A specialization for speech perception?
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Cognition↗
Biomedical subjects
S Greenberg
Publications and source records attributed to S Greenberg.
Celiprolol in systemic hypertension.
The safety and efficacy of orally administered celiprolol, a new beta 1-selective adrenergic blocking drug with peripheral beta 2-agonist properties, were assessed in 91 patients with mild to moderate systemic hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg without medication) using a placebo-controlled, double-blind, randomized, titration-to-effect study design. All patients received placebo for 4 weeks and were then randomized to receive placebo (n = 46) or once-daily celiprolol (n = 45), which was titrated every 2 weeks (200, 400, 600 mg/day) over a 6-week period to achieve a reduction in supine diastolic BP to less than or equal to 90 mm Hg. Plasma lipids and lipoproteins were also assessed at baseline, during placebo and after randomization to active therapy in a subgroup of patients. Compared with placebo, celiprolol reduced supine and standing BP (reduction of supine BP -0.4/-2.1 mm Hg with placebo, -5.7/-6.4 with celiprolol, p less than 0.05; reduction of standing BP -1.7/-1.0 with placebo, -7.2/-4.9 with celiprolol, p less than 0.05). Supine heart rate was reduced by 6.8 beats/min with celiprolol compared with 2.0 beats/min with placebo (p less than 0.05). No differences were seen when the effects of placebo and celiprolol on plasma lipoproteins were compared. Celiprolol is a safe, effective and well tolerated once-daily antihypertensive drug and has no detrimental effects on plasma lipids.
Antihypertensive Agents↗
The endothelium modulates adrenergic neurotransmission to canine pulmonary arteries and veins.
We tested the postulate that endothelium-derived relaxing factor (EDRF) modulates adrenergic neuroeffector transmission in isolated canine pulmonary arteries and veins, using the technique of superfusion and measurement of the efflux of [2-14C]NE during transmural nerve stimulation at 1, 2, 4, 8, 16 and 32 Hz for 10 and 30 min. In endothelium-rubbed artery and vein the contractile responses to low frequency nerve stimulation were enhanced, when compared to those from endothelium rubbed blood vessels. Transmural nerve stimulation of endothelium competent arteries and veins for 10 min released less [2-14C]NE than denuded arteries and veins, especially at 1, 2 and 4 Hz, with smaller differences evident at higher frequencies (16 and 32 Hz) of stimulation. Superfusion of endothelium rubbed blood vessels with effluent from canine thoracic aorta decreased the release of [2-14C]NE during nerve stimulation. These findings suggest that the endothelium and EDRF can inhibit release of adrenergic neurotransmitter from canine pulmonary arteries and veins. The endothelium may act as an endogenous modulator of adrenergic neurotransmission to canine vascular smooth muscle.
Acetylcholine↗
Pericardial effusion early in acute myocardial infarction.
The incidence and significance of pericardial effusions early in acute myocardial infarction remain unclear. Using two-dimensional echocardiography, 172 patients with an acute myocardial infarction were evaluated within 72 h of presentation. Thirty patients (17%) had a pericardial effusion (29 small, 1 moderate) while 142 (83%) did not. No patient developed cardiac tamponade or required pericardiocentesis. Patients with pericardial effusions had higher peak creatine kinase as compared to patients without effusions (2036 +/- 1466 vs. 1483 +/- 1241, p less than 0.05) and a greater number of aneurysms (20% vs. 6%, p less than 0.05). In-hospital mortality was higher in the patients with pericardial effusions (10% vs. 2%, p less than 0.05). In conclusion, pericardial effusions are common in the early AMI period but are generally small and hemodynamically insignificant. They are associated with larger infarcts and greater mortality.
Aged↗
Sustained high-dose nitroglycerin transcutaneous patch therapy in angina pectoris: evidence for attenuation of effect over time.
The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Cutaneous↗
Beta-adrenoceptor blocking activity of diprafenone in anesthetized dogs: comparison with propafenone and propranolol.
