[Individuality in medicine in light of new theory of logic].
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Fuzzy Logic↗
Biomedical subjects
R Gross
Publications and source records attributed to R Gross.
Effect of adherence to newly initiated antiretroviral therapy on plasma viral load.
OBJECTIVE: To determine whether differences in adherence to newly initiated antiretroviral therapy exist between subjects who do and do not achieve undetectable plasma viral loads. DESIGN: Observational cohort study monitoring adherence and virological and immunological parameters over the initial 4 months of therapy with nelfinavir. Adherence was measured using the microelectronic monitoring system (MEMS; APREX Corporation, Menlo Park, California, USA). SETTING: General Clinical Research Center at a tertiary care center. PARTICIPANTS: Forty-one protease inhibitor-naive subjects with viral loads > 10 000 copies/ml newly starting a regimen including nelfinavir, referred from HIV clinics in Philadelphia. MAIN OUTCOME MEASURES: The primary outcome was undetectable viral load (< 50 copies/ml) after 4 months. Secondary measures included changes in viral load and CD4 cell counts. We hypothesized that adherence would be greater in subjects who achieved undetectable viral loads. RESULTS: Adherence was greater in undetectable subjects, who took a median of 93% of prescribed doses [interquartile range (IQR) 84-96%], whereas detectable subjects took a median of 70% (IQR 46-93%). Adherence correlated with viral load decrease (Spearman's rho = 0.38, P < 0.01) and CD4 cell count increase (Spearman's rho = 0.25, P = 0.06). Despite differences between the groups over 4 months of therapy, there were no adherence differences over the first month [undetectables, 95% (IQR 88-98%) versus detectables, 94% (IQR 87-98%), P > 0.50]. CONCLUSIONS: Adherence is important in determining whether or not individuals achieve suppression with a newly initiated antiretroviral regimen. Adherence begins to wane after the first month of therapy. Therefore, closer assessment of adherence particularly after this first month is important.
Adult↗
A constitutive nitric oxide synthase modulates insulin secretion in the INS-1 cell line.
We provide immunocytochemical evidence that the neuronal isoform of constitutive NO synthase (cNOS) is expressed in the rat insulinoma cell line INS-1. Furthermore, using N omega-nitro-L-arginine methyl ester (L-NAME), a pharmacological inhibitor of cNOS activity, we show that this enzyme is implicated in the modulation of insulin secretion in INS-1 cells. Indeed, in the presence of 2.8 mM glucose, L-NAME induced a specific and dose-dependent increase in insulin release, suggesting that cNOS exerts an inhibitory tone on basal insulin secretion. Moreover, L-arginine, the physiological substrate of cNOS, significantly reduced the marked enhancing effect of L-NAME on insulin release and to a lesser extent, at low concentrations, that of 10 mM KCl. L-NAME also potentiated the insulin secretion stimulated by 5.5 and 8.3 mM glucose, but in this case, its effect was not reduced by L-arginine. In conclusion, our data show that the neuronal isoform of cNOS exerts a negative modulation on insulin secretion in INS-1 cells, confirming the previous results obtained in the isolated perfused rat pancreas or pancreatic islets.
Animals↗
Rational design and molecular characterization of a chimaeric response regulator protein.
BvgA and EvgA are closely related response regulators from Bordetella pertussis and Escherichia coli. To analyze the domain borders and linker sequences of these proteins, we used limited proteolysis and matrix-assisted laser desorption/ionization-mass spectrometry analysis of the in-gel-digested proteolytic fragments. The thermolysin-sensitive linker regions were found to extend from Leu130 to Thr144 for BvgA and from Leu127 to Ser133 for EvgA. These data provided the rationale for the construction of the chimaeric protein HA. HA carries the EvgA receiver and BvgA output domains, fused in the central part of the linker sequences of the parent proteins. Thermolysin-sensitive sites of HA were found at positions identical with those in the EvgA and BvgA linker sequences, indicating intact folding of its receiver and output domains. Consistent with this, the chimaera showed virtually unchanged phosphorylation and dimerization properties. However, BvgA and HA differed in the effect of phosphorylation on their DNA-binding activities. In the case of BvgA, phosphorylation resulted in an increased affinity and specificity in DNA binding, whereas the DNA-binding properties of HA were not affected by phosphorylation. The chimaera HA was unable to activate transcription of the BvgA-dependent fha promoter, either in vivo or in vitro. These results indicate that the phosphorylation-induced activation of BvgA requires specific interactions between the receiver and output domains that are disturbed in the chimaera.
