New Pregnane Glycosides from Mandevilla dardanoi and Their Anti-Inflammatory Activity.

Mandevilla Lindl. is an important genus of the Apocynaceae family, not only as ornamental plants but also for its medicinal uses. In Brazil, Mandevilla species are indicated to treat asthma and skin infections, their anti-inflammatory potential and wound healing properties are also reported in the literature. Concerning their chemical composition, this group of plants is a conspicuous producer of pregnane glycosides. Mandevilla dardanoi is an endemic species from the Brazilian semiarid region not studied by any phytochemical methods. In view of the medicinal potential of Mandevilla species, this study aimed to isolate new pregnane glycosides from M. dardanoi. To achieve this main goal, modern chromatography techniques were employed. Five new pregnane glycosides, dardanols A-E, were isolated from the roots of M. dardanoi by HPLC. Their structures were determined using extensive 1D and 2D-NMR and mass spectrometry (MSn and HRESIMS) data. The cytotoxicity and the anti-inflammatory potential of these compounds were evaluated. The first was evaluated by measuring proinflammatory cytokines and nitric oxide production by stimulated macrophages. Dardanols were able to inhibit the production of nitric oxide and reduce IL-1ß and TNF-α. The current work demonstrates the chemodiversity of Brazilian semiarid species and contributes to amplifying knowledge about the biological potential of the Mandevilla genus.

Nonoperative treatments for sciatica: a pilot study for a randomized clinical trial.

OBJECTIVES: To assess the feasibility of patient recruitment, the ability of patients and clinicians to comply with study protocols, and the use of data collection instruments to collect cost-effectiveness data, and to obtain variability estimates for sample-size calculations for a full-scale trial. STUDY DESIGN: Prospective, observer-blinded, pilot randomized clinical trial. SETTING: Primary contact chiropractic and medical clinics. PATIENTS: Ages 20 to 65 years, with low back-related radiating leg pain (sciatica). OUTCOME MEASURES: Self-report questionnaires were administered at baseline and 3 and 12 weeks after randomization. The measures included leg and back pain severity, frequency and bothersomeness of symptoms, leg/back disability, medication use, global improvement, satisfaction, and health care utilization. INTERVENTIONS: Medical care, chiropractic care, and epidural steroid injections. RESULTS: A total of 706 persons were screened by phone to determine initial eligibility. Of these, over 90% of those persons contacted did not meet the entrance criteria. The most common reason for disqualification was that the duration of the complaint was longer than 3 months. Twenty patients were randomized into the study. All 3 groups showed substantial improvements in the main patient-rated outcomes at the end of the 12-week intervention phase. For leg pain, back pain, frequency and bothersomeness of leg symptoms, and Roland-Morris disability score, the percent improvement varied from 50% to 84%, and the corresponding effect sizes ranged from 0.8 to 2.2. Bothersomeness of leg symptoms was the most responsive outcome associated with the largest magnitude of effect size. All within-group changes from baseline were statistically significant (P <.01). No between-group comparisons were planned or performed because of the insufficient sample size and high risk of committing type I and type II errors. CONCLUSIONS: Pilot studies such as these are important for the determination of the feasibility of conducting costly, larger scale trials. Recruitment for a full-scale study of sciatica of 2 to 12 weeks duration is not feasible, given the methods used in this pilot study. Our results do indicate, however, that there are substantial numbers of patients with sciatica more chronic in nature who would be interested in participating in a similar study. In addition, collaboration with a local health maintenance organization would likely facilitate clinician referrals and optimize the recruitment process. Patient and provider compliance was high in the pilot study, which indicates that most study protocols are feasible. Additionally, we were able to collect complete outcomes data, including those regarding health care use. A suggested modification by investigators and outside consultants has resulted in the replacement of the medication group with a minimal intervention control group (ie, self-care advice). As a result, a second pilot study of patients with sciatica of more than 4 weeks duration has been planned before a full-scale trial is attempted.

The efficacy of spinal manipulation, amitriptyline and the combination of both therapies for the prophylaxis of migraine headache.

