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Ultrastructure of rabbit retinal nerve fibre layer--neuro-glial relationships, myelination, and nerve fibre spectrum.

The ultrastructure of the rabbit retinal nerve fibre layer was studied both in retinal centre and periphery. The central nerve fibre layer was found to contain large masses of--mostly myelinated--nerve fibres, somata and processes of astrocytes and oligodendrocytes, vitreal processes of Müller cells, and blood vessels. Astrocyte and Müller cell processes could be discriminated both by their direction and by the thickness of their intermediate filaments which was about 7 nm in Müller cells and about 10 nm in astrocytes. Some peculiarities of nuclei and cytoplasmic organelles of rabbit retinal astrocytes and oligodendrocytes are described. Myelin sheaths are demonstrated to be derived from oligodendrocytes; in some cases, two axons were found within a common myelin sheath. In the retinal periphery, only sparse thin bundles of unmyelinated axons were found in between a thick row of big Müller cell endfeet; astrocytes, oligodendrocytes, and blood vessels were missing here. In both retinal regions, node-like membrane specializations of optic axons were found; these were always surrounded by a corona of fine glial processes arising from astrocytes as well as from Müller cells. The features of myelination within the rabbit nerve fibre layer were quantified, and compared with recent literature data. A hypothesis is offered relating the production of myelin to the release of diffusable substance(s) by active axons. This hypotheses allows to account for the striking finding that relatively thick axons remain unmyelinated in the nerve fibre layer of most mammalian retinae like in the rabbit retinal periphery whereas they become myelinated in the central rabbit retina like in central nervous system in general.

Animals↗

[The testicular feminization syndrome--a report of 9 cases].

We present the data of analysis of 9 cases (girls and young women) aged 14 to 20 years, with syndrome of testicular feminisation. The patients were diagnosed and treated at the departments of Paediatric and Adolescent Gynaecology and of Gynaecological Endocrinology at the University Ob. & Gyn. hospital in Sofia. The diagnosis was based on the clinical picture, karyogram and radioimmunoassay of gonadotropic and sex hormones. Described were some data as family history, clinical picture, from of the disease, appearance, genital and hormonal status, and histodiagnosis of the removed gonads. Out of nine, primarily diagnosed as a syndrome of testicular feminisation girls and women one ws with an incomplete from, in another further investigations evoked a suspicion of Swyer syndrome (a 14-years-old girl, on whom surgical treatment due to big gonadoblastoma was performed, she died a year later). One patient also developed an ovarian tumour, in six we performed gonadectomy. One patient did not come for any treatment. The differential diagnosis with some relatively rare syndromes, as well as the treatment of this patients were discussed.

Adolescent↗

Temperature data for phenological models.

In an arid environment, the effect of evaporation on energy balance can affect air temperature recordings and greatly impact on degree-day calculations. This is an important consideration when choosing a site or climate data for phenological models. To our knowledge, there is no literature showing the effect of the underlying surface and its fetch around a weather station on degree-day accumulations. In this paper, we present data to show that this is a serious consideration, and it can lead to dubious models. Microscale measurements of temperature and energy balance are presented to explain why the differences occur. For example, the effect of fetch of irrigated grass and wetting of bare soil around a weather station on diurnal temperature are reported. A 43-day experiment showed that temperature measured on the upwind edge of an irrigated grass area averaged 4% higher than temperatures recorded 200 m inside the grass field. When the single-triangle method was used with a 10 degrees C threshold and starting on May 19, the station on the upwind edge recorded 900 degree-days on June 28, whereas the interior station recorded 900 degree-days on July 1. Clearly, a difference in fetch can lead to big errors for large degree-day accumulations. Immediately after wetting, the temperature over a wet soil surface was similar to that measured over grass. However, the temperature over the soil increased more than that over the grass as the soil surface dried. Therefore, the observed difference between temperatures measured over bare soil and those over grass increases with longer periods between wettings. In most arid locations, measuring temperature over irrigated grass gives a lower mean annual temperature, resulting in lower annual cumulative degree-day values. This was verified by comparing measurements over grass with those over bare soil at several weather stations in a range of climates. To eliminate the effect of rainfall frequency, using temperature data collected only over irrigated grass, is recommended for long-term assessment of climate change effects on degree-day accumulation. In high evaporative conditions, a fetch of at least 100 m of grass is recommended. Our results clearly indicate that weather stations sited over bare soil have consistently higher degree-day accumulations. Therefore, especially in arid environments, phenology models based on temperature collected over bare soil are not transferable to those based on temperature recorded over irrigated grass. At a minimum, all degree-day-based phenology models reported in the literature should clearly describe the weather station site.

