Diagnostic antigenemia tests for penicilliosis marneffei

Disseminated penicilliosis marneffei is an emerging opportunistic mycosis seen in severely immunocompromised human immunodeficiency virus (HIV)-infected patients and is caused by the dimorphic fungus Penicillium marneffei. Early diagnosis and treatment improve clinical outcome. Proper diagnosis is complicated by nonspecific signs and symptoms and by difficulties in histologic recognition and species identification of the pathogen. Since no established immunodiagnostic methods for penicilliosis marneffei are available, we attempted to develop separate immunodiffusion tests to detect P. marneffei antigens and antibodies in patient serum specimens and a latex agglutination test for antigenemia. Antigens consisted of 2-week-old fission arthroconidial filtrates produced in Pine's broth at 37 degrees C. Rabbit antisera were prepared against the 10 x -concentrated filtrate antigens. Studies were carried out with 17 serum specimens from HIV-seropositive adult Thai patients with penicilliosis marneffei and 15 control serum specimens from Thai persons free of HIV and P. marneffei infection. The immunodiffusion tests detected P.marneffei antigenemia in 10 (58.8%) of 17 patients, whereas the latex agglutination test detected antigenemia in 13 (76.5%) of the 17 patients. Antibody was demonstrated in only 2 of the 17 patient sera. All of the tests appeared to be highly specific, since none were positive with sera from 15 Thai control patients, six serum samples containing cryptococcal antigen, or six urine specimens positive for Histoplasma polysaccharide antigens.     

Cervical conization and preterm delivery/low birth weight. A systematic review of the literature

OBJECTIVE: Evaluate the effect of cervical conization on preterm birth/low birth weight (LBW). DESIGN: A systematic review of the literature using external or internal controls. RESULTS: The typical odds ratio for preterm delivery in women with prior cervical conization using external controls was 3.23 (95% confidence interval 2.29-4.55). Using internal controls the typical odds ratio for LBW was 2.97 (95% confidence interval 1.09-8.05). Using external controls the typical odds ratio for LBW was 2.31 (95% confidence interval 1.33-3.99). CONCLUSION: Women with cervical conization are at higher risk for preterm birth than external controls, and the surgical intervention as such is a major determining factor.     

A systematic review of the evidence for hypodermoclysis to treat dehydration in older people

BACKGROUND: The purpose of the study was to evaluate the evidence supporting the use of hypodermoclysis (i.e., subcutaneous infusion of fluids) to treat dehydrated elderly patients, and to discuss clinical applications of this mode of therapy in the long-term care setting. METHOD: Articles reporting the use of hypodermoclysis were identified using a systematic MEDLINE search between January 1966 and May 1996. Articles were included in our sample if they contained original patient data that evaluated either the efficacy or adverse effects associated with the use of subcutaneous infusions to treat dehydration in adults, whether hyaluronidase was required to facilitate the absorption of subcutaneous fluid, or if potassium could be added to the solution. RESULTS: Eighteen articles met the inclusion criteria. Since we hypothesized that adverse effects associated with hypodermoclysis may have been related largely to the use of nonelectrolyte or hypertonic solutions, the studies were evaluated according to the type of fluid administered. Six hundred and eighty-five patients were described in 13 studies evaluating the efficacy and toxicity of subcutaneously administered fluid. Four studies evaluated hypodermoclysis using electrolyte-containing solutions in 25 patients. Two of these were randomized control trials (RCT) that compared hypodermoclysis to intravenous therapy. Both reported similar absorption of fluids. In the single RCT that evaluated adverse effects, 4 of 17 patients receiving hypodermoclysis reported minor side effects similar to those reported with intravenous therapy. Adverse effects were more severe when electrolyte-free or hypertonic solutions were evaluated. Of the 639 patients who may have received electrolyte-free solutions, 16 patients (2.5%) reported adverse effects, 8 of which were severe. Both patients reported to have received hypertonic solutions noted adverse effects, one of which was severe. The use of hyaluronidase to facilitate absorption was evaluated in 74 patients. These studies suggest that hyaluronidase improves the speed of fluid absorption but may not change the patient's comfort level. A single case report of 350 subcutaneous infusions in 67 patients investigated the administration of up to 34 mmol/L of potassium chloride (KCl) by hypodermoclysis. The only adverse reaction observed was discomfort at the infusion site. CONCLUSIONS: Hypodermoclysis can be used to most safely provide fluids when electrolyte-containing fluids are administered. Hypodermoclysis may have fallen into disuse because of reports of severe adverse reactions related to infusions of electrolyte-free or hypertonic solutions that would likely be considered inappropriate today. Whether or not hyaluronidase is required to promote subcutaneous fluid absorption remains unresolved. Limited evidence suggests that potassium chloride may, with caution, be safely added to subcutaneous infusions. The majority of the available studies evaluating hypodermoclysis are of poor quality. Because of the tremendous potential benefits of administering fluid subcutaneously, there is a need for good quality studies to evaluate the efficacy of hypodermoclysis.     

