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K Lawson

Publications and source records attributed to K Lawson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Is there a therapeutic future for "potassium channel openers'?

1. Potassium channels, which control cell electrical activity, are among the most regulated of all ion channels in biology. Promotion of activity in K+ channels by a wide range of physiological factors tends to stabilize cell function. 2. The discovery of synthetic molecules (e.g. cromakalim) that 'directly' open ATP-sensitive K+ channels has led to a new direction in pharmacology. ATP-sensitive K+ channel-opening properties have subsequently been demonstrated in a diverse range of chemical structures (synthetic and endogenous). 3. The existence of so many different subtypes of K+ channels has been an impetus in the search of new potassium channel openers with different channel selectivities and thus biological profiles. 4. The decrease in cell excitability following K+ channel opening implies a broad clinical potential in a number of pathological conditions for K+ channel openers. Preclinical and clinical evidence supports therapeutic roles of K+ channel openers in disorders of a wide range of biological cells. 5. Although lack of selectivity of current compounds remains a major hurdle, advances in K+ channel openers and K+ channel pharmacology are encouraging. Differences already observed in the pharmacology of K+ channel openers are important factors for the development of second-generation compounds, when tissue selectivity is sought. 6. The availability of subtype-selective K+ channel openers will facilitate detailed study, through a combined effort of electrophysiology, functional pharmacology and molecular biology, leading to focused therapeutic approaches for defined pathological conditions.

Adenosine Triphosphate↗
PubMed1996

Adverse psychological events occurring in the first year after predictive testing for Huntington's disease. The Canadian Collaborative Study Predictive Testing.

A total of 135 participants in the Canadian predictive testing programme for HD were followed for at least one year in one of four study groups: increased risk (n = 37), decreased risk ( n = 58), uninformative (n = 17), or not tested (n = 23). Clinical criteria for an adverse event were a suicide attempt or formulation of a suicide attempt plan, psychiatric hospitalisation, depression lasting longer than two months, a marked increase in substance abuse, and the breakdown of important relationships. Quantitative criteria, as measured by changes on the General Severity Index of the Symptom Checklist 90-R and the Beck Depression Inventory, were also used to identify people who had adverse events. Twenty of the 135 participants (14.8%) had an adverse event. There were no significant differences between those with or without an adverse event with respect to age, sex, marital status, education, psychiatric history, general psychiatric distress, or social supports at baseline. However, evidence for depression was associated with an increased frequency of adverse events (p < 0.04). The adverse events were similar and seen with equivalent frequency in those receiving an increased risk or decreased risk and persons at risk who did not receive a modification of risk. However, a significant difference was found in the timing of adverse events for the increased and decreased risk groups (p < 0.0002). In the increased risk group all of the adverse events occurred within 10 days after results whereas, in the decreased risk group, all of the adverse events occurred six months or later after reviewing test results. These results suggest that people entering into predictive testing with some evidence of clinical depression warrant special vigilance and also suggest that counselling and support should be available for all participants in predictive testing irrespective of the direction of test results.

Adolescent↗
PubMed1995

Breastfeeding duration: prenatal intentions and postnatal practices.

A study of 78 primiparas examined the role of prenatal intent and postnatal experiences in breastfeeding duration. Those fully breastfeeding 3 months after the birth of the baby had a higher level of education, timed their decision to breastfeed earlier, intended to breastfeed longer and had a more negative attitude to formula feeding. Commitment and confidence scores were not related to breastfeeding duration in first-time mothers. Breastfeeding duration was also related to the timing of the first breastfeed and extent of mother-infant contact in the 72 hours after birth but not to the number of feeding problems.

Adolescent↗
PubMed1994

Community placement for insanity acquittees: a preliminary study of residential programs and person-situation fit.

The present study, one of the first of its kind, describes the characteristics of community living placements for insanity acquittees conditionally released following hospitalization, along with the "fit" between living placement and individual characteristics. Although the small number of insanity acquittees (n = 13) and community placements (n = 9) precluded meaningful statistical analyses of results, the study provides a model for studying the characteristics of placements as well as personal characteristics of acquittees, and the interaction between the two. It also suggests the possible importance of this interaction, operationalized as "fit" between characteristics and placement. Consistent with research findings for other criminal defendants and for nonforensic psychiatric patients released from hospitalization, a better fit between acquittee and community placement may be associated with increased likelihood of success on conditional release.

