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Biomedical subjects

R G Evans

Publications and source records attributed to R G Evans.

At least 19 recordsLinked to original sources
PubMed1992

Effects of alpha-adrenoceptor antagonists and clonidine on the haemodynamic response to acute hypovolaemia in conscious rabbits.

In conscious rabbits an inferior vena caval cuff was progressively inflated so cardiac output fell at a constant approximately 8% of its baseline value. There was a biphasic haemodynamic response, consisting of an initial compensatory phase during which there was progressive systemic vasoconstriction and tachycardia, followed by a decompensatory phase in which systemic vasoconstriction failed abruptly, blood pressure plummeted and heart rate declined. We tested the effects on the haemodynamic response of prior 4th ventricular, and in some cases intravenous, infusions of saline, yohimbine, clonidine, yohimbine plus clonidine, and bunazosin. From the results we conclude that a yohimbine-sensitive mechanism in the brainstem, possibly alpha 2-adrenoceptor-mediated, may be an essential element of the cardiac receptor-mediated decompensatory phase of acute central hypovolaemia, but does not contribute to the arterial baroreflex-mediated compensatory phase.

Adrenergic alpha-Antagonists↗
PubMed1992

Management of advanced squamous cell carcinomas of the maxillary sinus.

From 1970 to 1988, 41 cases of advanced maxillary sinus cancers were treated at the University of Kansas Medical Center. Local control for the 37 evaluable patients was achieved in 21 (57%). Local control by radiation therapy alone was achieved in ten of 19 (53%) patients compared with eight of 14 (57%) treated with a combination of surgery and radiation therapy. A dose greater than 6500 cGy correlated with better local control in patients treated with radiation therapy alone. Neck node failure occurred in three of 35 (8%) patients when not electively treated. Neck metastasis either at presentation or at a later stage reduced survival. The overall absolute survival for the entire group at 5 years was 35%. A combination of preoperative radiation therapy and surgery is recommended for patients with advanced-stage maxillary sinus cancer. Radiation therapy is an equally good alternative for those who are not surgical candidates or refuse surgery.

Aged↗
PubMed1992

Intracerebral chemotherapy in the 9L rat brain tumor model.

We have used the 9L rat brain tumor model to search for effective chemotherapeutic approaches to the management of brain tumors. Several antineoplastic agents which have been proposed or are currently being used for human brain tumors, including 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), bleomycin, aziridinylbenzoquinone (AZQ), cis-Platinum, and acivicin, were administered intravenously (iv), intraperitoneally (ip), or intracerebrally (ic) to rats burdened with the intracranial 9L gliosarcoma. The results confirm that BCNU is the most effective systemic agent among the chemotherapeutic agents tested as indicated by its ability to significantly increase the median survival time (MST) and life span of the tumor-burdened animals. Bleomycin is an effective agent against the intracranial 9L tumor when administered ic. While neither systemic single iv dose AZQ (0.5-2.5 mg/kg) nor multiple ip treatments (0.5-1.0 mg/kg x 5, q 6 h) were effective in prolonging the survival, single ic dose AZQ (5-50 micrograms/rat) treatment significantly increased the MST of the treated animals (P < 0.05). Systemic AZQ treatments using higher doses produced a hematological toxicity, resulting in a decrease in MST of the treated animals. Cis-Platinum, either administered ip or ic, produced only a marginal effect on survival, although acute neurologic toxicity limited the dose of cis-Platinum that could be administered ic. Acivicin, either administered ip or ic, produced no effect on the survival of treated animals. Our results suggest that local treatment with certain antineoplastic agents may be an efficient therapy in the management of brain tumors.

Animals↗
PubMed1992

Heterogeneity of 5-fluorouracil radiosensitivity modulation in cultured mammalian cell lines.

