ATP, the 31P Spectral Modulus, and Metabolism.

Adenosine triphosphate (ATP) has a high intracellular millimolar concentration (ca. 2.4 mM) throughout the phylogenetic spectrum of eukaryotes, archaea, and prokaryotes. In addition, the function of ATP as a hydrotrope in the prevention of protein aggregation and maintenance of protein solubilization is essential to cellular, tissue, and organ homeostasis. The 31P spectral modulus (PSM) is a measure of the health status of cell, tissue, and organ systems, as well as of ATP, and it is based on in vivo 31P nuclear magnetic resonance (31P NMR) spectra. The PSM is calculated by dividing the area of the 31P NMR integral curve representing the high-energy phosphates by that of the low-energy phosphates. Unlike the difficulties encountered in measuring organophosphates such as ATP or any other phosphorylated metabolites in a conventional 31P NMR spectrum or in processed tissue samples, in vivo PSM measurements are possible with NMR surface-coil technology. The PSM does not rely on the resolution of individual metabolite signals but uses the total area derived from each of the NMR integral curves of the above-described spectral regions. Calculation is based on a simple ratio of the high- and low-energy phosphate bands, which are conveniently arranged in the high- and low-field portions of the 31P NMR spectrum. In practice, there is essentially no signal overlap between these two regions, with the dividing point being ca. -3 δ. ATP is the principal contributor to the maintenance of an elevated PSM that is typically observed in healthy systems. The purpose of this study is to demonstrate that (1) in general, the higher the metabolic activity, the higher the 31P spectral modulus, and (2) the modulus calculation does not require highly resolved 31P spectral signals and thus can even be used with reduced signal-to-noise spectra such as those detected as a result of in vivo analyses or those that may be obtained during a clinical MRI examination. With increasing metabolic stress or maturation of metabolic disease in cells, tissues, or organ systems, the PSM index declines; alternatively, with decreasing stress or resolution of disease states, the PSM increases. The PSM can serve to monitor normal homeostasis as a diagnostic tool and may be used to monitor disease processes with and without interventional treatment.

Phospholipid analyses of rabbit ocular surface tissues.

The tissues of the integument covering the ocular surface comprise a mucus membrane functioning as a protective physical barrier and has the ability to mount a defensive inflammatory response. Since lipid metabolism has a role in both of these functions, we studied normal membrane phospholipids (PL) of the cornea and bulbar conjunctiva to (1) determine baseline PL profiles of these tissues, (2) compare and contrast these individual PL metabolite profiles as well as groups of metabolites, and (3) describe pathway-specific metabolic interrelations among these tissues. Corneal and conjunctival tissue samples were isolated from rabbit eyes (n = 30) and extracted with chloroform-methanol using a modified Folch procedure. 31P nuclear magnetic resonance spectroscopy was used to qualitatively and quantitatively measure tissue PL profiles. The cornea and conjunctiva, respectively, have the following PL composition (mole % of total detected phospholipid): phosphatidylglycerol (PG) -, 0.4; lysophosphatidylethanolamine 1.2, -; phosphatidic acid -, 0.4; diPG (cardiolipin) 2.1, 3.5; unknown PL at the chemical shift of 0.13 δ 1.5, 0.9; ethanolamine plasmalogen 11.2, 13.0; phosphatidylethanolamine 11.5, 12.8; phosphatidylserine 8.9, 10.1; sphingomyelin 10.2, 10.7; lysophosphatidylcholine 0.9, 1.4; phosphatidylinositol 5.3, 5.3; phosphatidylcholine (PC) plasmalogen or alkylacylPC 2.2, 1.9; PC 45.1, 40.0. In addition, 28 PL metabolic indices were calculated from these data, which permitted pathway-specific lipid analyses. This study (1) establishes PL profiles of the two ocular tissues of the integument that cover the surface of the eye, (2) compares and contrasts indices comprised of ratios and combinations of PL, and (3) describes pathway-specific metabolic interrelations among these tissues to serve as baselines for studies involving the distribution of tissue phospholipids.

