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Biomedical subjects

R Gross

Publications and source records attributed to R Gross.

At least 55 records · Page 3Linked to original sources

Weekly supplementation with iron and vitamin A during pregnancy increases hemoglobin concentration but decreases serum ferritin concentration in Indonesian pregnant women.

We investigated whether weekly iron supplementation was as effective as the national daily iron supplementation program in Indonesia in improving iron status at near term in pregnancy. In addition, we examined whether weekly vitamin A and iron supplementation was more efficacious than weekly supplementation with iron alone. One group of pregnant women (n = 122)was supplemented weekly with iron (120 mg Fe as FeSO4) and folic acid (500 microg); another group (n = 121) received the same amount of iron and folic acid plus vitamin A [4800 retinol equivalents (RE)]. A third ("daily") group (n = 123), participating in the national iron plus folic acid supplementation program, was also recruited. Data on subjects with complete biochemical data are reported (n = 190). At near term, hemoglobin concentrations increased, whereas serum ferritin concentrations decreased significantly in the weekly vitamin A and iron group, suggesting that vitamin A improved utilization of iron for hematopoiesis. Iron status in the weekly iron group was not different from that of the "daily" group. However, iron status decreased with daily supplementation if <50 iron tablets were ingested. Serum transferrin receptor concentrations increased in all groups (P < 0.01). Serum retinol concentrations were maintained in the weekly vitamin A and iron group, but decreased in the other two groups (P < 0.01). Thus, delivery of iron supplements on a weekly basis can be as effective as ona daily basis if compliance can be ensured. Addition of vitamin A to the supplement improved hemoglobin concentration.

Adult↗

Difficult airway in a patient with Coffin-Siris syndrome.

We report on a patient with Coffin-Siris syndrome and consider a potential association between this condition and difficult intubation. Although this inherited condition is extremely rare, anesthesiologists should be aware of its existence and prepare for potential airway management problems whenever it is encountered.

Abnormalities, Multiple↗

How Israeli primary care physicians perceive their role in the health care system.

In some Western European countries, primary care physicians (PCPs) play a major role in the health care system, but in Israel the health care system is in the process of being reformed and the role of PCPs has not yet been established. The purpose of the study described in this article was to determine the attitude of PCPs toward the role that they should play in the health care system in Israel and the formal training they need to fill this role. PCPs cited 12 primary functions that they should carry out, including coordinating patient care and counseling patients. Also, 60% of PCPs have undergone specialty training, and 94% think that this training is essential. Among the conclusions of the study are that a higher percentage of PCPs should undergo specialty training in order to enhance their professional status and that continued medical education should emphasize specific issues, such as the consideration of economic factors in patient management decisions, responsibility for patients' administrative issues, 24-hour responsibility for patients, and house calls.

Adult↗

Bordetella petrii sp. nov., isolated from an anaerobic bioreactor, and emended description of the genus Bordetella.

A novel Bordetella species was isolated from an anaerobic, dechlorinating bioreactor culture enriched from river sediment. The only strain, Se-1111R(T) (= DSM 12804T = CCUG 43448T), for which the name Bordetella petrii is proposed, is designated the type strain of the novel species. Strain Se-1111R(T) was isolated from the dechlorinating mixed culture due to its ability to anaerobically reduce selenate to elemental selenium. Comparative 16S rDNA sequence analysis showed a close relationship between Se-1111R(T) and members of the genus Bordetella within the beta-Proteobacteria. This close phylogenetic relatedness was also reflected in several metabolic properties of Se-1111R(T), including its incapacity to utilize carbohydrates, by the high G+C content (63.8 mol%) of its DNA and by the presence of Q-8 as the major isoprenoid quinone. DNA-DNA hybridization experiments with type strains of all species of the genus Bordetella and closely related species Achromobacter xylosoxidans subsp. denitrificans provided further evidence for the assignment of strain Se-1111R(T) as a novel species of the genus Bordetella. This genus currently consists of seven aerobic species, all of which are known to occur in close pathogenic, opportunistic or possibly commensal relationships with various host organisms. B. petrii is the first member of this genus isolated from the environment and capable of anaerobic growth. The proposal of the novel species and an emended description of the genus Bordetella is presented.

