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Biomedical subjects

G B Weiss

Publications and source records attributed to G B Weiss.

At least 37 records · Page 2Linked to original sources
PubMed1987

Dissociation of actions of BRL 34915 in the rat portal vein.

In rat portal vein, 0.5 and 5.0 microM BRL 34915 [(+/-)-6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl++ +)-2H- benzo[b]pyran-3-ol] abolished spontaneous rhythmic movements and norepinephrine (NE)-induced tension responses, respectively. Only the higher (5 microM) concentration of BRL 34915 increased 42K efflux and inhibited the NE-induced increase in 42K efflux. These results suggest that BRL 34915 inhibits spontaneous rhythmic movements and NE-induced tension responses by differing mechanisms of action and that only the block of the NE-induced tension response is related to K+ permeability or conductance changes.

Animals↗
PubMed1987

Differential calcium movements induced by agonists in guinea pig tracheal muscle.

The effects of high potassium, carbachol and histamine on tension responses and 45Ca fluxes in tracheal smooth muscle were examined. Calcium depletion or nitrendipine (10(-8) M) inhibited potassium-induced contractile responses more than those obtained with either histamine or carbachol, whereas Sr2+ inhibited mainly responses to histamine or carbachol. The Ca2+ entry facilitator, CGP 28392 (3 X 10(-6) M), potentiated contractions induced only by potassium. Uptake of 45Ca in guinea pig tracheal muscle can be separated into high and low affinity components. The 45Ca efflux rate from tracheal muscle into a La3+-substituted solution was over four-fold higher than in other smooth muscles. Potassium, carbachol and histamine induced sustained increases in 45Ca efflux into solutions containing 1.5 mM Ca2+; only transient increases in 45Ca efflux with carbachol and histamine were obtained after Ca2+ depletion. These agonists elicit contractile responses in tracheal muscle by selectively mobilizing different cellular and extracellular Ca2+ components.

Animals↗
PubMed1987

Modification by decreased temperature and hypoxia of 45Ca movements in stimulated smooth muscle of rabbit aorta.

In rabbit aortic smooth muscle, contractile responsiveness to 10(-6) M norepinephrine or 60 mM added K+ was inhibited by hypoxia (induced by 100% N2) or decreased bath temperature. Hypoxia increased K+-induced 45Ca efflux, inhibited K+-induced 45Ca uptake, and inhibited norepinephrine-induced 45Ca release; lowering bath temperature by 10 degrees C decreased resting 45Ca uptake and norepinephrine-induced 45Ca release by 30-40% and decreased the 45Ca uptake elicited with norepinephrine or K+ by more than two-thirds. Thus, hypoxia and temperature variations affect different Ca2+ components. Hypoxia decreases the norepinephrine-sensitive membrane Ca2+ fraction and the K+-stimulated mitochondrial Ca2+ fraction whereas decreased temperature most strongly inhibits membrane-associated Ca2+ uptake increases elicited with either norepinephrine or high K+.

Animals↗
PubMed1987

Effects of metoprolol, alone and in combination with lidocaine, on ventricular fibrillation threshold: comparison with atenolol, propranolol, and pindolol.

