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Biomedical subjects

R F Morton

Publications and source records attributed to R F Morton.

At least 55 records · Page 3Linked to original sources
PubMed1991

Phase II evaluation of menogaril in patients with advanced cervical carcinoma. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic.

Fourteen patients with advanced/recurrent squamous cell carcinoma of the uterine cervix received menogaril, 200 mg/m2 by one hour intravenous infusion at four-week intervals. No objective regressions were observed. Median time to progression was less than two months and median survival was seven months. All patients experienced neutropenia. Platelet toxicity was negligible. Venous irritation and phlebitis occurred at the infusion site in 43% of patients. Menogaril as administered in this protocol is ineffective in treating previously irradiated advanced/recurrent squamous cell carcinoma of the uterine cervix and warrants no further investigation in this disease at the dosage and administration schedule used in this protocol.

Adult↗
PubMed1991

Bronchoconstriction and delayed rapid shallow breathing induced by cigarette smoke inhalation in anesthetized rats.

Bronchomotor and ventilatory responses to inhalation of cigarette smoke (50% concentration, 6 ml) were studied in anesthetized and vagotomized Sprague-Dawley rats. Low-nicotine cigarette smoke did not cause any detectable delayed response, whereas high-nicotine cigarette smoke induced rapid, shallow breathing, and a marked increase in airway resistance (RL). The increase in f reached a peak (delta f = 43 +/- 8%) at the 5th breath after the onset of smoke inhalation, preceding both the decrease in VT (delta VT = -27 +/- 4%) and the increase in RL (delta RL = 89 +/- 19%); the latter 2 reached their peaks at approximately the 10th breath, displaying a similar temporal pattern of responses between them. The bronchomotor response to high-nicotine cigarette smoke was slightly attenuated but not prevented by prior administration of isoproterenol (0.2 mg/kg, intravenously [iv]), nor was the smoke-induced rapid, shallow breathing. In contrast, prior administration of mecamylamine (0.9 mg/kg, iv) completely abolished both the bronchomotor and ventilatory responses to smoke inhalation, indicating that nicotine is the primary causative agent responsible for these changes.

Airway Resistance↗
PubMed1991

Phase II trial of recombinant leukocyte A interferon (IFN-alpha 2A) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the combination cimetidine with BCNU in patients with disseminated malignant melanoma.

Sixty-two patients with biopsy-proven, measurable disseminated malignant melanoma received either the combination IFN-alpha 2A with BCNU (30 patients) or the combination cimetidine with BCNU (32 patients) in parallel noncomparative Phase II trials. From patients receiving IFN-alpha 2A plus BCNU, we observed a 7% response rate: 1 complete response (CR) and 1 partial response (PR) (soft tissue disease with durations of 6.9 and 11.5+ months, respectively). Median time to progression (MTP) was 1.8 months and median survival time (MST) was 3.8 months. Myelosuppression and a flu-type illness were the most common toxicities. From patients receiving cimetidine plus BCNU, the response rate was 16%: 4 PRs (soft tissue disease, 3.8 months; visceral, 2.1, 4.0+, and 9.7 months) and 1 CR (soft tissue, 14.3+ months). MTP and MST were 1.9 and 5.5 months, respectively. Myelosuppression and nausea/vomiting were the most common side effects. Although each of these regimens had great conceptual allure, neither offered any durable impact on the natural history of disseminated malignant melanoma. Nevertheless, alternative combinations of biological response modifiers (BRMs) and BRMs with biochemical modulators or cytotoxic agents may provide some useful alternatives for further clinical investigations.

Adult↗
PubMed1990

Acute effects of cigarette smoke on breathing in rats: vagal and nonvagal mechanisms.

