The effects of Cannabis sativa L. seed (hempseed) in the ovariectomized rat model of menopause.

Cannabis sativa L. has been used for the treatment of various gynecological diseases in traditional medicine. The potential of this plant to protect against complications of menopause has been raised but rarely studied. Twenty female rats were divided into five groups: sham-operated (sham), ovariectomized (OVX) and three other ovariectomized groups: HST1%, HST2% and HST10% which received 1%, 2% and 10% hempseed, respectively, in their diet for 3 weeks. The effects of hempseed on plasma lipid and lipoprotein profiles, estradiol and calcium levels were evaluated. Rats were tested for behavioral changes using the forced swimming test. The results showed that ovariectomy, independent of the type of diet, caused elevation of plasma calcium, total cholesterol and HDL-cholesterol levels, while hempseed modified this effect. Plasma estradiol levels were significantly lower in the OVX group compared to other groups. The swimming times for the OVX and sham groups were significantly shorter than that of the HSD10% group. All hempseed-treated groups were less anxious and showed significant declines in fecal boli compared to the sham group. The exploratory diving percent decreased in the HST10% group compared with other groups. These results suggest that hempseed may improve post-ovariectomy complications in rats.

How can a proposed Cochrane diet and nutrition field work effectively?

The Cochrane Database currently provides relatively little evidence-based guidance about nutrition relevant to general practitioners. This situation could be improved by the establishment of a new Cochrane Field to identify relevant studies, prioritize topics to include nutrition, work with Cochrane methodologists on the inclusion of observational studies, and disseminate results of Cochrane reviews to general practitioners and their patients. A Diet and Nutrition Field could be established as a separate entity or as a Subgroup of the existing Primary Health Care (PHC) Field. The Field would be appropriate if the intent is to immediately cover nutritional interventions of all sorts, in all settings. However, if the focus is nutritional evidence for use by primary care clinicians, organization as a subField would provide a simpler registration process, allow Cochrane activities to begin sooner, and would allow members to focus on primary-care-relevant nutritional issues, conserving their resources and energy. A mechanism exists for conversion to a freestanding Field if the scope later expands. Of the core Field functions, identification and assembly of relevant trials into a specialized register would be among the most important. Special registers are generated by focused literature searches augmented by hand-searching of key journals. Given the importance of studies with observational designs, a nutrition field register will require some additional work on search strategies and inclusion criteria. Other key functions would include ensuring effective communication both with members of other Cochrane entities and with the scientific and clinical community with interests in diet and nutrition.

Are fluid-based cytologies superior to the conventional Papanicolaou test? A systematic review.

OBJECTIVE: We compared fluid-based cytologies (FBC) with conventional Papanicolaou (Pap) tests (CT) to determine if either is superior. STUDY DESIGN: This was a systematic review of original research reports evaluating both CT and FBC with respect to specimen adequacy, comparison with a reference standard, or both. Two reviewers independently reviewed the titles, abstracts, and full articles to determine inclusion status, with differences resolved by consensus with a third author. Risk differences (RD) between occurrence rates for FBC and CT were used for the specimen adequacy data. Sensitivity and specificity were pooled independently and weighted by the inverse of the variance using a random effects model. DATA SOURCES: Studies published between 1985 and November 1999 were identified from MEDLINE, Best Evidence, EMBASE, Biological Abstracts/RRM, and The Cochrane Library. OUTCOMES MEASURED: Sensitivity, specificity, area under the receiver operating characteristic curve (AuROC), and the proportion of satisfactory, unsatisfactory, and "satisfactory but limited by" test results were measured. RESULTS: There was no significant difference in AuROC (P = .37). FBC specimens were more likely to be satisfactory (RD=0.06; 95% confidence interval [CI], 0.03-0.09) or to have absent endocervical cells (RD=0.06; 95% CI, 0.02-0.10) but had 10% fewer "satisfactory but limited by - other" reports (RD = -0.10; 95% CI, -0.14 to -0.06). There was no difference in unsatisfactory Pap test results. CONCLUSIONS: For most women there is no reason to replace CT with FBC. For women at high risk of cervical cancer or who are screened infrequently, the possible increase in FBC sensitivity may outweigh the potential harms from additional false positives.

