Management of chronic back pain is a challenge for physicians. Although standard treatments exert a modest effect, they are associated with narcotic addiction and serious side effects from nonsteroidal antiinflammatory agents. Moreover, neurotransmitter depletion from both the pain syndrome and therapy may contribute to a poor treatment outcome. Neurotransmitter deficiency may be related both to increased turnover rate and inadequate neurotransmitter precursors from the diet, particularly for essential and semi-essential amino acids. Theramine, an amino acid blend 68405-1 (AAB), is a physician-prescribed only medical food. It contains neurotransmitter precursors and systems for increasing production and preventing attenuation of neurotransmitters. A double-blind controlled study of AAB, low-dose ibuprofen, and the coadministration of the 2 agents were performed. The primary end points included the Roland Morris index and Oswestry disability scale. The cohort included 122 patients aged between 18 and 75 years. The patients were randomized to 1 of 3 groups: AAB alone, ibuprofen alone, and the coadministration of the 2 agents. In addition, C-reactive protein, interleukin 6, and plasma amino acid concentrations were measured at baseline and 28 days time points. After treatment, the Oswestry Disability Index worsened by 4.52% in the ibuprofen group, improved 41.91% in the AAB group, and improved 62.15% in the combination group. The Roland Morris Index worsened by 0.73% in the ibuprofen group, improved by 50.3% in the AAB group, and improved 63.1% in the combination group. C-reactive protein in the ibuprofen group increased by 60.1%, decreased by 47.1% in the AAB group, and decreased by 36% in the combination group. Similar changes were seen in interleukin 6. Arginine, serine, histidine, and tryptophan levels were substantially reduced before treatment in the chronic pain syndrome and increased toward normal during treatment. There was a direct correlation between improvement in amino acid concentration and treatment response. Treatment with amino acid precursors was associated with substantial improvement in chronic back pain, reduction in inflammation, and improvement in back pain correlated with increased amino acid precursors to neurotransmitters in blood.

The etiology and pathophysiology of posttraumatic stress disorder (PTSD) remains poorly understood. The nutritional deficiencies associated with the altered metabolic processes of PTSD have not previously been studied in detail. This pilot study measured the reduction in symptoms in 21 military veterans reporting moderate to severe symptoms associated with PTSD. Two amino acid-based medical foods specifically formulated with biogenic amines and other nutrients were administered to study subjects targeting specific neurotransmitter deficiencies resulting from altered metabolic activity associated with PTSD. This study included the Physician Checklist - Military (PCL-M), Short Form General Health Survey (SF-36), and Epworth Sleepiness Scale to measure the change in each subject's score after 30 days of administration. An average decrease of 17 points was seen in the PCL-M, indicating a reduction in PTSD symptoms (P<0.001). The mental health component of the SF-36 showed an average 57% increase in the subjects' mental health rating (P<0.001). The results of this initial study demonstrate that addressing the increased dietary requirements of PTSD can improve symptoms of the disease while eliminating significant side effects. A larger, double-blind, randomized, placebo-controlled trial is warranted.

BACKGROUND:The authors of prior small studies raised the hypothesis that symptoms in veterans of the 1991 Gulf War, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction, are due to cholinergic autonomic dysfunction.OBJECTIVE:To perform a confirmatory test of this prestated hypothesis in a larger, representative sample of Gulf War veterans.DESIGN:Nested case-control study.SETTING:Clinical and Translational Research Center, University of Texas Southwestern Medical Center, Dallas.PARTICIPANTS:Representative samples of Gulf War veterans meeting a validated case definition of Gulf War illness with 3 variants (called syndromes 1-3) and a control group, all selected randomly from the US Military Health Survey.MAIN OUTCOME MEASURES:Validated domain scales from the Autonomic Symptom Profile questionnaire, the Composite Autonomic Severity Score, and high-frequency heart rate variability from a 24-hour electrocardiogram.RESULTS:The Autonomic Symptom Profile scales were significantly elevated in all 3 syndrome groups (P< .001), primarily due to elevation of the orthostatic intolerance, secretomotor, upper gastrointestinal dysmotility, sleep dysfunction, urinary, and autonomic diarrhea symptom domains. The Composite Autonomic Severity Score was also higher in the 3 syndrome groups (P= .045), especially in syndrome 2, primarily due to a significant reduction in sudomotor function as measured by the Quantitative Sudomotor Axon Reflex Test, most significantly in the foot; the score was intermediate in the ankle and upper leg and was nonsignificant in the arm, indicating a peripheral nerve length-related deficit. The normal increase in high-frequency heart rate variability at night was absent or blunted in all 3 syndrome groups (P< .001).CONCLUSION:Autonomic symptoms are associated with objective, predominantly cholinergic autonomic deficits in the population of Gulf War veterans.

To study the safety and efficacy of a new medical food (Theramine) in the treatment of low back pain, we performed a 28-day double-blind randomized controlled trial in 129 patients. Back pain was present for at least 6 weeks and was not mild. Patients were randomly assigned to receive medical food alone (n = 43), naproxen alone (250 mg/d, n = 42), or both medical food and naproxen (n = 44). All patients were assessed by using Roland-Morris Disability Questionnaire, Oswestry Low Back Pain Scale, Visual Analog Scale Evaluation and laboratory analysis performed at baseline and at 28 days for assessing the safety and impact on inflammatory markers, which included complete blood counts, C-Reactive protein (CRP), and liver function (alkaline phosphatase, aspartate transaminase, and alanine transaminase). At baseline, there were no statistically significant differences in low back pain when assessed by Roland-Morris function or Oswestry assessments nor were there differences in the blood indices of inflammation. At day 28, both the medical food group and combined therapy group (medical food with naproxen) were statistically significantly superior to the naproxen-alone group (P < 0.05). The medical food and naproxen group showed functional improvement when compared to the naproxen-alone group. The naproxen-alone group showed significant elevations in CRP, alanine transaminase, and aspartate transaminase when compared with the other groups. Medical food alone or with naproxen showed no significant change in liver function tests or CRP, with medical food potentially mitigating the effects seen with naproxen alone. The medical food (Theramine) appeared to be effective in relieving back pain without causing any significant side effects and may provide a safe alternative to presently available therapies.