The effects of diprafenone, a new class Ic antiarrhythmic agent, on canine hemodynamics and cardiac membrane beta-receptor antagonist binding activity, were compared with those of propafenone and propranolol. Mongrel dogs (4-5/group) were anesthetized intravenously (i.v.) with pentobarbital sodium (35 mg/kg) and instrumented for measurement of aortic and coronary blood flows (AF, CBF), blood pressure (BP), and heart rate (HR). Isoproterenol (ISO) was administered as bolus injections before (0.01, 0.03, and 0.1 micrograms/kg, i.v.) and after (0.01-3 micrograms/kg, i.v.) infusions of diprafenone or propafenone (0.3, 1, and 3 mg/kg) or propranolol (0.03, 0.1, and 0.3 mg/kg, i.v.). The ability of the antiarrhythmic agents to displace [3H]dihydroalprenolol (DHA) binding from isolated cardiac ventricular membranes in vitro was also evaluated. Each antiarrhythmic agent blocked the HR and BP responses to ISO in a competitive manner and decreased the specific binding of DHA to cardiac ventricular membranes. Propranolol was 2 to 7 times more potent as a beta-receptor blocking agent than diprafenone, which was 6 times more potent than propafenone. The equilibrium dissociation constants (Ki) for displacement of DHA by propranolol, diprafenone, and propafenone were 2.7, 14.3, and 252 nM, respectively, and have the same rank order of potency for in vivo inhibition of BP and HR responses to ISO. Diprafenone has significant beta-adrenoceptor blocking activity which may contribute to its efficacy as an antiarrhythmic agent and allow its use in treatment of arrhythmias refractory to therapy with class I and class II agents alone.
Adrenergic beta-Antagonists↗
Synthesis and photocytotoxicity of some new substituted phthalocyanines.
Some new, ring-substituted phthalocyanines have been synthesized and underwent preliminary testing for photodynamic activity using the colony forming ability of Chinese hamster cells in culture as an endpoint. Using 4-(3-N,N-diethylaminopropyl)phthalonitrile as a precursor, the previously unknown metal-free 2,9,16,23-tetra-(3-N,N-diethylaminopropyl)phthalocyanine was prepared and converted to its zinc (II) and its cationic water-soluble 2,9,16,23-tetramethylammonium zinc (II) iodide derivatives. Other new phthalocyanine derivatives tested, include a 2,9,16,23-tetra(2-hydroxymethyl-2-methylbutoxy)phthalocyaninato zinc (II) and 2,3,9,10,16,17,23,24-octahydroxyphthalocyaninato zinc (II) derivatives. Boron tribromide cleavage of the newly prepared and fully characterized 2,3,9,10,16,17,23,24-octamethoxyphthalocyanine gave the unstable metal-free octahydroxyphthalocyanine, which could only be characterized by ultraviolet-visible, NMR and IR spectroscopy.
Animals↗
Pediatric cochlear implantation: strategies to accommodate for head growth.
Accommodation for head growth presents one of several challenges unique to pediatric cochlear implantation. Given contemporary cochlear implant device designs, an electrode cable implanted at the age of 2 years must extend 2 to 3 cm as the head grows during childhood. In an initial study we found that model lead wires with redundant loops extended effectively when they were maintained within air-containing spaces such as the mastoid cavity or middle ear space. However, when looped leads traversed soft tissues overlying the parietal bone, they became embedded in fibrous tissue and did not extend. The present study evaluated three different configurations of expansile devices that were enclosed in polytetrafluoroethylene (PTFE) envelopes to deter fibrous ingrowth. This simple strategy was designed to ensure effective cable extension over cable pathlengths by protecting the redundant leads from any mechanically significant connective tissue ingrowth. Twelve such devices were implanted across the calvaria of four newly weaned piglets. Skull growth and changes in electrode dimensions were documented by sequential computed tomographic scans. At 3 months of age, cranial circumferences had increased substantially. Animals were then killed, the model cable extension appliances examined physically, and their implantation sites examined histologically. For all experimental devices, extension of redundant lead wires was satisfactory, and there was no mechanically significant invasion of fibrous connective tissue into the PTFE envelope. This indicates that enclosure of excess lead wire within a PTFE envelope may be an effective means of inhibiting fibrous ingrowth. This strategy should prove useful for ensuring effective electrode cable extension in cochlear implants applied in young children.
Animals↗
Effects of insulin-like growth factors I and II on growth and differentiation of transplanted rat embryos and fetal tissues.