Adenosine Triphosphate (ATP) and Protein Aggregation in Age-Related Vision-Threatening Ocular Diseases.

Protein aggregation is the etiopathogenesis of the three most profound vision-threatening eye diseases: age-related cataract, presbyopia, and age-related macular degeneration. This perspective organizes known information on ATP and protein aggregation with a fundamental unrecognized function of ATP. With recognition that maintenance of protein solubility is related to the high intracellular concentration of ATP in cells, tissues, and organs, we hypothesize that (1) ATP serves a critical molecular function for organismal homeostasis of proteins and (2) the hydrotropic feature of ATP prevents pathological protein aggregation while assisting in the maintenance of protein solubility and cellular, tissue, and organismal function. As such, the metabolite ATP plays an extraordinarily important role in the prevention of protein aggregation in the leading causes of vision loss or blindness worldwide.

Cutaneous Permeation of a Percutaneously Applied Glucocorticoid Using Plant-Based Anionic Phospholipids in Hydrogenated Vegetable Oil: A Preliminary Study.

Purpose: It is important that, when corticosteroids are used therapeutically, concentrations be reduced as much as possible to mitigate potential adverse events and side effects. This preliminary study compares the permeation for the delivery of a corticosteroid in a 1% hydrocortisone-supplemented topical cream containing anionic polar phospholipids (APP) in hydrogenated vegetable oil (triglyceride) versus a market-leading 1% hydrocortisone in a mineral hydrocarbon-based skin cream. Methods: Using the Franz diffusion cell method with cadaveric skin, the permeation of a 1% hydrocortisone-supplemented cream containing APP (test preparation) was compared with a commercially available 1% hydrocortisone cream (control preparation). The principal APP in the test preparation were phosphatidylinositol, phosphatidylserine and phosphatidylglycerol. Permeation was determined at 4 and 8 h time intervals. Results: The permeation values for the 1% hydrocortisone supplemental APP cream (test preparation) were comparatively very high 1180 ng/cm2 at 4 h and 2173 ng/cm2 at 8 h, in contrast to the 1% hydrocortisone cream (control preparation) values of 13 ng/cm2 at 4 h and 98 ng/cm2 at 8 h. Permeation of skin cream increased significantly from 0 to 4 and 8 h, when comparing the APP test preparation with the control preparation (p < 0.001). This translates, respectively, into the 90-fold greater and a 20-fold greater penetration of the test preparation APP cream over the 1% hydrocortisone cream at 4 h and 8 h time points. Conclusions: This preliminary study demonstrates the enhanced permeation of 1% hydrocortisone when applied topically to the skin in an APP skin cream vehicle. This enhanced permeation suggests the potential use of APP technology to deliver therapeutically effective hydrocortisone treatment to the skin at markedly reduced concentrations of steroid. As such, APP technology may offer an improved approach to the treatment of dermatoses associated with inflammatory diseases and conditions requiring prolonged topical corticosteroid therapy.

Phosphatic metabolism in dark- and light-adapted rat retinas.

This study defines retinal phosphatic metabolites and their adjustment to illumination in rat retinas under conditions that preserve retinal function. Metabolic data are measured using high-performance liquid chromatography (HPLC) and 31P nuclear magnetic resonance (31P NMR) spectroscopy after 10 min of light exposure in vivo compared with retinas from dark-adapted rats. Multiple high-energy and low-energy phosphatic metabolites of intermediary metabolism were quantified. The concentration of the high-energy phosphate adenosine triphosphate (ATP) remained unchanged from dark- to light-adaptation. Under the same conditions the concentrations of the high-energy phosphates guanosine triphosphate (GTP) and creatine phosphate increased, whereas the inorganic phosphate decreased. Comparing dark-adapted controls with retinas light-adapted either in vitro or in vivo, the evidence is consistent with a light-dependent increase in GTP and a decrease in cyclic guanosine monophosphate. Although cyclic adenosine monophosphate (cAMP) levels were lower in retinas light-adapted in vivo than in the dark-adapted controls, this did not seem to be an effect of light, as cAMP levels decreased similarly after 10 min incubation in dark or light in parallel with recovery of ATP/adenosine diphosphate ratios. This study: (1) reports on retinal metabolic changes with adjustment in illumination, (2) provides baseline measurements of retinal phosphatic metabolites in whole retinas, and (3) reports on the validity of chromatographic and spectroscopic methods used for studying retinal metabolism establishing a high correlation among measurements made using HPLC and 31P NMR.