Are beta2-agonists effective treatment for acute bronchitis or acute cough in patients without underlying pulmonary disease? A systematic review.

OBJECTIVE: Our goal was to determine whether beta2-agonists improve the symptoms of acute bronchitis or acute cough in patients who do not have underlying pulmonary disease. STUDY DESIGN: We performed a systematic review including meta-analysis. DATA SOURCES: We included randomized controlled trials comparing beta2-agonists with placebo or alternative therapies identified from the Cochrane Library, MEDLINE, EMBASE, conference proceedings, Science Citation Index, the System for Information on Grey Literature in Europe, and letters to manufacturers of beta2-agonists. OUTCOMES MEASURED: We measured duration, persistence, severity or frequency of cough, productive cough, and night cough; duration of activity limitations; and adverse effects. RESULTS: Two trials in children with cough and no obvious airway obstruction did not find any benefits from beta2-agonists. Five trials in adults with cough and with or without airway obstruction had mixed results, but summary statistics did not reveal any significant benefits from beta2-agonists. Studies that enrolled more wheezing patients were more likely to show benefits from beta2-agonists, and in one study only patients with evidence of airflow limitation were more likely to benefit. Patients given beta2-agonists were more likely to report tremor, shakiness, or nervousness than those in the control groups. CONCLUSIONS: There is no evidence to support using beta2-agonists in children with acute cough and no evidence of airflow obstruction. There is little evidence that the routine use of beta2-agonists for adults with acute cough is helpful. These agents may reduce symptoms, including cough, in patients with evidence of airflow obstruction, but this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with beta2-agonists.

Role of sigma(B) in adaptation of Listeria monocytogenes to growth at low temperature.

The activity of sigma(B) in Listeria monocytogenes is stimulated by high osmolarity and is necessary for efficient uptake of osmoprotectants. Here we demonstrate that, during cold shock, sigma(B) contributes to adaptation in a growth phase-dependent manner and is necessary for efficient accumulation of betaine and carnitine as cryoprotectants.

Economic analysis of step-wise treatment of gastro-oesophageal reflux disease.

BACKGROUND: To expose patients with gastro-oesophageal reflux disease (GERD) to the least amount of medication and to reduce health expenditures, it is recommended that their treatment is started with a small dose of an antisecretory or prokinetic medication. If patients fail to respond, the dose is increased in several consecutive steps or the initial regimen is changed to a more potent medication until the patients become asymptomatic. Although such treatment strategy is widely recommended, its impact on health expenditures has not been evaluated. METHODS: The economic analysis compares the medication costs of competing medical treatment strategies, using two different sets of cost data. Medication costs are estimated from the average wholesale prices (AWP) and from the lowest discount prices charged to governmental health institutions. A decision tree is used to model the step-wise treatment of GERD. In a Monte Carlo simulation, all transition probabilities built into the model are varied over a wide range. A threshold analysis evaluates the relationship between the cost of an individual medication and its therapeutic success rate. RESULTS: In a governmental health care system, a step-wise strategy saves on average $916 per patient every 5 years (range: $443-$1628) in comparison with a strategy utilizing only the most potent medication. In a cost environment relying on AWP, the average savings amount to $256 (-$206 to +$1561). The smaller the cost difference between two consecutive treatment steps, the longer one needs to follow the patients to reap the benefit of the small cost difference. However, even a small cost difference can turn into tangible cost savings, if a large enough fraction of GERD patients responds to the initial step of a less potent but also less expensive medication. CONCLUSIONS: The economic analysis suggests that a step-wise utilization of increasingly more potent and more expensive medications to treat GERD would result in appreciable cost savings.

Are antibiotics effective treatment for acute bronchitis? A meta-analysis.

