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At least 307 records · Page 17Linked to original sources

Larvicidal effects of grain sorghum (Sorghum bicolor) seedling extracts upon Culex pipiens larvae.

A study of laboratory and field reared 2nd and 3rd instar Culex pipiens larvae suggests that extracts from 2 varieties of Sorghum bicolor seedlings are significant (P less than 0.05) larvicides under laboratory conditions. These plant extracts contain the organic cyanogen dhurrin and were calibrated to produce 90% mortality in 2nd instar Culex pipiens larvae at 0.82 ppm and 90% mortality in 3rd instar larvae at 1.12 ppm. A preliminary behavioral assessment of late 3rd instar larvae exposed to 1.42 ppm suggests that these plant extracts produce 80% mortality after only 4-5 h of contact. Plant extracts appear stable when stored at up to 32 degrees C in a closed container. Once the extracts are infused in water and exposed to air, however, they biodegrade after 24 h. These laboratory results emphasize the need for field tests against natural populations of Culex pipiens and nontarget organisms.

Animals↗

Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS Clinical Trials Group virology laboratories.

A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log10 RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons.

Clinical Protocols↗

Safety evaluation of nabumetone in United States clinical trials.

A total of 1,924 persons (rheumatoid arthritis, 835; osteoarthritis, 1,073; volunteers, 16) received nabumetone in United States clinical trials. Nine hundred eighty-eight patients have received nabumetone treatment for periods of more than one year, and 375 patients have received treatment for longer than two years. Four hundred eighty patients over 65 years of age have received treatment with nabumetone, and 224 of these elderly patients have received treatment for periods of more than one year. The nabumetone dose most commonly used in all double-blind trials was 1,000 mg at night. In long-term, open-label studies, which were usually extensions of the double-blind trials, patients could increase the dose to 2,000 mg per day. Nine hundred nineteen patients received doses of more than 1,000 mg per day. Adverse experience information was collected at each visit, including information for some patients receiving treatment for more than three years. Laboratory data were collected periodically throughout the trials, and the data were assessed for trends over time. The adverse experience pattern observed for nabumetone is similar to that described for clinical trial data for other nonsteroidal anti-inflammatory drugs. However, it is noteworthy that the pattern observed for nabumetone is from clinical trials with approximately 1,000 patients receiving treatment for periods of one year or more. This long-term patient exposure in clinical trials far exceeds long-term clinical trial data for other agents. The types and frequencies of adverse experiences reported by persons treated with nabumetone are relatively constant over the long time period covered by these trials. Also, the adverse experience patterns remained generally constant over time for various populations: all patients, patients 65 or older, female patients, male patients, and patients who received an increased dose of nabumetone. Although some statistically significant trends were detected for some laboratory parameters, there was little indication of significant clinical patterns. Although there were patients with individually important laboratory values, nabumetone was not associated with clinically important adverse laboratory patterns. Overall, the adverse experience data and laboratory data indicate that nabumetone is safe for the treatment of adult patients with rheumatoid arthritis or osteoarthritis.

Adult↗

Lipid peroxidation in aging brain and Alzheimer's disease.

Lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products, both from fission and endocyclization of oxygenated fatty acids that possess neurotoxic activity. Numerous studies have demonstrated increased lipid peroxidation in brain of patients with Alzheimer's disease (AD) compared with age-matched controls. These data include quantification of fission and endocyclized products such as 4-hydroxy-2-nonenal, acrolein, isoprostanes, and neuroprostanes. Immunohistochemical and biochemical studies have localized the majority of lipid peroxidation products to neurons. A few studies have consistently demonstrated increased cerebrospinal fluid (CSF) levels of isoprostanes in AD patients early in the course of their dementia, and one study has suggested that CSF isoprostanes may improve the laboratory diagnostic accuracy for AD. Similar analyses of control individuals over a wide range of ages indicate that brain lipid peroxidation is not a significant feature of usual aging. Quantification of isoprostanes in plasma and urine of AD patients has yielded inconsistent results. These results indicate that brain lipid peroxidation is a potential therapeutic target in probable AD patients, and that CSF isoprostanes may aid in the assessment of antioxidant experimental therapeutics and the laboratory diagnosis of AD.

Adult↗

Acetaminophen-related acute renal failure without fulminant liver failure.

