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Opioids for the palliation of breathlessness in terminal illness.

BACKGROUND: Breathlessness is a common symptom in people with advanced disease. The most effective treatments are aimed at treating the underlying cause of the breathlessness but this may not be possible and symptomatic treatment is often necessary. Strategies for the symptomatic treatment of breathlessness have never been systematically evaluated. Opioids are commonly used to treat breathlessness: the mechanisms underlying their effectiveness are not completely clear and there have been few good-sized trials in this area. OBJECTIVES: To determine the effectiveness of opioid drugs given by any route in relieving the symptom of breathlessness in patients who are being treated palliatively. SEARCH STRATEGY: An electronic search was carried out of Medline, Embase, Cinahl, the Cochrane library, Dissertation Abstracts, Cancercd and SIGLE. Review articles and reference lists of retrieved articles were hand searched. Date of most recent search: May 1999 SELECTION CRITERIA: Randomised double-blind, controlled trials comparing the use of any opioid drug against placebo for the relief of breathlessness were included. Patients with any illness suffering from breathlessness were included and the intervention was any opioid, given by any route, in any dose. DATA COLLECTION AND ANALYSIS: Studies identified by the search were imported into a reference manager database. The full texts of the relevant studies were retrieved and data were independently extracted by two reviewers. Studies were quality scored according to the Jadad scale. The primary outcome measure used was breathlessness and the secondary outcome measure was exercise tolerance. Studies were divided into non-nebulised and nebulised and were analysed both separately and together. A qualitative analysis was carried out of adverse effects of opioids. Where appropriate, meta-analysis was carried out. MAIN RESULTS: Eighteen studies were identified of which nine involved the non-nebulised route of administration and nine the nebulised route. A small but statistically significant positive effect of opioids was seen on breathlessness in the analysis of studies using non-nebulised opioids. There was no statistically significant positive effect seen for exercise tolerance in either group of studies or for breathlessness in the studies using nebulised opioids. REVIEWER'S CONCLUSIONS: There is evidence to support the use of oral or parenteral opioids to palliate breathlessness although numbers of patients involved in the studies were small. No evidence was found to support the use of nebulised opioids. Further research with larger numbers of patients, using standardised protocols and with quality of life measures is needed.

Apnea↗

Fluoride varnishes for preventing dental caries in children and adolescents.

BACKGROUND: Topically applied fluoride varnishes have been used extensively as an operator-applied caries-preventive intervention for over two decades. OBJECTIVES: To determine the effectiveness and safety of fluoride varnishes in the prevention of dental caries in children and to examine factors potentially modifying their effect. SEARCH STRATEGY: Multiple electronic database searches, reference lists of articles, journal handsearch, selected authors and manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride varnish with placebo or no treatment in children up to 16 years during at least one year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Study authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF), that is the difference in caries increments between the treatment and control groups expressed as a percentage of the increment in the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects meta-regression analyses. MAIN RESULTS: Nine studies were included, involving 2709 children. For the seven that contributed data for the main meta-analysis, the D(M)FS pooled prevented fraction estimate was 46% (95% CI, 30% to 63%; p<0.0001). There was substantial heterogeneity, confirmed statistically (p<0.0001). The pooled d(e/m)fs prevented fraction estimate was 33% (95% CI, 19% to 48%; p<0.0001). No significant association between estimates of D(M)FS prevented fractions and baseline caries severity or background exposure to fluorides was found in meta-regression, and a funnel plot of the seven studies indicated no relationship between prevented fraction and study precision. In both methods, power is limited when only a few trials are included. REVIEWER'S CONCLUSIONS: The review suggests a substantial caries-inhibiting effect of fluoride varnish in both the permanent and the deciduous dentitions based largely on trials with no treatment controls. There is little information concerning acceptability of treatment or possible side effects in the included trials. Given the relatively poor quality of most of the included studies and the wide confidence intervals around the estimates of effect, there remains a need for further trials. It is important that these trials should be of high quality and include assessment of potential adverse effects.

Adolescent↗

Fluoride gels for preventing dental caries in children and adolescents.