Anaerobiosis↗

Gatekeeping: a challenge in the management of primary care physicians.

Assesses the degree of self-reported implementation of gatekeeping in clinical practice, and gains insight into primary care physicians' attitudes toward gatekeeping and their perceptions of necessary conditions for implementation of gatekeeping in daily practice. A self-administered questionnaire was mailed to a national sample of 800 primary care physicians in Israel, with a response rate of 86 per cent. Multivariate analysis indicated that sick fund affiliation was the main predictor of self-reported implementation of gatekeeping, while specialty training predicted primary care physicians' attitude toward this role. Close communication with specialists, continuous medical education, and management support of physician decisions were identified by respondents as being important conditions for gatekeeping. Discusses strategies to gain the cooperation of primary care physicians, which is necessary for implementing an effective gatekeeping system.

Adult↗

Self-rated health status and health care utilization among immigrant and non-immigrant Israeli Jewish women.

INTRODUCTION: Since 1989, Israel has absorbed over 700,000 Jewish immigrants from the former Soviet Union, among them about 375,000 women. Immigrants are known to have greater and/or different health needs than non-immigrant residents, and to face unique barriers to receiving care. However, research addressing the specific health problems of these immigrant women has been scarce. OBJECTIVES: To compare self-reported health status and health care utilization patterns among immigrant and non-immigrant Israeli Jewish women; and to explore ways to overcome existing barriers to their care. METHODS: A telephone survey was conducted in September and October 1998 among a random national sample of women age 22 and over, using a standard questionnaire. In all, 849 interviews were completed, with a response rate of 84%. In this article we present comparative data from a sub-set that included 760 immigrant respondents from the former Soviet Union and non-immigrant Jewish respondents. RESULTS: A greater proportion of immigrant versus non-immigrant women reported poor perceived health status (17% vs. 4%), chronic disease (61% vs. 38%), disability (31% vs. 18%) and depressive mood symptoms (52% vs. 38%). Lower rates of immigrant women visited a gynecologist regularly (57% vs. 83%) and were satisfied with their primary care physician. Lower rates of immigrants reported discussing health promotion issues such as smoking, diet, physical activity, HRT, and calcium intake with their physician. The article concludes with a discussion of the implications of the findings for designing services that will effectively promote immigrant women's health, both in Israel and elsewhere.

Adolescent↗

A neuronal isoform of nitric oxide synthase expressed in pancreatic beta-cells controls insulin secretion.

Evidence is presented showing that a neuronal isoform of nitric oxide synthase (NOS) is expressed in rat pancreatic islets and INS-1 cells. Sequencing of the coding region indicated a 99.8% homology with rat neuronal NOS (nNOS) with four mutations, three of them resulting in modifications of the amino acid sequence. Double-immunofluorescence studies demonstrated the presence of nNOS in insulin-secreting beta-cells. Electron microscopy studies showed that nNOS was mainly localized in insulin secretory granules and to a lesser extent in the mitochondria and the nucleus. We also studied the mechanism involved in the dysfunction of the beta-cell response to arginine and glucose after nNOS blockade with N(G)-nitro-L-arginine methyl ester. Our data show that miconazole, an inhibitor of nNOS cytochrome c reductase activity, either alone for the experiments with arginine or combined with sodium nitroprusside for glucose, is able to restore normal secretory patterns in response to the two secretagogues. Furthermore, these results were corroborated by the demonstration of a direct enzyme-substrate interaction between nNOS and cytochrome c, which is strongly reinforced in the presence of the NOS inhibitor. Thus, we provide immunochemical and pharmacological evidence that beta-cell nNOS exerts, like brain nNOS, two catalytic activities: a nitric oxide production and an NOS nonoxidating reductase activity, both of which are essential for normal beta-cell function. In conclusion, we suggest that an imbalance between these activities might be implicated in beta-cell dysregulation involved in certain pathological hyperinsulinic states.