Implications of a Diabetic Foot Xerosis Treatment With an Emulsion Containing the Plant-Based Anionic Phospholipids.

PURPOSE: This study compares and contrasts a skin cream containing plant-based anionic polar phospholipid (APP) technology with a mineral oil hydrocarbon (petrolatum)-based (MHB) skin cream technology in the treatment of skin xerosis (dryness) in diabetic feet. Skin cream with APP technology promotes phospholipid absorption, reparation of intercellular lamellae, and organization of water promoting hydration; whereas skin cream with mineral hydrocarbon-based (MHB) technology principally covers skin, preventing dehydration. METHODS: Subjects (n = 54) with diagnoses of diabetes mellitus and foot skin dryness were studied using a multicenter, double-blind, masked-study design. An emulsion cream containing 0.05% APP in triglycerides (APP preparation) was compared to MHB skin cream, Eucerin® (MHB preparation) applied topically to skin of the feet. Graded measurements were recorded on 4 efficacy variables including dryness, erythema, fissures, and itching and neurovascular assessments. Implications of the plant-based and mineral-based skin creams in the context of skin xerosis are contrasted. RESULTS: APP and MHB preparations were similar in effectiveness and safety. There was no significant difference among any of the 4 efficacy variables (P < .5) including neurovascular measurements. The APP preparation is absorbed into the skin, whereas the MHB skin cream leaves detectable residues after each application. CONCLUSION: Although the APP and MHB preparations were not significantly different in effectiveness and safety, distinctively, application of the APP skin cream preparation absorbed into the skin leaving no discernible residue in contrast to the MHB preparation leaving residues potentiating textile damage. Both of these technologies function in the hydration of skin; however, they differ in their modes of action. The plant-based APP preparation functions actively by phospholipid and triglyceride absorption, reparation of skin lamellae, and in the consequent delivery and organization of waters of hydration in skin. The MHB preparation functions passively, hydrating the skin it covers by sealing the skin against dehydration.

Intracellular ATP Concentration and Implication for Cellular Evolution.

Crystalline lens and striated muscle exist at opposite ends of the metabolic spectrum. Lens is a metabolically quiescent tissue, whereas striated muscle is a mechanically dynamic tissue with high-energy requirements, yet both tissues contain millimolar levels of ATP (>2.3 mM), far exceeding their underlying metabolic needs. We explored intracellular concentrations of ATP across multiple cells, tissues, species, and domains to provide context for interpreting lens/striated muscle data. Our database revealed that high intracellular ATP concentrations are ubiquitous across diverse life forms including species existing from the Precambrian Era, suggesting an ancient highly conserved role for ATP, independent of its widely accepted view as primarily "metabolic currency". Our findings reinforce suggestions that the primordial function of ATP was non-metabolic in nature, serving instead to prevent protein aggregation.

Did Cyclic Metaphosphates Have a Role in the Origin of Life?

How life began still eludes science life, the initial progenote in the context presented herein, being a chemical aggregate of primordial inorganic and organic molecules capable of self-replication and evolution into ever increasingly complex forms and functions.Presented is a hypothesis that a mineral scaffold generated by geological processes and containing polymerized phosphate units was present in primordial seas that provided the initiating factor responsible for the sequestration and organization of primordial life's constituents. Unlike previous hypotheses proposing phosphates as the essential initiating factor, the key phosphate described here is not a polynucleotide or just any condensed phosphate but a large (in the range of at least 1 kilo-phosphate subunits), water soluble, cyclic metaphosphate, which is a closed loop chain of polymerized inorganic phosphate residues containing only phosphate middle groups. The chain forms an intrinsic 4-phosphate helix analogous to its structure in Na Kurrol's salt, and as with DNA, very large metaphosphates may fold into hairpin structures. Using a Holliday-junction-like scrambling mechanism, also analogous to DNA, rings may be manipulated (increased, decreased, exchanged) easily with little to no need for additional energy, the reaction being essentially an isomerization.A literature review is presented describing findings that support the above hypothesis. Reviewed is condensed phosphate inorganic chemistry including its geological origins, biological occurrence, enzymes and their genetics through eukaryotes, polyphosphate functions, circular polynucleotides and the role of the Holliday junction, previous biogenesis hypotheses, and an Eoarchean Era timeline.

