Biomedical subjects

J Alexander

Publications and source records attributed to J Alexander.

At least 217 records · Page 12Linked to original sources

PubMed1997

Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon.

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose-dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.

Animals↗

PubMed1997

A fish oil derived concentrate enriched in eicosapentaenoic and docosahexaenoic acid as ethyl ester suppresses the formation and growth of intestinal polyps in the Min mouse.

We examined whether the n-3 polyunsaturated fatty acid ethyl ester enriched fish oil K85 (54.4% of eicosapentaenoic acid and 30.3% of docosahexaenoic acid as ethyl esters) could inhibit the intestinal tumorigenesis in Min mice, a murine model of familial adenomatous polyposis (FAP). Min mice that are heterozygous for a nonsense mutation in the Apc gene, develop spontaneously multiple intestinal neoplasms, primarily in the small intestine. K85 was dissolved in corn oil (vehicle) and mixed into the AIN-76A diet. The total oil content (K85 + corn oil) was 12% in all diets. The various experimental diets contained 0 (vehicle control), 0.4, 1.25 or 2.5% of K85. In the small intestine, the mean number of tumors/mouse was 105 +/- 18 (SEM) in control males and 70 +/- 11 in control females. Dietary K85 treatment reduced the number of small intestinal tumors: in males, the maximum reduction was 66% (P = 0.002) with 0.4% of K85; and in females, the maximum reduction was 48% (P = 0.043) with 2.5% of K85, but the inhibition was only slightly increased from 0.4% to 2.5% of K85. The mean tumor diameter was 1.33 +/- 0.08 mm in control males and 1.06 +/- 0.08 in control females, and the diameter ranged from <0.1 mm (monocryptal adenomas) to 4 mm. The small intestinal tumor diameter was reduced by K85 in a dose-dependent manner: in males, with a maximum reduction of 26% (r = -0.64, P = 0.004); and in females, with a maximum reduction of 38% (r = -0.61, P < 0.004). In the large intestine, the mean number of tumors/mouse was 1.0 +/- 0.5 in males and 0.8 +/- 0.2 in females. Although K85 treatment tended to reduce the number and diameter of the large intestinal tumors, these effects did not reach statistical significance. Aberrant crypt foci not elevated from the flat mucosa (ACF(Min)) occurring in the colon of Min mice were also scored. The mean number of ACF(Min)/colon (3.8 +/- 0.9) and the crypt multiplicity (1.49 +/- 0.28) in females were reduced by 73% (P = 0.03) and 60% (P = 0.048) with 2.5% of K85, respectively, whereas no significant effect could be observed in the males.

Adenomatous Polyposis Coli↗

PubMed1997

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine increases the numbers of tumors, cystic crypts and aberrant crypt foci in multiple intestinal neoplasia mice.

The multiple intestinal neoplasia (Min) mice have a mutation in the murine adenomatous polyposis coli (Apc) gene rendering them highly susceptible to spontaneous intestinal adenoma formation, similar to the familial adenomatous polyposis (FAP) syndrome in humans. We studied whether the most abundant mutagenic heterocyclic amine isolated from cooked food, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), could influence early intestinal neoplasia in C57BL/6J-Min/+ and C57BL/6J- +/+ (wild-type) mice of both sexes. PhIP was given in 4 weekly i.p. injections of 50 mg/kg. Ten weeks after the start of the experiment, PhIP had significantly increased the numbers of small tumors and cystic crypts in the proximal section of the small intestine in male Min/+ mice, and the numbers of aberrant crypt foci (ACF) in the large intestines of both males and females. The effects of PhIP were more pronounced in male than in female Min/+ mice. In +/+ mice, no tumors or cystic crypts in the small intestine, and no tumors and only a very few ACF in the large intestine, were induced by PhIP. These results show that a substance frequently present in the human diet is able to enhance the neoplastic process induced by a genetic lesion, which is also commonly found both in inherited and sporadic colon carcinomas in humans.

Animals↗

PubMed1997

Flat-panel x-ray detector using amorphous silicon technology. Reduced radiation dose for the detection of foreign bodies.