A critical review of the approach to birth order research.

The birth order literature was reviewed in order to demonstrate that the present emphasis on birth order differences with a de-emphasis on theory has resulted in confusion. Birth order research topics reviewed were: child-rearing practices, affiliation, dependence, and conformity, intelligence and achievement, and alcoholism. Following the review, two suggestions were made concerning the direction of future birth order research. The first concerned the importance of undertaking theoretically-derived research as opposed to research focused on differences. Developmental theories, particularly those considering the family and child-rearing practices were suggested. The second concerned the value of a moderator variable (Ghiselli, 1963) in birth order research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gastroduodenal inflammation associated with Helicobacter pylori infection. Diagnostic and therapeutic implications (a review)

Site-directed mutagenesis has proved an effective experimental technique to investigate catalytic mechanisms and to determine relations between enzyme structure and function. This article invokes an analytical model based on evolution by mutation and natural selection-Nature's analogue of site-directed mutagenesis-to derive a set of general rules relating enzyme structure and activity. The catalysts are described in terms of the structural parameters, rigidity and flexibility, and the functional variables, reaction rate and substrate specificity. The evolutionary model predicts the following structure-activity relations: (a) rigid enzyme-flexible substrate: large variation in reaction rates, broad substrate specificity; (b) rigid enzyme-rigid substrate: diffusion controlled rates, absolute specificity; (c) flexible enzyme-rigid substrate: intermediate reaction rates, group specificity; (d) flexible enzyme-flexible substrate: slow rates, absolute specificity. Spectroscopic methods and X-ray crystallography now yield important characteristics of enzyme-substrate complexes such as molecular flexibility. The evolutionary analysis we have exploited provides general principles for inferring catalytic activity from structural studies of enzyme-substrate complexes.     

Relaxation techniques for acute pain management: a systematic review

A papain-type cysteine endopeptidase with a molecular mass of 35 kDa for the mature enzyme, was purified from germinating castor bean (Ricinus communis L.) endosperm by virtue of its capacity to process the glyoxysomal malate dehydrogenase precursor protein to the mature subunit in vitro (C. Gietl et al., 1997, Plant Physiol 113: 863-871). The cDNA clones from endosperm of germinating seedlings and from developing seeds were isolated and sequence analysis revealed that a very similar or identical peptidase is synthesised in both tissues. Sequencing established a presequence for co-translational targeting into the endoplasmic reticulum, an N-terminal propeptide and a C-terminal KDEL motif for the castor bean cysteine endopeptidase precursor. The 45-kDa pro-enzyme stably present in isolated organelles was enzymatically active. Immunocytochemistry with antibodies raised against the purified cysteine endopeptidase revealed highly specific labelling of ricinosomes, organelles which co-purify with glyoxysomes from germinating Ricinus endosperm. The cysteine endopeptidase from castor bean endosperm, which represents a senescing tissue, is homologous to cysteine endopeptidases from other senescing tissues such as the cotyledons of germinating mung bean (Vigna mungo) and vetch (Vicia sativa), the seed pods of maturing French bean (Phaseolus vulgaris) and the flowers of daylily (Hemerocallis sp.).     