Corneal absorption of glycerylphosphorylcholine.

This study documents the absorption of glycerylphosphorylcholine (GPC) into corneas ex vivo. Corneas in quadruplicate were incubated in preservation medium containing 30 mM GPC, which is used as a reference marker. The GPC reference marker is used to calibrate 31P nuclear magnetic resonance (NMR) spectral chemical-shift positions for identification of phosphatic metabolites and to calculate intracorneal pH in intact tissues ex vivo. Following baseline NMR ex vivo analysis, corneas were stored in eye bank chambers in preservation medium containing 30 mM GPC at 4 °C overnight for 8 h. After returning to room temperature, NMR analysis was repeated on the same corneas in fresh GPC-free preservation medium. NMR analysis also was performed on the 30 mM GPC preservation medium alone from the eye bank chambers for detection of the GPC signal. The elevated GPC signal unexpectedly persisted in corneas incubated at 4 °C overnight even though GPC was not present in the fresh GPC-free preservation medium. In fact, the concentration of GPC in the intact cornea was many times higher than that found in the cornea endogenously. The levels of phosphatic metabolites and the energy modulus, after subtracting the spectral contribution of the 30 mM exogenous GPC, as well as the intracorneal pH remained unchanged from pre-refrigeration analyses. Corneas also retained transparency through the time-course of this study irrespective of temperature or change in temperature. The GPC signal in the NMR analysis of the preservation medium from the eye bank chambers was nearly undetectable. GPC was unexpectedly absorbed into the corneal tissue without detectable metabolic or physical toxicity. The intracorneal uptake of GPC at reduced temperatures parallels the increase in GPC that occurs naturally in muscle tissue in animals during wintering periods and the very high concentration of GPC in sperm, a cryogenically compatible cell, suggestive of a potential role for GPC in cryopreservation.

Hydrotropic function of ATP in the crystalline lens.

The hypothesis proposed herein is presented to explain the unexpectedly high concentration of ATP and provide evidence to support its hydrotropic function in the crystalline lens determined using 31P NMR. The lens, historically considered to be a metabolically quiescent organ, has the requisite machinery to synthesize ATP, such that the homeostatic level is maintained at about 3 mM. This relatively high concentration of ATP has been found to be consistent among multiple mammalian species including humans. This millimolar quantity is many times greater than the micromolar amounts required for the other known functions of ATP. The recent postulation that ATP at millimolar concentrations functions as a hydrotrope in various cell/tissue homogenates preventing protein aggregation coupled with observations presented herein, provide support for extending the hypothesis that ATP functions as a hydrotrope not only in homogenates but in an intact functioning organ, the crystalline lens. Concentrations of ATP of this magnitude are hypothesized to be required to maintain protein solubility and effectively prevent protein aggregation. This concept is important considering protein aggregation is the etiology for age-related cataractogenesis. ATP is a common ubiquitous intracellular molecule possessing the requisite hydrotropic properties for maintaining intracellular proteins in a fluid, non-aggregated state. It is proposed that the amphiphilic ATP molecule shields the hydrophobic regions on intralenticular fiber cell protein molecules and provides a hydrophilic interfacial surface comprised of the ATP negatively charged triphosphate side chain. Evidence is presented that this side chain is exposed to and has been reported to organize intracellular interstitial water to form an interfacial rheologically dynamic water layer. Such organization of water is substantiated with the effect of deuterium oxide (heavy water) on ATP line widths of the side chain phosphates measured ex vivo by 31P NMR. A novel model is presented to propose how this water layer separates adjacent lens fiber cell proteins, keeping them from aggregating. This hypothesis proposes that ATP can prevent protein aggregation in normal intact lenses, and with declining concentrations can be related to the disease process in age-related cataractogenesis, an affliction that affects every older human being.

