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Biomedical subjects

K Fox

Publications and source records attributed to K Fox.

At least 73 records · Page 4Linked to original sources
PubMed1999

Moclobemide in the treatment of major depressive disorder (DSM-3) following traumatic brain injury.

Major depression (MDD) following traumatic brain injury (TBI) is a common phenomenon. There are no adequate studies in the literature defining optimum treatments for this condition following TBI. The opportunity arose to analyse a group of patients who were included in a larger study of an antidepressant (moclobemide). As the treatment, but not the delivery, was known, this has the status of an open study. Twenty-six patients with major depression of late onset (mean 4.67 years post-TBI) were identified (18 male, 8 female), with a mean age at injury 28.49 years. The group was moderately depressed with Hamilton Depression score (HAM-D) of 23.385 and moderately anxious with Hamilton Anxiety score (HAM-A) of 21.231. Mean HAM-D reduction was 81% and HAM-A reduction 81%. Of the 26 subjects 23 were defined as responders. Onset of action was rapid, with 17 responding by day 3. Irritability scores showed a mean reduction of 57% and pain scores a reduction of 39%. It is concluded that moclobemide may be an effective treatment for MDD following TBI, but properly controlled studies must be carried out to confirm this.

Adolescent↗
PubMed1999

The effect of vibrissa deprivation pattern on the form of plasticity induced in rat barrel cortex.

Plasticity was induced in the barrel cortex of adolescent rats by depriving every second vibrissa on the contralateral vibrissa pad. This produced a chessboard pattern of barrels in the cortex where each barrel receiving its principal input from a spared vibrissa was surrounded by barrels for which the principal vibrissa had been deprived and conversely, each barrel receiving its principal input from a deprived vibrissa was surrounded by barrels for which the principal vibrissa had been spared. After 7 days' deprivation, responses to the regrown vibrissae were depressed in layers II/III (49% of control levels) and IV (60%). Depression was far greater than that seen with "all vibrissa" deprivation, suggesting that activity in the spared vibrissae accentuated the depression of the deprived vibrissae. Depression was not due to subcortical changes as thalamic Ventral Posterior Medial (VPM) responses to deprived vibrissa were unchanged. The short latency responses in layer IV (5-7 ms) were unaffected by deprivation, but the number of cells responding at intermediate latencies (8-13 ms) was markedly reduced (to 66% of control). Potentiation of the spared vibrissa response was substantial in the near side of the neighbouring barrel (2.2-fold increase in layers II/III, 2.9-fold in layer IV) but had not spread to the far side after 7 days' deprivation. Sparing multiple vibrissae may increase the rate of potentiation since 7 days is insufficient time for potentiation in single vibrissa spared animals. Potentiation was not due to subcortical changes as thalamic VPm responses to the spared vibrissa were normal. However, in the spared barrel the response latency decreased by 1-2 ms. Only the cells responding at short latency exhibited potentiated responses (39% increase) suggesting that some thalamocortical plasticity is still possible at P28-35. These results show that chessboard pattern deprivation is capable of inducing substantial plasticity over a wide area of barrel cortex. All the major forms of plasticity seen with other vibrissa deprivation patterns were present, although no other single deprivation pattern studied so far causes the complete repertoire seen with chessboard deprivation.

Algorithms↗
PubMed1999

Sampling of grossly benign breast reexcisions: a multidisciplinary approach to assessing adequacy.