BACKGROUND: Our patient experienced acute renal failure but not fulminant hepatic failure from acetaminophen toxicity. OBJECTIVE: To review the clinical and laboratory characteristics of similar cases of acetaminophen nephrotoxicity. METHODS: A MEDLINE search and medical record search at two large teaching hospitals. RESULTS: We reviewed our index case, a patient at Jackson Memorial Hospital, and 34 additional patients with acetaminophen nephrotoxicity reported in the literature. Oliguria was present in 23 of 31 patients. There was no difference in peak serum creatinine levels between patients treated with N-acetylcysteine and those not treated. The onset of acute renal failure was from 2-5 days after overdose, and peak serum creatinine levels occurred 3-16 days (average 7.3 days) after overdose. Thirteen patients required hemodialysis; all but one were oliguric. Renal failure was spontaneously reversible in all patients. CONCLUSION: Although uncommon, it is possible to have acute renal failure due to acetaminophen toxicity in the absence of fulminant hepatic failure.

Acetaminophen↗

Laboratory findings associated with thrombophilia are not more common in inflammatory bowel disease.

Thromboembolic disease (TED) has been recognized as a complication of inflammatory bowel disease (IBD) since the 1930s (Bargen & Barker 1936). The relative contributions of inherited or acquired thrombophilia and the inflammatory response to the mechanism of this tendency is unclear. Thrombotic events are more common in active disease although significant numbers also occur spontaneously, when the disease is in clinical remission (Talbot et al. 1986; Jackson et al. 1997). Studies looking at the prevalence of specific thrombophilic states such as Antithrombin III deficiency (Jackson et al. 1997; Lake, Stauffer & Stuart 1978; Cianco et al. 1996; Ghosh et al. 1983), Factor V Leiden mutation (APC Resistance) (Jackson et al. 1997; Probert et al. 1997; Ardizzone et al. 1998; Liebman et al. 1998), anticardiolipin antibodies (Ciancio et al. 1996), Protein C (Wyshock, Caldwell & Crowley 1988; Korsten & Reis 1992) and Protein S deficiencies (Jorens et al. 1990; Aadland et al. 1992) in IBD have been contradictory or equivocal. We had previously found that IBD patients with a history of TED are not more likely to have a laboratory thrombophilic abnormality than those with uncomplicated disease. We also demonstrated that the prevalence of heterogenous laboratory thrombophilic abnormalities (usually minor) in all IBD patients may be as high as 60%, much higher than the recognized prevalence of TED (Lim, Jones & Gould 1996). We wondered how this would compare with the healthy non-IBD population. We have therefore explored the prevalence of such thrombophilic abnormalities in a group of IBD patients who had no history of TED and compared them with healthy age and sex matched controls.

Adult↗

Return to TRI: Winston Churchill Fellow and Salford University Scholar travel to Miami and the Keys.

During May and June 2003, the 2 authors visited the internationally renowned Touch Research Institute based at the University of Miami and Jackson Memorial Hospital. For one of the authors, Peter Mackereth, this was a return visit. Both authors are Ph.D. students who have successfully obtained travel scholarships to participate in seminars and laboratory work. The paper will report on the experience of their visit, the current and future work of the TRI and its collaborators. Jacqui took the opportunity to spend time at the Dolphin Research Centre, this provided insight into the therapeutic value of interacting with these amazing mammals. Peter also took the opportunity to visit a group of massage therapists working in Key West.

Academic Medical Centers↗

Comparison of two sterile Mediterranean fruit fly (Diptera: Tephritidae) strains released in California's Preventative Release Program.

At Mediterranean fruit fly rearing centers, genetic sexing strains such as the male-only temperature sensitive lethal (tsl) strains, are replacing many of the older bisexual strains, such as Maui-93. Three tests were performed to compare the performance of the Vienna-4 (which carries tsl) and Maui-93 strains. Using standard laboratory quality control tests, the Maui-93 strain had higher percent fliers and a lower percentage deformed and partially eclosed flies. Analyses of data from field mark-recapture tests with Jackson traps failed to find significant differences in recapture numbers between the two strains. In field cage survivorship tests, the Vienna-4 strain showed significantly lower mortality in comparison to the Maui-93 strain. These results suggest that although the quality of Vienna-4 flies is lower than Maui-93 at the time of adult emergence, it is comparable with or better than Maui-93 several days later, because weaker flies have been eliminated from the cohort. The benefits of releasing only sterile males, instead of both males and females, was not factored into the quality assessment in this study, but would be an additional benefit in using a strain that carries a tsl mutation.

Animals↗

Are there differences in clinical and laboratory parameters between children and adults with American visceral leishmaniasis?