BACKGROUND: Most clinicians prescribe antibiotics for acute bronchitis in spite of recommendations against this practice. Because the results of individual clinical trials have been mixed, we conducted a meta-analysis to determine whether antibiotics are effective treatment for acute bronchitis. METHODS: We conducted a comprehensive search to identify all trials in which patients who had a diagnosis of acute bronchitis were randomly assigned to treatment with an antibiotic or placebo. Patient-oriented outcomes of importance that were reported in at least 3 studies were quantitatively summarized. RESULTS: Nine studies met the inclusion criteria, but not all trials provided data for each outcome. Patients given antibiotics were less likely to have a cough (relative risk [RR] = 0.69; 95% confidence interval [CI], 0.49 -0.98) and be considered unimproved (RR = 0.51; 95% CI, 0.30-0.88) at a follow-up visit; but they were not less likely to have a productive cough (RR = 0.79; 95% CI, 0.60-1.03), activity limitations (RR = 0.59; 95% CI, 0.24-1.44), or feel ill (RR = 0.70; 95% CI, 0.31-1.58). Antibiotic-treated patients had a slightly shorter duration of productive cough (weighted mean difference [WMD] = -0.56 days; 95% CI, -1.09 to -0.04), but not of overall cough (WMD = -0.94; 95% CI, -2.08 to 0.21) or activity limitations (WMD = -0.49; 95% CI, -1.07 to 0.10). Patients treated with antibiotics did not report significantly more adverse effects (RR = 1.47; 95% CI, 0.82-2.65). CONCLUSIONS: Antibiotics may be modestly effective for a minority of patients with acute bronchitis. It is not clear which patient subgroups might benefit, and the failure of some studies to report negative findings may have resulted in overestimates of the benefits of antibiotics. Antibiotics are not necessary for every patient with acute bronchitis.

Survival after in-hospital cardiopulmonary resuscitation. A meta-analysis.

OBJECTIVE: To determine the rates of immediate survival and survival to discharge for adult patients undergoing in-hospital cardiopulmonary resuscitation, and to identify demographic and clinical variables associated with these outcomes. MEASUREMENTS AND MAIN RESULTS: The MEDLARS database of the National Library of Medicine was searched. In addition, the authors' extensive personal files and the bibliography of each identified study were searched for further studies. Two sets of inclusion criteria were used, minimal (any study of adults undergoing in-hospital cardiopulmonary resuscitation) and strict (included only patients from general ward and intensive care units, and adequately defined cardiopulmonary arrest and resuscitation). Each study was independently reviewed and abstracted in a nonblinded fashion by two reviewers. The data abstracted were compared, and any discrepancies were resolved by consensus discussion. For the subset of studies meeting the strict criteria, the overall rate of immediate survival was 40.7% and the rate of survival to discharge was 13.4%. The following variables were associated with failure to survive to discharge: sepsis on the day prior to resuscitation (odds ratio [OR] 31.3; 95% confidence interval [CI] 1.9, 515), metastatic cancer (OR 3.9; 95% CI 1.2, 12. 6), dementia (OR 3.1; 95% CI 1.1, 8.8), African-American race (OR 2. 8; 95% CI 1.4, 5.6), serum creatinine level at a cutpoint of 1.5 mg/dL (OR 2.2; 95% CI 1.2, 3.8), cancer (OR 1.9; 95% CI 1.2, 3.0), coronary artery disease (OR 0.55; 95% CI 0.4, 0.8), and location of resuscitation in the intensive care unit (OR 0.51; 95% CI 0.4, 0.8). CONCLUSIONS: When talking with patients, physicians can describe the overall likelihood of surviving discharge as 1 in 8 for patients who undergo cardiopulmonary resuscitation and 1 in 3 for patients who survive cardiopulmonary resuscitation.

Molecular characterization and delineation of subtle deletions in de novo "balanced" chromosomal rearrangements.

