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Biomedical subjects

B Alexander

Publications and source records attributed to B Alexander.

At least 109 records · Page 6Linked to original sources
PubMed1991

Nitric oxide is the mediator of ATP-induced dilatation of the rabbit hepatic arterial vascular bed.

1. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs-Bülbring buffer via the hepatic artery (HA) and portal vein (PV) at constant flows of 23 +/- 1 and 77 +/- 1 ml min-1 100 g-1 respectively. The tone of the preparation was raised with noradrenaline (concentration: 10 microM). 2. Dose-response curves for the vasodilatation produced by adenosine 5'-triphosphate (ATP), acetylcholine (ACh), adenosine, and sodium nitroprusside (SNP) were obtained following injection into the HA supply. Injections were then repeated in the presence of the L-arginine to nitric oxide pathway inhibitors N-monomethyl-L-arginine (L-NMMA, n = 6) and N-nitro-L-arginine methyl ester (L-NAME, n = 4) at concentrations of 30 microM and 100 microM for each inhibitor. 3. Both L-NMMA and L-NAME antagonized the responses to ATP and ACh; L-NAME was 2-3 times more potent than L-NMMA as an inhibitor of these endothelium-dependent vasodilatations. Neither L-NMMA nor L-NAME attenuated responses of the endothelium-independent vasodilators, adenosine and SNP. 4. These results indicate that nitric oxide is the mediator of ATP-induced vasodilatation in the HA vascular bed of the rabbit and that the receptor responsible for the release of nitric oxide, the P2y-purinoceptor, is located predominantly on the endothelium.

Acetylcholine↗
PubMed1991

Adenosine-induced dilatation of the rabbit hepatic arterial bed is mediated by A2-purinoceptors.

1. This study was carried out in order to identify the receptor responsible for adenosine-induced dilatation of the hepatic arterial vascular bed. 2. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs-Bülbring buffer via the hepatic artery and the portal vein at constant flows of 26 and 77 ml min-1 100 g-1 liver respectively. The tone of the preparation was raised by the presence of noradrenaline in the perfusate (concentration: 10(-5) M). 3. Dose-response curves for adenosine and its analogues 5'-N-ethyl-carboxamido-adenosine (NECA), the 2-substituted NECA analogue CGS 21680C, and R- and S-N6-phenyl-isopropyl-adenosine (R- and S-PIA) were obtained after their injection into the hepatic arterial supply. 4. The order of vasodilator potency of these agents was: NECA greater than CGS 21680C greater than adenosine greater than R-PIA greater than S-PIA. Their potency, expressed relative to that of adenosine, was in the approximate ratio 10:3:1:0.3:0.1, consistent with that resulting from activation of P1-purinoceptors of the A2 sub-type (which mediate vasodilatation due to adenosine). 5. The P1-purinoceptor antagonist 8-phenyltheophylline (10(-5) M) caused significant attenuation of the vasodilatation to adenosine and analogues. 6. It is concluded that adenosine-induced dilatation of the hepatic arterial vascular bed is mediated by P1-purinoceptors of the A2 sub-type.

Acetylcholine↗
PubMed1991

Characterization of P2X- and P2Y-purinoceptors in the rabbit hepatic arterial vasculature.

1. Responses to adenosine 5'-triphosphate (ATP) and its agonists were studied in the isolated liver of the rabbit dually perfused through the hepatic artery and the portal vein. 2. In the hepatic arterial vascular bed at basal tone, ATP and its agonists elicited vasoconstrictor responses with the rank order of potency alpha,beta-methylene ATP greater than 2-methylthio ATP greater than ATP, consistent with their action at the P2X-purinoceptor. 3. When tone was raised with noradrenaline (10(-5) M), vasodilator responses were produced with ATP and 2-methylthio ATP; alpha,beta-methylene ATP produced only further constriction. The rank order of vasodilator potency was 2-methylthio ATP greater than ATP much greater than alpha,beta-methylene ATP, consistent with their action at the P2Y-purinoceptor. 4. Methylene blue (10(-5) M) antagonized vasodilator responses to acetylcholine and ATP, but not those to adenosine or sodium nitroprusside. Addition of 8-phenyltheophylline (10(-5) M) antagonized responses to adenosine but not those to sodium nitroprusside. Responses to ATP remaining after antagonism with methylene blue were not further antagonized by 8-phenyltheophylline. 5. These results present evidence for discrete P2X- and P2Y-purinoceptors in the rabbit hepatic arterial bed which mediate vasoconstrictor and vasodilator responses respectively. 6. Vasodilatation produced by ATP was entirely due to direct action at the P2Y-purinoceptor, and not at a P1-purinoceptor following breakdown to adenosine. The antagonism of these responses by methylene blue is consistent with the view that vasodilatation by ATP takes place largely via endothelial P2Y-purinoceptors that lead to release of endothelium-derived relaxing factor. However, we cannot exclude the possibility that P2y-purinoceptors located on the vascular smooth muscle play a contributory role in ATP-induced vasodilatation.

