Mainstream smoke chemistry analysis of samples from the 2009 US cigarette market.

A survey of selected mainstream smoke constituents from commercially marketed US cigarettes was conducted in 2009. The US cigarette market was segmented into thirteen (13) strata based on Cambridge Filter Method (CFM) "tar" category and cigarette design parameters. Menthol and non-menthol cigarettes were included. Sixty-one (61) cigarette brand styles were chosen to represent the market. Another thirty-four (34) brand styles of interest were included in the survey along with a Kentucky 3R4F reference cigarette. Twenty mainstream smoke constituents were evaluated using the Health Canada smoking regimen. By weighting the results of the 61 brand styles using the number of brand styles represented by each stratum, the mainstream smoke constituent means and medians of the US cigarette market were estimated. For nicotine, catechol, hydroquinone, benzo(a)pyrene and formaldehyde the mean yields increased with increasing "tar" yields. Constituent yields for the ultra-low "tar" and low "tar" cigarettes were not significantly different for most other analytes as ventilation blocking defeated any filter air dilution design features. In contrast, normalization per mg nicotine provided an inverse ranking of cigarette yields per CFM "tar" categories. Menthol cigarette mean constituent yields were observed to be within the range of the non-menthol cigarettes of similar "tar" categories.

Quantitative aspects of the release of leukocyte pyrogen from rabbit blood incubated with endotoxin.

This paper describes the relations between the endotoxin concentration and leukocyte pyrogen yield when endotoxin is incubated with whole rabbit blood for 24 hr. The results provide strong evidence for the view that leukocyte pyrogen is not modified endotoxin, and also show that the simplified assay method described in the previous paper works reasonably well.

The rate of release of leukocyte pyrogen from rabbit blood incubated with endotoxin.

The time course of leukocyte pyrogen liberation from whole rabbit blood incubated at 37 degrees C with various concentrations of proteus endotoxin was studied. The kinetics of the process provide further evidence for the view that leukocyte pyrogen is an independent entity. It was shown that complete liberation of all available leukocyte pyrogen from blood is too slow a process to account for the fevers seen when rabbits are injected with endotoxin. However, very small quantities of leukocyte pyrogen were demonstrated after short periods of incubation which are adequate to account for endotoxin fevers. It was also found that small, but definite, quantities of leukocyte pyrogen are liberated from rabbit blood incubated without endotoxin.

An assay method for leukocyte pyrogen.

A method for assaying leukocyte pyrogen is described which is shown to remain valid despite the presence of very large amounts of bacterial endotoxin. It uses a combination of two procedures to inactivate endotoxin: incubation in normal rabbit plasma for 24 hr at 37 degrees C, and injection into rabbits rendered refractory to endotoxin. The validity of the assay was confirmed by formal statistical methods. A simplified assay method is also described which lacks full statistical validity, but is more suitable for routine use.

Failure of rabbit neutrophils to secrete endogenous pyrogen when stimulated with staphylococci.

Cells obtained from acute peritoneal exudates in rabbits were separated into neutrophil and mononuclear populations by centrifugation on colloidal silica gradients. When these populations were separately incubated in tissue culture medium in the presence of opsonized Staphylococcus epidermidis, endogenous pyrogen was secreted only by the adherent cells of the mononuclear population. Pyrogen production by neutrophils could not have amounted to as much as 1% of the pyrogen produced by macrophages. When mononuclear cells were added back to purified neutrophils, no pyrogen was produced that could not be accounted for by the number of macrophages added. Rabbit blood cells were similarly fractionated on colloidal silica gradients. Again, endogenous pyrogen was made only by the adherent mononuclear population. The neutrophils isolated on these gradients appeared to be morphologically normal and were 85% viable as judged by dye exclusion. They showed normal random motility. Both blood and exudate neutrophils responded chemotactically to N-formyl Met-Leu-Phe, and blood neutrophils responded chemotactically to zymosan-activated serum. Both kinds of neutrophils phagocytosed zymosan particles and both killed opsonized S. epidermidis in a roller tube system. Both blood and exudate neutrophils showed normal superoxide production when stimulated with opsonized zymosan particles. This evidence suggests that macrophages are the only source of endogenous pyrogens, and that pyrogens secreted by cell populations that are rich in neutrophils are to be attributed to the monocytes or macrophages that they contain.

