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An immune hemagglutination procedure with very high sensitivity applied to the detection of hepatitis B antibody and antigen and immune complex.

An immune agglutination procedure is described in which red cells are coated with antigen and agglutination is observed after a short incubation with antibody in reagent serum. Conversely, the cells may be coated with antibody and used to test for the presence of antigen. Treatment of the reagent serum with cobra venom factor results in inhibition, and there is a marked lo-s of sensitivity with cells pretreated with formalin or chromic chloride, suggesting that C3 and some type of reactive sites on the cells are required. The distinctive features of the new procedure are that incubation time is very short, sensitivity is several orders of magnitude higher than with other related tests, and, within some limitations, bovine (steer) red cells with bovine serum can be used as an alternative to human red cells with human serum. It is necessary to remove an inhibitor from the reagent serum, human or steer. While the mechanism of the procedure needs further elucidation, the findings reported here suggest that it ought to be sufficiently sensitive to detect hepatitus B antigen if present in virtually any blood sample. With appropriate modifications it should be useful for blood donor screening, diagnosis, and for studying many other antigen-antibody systems.

Adsorption↗

The nature of gerontogenes and vitagenes. Antiaging effects of repeated heat shock on human fibroblasts.

Our survival and the physical quality of life depends upon an efficient functioning of various maintenance and repair processes. This complex network of the so-called longevity assurance processes is composed of several genes, termed vitagenes. The homeodynamic property of living systems is a function of such a vitagene network. Because aging is characterized by the failure of homeodynamics, a decreased efficiency and accuracy of the vitagene network can transmutate it into a gerontogene network. It is not clear how various components of the vitagene network operate and influence each other in a concordant or a discordant manner. Experimental strategies through which this transmutation of vitagenes into virtual gerontogenes may be elucidated include induction of molecular damage, antisense intervention, and genetic screening for varied efficiencies of the members of the vitagene family. A reversal of this approach by maintaining or recovering the activity of vitagenes will lead to a delay of aging, a decreased occurrence of age-related diseases, and a prolongation of a healthy life span.

Aging↗

Identification of genes induced by a macrophage activator, S-28463, using gene expression array analysis.

S-28463 and imiquimod are imidazoquinoline compounds which stimulate microbicidal activity by inducing a local immune response at the site of application. Imiquimod-containing cream is an effective clinical treatment against cervical warts caused by human papillomavirus infection. Imiquimod also induces leishmanicidal activity both in vitro in macrophages and in vivo in a mouse model for cutaneous leishmaniasis. The major target cells of S-28463 and imiquimod are macrophages. To explore the molecular basis in which imidazoquinolines generate macrophage microbicidal activity, a cDNA gene array analysis was undertaken to identify genes induced by S-28463. Out of 588 genes screened in this assay, only 13 genes were significantly induced by S-28463. Remarkably, virtually all of the induced genes are involved in macrophage activation and inflammatory response. This experimental approach defines the mechanism of action of this clinically relevant compound in the induction of microbicidal activity in macrophages and also potentially identifies novel genes associated with microbicidal activity in this cell type.

Aminoquinolines↗

Ecological distribution of Legionella pneumophila.

Bacteria were concentrated 500-fold from 20-liter water samples collected from 67 different lakes and rivers in the United States. The data suggest that Legionella pneumophila is part of the natural aquatic environment and that the bacterium is capable of surviving extreme ranges of environmental conditions. The data further demonstrate the effectiveness of the direct fluorescent-antibody technique for detecting L. pneumophila in natural aquatic systems. Smears of the concentrated samples were screened microscopically for serogroups of L. pneumophila by the direct fluorescent-antibody technique. Virtually all of the 793 samples were found to be positive by this method. The 318 samples containing the largest numbers of positive bacteria which were morphologically consistent with L. pneumophila were injected into guinea pigs for attempted isolations. Isolates were obtained from habitats with a wide range of physical, chemical, and biological parameters. Samples collected monthly from a thermally altered lake and injected into guinea pigs demonstrated a seasonality of infection, with the highest frequency of infection occurring during the summer months.

Animals↗

Distribution of the CorA Mg2+ transport system in gram-negative bacteria.

