strain, elicited marked HP-like pulmonary inflammation in wild-type mice. Although the inflammation was induced in mice lacking CD4 or CD8, the induction of HP-like responses was prevented in mice lacking myeloid differentiation factor (MyD)88 or Toll-like receptor (TLR)9. Cultured lung CD11c+ cells responded to M. avium in a TLR9-dependent manner, and reconstitution of TLR9-/- mice with lung CD11c+ cells from wild-type mice restored the inflammatory responses. Further investigation revealed that pulmonary exposure to M. avium HP strain increased the number of lung CD11b+ CD11c+ cells (dendritic cells) through TLR9 signalling. Our results provide evidence that hot tub lung develops via the mycobacterial engagement of TLR9-MyD88 signalling in lung CD11b+ dendritic cells independent of the mycobacterial infectious capacity.

Does Fever Relieve Autistic Behavior by Improving Brain Blood Flow?

Helt and coworkers (Helt et al. 2008) reported that significant fevers have improved autistic behavior, citing the sole controlled study (Curran et al. 2007). This study was prompted by anecdotal reports (Sullivan 1980; Cotterill 1985; Brown 1999) of dramatic improvements in social interaction and speech—core deficits of autism— during fever. Informal parent surveys indicate that fever benefits 30–40% of autistic children (Simons Foundation 2010). Helt et al pointed out that confirming fever’s ability to stimulate emotional contact and speech would be especially meaningful. They noted reports of low brain blood flow in these children, and proposed an intriguing explanation—swollen astrocytes compressing brain capillaries. Implicit in this evidence is a simple argument: In a disorder characterized by low brain blood flow, can high-level cortical functions like speech and social interaction become almost normal without more blood to the brain? Fever increases cerebral blood flow (CBF) for nutrients and cooling, which can improve well-being and performance in persons whose cerebral circulation is compromised (Kiyatkin 2010). The obvious inference is that fever may improve speech and social behavior in autistic children largely by increasing brain blood flow. The benefit of fever in autism was the focus of a recent workshop (Simons Foundation 2010). The effect of temperature to increase CBF was considered, but discounted because a sauna or hot tub doesn’t usually help (Miles 2010). The best explanation may be that fever increases brain temperature much more than ambient heat (Kiyatkin 2010): “In contrast [to fever], sauna or environmental warming affects brain temperature very little, especially in humans, because of sophisticated homeostatic mechanisms that maintain stability of body temperature.... While data in humans are limited, it appears that fluctuations due to stress, environmental warming, etc. are relatively weak (up to 1.0–1.5°C), but during fever this increase is much larger, especially in children.” The benefit of fever in autistic children appears to reach a maximum at elevations of 1.5–2.5°C (Cotterill 1985). One homeostatic mechanism that prevents brain hyperthermia from ambient heat or stress is elevation of GABA in interstitial fluid; fever, by contrast, reduces GABA, and elevates the free amino acid taurine (Frosini 2007). Blood GABA appears high in autistic children (Dhossche et al. 2002), brain GABA may be downregulated (Harada et al. 2010; Hasler et al. 2010); taurine is often depleted (Pangborn 2002). Downregulation of GABA elevates brain temperature therefore blood flow, but fever’s elevation of taurine may be more decisive because taurine carries water out of swollen astrocytes (Benarroch 2005). Various neurotoxins implicated in autism (e.g. ammonia, excess glutamine, organic mercury) cause astrocytes to swell, which can compress the lumen of brain capillaries by nearly half (Aschner et al. 1999) If swollen astrocytes compress brain capillaries in autism spectrum disorders, as Helt et al. suggested, elevation of taurine by fever may decompress these vessels and improve CBF. Taurine may also increase brain blood flow by suppressing release of GABA by neurons (Kuriyama and Hashimoto 1998). Autistic children who do not improve during fever may be those most depleted of taurine. Letter re: Helt et al. 2008. Can children with autism recover? If so, how? Neuropsychology Review, 18(4), 339–366.