Metoprolol and other beta-adrenergic blocking drugs are known to exert cardioprotective effects that include significant reduction in occurrence of ventricular fibrillation (VF) following myocardial ischemia and infarction. To help determine the mechanism of these cardioprotective effects, this study evaluated the effect of equipotent beta-blocking doses of metoprolol and three other beta-blockers with differing ancillary properties on ventricular fibrillation threshold (VFT) in the normal canine heart. Metoprolol tartrate (1.0 mg/kg i.v.), atenolol (0.3 mg/kg i.v.), propranolol hydrochloride (0.3 mg/kg i.v.), pindolol (0.03 mg/kg i.v.), or saline control (0.9% NaCl solution; vehicle) was given, alone and in combination with lidocaine (L), to groups of six pentobarbital (32.5 mg/kg i.v.) anesthetized mongrel dogs after control VFT and control isoproterenol-induced (ISO) positive chronotropic effects had been determined. The D- (membrane stabilizing, non-beta blocking) and L- (beta blocking) isomers of propranolol also were administered to separate groups of six anesthetized dogs in a dose of 0.3 mg/kg i.v. Blood samples (venous) were taken before drug or vehicle administration, 10 min after drug/vehicle administration and at half-hour intervals thereafter during experimentation. ISO responses and VFT were determined 5 and 15 min, respectively, after drug/vehicle administration and at half-hour intervals for a total experimental period of 165 min. VF was induced with a train of pulses (5 s, 100 Hz, 3-ms duration, 250-omega resistance) applied by bipolar platinum electrodes to a paced heart (200 beats/min). Voltage (V) was increased every 60 sec (0.25-V increments between 0-3.5 V and 0.5-V increments greater than 3.5 V) until VF occurred. Metoprolol increased VFT significantly (p less than 0.05) and maximally (max delta V = 2.3 +/- 0.7 V) at 135 min postdrug when the ISO-induced increase in heart rate was inhibited (%I ISO) by less than 53%. Max delta V was not significantly increased following i.v. administration of atenolol (0.8 +/- 0.6 V), pindolol (0.1 +/- 0.1 V), or saline (0.1 +/- 0.1 V). Max delta V was 0.5 +/- 0.2 in the D-propranolol-treated group and 0.5 +/- 0.3 in the L-propranolol-treated group. These values did not differ from max delta V obtained in the propranolol-treated group (0.6 +/- 0.4 V). Changes in VFT for all groups were, over time, negatively correlated with %I ISO and were not dependent on membrane stabilizing effect (metoprolol, propranolol (D,DL), pindolol), intrinsic sympathomimetic activity (pindolol), or cardioselectivity (metoprolol, atenolol).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Ethics and cancer: a survey of the literature.

We have identified 776 articles, books, book chapters, and letters published since 1945 dealing with both ethics and cancer. Of this number, 473 (61%) were discussions in medical and scientific journal articles; they were published in 188 journals, demonstrating the scattered nature of this literature. The recent increase of writing in ethics and cancer has been dramatic, the median year of publication being 1979. Although the majority of articles addressed more than one ethical issue, the most common topic was whether patients should be told the truth about their diagnosis and prognosis (found in 241 of the items identified). The ethics of cancer research has only recently assumed importance in the medical literature, the median year of publication being 1981. The great interest in the ethics of cancer research is evident in that 255 (33%) of the 776 items dealt with research, 104 of these focusing on randomized trials. Besides truth-telling and research, 78 other issues are being discussed, among them informed consent for adults (119 items), the physician's responsibility for psychologic management of patients (79 items) and their families (68 items), responsibilities of nurses (58 items), the use and testing of laetrile (55 items), and euthanasia (38 items). Surgery was discussed in 90 items, pediatrics in 71, and radiotherapy in 44. The authors of this literature relied upon at least nine identifiable ethical positions. Only a limited number of authors were aware of the philosophic literature and of the complexities inherent in defining such terms as "benefit," "harm," and "quality of life."

Behavioral Research↗
PubMed1987

Differentiation of mechanisms for mobilization of calcium in smooth muscle.