The CorA Mg2+ transport system is the dominant constitutive uptake mechanism in Salmonella typhimurium and Escherichia coli. Southern blot hybridization and PCR techniques were used to screen a panel of 18 additional gram-negative bacterial species for corA homologs. Virtually all strains tested positive for the presence of corA. Thus, corA appears to be ubiquitous within gram-negative bacteria and is likely their major Mg2+ influx system.

Bacterial Proteins↗

Trichomoniasis: clinical manifestations, diagnosis and management.

Trichomonas vaginalis was originally considered a commensal organism until the 1950s when the understanding of its role as a sexually transmitted infection (STI) began to evolve. Trichomoniasis has been associated with vaginitis, cervicitis, urethritis, pelvic inflammatory disease (PID), and adverse birth outcomes. Infection with T vaginalis could have an important role in transmission and acquisition of HIV. T vaginalis is site specific for the genitourinary tract and has been isolated from virtually all genitourinary structures. Asymptomatic disease is common in both men and women, thus screening for disease is important. Various sociodemographic factors have been correlated with presence of T vaginalis, and may be used to predict infection. Diagnosis is usually made from wet mount microscopy and direct visualisation, which are insensitive. DNA amplification techniques perform with good sensitivity, but are not yet approved for diagnostic purposes. In areas where diagnostic methods are limited, management of trichomoniasis is usually as part of a clinical syndrome; vaginal discharge for women and urethral discharge for men. A single dose of metronidazole is effective in the majority of cases. Outside of the United States, other nitroimidazoles may be used and are as effective as metronidazole. Metronidazole resistance is an emerging problem, but its clinical importance is not yet clear. Concomitant treatment of sexual partners is recommended.

Animals↗

Advances in abdominal MR imaging.

Major technical advances in MR imaging have led to its wider use in the evaluation of abdominal disease. The principle new pulse sequence is the RARE sequence for T2-weighted imaging. Multishot and breath-hold single-shot RARE techniques are now widely used, and both have performed as well as conventional spin-echo imaging with far shorter acquisition times. The most notable improvements have been in the detection and characterization of hepatic lesions. Two liver-specific contrast agents received FDA approval during 1997: SPIO particles or ferumoxide and mangafodipir trisodium, a hepatocyte-specific agent. Both of these agents provide considerable benefit in the detection and characterization of hepatic lesions. Manganese enhancement has also proved useful in MR imaging of the pancreas, although fat-suppressed T1-weighted imaging with dynamic gadolinium enhancement has also yielded results comparable with those of contrast-enhanced CT. MR hydrography, a generic term for static fluid imaging, is another derivative of RARE fast T2-weighted imaging. MRCP, the best known example of MR hydrography, has been rapidly and widely employed as a primary method for imaging the biliary and pancreatic ducts and has become competitive with ERCP. MR vascular imaging, especially portal venography, has been used for noninvasive imaging of portal venous disease in Budd Chiari disease, before placement of transjugular intrahepatic portosystemic shunts, and for pancreatic cancer staging. Finally, the development of conventional phased-array body coils and endorectal coils has enabled high-quality MR imaging of perirectal disease (including Crohn disease, fistula in ano, and postpartum sphincter dysfunction). Future abdominal applications of MR imaging will involve second-generation MR interventional techniques, including use of open systems, functional or diffusion-weighted imaging exploiting the molecular activity of tissues, and virtual MR endoscopy. Although CT continues to evolve as the premier technique for survey screening of the abdomen, the technical advances in MR imaging have enabled this modality to assume some special nitch roles (in which it adds unique value) in the evaluation of the abdomen. Radiologists can safely assume that there will undoubtedly be much more to come.

Abdomen↗

Digital radiography of the chest: design features and considerations for a prototype unit.

The general features of a prototype digital chest unit are described along with the rationale for the choice of design factors employed. It is shown that the scanning-slit, linear-detector-array approach employed can, with available x-ray tube technology, achieve a spatial resolution of 1 cy/mm and detector radiation levels comparable with those obtained with conventional screen-film systems. Also discussed are the unit's exposure latitude and its ability virtually to eliminate scatter.

Computers↗

Efficiency of tests used to screen for cerebello-pontine angle tumours: a prospective study.

