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A quality assurance program for the measurement of capillary blood cholesterol levels in private pediatric practices. The Children's Health Project.

OBJECTIVE: To develop an easy to use quality assurance program for the measurement of capillary blood cholesterol levels in private pediatric practices. The program needed to comply with the guidelines laid down by the National Cholesterol Education Program. DESIGN: Intervention study. SETTING: Nine private pediatric practices in and around northern Philadelphia, Pa. PARTICIPANTS: The analysts included clinic staff members with laboratory expertise ranging from none to some previous experience. None of the participants had previous experience with a quality assurance program. INTERVENTIONS: Progress was reported monthly to the Lipid Research Laboratory, Philadelphia, and action was taken to correct inaccuracies in bias or variance. MAIN OUTCOME MEASURE: Compliance with the analytical guidelines laid down by the National Cholesterol Education Program in that the coefficient of variation was no greater than 5% and the bias was no greater than +/- 5% in the first year of the study. RESULTS: Within the first year of the study, there were 152 monthly quality assurance returns for each of two lyophilized control materials. On four occasions the coefficient of variation was greater than 5% while the overall bias was within the desired +/- 5% on 143 (94%) of 152 occasions. After the first 3 months of the study, as user confidence increased, intervention by the Lipid Research Laboratory became minimal. The internal quality assurance was further evaluated by a successful performance in a quarterly external quality assurance program. CONCLUSIONS: It is possible to devise an easy to use quality assurance program for extra laboratory measurement of cholesterol levels in children, and, with minimal assistance, maintain acceptable standards of cholesterol analysis. The quality assurance improved following the first 3 months of training and education. Subsequent continuous quality improvement was maintained with minimal involvement of the specialist center. Should the controversial issue of private office measurement of blood cholesterol levels become universally acceptable, the implication from our study is that standards acceptable to the National Cholesterol Education Program and the Clinical Laboratory Improvement Amendments of 1988 are possible using a suitable quality assurance program.

Bias↗

Effect of starch and inorganic nitrogen on microbial transformations of organic compounds in soil.

It was found in long-term incubation experiments (100 weeks) that in soil non amended with organic compounds, mineralization proceeded in a steady state after an initial reactive respiration and corresponded approximately to the rate of mineralization of soil organic matter under natural conditions. The addition of nitrogen influenced this mineralization process only very slightly. The addition of starch decreased the stability of organic compounds in the soil at first but the newly formed organic substances were gradually stabilized again. The addition of nitrogen to starch increased the extent and the rate of these alterations. The overall extent of mineralization of the substrate after the addition of starch alone exceeds the amount of the added substrate; a small accumulation of the substrate could be observed after the addition of starch together with nitrogen.

Biotransformation↗

Gluconic acid production and phosphate solubilization by the plant growth-promoting bacterium Azospirillum spp.

In vitro gluconic acid formation and phosphate solubilization from sparingly soluble phosphorus sources by two strains of the plant growth-promoting bacteria A. brasilense (Cd and 8-I) and one strain of A. lipoferum JA4 were studied. Strains of A. brasilense were capable of producing gluconic acid when grown in sparingly soluble calcium phosphate medium when their usual fructose carbon source is amended with glucose. At the same time, there is a reduction in pH of the medium and release of soluble phosphate. To a greater extent, gluconic acid production and pH reduction were observed for A. lipoferum JA4. For the three strains, clearing halos were detected on solid medium plates with calcium phosphate. This is the first report of in vitro gluconic acid production and direct phosphate solubilization by A. brasilense and the first report of P solubilization by A. lipoferum. This adds to the very broad spectrum of plant growth-promoting abilities of this genus.

Azospirillum↗

Siegfried Oberndorfer: origins and perspectives of carcinoid tumors.

