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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 127 records · Page 7Linked to original sources
PubMed2001

Cardiac function following combination therapy with paclitaxel and doxorubicin: an analysis of 657 women with advanced breast cancer.

BACKGROUND: To determine the cardiotoxicity of paclitaxel (T) plus doxorubicin (A) combination therapy in women with advanced breast cancer. To define a dose range of A for use in AT. PATIENTS AND METHODS: The effect of cumulative A dose on risk of congestive heart failure (CHF) and alterations of myocardial contractility (left ventricular ejection fraction [LVEF] decrease > or = 20% or to <50%) was estimated from pooled data from 10 trials of AT. RESULTS: Thirty-one of 657 patients (4.7%) developed CHF at a median of 6.6 months (range 0.3-24.6) after initiation of AT. CHF was stabilized in 29 patients at a median of 17.3 months after diagnosis (range 4.1-31.2 months). The risk of developing CHF was < or = 5% at a total A dose < or = 380 mg/m2. In patients who received a total A dose > 440 mg/m2, the incidence of CHF was >25% but similar to that of A monotherapy. The risk of CHF was similar in women receiving AT or A monotherapy at a dose < or = 380 mg/m2 (2%-3%). LVEF progressively decreased in patients who received AT, especially at a cumulative A dose > 380 mg/m2. LVEF decreases were more frequent in patients who later developed CHF, but the majority of CHF patients did not experience LVEF alterations prior to symptoms. LVEF recovered after discontinuation of A in 25 of 67 women who developed LVEF < 50%. CONCLUSION: The reported cardiac effects are consistent with anthracycline-related cardiotoxicity. AT is associated with a cardiac risk similar to that of A monotherapy up to a cumulative A dose of 340-380 mg/m2.

Adult↗
PubMed2001

Long-term persistence and recall of immune responses in aged mice after mucosal immunization.

To evaluate the retention of memory in the mucosal immune system of aged animals, 2-year-old mice that had been immunized intragastrically at 3 months of age with Streptococcus mutans protein AgI/II coupled to the B subunit of cholera toxin (CTB) were evaluated by ELISA for antibodies to AgI/II and CT in serum, saliva, and vaginal wash. To evaluate recall responses, mice were then immunized intragastrically with AgI/II-CTB, in comparison with previously unimmunized controls. Those that had been primed in their youth showed a more rapid antibody response in serum (immunoglobulin G (IgG)) and secretions (IgA), but all animals eventually responded to a similar degree after the third dose. Mice immunized at 3 months also retained for 2 years spleen cells capable of proliferating in vitro in response to AgI/II. These data show that aged mice retain the ability to mount immune responses to mucosally presented immunogens and that memory to mucosally presented immunogens can persist for almost the whole lifetime of a mouse.

Adjuvants, Immunologic↗
PubMed2001

TNF-alpha dependent NF-kappa B activation in cultured canine keratinocytes is partly mediated by reactive oxygen species.

The cytokine TNF-alpha plays a major role in inflammatory and immunological reactions of canine skin. With respect to a possible therapeutic modulation, we investigated the role of the transcription factor NF-kappa B and the involvement of reactive oxygen species (ROS) in the TNF-alpha signalling pathway in cultured canine keratinocytes. TNF-alpha treatment resulted in activation of NF-kappa B which was partially inhibited by the antioxidant alpha-lipoic acid. Using the cytochrome c reduction test no superoxide production could be detected in the supernatant of TNF-alpha stimulated keratinocytes. However, TNF-alpha dependent intracellular hydrogen peroxide production was demonstrated spectroscopically. With electron energy loss spectroscopy (EELS) significant hydrogen peroxide formation was detected in the mitochondria, the endoplasmic reticulum, the cytosol and partially on the plasma membrane of the keratinocytes. Hence, ROS possibly play an important role in the TNF-alpha signalling pathway leading to NF-kappa B activation in canine skin. An adjunctive therapy with natural potent antioxidants modulating NF-kappa B overactivation in canine cutaneous inflammation may be of therapeutic benefit.