Techniques to dissociate different sites or stores important for Ca2+ entry or release in smooth muscle include washouts of 45Ca in cold La3+ -substituted solutions. Scatchard-coordinate plots of Ca2+ uptake, substitution of Sr2+ for Ca2+, and both desaturation and rate coefficient plots. Rabbit aortic smooth muscle is particularly useful because Ca2+ mobilization components can be clearly separated. Other vascular preparations investigated (e.g., renal vessels, coronary arteries) appear to have similar components, but their relative importance varies. Respiratory smooth muscle also has similar Ca2+ mobilization components, but they are less readily dissociated by techniques employed in vascular smooth muscles. In guinea pig trachea, cold La3+ washouts do not retain cellular Ca2+ as well as in other preparations: use of other experimental approaches including the Ca2+ channel entry stimulator, CGP 28392, can demonstrate different Ca2+ uptake mechanisms for K+ -stimulated and agonist-induced Ca2+ uptake. In rabbit aorta, CGP 28392 potentiates tension increases elicited with lower concentrations of added K+ but has no effect on norepinephrine-induced contraction. A general model illustrating different Ca2+ entry mechanisms present in three types of smooth muscle provides examples drawn from a spectrum of possible variations in smooth muscle specificity for Ca2+ mobilization.

Animals↗
PubMed1987

Specific actions of gallium on norepinephrine-induced tension and associated 45Ca movements in rabbit aortic smooth muscle.

Gallium ion (Ga) dose-dependently (60-360 microM) inhibited contractions induced by norepinephrine (NE, 1 microM) in rabbit aortic (and media intimal) strips, but did not affect contractions elicited with high K+ (80 mM) solution. The initial phasic portion of the NE-induced response was either unaffected or only slightly (less than 10%) reduced, but the tonic portion of the response was inhibited completely by higher concentrations (greater than or equal to 300 microM) of Ga . In resting muscles, the equilibrated (90 min) 45Ca uptake was not altered by Ga (360 microM). Also, 45Ca efflux from either high- or low-affinity Ca++ binding sites was unaltered by Ga . The effects of Ga (360 microM) on 45Ca retained after a subsequent 60-min washout at 0.5 degrees C in an isosmotic (80.8 mM) La solution were also examined. High affinity La -resistant 45Ca released by NE (1 microM) was not altered by Ga . Under conditions favoring low affinity Ca++ uptake, 45Ca retention in control and K+-treated muscles was not changed by Ga , but the additional incremental 45Ca uptake associated with NE (in the presence of high K+) was blocked. Thus, Ga appears to have a selective inhibitory action on NE-associated 45Ca uptake without affecting either resting and high K+-induced 45Ca uptake or that 45Ca fraction released by NE. This action may result from a selective blockade by Ga of receptor-linked Ca++ channels in rabbit aortic smooth muscle.

Animals↗
PubMed1986

Effects of the calcium channel facilitator, CGP 28,392, on different modes of contraction in smooth muscle of rabbit and rat aortae and guinea-pig taenia caeci.

Effects of a Ca2+ channel facilitator, CGP 28,392, on smooth muscle contractions were examined in order to delineate characteristics of Ca2+ channels in rabbit and rat aortae and guinea-pig taenia caeci. Application of increasing concentrations of KCl induced contractile responses in these smooth muscles and CGP 28,392 shifted the concentration-response curve for KCl to the left. The maximum response was also increased in rat aorta and guinea-pig taenia. CGP 28,392 also shifted the concentration-response curves for noradrenaline in rat aorta and for histamine in taenia to the left and increased the maximum response in rat aorta. However, the corresponding curve for noradrenaline in rabbit aorta was not affected by CGP 28,392. The sustained contractions induced by KCl were inhibited by cumulative application of verapamil in these smooth muscles. Pretreatment of the muscle with CGP 28,392 decreased the inhibitory effect of verapamil. The noradrenaline-induced contraction in rat aorta and the histamine-induced contraction in taenia were also inhibited by verapamil, and CGP 28,392 antagonized the effect of verapamil. The noradrenaline-induced contraction in rabbit aorta was only slightly inhibited by verapamil, and CGP 28,392 did not modify the effect of verapamil. In these smooth muscles, cumulative application of Ca2+ to the Ca2+-depleted, KCl-treated muscle induced contraction, and the concentration-response curve for Ca2+ was shifted to the left by CGP 28,392 and to the right by verapamil. The concentration-response curves for Ca2+ in Ca2+-depleted, noradrenaline-treated rabbit and rat aortae and in Ca2+-depleted, histamine-treated taenia were also shifted to the left by CGP 28,392 and to the right by verapamil. In some contractions, CGP 28,392 increased and verapamil decreased the maximum responses. CGP 28,392 antagonized the inhibitory effect of verapamil. 5 These results suggest that the Ca2 channel facilitator, CGP 28,392, has a relatively selective activating effect on voltage-dependent Ca2+ channels in rabbit aorta. However, it also activates receptor-linked Ca2+ channels in rabbit aorta when Ca2+ concentrations are low. In rat aorta and guinea-pig taenia this facilitator activates both types of Ca2+ channels.