BACKGROUND: Migraine headache affects approximately 11 million adults in the United States. Spinal manipulation is a common alternative therapy for headaches, but its efficacy compared with standard medical therapies is unknown. OBJECTIVE: To measure the relative efficacy of amitriptyline, spinal manipulation and the combination of both therapies for the prophylaxis of migraine headache. DESIGN: A prospective, randomized, parallel-group comparison. After a 4-wk baseline period, patients were randomly assigned to 8 wk of treatment, after which there was a 4-wk follow-up period. SETTING: Chiropractic college outpatient clinic. PARTICIPANTS: A total of 218 patients with the diagnosis of migraine headache. INTERVENTIONS: An 8-wk course of therapy with spinal manipulation, amitriptyline or a combination of the two treatments. MAIN OUTCOME MEASURES: A headache index score derived from a daily headache pain diary during the last 4 wk of treatment and during the 4-wk follow-up period. RESULTS: Clinically important improvement was observed in both primary and secondary outcomes in all three study groups over time. The reduction in headache index scores during treatment compared with baseline was 49% for amitriptyline, 40% for spinal manipulation and 41% for the combined group; p = .66. During the posttreatment follow-up period the reduction from baseline was 24% for amitriptyline, 42% for spinal manipulation and 25% for the combined group; p = .05. CONCLUSION: There was no advantage to combining amitriptyline and spinal manipulation for the treatment of migraine headache. Spinal manipulation seemed to be as effective as a well-established and efficacious treatment (amitriptyline), and on the basis of a benign side effects profile, it should be considered a treatment option for patients with frequent migraine headaches.

Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial.

OBJECTIVES: To study the relative efficacy of three different treatment for chronic low back pain (CLBP). Two preplanned comparisons were made: (a) Spinal manipulative therapy (SMT) combined with trunk strengthening exercises (TSE) vs. SMT combined with trunk stretching exercises, and (b) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug (NSAID) therapy combined with TSE. STUDY DESIGN: Interdisciplinary, prospective, observer-blinded, randomized clinical trial with a 1-yr follow-up period. The trial evaluated therapies in combination only and was not designed to test the individual treatment components. SETTING: Primary contact, college out-patient clinic. PATIENTS: In total, 174 patients aged 20-60 yr were admitted to the study. MAIN OUTCOME MEASURES: Patient-rated low back pain, disability, and functional health status at 5 and 11 wk. INTERVENTIONS: Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise, followed by and additional 6 wk of supervised exercise alone. RESULTS: Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinically important or statistically significant differences. There seemed to be a sustained reduction in medication use at the 1-yr follow-up. in the SMT/TSE group. Continuance of exercise during the follow-up year, regardless of type, was associated with a better outcome. CONCLUSION: Each of the three therapeutic regimens was associated with similar and clinically important improvement over time that was considered superior to the expected natural history of long-standing CLBP. For the management of CLBP, trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile. The magnitude of nonspecific therapeutic (placebo) effects, cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies.

Spinal manipulation vs. amitriptyline for the treatment of chronic tension-type headaches: a randomized clinical trial.

OBJECTIVE: To compare the effectiveness of spinal manipulation and pharmaceutical treatment (amitriptyline) for chronic tension-type headache. DESIGN: Randomized controlled trial using two parallel groups. The study consisted of a 2-wk baseline period, a 6-wk treatment period and a 4-wk posttreatment, follow-up period. SETTING: Chiropractic college outpatient clinic. PATIENTS: One hundred and fifty patients between the ages of 18 and 70 with a diagnosis of tension-type headaches of at least 3 months' duration at a frequency of at least once per wk. INTERVENTIONS: 6 wk of spinal manipulative therapy provided by chiropractors or 6 wk of amitriptyline treatment managed by a medical physician. MAIN OUTCOME MEASURES: Change in patient-reported daily headache intensity, weekly headache frequency, over-the-counter medication usage and functional health status (SF-36). RESULTS: A total of 448 people responded to the recruitment advertisements; 298 were excluded during the screening process. Of the 150 patients who were enrolled in the study, 24 (16%) dropped out: 5 (6.6%) from the spinal manipulative therapy and 19 (27.1%) from the amitriptyline therapy group. During the treatment period, both groups improved at very similar rates in all primary outcomes. In relation to baseline values at 4 wk after cessation of treatment, the spinal manipulation group showed a reduction of 32% in headache intensity, 42% in headache frequency, 30% in over-the-counter medication usage and an improvement of 16% in functional health status. By comparison, the amitriptyline therapy group showed no improvement or a slight worsening from baseline values in the same four major outcome measures. Controlling for baseline differences, all group differences at 4 wk after cessation of therapy were considered to be clinically important and were statistically significant. Of the patients who finished the study, 46 (82.1%) in the amitriptyline therapy group reported side effects that included drowsiness, dry mouth and weight gain. Three patients (4.3%) in the spinal manipulation group reported neck soreness and stiffness. CONCLUSIONS: The results of this study show that spinal manipulative therapy is an effective treatment for tension headaches. Amitriptyline therapy was slightly more effective in reducing pain at the end of the treatment period but was associated with more side effects. Four weeks after the cessation of treatment, however, the patients who received spinal manipulative therapy experienced a sustained therapeutic benefit in all major outcomes in contrast to the patients that received amitriptyline therapy, who reverted to baseline values. The sustained therapeutic benefit associated with spinal manipulation seemed to result in a decreased need for over-the-counter medication. There is a need to assess the effectiveness of spinal manipulative therapy beyond four weeks and to compare spinal manipulative therapy to an appropriate placebo such as sham manipulation in future clinical trials.