To test the hypothesis that the phenotypic abnormalities seen in cases with apparently balanced chromosomal rearrangements are the result of the presence of cryptic deletions or duplications of chromosomal material near the breakpoints, we analyzed three cases with apparently balanced chromosomal rearrangements and phenotypic abnormalities. We characterized the breakpoints in these cases by using microsatellite analysis by polymerase chain reaction and fluorescence in situ hybridization analysis of yeast artificial chromosome clones selected from the breakpoint regions. Molecular characterization of the translocation breakpoint in patient 1 [46,XY,t(2;6)(p22.2;q23.1)] showed the presence of a 4- to 6-Mb cryptic deletion between markers D6S412 and D6S1705 near the 6q23.1 breakpoint. Molecular characterization of the proximal inversion 7q22.1 breakpoint in patient 2 [46,XY,inv(7)(q22.1q32.1)] revealed the presence of a 4-Mb cryptic deletion between D7S651 and D7S515 markers. No deletion or duplication of chromosomal material was found near the breakpoints in patient 3 [46,XX,t(2;6)(q33.1;p12.2)]. Our study suggests that a systematic molecular study of breakpoints should be carried out in cases with apparently balanced chromosomal rearrangements and phenotypic abnormalities, because cryptic deletions near the breakpoints may explain the phenotypic abnormalities in these cases.

Identification of the gene encoding the alternative sigma factor sigmaB from Listeria monocytogenes and its role in osmotolerance.

Listeria monocytogenes is well known for its robust physiology, which permits growth at low temperatures under conditions of high osmolarity and low pH. Although studies have provided insight into the mechanisms used by L. monocytogenes to allay the physiological consequences of these adverse environments, little is known about how these responses are coordinated. In the studies presented here, we have cloned the sigB gene and several rsb genes from L. monocytogenes, encoding homologs of the alternative sigma factor sigmaB and the RsbUVWX proteins, which govern transcription of a general stress regulon in the related bacterium Bacillus subtilis. The L. monocytogenes and B. subtilis sigB and rsb genes are similar in sequence and physical organization; however, we observed that the activity of sigmaB in L. monocytogenes was uniquely responsive to osmotic upshifting, temperature downshifting, and the presence of EDTA in the growth medium. The magnitude of the response was greatest after an osmotic upshift, suggesting a role for sigmaB in coordinating osmotic responses in L. monocytogenes. A null mutation in the sigB gene led to substantial defects in the ability of L. monocytogenes to use betaine and carnitine as osmoprotectants. Subsequent measurements of betaine transport confirmed that the absence of sigmaB reduced the ability of the cells to accumulate betaine. Thus, sigmaB coordinates responses to a variety of physical and chemical signals, and its function facilitates the growth of L. monocytogenes under conditions of high osmotic strength.

Endogenous mu opioid systems and suckling in the neonatal rat.

Localized injections of the mu antagonist CTOP into intracisternal (i.c.) or intracerebroventricular (i.c.v.) sites altered the behavior of 1-day-old rat pups during continuous exposure to an artificial nipple. Blockade of mu opioid receptors by i.c. injection decreased oral responsiveness to the nipple, while blockade of receptors by i.c.v. injection of CTOP increased oral responsiveness. The injection of CTOP into the i.c. site produced a transient reduction in body weight gain in pups suckling from their mother, while injection into the i.c.v. site had no effect. When cesarean-delivered pups were tested prior to suckling, injection of CTOP into the i.c. site increased latency of the first nipple attachment and decreased total time attached to a surrogate nipple providing milk. Injection of CTOP into the i.c.v. site decreased latency to the first nipple attachment. The results indicate that there is a caudal population of opioid receptors that is involved in the initiation of suckling behavior and a rostral population that plays a role in decreasing responsiveness at the nipple.

Critical role of anteiso-C15:0 fatty acid in the growth of Listeria monocytogenes at low temperatures.