Corneal Cryopreservation Using Glycerylphosphorylcholine-Enriched Medium.

PURPOSE: To determine the effects of prolonged cryopreservation at subzero-degree temperatures on corneal transparency and histology after treatment with preservation medium containing the phosphodiester glycerylphosphorylcholine (GPC). METHODS: Rabbit corneas (n = 30) were immersed for 3 hours in K-Sol preservation medium containing 30 mM GPC. Three groups with 6 corneas each were refrigerated at -8°C for 2 weeks and liquid nitrogen temperature for 2 and 6 weeks, respectively. Two groups with 6 corneas each immersed in K-Sol preservation medium only were refrigerated at -8°C for 2 weeks and liquid nitrogen temperature for 6 weeks, respectively. Postthawing corneal transparency was measured on a grading scale after which corneas were prepared for and analyzed by light and transmission electron microscopy. RESULTS: All 3 groups of corneas preserved with GPC maintained a greater degree of corneal transparency compared with corneas preserved without GPC. The number of corneas retaining epithelial and endothelial layers increased in all groups where corneas were preserved in medium containing GPC, in contrast to corneas preserved in medium without GPC. Cytoplasmic vacuolization or nuclear damage was greater in corneas preserved without GPC. Similar findings were found in corneas stored at -8°C and liquid nitrogen temperatures. CONCLUSIONS: This study demonstrates a cryoprotective effect of corneas preserved in K-Sol containing the phosphodiester GPC at subzero-degree temperatures. In corneas immersed in preservation medium containing GPC, a higher degree of transparency is maintained and a lesser degree of histopathologic changes is observed with storage at both -8°C and in liquid nitrogen.

The effect of an alternative medical procedure upon low-frequency oscillations in cutaneous blood flow velocity.

OBJECTIVE: Compression of the fourth ventricle (CV-4) is a manual, noninvasive procedure that reportedly affects the cranial rhythmic impulse, a phenomenon recognized by practitioners of cranial manipulation, that is concomitant with low-frequency Traube-Hering (TH) oscillations in blood flow velocity. This study examines the CV-4 and its effect upon blood flow velocity. METHODS: Human subjects were paired with 28 individual physicians for application of the CV-4, and the duration of the application was recorded. Flowmetry records tracking the course of the procedure were obtained, 20 of which were useable for intergroup comparisons. Segments of these records (control, treatment, response) were Fourier-transformed; the Fourier-transformed spectra were subtracted from one another and the resultant difference-spectra compared. RESULTS: The mean CV-4 procedure length was 4.43 +/- 2.22 minutes. The mean frequency of the TH waveform visible in the blood flowmetry record was 7.10 +/- 2.07 cpm. The CV-4 procedure specifically affected the low-frequency oscillations in blood flow velocity. After application, the amplitude of the TH, 0.10 Hz, frequency wave increased (relative area units: control minus treatment [0.08010 units) compared with control minus response [-0.03358 units]; P = .011). CONCLUSIONS: This study showed that CV-4 has an effect on the TH frequency component of blood flow velocity. The practitioners of cranial manipulation who participated in this study affected their subjects in a quantifiable manner with the application of the CV-4 procedure.

Recording the rate of the cranial rhythmic impulse.

The rate of the cranial rhythmic impulse can be obtained by both palpation and instrumentation. However, the literature has reported higher rates obtained by instrumentation compared with palpation. The cranial rhythmic impulse has been demonstrated to be synchronous with the Traube-Hering oscillation, measured in blood flow velocity. The current study demonstrates that physicians tend to palpate the cranial rhythmic impulse and Traube-Hering oscillation in a 1:2 ratio. This finding provides an explanation for the difference between palpated and instrumentally recorded rates for the cranial rhythmic impulse.