BACKGROUND: Topically applied fluoride gels have been widely used as a caries-preventive intervention in dental surgeries and school-based programs for over two decades. OBJECTIVES: To determine the effectiveness and safety of fluoride gels in the prevention of dental caries in children and to examine factors potentially modifying their effect. SEARCH STRATEGY: Multiple electronic database searches, reference lists of articles, journal handsearch, selected authors and manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride gel with placebo or no treatment in children up to 16 years during at least one year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Study authors were contacted for missing data. The primary outcome measure was the prevented fraction (PF), that is the caries increment in the treatment group expressed as a percentage of the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects meta-regression analyses. MAIN RESULTS: Twenty-five studies were included, involving 7747 children. For the 23 that contributed data for meta-analysis, the D(M)FS pooled prevented fraction estimate was 28% (95% CI, 19% to 37%; p<0.0001). There was clear heterogeneity, confirmed statistically (p<0.0001). The effect of fluoride gel varied according to type of control group used, with D(M)FS PF on average being 19% (95% CI, 5% to 33%; p<0.009) higher in non-placebo controlled trials. A funnel plot of the 23 studies indicated a relationship between prevented fraction and study precision. Only two trials reported on adverse events. REVIEWER'S CONCLUSIONS: There is clear evidence of a caries-inhibiting effect of fluoride gel. The best estimate of the magnitude of this effect, based on the 14 placebo-controlled trials, is a 21% reduction (95% CI, 14 to 28%) in D(M)FS. This corresponds to an NNT of 2 (95% CI, 1 to 3) to avoid 1 D(M)FS in a population with a caries increment of 2.2 D(M)FS/year, or an NNT of 24 (95% CI, 18 to 36) based on an increment of 0.2 D(M)FS/year. There is little information concerning deciduous dentition, on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.

Adolescent↗

Cognitive rehabilitation for memory deficits following stroke.

BACKGROUND: Memory problems occur following stroke. Cognitive rehabilitation programmes are provided to retrain memory function or to teach patients strategies to cope despite memory impairment. OBJECTIVES: To determine the effects of cognitive rehabilitation for memory problems following stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register, Medline, EMBASE, CINHAL and CLIN PSYCH databases and reference lists from relevant articles. Date of most recent searches: December 1998. SELECTION CRITERIA: Controlled trials of memory retraining in stroke. Studies with mixed aetiology groups were excluded unless they had more than 75% of stroke patients or separate data were available for the stroke patients. DATA COLLECTION AND ANALYSIS: Two reviewers extracted trial data and assessed trial quality. Reviewers contacted investigators for further details of trials. MAIN RESULTS: One trial was identified with 12 participants. This showed memory strategy training had no significant effect on memory impairment or subjective memory complaints. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support or refute the effectiveness of cognitive rehabilitation for memory problems after stroke.

Attention↗

Cognitive rehabilitation for attention deficits following stroke.

BACKGROUND: Attention problems occur following stroke and are treated using computerised activities or paper and pencil tasks. OBJECTIVES: To determine the effects of cognitive rehabilitation for attention deficits following stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register, Medline, EMBASE, CINHAL and CLIN PSYCH databases and reference lists from relevant articles. Date of most recent searches: December 1998 SELECTION CRITERIA: Controlled trials of attention training in stroke. Studies with mixed aetiology groups were excluded unless they included more than 75% of stroke patients or separate data were available for the stroke patients. DATA COLLECTION AND ANALYSIS: Two reviewers extracted trial data and assessed trial quality. Reviewers contacted investigators for further details of trials. MAIN RESULTS: Two trials were identified with 56 participants. The two trials showed a benefit of training on measures of alertness and sustained attention. Only one trial included a measure of functional independence and this showed no significant effect of training. REVIEWER'S CONCLUSIONS: There is some indication that training improves alertness and sustained attention but no evidence to support or refute the use of cognitive rehabilitation for attention deficits to improve functional independence following stroke.

Attention↗

Erythropoietin for patients with malignant disease.