Animals↗
PubMed2001

Why is anti-microbial resistance a veterinary problem as well?

Resistance to anti-microbial agents has become one of the main issues in public health strategies world-wide. Much attention has been paid to the emergence of pathogenic micro-organisms such as enterococci or Salmonella that have developed resistance mechanisms that render them almost untreatable with current antibiotics. One of the alleged reasons for such an emergence is the non-medical use of antibiotics, especially in animals. However, only recently have veterinary forums and journals begun to discuss this topic. On the other hand, anti-microbial resistance has also become a problem in veterinary medicine and the number of reports indicating high rates of resistance among animal-originated micro-organisms is considerable. The present review deals with the mechanisms of resistance known for antibiotics in common veterinary use, the problem of anti-microbial resistance in veterinary medicine and the links between the use of antibiotics in animals and the emergence of anti-microbial resistance in humans.

Animals↗
PubMed2001

A simple, inexpensive, life-saving way to perform iterative laparotomy in patients with severe intra-abdominal sepsis.

Between 1 June 1993 and 31 December 1998, 17 patients underwent temporary abdominal closure with 3L urological irrigation bags, because in most cases, there was massive sepsis leading to the conclusion that primary closure was not advisable. Indicative of the seriousness of these conditions, Apache score averaged 19 (range 10-30). The technique consisted of suturing a double thickness of irrigation bags to each side of the wound, and joining the two bags in the midline with running sutures. Abdominal lavage with large quantities of fluid was performed every other day. This type of closure was used for a mean duration of 15 days. Mean length of hospitalization was 60 days. There were only three deaths (17.6%). No incisional hernia occurred after the iterative laparotomies. Deleting patients with acute pancreatitis would have reduced the death rate to only 7%. A 3L urological irrigation bag costs pound 11.60 (24.40 dollars CAN) while a Marlex mesh costs pound 81.40 (171.00 dollars CAN). We conclude that the usage of 3L urological plastic bags is a simple, safe and efficient method for temporary closure of the abdomen.

Journal Article↗
PubMed2001

Hepatitis B virus Dane particles bind to human plasma apolipoprotein H.

Human apolipoprotein H (apo H) was found to bind specifically to hepatitis B surface antigen (HBsAg) from hepatitis B virus (HBV)-infected individuals. We used recombinant HBsAg proteins to analyze HBV domains recognized by apo H. We showed that the myristylated pre-S1 domain of HBsAg strongly interacted with apo H. This binding involved phospholipid components of the HBV envelope because their removal by detergent prevented apo H-HBsAg interaction. The opposite effects of iron and zinc metal ions on binding suggest that the oxidation of phospholipids also affects apo H-HBsAg interaction. After fractionation of viral particles on a sucrose gradient, and their addition to microtiter plates coated with apo H or anti-HBsAg, we observed that the maximal anti-HBsAg capture activity corresponded to a sucrose concentration of 36%, whereas the maximal apo H capture activity corresponded to a concentration of 39%. Electron microscopy and polymerase chain reaction (PCR) Southern blot studies of these fractions showed that the fraction with maximal apo H binding predominantly contained full Dane particles. Finally, we studied apo H-HBsAg binding relative to the presence of hepatitis B virus markers and observed that apo H binding activity for HBsAg was higher in sera from patients in the active virus replication phase.

Animals↗
PubMed2001

Varying the importance of a prospective memory task: differential effects across time- and event-based prospective memory.

Only few studies have addressed the issue of task importance in prospective memory. Most of them, but not all, have shown that perceived task importance does improve prospective memory performance. However, there is little understanding of (1) the conditions under which importance of the prospective memory task makes a difference in performance and (2) the mechanisms by which perceived task importance has an effect on prospective memory performance. The present study reports two experiments that manipulate task importance in a time-based and an event-based prospective memory paradigm. Results show that importance has an effect on the time-based but not on the event-based task. Further analyses of the performance in the cover tasks as well as the monitoring behaviour indicate that importance improves prospective memory to the degree the task requires the strategic allocation of attentional resources.

