Aviad Haramati

Paradoxes in Acupuncture Research: Strategies for Moving Forward

In November 2007, the Society for Acupuncture Research (SAR) held an international symposium to mark the 10th anniversary of the 1997 NIH Consensus Development Conference on Acupuncture. The symposium presentations revealed the considerable maturation of the field of acupuncture research, yet two provocative paradoxes emerged. First, a number of well-designed clinical trials have reported that true acupuncture is superior to usual care, but does not significantly outperform sham acupuncture, findings apparently at odds with traditional theories regarding acupuncture point specificity. Second, although many studies using animal and human experimental models have reported physiological effects that vary as a function of needling parameters (e.g., mode of stimulation) the extent to which these parameters influence therapeutic outcomes in clinical trials is unclear. This White Paper, collaboratively written by the SAR Board of Directors, identifies gaps in knowledge underlying the paradoxes and proposes strategies for their resolution through translational research. We recommend that acupuncture treatments should be studied (1) “top down” as multi-component “whole-system” interventions and (2) “bottom up” as mechanistic studies that focus on understanding how individual treatment components interact and translate into clinical and physiological outcomes. Such a strategy, incorporating considerations of efficacy, effectiveness and qualitative measures, will strengthen the evidence base for such complex interventions as acupuncture.

Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis.

Objective To evaluate whether acupuncture improves rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation. Design Systematic review and meta-analysis. Data sources Medline, Cochrane Central, Embase, Chinese Biomedical Database, hand searched abstracts, and reference lists. Review methods Eligible studies were randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth. Two reviewers independently agreed on eligibility; assessed methodological quality; and extracted outcome data. For all trials, investigators contributed additional data not included in the original publication (such as live births). Meta-analyses included all randomised patients. Data synthesis Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. There was little clinical heterogeneity. Trials with sham acupuncture and no adjuvant treatment as controls were pooled for the primary analysis. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Because we were unable to obtain outcome data on live births for three of the included trials, the pooled odds ratio for clinical pregnancy more accurately represents the true combined effect from these trials rather than the odds ratio for live birth. The results were robust to sensitivity analyses on study validity variables. A prespecified subgroup analysis restricted to the three trials with the higher rates of clinical pregnancy in the control group, however, suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77). Conclusions Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation.

Impaired Nitric Oxide–Mediated Renal Vasodilation in Rats With Experimental Heart Failure Role of Angiotensin II

BACKGROUND Congestive heart failure (CHF) is associated with a decrease in renal perfusion. Because endothelium-derived NO is important in the regulation of renal blood flow (RBF), we tested the hypothesis that an impairment in the NO system may contribute to the decrease in RBF in rats with experimental CHF. METHODS AND RESULTS Studies were performed in rats with experimental high-output CHF induced by aortocaval (AV) fistula and sham-operated controls. In controls, incremental doses of acetylcholine (ACh, 1 to 100 microg x kg(-1) x min(-1)) increased RBF and caused a dose-related decrease in renal vascular resistance (RVR). However, the increase in RBF and decrease in RVR were markedly attenuated in rats with CHF. Likewise, the effects of ACh on urinary sodium and cGMP excretion were also diminished in CHF rats, as was the renal vasodilatory effect of the NO donor S-nitroso-N-acetylpenicillamine (SNAP). These attenuated responses to endothelium-dependent and -independent renal vasodilators in CHF rats occurred despite a normal baseline and stimulated NO2+NO3 excretion and normal expression of renal endothelial NO synthase (eNOS), as determined by eNOS mRNA levels and immunoreactive protein. Infusion of the NO precursor L-arginine did not affect baseline RBF or the response to ACh in rats with CHF. However, administration of the nonpeptide angiotensin II receptor antagonist A81988 before ACh completely restored the renal vasodilatory response to ACh in CHF rats. CONCLUSIONS This study demonstrates that despite a significant attenuation in the NO-related renal vasodilatory responses, the integrity of the renal NO system is preserved in rats with chronic AV fistula. This impairment in NO-mediated renal vasodilation in experimental CHF appears to be related to increased activity of the renin-angiotensin system and may contribute further to the decrease in renal perfusion seen in CHF.