Animals↗

A third crystal form of Wolinella succinogenes quinol:fumarate reductase reveals domain closure at the site of fumarate reduction.

Quinol:fumarate reductase (QFR) is a membrane protein complex that couples the reduction of fumarate to succinate to the oxidation of quinol to quinone. Previously, the crystal structure of QFR from Wolinella succinogenes was determined based on two different crystal forms, and the site of fumarate binding in the flavoprotein subunit A of the enzyme was located between the FAD-binding domain and the capping domain [Lancaster, C.R.D., Kröger, A., Auer, M., & Michel, H. (1999) Nature 402, 377--385]. Here we describe the structure of W. succinogenes QFR based on a third crystal form and refined at 3.1 A resolution. Compared with the previous crystal forms, the capping domain is rotated in this structure by approximately 14 degrees relative to the FAD-binding domain. As a consequence, the topology of the dicarboxylate binding site is much more similar to those of membrane-bound and soluble fumarate reductase enzymes from other organisms than to that found in the previous crystal forms of W. succinogenes QFR. This and the effects of the replacement of Arg A301 by Glu or Lys by site-directed mutagenesis strongly support a common mechanism for fumarate reduction in this superfamily of enzymes.

Amino Acid Substitution↗

Induction of syngeneic graft-versus-host disease in LPS hyporesponsive C3H/HeJ mice.

Syngeneic GVHD (SGVHD) develops following syngeneic bone marrow transplantation and treatment with cyclosporine A. Previous studies have demonstrated a role for IL-12, IFN-gamma, and TNF-alpha in the development of murine SGVHD. Macrophages can be activated to secrete IL-12 and TNF-alpha via a T-cell-dependent or T-cell-independent pathway (LPS or bacterial products). Studies were designed to determine if LPS participated in the development of SGVHD in C3H/HeN (LPS-responsive) and C3H/HeJ (LPS-hyporesponsive) mice. C3H/HeJ and C3H/HeN mice had similar levels of disease induction and pathology. Following induction of SGVHD, treatment of C3H/HeN, but not C3H/HeJ, mice with a sublethal dose of LPS resulted in mortality. However, neutralization of IL-12 abrogated the development of disease in C3H/HeJ mice, demonstrating that activated macrophages and their products participated in the development of SGVHD in these animals. These data suggested that LPS responsiveness was not a predisposing factor for SGVHD induction.

Animals↗

Primary care physicians in Israel: self-perception of their role in the healthcare system and policy makers' and patients' perception of them as gatekeepers.

BACKGROUND: The rapidly increasing costs of healthcare pose a major challenge to many governments, particularly in developed countries. Health policy makers in some Western European countries have adopted the policy of a strong primary healthcare system, partly due to their recognition of the value of primary care medicine as a means to restrain costs while maintaining the quality and equity of healthcare services. In these countries there is a growing comprehension that the role of the family physician should be central, with responsibility for assessing the overall health needs of the individual, for coordination of medical care and, as the primary caregiver, for most of the individual's medical problems in the framework of the family and the community. OBJECTIVES: To describe primary care physicians in Israel from their own perception, health policy makers' opinion on the role PCPs should play, and patients' view on their role as gatekeepers. METHODS: The study was based on three research tools: a) a questionnaire mailed to a representative sample of all PCPs employed by the four sick funds in Israel in 1997, b) in-depth semi-structured interviews with key professionals and policy makers in the healthcare system, and c) a national telephone survey of a random representative sample of patients conducted in 1997. RESULTS: PCPs were asked to rank the importance of 12 primary functions. A total of 95% considered coordination of all patient care to be a very important function, but only 43% thought that weighing economic considerations in patient management is important, and 30.6% thought that 24 hour responsibility for patients is important. Also, 60% of PCPs have undergone specialty training and 94% thought that this training is essential. With regard to the policy makers, most preferred highly trained PCPs (board-certified family physicians, pediatricians and internists) and believed they should play a central role in the healthcare system, acting as coordinators, highly accessible and able to weigh cost considerations. Yet, half opposed a full gatekeeper model. They also felt that the general population has lost faith in PCPs, and that most have a low status and do not have adequate training. Regarding the patients' viewpoint, 40% preferred that the PCP function as their "personal physician" coordinating all aspects of their care and fully in charge of their referrals; 30% preferred self-referral to sub-specialists, and 19% preferred their PCP to coordinate their care but wanted to be able to refer themselves to specialists. CONCLUSIONS: In order to maintain high quality primary care, it is important that all PCPs have board certification. In addition, PCP training systems should emphasize preventive medicine, health promotion, health economy, and cost-effectiveness issues. Efforts should be made to render PCPs a central role in the healthcare system by gradually implementing the elements of the gatekeeper model through incentives rather than regulations.

