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Biomedical subjects

M Hoffman

Publications and source records attributed to M Hoffman.

At least 109 records · Page 6Linked to original sources
PubMed1998

Development of a blocking enzyme-linked immunosorbent assay for detection of serum antibodies to O157 antigen of Escherichia coli.

The O157 antigen of Escherichia coli shares structural elements with lipopolysaccharide (LPS) antigens of other bacterial species, notably Brucella abortus and Yersinia enterocolitica 09, a fact that confounds the interpretation of assays for anti-O157 antibodies. To address this problem, a blocking enzyme-linked immunosorbent assay (bELISA) was designed with E. coli O157:H7 LPS as the antigen and a monoclonal antibody specific for E. coli O157, designated 13B3, as the competing antibody. The bELISA had equivalent sensitivity to, and significantly higher specificity than, the indirect ELISA (iELISA), detecting anti-O157 antibodies in sera from cattle experimentally inoculated with O157:H7. Only 13% of sera from naive heifers vaccinated for or experimentally infected with B. abortus had increased anti-O157 bELISA titers, while 61% of anti-O157 iELISA titers were increased. The bELISA is a sensitive and specific method for the detection of serum antibodies resulting from exposure to E. coli O157.

Animals↗
PubMed1998

Unilateral postural control of the functionally dominant and nondominant extremities of healthy subjects.

OBJECTIVE: To determine whether a difference in unilateral postural stability exists between the functionally dominant and nondominant legs of a healthy population. DESIGN AND SETTING: The unilateral postural control of both legs of healthy subjects was tested using a force plafform. Before the postural control examination, each subject performed a series of functional tests to determine functional leg dominance. SUBJECTS: Ten healthy young adults with a mean age of 19.2 +/- 3.2 years volunteered for this study. MEASUREMENTS: Functional leg dominance was determined through the use of a battery of tests that included 3 separate evaluations of lower extremity dominance for functional activity. Two measures of postural control, sway area (SA) and sway path length (SPL), were collected for both the dominant and nondominant legs of all subjects. An analysis of variance (ANOVA) was used to determine whether a difference in postural control between the 2 legs was present. RESULTS: A subject x leg repeated-measures ANOVA was conducted on both dependent variables, SA and SPL. The SA ANOVA value was not significant. The mean value for the dominant-leg SA measurement was 9737.43 +/- 303.36 mm(2), whereas the mean SA for the nondominant leg was 9431.74 +/- 349.97 mm(2). The SPL ANOVA also showed no significant difference in the bilateral comparison. The mean SPL for the dominant leg was 4321.57 +/- 630.0 mm, and the mean SPL for the nondominant leg was 4341.88 +/- 1,013.31 mm. CONCLUSIONS: We found no difference in unilateral postural stability between the functionally dominant and nondominant lower limbs in a healthy population of young adults. This is of particular interest to the clinician who commonly uses singleleg postural control evaluations in the assessment of an athlete's level of progress in the rehabilitation setting.

Journal Article↗
PubMed1998

Active site-inactivated factors VIIa, Xa, and IXa inhibit individual steps in a cell-based model of tissue factor-initiated coagulation.

Factors VIIa, Xa, and IXa play different roles in the initiation of tissue factor-dependent coagulation. The consequences of competing with the different enzymes were investigated, thereby examining the effects of inhibiting the initiation process at different steps. Active site-inactivated factors VIIa, Xa, and IXa (FVIIai, FXai, and FIXai, respectively) were added to various cell-based assays mimicking the individual steps in tissue factor-initiated coagulation. In an assay involving tissue factor-expressing monocytes, coagulation proteins and unactivated platelets, FVIIai and FXai inhibited platelet activation and thrombin generation while FIXai only inhibited thrombin generation. FVIIai inhibited factor Xa generation and subsequent thrombin generation on monocytes, while FXai inhibited thrombin generation on the monocytes as well as on the activated platelets. FIXai had no effect on factor Xa or thrombin generation on the monocytes, but inhibited factor Xa and subsequent thrombin generation on the activated platelets. FVIIai had no effect on the reactions taking place on the activated platelets. The data confirm a model where tissue factor/factor VIIa mediates factor Xa generation and subsequent prothrombin activation on the tissue factor-bearing cells. Thrombin then activates platelets, which serve as the physiologically important surface for large-scale thrombin generation.