Stress Biomarkers in Medical Students Participating in a Mind Body Medicine Skills Program

Georgetown University School of Medicine offers an elective Mind-Body Medicine Skills (MBMS) course to medical students to promote self-care and self-awareness. Participating medical students reported better management of academic stress and well-being than non-participants. In this study, we sought to assess the stress-reducing effects of MBMS by measuring physiological changes in first-year medical students. Saliva samples were collected before (January, time 1 (T1)-pre-intervention) and upon completion of the course (May, time 2 (T2p)-post-intervention), as well as from non-participating medical students (May, time 2 (T2c)-control). The T2p and T2c collections coincided with the period of final examinations. Cortisol, dehydroepiandrosterone-sulfate (DHEA-S), testosterone and secretory immunoglobulin A (sIgA) were measured. The mean morning salivary cortisol at T2p was 97% of the mean at baseline T1 which was significantly lower than for T2c (2.4) (95% confidence interval (CI) 0.57–1.60, P =  .001); DHEA-S showed similar pattern as cortisol where the T2p levels were significantly lower than T2c (P <  .001) in both morning and evening collections. Testosterone ratio at T2p (0.85) was also lower than T2c (1.6) (95% CI 0.53–1.3, P =  .01). sIgA levels were not statistically different. On direct comparison, the T2c and T2p means were significantly different for all cortisol, DHEA-S and testosterone values. Participants maintained their hormonal balance within the normal range throughout the academic semester while the control group showed significantly increased levels, probably exacerbated by the end of the semester exam stress. To our knowledge, this is the first study to assess the physiologic benefits of a MBMS program in medical students.

The Insulin-Like Growth Factor Family of Peptides, Binding Proteins and Receptors: Their Potential Role in Tissue Regeneration

The insulin-like growth factors (IGF-I and IGF-II) are mitogenic pep tides that are structurally related to insulin (Figure 1). Until recently, these growth factors were thought to be produced exclusively by the liver and to act solely in an endocrine manner.1-3 According to the “somatomedin hypothesis,” the synthesis of IGF-I by the liver and its secretion are regulated by growth hormone (GH) and, following its release into the circulation, IGF-I reaches its target tissues where it induces growth and development, thereby mediating the effect of GH during the growth period.

Regulation of renal phosphate reabsorption during development: implications from a new model of growth hormone deficiency

It has been hypothesized that the high rate of renal phosphate (Pi) reabsorption in the immature animal is a consequence of the increased demand for Pi associated with the rapid rate of growth. Although growth hormone (GH) has been proposed to play a role in this process, investigations of the relationship between GH, growth and the renal Pi transport have been hampered by the lack of methods available to specifically alter circulating GH levels. This review summarizes the findings from recent studies using a newly developed peptidic antagonist to GH-releasing factor (GRF-AN) as a method of specifically inhibiting GH release. Systemic injection of GRF-AN was effective in suppressing the pulsatile release of GH, and in significantly attenuating the rate of growth, in both immature and adult rats. However, the inhibition of growth was associated with a reduction in net Pi retention only in immature rats, resulting in a doubling in the urinary excretion of Pi. GRF-AN treatment of immature rats lead to a decrease in the maximum tubular capacity to transport Pi-down to the level seen in adult rats. However, GRF-AN treatment did not alter renal Pi reabsorption in adult rats. We conclude that chronic administration of an antagonist to GRF in rats provides a new model of GH deficiency with which to study the interrelationships between growth, GH and other physiological systems. Furthermore, the findings suggest that the pulsatile release of GH, directly or indirectly, contributes to the high rate of renal Pi reabsorption in young, growing animals and may play a critical role in regulating Pi homeostasis during development.