Adult↗

Enhancement of human immunodeficiency virus type 1-specific CD4 and CD8 T cell responses in chronically infected persons after temporary treatment interruption.

Immunologic and virologic outcomes of treatment interruption were compared for 5 chronically human immunodeficiency virus (HIV)-infected persons who have maintained antiretroviral therapy-mediated virus suppression, as compared with 5 untreated controls. After a median interruption of 55 days of therapy accompanied by rebound of virus, reinitiated therapy in 4 of 5 subjects resulted in suppression of 98.86% of plasma virus load by 21-33 days and no significant decrease in CD4 T cell percentage from baseline. Increased T helper responses against HIV-1 p24 antigen (P=. 014) and interferon-gamma-secreting CD8 T cell responses against HIV-1 Env (P=.004) were present during interruption of therapy and after reinitiation of treatment. The remaining subject whose treatment was interrupted did not resume treatment and continued to have a low virus load (<1080 HIV-1 RNA copies/mL) and persistent antiviral cell-mediated responses. In summary, cellular immunity against autologous HIV-1 has the potential to be acutely augmented in association with temporary treatment interruption in chronically infected persons.

Adult↗

Dimerization of signalling modules of the EvgAS and BvgAS phosphorelay systems.

Biophysical and biochemical properties of signalling proteins or domains derived from the unorthodox EvgAS and BvgAS two-component phosphorelay systems of Escherichia coli and Bordetella pertussis were investigated. Oligomerization of the effector proteins EvgA and BvgA and of truncated EvgS and BvgS derived signalling proteins containing the receiver and histidine containing phosphotransfer (HPt) domains or comprising only the HPt domains were characterized by native gel electrophoresis, gel permeation experiments and analytical ultracentrifugation. The results obtained by the different methods are consistent with non-phosphorylated EvgA and BvgA proteins being dimers in solution with a dissociation constant significantly below 1 microM. In contrast, all sensor derived domains of EvgS and BvgS were observed to be monomers in vitro. No indications for a phosphorylation induced stimulation of oligomerization of the C-terminal histidine kinase domains could be detected. In agreement with these data, surface plasmon resonance studies revealed a 2:1 stoichiometry in the interaction of EvgA with the immobilized EvgS HPt domain and an affinity constant of 1. 24x10(6) M(-1).

Bordetella pertussis↗

4-Hydroxyisoleucine: effects of synthetic and natural analogues on insulin secretion.