The acute ventilatory response to inhalation of cigarette smoke was studied in anesthetized Sprague-Dawley rats. Cigarette smoke (6 ml, 50%) generated by a machine was inhaled spontaneously via a tracheal cannula. Within the first two breaths of smoke inhalation, a slowing of respiration resulting from a prolonged expiratory duration (173 +/- 6% of the base line; n = 32) was elicited in 88% of the rats studied. This initial inhibitory effect on breathing was not affected either by an increase (410%) in the nicotine content of the cigarette smoke or by pretreatment with hexamethonium (33 mg/kg iv). However, bilateral vagotomy completely eliminated the initial ventilatory inhibition. Cooling both vagi to 5.1 degrees C blocked the reflex apneic response to lung inflation, but it did not abolish the inhibitory effect of smoke. After the initial response, a rapid shallow breathing pattern developed and reached its peak 5-12 breaths after inhalation of high-nicotine cigarette smoke; this delayed response could not be prevented by vagotomy and was undetectable after inhalation of low-nicotine smoke. We conclude that the initial inhibitory effect of smoke on breathing is mediated by vagal bronchopulmonary C-fiber afferents, which are stimulated by smoke constituents other than nicotine, whereas the delayed tachypneic response to smoke is caused by the absorbed nicotine.

Animals↗
PubMed1989

Alternating chemotherapy with or without VP-16 in extensive-stage small-cell lung cancer.

In this study, we evaluated the role of alternating chemotherapy with or without etoposide (VP-16) in patients with extensive-stage small-cell carcinoma (SCC) of the lung. All patients received initial treatment with CMC [cyclophosphamide, methotrexate, and chloroethyl-cyclohexyl-nitrosourea (CCNU)]. Four weeks after initial treatment, patients were stratified by performance score, central nervous system (CNS) metastasis, age, and response to initial CMC therapy and randomized to receive AO (doxorubicin and vincristine) or AVO (doxorubicin, VP-16, and vincristine) alternating with CMC. One hundred eighty-two eligible patients were treated with the initial cycle of CMC and 98 responded (54%). One hundred fifty-four patients were randomized to either AO/CMC or AVO/CMC. The response rates to AO/CMC and AVO/CMC were similar (72 vs. 68%). The time to progression and survival were not significantly different on the two treatment regimens. Toxicity was significantly greater for patients receiving AVO/CMC with six treatment-related deaths. Etoposide as used in this regimen did not significantly influence response rates, time to progression, or survival of patients with extensive small-cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Reflex bradypnea elicited by cigarette smoke inhaled through an isolated larynx.

The respiratory reflex responses elicited by laryngeal exposure to cigarette smoke were studied in 23 chloralose anesthetized dogs. A balloon-in-box system was connected to the breathing circuit, which allowed smoke to be inhaled spontaneously through an isolated larynx while preserving its normal respiratory flow and pressure. Our results in this study showed the following. (1) Two tidal breaths of cigarette smoke inhaled through the larynx triggered a mild but consistent bradypnea: expiratory duration (TE) increased from a control of 3.13 +/- 0.18 sec (mean +/- SEM) to a peak of 4.07 +/- 0.24 sec during smoke inhalation. The slowing of respiration occurred only during the period of smoke inhalation and returned quickly toward control after resuming air breathing. (2) No concomitant cardiovascular response was detected in these animals. (3) There was no significant difference in the prolongation of TE between responses to low- and high-nicotine cigarette smoke. (4) The bradypneic response to smoke was completely abolished by application of topical anesthetic (lidocaine hydrochloride) to the mucosa of this airway segment. These results suggest that the smoke-induced reflex bradypnea is probably elicited by a stimulation of laryngeal afferents.

Animals↗
PubMed1987

Role of bronchopulmonary C-fiber afferents in the apneic response to cigarette smoke.