Adult↗
PubMed1998

A possible mechanism of action of activated factor VII independent of tissue factor.

We have used a cell-based model system to examine some aspects of coagulation. Unactivated platelets and tissue factor (TF)-bearing cells were mixed with plasma levels of zymogen factors IX (FIX), FVIII, FX, FV, and prothrombin, as well as coagulation inhibitors antithrombin III and TF pathway inhibitor. Reactions were initiated with plasma levels (0.2 nmol/l) of activated factor VII (FVIIa). We were able to measure platelet activation and subsequent thrombin generation in this system and have established parameters for the normal amount of thrombin generation and the range of values seen with different individuals. If FIX or FVIII were not added to this system, platelet activation but not thrombin generation was seen. We have used this system to examine the mechanism of action of high-dose FVIIa. If platelets were activated with the thrombin receptor agonist peptide SFLLRN and incubated with inhibitors and zymogen factors X, V, and prothrombin, no thrombin generation was observed. Addition of increasing amounts of FVIIa gave increasing amounts of thrombin generation. At the FVIIa concentrations present in the plasma of patients given 60 microg/kg recombinant FVIIa (NovoSeven, Novo Nordisk, Bagsvaerd, Denmark), 10-40 nmol/l, thrombin generation in the model system approached the normal amount seen in the TF-initiated model system. When FIX and FVIII were included in the above reaction, FVIIa could initiate thrombin generation at levels three to four times the amount seen in the TF-initiated model system. We speculate that this platelet-localized thrombin generation may, in part, account for the clinical efficacy of high-dose FVIIa.

Blood Platelets↗
PubMed1998

The effects of activated factor VII in a cell-based model for tissue factor-initiated coagulation.

The importance of activated factor VII (FVIIa) in coagulation initiated by tissue factor (TF) was illustrated by competition of active site-inhibited FVIIa (FFR-FVIIa; FVIIa treated with D-Phe-Phe-Arg-chloromethyl ketone) with FVIIa in various cell-based assays mimicking TF-initiated coagulation. FFR-FVIIa inhibited the overall initiation process as measured by platelet activation and large-scale thrombin generation on the activated platelet surface. When the individual steps in the initiation process were separated, FFR-FVIIa affected only the reactions taking place on TF-bearing cells, demonstrating that FVIIa takes part only in the very first step in the initiation process. The dissociation constant (Kd) for FVIIa binding to TF and the inhibition constant (Ki) for FFR-FVIIa competing with FVIIa in binding to TF, measured in a factor X activation assay, were both around 10 pmol/l, showing that FVIIa and FFR-FVIIa bound to TF in the extrinsic pathway tenase complex with the same affinity.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Activated factor VII activates factors IX and X on the surface of activated platelets: thoughts on the mechanism of action of high-dose activated factor VII.

High levels of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) have been found to be effective in providing haemostasis in haemophiliacs and in normal individuals with acquired inhibitors to factor VIII (FVIII) or FIX. However, the mechanism of this therapeutic effect of FVIIa is unclear. Opinion is divided over whether high-dose FVIIa therapy works primarily by a tissue factor (TF)-dependent or -independent mechanism. Our group originally favoured a TF-dependent mechanism; however, we have recently found that, at levels comparable with those attained therapeutically, FVIIa activates enough FX on activated platelets to restore platelet surface thrombin generation. These data now lead us to favour a primarily (although not necessarily exclusively) TF-independent mechanism for the haemostatic effect of high-dose FVIIa. We believe that a platelet surface localization of FVIIa activity explains both its safety and efficacy, as well as its haemostatic effect in patients with thrombocytopenia and platelet function defects. Localization on activated platelets would tend to restrict the activity of FVIIa to sites of injury. Activation of FX on the platelet surface in haemophiliacs would provide FXa in a favourable location to escape inhibition by plasma protease inhibitors and be incorporated into platelet prothrombinase complexes. Activation of FIX and FX on platelet surfaces in thrombocytopenia would result in more thrombin generation per platelet, possibly leading to formation of a stable fibrin network even in the absence of an optimal initial platelet plug.

Dose-Response Relationship, Drug↗
PubMed1998

Direct and indirect memory measures of temporal order and spatial location: control versus closed-head injury participants.