Environmental Monitoring↗

Status of protozoan genome analysis: trypanosomatids.

The three trypanosomatid genome projects have employed common strategies which include: analysis of pulsed-field gel electrophoretic chromosomal karyotypes; physical mapping using big DNA (cosmid, pacmid P1, bacterial artificial chromosome, yeast artificial chromosome) libraries; partial cDNA sequence analysis to develop sets of expressed sequence tags (ESTs) for gene discovery and use as markers in physical mapping; genomic sequencing; dissemination of information through development of web-sites and ACeDB-based fully integrated databases; and establishment of functional genomics programmes to maximize useful application of genome data. Highlights of the projects to date have been the demonstration that, despite extensive chromosomal size polymorphisms for diploid homologues within Africa trypanosomes, T. cruzi or Leishmania, the physical linkage groups for markers on each chromosome are retained across all isolates/species studied within each group. For African trypanosomes, detailed analysis of chromosome 1 has demonstrated that repetitive sequences and the two retroposon-like elements RIME and INGI are localized to a defined region at one end of the chromosome, with the bulk of the central region of the chromosome containing genes coding for expressed proteins. Comparative mapping shows that, although subtelomeric changes account for a large proportion of the polymorphism in chromosome size in African trypanosomes, there are significant expansions and contractions in regions across the entire chromosome. The highlight of the genomic sequencing projects has been the demonstration of just 2 putative transcriptional units of chromosome 1 of Leishmania major, extending on opposite strands from a point in the central region of the chromosome. A similar observation made on 93.4 kb of contiguous sequence for T. cruzi chromosome 3 suggests the presence of promoter and regulatory elements at the junctions of large polycistronic transcriptional units. All data obtained from the genome projects are made available through the public domain, which has prompted changing philosophies in how we approach analysis of the biology of these organisms, and strategies that we can employ now in the search for new therapies and vaccines.

Animals↗

Application of MARSSIM at the Big Rock Point Restoration Project.

Big Rock Point was Michigan's first commercial power reactor and operated for 35 years. It was permanently shut down in August of 1997, and the site is currently being returned to its natural state. Guidance contained in the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) is being applied in preparation for the final status survey. Unlike other commercial power reactors currently undergoing decommissioning, all Big Rock Point structures will be removed prior to the final status survey. A historical site assessment along with characterization surveys formed the basis to designate 1.6 square kilometers (395.9 acres) of the site as non-impacted and the remaining 0.7 square kilometers (184.5 acres) as impacted as defined by MARSSIM. Also, a source term abstraction has been performed using historical waste stream data to identify radionuclides potentially present in site soils, hard-to-detect (HTD) radionuclides and surrogate radionuclides for the HTD radionuclides.

Decontamination↗

[The factors associated with the occurrence of immature forms of Aedes aegypti in Ilha do Governador, Rio de Janeiro, Brazil].

Aedes aegypti is the vector of dengue, a disease that can result in epidemics. Ecological studies are important because different geographical populations of the vector may differ in their bioecological characteristics, which can be helpful in guiding control actions. The objective of this study was to identify and to analyze some factors associated with the occurrence of immature forms of A. aegypti on Ilha do Governador, Rio de Janeiro, using data from the National Health Foundation (FNS). The results showed that 58.04% of all the containers examined were supports for plant pots, and plastic or glass cans discarded in the yard. The highest percentages of positive breeding sites were observed in tires (1.41%), wells and cisterns (0.93%), and barrels and large metal cans (0.64%). In the summer, the proportion of positivity was higher for big containers used for water storage and for containers discarded in the yard. In the winter the proportion was higher for small containers used for water storage. The highest rates of positive containers were observed after three months without FNS activities. Our results show the necessity to continue the control, and suggest that less attention was paid to small containers during the winter by FNS. Factorial analysis showed that the determinant factor for the occurrence of immature forms of A. aegypti is represented by environmental factors, while elimination and treatment of breeding sites by FNS play a less important role, a fact possibly causing the maintenance of immature forms of A. aegypti.