Adult↗
PubMed1993

Mortality of Mexican Americans with NIDDM. Retinopathy and other predictors in Starr County, Texas.

OBJECTIVE: To determine the rate and risk factors of mortality in a cohort of Mexican Americans with NIDDM. RESEARCH DESIGN AND METHODS: A cohort of 353 Mexican Americans with NIDDM were identified between 1981 and 1986. All individuals underwent extensive evaluations that included physical, historical, ophthalmological, and laboratory assessments. This cohort was followed prospectively for a mean of 8 yr. Follow-up included mortality surveillance, death certificate extraction, and a combination of annual and intermediate examinations. RESULTS: The cohort experienced 67 mortality events. One-third of all deaths were premature < 65 yr of age) and most often were attributed to diseases of the heart (60.0%). In no case was diabetes listed as the cause of death, although it was listed as a contributing cause in 25.5% of cases. Men had a higher mortality rate than women. In both sexes, baseline retinopathy was identified as an important predictor of subsequent mortality. Mortality was significantly elevated in those with nonproliferative retinopathy and even further elevated in those with proliferative disease (relative risks of > or = 4 for proliferative disease). CONCLUSIONS: Mexican Americans with NIDDM are experiencing premature and excessive mortality compared with the general population. The results clearly link microvascular complications with macrovascular disease, but this link is not explained by a more untoward profile of traditional cardiovascular risk factors. Retinopathy appears to serve as an important monitor of the progression of diabetes and when identified would warrant aggressive action to inhibit or slow the processes leading to subsequent mortality.

Age Factors↗
PubMed1992

The antiemetic effect of lorazepam after outpatient strabismus surgery in children.

The high incidence of postoperative emesis after strabismus surgery in pediatric outpatients can be reduced by the prophylactic administration of droperidol 75 micrograms/kg intravenously. However, this may be associated with profound sedation, delayed discharge, dysphoria, agitation, and extrapyramidal symptoms in this population. Because lorazepam used as an antiemetic in children during chemotherapy decreased the incidence of nausea and vomiting, we compared the antiemetic effects of lorazepam and droperidol in a randomized, double-blind, placebo-controlled study of 129 healthy children undergoing surgical correction of strabismus. The children, aged 1-13 yr, were randomly allocated into three groups. The children in group 1 received droperidol 75 micrograms/kg intravenously; those in group 2 received lorazepam 10 micrograms/kg intravenously; and those in group 3 received placebo. Anesthesia consisted of halothane, nitrous oxide in oxygen, and atracurium. Study drugs were administered intravenously after induction of anesthesia but before surgery. In children 3-13 yr old, administration of either lorazepam or droperidol was associated with a lower (P < 0.024) incidence of postoperative vomiting. There was no difference between the antiemetic effect of lorazepam and that of droperidol. The incidence of postoperative agitation was greater in the droperidol group (P < 0.001) than in the lorazepam and placebo groups. Postdischarge vomiting was less (P < 0.009) in children younger than 3 yr of age. Lorazepam, similar to droperidol, has an antiemetic effect in outpatient children 3-13 yr old undergoing strabismus correction, but it is associated with less postoperative agitation than is droperidol.

Adolescent↗
PubMed1992

Effects of the divalent cations nickel and cadmium on contractions of rat aorta to endothelin-1.