Sleep disorders are a common and poorly treated disease state. This double blind, four arm placebo-controlled, randomized trial compared (1) low dose trazodone, (2) Sentra PM, a neurotransmitter based medical food, (3) the joint administration of trazodone and the medical food Sentra PM and (4) placebo. There were 111 subjects studied in 12 independent sites. Subjects underwent baseline screening, informed consent and an initial sleep questionnaire. After 14 days subjects underwent a second evaluation by questionnaire. At baseline and Day 14 the subjects underwent 24 hour ECG recordings that were analyzed in the frequency domain of heart rate variability. The specific high frequency parasympathetic autonomic nervous system activity was analyzed. The primary endpoints were sleep latency and parasympathetic autonomic nervous system improvement in sleeping hours. The results showed improvement in sleep latency for the Sentra PM and combination of Sentra PM and trazodone (−41 and −56 minutes P < 0.001). There was an improvement in quality of sleep for the amino acid formulation Sentra PM and the combination (3.86 and 6.48 Likert units on a 10 point scale P < 0.001). There was an activation of circadian activity percent at night in the medical food and combination groups while there was no change in parasympathetic activity in either the placebo or trazodone group. These data indicate that Sentra PM can improve the quality of sleep, the response to trazodone as a sleep medication and parasympathetic autonomic nervous system activity.

Non-steroidal anti-inflammatory drugs are the leading cause of drug induced morbidity and mortality in the United States. Gastrointestinal hemorrhage is the most common concern, with hypertension, edema, renal complication and cardiovascular risk other considerations. These complications occur at higher rates in elderly patients. Strategies to reduce these risks have had mixed results. Theramine, a prescription only medical food, is used to treat pain and inflammation without risk of gastrointestinal or other side effects. We undertook a pharmacoeconomic analysis of Theramine versus NSAIDs in elderly patients; specifically examining the additional cost burden of the strategies to prevent GI side effects and complications. The higher acquisition costs for Theramine are offset by the reduction in side effects and need for testing and other protective medications in patients over the age of sixty-five taking NSAIDs. Theramine should be the preferred choice over NSAIDs in elderly patients.

Mutations of the sodium channel gene SCN5A can cause a variety of cardiac channelopathies. This study aimed to unmask the phenotype characteristics in delF1617 carriers and correlate them with functional expression results.

Infarct size was assessed quantitatively in 33 patients with acute myocardial infarction with a new technic based on analysis of serial serum creatine phosphokinase (CPK) changes to determine its relationship to prognosis. We have recently measured infarct size in the conscious dog with this method which takes into account CPK distribution space, fractional disappearance rate, proportion degraded in myocardium, and proportion released into the circulation, and we have validated the method by measurement of myocardial CPK depletion in the same animals. In the present study, CPK activity (determined spectrophotometrically) and isoenzyme profiles (assayed electrophoretically) were measured in patient serum samples obtained every 2 hours. Infarct size was estimated by mathematical analysis of serial CPK changes utilizing the method previously developed in the conscious dog model. CPK isoenzyme profiles demonstrated prominent anodal bands, absent from normal serum, indicating that enzyme elevations reflected CPK released from heart rather than skeletal muscle. In 19 class I-II survivors (New York Heart Association) estimated infarct size was 31 + 4 CPK-gram-equivalents (CPK-g-Eq). It was significantly larger (P < 0.01), 103 +14, in nine patients who died and in four class III or IV survivors (91 8). Estimation of cumulative infarct size differentiated patients with electrocardiographic changes and clinical sequelae from complications such as pericarditis from those patients with extension of infarction. Thus, infarct size can be assessed quantitatively in patients with acute myocardial infarction and provide a useful diagnostic and prognostic index based on the extent of myocardial damage.

BACKGROUND:Chronic heart failure is characterized by left ventricular dilation and abnormalities of cardiac autonomic function. Up to 20% of patients with chronic heart failure have QRS prolongation, which can lead to asynchronous left ventricular contraction. We tested the hypotheses that in patients with chronic heart failure, QRS > 150 ms is a risk factor for additional abnormalities of ventricular morphology, heart rate variability, and increased mortality. METHODS AND RESULTS:In 184 patients with left ventricular ejection fraction < 35%, QRS duration was > 150 ms in 53, and = 150 ms in 131. We evaluated patients with baseline chest radiographs, echocardiograms, and Holter recordings. Patients with QRS duration above and below 150 ms were similar in age, sex, functional class, renal function, serum sodium, and ejection fraction. In patients with QRS > 150 ms, left ventricular end-diastolic and end-systolic diameters were greater than patients with QRS duration =150 ms (P <.01). Patients with QRS > 150 ms had less low frequency R-R interval spectral power (P <.04). At 5 years 60% of patients with QRS > 150 ms had died compared with 35% of patients with QRS =150 ms (P <.001). This increase in mortality was predominantly the result of an increase in progressive heart failure. CONCLUSIONS:Chronic heart failure patients with QRS duration > 150 ms have exaggerated disturbance of cardiac autonomic function, and left ventricular remodeling and significantly higher mortality than patients with QRS duration = 150 ms.