With increasing use of imaging in the investigation of cerebello-pontine angle (CPA) tumours, the role of audio-vestibular and electrophysiological testing has changed. Field performance data on the efficiencies of these tests to screen for CPA tumours are lacking, but must be known to choose an appropriate testing strategy. A prospective observational study of 237 patients attending a neuro-otology clinic for audio-vestibular investigation was carried out. The aim was to provide field performance data on which to base an effective protocol to screen for CPA tumours. All patients presenting at the ENT department and meeting any of the following criteria were referred to the neuro-otology clinic and included in the study: (1) asymmetrical sensorineural hearing loss, (2) unexplained asymmetrical tinnitus with normal bearing thresholds, (3) unilateral bearing difficulties with normal hearing thresholds and (4) other neurological indications. In addition to audio-vestibular and auditory brainstem response (ABR) investigation, every patient underwent computed tomography (CT), with magnetic resonance imaging (MRI) in cases having marginal results on CT, to exclude or confirm the presence of a tumour. Pass or fail on each test was based on a priori criteria from other studies. Eighteen patients were found to have CPA tumours. ABR testing was the only effective procedure for screening, but had some limitations. A contingent protocol using ABR in all cases except those with asymmetrical tinnitus and normal bearing thresholds, those with severe hearing loss, and those with neurological signs, was retrospectively defined: the exceptions would go straight to CT. This protocol would have missed two of the 18 tumour patients. CT scanning alone would have missed one small intra-canalicular tumour, which was picked up on MRI triggered by abnormal ABR. Based on the results from the present study we conclude there is no effective screening protocol for detecting CPA tumours, as MRI scanning with gadolinium enhancement will identify virtually all tumours. Where MRI is available but waiting lists are long, the described strategy using ABR to select priority referrals for MRI scanning is recommended.

Adult↗

[New methodologic approaches in antimalarial molecular research].

The estimated worldwide incidence of Plasmodium falciparum malaria is about 500 million cases a year. In tropical areas, the dramatic increase of resistance to most antimalarial drugs is directly responsible for persistent widespread high endemicity and related morbidity. The search to identify new drug targets and agents is a high priority. However the value of standard pharmacological research methods is greatly diminished by technical problems involving in vitro and in vivo modeling of malaria infection. In recent decades new mathematical tools have been developed to predict drug properties and to estimate biological activity in silico. Various approaches have been proposed based on 2D or 3D descriptions of the chemical structure of the drug and target followed by mathematical and statistical characterization of their interaction. These techniques are now widely used in medicinal chemistry and have proven their efficacy for screening the anti-malarial activity of numerous molecules in large databases and for virtual synthesis. Incorporating new knowledge from the genomic studies of Plasmodium has markedly increased the performance and range of application of these tools for identifying new drug targets against malaria.

Antimalarials↗

[Early diagnosis of colorectal cancer].

Colorectal cancer is the fourth most common cancer in the world and the second most common and most frequently mentioned cause of cancer death in Poland. Death from colorectal cancer can be reduced through early diagnosis. Currently there are several screening methods: faecal occult blood tests, sigmoidoscopy, colonoscopy, barium enema and emerging methods like virtual colonoscopy and faecal DNA testing. In this article we show the efficacy of these tests with respect to their sensitivity, specificity, costs and safety. Patients at high-risk of colorectal cancer were also considered. There is an urgent need to standardize the methods of diagnosis in patients at high-risk to increasing accessibility and quality of tests.

Biopsy↗

Detection of major depressive disorder in primary care patients.

BACKGROUND: The aim of this study was to assess the utility of a two-phase case detection strategy for major depressive disorder and a quantitative self-rating instrument for dysphoria. METHODS: A convenience sample of 302 ambulatory patients received three self-administered depression rating instruments: a modified version of the Dartmouth Cooperative (COOP) Functional Health Assessment Chart on emotional condition, a three-question screening test for depression taken from the Diagnostic Interview Schedule (DIS), and the Inventory to Diagnose Depression (IDD). All patients' medical charts were reviewed after the administration of these instruments, and those charts of patients found to be depressed were reviewed again 6 months later. A family practice ambulatory patient center in a university hospital was the setting for the study. RESULTS: The IDD detected current major depressive disorder in 41 persons (13.6 percent of sample). Twenty-five of the 41 IDD-positive patients had not previously had a major depressive disorder diagnosed according to chart notes. Six months later, 16 of the 25 patients with newly diagnosed major depressive disorders had not returned to the clinic since the index visit. A single question (DIS question 073b), when compared with the IDD diagnosis of major depressive disorder, had a sensitivity of 95.1 percent, specificity of 78.9 percent, positive predictive value of 41.5 percent, and negative predictive value of 99 percent. Dysphoria, as measured by the modified COOP chart on emotional condition, was significantly worse among those with current major depression (IDD positive) than for those without (IDD negative). CONCLUSIONS: A two-phase case detection strategy for major depressive disorder consisting of a single screening question followed by a self-administered diagnostic instrument can efficiently pick out virtually all ambulatory primary care patients with a major depressive disorder. A brief functional assessment chart can quantify the extent of dysphoria.