1. The effects of inorganic and organic calcium channel antagonists on the contractile responses of rat isolated aortic rings to endothelin-1 (ET-1) were studied. 2. ET-1 (0.1-100 nM) evoked concentration-related contractile responses of the rat aorta (EC50 1.65 +/- 0.22 nM, Emax 125.8 +/- 4.5 %KClmax, n = 20). In Ca(2+)-free modified Krebs solution (containing 1 mM EGTA) aortic rings failed to contract to ET-1 (0.1-30 nM). 3. Nickel chloride (0.2-0.8 mM) attenuated the ET-1 (1-100 nM)-induced contraction of rat aorta (response (%KClmax) to 10 nM ET-1: control 132.0 +/- 8.7 and after 0.2 mM Ni2+ 90.3 +/- 14.8, 0.4 mM Ni2+ 54.7 +/- 12.3, 0.8 mM Ni2+ 10.3 +/- 4.4, n = 6/group). Cadmium chloride (10-30 microM) depressed the maxima of the concentration-response curves to ET-1 with an IC50 of 15.4 +/- 1.5 microM (n = 6). 4. The ET-1 evoked contractile responses were not modified by the dihydropyridine calcium channel antagonist, nicardipine (0.1 microM), or by omega-conotoxin (1.0 microM). Cinnarizine (10 microM), however, significantly attenuated the maximum response to ET-1 (96.9 +/- 6.0 vs 128.0 +/- 5.8 %KClmax for control), but failed to modify the EC50 value. 5. Amiloride, a Na(+)-Ca2+ exchange inhibitor, also depressed the maxima of the concentration-response curves to ET-1 with an IC50 of 0.45 +/- 0.05 mM (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1992

Differential effects of endothelin-1 on the vasorelaxant properties of benzopyran and non-benzopyran potassium channel openers.

1. The effects of endothelin-1 (ET-1) on the vasorelaxant properties of structurally different potassium channel openers (PCOs), BRL-38227, Ro 31-6930, SDZ PCO 400, EMD-52692, RP-49356 and pinacidil, were studied. 2. All PCOs evoked concentration-related relaxations of ET-1 (10 nM) or KCl (20 mM) contracted rat isolated aortic rings denuded of endothelium. BRL-38227, EMD 52692, SDZ PCO 400 and Ro 31-6930 were 11-42 times less potent in relaxing contractions to ET-1 than KCl. In contrast, this differential potency was not observed with RP-49356 or pinacidil. 3. BRL-38227 (0.06-3.0 microM), RP-49356 (0.3-3.0 microM) and pinacidil (0.3-3.0 microM) displaced KCl concentration-response curves to the right of controls, without modifying the maximum response. A subcontractile concentration of ET-1 (0.1 nM) prevented the inhibitory effects of low concentrations of BRL-38227 (0.06-0.1 microM) on KCl responses, but failed to modify those to RP-49356, pinacidil or high concentrations of BRL-38227 (0.3-3.0 microM). The inhibitory effects of BRL-38227 (0.1 microM) were also not changed by ET-3 (1.0 nM) or angiotensin II (0.1 nM). 4. In anaesthetized spontaneously hypertensive rats (SHR), cumulative bolus intravenous administrations of BRL-38227 (1-1000 micrograms kg-1, i.v.), Ro 31-6930 (1-1000 micrograms kg-1, i.v.), RP-49356 (10-1000 micrograms kg-1, i.v.) or nitrendipine (0.1-30 micrograms kg-1, i.v.) produced dose-dependent falls in diastolic blood pressure (DBP).ET-1 (i.v.) evoked a transient fall in DBP (1 pg kg- = 58 + 1 mmHg) which returnedto pre-administration levels within 4 min.5. Pretreatment of anaesthetized SHR with ET-l (1 pg kg-', i.v.) significantly increased the ED,5 (dose to evoke a 15% fall in DBP) values for BRL-38227 and Ro 31-6930. However, ET-l failed to modify the ED,5 values for RP-49356 or nitrendipine. The ED50 values for all of the vasodilators studied were not modified by ET-1.6. Infusion of BRL-38227 (2 pgkg-'min-', i.v.) or RP-49356 (4 pgkg-'min', i.v.) to anaesthetized SHR evoked dose-related falls in DBP, with a corresponding increase in descending aortic blood flow (DABF) and a decrease in total lower body vascular resistance (TLBVR). Pretreatment with ET-1 (1 ptg kg-', i.v.) significantly attenuated the decreases in DBP and TLBVR observed with low doses of BRL-38227, but not RP-49356 or high doses of BRL-38227. In contrast, ET-3 (3 pig kg-, i.v.) failed to modify the effects of BRL-38227 on DBP or TLBVR.7. In conscious SHR, the fall in DBP to BRL-38227 (30 pgkg-', p.o.) was significantly reduced following ET-1 (1 pig kg-', i.a.) treatment. ET-1 (1 pg kg-', i.a.) pretreatment, however, failed to modify the decrease in DBP induced by an equieffective oral dose of RP-49356 (1001pgkg-1).8. In conclusion, ET-1 selectively attenuated the vasorelaxant effects of the potassium channel opener,BRL-38227 and other substituted benzopyrans. The results are compatible with the hypothesis that benzopyran PCOs and ET-1 have affinity for a site that does not recognise RP-49356 or pinacidil. Thus,ET-l can differentiate between structurally unrelated potassium channel openers. The cardiovascular effects of some, but not all, PCOs might be radically modified in the clinical setting by elevated endogenous levels of ET-1 associated with certain diseased states.