Adult↗
PubMed2001

Age differences in stress, social resources, and well-being in middle and older age.

The present study examines the interrelationships among the constructs of social resources, stress, and well-being in middle-aged and older adults. Two samples of 489 middle-aged adults (41-43 years) and 449 older adults (61-63 years) from the Interdisciplinary Longitudinal Study of Adult Development were compared with respect to the availability of social resources, levels of stress, and well-being. The data were used to construct separate structural equation models explaining the influence of stress and social resources on well-being in the two groups. The results indicate higher levels of health-related stress and similar levels of social resources in the older group. Structural equation models and examination of total and indirect effects confirmed that a stress-suppression model has the best fit in explaining the interrelationships between stress, social resources, and well-being. There was a strong effect of stress on well-being, no direct effect of social resources on well-being, and a mediating effect of stress on well-being. The relative contributions of stress and resources to well-being were comparable between age groups.

Adult↗
PubMed2001

Systemic lupus erythematosus and rheumatoid arthritis patients differ from healthy controls in their cytokine pattern after stress exposure.

OBJECTIVE: To study whether patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) differ from healthy individuals in their immune responses to acute psychological stress. METHODS: The phenotype and function of peripheral blood lymphocytes were analysed before and after stress exposure in patients and healthy subjects. RESULTS: Natural killer (NK) cell numbers increased transiently in all groups under stress. NK activity, however, increased in healthy controls only. We observed a stress-induced increase in interleukin (IL)-4-producing (IL-4(+)) cells in SLE patients only, whereas interferon (IFN) gamma(+) cell numbers increased due to stress in all three groups. An analysis of supernatants from phytohaemagglutinin (PHA) cultures revealed increased IFN gamma and IL-10 levels in healthy subjects but not in SLE or RA patients after stress exposure. CONCLUSIONS: These data demonstrate that RA and SLE patients differ in their immune response to stress from healthy controls. Changes in cytokine patterns might be responsible for stress-induced exacerbation of disease activity in RA and SLE patients.

Adult↗
PubMed2001

Theoretical perspectives on the relation between catastrophizing and pain.

The tendency to "catastrophize" during painful stimulation contributes to more intense pain experience and increased emotional distress. Catastrophizing has been broadly conceived as an exaggerated negative "mental set" brought to bear during painful experiences. Although findings have been consistent in showing a relation between catastrophizing and pain, research in this area has proceeded in the relative absence of a guiding theoretical framework. This article reviews the literature on the relation between catastrophizing and pain and examines the relative strengths and limitations of different theoretical models that could be advanced to account for the pattern of available findings. The article evaluates the explanatory power of a schema activation model, an appraisal model, an attention model, and a communal coping model of pain perception. It is suggested that catastrophizing might best be viewed from the perspective of hierarchical levels of analysis, where social factors and social goals may play a role in the development and maintenance of catastrophizing, whereas appraisal-related processes may point to the mechanisms that link catastrophizing to pain experience. Directions for future research are suggested.

Adaptation, Psychological↗
PubMed2001

Enoximone in contrast to dobutamine improves hepatosplanchnic function in fluid-optimized septic shock patients.