Palpatory diagnosis of plagiocephaly.

INTRODUCTION: The term plagiocephaly, from the Greek plagios (oblique) and kephalê (head), means distortion of the head, and refers clinically to cranial asymmetry. Cranial Osteopathy, since it was first proposed, has focussed upon the diagnosis and treatment of birth trauma and cranial asymmetries, and consequently specific therapy for plagiocephalic deformities has been described. Osteopathic manipulation also has been proposed as a treatment for torticollis, a condition associated with plagiocephaly. For these reasons, we decided to look at the mechanics of the occipital bone and the adjacent atlas and bones of the cranial base, in relation to functional plagiocephaly. METHODS: The records of 649 children seen in an osteopathic practice in Lyon, France, were reviewed retrospectively, in compliance with the legal requirements of the Commission Nationale de l'Informatique et des Libertés (CRIL) and the Helsinki accord, for gender, age at presentation, birth history, obstetrical data (breech presentation, vacuum extraction, forceps delivery or Caesarean section), presenting complaint, side of posterior plagiocephaly, side of frontal plagiocephaly, torticollis, motion pattern of the occipital bone upon the atlas, and motion pattern of the spheno-occipital synchondrosis. RESULTS: We found significant correlations between plagiocephaly (right/left) and primipara (P=0.024), use of forceps (P=0.055) and extractor suction (P=0.055). Correlations were also found between flattening of the occiput (right/left) and lateral strain of the spheno-occipital synchondrosis (P=0.002) and between plagiocephaly (right/left) and occipito-atlantal motion (P=0.000). CONCLUSION: We found a significant correlation between the lateral strain pattern of the spheno-occipital synchondrosis and plagiocephaly and between rotational dysfunction of the occiput upon the atlas and the side of posterior plagiocephaly. We suggest that thorough neonatal osteopathic examination can identify individuals predisposed to develop posterior plagiocephaly.

The effect of two novel lubricant eye drops on tear film lipid layer thickness in subjects with dry eye symptoms.

PURPOSE: Because the lipid layer of the tear film is recognized as a critical component in dry eye disease, this study was designed to determine if a single eye drop of either Soothe or Systane produces a significant increase in lipid layer thickness (LLT) for subjects reporting symptoms indicative of dry eyes. METHODS: A double-blind, internally paired study was performed. A custom-built lipid layer interferometer, enabling characterization of lipid layer interference patterns, was used to quantify baseline LLT (OU) of eligible subjects. Inclusion criteria included: 1) presence of dry eye symptoms and 2) baseline LLT < or =75 nm. Subjects (n = 40) received a single eye drop of Soothe in one eye and a single eye drop of Systane in the contralateral eye. After the instillation of each test drop, LLT was reanalyzed for all subjects. RESULTS: The mean +/- standard error baseline LLT pre-eye drop instillation was 60.0 +/- 1.8 nm for eyes treated with Soothe and 61.5 +/- 1.8 nm for eyes treated with Systane. These means were not significantly different (p > 0.5). The mean LLT for eyes treated with Soothe increased to 124.4 +/- 4.9 nm (p < 0.0001). The mean LLT for eyes treated with Systane increased to 71.3 +/- 2.6 nm (p < 0.0001). The LLT increase from Soothe was significantly greater than that from Systane (p < 0.0001). CONCLUSIONS: In subjects with symptoms indicative of dry eye states and LLT < or =75 nm, one eye drop of Soothe more than doubled LLT, a 107% mean increase, whereas Systane increased LLT by 16%.

Outpatient Osteopathic SOAP Note Form: preliminary results in osteopathic outcomes-based research.