The role of vagal bronchopulmonary C-fiber afferents in eliciting the immediate changes in breathing pattern after acute inhalation of cigarette smoke was assessed with a selective blockade of myelinated vagal afferents (innervating both stretch and irritant receptors) utilizing the method of differential cooling. In 15 of 17 chloralose-anesthetized dogs tested, spontaneous inhalation of cigarette smoke (19.7% avg conc, 500-700 ml vol) reproducibly caused the following immediate responses: apnea, bradycardia, and hypotension. These responses occurred within 1 to 2 breaths of smoke inhalation and were followed by a delayed hyperpnea. The apneic duration reached 326 +/- 33% (SE) (n = 15) of the mean base-line expiratory duration. Differential cold block of both vagi (coolant temperature 8.4 +/- 0.3 degrees C) abolished the reflex apnea induced by a positive-pressure (7-10 cmH2O) lung inflation but did not affect the apneic response to smoke inhalation (345 +/- 35%). The smoke-induced apnea was completely abolished by lowering the coolant temperature to -1.3 +/- 0.2 degrees C (n = 10) or by bilateral vagotomy (n = 5) and returned to the control level after both vagi were rewarmed. Based on these results, we suggest that the immediate apneic response to inhaled cigarette smoke is elicited by a stimulation of vagal C-fiber afferents in the lungs and airways.

Afferent Pathways↗
PubMed1987

Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma.

We conducted parallel phase II trials of cimetidine as a single agent and the combination N-phosphonacetyl-L-aspartate (PALA) plus L-alanosine among 40 previously untreated patients with biopsy-proven, measurable disseminated malignant melanoma. We did not design the trial to be a comparative assessment of the two regimens. Among 19 patients treated with cimetidine, 300 mg orally four times daily, there was one complete response of extensive pleural and pulmonary metastases for 16+ months and two partial regressions of soft tissue lesions for 7 and 21+ months, respectively. Among 21 patients treated with the combination regimen, there was only one partial response in soft tissue for 1 month. The median times to progression and death were 1.4 and 6 months, respectively, for cimetidine, and 1.3 and 4 months, respectively, from the combination of PALA plus L-alanosine. Among patients who progressed on initial treatment, there were no responses in 12 who received crossover therapy with cimetidine and 11 with the combination regimen. Two patients treated with the combination program had severe stomatitis, two developed renal failure, and one had severe leukopenia and thrombocytopenia. Recognizing the limitations of small sample size, these early observations suggest that cimetidine may have intriguing implications in the management of disseminated malignant melanoma.

Alanine↗
PubMed1986

Hexamethonium aerosol prevents pulmonary reflexes induced by cigarette smoke in dogs.

The reflexogenic respiratory responses to spontaneous inhalation of cigarette smoke (500-750 ml, 12-20% concentration) were studied in chloralose anesthetized dogs before and after hexamethonium aerosol, a nicotinic receptor antagonist, was administered into the lungs. In 11 of 13 dogs studied, reproducible responses of either apnea (n = 9) or rapid shallow breathing (n = 2) were elicited immediately after the first or second breath of smoke inhalation: apneic duration reached 398 +/- 47% (mean +/- SEM) of the mean baseline expiratory duration. Pretreatment with hexamethonium aerosol (3-5 breaths, 10% concentration) completely abolished these immediate changes in breathing patterns, but did not significantly reduce the delayed hyperpnea induced by smoke inhalation. Hexamethonium aerosol alone did not cause any detectable systemic effects. To examine if a bronchoconstrictive effect of nicotine was involved, the response to cigarette smoke was also studied after bronchodilation was induced by isoproterenol aerosol (15 breaths, 0.5% concentration) in 6 of these dogs. However, neither immediate nor delayed responses to smoke inhalation was significantly affected. These results suggest that: (1) these immediate respiratory responses to smoke inhalation are elicited by a nicotine-induced stimulation of vagal sensory receptors in the lungs, and (2) bronchoconstriction is not responsible for causing these reflex effects.

Aerosols↗
PubMed1986

An isolated upper airway preparation in conscious dogs.