Amino Acid Sequence↗
Impact of a hospital-based antimicrobial management program on clinical and economic outcomes.
Inappropriate use of antimicrobial agents results in unnecessary exposure to medication, persistent or progressive infection, emergence of resistance, and increased costs. We implemented a program to control use of restricted agents while improving care. This study compared 2 major mechanisms for improving use of antimicrobial agents: (1) recommendations made by the Antimicrobial Management Team (AMT), which included a clinical pharmacist backed up by a physician from the Division of Infectious Diseases (ID), and (2) recommendations made by ID fellows. Outcome measures included appropriateness of recommendations, cure rate, number of treatment failures, and cost of care, which were assessed for 180 patients. The AMT outperformed the ID fellows in all outcomes examined by the study (including appropriateness [87% vs. 47%; P<.001], cure rate [64% vs. 42%; P=.007], and treatment failures [15% vs. 28%; P=.03]), although the differences in economic outcomes between cases managed by the AMT and those managed by the ID fellows were not statistically significant. In an academic setting with a restricted formulary, the AMT demonstrated better antimicrobial prescribing than ID fellows.
Adolescent↗
Managing depression in outpatients.
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Depression↗
Periplasmic methacrylate reductase activity in Wolinella succinogenes.
The cell homogenate and the soluble cell fraction of Wolinella succinogenes grown with formate and fumarate catalyzed the oxidation of benzyl viologen radical by methacrylate [apparent Km=0.23 mM, Vmax=1.0 U (mg cell protein) -1] or acrylate [apparent Km=0.50 mM, Vmax=0.77 U (mg cell protein) -1]. Crotonate did not serve as an oxidant. A mutant of W. succinogenes lacking the fccABC operon was unable to catalyze methacrylate or acrylate reduction. In contrast, the inactivation of fccC alone had no effect on these activities. Methacrylate reduction by benzyl viologen radical was not catalyzed by fumarate reductase isolated from the membrane of W. succinogenes. Cells grown with formate and fumarate did not catalyze methacrylate reduction by formate, and W. succinogenes did not grow with formate and methacrylate as catabolic substrates. The results suggest that the reduction of methacrylate or acrylate by benzyl viologen radical is most likely catalyzed either by the periplasmic flavoprotein FccA or by a complex consisting of FccA and the predicted c-type cytochrome FccB. The metabolic function of the fccABC operon remains unknown.
Cell Membrane↗
Reforming the Israeli health system: findings of a 3-year evaluation.
Israel, like many other European countries, has recently reformed its health care system. The regulated market created by the National Health Insurance (NHI) law embodies many of the principles of managed competition. The purpose of this paper is to present initial findings from an evaluation of the first 3 years of the reform (1995-1997) regarding the implementation of the reform and the extent to which it has achieved its main goals. The evaluation was conducted using multiple quantitative and qualitative research tools: interviews with key informants; analysis of documents and sick fund financial statements; analysis of trends in sick fund membership; and population surveys conducted in 1995 and 1997 to assess the impact of the reform on outcome measures related to level of services to the public. Data from the evaluation show that the NHI law achieved a considerable number of its goals: to provide insurance coverage for the entire population, to ensure freedom of movement among sick funds, and to standardize the way resources are allocated to sick funds. The incentives that are embodied in the law have encouraged the sick funds to improve the level of services provided to the average insuree, and to develop services in the periphery and for some of the weaker populations. From the financial perspective, concerns that NHI would lead to a rise in the national health expenditure were not realized as of 1997. In the wake of NHI, there has been a decline in the age adjusted per capita expenditure in three sick funds, with no reports by insurees, at least through 1997, on a decline in satisfaction or level of service. However, the Israeli experience shows that regulating competition does not necessarily lead to economic stability and equality. Regulating the competition also did not solve some of the major policy issues in the Israeli health system including level of resources allocated to health, organizational structure of the hospital system, manpower planning and the extent of government involvement in system. Additional policy changes may be needed to resolve these issues. Up-to-date information is essential in helping policymakers track the process of reform implementation and results, and identify problems which need to be addressed in the future.