The widespread use of breast-conserving therapy in the treatment of early-stage breast cancer has resulted in increasing numbers of reexcision specimens requiring histologic assessment for residual disease and margin status. Because many reexcisions are performed for only microscopically positive or close margins, reexcision specimens often appear grossly negative and directed tissue sampling cannot be performed. The issue of adequate sampling in these specimens has not been addressed in the literature. A multidisciplinary approach to identifying the clinically important lesions in breast reexcisions and a cost-effective approach to tissue sampling are needed. We reviewed 97 consecutive cases of grossly negative breast reexcisions in which all tissue had been embedded. Forty-seven specimens contained residual invasive or in situ carcinoma and 50 were histologically negative. Detailed histologic findings were presented to a medical oncologist, a radiation oncologist, and a surgeon, who assessed the clinical impact of each diagnosis. Of the 47 positive specimens, 30 resulted in a major change in patient management (recommendation for additional surgery), 10 resulted in minor changes (alteration in radiation dose or adjuvant chemotherapy regimen), and 7 did not alter management. A total of 1867 blocks were submitted. If one block per centimeter of maximal tissue dimension had been submitted and the remainder of the specimen examined only if initial sections revealed invasive or in situ carcinoma, then 901 blocks would have been processed (52% reduction), but we would have missed an average of 3.7 cases resulting in a major change in therapy, and 3.3 cases resulting in a minor change. In contrast, two blocks per centimeter would have missed an average of less than one case each of diagnoses resulting in major and minor therapy changes (0.9 and 0.8 cases, respectively), and 315 (17%) fewer tissue blocks would have been processed. We recommend submitting two blocks per centimeter in grossly benign reexcisions, and examining the remainder of the tissue only if carcinoma is detected on initial sections.

Adult↗
PubMed1999

Effect of an alpha(2) agonist (mivazerol) on limiting myocardial ischaemia in stable angina.

A specific alpha(2) agonist, mivazerol, known to be effective in reducing myocardial ischaemia when given intravenously immediately before an exercise tolerance test, produced a significant increase in exercise duration and time to the onset of angina when given orally over a two week period to 25 patients with stable angina. A non-significant trend to reduction in electrocardiographic signs of ischaemia was also noted. The clinical relevance of this improvement now needs to be tested in larger numbers.

Adrenergic alpha-Agonists↗
PubMed1999

A behaviour risk factor survey in Jamaica.

A population based probability sample of 958 persons (454 males and 504 females) aged 15 to 49 years was surveyed in Jamaica in late 1993 for lifestyle and behaviour risk factors. Demographic characteristics of the sample were comparable to the general population, 60% of persons visited a private doctor the last time that they were ill. Based on self-reporting, 18% of the women and 8% of the men were hypertensive and 4.8% of the women and 3.3% of the men were diabetic. 26% of the men and 8% of the women had never had their blood pressure taken. 40% of the women had never had a Papanicolaou smear, 29% had never had a breast examination and 33% said that they were overweight compared with 18% of men. Smoking cigarettes and marijuana was more common among men (36%) than women (11%), as were drinking alcohol (79% of men, 41% of women) and heavy alcohol use (30% of men, 9% of women). Injuries requiring medical attention in the previous five years were reported by 40% of the men and 15% of the women. 34% of the men and 12% of the women regularly carried a weapon and 18% of the sample had participated in or witnessed at least one violent act in the previous month. Most of the people interviewed used a contraceptive method; 10% were not sexually active. Significantly more men than women had two or more sexual partners in the previous year (54% vs 17%, p < 0.001) or reported ever having a sexually transmitted disease (29% vs 9%, p < 0.001). Younger persons were more sexually active and more likely to use condoms during their most recent sexual intercourse. Higher socio-economic status and educational level generally had a more positive effect on health behaviour. This survey provides vital information relevant to planning health promotion campaigns and assessing their success.

Adolescent↗
PubMed1999

Local cortical interactions determine the form of cortical plasticity.

Competitive interactions between left and right eye inputs to visual cortex during development are usually explained by the thalamocortical axons competing more or less well for cortical territory during retraction into eye specific domains. Here we review the evidence for competitive and co-operative interactions between cortical columns in barrel cortex which are present several weeks after retraction of thalamocortical axons into barrels. Sensory responses in barrel cortex can be altered by a period of vibrissa deprivation. It was found that responses to previously deprived vibrissae (that had been allowed to regrow) were depressed more if neighboring vibrissae were spared than if all vibrissae were removed simultaneously. Depression of the deprived vibrissa response was greater the closer the cell lay to a spared barrel. It was also found that spared vibrissae responses were potentiated more if several neighboring vibrissae were left intact than if only a single vibrissae was spared. These results suggest a mechanism of cooperative potentiation, perhaps due to intracortical summation of excitation evoked by neighbouring vibrissa stimulation. Thalamic responses to vibrissa stimulation were unaffected by deprivation indicating a cortical origin. One of the consequences of deprivation was that the speed of transmission between barrels was increased for spared and decreased for deprived vibrissa. These results imply that inherent interactions between cortical columns give rise to a property of competition and co-operativity which amplify the effects of sensory deprivation.

