Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A.

Psoriasis is a common chronic inflammatory skin disease restricted to humans. The understanding of its pathogenesis has long been hampered by the lack of suitable chronic mouse models. The cytokine IL-17A has emerged as a key player in epithelial immune responses and the defense against extracellular pathogens. Moreover, enhanced expression of IL-17A can turn pathologic and is closely associated with psoriasis. In this study, we generated a novel transgenic mouse model that recapitulates many characteristics of psoriasis. DC-IL-17Aind mice with constitutive low-level expression of IL-17A by CD11c+ cells gradually develop skin lesions during adult life. The lesions preferentially occur at sites of mechanical stress and exhibit macroscopic, histologic and genetic hallmarks of psoriatic plaques. Intriguingly, the age of disease onset depends on the levels of IL-17A and disruption of the epidermal barrier by tape-stripping triggers psoriatic plaque formation in the DC-IL-17Aind model. In summary, our results suggest that deregulated IL-17A together with epidermal trauma initiates skin inflammation and lesion formation in mice closely resembling plaque-type psoriasis. Due to the gradual development and chronic nature of disease, DC-IL-17Aind mice provide a unique tool to dissect the pathogenesis of human psoriasis and potentially could serve as a model to validate novel therapeutic strategies.

Lucigenin chemiluminesence. A new approach to study the redox activity of Ehrlich ascetic tumor cells.

OBJECTIVE: To study the mechanism and to measure the oxygenation/reduction activity of Ehrlich ascetic tumor cells in an isotonic solution by means of lucigenin dependent chemiluminescence. METHODS: All the measurements of the chemiluminescence redox activity of Ehrlich ascetic tumor cell samples in suspension medium, were carried out using a photon counting system especially designed to the purpose. The areas under the chemiluminescence kinetic curves were measured at different cell physiological conditions and at different agents concentrations effect. RESULTS: The rates of lucigenin chemiluminescence redox functional activity of Ehrlich ascetic tumor cells were significantly different from normal oxygenation/reduction activity at different physiological environments of Ehrlich ascetic tumor cells suspension conditions (i.e. cell membrane permeability changes, presence and absence of oxidative or reductive agents at different concentrations and oxy/hydroxy free radical protective agents). CONCLUSION: The results explain more fully the mechanism and the value of a lucigenin dependent chemiluminescence probe of the redox functional activity of Ehrlich ascetic tumor cells (at different physiological conditions of suspension).

Ocular Ferning test - effect of temperature and humidity on tear Ferning patterns.

BACKGROUND: The ocular ferning test is used as a diagnostic aid to evaluate patients with dry-eye disease. The ferning phenomenon is a dendritic growth form of dried tear fluid. The influence of temperature and relative humidity (rH) on the morphology of tear ferning patterns was investigated. METHODS: Two microliters of tear fluid of 5 volunteers with normal tear function were dropped onto a microscope slide with a pipette and were dried in a climatic chamber at four different temperatures (20, 22, 24 and 26 degrees C) and at four different grades of rH (30, 40, 50 and 60%) at each temperature. The dried droplet was divided according to distinct morphological features into a center, transition zone and margin. The center of the dried droplet was classified into four types according to the system of Rolando. RESULTS: In the temperature range between 20 and 26 degrees C, rH has a strong influence on the ferning patterns. At these temperatures, increasing rH resulted in a deterioration of type I ferning obtained at 30% rH to type II or type III at 60% rH in all subjects. Otherwise, at rH of 30, 40 and 50%, no definite influence of temperature between 20 and 26 degrees C was observed. At an rH of 60%, the ferning patterns changed with increasing temperature from 20 to 26 degrees C from type II to type III. CONCLUSION: High humidity can modify and deteriorate the ferning patterns of tear fluid from subjects with normal tear function. To obtain reproducible results using the ocular ferning test, stable conditions are necessary. An rH not higher than 50% at a temperature range between 20 and 26 degrees C produced ferning patterns without interstitial spaces which could be related to the best quality according to the system of Rolando.

Opioids inhibit febrile responses in humans, whereas epidural analgesia does not: an explanation for hyperthermia during epidural analgesia.