Consumer Behavior↗
Implementing managed competition in Israel.
As of January 1, 1995, Israel's National Health Insurance (NHI) Law laid the foundations for regulating competition among the country's four private, not-for-profit sick funds. Prior to NHI the sick funds (SFs) had competed without governmental control. Extensive research on NHI implementation and the behavior of the sick funds (SFs) after passage of NHI reveals a paradoxical development: The NHI bill drew on the rhetoric of managed competition and did indeed establish a legal and structural framework for regulating competition among the SFs. Nevertheless, in practice, SF autonomy was constrained and competition over provision of statutory care was limited. Rather than fostering competition, the main thrust of the NHI reforms was to enhance central government's control over SF expenses in order to constrain government expenditures. The NHI reforms did encourage the SFs to cut costs and make visible service improvements. However, the reforms did not lead the SFs to reorganize, expand the scope of their services, or improve clinical quality, as the reformers had hoped. Nor did the reforms help eliminate the SF's operating deficits or insure financial stability for the whole health system. Furthermore, the reforms had unanticipated and undesired outcomes, including aggressive and illegal marketing by SFs and collaboration among SFs to restrict the extent of care provided under compulsory insurance. The Israeli case suggests that the theory of managed competition contains unrealistic assumptions about the types of competitive behavior that result from exposure to managed competition and the capacity of government and health providers to monitor quality. In addition to stemming from universal limitations to the managed competition model, the implementation pattern in Israel reflects local, historical forces and the interplay of Israel's powerful health system actors.
Facility Regulation and Control↗
Intracellular survival strategies of mutualistic and parasitic prokaryotes.
Endosymbiotic bacteria closely related to mammalian pathogens are widespread in invertebrates. Mutualistic and parasitic bacteria-host interactions on the various evolutionary levels apparently involve similar factors, indicating that relevant genetic information developed early in evolution. The detailed characterization of symbiotic interactions of bacteria with non-mammalian hosts should provide profound insights into the basic mechanisms of bacteria-host interactions and their evolution.
Animals↗
Evolutionary trends in the genus Bordetella.
The genus Bordetella comprises seven species with pathogenic potential for different host organisms. This article attempts to review our current knowledge about the systematics and evolution of this important group of pathogens, their relationship to environmental microorganisms and about molecular mechanisms of host adaptation.
Animals↗
The tetraheme cytochrome c NrfH is required to anchor the cytochrome c nitrite reductase (NrfA) in the membrane of Wolinella succinogenes.
The electron-transport chain that catalyzes nitrite respiration with formate in Wolinella succinogenes consists of formate dehydrogenase, menaquinone and the nitrite reductase complex. The latter catalyzes nitrite reduction by menaquinol and is made up of NrfA and NrfH, two c-type cytochromes. NrfA is the catalytic subunit; its crystal structure is known. NrfH belongs to the NapC/NirT family of membrane-bound c-type cytochromes and mediates electron transport between menaquinol and NrfA. It is demonstrated here by MALDI MS that four heme groups are attached to NrfH. A Delta nrfH deletion mutant of W. succinogenes was constructed by replacing the nrfH gene with a kanamycin-resistance gene cartridge. This mutant did not form the NrfA protein, probably because of a polar effect of the mutation on nrfA expression. The nrfHAIJ gene cluster was restored by integration of an nrfH-containing plasmid into the genome of the Delta nrfH mutant. The resulting strain had wild-type properties with respect to growth by nitrite respiration and nitrite reductase activity. A mutant (stopH) that contained the nrfHAIJ locus with nrfH modified by two artificial stop codons near its 5' end produced wild-type amounts of NrfA in the absence of the NrfH protein. NrfA was located exclusively in the soluble cell fraction of the stopH mutant, indicating that NrfH acts as the membrane anchor of the NrfHA complex in wild-type bacteria. The stopH mutant did not grow by nitrite respiration and did not catalyze nitrite reduction by formate, indicating that the electron transport is strictly dependent on NrfH. The NrfH protein seems to be an unusual member of the NapC/NirT family as it forms a stable complex with its redox partner protein NrfA.