Animals↗
PubMed1991

Effects of haloperidol on motor and cognitive functioning in aged mice.

The effects of haloperidol on motor and functioning and cognitive functioning were studied in young (3-5 months old) and aged (20-22 months old) male mice by examining haloperidol-induced catalepsy and haloperidol-induced decrements in performance on a radial arm maze. The aged mice were much more sensitive to these adverse effects of haloperidol than were the young mice. Studies of the distribution of radioactivity from [3H]haloperidol to the brain indicated that the differences in sensitivity to this drug were not due to pharmacokinetic differences. The results demonstrate that mice are suitable for studies of aging-induced changes in the behavioral effects of neuroleptic agents.

Aging↗
PubMed1991

SK&F 87516, a close analog of fenoldopam, is a partial agonist at dopamine-1 and alpha-2 receptors and produces stimulation of 5-hydroxytryptamine-2 receptors in the cardiovascular system of the rat.

In pentobarbital-anesthetized rats, SK&F 87516 (1.25-80 micrograms/kg/min intravenously over 15 min), the fluoro analog of the selective DA-1 dopamine receptor agonist fenoldopam produced dose-related decreases in carotid artery blood pressure that faded during the infusion period. These effects were abolished by SCH 23390, prolonged by ritanserin, but unchanged by bilateral vagotomy, atenolol, ICI 118,551, idazoxan, methylatropine or S-sulpiride. SK&F 87516 also inhibited the hypotensive effects of clonidine and of the DA-1 receptor agonist fenoldopam, but not of acetylcholine. In pithed rats, SK&F 87516 produced a biphasic vasopressor response. The initial phase was enhanced by SCH 23390 and converted to a transient hypotension by idazoxan. The secondary response was inhibited by ritanserin and enalapril. In pithed, but not in intact rats, SK&F 87516 increased plasma renin activity. In intact rats, SK&F 87516 produced dose-related bradycardic effects that were inhibited (50%) by idazoxan, methylatropine or bilateral vagotomy and abolished by chlorisondamine or pithing. In pithed rats pretreated with either saline or idazoxan, SK&F 87516 reduced the tachycardia to electrical stimulation of preganglionic more than that to postganglionic cardioaccelerator nerve fibers. However, it did not modify heart rate increases evoked by intravenous norepinephrine. In conclusion, SK&F 87516 produces hypotension via vascular DA-1 receptor stimulation. The fading of this effect during the infusion of SK&F 87516 may be related to the partial agonist property of this compound at DA-1 receptors and the stimulation of 5-hydroxytryptamine-2 receptors. SK&F 87516 also behaves as a partial agonist at alpha-2 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Effectiveness of chlorhexidine and sodium fluoride in reducing dentin hypersensitivity.