BACKGROUND: Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (EPO) and red blood cell transfusions. OBJECTIVES: The aim of this systematic review was to assess the effect of erythropoietin to either prevent or treat anaemia in cancer patients. SEARCH STRATEGY: We searched the Central Register of Controlled Trials, MEDLINE (01/1985 to 12/2001), EMBASE (01/1985 to 12/2001), other databases and reference lists of articles. We also contacted experts in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing the use of recombinant human erythropoietin (plus transfusion if needed) with red blood cell transfusions alone for the treatment or prevention of anaemia in cancer patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. All authors from included studies were contacted for additional information. MAIN RESULTS: Twenty seven trials with 3,287 adults were included. Use of erythropoietin significantly reduced the relative risk of red blood cell transfusions (RR 0.67; 95% CI 0.62 to 0.73, 25 trials, n = 3,069). On average participants in the erythropoietin group received one unit of blood less than the control group (WMD -1.00; 95% CI-1.31 to -0.70, 13 trials, n = 2,056). For participants with baseline haemoglobin below 10 g/dL haematological response was observed more often in participants receiving EPO (RR 3.60; 95% CI 3.07 to 4.23, 14 trials, n = 2,347). There was inconclusive evidence whether EPO improves tumour response (fixed effect RR 1.36; 95% CI 1.07 to 1.72, seven trials, n = 1,150; random effects: RR 1.21; 95% CI 0.92 to 1.59) and overall survival (adjusted data: HR 0.81; 95% CI 0.67 to 0.99; unadjusted data: HR 0.84; 95% CI 0.69 to 1.02, 19 trials, n = 2,865). There were no statistically significant adverse effects. Evidence was inconclusive with respect to quality of life and fatigue. REVIEWERS' CONCLUSIONS: There is consistent evidence that the administration of erythropoietin reduces the risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 10 g/dL there is strong evidence that erythropoietin improves haematological response. There is inconclusive evidence whether erythropoietin improves tumour response and overall survival. Research on side effects is inconclusive.

Anemia↗

Iodine supplementation for preventing iodine deficiency disorders in children.

BACKGROUND: Iodine deficiency is the main cause of potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. OBJECTIVES: To assess the effects of iodine supplementation overall, and of different forms and dosages of iodine supplementation separately, in the prevention of iodine deficiency disorders in children. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE and reference lists, databases of ongoing trials and the Internet were searched. Date of latest search: October 2003. SELECTION CRITERIA: We included randomised controlled trials and prospective controlled trials not using randomisation of iodine supplementation in children living in areas of iodine deficiency. DATA COLLECTION AND ANALYSIS: Two reviewers did the initial data selection and quality assessment of trials independently. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. MAIN RESULTS: Twenty-six prospective controlled trials were related to our question, assessing a total of 29613 children. Twenty of them were classified as being of low quality, six of moderate quality. Most studies used iodised oil as a supplement, but other supplements were also used. The intervention groups were compared to a non-supplemented control group, different doses or different forms of iodine supplementation. There was a clear tendency towards goitre reduction with iodine supplementation; this was significant in several studies. Significant differences in physical development were not seen, except in one study. Results for differences in cognitive and psychomotor measures were mixed, with only few studies showing a positive intervention effect. One study suggested that infant mortality was lowered after iodine supplementation. Most studies showed a significant increase in urinary iodine excretion and levels recommended by the WHO were reached in most cases after supplementation. Thyroid-stimulating hormone (TSH) levels were significantly reduced in one study. In 1.8% of the children investigated, adverse effects were found, most of them were minor and transient. REVIEWERS' CONCLUSIONS: Despite most of the included studies being of low quality, the results suggest that iodine supplementation, especially iodised oil, is an effective means of decreasing goitre rates and improving iodine status in children. Indications of positive effects on physical and mental development and mortality were seen, although results were not always significant. Adverse effects were generally minor and transient. Insufficient evidence was available on non-oil supplements. High quality controlled studies investigating relevant long term outcome measures are needed to address the question of the best form of iodine supplementation in different population groups and settings.

Child↗

Dan Shen agents for acute ischaemic stroke.

BACKGROUND: Based mainly on experimental data which indicates improvement to the cerebral microcirculation, Dan Shen, a form of herbal medicine, is widely used in the treatment of acute ischaemic stroke in China. We aimed to assess the evidence from randomised controlled trials of their effects. OBJECTIVES: To review the randomised or quasi-randomised controlled trials of Dan Shen agents for acute ischaemic stroke. The primary objective was to determine whether Dan Shen agents improve functional outcome without causing undue harm in patients with acute ischaemic stroke. Secondary objectives were to assess the effect of Dan Shen agents on impairment and on quality of life. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2003), the register of the Cochrane Complementary Field (last searched September 2003) and the Chinese Stroke Trials Register (last searched September 2003). In addition we searched the following bibliographic databases: The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002), MEDLINE (1996 to December 2002), EMBASE (1980 to December 2002), CINAHL (1982 to December 2002), AMED (1985 to December 2002) and China Biological Medicine Database (CBM-disc 1979 to December 2002). We handsearched 10 Chinese journals, searched clinical trials and research databases, scanned reference lists and contacted the pharmaceutical company manufacturing Dan Shen. SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled clinical trials comparing Dan Shen agents with placebo or open control (no placebo) in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Eight potentially eligible trials were identified, of which three trials (304 patients) were included. Two trials were excluded and three trials are awaiting assessment. Numbers of deaths and dependent patients at the end of follow-up of at least three months were not reported in the three included trials. Only one trial reported adverse events. Three trials measured the outcome "significant improvement in neurological deficit at the end of treatment". Compound Dan Shen agents were associated with a significant increase in the number of patients with the outcome (Peto Odds Ratio (OR) 2.72, 95% Confidence Interval (CI) 1.10 to 6.72). No deaths were reported within the first two weeks of treatment or during the whole follow-up period (21 to 28 days). The trials did not include any assessment of quality of life. REVIEWERS' CONCLUSIONS: There were too few patients and outcome events to draw reliable conclusions from the present data. The methodological qualities of all included studies were poor. Further high-quality randomised controlled trials should be performed.