Carcinoid tumors are rare, indolent neoplasms that, although clinically well defined, are regarded as exotic and are consequently often unrecognized. Although little is known of the lives of the men who defined the tumor, described its distinct histology and cell type, and delineated the clinical hallmarks of the disease even less is known of the pathobiology of the lesion. In the nineteenth century, T. Langhans (1839-1915), O. Lubarsch (1860-1933), and W. B. Ransom (1860-1909) described unusual tumors in the small bowel but each failed to adequately investigate these novel entities. This responsibility fell to Siegfried Oberndorfer (1876-1944), who became the first to adequately characterize the nature of the tumors and refer to them as "benign carcinomas." During his tenure at the Pathological Institute of the University of Munich, Oberndorfer noted in 1907 that the lesions were distinct clinical entities and named them "karzinoide" ("carcinoma-like"), emphasizing in particular their benign features. In 1929 he amended his classification to include the possibility that these small bowel tumors could be malignant and also metastasize. Although the enterochromaffin cell, the carcinoid cell of origin, had been identified as early as 1897 by N. Kulchitsky (1856-1925), it was not until 1953 that F. Lembeck (1922-) established that such cells synthesized and secreted serotonin--a potent bioactive amine. Thereafter the protean clinical effects of serotonin, including "flushing," were recognized as was the associated relationship of carcinoid heart disease (Biörck in 1952) and fibrosis (Moertel in 1961). As the centennial of the observations of Oberndorfer approaches, it should be noted that the legacy of one of Germany's most distinguished pathologists, teachers, and scientists (whose career fell victim to the machinations of the Third Reich) has been largely unrecognized. Similarly, the biology and mechanistic analysis of these lesions remain to a large extent unexplored. The present article describes the contributions of the clinical and scientific pioneers in the elucidation of carcinoid disease and traces the evolution of the discovery and understanding of carcinoid tumor biology. It also serves to memorialize the extraordinary accomplishments of Oberndorfer, whose vision exceeded his times.

Carcinoid Tumor↗

Cultivation of mesophilic soil crenarchaeotes in enrichment cultures from plant roots.

Because archaea are generally associated with extreme environments, detection of nonthermophilic members belonging to the archaeal division Crenarchaeota over the last decade was unexpected; they are surprisingly ubiquitous and abundant in nonextreme marine and terrestrial habitats. Metabolic characterization of these nonthermophilic crenarchaeotes has been impeded by their intractability toward isolation and growth in culture. From studies employing a combination of cultivation and molecular phylogenetic techniques (PCR-single-strand conformation polymorphism, sequence analysis of 16S rRNA genes, fluorescence in situ hybridization, and real-time PCR), we present evidence here that one of the two dominant phylotypes of Crenarchaeota that colonizes the roots of tomato plants grown in soil from a Wisconsin field is selectively enriched in mixed cultures amended with root extract. Clones recovered from enrichment cultures were found to group phylogenetically with sequences from clade C1b.A1. This work corroborates and extends our recent findings, indicating that the diversity of the crenarchaeal soil assemblage is influenced by the rhizosphere and that mesophilic soil crenarchaeotes are found associated with plant roots, and provides the first evidence for growth of nonthermophilic crenarchaeotes in culture.

Crenarchaeota↗

New Food and Drug Administration requirements for inclusion of vitamin K in adult parenteral multivitamins.

The newly amended requirements by the Food and Drug Administration (FDA) for an effective adult parenteral multivitamin drug product increase the amounts of vitamins B1, B6, C, and folic acid currently in the product to better meet estimated needs, and specifies the inclusion of 150 microg of vitamin K. Infuvite Adult Multiple Vitamins for Infusion is the first adult parenteral multivitamin product to meet the revised FDA requirements. The inclusion of vitamin K in adult parenteral multivitamin products is intended to afford patients a consistent daily supply of vitamin K approximating usual levels of intake. This is a change to clinical practice in the United States, where vitamin K has not been included in adult parenteral vitamin preparations, and physicians prescribe vitamin K separately. The reformulation of adult parenteral multivitamins required by the FDA raises questions about the potential impact that inclusion of vitamin K will have on patient management. One clinical practice change is that patients on parenteral nutrition receiving Infuvite Adult should no longer need weekly subcutaneous (SC) or intramuscular (IM) vitamin K injections. In addition, the consistent and modest level of vitamin K provided by the reformulated adult parenteral multivitamins may make it easier for physicians to maintain the desired level of hypoprothrombinemia (low levels of prothrombin) in those patients also on anticoagulant therapy with warfarin. However, for physicians accustomed to administering vitamin K separately, it is important to highlight that it may be more difficult to titrate anticoagulant therapy, especially among patients receiving dual feeding or vitamin K from another source. If marketed globally, these clinical practice issues may be more pronounced outside of the United States, where dual feeding is common, and patients may receive vitamin K from other sources.

Adult↗

Blood transfusions before and on the day of transplantation: effects on cadaver graft survival.