Synthesis of endogenous pyrogen by rabbit leukocytes.

Rabbit ieukocytes from peritoneal exudates and from blood were stimulated to form leukocyte pyrogen in the presence of radiolabeled amino acids. The stimuli used were endotoxin, phagocytosis, and tuberculin. The crude leukocyte pyrogen samples were purified; pyrogen from exudate cells was rendered homogeneous; pyrogen from blood cells was still contaminated with other proteins. All the purified pyrogens were radioactive; and for all it was shown that radioactivity and pyrogenic activity coincided on electrophoresis at pH 3.5 and pH 9 in acrylamide and on isoelectric focusing in acrylamide. Furthermore, pyrogens obtained from exudate cells stimulated in different ways, or from blood cells and exudate cells stimulated with endotoxin, appeared to be identical. These results suggest that leukocyte pyrogen was synthesized de novo from amino acid precursors and that leukocytes made the same pyrogen whatever the stimulus used to activate them.

T cell receptor-independent immunosuppression induced by dexamethasone in murine T helper cells.

The immune and inflammatory responses are largely inhibited by glucocorticosteroids. In thymocytes, for example, glucocorticosteroids cause apoptosis, whereas they suppress the activity of phospholipase A2 and the production of eicosanoids in tissues actively engaged in inflammation. The immunosuppressive action of dexamethasone (DEX) was studied in vitro by employing a model cell system, namely the murine Th2 clone D10.G4.1 (D10) and its clonotypic anti-T cell receptor (TCR) mAb 3D3. Although the proliferative response of D10 cells to 3D3 stimulation was not affected by DEX, the costimulation provided by IL-1 was dramatically inhibited. Substitution of 3D3 by exogenous IL-4 (as the IL-1 costimulant) failed to prevent the inhibition of proliferation caused by DEX. Yet, when 3D3-mediated stimulation of TCR was supplemented with IL-2, D10 cells were capable of proliferating, even in the presence of DEX. Thus, TCR stimulation on D10 cells remained intact and their resulting propagation was not compromised by DEX treatment. These results provide evidence that immunosuppression caused by DEX is TCR independent and involves an early cytokine-signalling event.

Behavioural interventions for primary and secondary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition with considerable morbidity. The behavioural approach assumes that psychological and environmental factors interact with, and influence, physiological processes. Behavioural interventions for dysmenorrhoea may include both physical and cognitive procedures and focus on both physical and psychological coping strategies for dysmenorrhoeic symptoms rather than modification of any underlying organic pathology. OBJECTIVES: To determine the effectiveness of any behavioural interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or conventional medical treatments for example non-steroidal anti-inflammatory drugs (NSAIDs). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2005), Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1980 to April 2005), Social Sciences Index (1980 to April 2005), PsycINFO (1972 to April 2005) and CINAHL (1982 to April 2005) and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials comparing behavioural interventions with placebo or other interventions in women with dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Five trials involving 213 women were included. Behavioural intervention vs control: One trial of pain management training reported reduction in pain and symptoms compared to a control. Three trials of relaxation compared to control reported varied results, two trials showed no difference in symptom severity scores however one trial reported relaxation was effective for reducing symptoms in menstrual sufferers with spasmodic symptoms. Two trials reported less restriction in daily activities following treatment with either relaxation of pain management training compared to a control. One trial also reported less time absent from school following treatment wit pain management training compared to a control. Behavioural intervention vs other behavioural interventions: Three trials showed no difference between behavioural interventions for the outcome of improvement in symptoms. One trial showed that relaxation resulted in a decrease in the need for resting time compared to the relaxation and imagery. AUTHORS' CONCLUSIONS: There is some evidence from five RCTs that behavioural interventions may be effective for dysmenorrhoea however results should be viewed with caution as they varied greatly between trials due to inconsistency in the reporting of data, small trial size, poor methodological quality and age of the trials.