The objective of our study was to obtain comparative information on the roles of insulin-like growth factors (IGFs) I and II in the growth and differentiation of rat embryos and fetuses in an in vivo experimental system. Ten-day-old rat embryos or 16-day-old fetal rat paws were transplanted under the capsule of both kidneys of syngeneic hosts, where they grew rapidly, and tissue differentiation occurred in an essentially normal manner. Infusion of a rabbit antiserum to human (h) IGF-I for 6 days into the renal artery of one kidney caused only a slight inhibition (approximately 20%) of growth of transplanted embryos on that kidney. However, 9 days of treatment with the antiserum caused highly significant growth retardation of transplanted embryos by 40-45%. Exposure of fetal paws to the same antiserum for 9 days inhibited their growth by 27%. Infusion of synthetic hIGF-II or partially purified rat IGF-II [(MSA)multiplication-stimulating activity], for 6 days stimulated the growth of embryo transplants directly, and MSA was more effective than hIGF-II. By contrast, infusion of purified natural hIGF-I did not promote their growth. Growth of fetal paw transplants in hypophysectomized (HX) hosts was reduced by 70% compared to that in intact hosts. In the HX hosts infusion of the MSA was more effective than the hIGF-I at promoting the growth of paw transplants. Both MSA and IGF-I promoted ossification in the fetal paws in the HX hosts. These results suggest that both IGFs could be involved in regulating the growth and differentiation in prenatal rats, and IGF-II may be the more effective of the two factors as a growth-promoting agent in utero.
Animals↗
Adverse reactions to diphtheria, tetanus, pertussis-polio vaccination at 18 months of age: effect of injection site and needle length.
Adverse reactions after diphtheria, pertussis, tetanus, polio vaccination at 18 months of age were investigated in three groups: 74 children injected in the deltoid muscle with a 16-mm (5/8-in) needle, 64 in the anterolateral thigh with a 16-mm needle, and 67 in the anterolateral thigh with a 25-mm (1-in) needle. No significant differences in systemic reactions were observed. Severe pain occurred in 30.5% of the groups injected in the thigh compared with only 8.1% of the group injected in the arm (P less than .001). Children vaccinated in the thigh had decreased movement of the extremity significantly more often than those injected in the arm (49.9% v 25.6%, P less than .0005), and two thirds of the former limped for 24 to 48 hours. Redness and swelling were observed more often after injection in the arm than in the thigh (58.1% v 26.7%, P less than .0005). The only effect of changing needle length in the groups injected in the thigh was the occurrence of more redness and swelling in children vaccinated with the 16-mm needle compared with the 25-mm needle. Overall, parents rated more reactions as moderate to severe among children injected in the thigh than among children injected in the arm (64.2% v 37.9%, P less than .001). The deltoid muscle appears to be the preferred site for administration of diphtheria, pertussis, tetanus, polio vaccine at 18 months of age.
Arm↗
Extracellular nucleotides mediate Ca2+ fluxes in J774 macrophages by two distinct mechanisms.
We have studied the effects of extracellular nucleotides on the cytosolic free calcium concentration [( Ca2+]i) in J774 macrophages using quin2 and indo-1 as indicator dyes. Micromolar quantities of ATP induced a biphasic increase in [Ca2+]i: a rapid and transient increase (peak I) which was due to mobilization of Ca2+ from intracellular stores and a second more sustained elevation (peak II) due to influx of extracellular Ca2+. The sustained peak II elevation had two components, a "low threshold" (1 microM ATP) response which saturated at 10-50 microM ATP and a "high threshold" response, apparent at [ATP] greater than 100 microM. The latter component was not seen with nucleotides other than ATP and correlated with an ATP-induced generalized increase in plasma membrane permeability. A variant J774 cell line was isolated which does not demonstrate this ATP-induced increase in plasma membrane permeability; nevertheless, it demonstrated both the release of Ca2+ from intracellular stores and the low threshold component of the Ca2+ influx across the plasma membrane in response to nucleoside di- and triphosphates. Several lines of evidence indicate that the fully ionized (i.e. free acid) forms of nucleoside di- and triphosphates were the ligands that mediated these increases in [Ca2+]i. These data show that extracellular nucleotides mediate Ca2+ fluxes by two distinct mechanisms in J774 cells. In one, the rise in [Ca2+]i is due to release of Ca2+ from intracellular stores and Ca2+ influx across the plasma membrane. This response is elicited preferentially by the free acid forms of purine and pyrimidine nucleoside di- and triphosphates. In the other, the rise in [Ca2+]i reflects a more generalized increase in plasma membrane permeability and is elicited by ATP4- only.
Adenosine Triphosphate↗
Serotonergic blockade compared with beta-adrenergic blockade in systemic hypertension: a double-blind comparison of ketanserin with propranolol.