Animals↗
PubMed1998

Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. OASIS (Organisation to Assess Strategies for Ischaemic Syndromes) Registry Investigators.

BACKGROUND: There are wide variations between countries in the use of invasive cardiac catheterisation and revascularisation procedures for patients with acute ischaemic syndromes. We studied the relation between rates of such procedures and rates of cardiovascular death, myocardial infarction, stroke, refractory angina, and major bleeding in a prospective, registry-based study in six countries with widely varying intervention rates. METHODS: 7987 consecutive patients presenting with unstable angina or suspected myocardial infarction without ST-segment elevation were recruited prospectively from 95 hospitals in six countries and followed up for 6 months. FINDINGS: The rates of all procedures were highest in patients in Brazil and the USA, intermediate in Canada and Australia, and lowest in Hungary and Poland. There were no significant differences in rates of cardiovascular death or myocardial infarction among these countries (4.7% overall [range 3.7-5.6] at 7 days; 11% overall [9-12] at 6 months). For the countries with the highest rates of invasive procedures (59%) versus the rest (21%) there was no difference in rate of cardiovascular death or myocardial infarction (adjusted odds ratio 0.88 at 7 days and 1.0 at 6 months). Rates of stroke were higher in Brazil and the USA than in the countries with lower intervention rates (adjusted odds ratio at 7 days 3.0, p=0.012; at 6 months 1.8, p=0.004) but rates of refractory angina at 7 days (0.7, p<0.001) and readmission for unstable angina at 6 months were lower (0.70, 0.63; both p<0.001). Comparison of results for hospitals without cardiac-catheterisation facilities and for those with such facilities gave adjusted odds ratios for cardiovascular death, myocardial infarction, or stroke at 6 months of 0.83 (10.6% vs 12.5%, p=0.05) and for refractory angina of 1.25 (19.3% vs 16.1%, p=0.09). INTERPRETATION: Higher rates of invasive and revascularisation procedures were associated with lower rates of refractory angina or readmission for unstable angina, no apparent reduction in cardiovascular death or myocardial infarction, but with higher rates of stroke. Randomised trials should assess the relative impact of conservative and more aggressive approaches to invasive cardiac procedures and revascularisations in patients with unstable angina.

Aged↗
PubMed1998

Functional intracellular P-glycoprotein.

Efflux of chemotherapy drugs by P-glycoprotein (P-gp) at the plasma membrane is thought to be a major cause of cancer multidrug resistance. In this report, we show by flow cytometry that P-gp also concentrates large amounts of 2 different drugs, Hoechst 33342 and daunorubicin, within a cytoplasmic compartment of multidrug resistant CHRC5 cells. A quantitative assay of Hoechst 33342 revealed that cytoplasmic sequestration by P-gp in CHRC5 cells accounted for about half of the amount of Hoechst 33342 accumulated by the drug-sensitive parental Aux BI cells. Daunorubicin sequestered in the cytoplasm of CHRC5 cells could be released by inhibiting P-gp function with cyclosporin A, resulting in cell death. A likely site of drug sequestration is P-gp-containing cytoplasmic vesicles, in which the P-gp is oriented so that drugs are transported and concentrated in the interior of the vesicles. P-gp was detected in the membranes of cytoplasmic vesicles of CHRC5 cells by confocal immunofluorescence microscopy and immunoelectron microscopy with anti-P-gp monoclonal antibodies (MAbs). Vesicular localization of daunorubicin was observed by epifluorescence microscopy. The origin and nature of the P-gp-containing vesicles are unknown, but they do not correspond to endocytic vesicles. Our results directly demonstrate that chemosensitizer-induced release of drugs sequestered in cytoplasmic vesicles by P-gp can be used to overcome multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Downregulation of immunodetectable connexin43 and decreased gap junction size in the pathogenesis of chronic hibernation in the human left ventricle.