Aedes↗

Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma.

Plasma and cerebrospinal fluid (CSF) concentrations of endothelin (ET)-1, ET-3, and big ET-1 in patients with aneurysmal rupture were measured serially for 2 weeks after the onset of aneurysmal subarachnoid hemorrhage (SAH) and compared with levels of ETs in patients without SAH and the plasma concentrations of ETs in normal volunteers. Big ET-1 was the predominant peptide present in the CSF of SAH patients. The CSF concentrations of big ET-1, ET-1, and ET-3 were significantly higher in older patients than in younger patients. In SAH patients with cerebral vasospasm (CVS) documented by transcranial Doppler sonography and clinical signs, postoperative concentrations of ETs in the CSF remained at or were increased above levels measured before surgery. In SAH patients without CVS, the concentrations of ETs in the CSF decreased with time, whereas the time course of CVS coincided with the increase in concentrations of big ET-1 and ET-1. The temporal dependence of concentrations of big ET-1 and ET-1 in SAH patients with and without CVS were significantly different. The volume of hematoma in the basal cisterns as detected by computerized tomography was predictive of the concentrations of ETs in the CSF. Plasma concentrations of ETs were not correlated with CVS. The possible role of ETs in the pathogenesis of CVS associated with SAH and the controversial data reported to date are discussed.

Adolescent↗

Injured workers' perceptions of case management services. A descriptive study.

This article describes the findings from a study of injured workers conducted as part of a multifaceted evaluation study of a case management program. The sample consisted of workers who filed a workers' compensation claim between January 1 and September 30, 1995. Data collection consisted of written surveys (n = 45), personal interviews (n = 27), and telephone interviews (n = 16). The findings from this study provided many insights into the injured workers' personal and work experiences, and, in particular, their perceptions of their experience with the nurse case management program. Workers satisfied with services described the nurse case manager (NCM) as having the ability to see the "big picture," to develop appropriate goals, and to anticipate client needs. Dissatisfied workers reported feeling unimportant in terms of service provision. They reported feeling that "the system" did not respond to their needs, and that the NCM was uninterested and disrespectful. This vivid portrayal of workers' experiences and perceptions of case management services provides valuable information about the world view of the injured worker.

Accidents, Occupational↗

Drug-related visits to the emergency department: how big is the problem?

OBJECTIVES: To review the literature concerning drug-related problems that result in emergency department visits, estimate the frequency of these problems and the rates of hospital admissions, and identify patient risk factors and drugs that are associated with the greatest risk. METHODS: A systematic search of MEDLINE (January 1966-December 2001), EMBASE (January 1980-December 2001), and PubMed (January 1966-December 2001) databases for full reports published in English was performed. The Ottawa Valley Regional Drug Information Service database of nonindexed pharmacy journals also was searched. RESULTS: Data from eight retrospective and four prospective trials retrieved indicated that as many as 28% of all emergency department visits were drug related. Of these, 70% were preventable, and as many as 24% resulted in hospital admission. Drug classes often implicated in drug-related visits to an emergency department were nonsteroidal antiinflammatory drugs, anticonvulsants, antidiabetic drugs, antibiotics, respiratory drugs, hormones, central nervous system drugs, and cardiovascular drugs. Common drug-related problems resulting in emergency department visits were adverse drug reactions, noncompliance, and inappropriate prescribing. CONCLUSION: Drug-related problems are a significant cause of emergency department visits and subsequent resource use. Primary caregivers, such as family physicians and pharmacists, should collaborate more closely to provide and reinforce care plans and monitor patients to prevent drug-related visits to the emergency department and subsequent morbidity and mortality.

Clinical Trials as Topic↗

Conversion of big endothelin-1 by membrane-bound metalloendopeptidase in cultured bovine endothelial cells.