Evidence for induction of a phosphate appetite in juvenile rats

This study examined whether dietary phosphate (Pi) restriction stimulates an appetite for Pi in the juvenile rat, which normally has a high metabolic Pi demand for growth. Juvenile Wistar rats were placed in individual cages with unrestricted access to tap water and a low (LPD, 0.02% Pi) or normal Pi diet (NPD, 0.6% Pi) for 7 days. On day 8, both groups of rats were given unlimited access to a solution of 0.3 M potassium phosphate water (PiH2O) for 8 additional days. Rats fed LPD consumed 70-100% more PiH2O then those rats fed NPD (P < 0.001). The increase in PiH2O intake resulted in a marked rise in the growth rate of rats fed LPD during days 8-15. A similar Pi intake was inducible after only 2 days of LPD and was associated with significant reductions in both plasma and cerebrospinal fluid (CSF) Pi levels; these levels remained low throughout Pi restriction, despite a significant PiH2O intake. Furthermore, the renal adaptation to enhance Pi reabsorption (TmPi) during Pi deprivation remained elevated despite enhanced PiH2O intake. Replenishment with a high-Pi diet rapidly quenched the PiH2O appetite and was associated with restoration of both plasma and CSF Pi levels. These findings suggest that an appetite for Pi can be induced in juvenile rats, perhaps through lowered plasma and CSF Pi levels. This behavioral response may serve as an additional mechanism to maintain an adequate supply of Pi necessary for growth and development of the animal.

The impact of mind-body medicine facilitation on affirming and enhancing professional identity in health care professions faculty.

Problem Georgetown University School of Medicine (GUSOM) offers medical students a course in mind–body medicine (MBM) that introduces them to tools that reduce stress and foster self-awareness. Previous studies reported decreases in students’ perceived stress and increases in mindfulness—changes that were associated with increased empathic concern and other elements of professional identity formation. However, no reports have described the impact of an MBM course on the facilitators themselves. Approach To explore whether MBM facilitation is associated with changes in professional identity, self-awareness, and/or perceived stress, 62 facilitators, trained by the GUSOM MBM program, were invited to complete two validated surveys: the Freiburg Mindfulness Inventory (FMI) and the Perceived Stress Scale (PSS). Forty-two participants also completed a six-item open-ended questionnaire addressing their experience in the context of their professional identity. Outcomes Facilitators’ scores were significantly lower on PSS and higher on FMI compared with normative controls (P < .05), and the two parameters were inversely correlated (−0.46, P < .01). Qualitative analysis revealed three main themes: (1) aspects of professional identity (with subthemes of communication; connections and community; empathy and active listening; and self-confidence); (2) self-care; and (3) mindful awareness. Next Steps Preliminary findings will be extended with larger studies that examine longitudinal quantitative assessment of communication, connection, and self-confidence outcomes in MBM facilitators, and the impact of MBM facilitation on burnout and resilience.

OA05.03. Impact of a mind-body medicine skills course on medical students’ perceived stress, mindfulness and elements of emotional intelligence

Purpose Most medical schools list self-awareness, self-care and personal growth as key educational competencies. Yet, studies have reported that traits such as altruism and empathy tend to decline throughout medical school training. To foster medical student self-awareness and mindfulness, which may improve their emotional intelligence (EI), Georgetown University School of Medicine (GUSOM) offers an experiential course to medical students in mind-body medicine skills. The purpose is to expose students to a variety of mind-body approaches (e.g., mindfulness meditation, autogenic training, guided imageries, movement, and writing exercises), as well as group sharing that involves listening generously and without judgment.

Morphometric analysis of atrial natriuretic peptide-containing granules in atriocytes of rats with experimental congestive heart failure.

The morphometric characteristics of atrial natriuretic peptide-containing granules were studied in atrial myoendocrine cells of rats with aorto-caval fistula, an experimental model of congestive heart failure. A total of 6680 granules of control and aorto-caval rats were analyzed by a computerized image analysis system that evaluated the number and sectioned surface area of granules and their subcellular location. Compared with control animals, rats with congestive heart failure displayed a slight increase in the number of peripheral granules, adjacent to the sarcolemma, but not centrally located in the Golgi areas. The mean sectioned surface area of granules in rats with congestive heart failure was about 50% of that in controls, both in the right and left atria. Rats with aortocaval fistula had a higher percent of small granules and lower percent of large granules compared with controls. The data demonstrate different morphometric characteristics in atrial natriuretic peptide-containing granules in atriocytes in rats with experimental congestive heart failure; this may reflect the enhanced synthesis and release of atrial natriuretic peptide in heart failure.