BACKGROUND: The regional wall motion impairment and predisposition to arrhythmias in human ventricular hibernation may plausibly result from abnormal intercellular propagation of the depolarizing wave front. This study investigated the hypothesis that altered patterns of expression of connexin43, the principal gap junctional protein responsible for passive conduction of the cardiac action potential, contribute to the pathogenesis of hibernation. METHODS AND RESULTS: Patients with poor ventricular function and severe coronary artery disease underwent thallium scanning and MRI to predict regions of normally perfused, reversibly ischemic, or hibernating myocardium. Twenty-one patients went on to coronary artery bypass graft surgery, during which biopsies representative of each of the above classes were taken. Hibernation was confirmed by improvement in segmental wall motion at reassessment 6 months after surgery. Connexin43 was studied by quantitative immunoconfocal laser scanning microscopy and PC image software. Analysis of en face projection views of intercalated disks revealed a significant reduction in relative connexin43 content per unit area in reversibly ischemic (76.7+/-34.6%, P<.001) and hibernating (67.4+/-24.3%, P<.001) tissue compared with normal (100+/-30.3%); ANOVA P<.001. The hibernating regions were further characterized by loss of the larger gap junctions normally seen at the disk periphery, reflected by a significant reduction in mean junctional plaque size in the hibernating tissues (69.5+/-20.8%) compared with reversibly ischemic (87.4+/-31.2%, P=.012) and normal (100+/-31.5%, P<.001) segments; ANOVA P<.001. CONCLUSIONS: These results indicate progressive reduction and disruption of connexin43 gap junctions in reversible ischemia and hibernation. Abnormal impulse propagation resulting from such changes may contribute to the electromechanical dysfunction associated with hibernation.

Adult↗
PubMed1998

Electrocardiographic consequences of a peripatetic lifestyle in gray wolves (Canis lupus).

Cardiac chamber enlargement and hypertrophy are normal physiologic responses to repetitive endurance exercise activity in human beings and domestic dogs. Whether similar changes occur in wild animals as a consequence of increased activity is unknown. We found that free-ranging gray wolves (Canis lupus, n = 11), the archetypical endurance athlete, have electrocardiographic evidence of cardiac chamber enlargement and hypertrophy relative to sedentary captive gray wolves (n = 20), as demonstrated by significant increases in QRS duration, QT interval, and QT interval corrected for heart rate, a tendency towards increased Q, R, and S wave voltages in all leads, and a significant decrease in heart rate. We conclude that exercise activity level and therefore lifestyle affects physiologic variables in wild animals. An immediate consequence of this finding is that physiologic measurements obtained from a captive wild-animal population with reduced exercise activity level may not accurately reflect the normal physiologic state for free-ranging members of the same species.

Adaptation, Physiological↗
PubMed1998

Experience-dependent depression of vibrissae responses in adolescent rat barrel cortex.

A short period of vibrissae deprivation in an adolescent (approximately 1 month old) rat can lead to depression of the cortical response to stimulation of the regrown vibrissae. In a barrel column representing the deprived vibrissa, depression is greater for neurons located close to the barrel column representing the spared vibrissa. One possible explanation is that the spared vibrissa produces heterosynaptic depression of the principal vibrissa response (Glazewski & Fox, 1996). To test this idea further, we compared the effect of depriving all vibrissae (no heterosynaptic influence at all) with depriving a single vibrissa (maximal heterosynaptic influence expected). In addition we tested the origin of the depression by recording from subcortical structures. After 7 days' deprivation and 6-8 days' regrowth, we tested the responses of barrel cortex cells, thalamic VPm neurons and trigeminal ganglion cells to stimulation of the regrown vibrissae. We found that depression was greater in cortex if a single vibrissa had been deprived than if all vibrissae had been deprived. (Average principal vibrissae responses in single vibrissae deprived animals were 36% of those in all vibrissae deprived animals for layer II/III and 41% for layer IV.) This implicates the spared vibrissae in actively down-regulating responses to the deprived vibrissae. However, some depression could also be produced in animals deprived of all vibrissae (layers II/III were 39% and layer IV 74% of control levels). These results indicate that simple withdrawal of activation has a depressive effect on responses but that depression is far greater if some active inputs remain. Neither form of deprivation had an effect on responses to principal vibrissa stimulation in the thalamus or trigeminal ganglion however, suggesting that depression originates in the cortex. Within the cortex, intracortical connections seem most affected as the greatest depression was found in layers II/III and in layer IV among cells responding at intermediate latencies (9-14 ms).