Pre-BTs significantly improve the survival rate for first cadaver transplants, by a mechanism that remains obscure. The maximal influence is seen with smaller numbers of pre-BTs (1-5 units), but is also observed with larger numbers of pre-BTs. The possible beneficial influence of Tx-BTs on graft survival is not proven, and if it exists at all is not nearly as striking as the effect seen with pre-BTs. Tx-BTs neither potentiate nor nullify the benefit of pre-BTs on graft survival. It is therefore recommended that pre-BTs in smaller numbers, such as 1-5 units, be administered to candidates for first cadaver transplants to increase the probability of a successful outcome. Tx-BTs should be utilized when clinically indicated but not with the expectation that they will necessarily improve graft survival.

Antilymphocyte Serum↗

Oral acute toxic class method: a successful alternative to the oral LD50 test.

The oral acute toxic class method (ATC method) was developed as an alternative to replace the oral LD50 test. The ATC method is a sequential testing procedure using only three animals of one sex per step at any of the defined dose levels. Depending on the mortality rate three but never more than six animals are used per dose level. This approach results in the reduction of numbers of animals used in comparison to the LD50 test by 40-70%. The principle of the oral ATC method is based on the Probit model and it was first evaluated on a biometric basis before a national and subsequently an international ring study were conducted. The results demonstrated an excellent agreement between the toxicity and the animal numbers predicted biometrically and observed in the validation studies. The oral ATC method was adopted as an official test guideline by OECD in 1996 and was slightly amended in 2001. The ATC method has been successfully used in Germany and in 2003 >85% of all tests on acute oral toxicity testing was conducted as oral ATC tests. In member states of the European Union the ATC method is used in the range of 50% of all tests conducted. Meanwhile the oral LD50 test has been deleted by OECD, by the European Union and by the USA, making the use of alternatives to the oral LD50 test mandatory.

Administration, Oral↗

[Update on childhood immunization in Switzerland].

The recommendations for routine childhood immunizations undergo continuous re-evaluation and are periodically amended. As a result of the near complete elimination of wild-type poliomyelitis, the oral poliomyelitis live vaccine (OPV) has been replaced by the inactivated vaccine (IPV) for the primary series in infancy. Recent seroepidemiologic data on the dynamics of decay of maternal measles antibodies in infants may lead to the recommendation of administering the first dose of the measles mumps rubella (MMR) vaccine at twelve months rather than at 15 to 23 months of age. The recently introduced hexavalent vaccines for the primary series in infancy provide immunization against hepatitis B without the need for additional injections. Finally, the introduction of pneumococcal conjugate vaccines, which are highly efficacious in infants and young children, will provide the opportunity for successful prevention of vaccine-type invasive pneumococcal infections.

Adolescent↗

Of genes and antigens: the inheritance of psoriasis.

Psoriasis is one of a number of autoimmune diseases that display significant HLA associations. In particular, individuals with onset of disease prior to 40 years of age display striking associations with HLA-Cw6 and are much more likely to have a positive family for psoriasis. However, only about 10% of Cw6-positive individuals develop disease, suggesting that other genetic and/or environmental factors must be involved. Several compelling lines of epidemiologic evidence indicate that psoriasis susceptibility is inherited, albeit not in a simple monogenic fashion, and that genetic, rather than environmental, factors are primarily responsible for the variability in inheritance of psoriasis. Taken together, these observations suggest that one or more loci in addition to HLA are necessary for the development of psoriasis. The number of additional loci is likely to be small, because i) the disease is very common ii) substantial excess risk of psoriasis is observed in first degree relatives, and iii) nevoid variants of psoriasis have been reported, suggestive of somatic mutation of a single gene during development. The substantial homogeneity of the psoriatic phenotype and the clear evidence for increased HLA association and heritability in juvenile onset disease indicate that despite its complexity, psoriasis is a common disease whose etiology is amendable to elucidation through the techniques of modern molecular genetics.

Age of Onset↗

ECOs, FOBs, and UFOs: making sense of observational data.