Animals↗
PubMed1986

Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung. A Southwest Oncology Group Study.

Using a randomized prospective trial design, chemotherapy with 5-fluorouracil, vincristine, and mitomycin C (FOMi) was compared with cyclophosphamide, doxorubicin, and cisplatin (CAP) and with FOMi alternating with CAP (FOMi/CAP) in 452 eligible patients with metastatic large-cell undifferentiated and adenocarcinoma of the lung. Objective responses were obtained in 26%, 17%, and 22% of patients treated with FOMi, CAP, and FOMi/CAP, respectively. The median survival was similar for FOMi, CAP, and FOMi/CAP therapies (20, 24, and 23 weeks, respectively), but the overall survival (log rank test), 1-year survival, and remission duration were longer for FOMi/CAP-treated patients. Survival was significantly longer for fully ambulatory FOMi/CAP-treated patients compared with either FOMi (P = .01) or CAP (P = .04). Younger patients treated with full doses of therapy responded more often than older patients receiving reduced drug doses (26% and 11%, respectively; P = .003). A prognostic factor regression analysis of all eligible patients indicates that sex, performance status, stage, and treatment assigned were important independent variables determining survival (P less than .05). Toxicity was comparable in each treatment group.

Adenocarcinoma↗
PubMed1986

Frequency and diversity of use of statistical techniques in oncology journals.

We describe the frequency with which various statistical techniques are reported in almost 5,000 articles published in five major American oncology journals during 1983 and 1984. A reader familiar with about a dozen techniques can expect to understand approximately 90% of the quantitative concepts cited in these journals. With the exception of survival analysis, these were typically the techniques encountered in many introductory statistical texts. Oncology training program preceptors concerned about making their graduates more effective consumers of the literature can use these findings in structuring exposure to quantitative skills. In four of the five journals reviewed, failure to identify the statistical methodology was among the ten most commonly encountered "techniques." This made it impossible to identify the analytical procedures used in many articles, and hence to judge their scientific validity. We encourage more editorial boards to adopt guidelines requiring a standardized format for presenting results based on a statistical analysis.

Actuarial Analysis↗
PubMed1986

Concurrent chemotherapy and radiotherapy for limited small-cell carcinoma of the lung: a Southwest Oncology Group Study.

This pilot study in limited-stage small-cell carcinoma of the lung using concurrent cisplatin (Platinol) and etoposide (VePesid) chemotherapy with radiotherapy has yielded a high complete response rate in 23 of 40 patients evaluable for response. Five of these responders have survived greater than 2 years off all therapy with a stable, high performance status. Median survival of all patients is 18 months. Toxicity has been acceptable, the most common being neutropenia. Radiation toxicities include 17 of 40 patients experiencing mild to moderate esophagitis, with one severe toxicity; and three of 40 patients developing mild to moderate radiation pneumonitis. The high complete remission observed with this program and the long tumor-free interval seen off maintenance therapy deserve further exploration. Toxicities appear only moderately greater than with other programs currently utilized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Phospholipids, calcium binding and arterial smooth muscle membranes.