Animals↗
PubMed1998

Long-term (5 year) effects of transient (silent) ischaemia on left ventricular systolic function in stable angina. Clinical and radionuclide study.

AIMS: (a) to assess short (1 year) and long-term (5 year) changes in left ventricular ejection fraction in patients with stable coronary disease with or without ECG evidence of transient ischaemia during daily life on routine therapy, and (b) to assess whether patients with recurrent transient ischaemic episodes have a particular propensity to gradual deterioration in left ventricular ejection fraction in the absence of infarction. METHODS AND RESULTS: One hundred and forty eight patients (127 males; mean age 59 years), part of a natural history cohort of 172 patients who had undergone exercise testing, 48 h ambulatory ST monitoring, and resting radionuclide ventriculography at baseline, and who had not suffered any intervening cardiac event, underwent repeat radionuclide ventriculography at 1 year follow-up on identical or very similar medications. Furthermore, 56 patients (50 males; mean age 65 years) of this cohort, who had ischaemia both on exercise testing and ambulatory monitoring at baseline (n=33), or no ischaemia on either test at baseline (n=23), and who had suffered no intervening event, underwent repeat exercise testing, ambulatory monitoring and radionuclide ventriculography at a mean of 61.8 months follow-up. In 38 of these 56 cases, long-term testing mirrored baseline testing in terms of presence or absence of ischaemia (both tests +, n=25; both tests -, n=13). At one year there was no change in left ventricular ejection fraction, either for the whole group (n=148; left ventricular ejection fraction 47=11.6% - 47.13+11.07%, P=ns) or for subgroups with (n=62; left ventricular ejection fraction 48+12.1%-48.5+10.5%, P=ns) and without (n=86; left ventricular ejection fraction 46.2+10.4%-46.2+11.3%, P=ns) evidence of transient ischaemia at baseline. At 61 months, there was a small fall in mean left ventricular ejection fraction for the total study group (n=56; left ventricular ejection fraction 45.8+9.3%-42.1+8.8%, P<0.05); however, this fall was not significant for those patients with both baseline and 5 year evidence of transient ischaemia (n=25; left ventricular ejection fraction 44.9+8.7%-41.3+7.5%, P=0.056). CONCLUSION: In medically treated stable coronary patients who do not suffer any intervening cardiac event, recurrent transient (silent) ischaemic episodes do not, in themselves, lead to gradual deterioration in left ventricular systolic function over a 1-5 year period.

Adult↗
PubMed1998

Increased platelet responsiveness following coronary stenting. Heparin as a possible aetiological factor in stent thrombosis.