Spinal manipulation for primary and secondary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition. One possible treatment is spinal manipulation therapy. One hypothesis is that mechanical dysfunction in certain vertebrae causes decreases spinal mobility. This could affect the sympathetic nerve supply to the blood vessels supplying the pelvic viscera, leading to dysmenorrhoea as a result of vasoconstriction. Manipulation of these vertebrae increases spinal mobility and may improve pelvic blood supply. Another hypothesis is that dysmenorrhoea is referred pain arising from musculoskeletal structures that share the same pelvic nerve pathways. The character of pain from musculoskeletal dysfunction can be very similar to gynaecological pain as it can present as cyclic pain altered by hormonal influences associated with menstruation. OBJECTIVES: To determine the safety and efficacy of spinal manipulative interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or other medical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1980 to April 2006), CINAHL (1982 to March 2006), AMED (1985 to April 2006), Biological Abstracts (1969 to March 2006), PsycINFO (1806 to April 2006), and SPORTDiscus (1830 to April 2006). Attempts were also made to identify trials from the metaRegister of Controlled Trials and the citation lists of review articles and included trials. In most cases the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Any randomised controlled trials (RCTs) including spinal manipulative interventions (for example chiropractic, osteopathy, or manipulative physiotherapy) versus each other, placebo, no treatment, or other medical treatment were considered. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an intrauterine device (IUD). DATA COLLECTION AND ANALYSIS: Four trials of high velocity, low amplitude manipulation (HVLA), and one of the Toftness manipulation technique were included. Quality assessment and data extraction were performed independently by two review authors. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis were reported as descriptive data and were also included for discussion. The outcome measures were pain relief or pain intensity (dichotomous, visual analogue scales, descriptive) and adverse effects. MAIN RESULTS: Results from the four trials of high velocity, low amplitude manipulation suggest that the technique was no more effective than sham manipulation for the treatment of dysmenorrhoea, although it was possibly more effective than no treatment. Three of the smaller trials indicated a difference in favour of HVLA, however the one trial with an adequate sample size found no difference between HVLA and sham treatment. There was no difference in adverse effects experienced by participants in the HVLA or sham treatment. The Toftness technique was shown to be more effective than sham treatment by one small trial, but no strong conclusions could be made due to the small size of the trial and other methodological considerations. AUTHORS' CONCLUSIONS: Overall there is no evidence to suggest that spinal manipulation is effective in the treatment of primary and secondary dysmenorrhoea. There is no greater risk of adverse effects with spinal manipulation than there is with sham manipulation.

Effects of fluoridated drinking water on bone mass and fractures: the study of osteoporotic fractures.

To determine if optimal fluoridation of public water supplies influences bone mass and fractures, we studied 2076 non-black women, all aged > or = 65 years recruited into the Study of Osteoporotic Fractures at the Pittsburgh clinic. Information on fluoride exposure was limited to community water supplies. The variable used in the analysis was years of exposure to fluoridated water in community drinking water supplies. Bone mineral density (BMD) was measured at the spine and hip using dual energy X-ray absorptiometry and at the midpoint and ultradistal radius and calcaneus using single photon absorptiometry. Prevalent and incident vertebral fractures were determined by morphometry. Incident nonspine fractures were ascertained every 4 months and confirmed by radiographic report. Exposure to residential fluoridated water had no effect on bone mass. Women exposed to fluoride for > 20 years had similar axial and appendicular bone mass to women not exposed or women exposed for < or = 20 years. There was some suggestion that women exposed to fluoride for > 20 years had a lower relative risk of nonspine fractures (relative risk, RR, = 0.73; 95% confidence interval [CI] 0.48-1.12), osteoporotic fractures, RR = 0.74 (CI 0.46-1.19), and hip fractures, RR = 0.44 (CI 0.10-1.86), compared with women not exposed, but none of these relative risks was statistically significant. There was no association with wrist or spinal fractures. Our results do not support the findings from recent ecological studies which showed an increased risk of hip fracture among individuals exposed to fluoridated public water.

Soy isoflavone analysis: quality control and a new internal standard.