OBJECTIVE: To investigate the impact of dobutamine and enoximone on hepatosplanchnic perfusion and function in fluid-optimized septic patients. DESIGN: Prospective, randomized, double-blinded interventional study. SETTING: Intensive care unit of a university hospital. PATIENTS: Forty-eight septic shock patients were examined within 12 hrs after onset of septic shock. Patients were conventionally resuscitated, achieving an optimal pulmonary artery occlusion pressure at which the left ventricular stroke work was on the maximal plateau. Liver blood flow was estimated by venous suprahepatic catheterization using the continuous indocyanine green infusion technique. Microsomal liver function was assessed by the plasma appearance of monoethylglycinexylidide, and release of hepatic tumor necrosis factor-alpha (TNF-alpha) was measured to estimate the severity of hepatic ischemia-reperfusion syndrome. INTERVENTIONS: Patients were randomly treated with dobutamine or enoximone. Within the first 10 hrs after baseline measurements, the dosage was increased until no further increase in the left ventricular stroke work index occurred. Then, positive inotropes were kept constant throughout the study. MEASUREMENTS AND MAIN RESULTS: Measurements were performed at baseline and after 12 and 48 hrs after baseline measurements. Cardiac index, systemic oxygen delivery, systemic oxygen consumption, and liver blood flow increased significantly in both groups during treatment (p <.01) without a significant difference between groups. Fractional liver blood flow (liver blood flow/cardiac index) did not change in the enoximone group and showed a significant but only minor (median, 10%) decrease in the dobutamine group (p <.05 after 12 hrs and p <.01 after 48 hrs vs. baseline). After 12 hrs of enoximone treatment, monoethylglycinexylidide kinetics and hepatosplanchnic oxygen consumption demonstrated a significant increase (p <.05). The release of hepatic TNF-alpha after 12 hrs of dobutamine treatment was twice as high (p <.05) as during enoximone. CONCLUSION: The increase in hepatosplanchnic oxygen consumption, together with an increased lignocaine metabolism and decreased release of hepatic TNF-alpha, indicates improved hepatosplanchnic function and antiinflammatory properties after 12 hrs of enoximone treatment. Therefore, if the inflammatory response should be attenuated in high-risk patients, administration of enoximone in fluid-optimized septic shock patients may be favorable compared with dobutamine.

APACHE↗
PubMed2001

Pilot study of strategies for effective weight management in type 2 diabetes: Pounds Off with Empowerment (POWER).

This pilot test effort focused on weight management strategies for individuals with type 2 diabetes living in rural, medically under-served communities. Randomly selected patients from the diabetes registry of a federally funded primary care practice in a rural community were randomized to one of two 8-week interventions: intensive lifestyle (reduced fat and calorie intake and increased activity) or intensive lifestyle plus ongoing formal evaluation for continuous quality improvement. Mean weight loss was 1.15 +/- 1.90 kg (96.4% African American, n = 23, p < 0.01) with no difference between groups. Among the 78% who lost weight, mean loss was 2.00 kg. Mean difference in pre- vs. postintervention fasting blood glucose was -24.23 mg/dL (n = 23, p < 0.05). In this rural, medically under-served community, the interventions were moderately successful in facilitating weight loss and improving fasting glucose concentration. For purposes of state-of-the-art weight management interventions with diabetics, the addition of formal evaluation did not result in improved outcomes.

Black or African American↗
PubMed2001

The predictive value of muscularis mucosae invasion and p53 over expression on progression of stage T1 bladder carcinoma.

PURPOSE: We determine the significance of muscularis mucosae invasion and nuclear p53 over expression on the progression of stage T1 transitional cell bladder cancer. MATERIALS AND METHODS: The pathological findings in 149 cases of T1 tumors diagnosed between 1973 and 1996 were reviewed. Diagnosis was stage T1 in 94 tumors in which the muscular layer was clearly identifiable and disease-free. Mean followup was 64.9 months (range 5 to 288). T1 bladder cancers were subclassified into 2 groups, with (T1b) or without (T1a) muscularis mucosae invasion. The p53 nuclear antibody immunoreactivity was determined with antibody D07 and a cutoff point at 15%. RESULTS: T1 subclassification was possible in all 94 patients. Of all tumors 37.2% expressed p53 nuclear over expression. Univariate statistical analysis showed that p53 expression (p <0.05) and tumor invasion depth (p <0.001) significantly correlated with progression. However, on multivariate analysis only invasion depth (p <0.0001) and associated carcinoma in situ (p <0.03) remained independently significant as predictors of progression. CONCLUSIONS: In our study the depth of tumor invasion was a significant independent predictor of progression in patients with T1 bladder cancer. This result suggests that the depth of invasion in stage T1 should be included in the histopathological report.