Acetylcholine↗
PubMed1991

NG-nitro-L-arginine methyl ester attenuates vasodilator responses to acetylcholine but enhances those to sodium nitroprusside.

The effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the synthesis of the endothelium-derived relaxing factor nitric oxide, were studied in two isolated perfused vascular beds: the rat mesenteric arterial bed and the hepatic arterial bed of the rabbit liver. The tone of both preparations was raised with noradrenaline (10 and 30 microM for rabbit and rat preparations, respectively). In both preparations, L-NAME (30 microM) significantly attenuated vasodilator responses to the endothelium-dependent vasodilator acetylcholine, but enhanced responses to sodium nitroprusside (a direct smooth muscle dilator). The evidence supports the view, previously established from work carried out in isolated vessels, that in addition to acting as an inhibitor of nitric oxide, L-NAME enhances the responsiveness of smooth muscle to direct relaxation by nitrovasodilators.

Acetylcholine↗
PubMed1991

Possible neuroendocrine actions of endothelin-3.

The presence of endothelin (ET) immunoreactivity and binding sites in hypothalamus and pituitary gland suggests potential neuroendocrine actions of this family of vasoactive peptides. ET-3, the predominant member of the ET family in brain, exerted significant dose-related (1, 10, and 100 nM) inhibitory effects on PRL release from dispersed anterior pituitary cells in static incubations. The effect was not dependent on voltage-sensitive calcium channels, since the dihydropyridine calcium channel antagonist nifedipine failed to block this action. Nifedipine did, however, significantly reduce the transient acute stimulatory effect of ET-3 on PRL release in cultured cells incubated in dynamic perifusion. The longer lasting inhibitory effect on PRL release that followed the brief stimulatory action was not affected by nifedipine. ET-3 also stimulated a transient but significant release of LH from cells harvested from random cycle female rats, an effect that was not antagonized by a LHRH antagonist, but was blocked by nifedipine, suggesting the mobilization of extracellular calcium as a mechanism of action of ET-3. Nifedipine also reversed the acute stimulatory effect of ET-3 on GH secretion from these cells. Cerebroventricular injections of ET-3 (6 or 60 ng) failed to significantly alter PRL or LH secretion in conscious rats, suggesting that brain-derived ET does not act within the hypothalamus to alter the release of these two hormones. Similarly, iv infusion of even pressor doses of ET-3 (10, 30, or 300 ng) failed to significantly alter PRL, LH, or GH release; thus, it is unlikely that ET of peripheral origin acts within the gland. Our results suggest that locally produced ET may act as a neuroendocrine or paracrine factor controlling pituitary function in the rat.

Animals↗
PubMed1991

Alcohol abuse in adolescents.

Alcohol abuse among teenagers is an increasing problem with serious physical and social consequences. Early diagnosis of adolescent alcoholism may be delayed for two reasons: the physical indicators of alcohol abuse seen in adults are often not identifiable in teenagers, and alcoholism is generally believed to be an adult problem. If the history is taken carefully, with respect and confidentiality, it can help the family physician determine the extent of a young person's alcohol abuse and begin the process of treatment for both the adolescent patient and the family.

Adolescent↗
PubMed1991

Adolescent sexuality issues in office practice.