Listeria monocytogenes is a food-borne pathogen capable of growth at refrigeration temperatures. Membrane lipid fatty acids are major determinants of a sufficiently fluid membrane state to allow growth at low temperatures. L. monocytogenes was characterized by a fatty acid profile dominated to an unusual extent (> 95%) by branched-chain fatty acids, with the major fatty acids being anteiso-C15:0, anteiso-C17:0, and iso-C15:0 in cultures grown in complex or defined media at 37 degrees C. Determination of the fatty acid composition of L. monocytogenes 10403S and SLCC 53 grown over the temperature range 45 to 5 degrees C revealed two modes of adaptation of fatty acid composition to lower growth temperatures: (i) shortening of fatty acid chain length and (ii) alteration of branching from iso to anteiso. Two transposon Tn917-induced cold-sensitive mutants incapable of growth at low temperatures had dramatically altered fatty acid compositions with low levels of i-C15:0, a-C15:0, and a-C17:0 and high levels of i-C14:0, C14:0, i-C16:0, and C16:0. The levels of a-C15:0 and a-C17:0 and the ability to grow at low temperatures were restored by supplementing media with 2-methylbutyric acid, presumably because it acted as a precursor of methylbutyryl coenzyme A, the primer for synthesis of anteiso odd-numbered fatty acids. When mid-exponential-phase 10403S cells grown at 37 degrees C were temperature down-shocked to 5 degrees C they were able, for the most part, to reinitiate growth before the membrane fatty acid composition had reset to a composition more typical for low-temperature growth. No obvious evidence was found for a role for fatty acid unsaturation in adaptation of L. monocytogenes to cold temperature. The switch to a fatty acid profile dominated by a-C15:0 at low temperatures and the association of cold sensitivity with deficiency of a-C15:0 focus attention on the critical role of this fatty acid in growth of L. monocytogenes in the cold, presumably through its physical properties and their effects, in maintaining a fluid, liquid-crystalline state of the membrane lipids.

Balanced translocation 46,XY,t(2;15)(q37.2;q11.2) associated with atypical Prader-Willi syndrome.

The lack of normally active paternal genes in 15q11-q13, as an outcome of either a paternal deletion or maternal disomy, accounts for >95% of all patients with Prader-Willi syndrome. Other mechanisms, including imprinting mutations and unbalanced translocations involving pat 15q11-q13, have been described elsewhere. In this study, we present a patient with a rare balanced, de novo translocation-46,XY,t(2;15)(q37.2;q11.2)-involving breakage within the Prader-Willi/Angelman syndrome region of the paternal homologue, without an apparent deletion. The patient demonstrated several manifestations of the Prader-Willi syndrome but was clinically atypical. Cytogenetic and molecular studies of this case demonstrated the translocation breakpoint to be between SNRPN and IPW, with mRNA expression of SNRPN and PAR-5 but absence of IPW and PAR-1 expression. These results suggest that disruption of either IPW expression or a nearby gene by an upstream break may contribute to the Prader-Willi syndrome phenotype and that expression of SNRPN or other upstream genes is responsible for other aspects of the classical Prader-Willi syndrome phenotype.

Fifteen-month follow-up of eye movement desensitization and reprocessing (EMDR) treatment for posttraumatic stress disorder and psychological trauma.

The present study is a 15-month follow-up of the effects of eye movement desensitization and reprocessing (EMDR) therapy on the functioning of 66 participants, 32 of whom were diagnosed with posttraumatic stress disorder (PTSD) prior to treatment, PTSD participants improved as much as those without the diagnosis, with both groups maintaining their gains at 15 months. At 15-month follow-up, the three 90-min sessions of EMDR previously administered (S.A. Wilson, L.A. Becker, & R. H. Tinker, 1995) produced an 84% reduction in PTSD diagnosis and a 68% reduction in PTSD symptoms. The average treatment effect size was 1.59; the average reliable change index was 3.37. Implications of the maintenance of EMDR treatment effects are discussed.

Manipulation of the dopamine system affects fetal and neonatal responses to an artificial nipple.

Rat fetuses respond to stimuli that they will encounter later while suckling. When exposed to an artificial nipple (AN) E21 fetuses show overall behavioral activation, mouthing, facial wiping, and oral grasping of the AN. The present experiments examined fetal and neonatal responses to the AN after central nervous system injection of receptor-binding drugs for the dopamine system. The D2 agonist drug quinpirole increased appetitive responses to the AN in the fetus and neonate. Activity at the D2 dopamine receptor promotes expression of fetal behavioral responses that are similar to those shown by the neonatal rat at the nipple. Motor responses also were elicited in neonatal pups that normally do not attach to the artificial nipple. These findings suggest that the dopamine system may regulate oral capture of the nipple in the neonatal rat.