BACKGROUND: Epidural analgesia is frequently associated with hyperthermia during labor and in the postoperative period. The conventional assumption is that hyperthermia is caused by the technique, although no convincing mechanism has been proposed. However, pain in the "control" patients is inevitably treated with opioids, which themselves attenuate fever. Fever associated with infection or tissue injury may then be suppressed by opioids in the "control" patients while being expressed normally in patients given epidural analgesia. The authors therefore tested the hypothesis that fever in humans is manifested normally during epidural analgesia, but is suppressed by low-dose intravenous opioid. METHODS: The authors studied eight volunteers, each on four study days. Fever was induced each day by 150 IU/g intravenous interleukin 2. Volunteers were randomly assigned to: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using ropivacaine alone; (3) epidural analgesia using ropivacaine in combination with 2 microg/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml. RESULTS: Fentanyl halved the febrile response to pyrogen, decreasing integrated core temperature from 7.0 +/- 3.2 degrees C. h on the control day, to 3.8 +/- 3.0 degrees C. h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine-fentanyl did not inhibit fever. The fraction of core-temperature measurements that exceeded 38 degrees C was halved by intravenous fentanyl, and the fraction exceeding 38.5 degrees C was reduced more than fivefold. CONCLUSIONS: These data support the authors' proposed mechanism for hyperthermia during epidural analgesia. Fever during epidural analgesia should thus not be considered a complication of the anesthetic technique per se.

Prolonged episodes of persistent asthma: A distinct clinical pattern with characteristic clinical features.

STUDY OBJECTIVES: To investigate a clinical pattern of unexplained persistent asthma that is episodic in nature and lasts for months to years. This pattern of prolonged episodes of unexplained, persistent asthma was not defined previously. DESIGNS: Investigating the clinical features using a retrospective cohort design. SETTING AND PATIENTS: Eighteen subjects (ages, 13 to 64 years) from an allergy practice in a large prepaid health maintenance organization who had two or more prolonged episodes of unexplained persistent asthma lasting >/= 2 months during a 12-year period. RESULTS: These subjects accounted for 39 asthmatic episodes lasting from 2 to 74 months (median, 7 months). The duration of the episodes positively correlates with the severity of asthma (p = 0.02) at the initial part of the episodes. All episodes demonstrated a similar pattern, with symptom severity greatest at the onset and gradually diminishing until recovery. The relatively symptom-free intervals between the episodes ranged from 1.5 to 63 months (median, 13 months). Fifty-six percent of the episodes (95% confidence interval [CI], 40% to 72%) were associated with symptoms very suggestive or suggestive of an infection of the upper respiratory tract at the onset of the episodes; 33% of the episodes (95% CI, 19% to 50%) had possible symptoms suggestive of an infection; whereas only 10% of the episodes (95% CI, 3% to 24%) had questionable or no symptoms suggestive of an infection of the upper respiratory tract. Thirty-four episodes had the onset between September and March, whereas only 5 episodes occurred between April and August (p < 0. 001). CONCLUSIONS: These observations indicate that prolonged episodes of unexplained, persistent asthma lasting for months to years constitute a distinct clinical pattern of asthma with characteristic clinical features.

Diagnosis of symptomatic postmenopausal women by traditional Chinese medicine practitioners.

OBJECTIVE: To learn more about the way that practitioners of traditional Chinese medicine (TCM) diagnose women who have menopausal symptoms. DESIGN: We assembled a cohort of 23 postmenopausal women who had hot flushes and were otherwise healthy. Each woman was examined independently by nine practitioners of TCM on the same day. Examination consisted of medical history and physical examination. Diagnoses were recorded and counted. RESULTS: The most frequent diagnosis made by the practitioners of TCM was kidney yin deficiency, which was the diagnosis made after 168 of 207 visits (81%); 23 women seen by nine TCM practitioners. Practitioners showed good agreement regarding presence of kidney yin deficiency: in 12 women (52%), this diagnosis was made by eight of nine practitioners; in 16 women (70%), seven of nine practitioners made this diagnosis; and in all 23 women (100%), at least five of nine practitioners made this diagnosis. CONCLUSIONS: Practitioners of TCM who diagnose postmenopausal women with vasomotor symptoms are likely to make a diagnosis that includes kidney yin deficiency.

The effect of pyrogen administration on sweating and vasoconstriction thresholds during desflurane anesthesia.