We propose a candidate for the "putative" endothelin (ET) converting enzyme in the cultured endothelial cells (ECs) of bovine carotid artery. The enzyme is membrane-bound, soluble in 0.5% Triton X-100, and capable of converting human big ET-1 to ET-1 by a specific cleavage between Trp21 and Val22. The conversion reached 90% after a 5-hr incubation in the presence of DFP, PCMS and pepstatin A, but it was inhibited by EDTA, omicron-phenanthroline or phosphoramidon. The enzyme is very sensitive to pH, and active only between pH 6.6 and pH 7.6. Conversion of big ET-3 by this enzyme was only 1/9 that of big ET-1. From these results, ET-1 converting enzyme in the bovine EC is most likely to be a membrane-bound, neutral metalloendopeptidase, which is much less susceptible to big ET-3.

Amino Acid Sequence↗

Health care prices, the federal budget, and economic growth.

Rising health care spending, led by rising prices, has had an enormous impact on the economy, especially on the federal budget. Our work shows that if rapid growth in health care prices continues, under current institutional arrangements, real economic growth and employment will be lower during the next two decades than if health price inflation were somehow reduced. How big the losses are and which sectors bear the brunt of the costs vary depending on how society chooses to fund the federal budget deficit that stems from the rising cost of federal health care programs.

Budgets↗

The big-bang-for-your-buck theory.

Do it right, and your investment in information technology can have all sorts of strategic payoffs. Do it wrong, and you'll be paying, dearly, for nothing. Here's a guide to evaluating IT and measuring its impact.

Budgets↗

Intention-to-treat analysis in the chronic suppurative otitis media trials.

OBJECTIVE: To determine the extent of application of the intention to treat principle in the chronic suppurative otitis media (CSOM) randomised controlled trials. DESIGN: Data were extracted from 28 CSOM randomised controlled trials. MAIN OUTCOME MEASURES: Conceptual and methodological approaches of dealing with protocol deviations with respect to withdrawal, missing response and non-compliance. RESULTS: Of the 28 CSOM trials included in this study, only one (4%) trial mentioned intention-to-treat (ITT) analysis. However, 10(36%) other trials which did not mention ITT, had no protocol deviations and thus carried out an ITT analysis by default. It is highly likely that a biased treatment effect existed in the trial that mentioned ITT since the authors undertook a complete case analysis disregarding the 22% protocol deviators. There were no attempts in any of the trials to impute for missing responses and carrying out a sensitivity analysis. For trials with a big percentage of protocol deviations, the validity of their results are brought to question. CONCLUSIONS: In practice, not all those entered into a randomised-controlled trial will complete the trial. Thus intention-to-treat analysis is an important aspect of randomised controlled trials of health care interventions which tries to bridge this gap. It is important for authors to explicitly state the protocol deviations, the methods used to handle them and the potential effect with reference to bias and study outcome.

Data Collection↗

Binding protein for human growth hormone: effects of age and weight.

In human serum, a specific binding protein with high affinity for human growth hormone (GHBP) is found which is identical to the extracellular portion of the hepatic GH receptor. GHBP is assessed by incubating serum samples with [125I]-GH, followed by separation of bound and free radioactivity using gel chromatography. In newborns and children younger than 2 months, GHBP was practically absent and no 'big-big' GH could be found. GHBP values increased rapidly during the first 2 years of life, followed by a slower increase during childhood and puberty. No difference was found between male and female subjects. Apart from age, standardized weight (SDS = z score) had a major positive effect on GHBP concentration. Interestingly, SDS height correlated negatively with GHBP when weight and age were controlled for. These data may relate to two clinical findings: (1) the developmental switch between GH-independent intrauterine and GH-dependent postnatal growth mechanisms, and (2) the accelerated growth velocity encountered in adipose children.

Adolescent↗

The dilemma of new drugs. Are costs rising faster than effectiveness?

