Developments in acupuncture research: big-picture perspectives from the leading edge

On November 8-9, 2007, the Society for Acupuncture Research (SAR) hosted an international conference to mark the tenth anniversary of the landmark NIH [National Institutes of Health] Consensus Development Conference on Acupuncture. More than 300 acupuncture researchers, practitioners, students, funding agency personnel, and health policy analysts from 20 countries attended the SAR meeting held at the University of Maryland School of Medicine, Baltimore, MD. This paper summarizes important invited lectures in the area of how the field has developed in the past decade, along with a focus on appropriate strategies for advancing the field. Specific topics include: the impact of the 1997 NIH Acupuncture Consensus Conference on acupuncture research; whole-system strategies for developing the evidence without distorting the medicine; use of qualitative research methods to explore acupuncture as a complex intervention; use of qualitative research approaches to explore some "missing" topics in acupuncture research; and the impact of acupuncture research on clinical practice. A concluding section focuses on future directions in acupuncture research.     

Maternal heart rate variability and fetal behavior in hypertensive and normotensive pregnancies

The relation between maternal heart rate variability (HRV) and fetal behavior was examined in hypertensive and normotensive pregnant women. A total of 40 mother-fetal pairs (n = 20 normotensive mothers; n = 20 hypertensive mothers) at 33-41 weeks' gestation were observed using a standardized procedure lasting approximately 50 min. It included the following measurements: maternal beat-by-beat arterial blood pressure and HRV; spontaneous fetal heart rate (HR), body and breathing movements; and an estimate of amniotic fluid volume. The women in the hypertensive group had higher average body mass index (BMI) (33.7 vs. 28.8 kg/m2) than the normotensive group. In the normotensive group, there was no association between maternal HRV and fetal gestational age, HR, body or breathing movements. In the hypertensive group, maternal HRV measures of low-frequency, high-frequency, and total power were associated with fetal gestational age; also, there was an association between maternal autonomic modulation of HR and fetal spontaneous HR. These findings suggest that the maternal autonomic system influences fetal cardiac function in pregnancies complicated by hypertension.     

The integrate model of emotion, thinking and self regulation: an application to the "paradox of aging"

This study was undertaken using the INTEGRATE Model of brain organization, which is based on a temporal continuum of emotion, thinking and self regulation. In this model, the key organizing principle of self adaption is the motivation to minimize danger and maximize reward. This principle drives brain organization across a temporal continuum spanning milliseconds to seconds, minutes and hours. The INTEGRATE Model comprises three distinct processes across this continuum. Emotion is defined by automatic action tendencies triggered by signals that are significant due to their relevance to minimizing danger-maximizing reward (such as abrupt, high contrast stimuli). Thinking represents cognitive functions and feelings that rely on brain and body feedback emerging from around 200 ms post-stimulus onwards. Self regulation is the modulation of emotion, thinking and feeling over time, according to more abstract adaptions to minimize danger-maximize reward. Here, we examined the impact of dispositional factors, age and genetic variation, on this temporal continuum. Brain Resource methodology provided a standardized platform for acquiring genetic, brain and behavioral data in the same 1000 healthy subjects. Results showed a "paradox" of declining function in the "thinking" time scale over the lifespan (6 to 80+ years), but a corresponding preservation or even increase in automatic functions of "emotion" and "self regulation". This paradox was paralleled by a greater loss of grey matter in cortical association areas (assessed using MRI) over age, but a relative preservation of subcortical grey matter. Genetic polymorphisms associated with both healthy function and susceptibility to disorder (including the BDNFVal(66)Met, COMTVal(158/108)Met, MAOA and DRD4 tandem repeat and 5HTT-LPR polymorphisms) made specific contributions to emotion, thinking and self regulatory functions, which also varied according to age.     

The effects of passive exercise therapy initiated prior to or after the development of hyperreflexia following spinal transection

Hyperreflexia develops after spinal cord injury (SCI) in the human and in the spinal cord transected animal, and can be measured by the loss of low frequency-dependent depression of the H-reflex. Previous studies demonstrated normalization of low frequency-dependent depression of the H-reflex using passive exercise when initiated prior to the development of hyperreflexia. We examined the effects of passive exercise prior to compared to after the development of hyperreflexia in the transected rat. Adult female rats underwent complete transection (Tx) at T10. Frequency-dependence of the H-reflex was tested following passive exercise for 30 days, initiated prior to hyperreflexia in one group compared to initiation after hyperreflexia became established, and compared to intact and untreated Tx groups. An additional Tx group completed 60 days of exercise initiated after hyperreflexia was established. Lumbar enlargement tissue was harvested for western blot to compare Connexin-36 protein levels in control vs Tx animals vs Tx animals that were passively exercised. No differences in whole tissue were evident, although regional differences may still be present in Connexin-36 levels. Statistically significant decreases in low frequency-dependent depression of the H-reflex were observed following 30 days of exercise initiated prior to the onset of hyperreflexia, and also after 60 days of exercise when initiated after hyperreflexia had been established, compared with Tx only animals. We concluded that modulation of spinal circuitry by passive exercise took place when initiated before and after the onset of hyperreflexia, but different durations of exercise were required.     