There is ample evidence that 5-fluorouracil (5-FU) improves both local control and survival of a variety of gastrointestinal tumors when added to radiotherapy. However, the modulation of radiosensitivity by 5-FU is incompletely understood and some reports are apparently contradictory. Therefore, we have reevaluated the modulation of radiosensitivity by 5-FU in a variety of mammalian cells. HT-29 and WiDr (human colon adenocarcinoma), DU-145 (human prostate adenocarcinoma), V-79 (Chinese hamster lung fibroblast), and HeLa cell lines were maintained in exponential growth as monolayer cultures. Cell survival following treatment with drug and/or radiation was determined by colony formation assay. Radiation was delivered either alone; midway through a 1 hr exposure to 7-25 micrograms/ml 5-FU (pulse); or following initiation of 0.1-1.5 micrograms/ml 5-FU present throughout the entire incubation for assay of colony forming ability (continuous exposure). These 5-FU levels were selected to approximate those achieved in vivo in humans. The results indicate that mammalian cell lines may vary substantially insofar as modulation of their radiosensitivity by 5-FU is concerned. Radiosensitization, defined by reduction in D0, was observed for continuous exposure only in V-79, WiDr, and HT-29 cell lines, was observed for both pulse exposure and continuous exposure in DU-145, and was not present in HeLa cells. Radioenhancement, defined by reduction in n, was observed in V-79, WiDr, and HT-29 but not in the other cell lines. This effect, characterized by reduction in the shoulder portion of the curve, is naturally accompanied by a decrease of Dq. This indicates that mammalian cell lines may have different responses to radiosensitivity modulation by 5-FU. Though the cell lines may exhibit radiosensitivity by either alterations in the slope or shoulder of the cell survival curve, the mechanisms responsible for both the heterogeneity as well as the radiosensitization itself are completely unknown at this time. Insight into the mechanisms for both the heterogeneity and the radiosensitization will be important areas for further investigation.

Animals↗
PubMed1992

A CNS serotonergic mechanism in acute central hypovolemia in conscious rabbits?

We tested whether a brainstem serotonergic mechanism influences the hemodynamic response to acute central hypovolemia. An inferior vena caval cuff was gradually inflated so that mean cardiac index (MCI) fell at a constant rate (approximately 8%/min). Under control conditions, mean systemic vascular conductance index (MSVCI) fell progressively until MCI had fallen by approximately 50% (compensatory phase), at which point MSVCI rose abruptly and arterial pressure fell to approximately 40 mm Hg (decompensatory phase). Intravenous methysergide delayed the decompensatory phase and at a critical dose (300-3,000 nmol) abolished it. Methysergide had similar effects when injected into the fourth ventricle, pontomedullary cistern, or lateral ventricle in doses that were 7-10% of the critical i.v. dose, but had no effect when injected into the spinal subarachnoid space. LY53857 was equipotent to methysergide. None of these treatments attenuated the vasoconstriction of the first, compensatory, phase. Partial depletion of neuronal serotonin (after p-chlorophenylalanine or 5,7-dihydroxytryptamine treatment) had no effect on either phase. We conclude that a serotonergic mechanism, probably located in the brainstem, may be involved in the decompensatory phase of acute central hypovolemia.

5,7-Dihydroxytryptamine↗
PubMed1992

Does the haemodynamic response to acute central hypovolaemia depend on the rate of fall of cardiac output?

1. In published studies of the effects of acute blood loss in conscious rabbits, the rates of haemorrhage have ranged for 3-9% of blood volume/min. This is potentially a confounding factor when it comes to comparing the results of different studies. We have therefore tested whether the haemodynamic response to acute central hypovolaemia depends on the rate of fall of cardiac output. 2. Cardiac output in six conscious rabbits was reduced by 4, 8 and 12% of baseline levels per min by gradual inflation of a cuff around the thoracic inferior vena cava. These rates correspond approximately to blood loss at rates of 3, 6 and 9% of blood volume/min. 3. The haemodynamic responses were biphasic. In Phase I (compensatory) there was progressive systemic vasoconstriction and tachycardia, and only a small fall in blood pressure. In Phase II (decompensatory), systemic vasoconstriction failed abruptly, arterial pressure plummeted and heart rate declined. 4. We could detect no effect of rate of fall of cardiac output on the pattern of the haemodynamic responses in either Phase I or Phase II. 5. We conclude that the rate of blood loss in different studies of haemorrhage in conscious rabbits, within the range 3 to 9 per cent of blood volume per minute, need not be regarded as a confounding factor when it comes to interpreting the results. It is likely that this conclusion can be generalized to studies of haemorrhage in other mammalian species.

Animals↗
PubMed1992

Canada: the real issues.

