A novel bioassay for human somatogenic activity in serum samples supports the clinical reliability of immunoassays

OBJECTIVE Because there is discordance between different immunoassay values for serum hGH, and because clinical state may not correlate with immunoreactive hGH, we have developed an assay to accurately measure serum hGH somatogenic bioactivity. The results of this assay were compared with the Elegance two-site ELISA assay across 135 patient samples in a variety of clinical states. DESIGN The somatogenic assay was based on stable expression of hGH receptor in the murine BaF line, allowing these cells to proliferate in response to hGH. To eliminate interference by other growth factors in serum, we created a specific antagonist of the hGH receptor (similar to Trovert or Pegvisomant) which allowed us to obtain a true measure of hGH somatogenic activity by subtraction of the activity in the presence of the antagonist. The assay was carried out in microtiter plates over 24 h, with oxidation of a chromogenic tetrazolium salt (MTT) as the endpoint. PATIENTS These encompassed a number of different clinical conditions related to short stature, including idiopathic short stature, neurosecretory dysfunction and renal failure, as well as obese patients on dietary restriction and normal volunteers. MEASUREMENTS In addition to the colourimetric (MTT) response to hGH, we measured free hGH by stripping out GHBP-bound hGH using beads coupled to a monoclonal antibody to the GHBP (GH binding protein). All samples were measured in both bioassay and ELISA assay. RESULTS This bioassay was sensitive (5 mU/l or 2 mug/l) and precise, and not subject to interference by the GHBP. There was a good correlation (r = 0.95) between bioactivity and immunoactivity across clinical states. There was, however, an increased bioactivity during secretory peaks (over 25 mU/l), which has been reported previously for the Nb2 bioassay. Free hGH did not correlate with clinical state. CONCLUSIONS Because the results of the Elegance ELISA and the bioassay correlate well, even though there is greater bioactivity at higher hormone concentrations, it is evident that an appropriate immunoassay is able to act as a reliable indicator for clinical assessment. In those rare cases where bio-inactive GH exists, our bioassay should provide an appropriate means to demonstrate this.

A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation

Background & Aims: Two major mutations are defined within the hemochromatosis gene, HFE. Although the effects of the C282Y mutation have been well characterized, the effects of the H63D mutation remain unclear. We accessed a well-defined population in Busselton, Australia, and determined the frequency of the H63D mutation and its influence on total body iron stores. Methods: Serum transferrin saturation and ferritin levels were correlated with the H63D mutation in 2531 unrelated white subjects who did not possess the C282Y mutation. Results: Sixty-two subjects (2.1%) were homozygous for the H63D mutation, 711 (23.6%) were heterozygous, and 1758 (58.4%) were wild-type for the H63D mutation. Serum transferrin saturation was significantly increased in male and female H63D homozygotes and heterozygotes compared with wild-types. Serum ferritin levels within each gender were not influenced by H63D genotypes. Elevated transferrin saturation greater than or equal to45% was observed in a greater proportion of male H63D carriers than male wild-types. Male H63D homozygotes (9%) and heterozygotes (3%) were more likely to have both elevated transferrin saturation and elevated ferritin greater than or equal to300 ng/mL than male wild-types (0.7%). Homozygosity for H63D was not associated with the development of clinically significant iron overload. Conclusions: Presence of the H63D mutation results in a significant increase in serum transferrin saturation but does hot result in significant iron overload. In the absence of the C282Y mutation, the H63D mutation is not clinically significant.

Control of Aedes vectors of dengue in three provinces of Vietnam by use of Mesocyclops (Copepoda) and community-based methods validated by entomologic, clinical, and serological surveillance

We describe remarkable success in controlling dengue vectors, Aedes aegypti (L.) and Aedes albopictus (Skuse), in 6 communes with 11,675 households and 49,647 people in the northern provinces of Haiphong, Hung Yen, and Nam Dinh in Vietnam. The communes were selected for high-frequency use of large outdoor concrete tanks and wells. These were found to be the source of 49.6-98.4% of Ae. aegypti larvae, which were amenable to treatment with local Mesocyclops, mainly M. woutersi Van der Velde, M. aspericornis (Daday) and M. thermocyclopoides Harada. Knowledge, attitude, and practice surveys were performed to determine whether the communities viewed dengue and dengue hemorrhagic fever as a serious health threat; to determine their knowledge of the etiology, attitudes, and practices regarding control methods including Mesocyclops; and to determine their receptivity to various information methods. On the basis of the knowledge, attitude, and practice data, the community-based dengue control program comprised a system of local leaders, health volunteer teachers, and schoolchildren, supported by health professionals. Recycling of discards for economic gain was enhanced, where appropriate, and this, plus 37 clean-up campaigns, removed small containers unsuitable for Mesocyclops treatment. A previously successful eradication at Phan Boi village (Hung Yen province) was extended to 7 other villages forming Di Su commune (1,750 households) in the current study. Complete control was also achieved in Nghia Hiep (Hung Yen province) and in Xuan Phong (Nam Dinh province); control efficacy was greater than or equal to 99.7% in the other 3 communes (Lac Vien in Haiphong, Nghia Dong, and Xuan Kien in Nam Dinh). Although tanks and wells were the key container types of Ae. aegypti productivity, discarded materials were the source of 51% of the standing crop of Ae. albopictus. Aedes albopictus larvae were eliminated from the 3 Nam Dinh communes, and 86-98% control was achieved in the other 3 communes. Variable dengue attack rates made the clinical and serological comparison of control and untreated communes problematic, but these data indicate that clinical surveillance by itself is inadequate to monitor dengue transmission.