Chronic post-traumatic headache after head injury in children and adolescents

This was a prospective, observational study of children aged 3 to 15 years admitted to hospital with head injury (HI). Demographic data and information on the nature of the HI, and history of premorbid headache were collected. A structured telephone questionnaire was used to interview parents and children 2 months after injury and at 4-monthly intervals for up to 3 years, if headache was reported. One hundred and ninety children were admitted with HI. Data were available on 117 children (81 males, 36 females; mean age 8y 5mo [SD 3y 1mo]). HI was minor in 93 patients and significant in the rest. Minor HI was defined as a closed injury, no loss of consciousness, and a Glasgow Coma Score (GCS) of 13 to 15. Significant HI was associated with loss of consciousness for >30 minutes, GCS of <13, and post-traumatic amnesia for >48 hours. Eight children (five males, three females; mean age 10y 7mo [SD 2y]) reported chronic post-traumatic headache (CPTH). Five children had episodic tension-type headache and three had migraine with or without aura. Headache resolved over 3 to 27 months in all except one child who was lost to follow-up. Premorbid headache in three children transformed in frequency and type following HI. These patients were excluded from the study. CPTH is common after minor and significant HI. It has the clinical features of tension-type headache and migraine and has a good prognosis.     

Longitudinal variations and predictors of increased perceived impact of multiple sclerosis, a two-year study

OBJECTIVE: To explore variations and the capacity of selected factors - contextual factors, disease-related characteristics, cognition, fatigue, mood and time - to predict an increase in the perceived physical and psychological impact of multiple sclerosis (MS) over a two-year period. METHODS: At an MS specialist clinic, 219 outpatients were included in the study and data were collected every 6 months. The Multiple Sclerosis Impact Scale was used for assessment of the perceived physical and psychological impact of MS. For statistical analysis of changes in impact during the study period, Friedman ANOVA was used and predictors of increased impact were explored with Generalized Estimating Equations employing proportional odds models. RESULTS: The majority had changes in perceived physical impact of established important magnitude and the psychological impact varied significantly. A period of more than 10 years since diagnosis, cognitive disability, fatigue and signs of depression were independent predictors of increase in physical impact. Weak or moderate sense of coherence, absence of immunomodulatory treatment, fatigue and signs of depression were independent predictors of increase in psychological impact. CONCLUSION: The fluctuation in perceived impact should be taken into account in clinical decision-making and when designing studies and interpreting the results. This study identifies the predictors of increased perceived physical and psychological impact that health-related services should pay special attention to, in order to provide interventions aimed at minimizing the perceived impact of MS.     

Body mass index and prognostic markers at radical prostatectomy

OBJECTIVE: Obesity is increasing rapidly in Western countries. Approximately 40% of adult Danes are overweight and approximately 15% of these are obese. Epidemiological studies of obesity in relation to prostate cancer have provided conflicting results. Therefore, we examined correlations between body mass index (BMI) and clinicopathological prognostic markers, biochemical recurrence and operative morbidity in patients who had undergone radical prostatectomy. MATERIAL AND METHODS: The sample consisted of 293 Danish men treated with radical prostatectomy between 2000 and 2005 at Aarhus University Hospital. BMI was calculated as an indicator of obesity. Prospectively collected clinical and pathologic data from this population were used. RESULTS: The median BMI value was 26.2 kg/m(2) (range 19.6-41.7 kg/m(2)), which is slightly above the upper limit of normal. Currently accepted prognostic markers, such as prostate-specific antigen level, Gleason score and pT class, showed no statistically significant correlations with BMI. Patients with biochemical recurrence were evenly distributed among four different BMI quartiles and there was no difference in the length of hospitalization, indicating no differences in pre- or postoperative morbidity. Computations were repeated using only patients with the lowest (19.6-21.3 kg/m(2)) and highest (34.2-41.7 kg/m(2)) BMI values but statistically significant correlations were still not found. CONCLUSIONS: Several American studies have shown that obesity can lead to prostate cancer becoming more aggressive. The results of the present study involving a Danish prostate cancer population do not substantiate this or suggest any connection between BMI and operative morbidity. A possible explanation is that Danish obesity problems are not yet as severe as those in the USA.     

Post-marketing safety monitoring of a new group B meningococcal vaccine in New Zealand, 2004-2006

New Zealand introduced a new outer membrane vesicle vaccine in 2004 to combat an epidemic of group B meningococcal disease. An Independent Safety Monitoring Board oversaw intensive safety monitoring, which included hospital surveillance, health professional reporting (passive and active) and mortality monitoring. With over three million doses administered to individuals aged under 20 years, the monitoring results provide consistent evidence supporting the vaccine's safety.     

From bacterial genomes to novel antibacterial agents: discovery, characterization, and antibacterial activity of compounds that bind to HI0065 (YjeE) from Haemophilus influenzae

As part of a fully integrated and comprehensive strategy to discover novel antibacterial agents, NMR- and mass spectrometry-based affinity selection screens were performed to identify compounds that bind to protein targets uniquely found in bacteria and encoded by genes essential for microbial viability. A biphenyl acid lead series emerged from an NMR-based screen with the Haemophilus influenzae protein HI0065, a member of a family of probable ATP-binding proteins found exclusively in eubacteria. The structure-activity relationships developed around the NMR-derived biphenyl acid lead were consistent with on-target antibacterial activity as the Staphylococcus aureus antibacterial activity of the series correlated extremely well with binding affinity to HI0065, while the correlation of binding affinity with B-cell cytotoxicity was relatively poor. Although further studies are needed to conclusively establish the mode of action of the biphenyl series, these compounds represent novel leads that can serve as the basis for the development of novel antibacterial agents that appear to work via an unprecedented mechanism of action. Overall, these results support the genomics-driven hypothesis that targeting bacterial essential gene products that are not present in eukaryotic cells can identify novel antibacterial agents.