A systematic review of compression treatment for venous leg ulcers

OBJECTIVE: To estimate the clinical and cost effectiveness of compression systems for treating venous leg ulcers. METHODS: Systematic review of research. Search of 19 electronic databases including Medline, CINAHL, and Embase. Relevant journals and conference proceedings were hand searched and experts were consulted. MAIN OUTCOME MEASURES: Rate of healing and proportion of ulcers healed within a time period. STUDY SELECTION: Randomised controlled trials, published or unpublished, with no restriction on date or language, that evaluated compression as a treatment for venous leg ulcers. RESULTS: 24 randomised controlled trials were included in the review. The research evidence was quite weak: many trials had inadequate sample size and generally poor methodology. Compression seems to increase healing rates. Various high compression regimens are more effective than low compression. Few trials have compared the effectiveness of different high compression systems. CONCLUSIONS: Compression systems improve the healing of venous leg ulcers and should be used routinely in uncomplicated venous ulcers. Insufficient reliable evidence exists to indicate which system is the most effective. More good quality randomised controlled trials in association with economic evaluations are needed, to ascertain the most cost effective system for treating venous leg ulcers.     

Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection

An invading pathogen must be held in check by the innate immune system until a specific immune response can be mounted. In the case of Gram-negative bacteria, the principal stimulator of the innate immune system is lipopolysaccharide (LPS), a component of the bacterial outer membrane. In vitro, LPS is bound by lipopolysaccharide-binding protein (LBP) and transferred to CD14--the LPS receptor on the macrophage surface--or to high-density lipoprotein (HDL) particles. Transfer to CD14 triggers an inflammatory response which is crucial for keeping an infection under control. Here we investigate how LBP functions in vivo by using LBP-deficient mice. Surprisingly, we find that LBP is not required in vivo for the clearance of LPS from the circulation, but is essential for the rapid induction of an inflammatory response by small amounts of LPS or Gram-negative bacteria and for survival of an intraperitoneal Salmonella infection.     

Feverfew as a preventive treatment for migraine: a systematic review

BACKGROUND: Feverfew is a popular herbal remedy advocated for the prevention of migraine. AIM: The aim of this systematic review was to look at the evidence for or against the clinical effectiveness of feverfew in migraine prevention. DATA SOURCES: Literature searches were performed using the following databases: Medline, Embase, Biosis, CISCOM, and the Cochrane Library (all from their inception to April 1998). STUDY SELECTION: Only randomized, placebo-controlled, double-blind trials were included. DATA EXTRACTION: All articles were read by two independent reviewers. Data were extracted in a predefined, standardized fashion. The methodological quality of all trials was evaluated using the Jadad score. MAIN RESULTS: Five trials met the inclusion/exclusion criteria. The majority favor feverfew over placebo. Yet important caveats exist. CONCLUSION: The clinical effectiveness of feverfew in the prevention of migraine has not been established beyond reasonable doubt.     