Acute Disease↗

Megestrol acetate for the treatment of anorexia-cachexia syndrome.

BACKGROUND: Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993 MA was approved by the USA's Federal Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic and AIDS patients is under investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. SEARCH STRATEGY: Studies were sought thorough an extensive search of the electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search was carried out on October 2002. SELECTION CRITERIA: Studies were included in the review if they assessed megestrol acetate compared to placebo or other drug treatments in randomized controlled trials of patients with a clinical diagnosis of anorexia-cachexia related to cancer, AIDS or another underlying pathology. DATA COLLECTION AND ANALYSIS: Data extraction was conducted by two independent authors, and methodological quality evaluated. Quantitative analyses were performed using appetite and quality of life as a dichotomous variable, and weight gain was analysed as continuous and dichotomous variables. Studies with more than 50% of patients lost to follow-up were excluded from the analysis. MAIN RESULTS: Thirty trials met the inclusion criteria (4123 patients). Twenty-one trials compared MA at different doses with placebo; four compared different doses of MA versus other drugs; two compared MA with other drugs and placebo; and three compared different doses of MA. For all patient conditions, meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer patients. Analysing quality of life, clinical and statistical heterogeneity was found and discussed. There was insufficient information to define the optimal dose of MA. AUTHORS' CONCLUSIONS: This review demonstrates that MA improves appetite and weight gain in patients with cancer. No overall conclusion about quality of life (QOL) could be drawn due to heterogeneity. The small number of patients, methodological shortcomings and poor reporting have not allowed us to recommend megestrol acetate in AIDS patients or with other underlying pathologies.

Acquired Immunodeficiency Syndrome↗

African swine fever virus-induced polypeptides in porcine alveolar macrophages and in Vero cells: two-dimensional gel analysis.

High-resolution two-dimensional electrophoresis followed by computer analysis has been used to study quantitatively the patterns of protein synthesis produced in porcine alveolar macrophages and in Vero cells infected with African swine fever virus (ASFV). Initially, a protein database for each cell type was constructed. The porcine alveolar macrophage database includes 995 polypeptides (818 acidic, isoelectric focusing (IEF) and 177 basic, nonequilibrium pH gradient electrophoresis (NEPHGE)) whereas the Vero database contains 1,398 polypeptides (1,127 acidic, IEF and 271 basic, NEPHGE). Taking these databases as reference, ASFV highly virulent strain E70 induces 57 acid and 43 basic polypeptides in porcine alveolar macrophages, which account for most of the information content of the virus DNA. The kinetics of synthesis of the virus-induced polypeptides showed the existence of three classes of proteins: one whose synthesis starts early after infection, continues for a period and then switches off; another whose synthesis also starts early but continues for prolonged periods; and a third which requires DNA replication. The attenuated, cell adapted, strain BA71V induces 92 acidic and 37 basic proteins in Vero cells. Significant differences were observed when comparing the patterns of polypeptides induced by the two viral strains. In both cell systems studied, ASFV infection produces a general shutoff of protein synthesis that affects up to 65% of the cellular proteins. Interestingly, 28 proteins of porcine alveolar macrophages and 48 proteins of Vero cells are stimulated at least two times by ASFV infection.

African Swine Fever Virus↗

Occurrence of A-waves in F-wave studies of healthy nerves.