RATIONALE AND OBJECTIVES: The authors evaluate a new flat-panel x-ray detector (FD) with respect to foreign body detection and reduction of radiation dose compared with screen-film radiography. METHODS: Flat-panel x-ray detector is based on amorphous silicon technology and uses a 1 k x 1 k photo-detector matrix with a pixel size of 143 x 143 microns and 12-bit digital output. A thallium-dotted cesium iodide scintillation layer converts x-rays into light. An ex vivo experimental model was used to determine the detectability of foreign bodies. Foreign bodies with varying sizes were examined: glass with and without addition of lead, bone, aluminium, iron, copper, gravel fragments, and graphite. Four hundred observation fields were examined using conventional radiography (speed, 400; system dose: 2.5 microGy) as well as FD with a simulated speed of 400, 800, 1200, and 1600, corresponding to a detector dose of 2.5 microGy, 1.25 microGy, 0.87 microGy, and 0.625 microGy, respectively. Four independent radiologists performed receiver operating characteristic analysis of 8000 observations. RESULTS: Flat-panel x-ray detector with a simulated speed of 400 was significantly superior (P = 0.012) to screen-film radiography (speed, 400). At a simulated speed of 800 and 1200 FD yielded results equivalent to screen-film radiography. Flat-panel x-ray detector was significantly inferior to screen-film radiography at a simulated speed of 1600 (P = 0.012). CONCLUSIONS: Flat-panel x-ray detector technology allows significant reduction in radiation dose compared with screen-film radiography without loss of diagnostic accuracy.

Foreign Bodies↗

PubMed1997

The health of Filipinas in the Hunter region.

An interview survey found life-style behaviours (including risk factors and screening), social support and psychological health (GHQ-12) among a sample of 198 Filipina-Australians to be conducive to good health. Knowledge of local health services was good, and most women expressed general satisfaction with all aspects of life in Australia, except in the area of employment prospects. Despite these indications of good health in the group, there remains a need for health service providers to be aware of the difficulties faced by a proportion of Filipina migrants to Australia.

Adult↗

PubMed1997

Determination of gas-trapping during high frequency oscillatory ventilation.

OBJECTIVE: To determine the effect of frequency and percent inspiratory time on tidal volume and gas-trapping during high-frequency oscillatory ventilation (HFOV). SUBJECTS: Nine preterm infants with respiratory distress syndrome tested in the first 48 h of life. METHODS: Tidal volumes and the presence of gas-trapping were measured by respiratory jacket plethysmography at frequencies of 10, 14, and 17.8 Hz and at inspiratory times of 30%, 50% and 70%, using a commercially available high frequency oscillator.74 RESULTS: Mean (SD) tidal volumes were 2.40 (1.06) ml/kg at 10 Hz, 2.52 (1.07) ml/kg at 14 Hz and fell significantly to 1.96 (0.92) at 17.8 Hz (p < 0.05). Tidal volumes at 50% inspiratory time were significantly greater than at 30% inspiratory time [2.81 (1.42) ml/kg and 2.32 (1.18) ml/kg, respectively] but fell to baseline levels at 70% inspiratory time. There was no significant gas-trapping with increases in either frequency or percent inspiratory time. CONCLUSIONS: Gas-trapping is not a significant problem during HFOV in premature infants. Changes in tidal volume with increases in frequency and percent inspiratory time are similar to that seen in animal models.

High-Frequency Ventilation↗

PubMed1997

Innate immunity to Toxoplasma gondii is influenced by gender and is associated with differences in interleukin-12 and gamma interferon production.

Given that differences between the sexes in relative susceptibility to parasitic infections have been noted, this study further elucidates the mechanisms responsible by demonstrating that male SCID mice are more resistant than female mice to infection with Toxoplasma gondii and that this difference correlates with enhanced innate immune responses in these animals. Male SCID mice exhibited longer survival times, lower parasite burdens, and less severe pathological changes postinfection. An immunological basis for these differences is demonstrated in that these animals produced interleukin-12 more rapidly and exhibited higher levels of gamma interferon earlier postinfection.

Animals↗

PubMed1997

Uncovering subdominant cytotoxic T-lymphocyte responses in lymphocytic choriomeningitis virus-infected BALB/c mice.