Aged↗
PubMed2001

Estimation of cerebral oxygenation and hemodynamics in cerebral vasospasm using indocyaningreen dye dilution and near infrared spectroscopy: a case report.

Changes in cerebral hemodynamics and oxygenation patterns in cerebral vasospasm might be underestimated if transcranial doppler sonography and angiography findings are considered singularly. This report describes preliminary findings in further development of a noninvasive method that estimates regional cerebral oxygenation and perfusion. A 50-year-old patient suffering from cerebral vasospasm after subarachnoid hemorrhage before and after superselective papaverine infusion was examined. Measurements were taken by using a technique combining indocyaningreen dye dilution and near infrared spectroscopy. Our first results suggest that the technique could be suitable for estimation of cerebral hemodynamics. This noninvasive technique can be performed at the bedside and in special environments, such as neurocritical care units. It seems to be safe, easy to perform, and less time-consuming than conventional techniques. Combination of indocyaningreen dye dilution and near infrared spectroscopy might become a powerful tool in the detection and treatment of cerebral vasospasm causing delayed cerebral ischemic deficit. Further larger-scale investigations are necessary to evaluate the diagnostic accuracy of this technique. Our preliminary observations however, based on measurements before and after superselective papaverine infusion in vasospastic vessels, helped to clarify the influence of extracerebral contamination on the cerebral near infrared spectroscopy signal in the adult head.

Brain Chemistry↗
PubMed2001

The effect of trauma on neutrophil L-selectin expression and sL-selectin serum levels.

Among identified adhesion molecules, the L-selectin on neutrophils enables the first step of leukocyte adherence to activated endothelial cells. To allow firm adhesion of neutrophils, L-selectin is then split off the cell membrane. It was hypothetized that an increase of the constitutively high serum level of soluble L-selectin may indicate an ongoing pathological neutrophil sequestration to the endothelial cells associated with activation and injury of the cells. To evaluate this hypothesis, sL-selectin serum levels and neutrophil L-selectin expression of healthy volunteers (group A, n = 15), as well as of surgical patients, were investigated. Group B (n = 26) included patients subjected to elective limb surgery (mean operation time, 122 min), and group C (n = 45) comprised trauma patients. sL-selectin serum levels were measured daily over a 14-day period. Neutrophil L-selectin expression was evaluated by FACS analysis using the humanized anti-L-selectin antibody HuDreg 55 over a period of 3 days at minimum in both experimental groups. The binding of sL-selectin to endothelial cells was also examined in vitro. Elective limb surgery resulted in lower pre- and post-operative sL-selectin plasma levels (800-1,000 ng/mL) compared to healthy volunteers (1,100-1,200 ng/mL) with insignificant changes throughout the study period. Trauma patients revealed even lower sL-selectin levels (400-600 ng/mL). When these patients were discriminated by the multiple organ dysfunction (MOD) score of Moore in +MOD (n = 9, ISS = 31.7) and -MOD (n = 36, ISS = 25.0), a significant difference became evident. In +MOD patients sL-selectin levels remained on a low basis of 350 ng/mL, whereas in -MOD patients the initial low sL-selectin level subsequently rose to 800 ng/mL, similar to that of elective surgery patients. FACS analysis revealed a significant drop in neutrophil L-selectin expression 24 h after trauma compared to normal. Also, +MOD and -MOD patients were significantly discriminated by the L-selectin expression at this time. The in vitro studies revealed evidence for binding of sL-selectin to endothelial cells independently on the presence of neutrophils. According to our data, increasing severity of the post-operative/posttraumatic course is associated with decreasing sL-selectin serum levels and also reduced neutrophil L-selectin expression. In view of the in vitro results, this probably indicates competitive enhanced binding of sL-selectin to endothelial cells, thus masking the elevated activation of neutrophils and their ability for endothelial adherence.