A-waves are compound muscle action potentials that follow the M-wave with a constant shape and latency; usually they are detected during F-wave studies. A large reference value database for F-wave parameters from the median, ulnar, peroneal, and tibial nerves was collected from 121-196 subjects aged 14 to 95 years without known pathology involving the studied nerves. From this material, we studied retrospectively the occurrence of A-waves. To be included, an A-wave had to be clearly discriminated from the baseline in at least 8 of 20 traces with a jitter of less than 0.5 ms. A-waves occurred in 25% of the tibial nerves studied and 14% of the peroneal nerves but in only 2% of median and ulnar nerves. In the peroneal and tibial nerves, the frequency of A-waves increased with age, suggesting that A-waves may be related to normal age-related mild neuropathic changes of alpha motor neurons. Thus, A-waves are frequently found in lower-extremity nerves in healthy subjects and less commonly in upper-extremity nerves. Their presence must therefore be interpreted with caution and cannot be taken as necessarily indicative of abnormality.

Adolescent↗

Health promotion in the city: a structured review of the literature on interventions to prevent heart disease, substance abuse, violence and HIV infection in US metropolitan areas, 1980-1995.

To achieve its national public health goals, the US must improve the health of low-income urban populations. To contribute to this process, this study reviewed published reports of health promotion interventions designed to prevent heart disease, HIV infection, substance abuse, and violence in US cities. The study's objectives were to describe the target populations, settings, and program characteristics of these interventions and to assess the extent to which these programs followed accepted principles for health promotion. Investigators searched five computerized databases and references of selected articles for articles published in peer-reviewed journals between 1980 and 1995. Selected articles listed as a main goal primary prevention of one of four index conditions; were carried out within a US city; included sufficient information to characterize the intervention; and organized at least 25% of its activities within a community setting. In general, programs reached a diverse population of low-income city residents in a variety of settings, employed multiple strategies, and recognized at least some of the principles of effective health promotion. Most programs reported a systematic evaluation. However, many programs did not involve participants in planning, intervene to change underlying social causes, last more than a year, or tailor for the subpopulations they targeted, limiting their potential effectiveness. Few programs addressed the unique characteristics of urban communities.

HIV Infections↗

Value of routine preoperative chest x-rays: a meta-analysis.

The purpose of this study was to estimate the frequency with which routine postoperative chest x-rays lead to clinically relevant new information. All articles in English, French and Spanish relating to routine chest radiography in North American or European populations were reviewed, using the Medline database and references listed in reviews and periodicals published from 1966 to 1992, inclusive. Twenty-one reports which supplied sufficient information were included for meta-analysis. On average, abnormalities were found in 10% of routine preoperative chest films. In only 1.3% of films were the abnormalities unexpected, i.e., were not already known or would not otherwise have been detected (95% CI: 0 to 2.8%). These findings were of sufficient importance to cause modification of management in only 0.1% (95% CI: 0 to 0.6%). The frequency with which the new information influenced health could not be estimated. Assuming only the direct cost to the health care system of each radiograph ($23), each finding which influenced management in any way would cost $23,000. It is concluded that in North American or European populations when a reliable history and a clinical examination are carried out, the cost of this test is so high relation to the clinical information provided that it is no longer justifiable.

Age Factors↗

[Minimum requirements in total knee replacement. Evidence report and model calculation of the healthcare situation].

This report assesses the volume-outcome relationship of total knee replacement and the effects of its application on medical care in Germany. Electronic bibliographic databases, the reference lists of relevant articles, and research-related resources of various health services were searched and selected studies were assessed. Additionally, the consequences of implementing a regulation based on volume-outcome relationship were calculated using different models. The results in the literature concerning defined outcome parameters are inconsistent, but in all but one publication a general correlation between high volume and low complication rate could be identified. Implementing a regulation based on volume-outcome relationship with cutoff points of 20/50/100 total knee replacements/year would lead to an exclusion of 242/502/709 hospitals, respectively, from medical care. This would result in a reallocation of 2358 (2.9%)/10752 (13.2%)/25482 (31.2%) patients/year, respectively (extrapolation). The application of a regulation based on volume-outcome considerations in the German healthcare system must be performed very carefully because significant effects are to be expected.

Arthroplasty, Replacement, Knee↗

St. John's wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature.