Recruitment patterns in the cervical paraspinal muscles during cervical forward flexion: evidence of cervical flexion-relaxation.

The phenomenon of lumbar paraspinal flexion-relaxation has been well established and its clinical significance to low back pain has been demonstrated. Conversely, cervical paraspinal flexion-relaxation has not been consistently observed. This may be attributable to the inappropriate use of trunk flexion motion used to observe the phenomenon in previous studies. This investigation reports on the observance of cervical flexion-relaxation when flexion is limited to the cervical spine. Results demonstrate the observance of cervical flexion-relaxation in ten of ten asymptomatic subjects when flexion is limited to the cervical region in the seated orthograde position.

Palpable abnormalities of the breast not requiring excisional biopsy.

The evaluation of a patient with a palpable abnormality of the breast typically includes physical examination, mammography and fine needle aspiration biopsy (FNAB) with cytologic interpretation of the aspirate. If the findings of these three diagnostic modalities are negative for malignancy, the current standard of care is to proceed to surgical biopsy to confirm the benign nature of the lesion. The current study was done to identify a subset of patients who could be safely observed without surgical (histologic) biopsy. These patients fulfilled specified criteria on physical examination, mammogram and needle sensation when the FNAB needle entered the lesion. Results of the cytologic studies of the FNAB were used as a corroborative rather than as a diagnostic test. Of 305 patients with mammary abnormalities, 106 were identified with "subsuspicious" lesions. Seven of the latter patients underwent surgical biopsy, four because the results of cytologic studies of FNAB revealed cytologic atypia. One of the four patients had infiltrating ductal carcinoma. All other patients have had follow-up evaluation for a mean of 61 months (range of 43 to 74 months). No carcinomas have developed at the subsuspicious site. The current study is the first to clearly define a subset of patients with palpable abnormalities of the breast who do not require surgical biopsy.

Interexaminer reliability and discriminant validity of inclinometric measurement of lumbar rotation in chronic low-back pain patients and subjects without low-back pain.

The interexaminer reliability of an inclinometer procedure to measure lumbar rotation was evaluated by two chiropractic clinicians who examined 25 chronic (greater than 6 months) low-back pain patients and 25 subjects without low-back pain. These groups were compared for differences in mean left, right, and total rotation. Patients who had lumbar spinal surgery were excluded. Twenty-eight men and 22 women, ranging in age from 28-38 years, were evaluated. Reliability between examiners was evaluated by Pearson's correlation coefficient and the intraclass correlation coefficient. All coefficients were significant (P less than 0.01). Errors in prediction and examiner disagreement were evaluated by the standard error of estimate and the interexaminer measurement error. The standard errors of estimate (range: 1.4-4.4) and the interexaminer measurement errors (range: 3.8-10.4) were large compared to the scale of measurement. An analysis of variance of differences between the chronic low-back pain patients and asymptomatics revealed significantly more left rotation in the asymptomatic subjects (F = 8.4; df = 1; P less than 0.006). Also, there was significantly more total rotation in the asymptomatic subjects (F = 4.143; df = 1; P less than 0.048). However, because of the large error attributed to this procedure, it is not possible to say whether the difference between the two groups is a result of the large error or some "real" difference. Therefore, the procedure described in this study should not be used as a clinical outcome measure.