BACKGROUND: General anesthetics increase the sweating-to-vasoconstriction interthreshold range (temperatures not triggering thermoregulatory defenses), whereas fever is believed to only increase the setpoint (target core temperature). However, no data characterize thresholds (temperatures triggering thermoregulatory defenses) during combined anesthesia and fever. Most likely, the combination produces an expanded interthreshold range around an elevated setpoint. The authors therefore tested the hypothesis that thermoregulatory response thresholds during the combination of fever and anesthesia are simply the linear combination of the thresholds resulting from each intervention alone. METHODS: The authors studied eight healthy male volunteers. Fever was induced on the appropriate days by intravenous injection of 30 IU/g human recombinant interleukin 2 (IL-2), followed 2 h later by an additional 70 IU/g. General anesthesia consisted of desflurane 0.6 minimum alveolar concentration (MAC). The volunteers were randomly assigned to the following groups: (1) control (no desflurane, no IL-2); (2) IL-2 alone; (3) desflurane alone; and (4) desflurane plus IL-2. During the fever plateau, volunteers were warmed until sweating was observed and then cooled to vasoconstriction. Sweating was evaluated from a ventilated capsule and vasoconstriction was quantified by volume plethysmography. The tympanic membrane temperatures triggering significant sweating and vasoconstriction identified the respective response thresholds. Data are presented as the mean +/- SD; P < 0.05 was considered significant. RESULTS: The interthreshold range was near 0.40 degrees C on both the control day and during IL-2 administration alone. On the IL-2 alone day, however, the interthreshold range was shifted to higher temperatures. The interthreshold range increased significantly during desflurane anesthesia to 1.9+/-0.6 degrees C. The interthreshold range during the combination of desflurane and IL-2 was 1.2+/-0.6 degrees C, which was significantly greater than on the control and IL-2 alone days. However, it was also significantly less than during desflurane alone. CONCLUSION: The combination of desflurane and IL-2 caused less thermoregulatory inhibition than would be expected based on the effects of either treatment alone. Fever-induced activation of the sympathetic nervous system may contribute by compensating for a fraction of the anesthetic-induced thermoregulatory impairment.

Specialty differences in the management of asthma. A cross-sectional assessment of allergists' patients and generalists' patients in a large HMO.

OBJECTIVE: To examine the differences in medical management and quality of life between patients with asthma who receive their primary asthma care from allergists and those who receive their care from generalists in a large health maintenance organization (HMO). METHODS: We conducted a cross-sectional study of patients with asthma in a large HMO (Kaiser Permanente, Northwest Region, Portland, Ore). Participants were 392 individuals aged 15 through 55 years with physician-diagnosed asthma, taking antiasthma medications, reporting current asthma symptoms, and receiving asthma care from an allergist or from a generalist. Primary outcomes include characteristics of asthma, health care utilization, and quality of life. RESULTS: Patients cared for by allergists tended to have more severe asthma than those cared for by generalists (P < .01). The allergists' patients tended to be older (38.6 +/- 9.6 years vs 35.7 +/- 12.6 years, P < .01), more atopic (91% vs 78%, P < .01), and more likely to report perennial (rather than seasonal) asthma (26% vs 36%, P < .04) than the generalists' patients. Patients receiving their primary asthma care from an allergist were considerably more likely than generalists' patients to report using inhaled anti-inflammatory agents (P < .01), oral steroids (P < .01), and regular (daily) breathing medications to control their asthma (P < .01). Allergists' patients were more likely to have asthma exacerbations treated in a clinic setting rather than an emergency department (P < .01). Furthermore, allergists' patients reported significantly improved quality of life as measured by several dimensions of the SF-36 scale (physical functioning, role emotional, bodily pain, and general health; P < .05). CONCLUSIONS: These findings suggest that specialist care of asthma is of benefit for patients with asthma in a large HMO. Specifically, the allergists' patients conformed more closely to national asthma management guidelines and reported better quality of life than did the generalists' patients.

The Aberdeen Mark II single-photon-emission tomographic scanner: specification and some clinical applications.

The construction, operation and physical characteristics of a single-section multi-detector single-photon-emission scanner are described. The machine has 24 detectors arranged along the sides of a square. Movements and data collection are under the control of a series of distributed microprocessors. Both head and trunk tomograms can be produced. The spatial resolution at the collimator focus is 9 mm in the transverse plane, and the effective slice thickness is 14 mm. The volume sensitivity is 300 counts/s kBq ml with a 20 cm diameter cylindrical phantom filled with 99Tcm solution. The application of this machine to the examination of the brain, liver and heart has been found to be clinically useful.

Lyoluminescence dosimetry part II. State-of-the-art.

This is the second part of a review dealing with the development and current state-of-the-art of lyoluminescence dosimetry. Readout equipment described in the review covers a range of devices from simple manually-operated apparatus to semi-automatic machines suitable for loose powders and for encapsulated dosimeters. The survey of dosimetric properties of mannose and glutamine includes response to X- and gamma-rays, electrons, heavy charged particles and to neutrons. Current applications of lyoluminescence dosimetry include radiotherapy, radiation processing of foods and sterilization of medical products, as well as the use of lyoluminescent phosphors for gamma-ray dose intercomparisons in the high-dose range.