Adolescent↗
PubMed2001

Flow cytometric microsphere-based immunoassay: analysis of secreted cytokines in whole-blood samples from asthmatics.

The ability of flow cytometry to resolve multiple parameters was used in a microsphere-based flow cytometric assay for the simultaneous determination of several cytokines in a sample. The flow cytometer microsphere-based assay (FMBA) for cytokines consists of reagents and dedicated software, specifically designed for the quantitative determination of cytokines. We have made several improvements in the multiplex assay: (i) dedicated software specific for the quantitative multiplex assay that processes data automatically, (ii) a stored master calibration curve with a two-point recalibration to adjust the stored curve periodically, and (iii) an internal standard to normalize the detection step in each sample. Overall analytical performance, including sensitivity, reproducibility, and dynamic range, was investigated for interleukin-4 (IL-4), IL-6, IL-10, IL-12, gamma interferon (IFN-gamma), and tumor necrosis factor alpha. These assays were found to be reproducible and accurate, with a sensitivity in the picograms-per-milliliter range. Results obtained with FMBA correlate well with commercial enzyme-linked immunosorbent assay data (r > 0.98) for all cytokines assayed. This multiplex assay was applied to the determination of cytokine profiles in whole blood from atopic and nonatopic patients. Our results show that atopic subjects' blood produces more IL-4 (P = 0.003) and less IFN-gamma (P = 0.04) than the blood of nonatopic subjects. However, atopic asthmatic subjects' blood produces significantly more IFN-gamma than that of atopic nonasthmatic subjects (P = 0.03). The results obtained indicate that the FMBA technology constitutes a powerful system for the quantitative, simultaneous determination of secreted cytokines in immune diseases.

Adult↗
PubMed2001

Recombinant antigen-enterotoxin A2/B chimeric mucosal immunogens differentially enhance antibody responses and B7-dependent costimulation of CD4(+) T cells.

The ADP-ribosylating enterotoxins, cholera toxin (CT) and the Escherichia coli heat-labile toxin (LT-IIa), have been shown to enhance mucosal and systemic antibody (Ab) responses to coadministered antigens. The purpose of the present study was to compare the ability of the nontoxic A2/B subunits of these toxins, which have distinct targeting properties, to augment the immunogenicity of a genetically coupled protein antigen. Structurally similar chimeric proteins were generated by genetically replacing the toxic A1 subunit of CT or LT-IIa with the saliva-binding region (SBR) from the streptococcal adhesin AgI/II. Intranasal immunization of BALB/c mice with either chimeric protein induced significantly higher plasma and mucosal anti-SBR immunoglobulin A (IgA) and IgG Ab responses than SBR alone. Moreover, compared to SBR-LT-IIaA2/B, SBR-CTA2/B elicited significantly higher levels of plasma IgG1 and salivary IgA anti-SBR Ab responses. Ex vivo and in vitro experiments revealed that SBR-CTA2/B selectively up-regulated B7-2 expression on murine B cells isolated from both the nasal associated lymphoid tissue, cervical lymph nodes, and spleen. In contrast, SBR-LT-IIaA2/B had little effect on B7-1 or B7-2 expression on B220(+), CD11b(+), or CD11c(+) cells. Analysis of the functional costimulatory activity of SBR-CTA2/B-treated B cells revealed a significant enhancement in anti-CD3-stimulated CD4(+) T-cell proliferative responses, and this proliferation was significantly reduced by treatment with anti-B7-2 but not with anti-B7-1 or isotype control Abs. Thus, SBR-CTA2/B and SBR-LT-IIaA2/B exhibit distinct patterns of antibody responses associated with differential effects on B7-2 expression and subsequent costimulatory effects on CD4(+) T cells.

Animals↗