AIMS: Platelet activation may be a determinant of thrombotic and restenotic complications following intracoronary stenting. In order to measure the effect of stenting on platelet activation antigen expression we used whole blood flow cytometry in 18 patients undergoing Palmaz-Schatz stenting (treated with full anticoagulation) and compared these with a group of 18 patients undergoing elective angioplasty. The effects of low molecular weight heparin and unfractionated heparin on platelet behaviour were also studied, both in vitro and in vivo to determine the contribution of prolonged heparin therapy to platelet activation following stenting. METHODS AND RESULTS: Fibrinogen binding to activated GPIIb-IIIa, and surface expression of P-selectin, GPIb and GPIIb-IIIa antigens were measured in unstimulated peripheral blood samples (rest) and on stimulation with adenosine diphosphate (0.1-10 micromol x 1(-1)) and thrombin (0.02-0.16 U x ml(-1)). No changes were seen in resting samples following angioplasty or stenting. Agonist responsiveness was unaltered after angioplasty, but in stented patients antigen expression in response to thrombin was significantly reduced (P< or =0.04), whilst the adenosine diphosphate response was significantly increased (P=0.01). Similar effects were observed in patients with unstable angina treated with either low molecular weight heparin or unfractionated heparin in vivo. In vitro, both unfractionated and low molecular weight heparin inhibited thrombin-induced platelet activation, but stimulation of adenosine diphosphate responses was more marked with unfractionated than low molecular weight heparin. CONCLUSIONS: There was a significant increase in platelet responsiveness to adenosine diphosphate following intracoronary stenting in patients treated with conventional anticoagulants. This was probably a consequence of treatment with heparin. Activation of platelets by heparin may explain the increased rate of stent thrombosis in patients treated with anticoagulant therapy. Low molecular weight heparins stimulate platelets less than unfractionated heparin.

Adenosine Diphosphate↗
PubMed1998

Total and viable airborne bacterial load in two different agricultural environments using gas chromatography-tandem mass spectrometry and culture: a prototype study.

Airborne exposure to bacterial components found in agricultural environments can lead to pulmonary inflammation. Total (viable and nonviable) bacterial load was monitored in a stable and a dairy by a new approach, gas chromatography-tandem mass spectrometry measurement of muramic acid, a component of gram positive and gram negative bacterial peptidoglycan. Also used to assess the gram negative bacterial load were 3-hydroxy fatty acids, markers of bacterial lipopolysaccharide. Culture, an established procedure for assessing the viable bacterial portion of airborne dust, served as a basis for comparison. The muramic acid and 3-hydroxy fatty acid concentrations (total C12:0, C14:0, and C16:0) showed a correlation with an R2 of 0.81. Dust and muramic acid levels also correlated. However, although relative muramic acid levels were lower in the stable than the dairy, colony forming units (CFU) were considerably higher in the stable. The total bacterial load (estimated from muramic acid values) for both the stable and dairy was also higher than would have been predicted from culture. These results suggest that nonculture based approaches and culture provide complementary but independent measurements of airborne biopollution.

Agriculture↗
PubMed1998

Paclitaxel plus carboplatin in advanced carcinoma of the urothelium: an active and tolerable outpatient regimen.

PURPOSE: To determine the toxicity and efficacy of an outpatient regimen of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium. PATIENTS AND METHODS: Patients received paclitaxel 150 to 225 mg/m2 over 3 hours followed by carboplatin (targeted area under the concentration-time curve [AUC], 6 mg/mL x min) every 3 weeks. During phase I accrual, 16 patients were treated; 17 additional patients were enrolled at the phase II dose. The median age was 70 years (range, 47 to 82). The median serum creatinine concentration was 1.1 mg/dL (range, 0.7 to 2.7) and the median estimated creatinine clearance was 52 mL/min (range, 24 to 110). RESULTS: During phase I accrual, the maximum-tolerated dose (MTD) of the regimen was not defined. Phase II accrual occurred at the paclitaxel 225 mg/m2 dose level. A total of 156 cycles were administered. The median number of cycles received was five (range, one to eight). Sensorimotor neuropathy was the principal nonhematologic toxicity. Significant granulocytopenia was common, but significant thrombocytopenia was not. Objective responses were demonstrated at all dose levels. At the phase II dose (paclitaxel 225 mg/m2 followed by carboplatin at AUC 6 mg/mL x min), the objective response rate was 50% (95% confidence interval [CI], 28% to 72%). CONCLUSION: Paclitaxel plus carboplatin is an active and tolerable outpatient treatment for patients with advanced carcinoma of the urothelium. The ability to administer this combination over multiple cycles even to patients with advanced age and abnormal renal function makes it well suited for this patient population. Confirmatory trials of this regimen are ongoing.

Aged↗