Silicon measurement in a lung phantom by neutron inelastic scattering.

A study was made to assess the feasibility of determining the silicon level in human lungs in vivo by measuring the gamma rays arising from the neutron inelastic scattering reaction 28Si(n, n' gamma)28Si. Neutron energies in the range 5--8 MeV represent the best compromise between the conflicting requirements of high energy for good detection statistics and low energy to minimize the dose to the subject. The sensitivity of measurement was enhanced by pulsing the neutron beam and counting only during the period of bombardment. This effectively reduced the background counts emanating from thermal neutron reactions in the phantom and from the fast neutron reaction 31P(n, alpha)28 A1. In measurements with an anthropomorphic phantom, no interference peaks from other prompt inelastic scattering reactions were observed. With one Ge(Li) detector of 19% relative efficiency, a detection limit of 0.6 g of silicon per 10 mSv was obtained. On this basis, it is estimated that six Ge(Li) detector of 25% efficiency each would be capable of measuring 0.15 g of silicon in the lungs, the average level found in nonoccupationally exposed adults.U

Radiation enhancement with iodinated deoxyuridine.

A technique, Photon Activation Therapy (PAT), is described in which high Linear Energy Transfer (LET) radiations in the form of Auger electron distributions are generated by a photon beam through photoactivation of stable iodine incorporated as an analog of thymidine (Tyd) in DNA. Of the several halogenated deoxyribonucleosides evaluated, iodinated deoxyuridine (IdUrd) was found to be the only viable choice as a Tyd analog for PAT. Calculations show that 5% replacement of Tyd in tumor DNA multiplies the biologic effectiveness of a given photon radiotherapy dose by a factor of approximately 3. If further therapeutic advantages accorded to high LET radiations are taken into account, as well as repair and regeneration of normal tissues during protracted irradiations, an advantage of approximately 6 is realized. Five percent replacement of Tyd has already been reported for human tumor in vivo. Higher replacements of Tyd with IdUrd would provide proportionately greater advantages. The expectation is that previous clinical results with BrdUrd and high-energy X-rays can be significantly improved upon through the use of IdUrd and suitable lower energy activating photons (35-50 keV). In particular, it is suggested that protracted irradiations with implanted sources such as 145Sm or 145Pm may provide unique advantages at selected sites such as brain or head and neck tumors.

Renal osteopenia - an assessment of long-term therapy with vitamin D analogues.

Renal bone disease was assessed for an average of 5.5 years in 9 patients on maintenance haemodialysis. The investigative methods included serial biochemical estimations, radiographic skeletal surveys and quantitative bone histology. Repeated bone mineral analyses and neutron activation analyses of a hand were also performed in order to monitor changes in skeletal calcium content. Before treatment, progressive osteodystrophy was demonstrated by all techniques. Following therapy with the vitamin D analogues, all patients noted symptomatic improvement; serum alkaline phosphatase reverted to normal and serum parathyroid hormone concentrations decreased. Radiographically, subperiosteal erosions healed while the histological features of osteomalacia and osteitis fibrosa were abolished. Both bone mineral and neutron activation analyses indicated that progressive skeletal demineralisation had been halted. However, a sustained increase in the overall mineral content of bone was not demonstrated. Thus, vitamin D therapy although improving the biochemical, radiological, and histological features of renal osteodystrophy may not restore bone mass to osteopenic bone.

Lyoluminescence dosimetry with some saccharides.

Lyoluminescent properties of mannose, glucose monohydrate, sucrose and trehalose dihydrate were investigated from the point of view of suitability as dosimetric materials in a new system of solid state dosimetry. Distilled water was used as a solvent. With a reader equipped with an uncooled PM tube it was possible to measure doses of X- and gamma-rays in the range from a few rad to about 100 krad. Various experimental factors which could affect the dose measurements using lyoluminescence are discussed, including the energy response for X-rays. Some preliminary information on the response of saccharides to fast neutrons is also included.

Transmission detectors for cyclotron in-vivo irradiations with neutrons.

The neutron fluence imparted to the irradiated subjects needs to be measured accurately in order to obtain meaningful results from diagnostic irradiations. A convenient neutron detector for this purpose is in the form of a transmission chamber, which covers the whole beam directed at the subject. In one design the detector is an ionization chamber, filled with propane gas, in another a thin sheet of plastic scintillator is coupled to a pair of photomultipliers.