This investigation was conducted to evaluate the effect of chlorhexidine, sodium fluoride, and sequential rinses of chlorhexidine (Cx) and sodium fluoride (NaF) on dentin hypersensitivity. Forty-four adult patients with dentin hypersensitivity on three teeth were randomly assigned to receive one of four treatment rinses: (1) placebo; (2) 0.12% Cx; (3) 0.2% NaF; or (4) 0.12% Cx plus 0.2 NaF. Patients' responses to cold stimulation were recorded at baseline, two weeks, and four weeks. Pain response was quantified by applying successively decreasing temperature intervals of water (20 degrees C, 15 degrees C, 10 degrees C, 5 degrees C, and 0 degrees C) to exposed dentin. Plaque Index (Silness and Löe) was recorded at baseline only. Data on dentin sensitivity over time were analyzed using a repeated measures ANOVA. This ANOVA was conducted to generate an error term for calculation of Dunn's multiple mean comparison test. A Spearman rank order test was computed to assess correlation between plaque and hypersensitivity at baseline. Results showed the Cx and NaF rinses alone significantly reduced hypersensitivity (p less than .01) at four weeks compared to baseline. Sequential Cx and NaF rinses significantly decreased sensitivity (p less than .01) at both the two- and four-week intervals compared to baseline. At the four-week interval, the sequential Cx/NaF rinse group showed a significantly greater reduction (p less than .01) in hypersensitivity response when compared to placebo. Cx alone, or NaF alone groups. A moderate, positive correlation (r = 0.55) was demonstrated between plaque and dentin hypersensitivity. This was statistically significant at the (p less than .05) level.

Adult↗
PubMed1989

(-)-Bay K 8644 liberates a contractant factor from the endothelium of the rat aorta.

The contractile activity of (-)-Bay k 8644 was assessed in rat isolated aortic ring preparations bathed in a potassium-free medium. (-)-Bay k 8644 (0.01-3 microM) caused extracellular calcium-dependent contractile responses, which were significantly greater in tissues with, than deprived of a functional endothelium. In preparations with an endothelium, the contraction was attenuated by quinacrine (1 microM), indomethacin (10 microM) and diclofenac (0.1 microM), but not changed by nordihydroguaiaretic acid (30 microM) or dazoxiben (10 microM). Thus, in the rat aorta bathed in K(+)-free medium, (-)-Bay k 8644 can cause contractile effects, apparently due to the release of an endothelium-derived contractant factor (EDCF) which is proposed to be a cyclo-oxygenase product.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Effects of Ca2+ antagonists and K+-channel activators on K+-induced contractions in the rat aorta.

1. In the rat aortic ring with endothelium, suspended in a K+-free salt solution containing 1.25 mM Ca2+, the concentration-response curve to K+ (2-50 mM) was characterized by an initial small contractile phase occurring at 2-5 mM (Emax 1 = 0.67 +/- 0.18 g, n = 9) followed by a plateau (4-8 mM) and then a secondary contractile response (Emax2 = 1.64 +/- 0.13 g). 2. (-)-Bay k 8644 (0.01-0.3 microM) increased greatly the maximum of the first and only slightly that of the second contractile phase to K+. 3. In preparations treated with 0.3 microM (-)-Bay k 8644, only the contractile responses to low concentrations of K+ were inhibited by RP 49356 (0.1-1.0 microM), cromakalim (0.1-1.0 microM), nicorandil (1-10 microM), minoxidil sulphate (10 microM) or HA 1004 (1 microM). 4. In contrast, nitrendipine (0.01-0.1 microM) and diltiazem (1.0 microM) inhibited contractile responses to all concentrations of K+, whereas bucindolol (3 microM), dihydralazine (100 microM) and cinnarizine (1.0 microM) depressed only the second phase of the K+ concentration-response curve. 5. These results indicate that the enhancement by (-)-Bay k 8644 of the contractile response to low K+ (2-10 mM) is possibly due to activation of voltage-operated calcium channels (VOCs). The inhibition by purported K+ channel activators (cromakalim, RP 49356, nicorandil, minoxidil sulphate) of these contractions is compatible with membrane hyperpolarization mediated by an increase in outward K+ current. This mechanism would lead to VOC closure and therefore a fall in free cytosolic Ca2+. 6. Thus, the determination of the effects of myorelaxant agents on the concentration-response curve to K+ in the presence of (-)-Bay k 8644, is a novel and simple functional approach to the discrimination quantitatively and qualitatively of activators of K+ channels from other classes of compounds (such as calcium entry blockers) or vasodilators with an as yet undetermined cellular mechanism (e.g. bucindolol).

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Contractile responses to calcium chloride in rat aortic rings bathed in K+-free solution are resistant to organic calcium antagonists.