This century has seen a phenomenal growth in the development, understanding and use of pharmaceuticals. Additionally, this period has seen the balance of the treatment needs of patients shift dramatically from infectious to cardiovascular and cancer diseases, and from infancy and middle-age to old age. The value of modern pharmaceuticals to society is undoubted. However, the benefits in terms of health gain, when adequately evaluated, are often more modest than first supposed, and are often achieved at considerable costs and sometimes considerable risks to patients. Data are seldom adequate to attempt a robust evaluation of the cost effectiveness of drugs and compare how cost effectiveness may have changed over time. Rapid increases in development costs coupled with the increasing focus on chronic and old-age diseases make it probable that the cost effectiveness of new drugs is broadly declining, but such a conclusion should be interpreted with caution. The big challenge for the next century with its likely genetic and biotechnological discoveries, bringing as yet unforeseen benefits, risks and costs, is to radically improve the manner in which new drugs are evaluated and diffuse into health systems.

Drug Approval↗

The statistical big bang of 1911: ideology, technological innovation and the production of medical statistics.

This paper examines the relationship between intellectual debate, technologies for analysing information, and the production of statistics in the General Register Office (GRO) in London in the early twentieth century. It argues that controversy between eugenicists and public health officials respecting the cause and effect of class-specific variations in fertility led to the introduction of questions in the 1911 census on marital fertility. The increasing complexity of the census necessitated a shift from manual to mechanised forms of data processing within the GRO. The subsequent increase in processing power allowed the GRO to make important changes to the medical and demographic statistics it published in the annual Reports of the Registrar General. These included substituting administrative sanitary districts for registration districts as units of analysis, consistently transferring deaths in institutions back to place of residence, and abstracting deaths according to the International List of Causes of Death.

Censuses↗

High-yield production of human big endothelin-1 by a combination of chemical modification and proteolysis of a fusion protein in Escherichia coli.

A protein modification method has been developed for the production of human big endothelin (ET)-1. Production of a large quantity of big ET-1 by the method described here is expected to facilitate future experiments such as X-ray crystallography and nuclear magnetic resonance studies, aimed at understanding the tertiary structure of big ET-1 and its dynamics. The plasmid pETB-50 used for the synthesis carries the gene for a fusion protein consisting of 34-amino acid (aa) residues of an N-terminal portion of beta-galactosidase and the 38-aa residues of big ET-1. The fusion protein ETB-50P contains an arginine residue in the big ET-1 portion at its second C-terminal site and three lysine residues including the C-terminal site in the beta-galactosidase portion, all of which are susceptible to trypsin. Tryptic digestion of the fusion protein quantitatively produced big ET-1 (1-37), which is depleted in the C-terminal serine. However, a treatment of the fusion protein with 1,2-cyclohexanedione prior to tryptic digestion gave full-length big ET-1 with N7, -N8-(1,2-dihydroxycyclohex-1,2- ylene)-arginine. This modification was reversed to the intact arginine residue when the modified big ET-1 was incubated in 0.5 M TRIS-HCl buffer, pH 8.0. Consequently, a combination of such a reversible protein modification and tryptic digestion gave 1.74 mg of recombinant big ET-1 from 2.01 of culture broth. The procedure described here may be applied to produce other arginine-containing peptides from fusion proteins.

Amino Acid Sequence↗

Co-operative interactions control conjugative transfer of broad host-range plasmid RK2: full effect of minor changes in TrbA operator depends on KorB.

A network of circuits, with KorB and TrbA as key regulators, controls genes for conjugative transfer of broad host range plasmid RK2. To assess the importance of the TrbA regulon, mutational analysis was applied to the TrbA operator at the trbB promoter and then to other TrbA-regulated promoters in the tra region. All identified TrbA operators are submaximal; in the case of trbBp, a G to A transition that made the operator core a perfect palindrome increased repression by about 50% compared to the wild type. When this change was introduced into the RK2 genome, decreases in transfer frequency of up to three orders of magnitude were observed, with bigger effects when Escherichia coli was the donor compared to Pseudomonas putida. Western blotting showed a significant decrease in Trb protein levels. These effects were much greater than the effect of the mutation on repression by TrbA alone. When KorB was introduced into the reporter system, the effects were closer to those observed in the whole RK2 context. These results indicate that co-operativity, previously observed between TrbA and KorB, allows big changes in transfer gene expression to result from small changes in individual regulator activities.

Bacterial Proteins↗