Systematic observations of rat behavior are required for both standard subchronic safety studies and for neurotoxicity studies. The requirements specify subjective out-of-cage observations (eg, posture, gait, and reactivity to various stimuli such as, auditory, tactile, and noxious) using defined scales. Measurement of forelimb/hind limb grip strength, landing foot splay, and locomotor activity are also required. The observational endpoints are organized into a battery, eg, the Environmental Protection Agency functional observational battery (FOB) or expanded clinical observations (ECO). Functional and neuropathologic data are most easily integrated when the functional endpoints are organized as a neurologic exam (ie, each endpoint has a known anatomical basis and there are sufficient endpoints to cover the nervous system). Current batteries do not constitute a neurologic exam. Although ECOs and FOBs contain some components of a neurologic exam (ie, observations of gait, response to pinch), the anatomic basis for other components (eg, hind limb splay) is poorly defined. And although some functions (eg, somatomotor) are well characterized by current batteries, others (eg, vision, somatosensation) are evaluated less effectively. The measurement of locomotor activity in a novel environment is one of the most problematic parts of current functional testing batteries, although contemporary technology may provide opportunities for improving this test. The influence of inherent limitations of functional test methods is magnified by factors associated with testing for neurotoxicant-related effects during safety studies. First, most personnel at contract laboratories have little or no formal training in conducting and interpreting a neurologic examination. Second, most neurotoxicant-related lesions are bilateral, which paradoxically may produce more subtle effects than unilateral lesions. Third, most chemicals will be tested only once, and sponsors are reluctant to evaluate results in "real time" and amend protocols to add endpoints (eg, neurophysiological tests) to clarify functional effects. Pathologists should have realistic expectations about the opportunities for integrating functional and neuropathologic findings.

Animals↗

The tenuous nature of the Medicaid entitlement.

Although Medicaid is regarded as a federal entitlement program, nowhere does the Medicaid statute explicitly recognize a federal right of action to enforce recipients' rights. Arguably, the Supreme Court, rather than Congress, first recognized the right of Medicaid recipients to protection of federal law. A controversial 2001 federal court decision, however, called into question the continuing existence of federally enforceable Medicaid rights. Although this decision has been reversed, it illuminates the tenuous nature of the Medicaid entitlement, as do recent Supreme Court decisions narrowing federal rights. Congress should amend the Medicaid statute to ensure the rights of Medicaid recipients.

Civil Rights↗

Growth responses of scots pine seedlings grown in peat-based media amended with natural zeolite.

Zeolite has many good features that makes it very attractive for nursery use as a growing media over others. This study was designed to investigate influence of different growing media and their mixtures (with zeolite and without zeolite) on morphological characters of scots pine seedlings. Twenty-one treatments of varying amounts of peat, fine pumice, coarse pumice, river sand, perlite and river sand were established and were sown with scots pine seeds. At the end of first growing period, 30 seedlings from each treatment were harvested and measured for height (SH), root collar diameter (RCD), root dry weight (RDW), stem dry weight (SDW) and total dry weight (TSDW). These parameters varied significantly among treatments and were lower in zeolite added media. SH negatively correlated with Na and K content and C/N ratio of growing media but positively correlated with Mn content of media. SDW and TSDW had positive correlation with N, Fe, Mn, total porosity and loss of ignition, and had negative correlation with pH, Ca, Na and K content.

Culture Media↗

Periconceptional health and lifestyle factors of both parents affect the risk of live-born children with orofacial clefts.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (CL/P) or cleft palate only (CPO) are orofacial clefts and have a multifactorial etiology. The identification of amendable parental risk factors may contribute to a reduced occurrence of these malformations in the future. METHODS: Standardized demographic and periconceptional exposure data from 284 parents of a child with CL/P, 66 parents of a child with a CPO and 222 parents of a child without congenital malformations were collected at approximately 24 months after the periconceptional period of the index child. Univariate and multivariate logistic regression analyses were used to estimate relative risks by odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Univariate results suggest that low parental education, periconceptional maternal medication use and illnesses, paternal smoking, and first-trimester maternal common cold increased CL/P risk. Pregnancy planning and periconceptional folic acid supplementation, however, reduced CL/P risk by approximately 50% (OR, 0.5; 95% CI, 0.3-0.8) and 40% (OR, 0.6; 95% CI, 0.4-0.9), respectively. Mostly comparable results were obtained for CPO. Being a boy (OR, 2.0; 95% CI, 1.4-3.0), folic acid supplementation (OR, 0.6; 95% CI, 0.4-0.9), and low paternal education (OR, 1.6; 95% CI, 1.0-2.3) mainly determined CL/P in the multivariate analyses, compared to low paternal (OR, 4.5; 95% CI, 2.1-9.4) and maternal medication use (OR, 2.0; 95% CI, 1.0-4.0) for CPO. CONCLUSIONS: Preconceptional counseling for orofacial cleft risk assessment should pay attention to maternal medication use, periconceptional folic acid supplementation, and exposures of the father. These determinants can be amended, thereby modifying orofacial cleft risk.

Adult↗

Effects of humic substances on fluorometric DNA quantification and DNA hybridization.