Canadians are, by and large, satisfied with their health care system. It is for them a symbol of their community and distinguishes them from the United States. Unlike the health system of that country, it is universal, comprehensive, and accessible, and it costs less as a percentage of GNP to run. The difference between the two systems is rooted in differences in funding. By providing coverage of medically necessary care under a single nonprofit payer (the provincial governments, with guidance and some funds from the federal government), the Canadian system avoids the large overheads and profit incentives that make a fragmented private insurance industry so expensive and inequitable. Whereas health insurance in Canada is socialized, care is not: patients are free to choose among providers, physicians are primarily in private practice, and hospitals are independent, nonprofit institutions overseen by boards of trustees. Canada and the United States view the challenges confronting the Canadian system differently. To Canadians, the real issue is how to improve the management of a popular, effective, and heretofore affordable system, so as to preserve it in a more hostile economic environment. The specific areas of concern are common to all health care systems in the developed world but bear little resemblance to the misleading images of Canada fabricated in the United States for internal political purposes. For Canadians, the proof of their system is that it works, while millions in the United States go without.

Aged↗
PubMed1992

Bronchoalveolar lavage cell count and differential are not reliable indicators of amiodarone-induced pneumonitis.

Amiodarone-induced interstitial pneumonitis is a serious, frequently fatal untoward effect of a commonly used antiarrhythmic agent. Recent reports suggest that bronchoalveolar lavage (BAL) fluid cellular analysis might be used to diagnose amiodarone-induced pneumonitis. The purpose of this study was to determine if the diagnosis of amiodarone-induced pneumonitis could be made by patient history, pulmonary function evaluation, and examination of BAL fluid. We studied five groups of patients. Three of the five groups received amiodarone: patients receiving amiodarone without evident lung toxic reaction, patients with amiodarone-induced pneumonitis, and amiodarone-treated patients diagnosed as having other pathologic processes involving the lung. The two other groups examined were healthy volunteers and patients with interstitial lung disease from causes other than amiodarone. Pulmonary function tests included vital capacity (FVC), first second forced exhaled volume (FEV1), total lung capacity (TLC), and diffusing capacity for carbon monoxide (DCO). BAL fluid analysis included total and differential cell counts. We found that amiodarone-induced interstitial pneumonitis was not associated with an alteration in pulmonary function or BAL cellular composition which could permit its distinction from amiodarone-treated patients diagnosed as having an unrelated pulmonary process or patients with interstitial lung disease from other causes. The most frequent abnormality encountered in patients with amiodarone toxicity was a reduction in the percentage of macrophages in the differential cell count. The sensitivity, specificity, and predictive value of this finding was 82 percent, 69 percent, and 69 percent, respectively. The sensitivity, specificity, and predictive value of a > or = 15 percent reduction in DCO was 44 percent, 50 percent, and 36 percent, respectively. We conclude that amiodarone-induced interstitial pneumonitis remains a diagnosis of exclusion, and the role of BAL fluid analysis is to narrow the differential diagnosis through microbiologic culture and cytologic examination.

Aged↗
PubMed1992

Increased incidence of stings in venom-sensitive patients.

We compared the histories of 29 venom-sensitive and 28 control subjects who were selected from our venom referral and general allergy clinics respectively. The variables in the study included insect avoidance knowledge, the number of stings during the previous 2 years, insects involved, and time spent out of doors per week. There was no significant difference between the two groups with respect to age. All venom-sensitive patients were well versed in avoidance techniques while only 3 of 28 controls (11%) claimed such knowledge. Venom-sensitive subjects were stung almost ten times more frequently than control subjects. Wasp stings were the most common, followed by yellow jacket, honey bee, and hornet. The venom-sensitive patients also reported spending a greater amount of time outdoors (x 17.4 hours versus x 11.8, P < .05). An analysis of covariance showed that this difference in outdoor exposure was insufficient to account for the disparity in the number of stings. We conclude that other factors such as intrinsic attractants must be responsible for this phenomenon.

Adolescent↗
PubMed1991

Influence of higher brain centres and vasopressin on the haemodynamic response to acute central hypovolaemia in rabbits.

We tested whether suprapontine brain centres contribute to the sudden failure of vasoconstriction that occurs in unanaesthetized rabbits during acute reduction in central blood volume. Haemorrhage was simulated by gradually inflating a cuff around the thoracic inferior vena cava so that cardiac output fell by about 8% per min. In intact rabbits, and in rabbits that had undergone craniectomy but not decerebration, the haemodynamic response to simulated haemorrhage was always biphasic. During the first, compensatory phase, systemic vascular conductance fell almost in proportion to the fall in cardiac output so that arterial pressure fell by only about 10 mmHg. When cardiac output had fallen by about 50%, a decompensatory phase supervened in which systemic vascular conductance rose abruptly, arterial pressure fell steeply to less than 40 mmHg, and the plasma arginine vasopressin (AVP) level rose. High mesencephalic decerebration did not affect the compensatory phase, but it abolished the decompensatory phase and there was no rise in the plasma AVP level. The decompensatory phase was not restored by intravenous administration of AVP. We came to two conclusions as a result of this study. Suprapontine brain centres do not influence the arterial baroreflex-mediated vasoconstriction that occurs during the first phase of acute central hypovolaemia. However, the sudden failure of vasoconstriction that occurs during the second phase of acute central hypovolaemia, attributable to a signal from the heart and mediated by a delta-opioid receptor mechanism in the brainstem, does depend on the integrity of suprapontine brain centres, though not on neurohypophysial AVP release.