The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin (-7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension.
Adrenergic beta-Antagonists↗
Substituted phthalocyanines as photodynamic sensitizers.
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Animals↗
A comparison of lexical-semantic impairments in left hemisphere stroke and Alzheimer's disease.
Patients with aphasia due to left hemisphere stroke and patients with Alzheimer's disease, who were matched for severity of naming impairment, were compared on tests of lexical-semantic processing. The results suggest that the lexical-semantic impairments in both groups are due to a combination of impaired access to, and loss of, lexical-semantic information, but that impaired access is more prominent in stroke patients, whereas Alzheimer's disease patients suffer a greater loss of information. The results are discussed in terms of a brain model of the storage and processing of lexical-semantic information, and with respect to implications for treatment strategies.
Aged↗
Calcium channel blockers in systemic hypertension.
Alterations in transmembrane flux of calcium ions may be playing a role in the pathophysiology of systemic hypertension. Calcium channel blockers have been shown to be effective antihypertensive drugs with excellent safety profiles. They are efficacious in the long term treatment of systemic hypertension in all population subgroups, and have special applicability for treating patients with hypertensive urgencies and individuals with concomitant diseases such as angina pectoris and arrhythmias.
Animals↗
Fc receptor-mediated phagocytosis occurs in macrophages at exceedingly low cytosolic Ca2+ levels.
Cytosolic free Ca2+ ([Ca2+]i) homeostasis was investigated in mouse peritoneal macrophages and in the macrophage-like cell line J774. [Ca2+]i measurements were performed in both cells in suspension and cells in monolayers loaded with either quin2 or fura-2. Resting [Ca2+]i was 110-140 and 85-120 nM for cell suspensions and monolayers, respectively. There were no significant differences in [Ca2+]i between the two macrophage populations whether quin2 or fura-2 were used as Ca2+ indicators. Addition of heat-aggregated IgG, IgG-coated erythrocyte ghosts, or a rat monoclonal antibody (2.4G2) directed against mouse Fc receptor II induced a rise in [Ca2+]i. This [Ca2+]i increase was consistently observed in J774 and peritoneal macrophage suspensions and in J774 macrophage monolayers; in contrast it was observed inconsistently in peritoneal macrophages in monolayer cultures. The increase in [Ca2+]i induced by ligation of Fc receptors was inhibited totally in macrophages in suspension and by 80% in macrophages in monolayers by a short preincubation of macrophages with PMA; however, phagocytosis itself was unaffected. The effect of reducing cytosolic Ca2+ to very low concentrations on Fc receptor-mediated phagocytosis was also investigated. By incubating macrophages with high concentrations of quin2/AM in the absence of extracellular Ca2+, or by loading EGTA into the cytoplasm, the [Ca2+]i was buffered and clamped to 1-10 nM. Despite this, the phagocytosis of IgG-coated erythrocytes proceeded normally. These observations confirm the report of Young et al. (Young, J. D., S. S. Ko, and Z. A. Cohn. 1984. Proc. Natl. Acad. Sci. USA. 81:5430-5434) that ligation of Fc receptors causes Ca2+ mobilization in macrophages. However, these results confirm and extend the findings of McNeil et al. (McNeil, P. L., J. A. Swanson, S. D. Wright, S. C. Silverstein, and D. L. Taylor. 1986. J. Cell Biol. 102:1586-1592) that a rise in [Ca2+]i is not required for Fc receptor-mediated phagocytosis; and they provide direct evidence that Fc receptor-mediated phagocytosis occurs normally even at exceedingly low [Ca2+]i.
Animals↗
[Specific IgE for Schistosoma mansoni in Ethiopian immigrants].
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Adolescent↗
Trigeminal origin of beta-preprotachykinin products in feline pial blood vessels.
A specific and sensitive radioimmunoassay measured the presence of immunoreactive neurokinin A within feline and human pial arteries. Immunoreactivity exhibited a retention time identical to that of synthetic peptide when acid extracts from feline and human blood vessels were subjected to reverse-phase high-performance liquid chromatography. As shown previously for substance P, levels of immunoreactive neurokinin A decreased significantly in the vessels from the ipsilateral rostral circle of Willis 19-24 days following unilateral trigeminal ganglionectomy. Hence, trigeminal projections to cerebral blood vessels contain both products of beta-preprotachykinin mRNA.
Animals↗