A prospective study on 23 patients with American visceral leishmaniasis (VL), comparing clinical and laboratory parameters of 14 children (mean age of 3.85+/-3.39 years) to nine adults (27.4+/-10.90 years) was performed in São Luís, Maranhão, Brazil, between August 2000 and July 2002. Data were collected at entrance (day 0), end of treatment, as well as 120 and 210 days after treatment using a protocol chart containing patient identification, clinical and laboratory data. N-Methylglucamine antimonate administered at the dose of 20mg/Sb5+/kg/day for 20-30 days was successfully used in all patients. Patients were followed for 1 year after treatment, and no relapses were observed. A prolonged duration of the disease, lymphadenopathy and bleeding predominated in adult patients, while hepatomegaly and skin-mucosal pallor were more frequent in children. Disease was longer and more severe in adults than in children. Although both groups exhibited a trend toward normalization of hematological and biochemical parameters, more children returned sooner to normal values than adults. Difference in clinical or laboratory parameters between children and adults did not indicate the need for different clinical or therapeutic approaches.

Adolescent↗

Disseminated Kaposi's sarcoma in pregnancy: a manifestation of acquired immune deficiency syndrome.

The first case of acquired immune deficiency syndrome (AIDS) in pregnancy is reported. The patient, a drug addict, presented with lymphadenopathy, pulmonary infiltrates, and skin lesions of Kaposi's sarcoma, a tumor rarely found in young women in this country. The helper T-lymphocyte to suppressor T-lymphocyte ratio showed the profound inversion characteristic of this cell-mediated immune deficiency disease. Chemotherapy, a combination of doxorubicin, bleomycin, and vinblastine, was initiated during pregnancy. A growth-retarded infant was delivered vaginally. At four months of life, the infant had no apparent evidence of immune deficiency. Transplacental transmission of AIDS has not, as yet, been demonstrated. The social factors, clinical and laboratory features, and the controversies surrounding this new disease are discussed.

Acquired Immunodeficiency Syndrome↗

Immunosuppressive treatment of motor neuron syndromes. Attempts to distinguish a treatable disorder.

OBJECTIVE: To determine if response to immunosuppressive treatment in motor neuron syndromes could be predicted on the basis of clinical features, anti-GM1 antibodies, or conduction block. DESIGN: Prospective, uncontrolled, treatment trial using prednisone for 4 months followed by intravenous cyclophosphamide (3 g/m2) continued orally for 6 months. SETTING: All patients were referred to university hospital medical centers. PATIENTS: Sixty-five patients with motor neuron syndromes were treated with prednisone; 11 patients had elevated GM1 antibody titers, and 11 patients had conduction block. Forty-five patients received cyclophosphamide, eight of whom had elevated GM1 antibodies and 10 had conduction block. RESULTS: One patient responded to prednisone, and five patients responded to cyclophosphamide treatment. Only patients with a lower motor neuron syndrome and conduction block improved with either treatment. Response to treatment did not correlate with GM1 antibodies. CONCLUSIONS: GM1 antibodies did not serve as a marker for improvement in patients with motor neuron syndrome treated with immunosuppressive drugs. Patients with amyotrophic lateral sclerosis failed to improve irrespective of laboratory findings.

Adult↗

Responses of benthic fish exposed to contaminants in outdoor microcosms--examining the ecological relevance of previous laboratory toxicity tests.

Previous laboratory studies indicate that coal combustion wastes (a mixture composed of fly ash and other lower volume wastes such as bottom ash; hereafter collectively referred to as ash) adversely affect the health of benthic fish (Erimyzon sucetta; lake chubsucker), but fish in these studies were provided with ample uncontaminated food resources. Because aquatic disposal of ash can also adversely affect food resources for benthic fish, we hypothesized that changes in resources might exacerbate the effects of ash on fish observed in laboratory studies. We exposed juvenile E. sucetta in outdoor microcosms to water, sediment, and benthic resources from an ash-contaminated site or a reference site for 45 days and compared our findings to previous laboratory studies. Benthic invertebrate biomass was nearly three times greater in controls compared to ash microcosms. Total organic content of control sediment (41%) was also greater than in ash sediments (17%), suggesting that additional benthic resources may have also been limited in ash microcosms. Benthic invertebrates isolated from the ash microcosms had trace element concentrations (As, Cd, Co, Cr, Cs, Se, Sr, and V) up to 18 times higher than in weathered ash used in laboratory studies. The concentrations of trace elements accumulated by fish reflected the high dietary concentrations encountered in the ash microcosms and were associated with reduced growth (final mass = 0.07 g) and survival (25%) compared to controls (0.37 g and 67%, respectively). Accumulation of trace elements, as well as reductions in growth and survival, were more pronounced than in previous laboratory studies, suggesting that resource conditions may be important in mediating ash toxicity. Taken together, our studies suggest that ash discharge into aquatic systems is a more serious threat to the health of benthic fish than previously predicted based upon laboratory toxicity tests.