One of the persistent challenges facing the osteopathic medical profession has been the lack of a reliable, easy-to-use, validated system for recording, collecting, and evaluating clinical findings in a format that is suitable for long-term data collection. As a result of the recent emphasis on outcomes-based research in the field of medicine, the creation and use of a standardized tool for the osteopathic profession has been pursued with increased urgency. In this study, the authors used participant-completed and previously validated Outpatient Osteopathic SOAP (Subjective, Objective, Assessment, Plan) Note Forms (SNFs) and Outpatient Osteopathic SOAP (Subjective, Objective, Assessment, Plan) Note--Follow-up Forms to obtain answers to 17 outcomes-based questions that the profession must address to meet the new challenges and demands of outcomes-based research. A consortium of 10 osteopathic physicians and 196 osteopathic residents and undergraduate fellows submitted a total of 3908 patient SNFs for analysis. Answers to these 17 questions were computed using appropriate statistical determinants (eg, frequencies, correlations). Retrospective analysis indicated that, in addition to the outcomes addressed in this study, use of the SNF could be extended to the following functions: pre- and postdoctoral tracking, outcomes research into the efficacy of osteopathic intervention, medical science research, autonomic correlation with disease entities, etiology of musculoskeletal dysfunction, billing information, and internal comparison studies between osteopathic physicians. A long-term goal of the SNF project is to create an electronic national database for osteopathic outcomes-based research.

Osteopathic manipulative treatment of somatic dysfunction among patients in the family practice clinic setting: a retrospective analysis.

CONTEXT: Relatively little has been published about contemporary use of osteopathic manipulative treatment (OMT) in family practice. OBJECTIVE: To provide an "epidemiology" of somatic dysfunction, assessing prevalence and severity of somatic dysfunction encountered in the family practice setting, also characterizing physician use of OMT. DESIGN: Retrospective analysis of Outpatient Osteopathic SOAP Note Form data collected in 1998 and 1999 by 20 osteopathic medical trainee-investigators under the supervision of seven site-based osteopathic physicians. SETTING: Three university-based, osteopathic family practice clinics. RESULTS: The authors analyzed records for 1331 patient encounters and 424 adult patients. The mean (SD) age of patients was 56.9 years (16.2 years), and 71% were women. The median number of days between repeat encounters was 29 days. Somatic dysfunction was diagnosed in 418 (31%) patient encounters, affecting a total of 1199 anatomic regions (2.9+/-1.2 anatomic regions per patient). Investigators used OMT in 335 (25%) patient encounters to treat a total of 952 anatomic regions (2.8+/-1.2 anatomic regions per patient). For women, the odds ratio for receiving OMT was 1.4 (95% confidence interval [CI], 1.0-2.2); for patients using analgesics, anti-inflammatory agents, or muscle relaxants, the odds ratio was 2.2 (95% CI, 1.2-4.1). Immediately after OMT, investigators reported that patients' somatic dysfunction resolved or improved in a total of 747 (96%) anatomic regions and remained unchanged in 32 (4%) anatomic regions (P<.001). The authors used cluster analysis to classify anatomic regions by prevalence and severity of somatic dysfunction. CONCLUSION: Somatic dysfunction was diagnosed in almost one-third of patient encounters. In one-quarter of patient encounters, investigators used OMT.

Outpatient Osteopathic Single Organ System Musculoskeletal Exam Form series: validation of the Outpatient Osteopathic SOS Musculoskeletal Exam Form, a new standardized medical record.

The authors validate the Outpatient Osteopathic SOS (Single Organ System) Musculoskeletal Exam Form (SOS MSEF), a 1-page form contained within the 4-page Outpatient Osteopathic Single Organ System Musculoskeletal Exam Form Series (SOS-FS). Handwritten physician progress notes (PPNs) in the medical record (considered to be the "gold standard" for clinical records) were compared with information placed on the SOS MSEF for the same patient encounter. Data recorded by 14 trained and certified investigators on the standardized SOS MSEF-which was designed for use with the previously validated Outpatient Osteopathic SOAP (Subjective, Objective, Assessment, Plan) Note Form (SNF)-was compared with data recorded by the same investigators in PPNs. The authors compared the accuracy and efficiency of physicians recording musculoskeletal information in these two formats for 165 patient encounters. Descriptive statistics and t tests were used to compare data recorded after patient encounters. Ninety-seven variables input from the PPNs or SOS MSEFs were significantly different at the P < or = .05 level, whereas 38 variables were not. Insufficient data was recorded for a determination of significance in 3 variables. For 121 variables, more data were recorded using the SOS MSEFs than PPNs; for 84 variables, the amount of data recorded exceeded twice that recorded using PPNs. For 10 variables, more data were recorded in PPNs; however, these differences were not significant. The authors conclude that the SOS MSEF is superior to PPNs for recording patient-encounter data in the osteopathic care setting. Moreover, they argue that the use of the validated SOS MSEF nationwide would ensure that osteopathic physicians would be recording data in a similar manner for uniform insurance claim coding, easy tracking of physicians-in-training and patient outcomes, and data collection for future research.