Base Sequence↗
Matrilinear phylogeography of Atlantic salmon (Salmo salar L.) in Europe and postglacial colonization of the Baltic Sea area.
Sixty-four samples from 46 salmon populations totalling 2369 specimens were used for polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial ND1 region. The final analyses included 3095 specimens from 60 populations in Northern Europe. A subsample was analysed by RFLP of ND3/4/5/6. Representative RFLP haplotypes from different parts of the distribution area were sequenced and the phylogeny of European haplotypes and their relations to the North American lineage was described. The four common European haplotypes derive from the ancestral ND1-BBBA (rooting the European clade to the North American) by one-step substitutions: AAAA < AABA < BBBA > BBBB. The Swedish west-coast populations differ from the geographically close southern Baltic, indicating absence of inward and limited outward gene flow through the Danish straits during the last 8000 years. Within the Baltic Sea, only three ND1 haplotypes were detected and there was no variation for ND3/4/5/6. In the whole southern Baltic and in lakes Vänern, Ladoga and Onega the haplotype AABA dominated. Proposed postglacial colonization routes to the Baltic Sea are discussed in relation to the haplotype distribution pattern.
Animals↗
Identification of the origin of an Atlantic salmon (Salmo salar L.) population in a recently recolonized river in the Baltic Sea.
The founder event in a recently recolonized salmon population in the Baltic Sea (Gulf of Finland) was investigated. To identify the origin of the founders, four wild populations and two hatchery stocks were analysed using six microsatellite loci. The results of assignment tests and factorial correspondence analysis suggest that the initial recolonizers of the river Selja originated from the geographically nearest (7 km) wild population (river Kunda) but as the result of stocking activities, interbreeding between recolonizers and hatchery individuals has occurred in subsequent years. Although the hatchery releases are outnumbering the wild salmon recruitment in the Baltic Sea at present, our results suggest that the native populations may still have an important role in colonization processes of the former salmon rivers.
Animals↗
Temporary stability of urban food and nutrition security: the East Jakarta study.
The food and nutrition situation in households of East Jakarta was assessed in 1993/1994 and 1998/1999 with the aim of identifying the determinants of potential problems and the dynamics of change. In 1993/1994, the nutritional status of approximately 73% of children under 5 years of age and 60% of mothers was within the normal range, although underweight and overweight were prevalent in almost all households. Between 1998 and 1999, there was a sharp increase in fathers reporting unemployment. The consumption of animal food sources decreased, whereas the consumption of food derivatives such as oils and sugar remained high. Approximately 90% of the population obtained drinking water from wells. By 1998, the public garbage collection system had almost completely collapsed in East Jakarta. Between 1993 and 1998, the prevalence of diarrhoea and acute respiratory infections in children aged under 5 years increased dramatically, from 8 and 44% to 24 and 70%, respectively. The urban environment has undergone significant changes. In Indonesia, as a whole, many achievements in the improvement of household food security and care have been lost due to the economic and political crisis. The statistical association between mothers' and fathers' education and the nutritional status of their children that was observed in 1993/94 did not appear in the 1998 survey. It seems that the education-related coping mechanisms of the parents were inadequate to deal with the rapid deterioration in the economic and political situation.
Adult↗
The reform of the Israeli health care system: a comparison between older and younger consumers, one year and three years after its implementation.