The cytotoxic T-lymphocyte response against lymphocytic choriomeningitis virus (LCMV) in BALB/c mice is predominantly directed against a single, Ld-restricted epitope in the viral nucleoprotein (residues 118 to 126). To investigate whether any Kd/Dd-restricted responses were activated but did not expand during the primary response, we used a BALB/c mutant, BALB/c-H-2dm2, which does not express the Ld molecule. Splenocytes from LCMV-infected BALB/c mice were transferred into irradiated BALB/c-H-2dm2 mice and rechallenged with LCMV. Thus, they were exposed to an antigenic stimulus without the involvement of the immunodominant Ld-restricted epitope. In this adoptive transfer model, the donor splenocytes protected the recipient mice against chronic LCMV infection by mounting a potent Kd- and/or Dd-restricted secondary antiviral response. Analysis of a panel of Kd binding LCMV peptides revealed that residues 283 to 291 from the viral glycoprotein (GP(283-291)) comprise a major new epitope in the adoptive transfer model. Because the donor splenocytes were first activated during the primary infection in BALB/c mice, the GP(283-291) epitope is a subdominant epitope in BALB/c mice that becomes dominant after rechallenge in BALB/c-H-2dm2 mice. This study makes two points. First, it shows that subdominant CTL responses can be protective, and second, it provides a general experimental approach for uncovering subdominant CTL responses in vivo. This strategy can be used to identify subdominant T-cell responses in other systems.

Animals↗

PubMed1997

Respiratory status and allergy nine to 10 years after acute bronchiolitis.

In order to evaluate further the relationship between acute bronchiolitis in infancy and subsequent respiratory problems, children prospectively followed up from the time of their admission to hospital were reviewed along with a group of matched controls recruited at the previous five and a half year assessment. Sixty one index children and 47 controls took part. The groups were well matched for age, height, parental smoking, and social class. Although the prevalence of respiratory symptoms had fallen when related to the previous review, there remained an excess of coughing (48 and 17% in index and control children respectively; odds ratio 4.02) and wheezing (34 and 13% in index and control children respectively; odds ratio 3.59). Bronchodilator therapy was used by 33% of index children compared with 3% of controls. Lung function tests revealed no significant differences in the measurements of lung growth-for example, forced vital capacity, functional residual capacity, and total lung capacity-but the index children had significant reductions in measurements of airways obstruction-for example, forced expiratory volume in one second, maximum expiratory flow at 75, 50 and 25% of vital capacity, and airways resistance. Family history and personal skin tests showed no excess of atopy in the index group. This study supports the claim that the excess respiratory symptoms after acute bronchiolitis are not due to familial or personal susceptibility to atopy.

Acute Disease↗

PubMed1997

Dynamic vagosympathetic interaction augments heart rate response irrespective of stimulation patterns.

We previously demonstrated that tonic stimulation of either the sympathetic or the vagal nervous system augmented the dynamic heart rate response to the other of the two systems. We characterized the phenomenon as bidirectional augmentation of heart rate regulation. The question remained unanswered, however, as to whether such augmentation could occur under simultaneous dynamic stimulation of the two systems. The transfer characteristics from nerve stimulation to heart rate were well described by linear systems analysis, although no attention was paid to the aphasic nature of the stimuli in relation to each R-R interval. When we stimulated the two nerves with statistically independent Gaussian white noises, gain of the transfer function increased by 63.2 +/- 47.4% relative to individual stimulation (P < 0.05). When we stimulated the two nerves with mutually reciprocal Gaussian white noises, gain of the transfer function increased by 54.9 +/- 49.1% (P < 0.05). Thus simultaneous dynamic stimulation of the sympathetic and vagal systems bidirectionally augmented heart rate regulation irrespective of the pattern of the stimulation signals.

Animals↗

PubMed1997

Inhibition of NO synthesis minimally affects the dynamic baroreflex regulation of sympathetic nerve activity.