Development of a database of the soy isoflavone content of foods requires accurate and precise evaluation of different food matrixes. To evaluate accuracy, we estimated recoveries of both internal and external standards in 5 different soyfoods weekly. Standards were evaluated daily for system quality assurance. To evaluate sample precision, we analyzed soybeans and soymilk bimonthly for within-day precision and over 4 d for day-to-day precision. CVs should be < or = 8%. We validated our methods for single and multiple recovery concentrations by using our new internal standard, 2,4,4'-trihydroxydeoxybenzoin, and the external standards daidzein, genistein, and genistin. Concentrations of 12 isoflavone isomers, 3 aglycones (daidzein, genistein, and glycitein), and 9 glucosides (daidzin, genistin, glycitin, acetyldaidzin, acetylgenistin, acetylglycitin, malonyldaidzin, malonylgenistin, and malonylglycitin) were measured in a variety of soybeans and soyfoods. The extraction methods used depended on soyfood type. The HPLC conditions for soy isoflavone analysis were improved, leading to good separation with a short analysis time (60 min/sample). A data bank of concentration and distribution of isoflavones in different soybean products was assembled. A wide range of isoflavone concentrations, from < 50 microg/g to > 20,000 microg/g, was found in different soy products. The glucoside forms are almost twice the molecular weight of the aglycones; reported isoflavone concentrations should be normalized to the aglycone mass (or an isoflavonoid equivalent) rather than a simple sum of all isomers.

The polyp prevention trial I: rationale, design, recruitment, and baseline participant characteristics.

The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy: age 35 years of more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and 10% are minorities. At study entry, participants averaged 61.4 years of age; 14% of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of participants had two or more adenomas, and 29% had at least one large (> of = 1 cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are comparable across the two study arms. Participants have repeat colonoscopies after 1 (T(1)) and 4 (T(4)) years of follow-up. The primary end point is adenoma recurrence; secondary end points include number, size, location, and histology of adenomas. All resected lesions are reviewed centrally by gastrointestinal pathologists. The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based is 3 years (T(1) to T(4)), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1), given that at least 10-15% of polyps may be missed at baseline. The final (T(4)) colonoscopies are expected to be completed in early 1998.

Accumulation of indium-111-labeled neutrophils and gallium-67 citrate in rabbit abscesses.

A rabbit abscess model was developed to study the effect of abscess age on the accumulation of indium-111-labeled neutrophils ([111In]N) versus gallium-67 citrate (67Ga). Abscesses 1-2 hr, 6-8 hr, 24 hr, and 7 days old were induced by subcutaneous injection of autoclaved colon contents prior to i.v. administration of either [111In]N or 67Ga. Radioactivity in the abscesses was determined 48 hr postinjection. Accumulation of [111In]N was inversely proportional to abscess age. Seven-day-old abscesses were inconsistently seen on [111In]N scans. In contrast, 67Ga accumulation was not affected by abscess age and all abscesses could be identified on a scan 48 hr postinjection. Scans with [111In]N were clearly superior to 67Ga scans for demonstrating early abscesses. Since 67Ga accumulated to a greater extent than [111In]N in abscesses 7 days old, it may be a superior imaging agent for older abscesses.

Reduction of spike frequency adaptation and blockade of M-current in rat CA1 pyramidal neurones by linopirdine (DuP 996), a neurotransmitter release enhancer.

1. Linopirdine (DuP 996) has been shown to enhance depolarization-induced release of several neurotransmitters in the CNS through a mechanism which may involve K+ channel blockade. The electrophysiological effects of linopirdine were therefore investigated directly, by use of conventional voltage recording and single electrode voltage-clamp. 2. Linopirdine (10 microM) reduced spike frequency adaptation (SFA) in rat hippocampal CA1 pyramidal neurones in vitro. The reduction of SFA comprised an increase in number of spikes and a reduction in inter-spike intervals after the first, but with no effect on time to first spike. Linopirdine also caused a voltage-dependent depolarization of resting membrane potential (RMP). 3. M-current (IM), a current known to underlie SFA and to set RMP, was blocked by linopirdine in a reversible, concentration-dependent manner (IC50 = 8.5 microM). This block was not reversed by atropine (10 microM). 4. Linopirdine did not affect IQ, the slow after-hyperpolarization following a spike train, or spike duration. 5. Linopirdine may represent a novel class of K+ blocker with relative selectivity for the M-current. This block of IM is consistent with the suggestion from a previous study that linopirdine may affect a tetraethylammonium-sensitive channel, and it could be speculated that IM blockade may be involved with the enhancement of neurotransmitter release by linopirdine.