Adolescent↗

Intrapartum amniotic fluid index. A poor diagnostic test for adverse perinatal outcome.

OBJECTIVE: To determine if an intrapartum amniotic fluid index (IAFI) < or = 5.0 cm, or any other level, is associated with abdominal delivery for fetal intolerance to labor or Apgar scores < 7 at one and five minutes. STUDY DESIGN: Prospectively IAFI was obtained in the latent phase of labor in 1,000 parturients at > 26 weeks. Receiver operating characteristic curves were utilized to determine if any IAFI could be utilized to predict adverse outcome among (1) the entire population, (2) complicated pregnancies, (3) uncomplicated pregnancies, (4) term, or (5) preterm gestation. RESULTS: The frequencies of abdominal delivery for suspected fetal intolerance and low Apgar scores were similar among patients with IAFI < or = 5.0 cm (n = 288) versus those with IAFI > 5.0 cm. All five receiver operating characteristic curves indicated that IAFI is a poor predictor of adverse outcomes. At all the discriminatory IAFIs (0-20 cm), the false positive rate was virtually identical to the true positive rate. CONCLUSION: IAFI appears to be a poor screening test for identifying those at risk for abdominal delivery for presumed fetal distress or for birth of an infant with low Apgar scores.

Amniotic Fluid↗

The Quebec Association of Gastroenterology position paper on colorectal cancer screening - 2003.

Colorectal cancer is a leading cause of death and the third most common cancer in Canada. Evidence suggests that screening can reduce mortality rates and the cost effectiveness of a program compares favourably with initiatives for breast and cervical cancer. The objectives of the Association des gastro-entérologues du Québec Task Force were to determine the need for a policy on screening for colorectal cancer in Quebec, to evaluate the testing methods available and to propose one or more of these alternatives as part of a formal screening program, if indicated. Fecal occult blood testing (FOBT), endoscopy (including sigmoidoscopy and colonoscopy), barium enema and virtual colonoscopy were considered. Although most clinical efficacy data are available for FOBT and sigmoidoscopy, there are limitations to programs based on these strategies. FOBT has a high false positive rate and a low detection yield, and even a combination of these strategies will miss 24% of cancers. Colonoscopy is the best strategy to both detect and remove polyps and to diagnose colorectal cancer, with double contrast barium enema also being a sensitive detection method. The Task Force recommended the establishment, in Quebec, of a screening program with five- to 10-yearly double contrast barium enema or 10-yearly colonoscopy for individuals aged 50 years or older at low risk. The program should include outcome monitoring, public and professional education to increase awareness and promote compliance, and central coordination with other provincial programs. The program should be evaluated; specific billing codes for screening for colorectal cancer would help facilitate this. Formal feasibility, effectiveness and cost-effectiveness studies in Quebec are now warranted.

Barium Sulfate↗

Breast cancer: new technologies for risk assessment and diagnosis.