The purpose of this investigation was to examine the role of nitric oxide (NO) in the dynamic baroreflex regulation of cardiac sympathetic nerve activity. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses before and after the intravenous administration of NG-monomethyl-L-arginine. We characterized the dynamic properties relating carotid sinus pressure input to sympathetic nerve activity by means of a transfer function analysis. NG-monomethyl-L-arginine decreased the corner frequency of the transfer function (0.100 +/- 0.054 vs. 0.074 +/- 0.035 Hz; P < 0.05), whereas other parameters such as the steady-state gain and transmission lag time remained unchanged. Although cursory examination of these findings would suggest a possible contribution of NO in the dynamic baroreflex regulation of sympathetic nerve activity, quantitative assessment of the transfer function reveals only a minimal effect on the baroreflex regulation of arterial pressure, particularly under closed-loop conditions. We conclude that NO noticeably affects the dynamic baroreflex regulation of sympathetic nerve activity. However, it may not significantly affect arterial pressure regulation through central modulation of the carotid sinus baroreflex.

Animals↗

PubMed1997

Inhibition of NO synthesis does not potentiate dynamic cardiovascular response to sympathetic nerve activity.

We examined whether the inhibition of nitric oxide (NO) synthesis potentiates the dynamic sympathetic regulation of the cardiovascular system through the baroreflex. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses to evoke random changes in sympathetic nerve activity (SNA). We estimated the transfer functions from SNA to both aortic pressure (AoP) and heart rate (HR). The inhibition of NO synthesis by NG-monomethyl-L-arginine (L-NMMA, 40 mg/ kg) altered neither the transfer function from SNA to AoP nor that from SNA to HR. In contrast, sodium nitroprusside (3-6 micrograms.kg-1.min-1) significantly decreased the steady-state gain (40.3 +/- 11.7% of the control, P < 0.05) of the transfer function from SNA to AoP without affecting the HR responses. We conclude that the basal release of NO may have a role in the tonic blood pressure regulation, whereas it may not be involved in the dynamic sympathetic regulation of AoP or HR through the baroreflex.

Animals↗

PubMed1997

Closed-loop identification of carotid sinus baroreflex open-loop transfer characteristics in rabbits.

In the circulatory system, a change in blood pressure operates through the baroreflex to alter sympathetic efferent nerve activity, which in turn affects blood pressure. Existence of this closed feedback loop makes it difficult to identify the baroreflex open-loop transfer characteristics by means of conventional frequency domain approaches. Although several investigators have demonstrated the advantages of the time domain approach using parametric models such as the autoregressive moving average model, specification of the model structure critically affects their results. Thus we investigated the applicability of a nonparametric closed-loop identification technique to the carotid sinus baroreflex system by using an exogenous perturbation according to a binary white-noise sequence. To validate the identification method, we compared the transfer functions estimated by the closed-loop identification with those estimated by open-loop identification. The transfer functions determined by the two identification methods did not differ statistically in their fitted parameters. We conclude that exogenous perturbation to the baroreflex system enables us to estimate the open-loop baroreflex transfer characteristics under closed-loop conditions.

Animals↗

PubMed1997

Vagal stimulation decreases left ventricular contractility mainly through negative chronotropic effect.

Although an increase in vagal tone is known to slow heart rate (HR), whether it also depresses left ventricular contractility through mechanisms independent of the bradycardic effect remains unknown. The chief aim of this investigation, therefore, was the separation of the observed vagally mediated depression of ventricular contractility into direct and indirect vagal effects, the latter resulting via negative chronotropism. In 12 anesthetized, sympathectomized open-chest rabbits, we measured left ventricular contractility through determination of the end-systolic elastance (Ees). We found that tonic vagal stimulation administered at 0, 5, and 10 Hz decreased both HR (226.9 +/- 39.7, 201.9 +/- 25.7, and 171.3 +/- 18.5 beats/min, respectively; P = 0.0003) and Ees (109.5 +/- 25.7, 85.1 +/- 34.1, and 71.9 +/- 33.1 mmHg/ml, respectively; P = 5 x 10(-6)) in a frequency-dependent fashion. However, we observed that as long as HR was kept constant through fixed-rate atrial pacing, vagal stimulation resulted in little or no change in Ees. Thus we conclude that the negative inotropic effect of vagal stimulation is attributable primarily to its negative chronotropic effect when sympathetic tone is minimal.

Animals↗

PubMed1997

Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility.