The purpose of this study was to develop an isolated upper airway preparation in conscious dogs. Each of the four dogs was trained to wear an individually fitted respiratory mask and surgically prepared with two side-hole tracheostomies. After full recovery, one endotracheal tube was inserted caudally into the lower tracheostomy hole and another tube cranially into the upper tracheostomy. When the two endotracheal tubes were connected to a breathing circuit including a box-balloon system, the magnitude and pattern of the inspiratory flow through the upper airway were identical to that inhaled spontaneously into the lungs by the dogs, but the gas medium inhaled into the upper airway could be independently controlled. Thus it allowed test gas mixtures to be inhaled spontaneously through an isolated upper airway. One limitation was that the inspired gas remained in the upper airway during expiration, but this can be corrected by a simple modification of the breathing circuit. This preparation was tested in studying the respiratory effects of upper airway exposure to CO2 gas mixtures. Our results showed small but significant reduction in both rate and volume of respiration when the concentration of CO2 gas mixture inhaled through the upper airway exceeded 5%. Irregular breathing patterns were frequently elicited in these dogs by higher concentrations (greater than 12%) of CO2.

Airway Resistance↗
PubMed1985

Influence of nicotine in cigarette smoke on acute ventilatory responses in awake dogs.

To determine whether the acute ventilatory responses to inhaled cigarette smoke are affected by a difference in nicotine level, control cigarettes (low-nicotine research cigarettes) were laced with nicotine to generate an increase of 330% (mean) in nicotine content with little or no change in the levels of other smoke constituents. Acute ventilatory responses to both control and nicotine-laced cigarettes were determined and compared in six awake chronic dogs. Spontaneous inhalation of nicotine-laced cigarette smoke (10% concn, 750 ml vol) via a tracheostomy tube caused distinct and consistent changes in breathing pattern on the first or second breath of inhaled smoke: an apnea in three dogs, an augmented inspiration in two dogs, and rapid shallow breathing in one dog. No significant change in breathing pattern was found immediately following inhalation of control cigarette smoke. Both types of cigarettes caused a delayed hyperpnea. However, the increase in minute ventilation induced by nicotine-laced cigarettes (from a base line of 2.8 to a peak of 25.7 l/min) was significantly greater than that by control cigarettes (from 2.9 to 5.5 l/min). Results of this study suggest that nicotine is responsible for the elicitation of both the immediate and delayed ventilatory responses to inhaled cigarette smoke generated under our experimental conditions.

Animals↗
PubMed1983

Reflex control of breathing following inhalation of cigarette smoke in conscious dogs.

The acute ventilatory response to spontaneously inhaled cigarette smoke (750 ml, 10% concentration) was studied in 92 experiments on 6 awake resting dogs. Upon the first or second breath of smoke inhalation, either an apnea or an augmented breath was elicited consistently in each dog, and a hyperpnea occurred subsequently. Minute ventilation (VE) increased from a base line of 3.2 to a peak of 23.9 l/min at 8.3 s (mean values) after the smoke was completely inhaled and returned toward base line in 1-3 min. Cold blocking of both vagi (exteriorized in skin loops) eliminated the initial change in breathing pattern but did not significantly reduce the delayed hyperpnea. Denervation of carotid body chemoreceptors alone abolished 71.5% of the increase in VE induced by cigarette smoke. These results suggest that the apnea or augmented breath immediately following the smoke inhalation is mediated through vagal afferents, whereas the delayed hyperpnea results primarily from the stimulation of carotid body chemoreceptors, presumably by the absorbed nicotine.

Animals↗
PubMed1979

Experience with an independent study programme in epidemiology and biostatistics.

An independent study programme (ISP) was devised to permit self-paced learning in a combined epidemiology and biostatistics course for second-year medical students. The ISP was offered as an alternative to lecture instruction and the enrolment was restricted to 40 students out of a class of 176. The students who selected the ISP were superior to the remainder of the class with regard to MCAT scores and performance in first-year subjects. The ISP group scored higher on the examinations given in the course, including a set of 35 final examination questions which were identical for all students. This difference persisted even when the scores were adjusted for ability by use of MCAT scores. The time taken to complete the ISP varied considerably and there was no correlation between completion time and performance. Almost all the ISP students indicated satisfaction with the course and expressed a desire to have a similar option in subsequent courses.

Education, Medical, Undergraduate↗