OBJECTIVE: One of the main objectives of the National Health Insurance Law, which was implemented in Israel in January 1995, was to increase equity among different population groups and improve services for weaker populations, such as older people. It is not clear, however, whether the law's goals are being achieved. This study aimed to examine changes in the satisfaction and perceived quality of healthcare services among older people one year and three years after enactment of the law, and to compare the satisfaction and perceptions of older people with those of young adults. DESIGN: Two cross-sectional telephone surveys conducted by the JDC-Brookdale Institute. SETTING: Israel. PARTICIPANTS: Two random samples of the adult residents of Israel at the end of 1995 and at the end of 1997. Two hundred and eighteen older people (of 1,116 respondents) were included in the first survey, and 198 older people (of 1,205 respondents) were included in the second survey. Sixty-seven percent of older respondents in both surveys were 65 to 74 years old and the remaining 33% were 75 years old and over. Forty-three percent were men. Sixty-four percent reported having had at least one chronic illness. There were no differences between the two samples, with the exception of a higher percentage of new immigrants in the second survey. MEASUREMENTS: Perception of changes in the level of services, satisfaction with services, and perceived quality of care (availability, accessibility, early detection procedures). RESULTS: Older people felt there had been an improvement in the level of sick fund (who operate as health maintenance organizations [HMOs] in the United States) services since implementation of the law. The proportion reporting improvement increased from 13% in 1995 to 28% in 1997. At the same time, the proportion of older people who sensed a decline in the level of services also increased, albeit at a much lower rate (4% in 1995 and 8% in 1997). The percentage of younger adults reporting an improvement in services and the percentage reporting a decline were greater than the percentages of older people, in both surveys. Regarding access to services, 69% waited up to 15 minutes to see their physician and 56% received an appointment to see a specialist within one week; this was an improvement. While a higher proportion of younger adults received an appointment within a shorter time span in 1995, the gap had diminished by 1997. Most of the older people felt that the office hours of their family physicians, specialists, administrative services, and laboratories were convenient. The proportion of elderly reporting so increased between 1995 and 1997, and in both surveys was higher than among younger adults. CONCLUSION: The study's findings show that older people perceived an improvement in a number of areas during the first three years of the law's implementation. Their experience was similar to that of younger adults and was even better in some areas. It is necessary to continue monitoring the impact of the law on the need for health services of vulnerable groups such as the chronically ill and disabled older people.
Adult↗
Clinical anatomy of the nasal process of the frontal bone (spina nasalis interna).
OBJECTIVES: During endonasal frontal sinusotomy with the sharp spoon, a solid piece of bone is frequently encountered anterior to the neo-ostium. This bone may be referred to as the nasal process of the frontal bone or internal nasal spine (spina nasalis interna). A prominent spina may render an extended sinusotomy difficult and may call for use of the drill. A series of anatomic measurements is presented to illustrate the 3-dimensional anatomy of the spina nasalis and the regional anatomy. METHODS: A maximum endonasal frontal sinusotomy (Draf type I-II procedure, nasofrontal approach type II) was performed on 36 anatomic specimens by means of a sharp spoon. The dimensions of the remaining nasal spine were measured subsequently together with the anterior-posterior diameter of the inferior frontal sinus, the thickness of the anterior frontal sinus wall, and the distance from the neo-ostium to the anterior ethmoidal artery. RESULTS: The individual microanatomy of the medial floor of the frontal sinus showed a wide range of variation. The average height of the individual spine was 10 mm, the maximum depth 6 mm. A correlation was found between the nasofrontal angle of the specimen and the anterior-posterior dimension of the spine: the more acute the angle, the thicker the spine. In three quarters of the cases, the neo-ostium was separated by just one anterior ethmoidal cell from the anterior ethmoidal artery. CONCLUSIONS: The presented investigations provide the surgeon with quantitative data on the individual anatomy of the nasal spine and offer additional information for selecting the appropriate surgical procedure in the individual patient.
Cadaver↗
The BvgAS two-component system of Bordetella spp.: a versatile modulator of virulence gene expression.
Bordetella pertussis and the closely related species B. parapertussis and B. bronchiseptica colonize the respiratory tract and cause related diseases in man or mammalian species, respectively. Expression of virulence factors by these pathogens is coordinately regulated by the BvgAS two-component system according to changes in the growth conditions. Signal transduction by the BvgAS system is characterized by a complex His-Asp-His-Asp phosphorelay. This system controls the expression of two distinct subsets of genes either in a positive (vag genes) or in a negative (vrg genes) manner. Most of the known virulence factors such as several toxins and adhesins are encoded by vag genes, whereas the functions of most vrg genes and the biological significance of the vrg regulon are not yet clear. This review discusses the current knowledge about the molecular mechanisms of virulence regulation and their relevance for infection by these respiratory pathogens.
Adaptation, Biological↗