Outcomes of intended home births in nurse-midwifery practice: a prospective descriptive study.

OBJECTIVE: To describe the outcomes of intended home birth in the practices of certified nurse-midwives. METHODS: Twenty-nine US nurse-midwifery practices were recruited for the study in 1994. Women presenting for intended home birth in these practices were enrolled in the study from late 1994 to late 1995. Outcomes for all enrolled women were ascertained. Validity and reliability of submitted data were established. RESULTS: Of 1404 enrolled women intending home births, 6% miscarried, terminated the pregnancy or changed plans. Another 7.4% became ineligible for home birth prior to the onset of labor at term due to the development of perinatal problems and were referred for planned hospital birth. Of those women beginning labor with the intention of delivering at home, 102 (8.3%) were transferred to the hospital during labor. Ten mothers (0.8%) were transferred to the hospital after delivery, and 14 infants (1.1%) were transferred after birth. Overall intrapartal fetal and neonatal mortality for women beginning labor with the intention of delivering at home was 2.5 per 1000. For women actually delivering at home, intrapartal fetal and neonatal mortality was 1.8 per 1000. CONCLUSION: Home birth can be accomplished with good outcomes under the care of qualified practitioners and within a system that facilitates transfer to hospital care when necessary. Intrapartal mortality during intended home birth is concentrated in postdates pregnancies with evidence of meconium passage.

Age-related changes in the gastrointestinal system. Effects on drug therapy.

Although there are many changes in the gastrointestinal tract with aging, only those in the liver substantially influence blood concentrations and clearance of drugs. The liver mass, overall function, and blood flow decrease approximately 1% per year after age 40 to 50 years, and accordingly, the hepatic metabolism or clearance of drugs decreases in this proportion. The sensitivity of the gastrointestinal tract to usual concentrations of drugs is increased, and this, in part, accounts for the increased frequency of adverse drug reactions in elderly patients.

Internal locus of control and social support associated with some dietary changes by elderly participants in a diet intervention trial.

OBJECTIVE: Measure relationships of locus of control and social support to diet changes in an intervention trial. DESIGN: Participants in the Polyp Prevention Trial (PPT) completed Multidimensional Health Locus of Control (MHLC) and Norbeck Social Support Questionnaires (NSSQ) and modified Block food frequency questionnaires. Data were collected at baseline and 1 year later. SUBJECTS/SETTING: A convenience sample of PPT intervention (N = 68) and control (n = 43) participants at 1 clinical center participated in this ancillary study. MAIN OUTCOME MEASURES: Mean daily dietary intakes after 1 year were compared with baseline values. Intervention participants' scores for MHLC internal locus of control and NSSQ total functional network were correlated with diet changes. STATISTICAL ANALYSES PERFORMED: Group percentages were compared using the Fisher exact test; means were compared by t test. RESULTS: Groups were comparable in demographics, baseline diet, and scores for internal locus of control and total functional network. Intervention group participants made greater diet changes than control participants in intake of fat (-27 g vs -8 g), fat as a percentage of kilocalories (-8% vs -2%), fiber as grams per 1,000 kcal (7 g vs 0.3 g), and daily fruit/vegetable servings (2.0 vs 0.2). Pearson correlations of diet changes with internal locus of control scores (all P > .05) were fat grams, r = 0.031; fat as percentage of kilocalories, r = 0.023; fiber grams per 1,000 kcal; r = 0.230; and fruit/vegetable servings, r = 0.186. Correlations with total functional network scores were: fat grams, r = 0.022 (P > .05); fat as percentage of kilocalories, r = -0.108 (P > .05); fiber grams per 1,000 kcal, r = 0.276, P < .05; and daily fruit/vegetable servings, r = 0.326, P < .05. APPLICATIONS/CONCLUSIONS: Intensive and skillful dietary intervention can succeed whether or not clients bring strong internal locus of control or social support to the diet change program.