Newborn screening for inborn errors of metabolism: a systematic review

OBJECTIVES. To establish a database of literature and other evidence on neonatal screening programmes and technologies for inborn errors of metabolism. To undertake a systematic review of the data as a basis for evaluation of newborn screening for inborn errors of metabolism. To prepare an objective summary of the evidence on the appropriateness and need for various existing and possible neonatal screening programmes for inborn errors of metabolism in relation to the natural history of these diseases. To identify gaps in existing knowledge and make recommendations for required primary research. To make recommendations for the future development and organisation of neonatal screening for inborn errors of metabolism in the UK. HOW THE RESEARCH WAS CONDUCTED. There were three parts to the research. A systematic review of the literature on inborn errors of metabolism, neonatal screening programmes, new technologies for screening and economic factors. Inclusion and exclusion criteria were applied, and a working database of relevant papers was established. All selected papers were read by two or three experts and were critically appraised using a standard format. Seven criteria for a screening programme, based on the principles formulated by Wilson and Jungner (WHO, 1968), were used to summarise the evidence. These were as follows. Clinically and biochemically well-defined disorder. Known incidence in populations relevant to the UK. Disorder associated with significant morbidity or mortality. Effective treatment available. Period before onset during which intervention improves outcome. Ethical, safe, simple and robust screening test. Cost-effectiveness of screening. A questionnaire which was sent to all newborn screening laboratories in the UK. Site visits to assess new methodologies for newborn screening. The classical definition of an inborn error of metabolism was used (i.e., a monogenic disease resulting in deficient activity in a single enzyme in a pathway of intermediary metabolism). RESEARCH FINDINGS. INBORN ERRORS OF METABOLISM. Phenylketonuria (PKU) (incidence 1:12,000) fulfilled all the screening criteria and could be used as the 'gold standard' against which to review other disorders despite significant variation in methodologies, sample collection and timing of screening and inadequacies in the infrastructure for notification and continued care of identified patients. Of the many disorders of organic acid and fatty acid metabolism, a case can only be made for the introduction of newborn screening for glutaric aciduria type 1 (GA1; estimated incidence 1:40,000) and medium-chain acyl CoA dehydrogenase (MCAD) deficiency (estimated incidence 1:8000-1:15,000). Therapeutic advances for GA1 offer prevention of neurological damage but further investigation is required into the costs and benefits of screening for this disorder. MCAD deficiency is simply and cheaply treatable, preventing possible early death and neurological handicap. Neonatal screening for these diseases is dependent upon the introduction of tandem mass spectrometry (tandem MS). This screening could however also simultaneously detect some other commonly-encountered disorders of organic acid metabolism with a collective incidence of 1:15,000.(ABSTRACT TRUNCATED)     

Relaxation for the relief of chronic pain: a systematic review

The effectiveness of relaxation techniques in the management of chronic pain was determined in this systematic review of published randomized controlled trials. Reports were sought by searching MEDLINE, psycLIT, CINAHL, EMBASE and the Oxford Pain Relief Database. Studies were included in this review if they were randomized controlled trials of relaxation techniques in chronic pain. Studies which investigated the effects of relaxation in combination with other interventions were not considered. Nine studies involving 414 patients met the predefined inclusion criteria and are critically appraised in this review. Meta-analysis was not possible, due to lack of quantitative data in the primary studies. Studies involved patients with a range of chronic pain conditions. The McGill Pain Questionnaire was the most common pain outcome used. Whilst four studies were able to show a significant difference for the pain outcomes in favour of relaxation for the pre- and post-treatment assessments, few statistically significant differences were reported in favour of relaxation when between treatment comparisons were used. Only three studies reported statistically significant differences in favour of relaxation (judged as a significant difference for at least 1 of the pain outcomes) compared to the other treatment groups. In rheumatoid arthritis the McGill Pain Questionnaire scores were significantly lower for patients receiving relaxation compared to those who were in the routine treatment control group. In ulcerative colitis significant differences were reported for six of seven different pain outcome measures in favour of progressive muscle relaxation compared to patients in the waiting list control group. In one of the two cancer pain studies, relaxation taught by nurses produced significantly lower pain sensation scores compared to the control group. Two studies reported significant differences in favour of the experimental control groups rather than for relaxation. There is insufficient evidence to confirm that relaxation can reduce chronic pain. Many of the studies both positive and negative suffer methodological inadequacies. Recommendations for future research into the effectiveness of relaxation techniques for chronic pain are made.     