Animals↗
PubMed1991

Local recurrence of soft tissue sarcoma following brachytherapy.

Twenty-five patients with soft tissue sarcomas were treated with Ir192 implants following wide local excision at our institution between 1982 and 1987. External beam radiotherapy was given in addition to the implant in a majority of patients. The median follow-up in these 25 patients is 36 months (12 to 75 months). Twenty patients have had no evidence of local recurrence following their primary treatment (FFR = 80%). A multivariate analysis using stepwise logistic regression was used to predict failure in 3 years or less. Potential predictors examined included age, sex, tumor location, primary versus recurrent disease, grade, histology, surgical margins, implant only versus implant plus external beam, and a ratio of the volume of tissue which received 65 Gy (TV65) to the tumor volume (TV), that is (TV65/TV). The single variable which was significantly associated with local failure by 3 years was a TV65/TV of less than one. Once this variable was entered into the analysis, no other factor proved statistically significant. Our data suggest that when attempting local control of soft tissue sarcomas with brachytherapy, the volume of tissue receiving 65 Gy (TV65) from both implant and external beam must exceed the volume of the excised lesion (TV). Since the volume of a tumor can be readily determined prior to surgical excision either by CT or MRI scanning, pre-planning of the implant volume could potentially reduce the rate of local failure.

Adolescent↗
PubMed1991

5-Fluorouracil modulation of radiosensitivity in cultured human carcinoma cells.

We evaluated conventional pulse exposure versus continuous exposure models of 5-fluorouracil (5-FU) radiosensitization in HT-29 (human colon adenocarcinoma) and DU-145 (human prostate cancer adenocarcinoma) cell lines. Cell survival following treatment with drug and/or radiation was determined by colony formation assays. Radiation was delivered either by itself, approximately midway through a 1-hr exposure to 5-FU (10 micrograms/ml), or at various times following initiation of exposure to 5-FU (0.5 microgram/ml) present throughout the entire period of incubation. Drug concentrations were selected to approximate those achieved in vivo in humans. HT-29 cells showed a plating efficiency of 87% and similar cytotoxicity (survival reduced to 0.57-0.71) for all 5-FU conditions. The Do's of the radiation survival curves were not different for 1 hr of 5-FU exposure versus radiation alone. However, continuous exposure conditions demonstrated statistically significantly different Do's from radiation alone and pulse 5-FU exposure. DU-145 cells displayed a plating efficiency of 17% and cytotoxicities of 0.10-0.91 for the 5-FU conditions. DU-145 cells showed different radiation 5-FU interactions: 5-FU produced statistically significant changes in Do well as the differences between cell lines insofar as their radiosensitization by 5-FU underscore the caution required in extrapolating these radiobiologic models to the clinical setting.

Adenocarcinoma↗
PubMed1991

Cardiac chemoreceptors: pharmacological curiosities or physiological tools?

1. We have tested in unanaesthetized rabbits two hypotheses regarding a physiological role for cardiogenic chemoreflexes in acute central hypovolaemia. 2. In rabbits, the sympathoinhibitory phase of acute central hypovolaemia depends on the activation of a brain-stem delta-opioid receptor mechanism by a signal from the heart. Blockade of this by fourth ventricular injection of the delta-receptor antagonist ICI 174864 had no effect on the reflex haemodynamic responses to left atrial phenylbiguanide or intrapericardial nicotine. 3. Intravenous administration of the 5-HT3 receptor antagonist MDL 72222, or intrapericardial administration of the nicotinic ganglionic cholinoceptor antagonist mecamylamine HCl, had no effect on the haemodynamic response to acute central hypovolaemia. 4. We conclude that phenylbiguanide-sensitive myocardial afferents and nicotine-sensitive epicardial afferents play no part in the response to acute hypovolaemia in rabbits, and that the reflex effects evoked by chemically exciting these afferents do not depend on a brain-stem delta-opioid mechanism.

Afferent Pathways↗