Prevention of hospital liability for granting privileges to unqualified physicians.

The rise in medical malpractice claims has resulted in the widespread development of risk management programs. These programs have relevance to the practice of gastrointestinal endoscopy with regard to identifying and addressing factors that place the gastrointestinal endoscopist and his or her patient at risk for procedure-related complications and adverse outcomes. Illustrative clinical examples and commentary regarding gastrointestinal endoscopy as it relates to the tort of professional liability are provided. Recommendations regarding gastrointestinal risk management are formulated.

Herbal and dietary therapies for primary and secondary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological complaint. Common treatment for dysmenorrhoea is medical therapy such as nonsteroidal anti-inflammatories (NSAIDs) or oral contraceptive pills (OCPs) which both work by reducing myometrial activity (contractions of the uterus). The efficacy of conventional treatments such as nonsteroidals is considerable, however the failure rate is still often 20-25%. Many consumers are now seeking alternatives to conventional medicine and research into the menstrual cycle suggests that nutritional intake and metabolism may play an important role in the cause and treatment of menstrual disorders. Herbal and dietary therapies number among the more popular complementary medicines yet there is a lack of taxonomy to assist in classifying them. In the US, herbs and other phytomedicinal products (medicine from plants) have been legally classified as dietary supplements since 1994. Included in this category are vitamins, minerals, herbs or other botanicals, amino acids and other dietary substances. For the purpose of this review we use the wider term herbal and dietary therapies to include the assorted herbal or dietary treatments that are classified in the US as supplements and also the phytomedicines that may be classified as drugs in the European Union. OBJECTIVES: To determine the efficacy and safety of herbal and dietary therapies for the treatment of primary and secondary dysmenorrhoea when compared to each other, placebo, no treatment or other conventional treatments (e.g. NSAIDS). SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials, CCTR, MEDLINE, EMBASE, CINAHL, Bio extracts, and PsycLIT were performed to identify relevant randomised controlled trials (RCTs). The Cochrane Complementary Medicine Field's Register of controlled trials (CISCOM) was also searched. Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. In most cases, the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were RCTs of herbal or dietary therapies as treatment for primary or secondary dysmenorrhoea vs each other, placebo, no treatment or conventional treatment. Interventions could include, but were not limited to, the following; vitamins, essential minerals, proteins, herbs, and fatty acids. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an IUD. DATA COLLECTION AND ANALYSIS: Seven trials were included in the review. Quality assessment and data extraction were performed independently by two reviewers. The main outcomes were pain intensity or pain relief and the number of adverse effects. Data on absence from work and the use of additional medication was also collected if available. Data was combined for meta-analysis using Peto odds ratios for dichotomous data or weighted mean difference for continuous data. A fixed effects statistical model was used. If data suitable for meta-analysis could not be extracted, any available data from the trial was extracted and presented as descriptive data. MAIN RESULTS: MAGNESIUM: Three small trials were included that compared magnesium and placebo. Overall magnesium was more effective than placebo for pain relief and the need for additional medication was less. There was no significant difference in the number of adverse effects experienced. VITAMIN B6: One small trial of vitamin B6 showed it was more effective at reducing pain than both placebo and a combination of magnesium and vitamin B6. MAGNESIUM AND VITAMIN B6: Magnesium was shown to be no different in pain outcomes from both vitamin B6 and a combination of vitamin B6 and magnesium by one small trial. The same trial also showed that a combination of magnesium and vitamin B6 was no different from placebo in reducing pain. VITAMIN B1: One large trial showed vitamin B1 to be more effective than placebo in reducing pain. VITAMIN E: One small trial comparing a combination of vitamin E (taken daily) and ibuprofen (taken during menses) versus ibuprofen (taken during menses) alone showed no difference in pain relief between the two treatments. OMEGA-3 FATTY ACIDS: One small trial showed fish oil (omega-3 fatty acids) to be more effective than placebo for pain relief. JAPANESE HERBAL COMBINATION: One small trial showed the herbal combination to be more effective for pain relief than placebo, and less additional pain medication was taken by the treatment group. REVIEWER'S CONCLUSIONS: Vitamin B1 is shown to be an effective treatment for dysmenorrhoea taken at 100 mg daily, although this conclusion is tempered slightly by its basis on only one large RCT. Results suggest that magnesium is a promising treatment for dysmenorrhoea. It is unclear what dose or regime of treatment should be used for magnesium therapy, due to variations in the included trials, therefore no strong recommendation can be made until further evaluation is carried out. Overall there is insufficient evidence to recommend the use of any of the other herbal and dietary therapies considered in this review for the treatment of primary or secondary dysmenorrhoea.