Cancer risks among workers exposed to metalworking fluids: a systematic review

Metalworking fluids (MWFs) are commonly used in a variety of industrial machining and grinding operations. The National Institute for Occupational Safety and Health (NIOSH) estimates that more that one million workers are exposed to MWFs. NIOSH conducted a comprehensive and systematic review of the epidemiologic studies that examined the association between MWF exposure and cancer. Substantial evidence was found for an increased risk of cancer at several sites (larynx, rectum, pancreas, skin, scrotum, and bladder) associated with at least some MWFs used prior to the mid-1970s. This paper provides the evidence pertaining to cancer at these sites. Cancer at those sites found to have more limited or less consistent evidence for an association with MWF (stomach, esophagus, lung, prostate, brain, colon, and hematopoietic system) will not be discussed in this paper but are discussed in the recent NIOSH Criteria for a Recommended Standard-Occupational Exposure to MWFs. Because the changes in MWF composition that have occurred over the last several decades may not be sufficient to eliminate the cancer risks associated with MWF exposure, reductions in airborne MWF exposures are recommended.     

A review of tonsillectomy for recurrent throat infection

Tonsillectomy is most frequently carried out for recurrent throat infection, but there is uncertainty about its effectiveness. This paper reviews the evidence of its effectiveness obtained from a search of the Cochrane database and MEDLINE for randomized controlled trials comparing tonsillectomy with non-surgical management of recurrent throat infection. The results show that the effectiveness of a procedure such as tonsillectomy, needs to be considered in the light of its adverse effects. Attempts should be made to inform patients about the uncertainty surrounding the procedure.     

Clinical and angiographic predictors of stroke and death from carotid endarterectomy: systematic review

OBJECTIVE: To identify risk factors for operative stroke and death from carotid endarterectomy. DESIGN: Systematic review of all studies published since 1980 which related risk of stroke and death to various preoperative clinical and angiographic characteristics, including unpublished data on 1729 patients from the European carotid surgery trial. MAIN OUTCOME MEASURE: Operative risk of stroke and death. RESULTS: Thirty six published studies fulfilled our criteria. The effect of 14 potential risk factors was examined. The odds of stroke and death were decreased in patients with ocular ischaemia alone (amaurosis fugax or retinal artery occlusion) compared with those with cerebral transient ischaemic attack or stroke (seven studies; odds ratio 0.49; 95% confidence interval 0.37 to 0.66; P < 0.00001). The odds were increased in women (seven studies; 1.44; 1.14 to 1.83; P < 0.005), subjects aged > or = 75 years (10 studies: 1.36; 1.09 to 1.71; P < 0.01), and with systolic blood pressure > 180 mm Hg (four studies; 1.82; 1.37 to 2.41; P < 0.0001), peripheral vascular disease (one study; 2.19; 1.40 to 3.60; P < 0.0005), occlusion of the contralateral internal carotid artery (14 studies; 1.91; 1.35 to 2.69; P < 0.0001), stenosis of the ipsilateral internal carotid siphon (five studies; 1.56; 1.03 to 2.36; P = 0.02), and stenosis of the ipsilateral external carotid artery (one study; 1.61; 1.05 to 2.47; P = 0.03). Operative risk was not significantly related to presentation with cerebral transient ischaemic attack versus stroke, diabetes, angina, recent myocardial infarction, current cigarette smoking, or plaque surface irregularity at angiography. Multiple regression analysis of data from the European carotid surgery trial identified cerebral versus ocular events at presentation, female sex, systolic hypertension, and peripheral vascular disease as independent risk factors. CONCLUSIONS: The risk of stroke and death from carotid endarterectomy is related to several clinical and angiographic characteristics. These observations may help clinicians to estimate operative risks for individual patients and will also facilitate more meaningful comparison of the operative risks of different surgeons or at different institutions by allowing some adjustment for differences in case mix.