DNA extracts from sediment and water samples are often contaminated with coextracted humic-like impurities. Estuarine humic substances and vascular plant extract were used to evaluate the effect of the presence of such impurities on DNA hybridization and quantification. The presence of humic substances and vascular plant extract interfered with the fluorometric measurement of DNA concentration using Hoechst dye H33258 and PicoGreen reagent. Quantification of DNA amended with humic substances (20-80 ng/microl) using the Hoechst dye assay was more reliable than with PicoGreen reagent. A simple procedure was developed to improve the accuracy for determining the DNA concentration in the presence of humic substances. In samples containing up to 80 ng/microl of humic acids, the fluorescence of the samples were measured twice: first without Hoechst dye to ascertain any fluorescence from impurities in the DNA sample, followed with Hoechst dye addition to obtain the total sample fluorescence. The fluorescence of the Hoechst dye-DNA complex was calculated by subtracting the fluorescence of the impurities from the fluorescence of the sample. Vascular plant extract and humic substances reduced the binding of DNA onto the nylon membrane. Low amounts (<2.0 microg) of humic substances derived from estuarine waters did not affect the binding of 100 ng of target DNA to nylon membranes. DNA samples containing 1.0 microg of humic substances performed well in DNA hybridizations with DIG-labeled oliogonucleotide and chromosomal probes. Therefore, we suggest that DNA samples containing low concentrations of humic substances (<20 ng/microl) could be used in quantitative membrane hybridization without further purification.

Bisbenzimidazole↗

Bothriocephalus gadellus n. sp. (Cestoda: Bothriocephalidae) from the beardless codling Gadella imberbis (Vaillant) (Moridae) in the southwestern Gulf of Mexico, with a review of species of Bothriocephalus Rudolphi, 1808 reported from gadiform fishes.

Bothriocephalus gadellus n. sp. is described from the intestine of the beardless codling Gadella imberbis (Gadiformes: Moridae) from the southwestern Gulf of Mexico. It resembles B. scorpii, the type-species of Bothriocephalus, and B. manubriformis, the only species of the genus reported from the Gulf of Mexico. B. gadellus n. sp. differs from both species in having four excretory canals on each side of the proglottid (three per side in B. scorpii; two per side anastomosing to form an extensive plexus throughout the medulla in B. manubriformis ), 24-33 testes per proglottid (30-60 in B. scorpii; 60-100 in B. manubriformis), a total length of 31-47 mm (32-950 mm in B. scorpii; 130-1,000 mm in B. manubriformis), and a seminal receptacle and wing-like expansions on each proglottid (absent in B. scorpii and B. manubriformis), as well as lacking two sets of reproductive organs per proglottid (present in B. scorpii) and a vagina with a bulbous sphincter near the opening (present in B. manubriformis). An amendment to the generic diagnosis of Bothriocephalus might be warranted if other species of this genus are found to possess a seminal receptacle. B. gadellus n. sp. appears to be like those species of Bothriocephalus that can utilise two intermediate hosts (copepod and fish). B. ellipticus and B. neglectus are designated as species inquirendae. This is the first report of a cestode from a morid fish in the Gulf of Mexico, and the first report of a parasite from a species of Gadellus.

Animals↗

June, bioethics and the Supreme Court.

These decisions regarding the treatment of handicapped newborns and a woman's right to privacy in the abortion decision reflect the controversies in our society regarding decisions to treat severely defective newborns or to terminate a pregnancy. In the first decision, the court was divided 5 to 3. In the second decision, the court was divided 5 to 4. It is clear that we as a society are unclear about what a policy should be. In the end, however, constitutional rights to privacy and the rights of parents over their children should not be open to amendments by majoritarian forces.

Abortion, Induced↗

[Proper use of laboratory tests from a perspective of health insurance administration].

The national medical expenditure increases at a rate of 1 trillion yen a year, and the expenditure for 1992 is estimated to be about 23 trillion yen. One of the most important jobs of the Health Insurance Administration is to control the medical expenditure. Every time the medical fee is amended, laboratory tests are always the target of the cost containment. In the past, the biochemical tests have been separated into the cost for performance of test, and the cost for assessment of the results, the cost of tests for specific diseases has been comprised, or fixed, and the fee of EKG, EEG, Echo etc after the first has been forced to be reduced. These are all administrative policies, but ultimately, they must be selected properly by the physician who requests these tests. In the future, a system should be established which enables the physician to efficiently (cost-efficiently) select the most appropriate test. For this purpose, undergraduates and post-graduates should learn the concepts of clinical epidemiology and clinical economics. These academic disciplines should be incorporated to increase the value of the treatment. Furthermore, the physician should be given economical incentive of proper use of medical resources.

Clinical Laboratory Techniques↗