Spinal manipulation for primary and secondary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition. The efficacy of medical treatments such as nonsteroidal anti-inflammatories (NSAIDs) or oral contraceptive pills (OCPs) is considerable, however the failure rate can still be as high as 20-25% and there are also a number of associated adverse effects. Many women are thus seeking alternatives to conventional medicine. One popular treatment modality is spinal manipulation therapy. There are several rationales for the use of musculoskeletal manipulation to treat dysmenorrhoea. The parasympathetic and sympathetic pelvic nerve pathways are closely associated with the spinal vertebrae, in particular the 2nd-4th sacral segments and the 10th thoracic to the 2nd lumbar segments. One hypothesis is that mechanical dysfunction in these vertebrae causes decreased spinal mobility. This could affect the sympathetic nerve supply to the blood vessels supplying the pelvic viscera, leading to dysmenorrhoea as a result of vasoconstriction. Manipulation of these vertebrae increases spinal mobility and may improve pelvic blood supply through an influence on the autonomic nerve supply to the blood vessels. Another hypothesis is that dysmenorrhoea is referred pain arising from musculoskeletal structures that share the same pelvic nerve pathways. The character of pain from musculoskeletal dysfunction can be very similar to gynecological pain and can present as cyclic pain as it can also be altered by hormonal influences associated with menstruation. OBJECTIVES: To determine the safety and efficacy of spinal manipulative interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or other medical treatment. SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, CCTR, MEDLINE, EMBASE, CINAHL, Bio extracts, Psyclit and SPORTDiscus were performed to identify relevant randomised controlled trials (RCTs). The Cochrane Complementary Medicine Field's Register of controlled trials (CISCOM) was also searched. Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. In most cases, the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Any RCTs including spinal manipulative interventions (e.g. chiropractic, osteopathy or manipulative physiotherapy) vs each other, placebo, no treatment, or other medical treatment were considered. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an IUD. DATA COLLECTION AND ANALYSIS: Five RCTs were identified that fulfilled the inclusion criteria for this review. Four trials involving high velocity, low amplitude manipulation (HVLA), and one involving the Toftness manipulation technique were included. Quality assessment and data extraction were performed independently by two reviewers. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis were reported as descriptive data and were also included for discussion. The outcome measures were pain relief or pain intensity (dichotomous, visual analogue scales, descriptive) and adverse effects. MAIN RESULTS: Results from the four trials of high velocity, low amplitude manipulation suggest that the technique was no more effective than sham manipulation for the treatment of dysmenorrhoea, although it was possibly more effective than no treatment. Three of the smaller trials indicated a difference in favour of HVLA, however the one trial with an adequate sample size found no difference between HVLA and sham treatment. There was no difference in adverse effects experienced by participants in the HVLA or sham treatment. The Toftness technique was shown to be more effective than sham treatment by one small trial, but no strong conclusions could be made due to the small size of the trial and other methodological considerations. REVIEWER'S CONCLUSIONS: Overall there is no evidence to suggest that spinal manipulation is effective in the treatment of primary and secondary dysmenorrhoea. There is no greater risk of adverse effects with spinal manipulation than there is with sham manipulation.