Sexuality is an important aspect of development during adolescence. A knowledge of the sexual issues relevant to each stage of adolescence will help the physician address sexual issues with adolescent patients. The ability to identify and communicate with adolescents who may be at high risk of premature sexual activity is particularly important since sexual intercourse at an early age can have serious short- and long-term consequences. A nonjudgmental manner, an emphasis on confidentiality and an honest appraisal of the implications of early sexual activity will enhance discussions about sexual issues with adolescents.

Adolescent↗
PubMed1990

Numerical classification and identification of Bacillus sphaericus including some strains pathogenic for mosquito larvae.

Ninety-one strains of Bacillus sphaericus, including representatives of all the established DNA homology groups, related round-spored and oval-spored species, and six strains pathogenic for mosquito larvae, were examined for 155 characters. Numerical analyses (Jaccard coefficient/average linkage clustering) based on the 88 variable features revealed 14 clusters at the 79% similarity level that contained more than one strain and 17 single member clusters. All insect pathogenic strains were recovered in a single cluster and the classification was in accord with an established classification based on DNA sequence homology. Two frequency matrices for probabilistic identification were constructed and tested. A comprehensive matrix comprising 14 mesophilic, round-spored taxa and 27 tests gave good results for identification of hypothetical median organisms, cluster overlap and identifications of representative strains (based on data generated in the classification study). Reference strains for the 14 taxa and eight additional insect pathogenic strains were examined for the 27 tests and were correctly identified with high scores using this matrix. A second matrix comprising seven taxa and 13 tests also performed well in the theoretical evaluation and correctly identified the reference strains and insect pathogenic strains.

Animals↗
PubMed1990

The role of adenosine in the hyperaemic response of the hepatic artery to portal vein occlusion (the 'buffer response').

1. Adenosine has been shown to be responsible for the hyperaemic response of the hepatic artery to portal vein occlusion (the hepatic arterial 'buffer response'). 2. The effect of adenosine receptor blockade and of adenosine uptake inhibition on the hepatic arterial response to portal vein occlusion was investigated in three groups of anaesthetized dogs. 3. Venous return and arterial blood pressure were maintained during periods of portal occlusion by establishing a side-to-side portacaval shunt. Hepatic artery and portal vein blood flows were measured with electromagnetic flowmeters. 4. Hepatic arterial infusions of 8-phenyltheophylline (500 micrograms kg-1 and 3-isobutyl-1-methylxanthine min-1) and 3-isobutyl-1-methylxanthine (75 micrograms kg-1 min-1), doses sufficient to block the vasodilator response of the hepatic artery to exogenously applied adenosine, reduced the magnitude of the 'buffer response' by 50% and 75%, respectively. 5. Intravenous infusion of dipyridamole (100 micrograms kg-1 min-1), a dose sufficient to potentiate the vasodilator response of the hepatic artery to exogenously applied adenosine, had little effect on the 'buffer response'. 6. It is concluded that adenosine is an important, but not the sole, agent responsible for the hepatic arterial 'buffer response'.

1-Methyl-3-isobutylxanthine↗
PubMed1990

A retrospective study of compliance with recommended hematologic monitoring of carbamazepine.

Early case reports of fatal hematologic effects associated with carbamazepine (CBZ) resulted in manufacturer recommendations for extensive laboratory monitoring. Several alternative monitoring protocols have been published, indicating disagreement with those recommendations. The manufacturer has removed specific monitoring guidelines allowing physicians to monitor CBZ during treatment based on their clinical judgment. This study was designed to determine the frequency of CBZ hematologic monitoring in one academic setting. Data on complete blood counts (CBCs) were retrospectively obtained and were compared with 1975-88 Physicians' Desk Reference recommendations for weekly CBCs during the first three months of treatment. Eighty-three patients were identified: 32 psychiatry, 37 neurology, and 14 from other clinics. Only one patient met guidelines for monitoring during the entire first three months of treatment. Comparisons between clinics demonstrated no statistically significant differences in monitoring rates. Prospective studies in academic and private practice settings are needed to provide more information on actual monitoring practices. Due to the removal of specific manufacturer recommendations, a standard approach is needed to establish consistent and adequate monitoring and to provide legal support to prescribers.

Adult↗
PubMed1990

A review of carbamazepine's hematologic reactions and monitoring recommendations.