1. In rat aortic rings, devoid of functional endothelium, suspended in a modified Krebs solution (KCl: 0 mM; CaCl2: 0.63 mM), addition of CaCl2 (0.89-10 mM) produced concentration-related increases in tension (Emax = 2.38 +/- 0.10 g, EC50 = 2.31 +/- 0.15 mM, n = 36). 2. The Ca2+ evoked contractile responses were not modified by cinnarizine (10 microM), diltiazem (1 microM), ryanodine (10 microM), verapamil (1 microM), or the dihydropyridines, nitrendipine (1 microM) and (-)-Bay K 8644 (0.003-0.3 microM). 3. Cobalt chloride (0.1-1 mM) competitively antagonized the Ca2+ concentration-response curve; the Schild plot (slope 1.08 +/- 0.04), gave a pA2 value of 3.3 +/- 0.01 (n = 27). Nickel chloride (0.5-1 mM) displaced the Ca2+ concentration-response curve to the right, without an effect on the maximum response. Cadmium chloride (3-30 microM) depressed the maxima of concentration-response curves to Ca2+ with an IC50 of 15.5 +/- 1.1 microM (n = 6). 4. Monochlorobenzamil (100 microM), a Na+-Ca2+ exchange inhibitor, failed to modify the Ca2+-induced contractions. 5. In conclusion, Ca2+ evoked concentration-related contractile responses of rat aortic rings bathed in a K+-free medium; these effects were attenuated by the divalent cations cobalt, nickel and cadmium, but not modified by several organic calcium antagonists. The lack of effect of diltiazem verapamil and the dihydropyridines would suggest that, under these experimental conditions, extracellular Ca2+ enters the cytosol via pathways which are distinct from the slow (L-type) calcium channels.

Animals↗
PubMed1989

Oral-dental concerns of the pediatric oncology patient.

One of the main concerns of all disciplines in health care today is maintaining the patient's quality of life and comfort during cancer therapy. Oral complications resulting from radiation or chemotherapy can be expected in a large percentage of patients. Conducting a dental evaluation and performing treatment before therapy can help prevent or lessen potential complications. With preventive care and fewer infections, the patient will be able to communicate with friends and family, and optimum care and comfort can be provided.

Antineoplastic Agents↗
PubMed1987

Cardiovascular characterization of DA-1 and DA-2 dopamine receptor agonists in anesthetized rats.

This report summarizes studies aimed to characterize pharmacologically, hemodynamically and biochemically DA-1 (fenoldopam) and DA-2 (quinpirole) dopamine receptor agonists in anesthetized rats. Fenoldopam (20 micrograms/kg/min i.v. over 15 min) and quinpirole (10 micrograms/kg/min i.v. over 15 min) share the common property of decreasing mean carotid artery blood pressure by lowering peripheral vascular resistance. Fenoldopam increased mesenteric and renal blood flows whereas quinpirole decreased the former blood flow, but enhanced the latter. These effects of quinpirole were antagonized selectively by S-sulpiride, but not SCH 23390; however, with fenoldopam the reverse was found. In chlorisondamine-pretreated rats with blood pressure supported by vasopressin, fenoldopam, but not quinpirole, caused hypotension. In nephrectomized rats, the blood pressure effects of fenoldopam (assessed as area under the infusion time-response curve) were more pronounced than in sham-operated controls. The hypotensive effects due to an i.v. bolus injection of fenoldopam, but not to acetylcholine, histamine, salbutamol or quinpirole, were significantly inhibited in rats pretreated with an infusion of fenoldopam. In pithed rats, quinpirole reduced the pressor responses to electrical stimulation of the spinal cord without affecting those to exogenous norepinephrine, angiotensin II or 5-hydroxytryptamine which, on the contrary, were inhibited by fenoldopam. The plasma renin activity (in intact rats) was reduced by quinpirole, but elevated by fenoldopam. The latter effect also occurred in pithed rats and was blocked by SCH 23390. Quinpirole lowered heart rate, whilst fenoldopam produced tachycardia. These effects of quinpirole and fenoldopam were significantly inhibited by S-sulpiride and SCH 23390, respectively. In chlorisondamine-pretreated rats quinpirole failed to change heart rate whereas fenoldopam still increased it. In conclusion, these results indicate that DA-1 and DA-2 dopamine receptor agonists can be easily discriminated on the basis of their cardiovascular profiles.

Anesthesia↗