RATIONALE: St. John's wort (Hypericum perforatum) has recently gained popularity as an alternative treatment for mild to moderate depression. Given the current widespread use of this herbal remedy, it is important for medical professionals to understand the potential pharmacological pathways through which Hypericum may exert an antidepressant effect. OBJECTIVES: (1) To review the current pharmacological, toxicological, and clinical literature available on Hypericum, and (2) to provide a synthesis of this information into a form that may be easily used by health care providers. METHOD: A comprehensive review of the recent scientific literature (January 1990-March 2000) was performed using the following electronic databases and reference publications: MEDLINE, The Cochrane Library, HealthSTAR, Current Contents (all editions), European Scientific Cooperative on Phytotherapy monographs, German Commission E monographs, and the Physicians' Desk Reference for Herbal Medicines, 1st edition. RESULTS: One hundred and seven (107) publications in the English language and three publications in German were included in the review. Collectively, the data suggest that therapeutic preparations of Hypericum extract appear to exert potentially significant pharmacological activity within several neurochemical systems believed to be implicated in the pathophysiology of depression. However, little information exists regarding the safety of Hypericum, including potential herb-drug interactions. CONCLUSIONS: Additional research on the pharmacological and biochemical activity of Hypericum and its several bioactive constituents is necessary to further elucidate the mode(s) of antidepressant action. Given what is currently known and unknown about the biological properties of Hypericum, those who choose to use this herb should be closely monitored by a physician.

Animals↗

Species identification by means of pyrosequencing the mitochondrial 12S rRNA gene.

The aim of this study was to develop a new method for species identification based on the analysis of a very short nucleotide sequence. For this reason, the mitochondrial 12S rRNA gene, together with the new method of pyrosequencing, was used. The detection of only 20 nucleotides, following the sequencing primer within a 149-bp fragment by pyrosequencing, was sufficient to identify the biological origin of the samples by alignment with a reference sequence database. A case example with a piece of skin is presented, and the question whether this piece of skin came from a missing wife or from an animal could be answered.

Animals↗

Inference from the relationships between linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related genes in four Asian populations.

The extensive nucleotide diversity in drug-related genes predisposes individuals to different drug responses and is a major problem in current clinical practice and drug development. Striking allelic frequency differences exist in these genes between populations. In this study, we genotyped 240 sites known to be polymorphic in the Japanese population in each of 270 unrelated healthy individuals comprising 90 each of Malaysian Malays, Indians, and Chinese. These sites are distributed in 109 genes that are drug related, such as genes encoding drug-metabolizing enzymes and drug transporters. Allele frequency and linkage disequilibrium distributions of these sites were determined and compared. They were also compared with similar data of 752 Japanese. Extensive similarities in allele frequency and linkage disequilibrium distributions were observed among Japanese, Malaysian Chinese, and Malays. However, significant differences were observed between Japanese and Malaysian Chinese with Malaysian Indians. These four populations were grouped into two genetic clusters of different ancestries. However, a higher correlation was found between Malaysian Malays and Indians, indicating the existence of extensive admixture between them. The results also imply the possible and rational use of existing single nucleotide polymorphism databases as references to assist future pharmacogenetic studies involving populations of similar ancestry.

Alleles↗

Clinical laboratory differentiation of infectious versus non-infectious systemic inflammatory response syndrome.

OBJECTIVE: To evaluate the accuracy of C-reactive protein (CRP), procalcitonin (PCT), neopterin, and endotoxin in the differential diagnosis of sepsis and non-infectious systemic inflammatory response syndrome (SIRS). METHODS: A Medline database and references from identified articles were used to perform a literature search relating to the differential diagnosis of sepsis versus non-infectious SIRS. RESULTS: CRP, PCT, and neopterin are released both in sepsis and in non-infectious inflammatory disease. CRP and PCT are equally effective, although not perfect, in differentiating between sepsis and non-infectious SIRS. However, CRP and PCT have different kinetics and profiles. The kinetics of CRP is slower than that of PCT, and CRP levels may not further increase during more severe stages of sepsis. On the contrary, PCT rises in proportion to the severity of sepsis and reaches its highest levels in septic shock. PCT tends to be higher in nonsurvivor than in survivor. Therefore, PCT demonstrated a closer correlation with the severity of sepsis and outcome than CRP. Unlike CRP and PCT, neopterin is increased in viral infection as well as bacterial infection, and neopterin is also a useful indicator of sepsis. Endotoxemia was detected in no more than half of patients with Gram-negative bacteremia, and Gram-negative bacteremia was detected in half of patients with endotoxemia. CONCLUSIONS: The diagnostic capacity of PCT is superior to that of CRP due to the close correlation between PCT levels and the severity of sepsis and outcome. Neopterin is very useful in the diagnosis of viral infection. The endotoxin assay in combination with CRP, PCT, or neopterin may help as a diagnostic marker for Gram-negative bacterial infection.

Animals↗