Early case reports of fatal hematologic effects attributed to carbamazepine (CBZ) resulted in extensive monitoring recommendations by the manufacturer. The rarity of blood dyscrasias led many authors to question the manufacturer's guidelines. Thus the manufacturer removed specific monitoring guidelines, allowing physicians to monitor CBZ using their clinical judgment. This article reviews case reports and studies of CBZ's hematologic effects. Due to their rapid onset, daily laboratory checks would be necessary to monitor for aplastic anemia, agranulocytosis, and thrombocytopenia. These adverse effects are best monitored by informing patients and physicians to carefully watch for signs and symptoms. Leukopenia develops more slowly, occurring in approximately 12 percent of children and 7 percent of adults. Its onset is typically within the first three months of treatment, with patients at risk having a low or low-normal pretreatment white blood cell (WBC) count. Leukopenia often reverses, even if CBZ is continued. Based upon our review of the literature, we recommend monitoring of those high-risk patients during the first three months of treatment with the frequency being determined by results of each laboratory value. WBC counts less than 3000/mm3 or neutrophil counts below 1000/mm3 warrant a decrease in dose with frequent monitoring or CBZ discontinuation, if necessary.

Adult↗
PubMed1990

Therapy of affective disorders.

The key to the proper treatment of affective disorder is a correct diagnosis of the subtype of depressive illness. Thus, primary treatment recommendations include the TCAs for a depressive episode; ECT for a depressive episode with psychotic features; and MAOIs for dysthymic disorder and atypical depressive episodes. Nonresponding patients are treated with either lithium augmentation of TCA therapy, an MAOI, or ECT. Second-generation antidepressants are not usually indicated as initial treatments. They are recommended in situations in which their adverse-effect profiles offer significant advantages over TCAs in an individual patient. Second-generation antidepressants have not been extensively studied in patients who do not respond to TCAs. Maintenance antidepressant may be necessary to prevent recurrent depressive episodes. Lithium remains the mainstay of acute treatment of mania and for prophylaxis of subsequent affective episodes. In lithium-refractory or lithium-intolerant patients, carbamazepine is recommended. Valproic acid and verapamil have been useful, primarily in patients who do not respond to lithium and carbamazepine.

Antidepressive Agents, Tricyclic↗
PubMed1989

The relationship between clinical stage, natural killer activity and related immunological parameters in adenocarcinoma of the prostate.

Several immunological in vitro tests were performed on peripheral blood mononuclear cells of patients with adenocarcinoma of the prostate, stages A, B, C, D. The cytotoxicity of effector natural killer cells towards K-562 targets decreased with increasing disease spread, while their percentage was not significantly changed. The proportion of CD4 (helper/inducer) cells tended to fall with tumor advance, but the proportion of CD8 (suppressor/cytotoxic) cells remained almost constant. Secretion of interleukin-2 from peripheral blood mononuclear cells was diminished with disease progression. Pretreatment of a patient's lymphocytes with cimetidine (antagonist of H-2-bearing suppressor T cells) or indomethacin (inhibitor of prostaglandin synthesis) enhanced natural killer activity. Our data point to the existence of aberrant immune functions in early stages of carcinoma of the prostate and to aggravation of these immune abnormalities in advanced disease.

Adenocarcinoma↗
PubMed1989

The effect of propranolol on the hyperaemic response of the hepatic artery to portal venous occlusion in the dog.

1. It has been reported that activation of beta-adrenoceptors may be responsible for the hyperaemic response of the hepatic artery to portal venous blood flow reduction. 2. The effect of beta-adrenoceptor blockade on the hepatic arterial response to portal vein occlusion was investigated in 6 anaesthetized dogs. A side-to-side portacaval shunt was established to prevent loss of venous return and arterial blood pressure during periods of portal occlusion. Measurements of hepatic arterial and portal venous blood flows were made by use of electromagnetic flow probes. 3. Intravenous propranolol injection, at a dose sufficient to block the vasodilator effect of low doses of exogenous adrenaline, did not alter the magnitude of the hyperaemic response of the hepatic artery. Propranolol also produced no change in baseline portal venous pressure. 4. It is concluded that hepatic beta-adrenoceptors are unlikely to be involved in the arterial response to portal occlusion. The absence of any reduction in basal portal venous pressure by propranolol is of interest in view of the current application of the drug in the treatment of patients with portal hypertension.

Animals↗