Analysis of Variance↗

Nondestructive indices of trace element exposure in squamate reptiles.

Compared with birds, mammals, fish, and even amphibians, very little is known about the effects of contaminants on reptiles. Recent evidence that many reptile populations may be declining has stimulated demand for toxicological studies of reptiles as well as development of nondestructive sampling techniques useful for assessing and monitoring contaminant exposure. The current study experimentally evaluated the utility of shed skins, tail clips, and blood samples as nondestructive indices of trace element exposure in banded water snakes, Nerodia fasciata. For 13.5 months, snakes were either fed fish from a coal ash-contaminated site or uncontaminated food from a reference site. Snakes fed contaminated prey accumulated As, Cd, Se, Sr, and V in various organs (i.e. liver, kidney, and/or gonads). Moreover, non-parametric discriminant function analysis revealed that snakes could be placed in two groups that reliably reflected their experimental diet based upon Se, Sr, and As concentrations in tail clips, blood, and/or shed skins. We suggest that nondestructive sampling techniques, particularly analyses of blood and tail clips, may be easily applied in evaluations of contaminant exposure in the field and laboratory and may prevent excessive destructive sampling of potentially threatened reptile species.

Animals↗

TNF blockade: an inflammatory issue.

Tumor necrosis factor (TNF), initially discovered as a result of its antitumor activity, has now been shown to mediate tumor initiation, promotion, and metastasis. In addition, dysregulation of TNF has been implicated in a wide variety of inflammatory diseases including rheumatoid arthritis, Crohn's disease, multiple sclerosis, psoriasis, scleroderma, atopic dermatitis, systemic lupus erythematosus, type II diabetes, atherosclerosis, myocardial infarction, osteoporosis, and autoimmune deficiency disease. TNF, however, is a critical component of effective immune surveillance and is required for proper proliferation and function of NK cells, T cells, B cells, macrophages, and dendritic cells. TNF activity can be blocked, either by using antibodies (Remicade and Humira) or soluble TNF receptor (Enbrel), for the symptoms of arthritis and Crohn's disease to be alleviated, but at the same time, such treatment increases the risk of infections, certain type of cancers, and cardiotoxicity. Thus blockers of TNF that are safe and yet efficacious are urgently needed. Some evidence suggests that while the transmembrane form of TNF has beneficial effects, soluble TNF mediates toxicity. In most cells, TNF mediates its effects through activation of caspases, NF-kappaB, AP-1, c-jun N-terminal kinase, p38 MAPK, and p44/p42 MAPK. Agents that can differentially regulate TNF expression or TNF signaling can be pharmacologically safe and effective therapeutics. Our laboratory has identified numerous such agents from natural sources. These are discussed further in detail.

Animals↗

Cadmium and prostate cancer: a critical epidemiologic analysis.

Laboratory data implicate cadmium as a prostate carcinogen. However, epidemiological studies concerning the association between cadmium and prostate cancer are inconclusive. This article reviews the epidemiological literature on cadmium and prostate cancer with a special focus on highly exposed occupational cohorts. We searched the MEDLINE database from 1966 to 2002 for articles on cadmium and prostate cancer. All published analytical and descriptive studies that included relevant data were reviewed. In addition, we reviewed the experience of cohorts highly exposed to cadmium in nickel-cadmium battery plants. Of 4 descriptive studies, 3 reported a positive association between cadmium and prostate cancer. Of 10 case-control studies, 5 (50%) reported a positive association. Of 11 cohorts studies, 3 (33%) found a positive association. Finally, 4 studies on cohorts exposed in occupational nickel-cadmium batteries were identified and analyzed. The summary score of the standardized mortality ratios (SMRs) was weakly but not significantly positive 126 (95% confidence interval C.I.: 83-184). In contrast to laboratory studies, epidemiological studies do not convincingly implicate cadmium as a cause of prostate cancer. Future epidemiological studies that attempt to resolve the discrepancy between laboratory and epidemiological studies of cadmium carcinogenesis may benefit from incorporating biological measures of cadmium exposure.

Cadmium↗