OBJECTIVE: The goal of the study was to compare control participants and participants with closed-head injury (CHI) on direct and indirect memory measures of temporal order and spatial location. METHOD: Twenty-seven CHI patients and 27 control participants were tested on "item" (i.e., words) and "contextual" (temporal order and spatial location) information. Contextual information was tested directly and indirectly by means of a format in which lists of words were presented repeatedly eight times in fixed or varying order for the temporal task and in a fixed or varying spatial position for the spatial task. The number of words recalled as well as their temporal and spatial judgment were the direct measure of item and contextual memory, respectively. The effect of the consistency of order or location was the indirect measure of contextual memory. RESULTS: As expected, the CHI group was impaired on the direct measures of item memory. Also as expected, the groups did not differ in the indirect memory measures of contextual information. Contrary to predictions, however, the groups did not differ in the direct measure of contextual information. CONCLUSIONS: Item memory, when measured directly, is impaired in CHI patients. The finding that the groups did not differ on the direct measure of contextual information is possibly due to ceiling-level performance of the control group. Contextual information seems to be preserved in CHI patients when measured indirectly.

Adult↗
PubMed1997

Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions.

Our previous analysis of the T cell reactivity to myelin antigens in a group of 24 patients with multiple sclerosis (MS) and 16 control individuals revealed that the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) predominates in MS over that to myelin basic protein (MBP), proteolipid protein or myelin-associated glycoprotein, suggesting a prevalent role for the autoimmune response to MOG in the pathogenesis of MS. Using a recombinant human MOG (rhMOG) preparation corresponding to the extracellular immunoglobulin-like domain of the MOG molecule, we have now analyzed another group of 52 MS patients and 49 control individuals for reactivity of their peripheral blood lymphocytes (PBL) to rhMOG and to MBP concomitantly. Of the 52 MS patients tested 24 responded to MOG and 10 out of 49 responded to MBP, whereas only 5 MOG-reactive and 4 MBP-reactive control individuals were detected out of the 49 tested. These results are therefore highly confirmatory of the predominant reactivity to MOG in MS. The analysis of the primary proliferative response to 11 synthetic overlapping peptides (phMOG) spanning the extracellular domain of human MOG by PBL from 9 MS patients and 15 control individuals (9 healthy controls and 6 patients with neurological diseases other than MS) further supports a prevalent role for the autoimmune response to MOG in MS, as only 1 of the 15 controls tested showed reactivity to any of the phMOG, whilst 5 out of the 9 patients studied reacted to at least 1 of the phMOG. PBL from 10 MS patients, and from 4 controls, were selected in vitro with each of the phMOG. Of the 10 patients studied 7 reacted to at least 1 phMOG upon secondary stimulation and the reactivity was mostly directed to epitopes localized within three main regions (amino acids 1-22, 34-56 and 64-96), as was observed for the primary response of PBL. The predominant response to MOG of PBL from MS patients as demonstrated in two separate studies using native MOG and rhMOG as antigens, and the high incidence of reactivity of these PBL compared to the lack of response to phMOG by control PBL, emphasize the relevance of MOG in MS pathogenesis and support a primary role for the autoimmune T cell response to MOG in disease development.

Adult↗
PubMed1997

Sleep benefit in Parkinson's disease.

Sleep benefit (SB) In Parkinson's disease (PD) is not well characterized. To determine SB frequency, as well as to characterize and correlate it with other disease variables, we evaluated prospectively a consecutive series of 312 PD patients by means of a structured questionnaire: 55% reported having SB and 35% reported that awakening was their best time of the day. Because of SB, 21% of the entire population were able to skip or delay medication. The mean duration of the phenomenon was 85.4 +/- 67 min. Patients with SB were significantly older (p < 0.0002), had disease longer (p < 0.05), and were often men (chi 2 = 3.5, df 1, p = 0.05). Patients with SB took sleep medication with similar frequency as those without SB. There were no differences in hours of sleep or sleep latency. Sleep problems such as nightmares or somnambulism, but not the number of sleep awakenings, were similar in both groups. In conclusion, SB is a frequent phenomenon, especially in men, elderly patients, and patients with longer disease duration. SB enables the morning L-dopa dose to be postponed in approximately 50% of patients.

Aged↗
PubMed1997

Women's health status and use of health services in a rapidly growing peri-urban area of South Africa.