The effects of phosphatidylserine (PS), phosphatidylinositol (PI), and phosphatidylcholine (PC) on 45Ca uptake, binding and efflux in canine aortic microsomes and of PS on 45Ca distribution and tension in rabbit aortic smooth muscle are reviewed. PS potentiated contractile responses to histamine and norepinephrine, and these effects were correlated with PS-induced removal of superficial Ca++ and decreased exchangeability of membrane Ca++. In microsomal preparations, PS and PI (but not PC) increased high affinity 45Ca binding but not 45Ca uptake. Only PI increased low affinity 45Ca uptake, and both PS and PI decreased oxalate-potentiated 45Ca uptake. The Ca++ ionophore A23187 removed membrane Ca++ in contrast to PS and PI. Exogenous negatively-charged PS or PI may enter plasma membranes and increase Ca++ binding levels. The roles of endogenous phospholipids in altered vascular responsiveness and function in disease states may be of critical importance.

Animals↗
PubMed1986

Cellular redistribution of 45Ca in rabbit renal artery determined by electron microscopic autoradiography: changes in response to K+-induced depolarization and nitrendipine.

Redistribution of Ca++ in response to K+-induced depolarization and/or nitrendipine (10(-6) M) was studied in isolated rabbit renal arteries using 1) isometric tension measurements, 2) 45Ca uptake measurements and 3) 45Ca electron microscopic autoradiography. Renal artery rings developed a mean tension of 1.67 +/- 0.30 g in response to high K+. Preincubation with 10(-6) M nitrendipine for 1 hr inhibited 80% of the initial portion and 100% of the sustained portion of the K+-induced contraction, without affecting rest tension. Using the modified lanthanum technique, cellular uptake of 45Ca increased 25% in muscles exposed to K+-substituted solution compared to control muscles (P less than .001). Preincubation with nitrendipine for 1 hr inhibited the K+-induced increase, whereas exposure to nitrendipine alone decreased 45Ca uptake compared to control muscles (P less than .001). Electron microscopic autoradiography of control renal arteries showed that relative 45Ca activities for the plasma membrane (PM), sarcoplasmic reticulum (SR) and mitochondria were higher than the cytoplasmic 45Ca activity, whereas activities for the nucleus were similar to that for the cytoplasm. Exposure to high K+ solution substantially decreased 45Ca activities of both the PM and SR (P less than .001), but changes in relative activities of other sites were insignificant. Muscles exposed to nitrendipine alone or nitrendipine plus high K+ had SR and PM activities intermediate with values from control and high K+ groups. Thus, Ca++ is released from both the SR and PM during exposure to high K+ and this Ca++ may contribute to the Ca++ pool involved in a depolarization-induced contraction.

Animals↗
PubMed1985

Effects of manganese on 45Ca mobilization and contractile responses in rabbit aortic smooth muscle.

In rabbit aortic smooth muscle, 1.5 mM Mn2+ inhibits contractile responses to norepinephrine more than those to high K+. Other associated effects include decreases in the La3+-resistant high affinity Ca2+ fraction, the high affinity Ca2+ uptake component in the Scatchard-coordinate plot, and high affinity Ca2+ uptake and binding in canine aortic microsomes. Higher (15 mM) concentrations of Mn2+ are less selective. Thus, those Ca2+ mobilization components and contractile responses associated with high affinity bound Ca2+ are more sensitive to inhibition by Mn2+.

Animals↗
PubMed1985

Paternalism modernised.

The practice of paternalism has changed along with developments in medicine, philosophy, law, sociology and psychology. Physicians have learned that a patient's values are a factor in determining what is best for that patient. Modern paternalism continues to be guided by the principle that the physician decides what is best for the patient and pursues that course of action, taking into account the values and interests of the patient. In the autonomy model of the doctor-patient relationship, patient values are decisive. In the paternalistic model, they are but one among several factors the physician must consider in making a medical decision. Although difficult to practise because of limitations in empathising with another person, modern paternalism remains a way to achieve maximum patient benefit.

Beneficence↗