Although a cardiac microdialysis technique has made it possible to estimate myocardial interstitial norepinephrine (NE) levels, whether such levels reflect the local NE concentration that would regulate ventricular contractility remains unknown. If such levels indicate locally regulating NE concentration, then ventricular contractility should be a unique function of the interstitial NE level regardless of how the latter is altered. To examine this hypothesis, we altered the interstitial NE level endogenously by stimulating the cardiac sympathetic nerves at 1 and 2 Hz while monitoring ventricular contractility. We also altered the interstitial NE level exogenously by means of intravenous NE infusions at 10 and 40 micrograms.kg-1.h-1. The basal NE levels did not differ between the stimulation and the infusion experiments (42.9 +/- 11.2 vs. 40.1 +/- 6.2 pg/ml, means +/- SE). The slopes of regression lines relating ventricular contractility and interstitial NE level were also not different between the two experiments [1.13 +/- 0.20 vs. 1.17 +/- 0.20%/(pg/ml), means +/- SE]. We conclude that the interstitial NE level estimated by cardiac microdialysis reflects the local NE concentration regulating ventricular contractility.

Animals↗

PubMed1997

Randomised controlled trial of psychological debriefing for victims of acute burn trauma.

BACKGROUND: Psychological debriefing (PD) is widely used following major traumatic events in an attempt to reduce psychological sequelae. METHOD: One hundred and thirty-three adult burn trauma victims entered the study. After initial questionnaire completion, participants were randomly allocated to an individual/couple PD group or a control group who received no intervention; 110 (83%) were interviewed by an assessor blind to PD status three and 13 months later. RESULTS: Sixteen (26%) of the PD group had PTSD at 13-month follow-up, compared with four (9%) of the control group. The PD group had higher initial questionnaire scores and more severe dimensions of burn trauma than the control group, both of which were associated with a poorer outcome. CONCLUSION: This study seriously questions the wisdom of advocating one-off interventions post-trauma, and should stimulate research into more effective initiatives.

Adolescent↗

PubMed1997

Promoting clinical involvement in hospital quality improvement efforts: the effects of top management, board, and physician leadership.

STUDY QUESTION: An examination of the effects of top management, board, and physician leadership for quality on the extent of clinical involvement in hospital CQI/TQM efforts. DATA SOURCES: A sample of 2,193 acute care community hospitals, created by merging data from a 1989 national survey on hospital governance and a 1993 national survey on hospital quality improvement efforts. STUDY DESIGN: Hypotheses were tested using Heckman's two-stage modeling approach. Four dimensions of clinical involvement in CQI/TQM were examined: physician participation in formal QI training, physician participation in QI teams, clinical departments with formally organized QA/QI project teams, and clinical conditions and procedures for which quality of care data are used by formally organized QA/QI project teams. Leadership measures included CEO involvement in CQI/TQM, board quality monitoring, board activity in quality improvement, active-staff physician involvement in governance, and physician-at-large involvement in governance. Relevant control variables were included in the analysis. PRINCIPAL FINDINGS: Measures of top management leadership for quality and board leadership for quality showed significant, positive relationships with measures of clinical involvement in CQI/TQM. Active-staff physician involvement in governance showed positive, significant relationships with clinical involvement measures, while physician-at-large involvement in governance showed significant, negative relationships. CONCLUSIONS: Study results suggest that leadership from the top promotes clinical involvement in CQI/TQM. Further, results indicate that leadership for quality in healthcare settings may issue from several sources, including managers, boards, and physician leaders.

Chief Executive Officers, Hospital↗

PubMed1997

Adjunctive therapy for acute myocardial infarction.

Based on results from a multitude of clinical trials of acute myocardial infarction, the beneficial role of a variety of pharmacologic agents, used in conjunction with thrombolytic therapy, has emerged. This is particularly true for aspirin, beta-blockers, heparin, and angiotensin-converting enzyme inhibitors. In addition, the dosage and timing of their administration have been shown to be crucial to their efficacy. The scientific and pathophysiologic basis as well as practical recommendations regarding their use are discussed. The exact role of nitrate therapy and potential for magnesium are presented in addition to data on agents that might be detrimental in the early stages of acute myocardial infarction.

Cardiovascular Agents↗