Outpatient osteopathic single organ system musculoskeletal exam form: training and certification.

The Outpatient Osteopathic Single Organ System Musculoskeletal Exam Form (SOS form) is a standardized examination data form. A standardized form is necessary to ensure that essential quality data are collected during osteopathic studies and that each submitted form is completed adequately and uniformly. Use of the standardized form permits reliable statistical computations from the collected data. The training process for the SOS form incorporated the following elements: (1) training investigators to use the form; (2) having trainees transcribe three clinical case examples onto SOS forms; (3) comparing each transcribed clinical case to a prepared key; (4) evaluating the trainees' work for accuracy; and (5) statistically evaluating the trainees' records for intraexaminer and interexaminer reliability. The success or failure of trainees to receive certification in their training process involved evaluating their ability to accurately and appropriately record data collected from three case examples. These cases were designed to evaluate recording accuracy and intraexaminer and interexaminer reliability. All trainees scored 80% or better for accuracy, and their work had good intraexaminer and interexaminer reliability. As a result, all trainees were awarded a numbered certificate for successful completion of the training process. Having a pool of well-trained, certified investigators available and ready to participate in the gathering of data through the use of the SOS form ensures that necessary data are collected and that the resulting databases are unified. It will also facilitate comparisons and statistical analysis of osteopathic research projects. Standardized forms and certified investigators will improve the quality of osteopathic research throughout the profession.

The effect of cranial manipulation on the Traube-Hering-Mayer oscillation as measured by laser-Doppler flowmetry.

CONTEXT: A correlation has been established between the Traube-Hering-Mayer oscillation in blood-flow velocity, measured by laser-Doppler flowmetry, and the cranial rhythmic impulse. OBJECTIVE: To determine the effect of cranial manipulation on the Traube-Hering-Mayer oscillation. DESIGN: Of 23 participants, 13 received a sham treatment and 10 received cranial manipulation. SETTING: Osteopathic Manipulative Medicine Department, Midwestern University, Downers Grove, Ill. PARTICIPANTS: Healthy adult subjects of both sexes participated (N = 23). INTERVENTION: A laser-Dopper flowmetry probe was placed on the left earlobe of each subject to obtain a 5-min baseline blood-flow velocity record. Cranial manipulation, consisting of equilibration of the global cranial motion pattern and the craniocervical junction, was then applied for 10 to 20 min; the sham treatment was palpation only. MAIN OUTCOME MEASURE: Immediately following the procedures, a 5-min posttreatment laser-Doppler recording was acquired. For each cranial treatment subject, the 4 major components of the blood-flow velocity record, the thermal (Mayer) signal, the baro (Traube-Hering) signal, the respiratory signal, and the cardiac signal, were analyzed, and the pretreatment and posttreatment data were compared. RESULTS: The 10 participants who received cranial treatment showed a thermal signal power decrease from 47.79 dB to 38.49 dB (P < .001) and the baro signal increased from 47.40dB to 51.30 dB (P < .021), while the respiratory and cardiac signals did not change significantly (P > .05 for both). CONCLUSION: Cranial manipulation affects the blood-flow velocity oscillation in its low-frequency Traube-Hering-Mayer components. Because these low-frequency oscillations are mediated through parasympathetic and sympathetic activity, it is concluded that cranial manipulation affects the autonomic nervous system.