Impact of osteoarthritis on individuals and society: how much disability? Social consequences and health economic implications

Osteoarthritis is a major cause of disability in both the developed and developing world. With the population aging, the prevalence of osteoarthritis is increasing and its consequences are impacting significantly on society. This is one of the reasons why osteoarthritis has been adopted as a major focus (along with osteoporosis, rheumatoid arthritis, back pain, and musculoskeletal trauma) by the global initiative-the Decade of Bone and Joint Disease. Adequate studies on the costs of osteoarthritis are urgently required so that cogent arguments can be made to governments to appropriately fund prevention and treatment programs for this condition. Its recognition as a major cause of disability, particularly in the aging population, should increase community focus on this important condition. (C) 2002 Lippincott Williams Wilkins, Inc.

Consumers' perceived risk: Sources versus consequences

In this study, we examine an important factor that affects consumers' acceptance of business-to-commerce (B2C) electronic commerce - perceived risk. The objective of this paper is to examine the definition of perceived risk in the context of B2C electronic commerce. The paper highlights the importance of perceived risk and the interwoven relation between perceived risk and trust. It discusses the problem of defining perceived risk in prior B2C research. This study proposes a new classification of consumers' perceived risk based on sources. It highlights the importance of identifying the sources of consumer's risk perceptions in addition to the consequences dimensions. Two focus group discussion sessions were conducted to verify the proposed classification. Results indicate that Internet consumers perceive three sources of risk in B2C electronic commerce: technology, vendor, and product. © 2003 Elsevier B.V. All rights reserved.

Neonatal respiratory therapy in the new millennium: Does clinical practice reflect scientific evidence?

Respiratory therapy has historically been considered the primary role of the physiotherapist in neonatal intensive care in Australia. In 2001 a survey was undertaken of all level three neonatal intensive care units in Australia to determine the role of the physiotherapist and of respiratory therapy in clinical practice. It appears that respiratory therapy is provided infrequently, with the number of infants treated per month ranging from 0 to 10 in 15 of the 20 units who provide respiratory therapy, regardless of therapist availability. The median number of respiratory treatments per month during the week was three, and on weekends it was one. Respiratory therapy was carried out by physiotherapists and nurses in 54.6% of units, by physiotherapists only in 36.4% of units, and by nurses only in the remaining 9% of units surveyed. There was also a diminution of the role of respiratory therapy in the extubation of premature infants. A review of the literature shows that overall the use of respiratory therapy reflects current evidence. The question remains whether it is possible to maintain the competency of staff and justify the cost of training in the current healthcare economic climate. It seems probable that the future role of physiotherapists in neonatal intensive care unit may be in the facilitation of optimal neurological development of surviving very low birth weight infants.

Play Preferences and Behavior of Preschool Children with Autistic Spectrum Disorder in the Clinical Environment

The play of children with autistic spectrum disorder (ASD) is a valuable medium for assessment and intervention, and its analysis has the potential to aid diagnosis. This study investigated spontaneous play behavior and play object preferences for 24 preschool children with ASD in a typical occupational therapy clinical environment. Play behavior was rated and choice of play object noted at 10-second intervals from a 15-minute video recording of unstructured play. Statistical analyses indicated that play behavior was consistent with descriptions in the literature. In addition, the children demonstrated clear preferences for play objects in the form of popular characters (e.g., Thomas the Tank Engine) and those with sensorimotor properties. We propose that the inclusion of preferred play objects in a clinical environment may increase intrinsic motivation to play, and thereby enhance assessment and intervention.

Clinical Research: Room for all?

no abstract

Lateral epicondylalgia: a musculoskeletal physiotherapy perspective

Tennis elbow or lateral epicondylalgia (LE) is a challenging musculoskeletal condition to treat. This is largely due to the lack of research-based evidence of the clinical efficacy of the myriad of treatment approaches espoused in the literature. In view of this, successful rehabilitation of LE is based on choosing treatments that address the physical impairments found during clinical examination. The primary physical impairment in LE is a deficit in grip strength predominately due to pain and its consequences on motor function. Hence the mainstay of successful management of this condition is therapeutic exercise, providing it is not pain provocative. Adjunctive procedures such as manipulative therapy and sports taping techniques have recently been shown to provide substantial initial pain relief. Early relief of pain in the rehabilitation program helps accelerate recovery and most importantly motivates the client to persist with the therapeutic exercise program. The manipulative therapy and taping treatments presented in this masterclass warrant consideration in the clinical best practice management of LE, and serve as a model for other similar musculoskeletal conditions. (C) 2003 Elsevier Science Ltd. All rights reserved.

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations

Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain.

Outcome variables for osteoarthritis clinical trials: the OMERACT-OARSI set of responder criteria

Improvement in analysis and reporting results of osteoarthritis (OA) clinical trials has been recently obtained because of harmonization and standardization of the selection of outcome variables (OMERACT 3 and OARSI). Moreover, OARSI has recently proposed the OARSI responder criteria. This composite index permits presentation of results of symptom modifying clinical trials in OA based on individual patient responses (responder yes/no). The 2 organizations (OMERACT and OARSI) established. a task force aimed at evaluating: (1) the variability of observed placebo and active treatment effects using the OARSI responder criteria; and (2) the possibility of proposing a simplified set of criteria. The conclusions of the task force were presented and discussed during the OMERACT 6 conference, where a simplified set of responder criteria (OMERACT-OARSI set of criteria) was proposed.