In the US, one in every eight women will develop breast cancer in her lifetime. Despite the advances made in treating breast cancer, the causal mechanisms underlying this disease have yet to be fully elucidated; 85% of breast cancer cases occur sporadically without any known genetic mutation. Too little is known about the pathogenesis of breast cancer for primary prevention to be feasible in the near- to mid-term. Secondary prevention through screening offers an alternative that has been widely adopted. For decades, breast self-examination has been touted as a technique for the early identification of breast cancer. However, it has been recently suggested that this technique is a waste of time and resources for both doctors and patients. Mammography finds breast cancer earlier than breast self-examination, and will reduce the risk of death from breast cancer by approximately 30% in women over 50 years old. Mammography is limited in that cancer, like breast tissue, appears white on the x-ray; therefore lesions may be difficult to detect in women with very dense breasts, and a tumor may not cast a significant shadow until it is quite large. Some cancers are so aggressive that they can spread quickly, before routine screening can detect them. Despite these limitations, mammography is still viewed as the best tool currently available for screening and early diagnosis. Improved methods to detect and diagnose breast cancer early, when it is most curable, are required if a significant impact on morbidity and mortality from breast cancer is to be made. Various new and innovative technologies are being investigated for improving the early detection and diagnosis of breast cancer. About 85% of breast cancers begin in the milk ductal system of the breast. As cancer develops in the breast, abnormalities occur, including atypical hyperplasia, ductal carcinoma in situ, and invasive breast carcinoma. Thus, the early screening of ductal cells can provide a parallel benefit to the 'Pap' smear, which is used virtually universally to identify the abnormal cells that can lead to cervical cancer. Two technologies to monitor for atypical ductal epithelial cells are Cytyc Corporation's FirstCyte Ductal Lavage system and Nastech Pharmaceutical Company's Mammary Aspiration Cytology Test. Matritech, Inc. is searching for biomarkers linked to breast cancer. Researchers at Matritech have detected the presence of nuclear matrix protein (NMP) in the blood of women at the early stage of breast cancer, which is absent in the blood of healthy women, as well as those with fibroadenoma, a benign breast disease. NMP66 has been selected as a marker for further development and clinical trials of a test for use in the detection and monitoring of women with, or at risk for, breast cancer have been initiated. Technologies developed by the US Department of Defense are under investigation as breast cancer screening. Advanced Image Enhancement, Inc. has licensed naval sonar technology for digital image enhancement of mammograms. New thermography applications are also being investigated in two separate projects sponsored by the US Department of Defense using military thermal surveillance tools adapted for cancer detection. Both are enhancements of older thermal imaging technology based on the principle that heat equates to unwanted activity, in the case of breast cancer, abnormal cell proliferation.

BRCA1 Protein↗

Can the Internet help to meet the challenges in ADME and e-ADME?

The high-throughput screening (HTS) of large proprietary compound collections and combinatorial libraries has put an increased pressure on getting pharmacokinetic and drug metabolism data as early as possible. Properties related to absorption, distribution, metabolism and excretion (ADME) can be estimated by a range of in vivo and in vitro methods. Most are now available or under development in high(er) throughput modus. In addition progress has been made in in silico methods using various QSAR and modeling techniques using a range of recently introduced descriptors tailored to e-ADME. These approaches are promising as a filter for virtual libraries to decide on synthesis as well as in the selection of compounds for acquisition and screening. This paper will discuss a number of Internet resources relevant to ADME studies and predictions. We have focused on areas related to metabolism including metabolic pathways and P450 metabolism, transporters, bioavailability and absorption, pharmacokinetics and pharmacodynamics, molecular properties and tools for data analysis.

Adsorption↗

Neonatal screening for congenital dislocation of the hip. A prospective 21-year survey.

A prospective neonatal screening programme for congenital dislocation of the hip is reported. This covered over 20,000 live births including all the babies born in one area, with a virtually complete follow-up. All babies were examined within the first seven days of life and all hips which were dislocated or unstable after four days (1.6%) were splinted. Only two screened cases were "missed" and subsequently detected at 15 and 18 months. No later cases were discovered, and patients between 10 and 20 years of age had apparently remained asymptomatic. The detailed results show that neonatal screening is effective in detecting and preventing a crippling disorder in otherwise normal people. The examination, though brief, is difficult to perform well; it is considered that failure of the method lies with the examiner and not with the tests.

Female↗

Review article: balancing the ideal versus the practical-considerations of colorectal cancer prevention and screening.

Colorectal cancer is responsible for over 500 000 deaths annually world-wide. Death from colorectal cancer is preventable, primarily through early diagnosis of disease that has not metastasized. The disease itself may be prevented by the detection and removal of colorectal adenomas, from which more than 95% of colorectal cancers arise. Currently there are several screening methods for the disease. These include faecal occult blood tests, sigmoidoscopy, barium enema and colonscopy as well as emerging methods of virtual colonoscopy and faecal DNA testing. While direct and indirect evidence support the efficacy of these tests they differ from each other in their sensitivity, specificity, cost, and safety. Various professional organizations in different geographical regions of the world have published recommendations on which screening methods to use and when in patients at average- or high-risk. The challenge in reducing the incidence and mortality of this disease lies in increasing accessibility to and compliance with screening and delivery within a quality assured programme.

Barium Sulfate↗