4-Hydroxyisoleucine, a peculiar amino acid extracted from fenugreek seeds and never found in mammalian tissues, exhibits interesting insulinotropic activity. To investigate the structural requirements for this stimulating effect, the insulinotropic activity of the major isomer (2S,3R,4S) of 4-hydroxyisoleucine, in the presence of 8. 3 mM glucose, was compared to that of (1) its minor isomer (2R,3R, 4S) (2) its lactone form, (3) classical structurally related amino acids, and (4) synthetic monomethylated analogues. In the isolated, ex vivo, perfused rat pancreas, only the major isomer of 4-hydroxyisoleucine (200 microM) potentiated insulin release. On incubated isolated rat islets, the threshold concentration for a significant increase (P<0.05) in insulin release was 200 microM for (2S,3R,4S) 4-hydroxyisoleucine, 500 microM for (2S,4R) and (2S,4S) gamma-hydroxynorvalines as well as (2S,3S) and (2S,3R) gamma-hydroxyvalines, and 1 mM or more for other congeners. In conclusion, the insulinotropic properties of 4-hydroxyisoleucine, in the micromolar range, are seen only in the presence of the linear major isoform; they also require carbon alpha in S-configuration, full methylation and carbon gamma-hydroxylation.

Animals↗

Contralateral effect of topical beta-adrenergic antagonists in initial one-eyed trials in the ocular hypertension treatment study.

PURPOSE: To evaluate the magnitude of the contralateral effect of topically administered beta-blockers on intraocular pressure. METHODS: The Ocular Hypertension Treatment Study enrolled 1,636 subjects. Of these, 817 subjects were randomized to receive topical ocular hypotensive medication and 819 subjects were randomized to close observation (i.e., no topical medication). We compared the intraocular pressure of the contralateral eye of subjects at the baseline visit and after an initial one-eyed therapeutic trial of topical beta-blockers. We examined differences between baseline and follow-up intraocular pressure in untreated eyes of subjects randomized to close observation. RESULTS: The mean reduction in intraocular pressure in the beta-blocker-treated eyes was -5.9 +/- 3. 4 mm Hg (-22% +/- 12%; Student t test, P <.0001). In the contralateral eyes, mean intraocular pressure reduction was -1.5 +/- 3.0 mm Hg (-5.8% +/- 12%; P <.0001). Of the contralateral eyes, 35% showed a reduction of 3 mm Hg or more, and 10% showed a reduction of 6 mm Hg or more. The contralateral effect of the relatively selective beta-blocker betaxolol did not differ from that of any of the nonselective beta-blockers. Factors associated with the magnitude of the contralateral effect were the degree of intraocular pressure reduction in the treated eye and baseline intraocular pressure of the contralateral eye. In the close observation group, no significant reduction in intraocular pressure was noted between the baseline and follow-up visit. CONCLUSIONS: The contralateral effect is important in clinical practice and in clinical trials when the hypotensive effect of a topical beta-blocker is evaluated by means of a one-eyed therapeutic trial.

Administration, Topical↗

The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats.

Nicotinic acetylcholine systems play important roles in addiction, and nicotinic receptor stimulation stimulates dopamine release while the nicotinic antagonist mecamylamine reduces it. Reid et al. [Neuropsychopharmacology 20 (1999) 297.] recently found in human cocaine addicts that mecamylamine reduced cue-elicited cocaine craving. The current study assessed the impact of mecamylamine on cocaine self-administration in rats. Female Sprague-Dawley rats (N=7) were implanted with intravenous (iv) catheters and trained to lever press for cocaine (0.32 mg/kg/infusion FR-1 with a 60-s timeout) in 45-min sessions. After 2 weeks of training, the rats were injected with saline or mecamylamine (1, 2, or 4 mg/kg sc) 10 min before the session. They received the same dose for 1 week with 1 week of uninjected testing between doses. Mecamylamine, compared to saline, significantly (P<.05) reduced the number of cocaine infusions per session with each of these doses. This effect did not appear to be due to a generalized reduction in behavioral activity. Another set of female Sprague-Dawley rats (N=8) were trained to lever press for food reinforcement. In these rats, the 1 and 2-mg/kg mecamylamine doses had no effect on food self-administration. Significant reductions in food self-administration were not seen unless the high dose of 4-mg/kg mecamylamine was used. Nicotinic antagonist treatment reduces cocaine self-administration in rats at doses that do not cause generalized effects on food-reinforced responding. Nicotinic antagonistic treatment may be a useful new approach to treat cocaine addiction.

Animals↗