Women's health in South Africa and particularly women living in peri-urban areas is being influenced by three major factors. These include the political transition that is occurring in the country, urbanization and the international interest in women's health. Changes in the delivery of health care to the population, and in particular to women are being planned. It is therefore important that data are available for the purpose of planning and evaluation of health services. This paper describes a household survey in which 661 women were interviewed. Socio-demographic patterns of women living in a rapidly urbanizing area were determined and related to health status, use of health services and knowledge of the services. Poverty appeared to be an overriding factor affecting the health of the population. One third of the women were living in unserviced shacks. There was a high rate of unemployment and those who were employed worked in low status jobs and earned very little. Rates of reported acute and chronic illness were lower than described elsewhere in similar household interview surveys. A third of the acute illnesses were due to respiratory disease. Reported rates of diabetes and hypertension were low indicating undiagnosed disease in the area. Being a member of an alliance household-a mixture of family, friends and lodgers-was the main predictor of acute illness. For chronic disease, age and increasing educational status were the main predictors. Knowledge of services apart from those for cervical cancer screening was good. The latter improved with increasing education, urbanization and being a member of an alliance household. As many of the women lived in unserviced areas and had little or no income the provision of infrastructural services and development programs are essential if their health is to be improved. The existing health services need to be developed to provide a comprehensive primary care service with special attention being paid to the health of women. The service should be close to their homes and be affordable. The information gathered in this survey will be used to plan services for women in the area and will act as baseline data for evaluation.

Acute Disease↗
PubMed1997

Susceptibility of beta-hemolytic streptococci to nine antimicrobial agents among four medical centers in Salt Lake City, Utah, USA.

A multicenter study was performed to evaluate the susceptibility of beta-hemolytic streptococci to nine antimicrobial agents. MICs were performed in cation-supplemented Mueller-Hinton broth with 3.5% lysed sheep red blood cells according to NCCLS guidelines. A total of 646 isolates were tested: 300 (46%) group A; 170 (26%) group B; 38 (6%) group C, 35 (5%) group F; 83 (17%) group G; and 20 (3%) nongroupable. Six percent of the total isolates were resistant to one or more of the antibiotics tested. Approximately 7% of 387 strains from the University of Utah Hospital and Clinics were resistant to erythromycin. Four isolates were resistant to clindamycin. Six strains (3%) from Primary Children's Medical Center (207 tested) were resistant to one or more of the macrolides. Resistance was rare at the LDS Hospital and the Salt Lake Veteran's Affairs Hospital. Overall, resistance among beta-hemolytic streptococci in this geographic location does not seem to be a significant problem, except at the tertiary care university hospital.

Anti-Bacterial Agents↗
PubMed1997

The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats.

1. The therapeutic use of nifedipine is limited by the rapidity of the onset of its action and its short biological half-life. In order to produce a form devoid of these disadvantages we made nanoparticles of nifedipine from three different polymers, poly-epsilon-caprolactone (PCL), polylactic and glycolic acid (1:1) copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene glycol 400 (PEG) solution was used as a control. 2. The average diameters of the nanoparticles ranged from 0.12 to 0.21 micron; the encapsulation ratio was 82% to 88%. 3. In spontaneously hypertensive rats (SHR), the initial rapid fall in systolic arterial blood pressure following oral administration of nifedipine in PEG solution (from 193 +/- 3 to 102 +/- 2 mmHg) was not seen following administration of the same dose in Eudragit nanoparticles (from 189 +/- 2 to 156 +/- 2 mmHg); with PCL and PLAGA nanoparticles the initial fall in blood pressure was significantly reduced (nadirs PCL 124 +/- 2 and PLAGA 113 +/- 2 mmHg). Ten hours following administration, blood pressure in rats administered the nifedipine/PEG preparation had returned to normal (183 +/- 3 mmHg) whereas that of animals given nifedipine in nanoparticles (PCL 170 +/- 3, PLAGA 168 +/- 2, Eudragit 160 +/- 3 mmHg) was still significantly reduced. 4. All of the nanoparticle dosage forms decreased Cmax and increased Tmax and the mean residence time (MRT) values. Relative bioavailability was significantly increased with Eudragit nanoparticles compared to the nifedipine/PEG solution. 5. There was an inverse linear correlation between the fall in blood pressure and plasma nifedipine concentration with all preparations. 6. The nanoparticle nifedipine preparations represent sustained release forms with increased bioavailability, a less pronounced initial antihypertensive effect and a long-lasting action.

Acrylic Resins↗