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Biomedical subjects

G S Allen

Publications and source records attributed to G S Allen.

At least 55 records · Page 3Linked to original sources
PubMed1984

The calcium antagonist properties of cyproheptadine: implications for antimigraine action.

Cyproheptadine is equipotent (IC50 = 41 to 45 nM) in blocking contractions of canine basilar artery segments induced by serotonin, norepinephrine, potassium, or calcium. Methysergide and amitriptyline display variable potencies in inhibiting contractions depending on the initiating agent. Propranolol, at concentrations to 10 micromolar, had minimal effect on vessel contractions. We conclude that the primary action of cyproheptadine in preventing induced contractions of the canine basilar artery is antagonism of calcium channels. This action is unique among drugs used for migraine prophylaxis and may have important implications for the treatment of headache and other neurologic disorders.

Animals↗
PubMed1983

Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage.

We enrolled 125 neurologically normal patients with intracranial aneurysms in a multi-institution, prospective, double-blind, randomized, placebo-controlled trial within 96 hours of their subarachnoid hemorrhage, to determine whether treatment with the calcium blocker nimodipine would prevent or reduce the severity of ischemic neurologic deficits from arterial spasm. A deficit from cerebral arterial spasm that persisted and was severe or caused death by the end of the 21-day treatment period occurred in 8 of 60 patients given placebo and in 1 of 56 given nimodipine (P = 0.03, Fisher's exact test). Analysis of the amount of basal subarachnoid blood on pre-entry CAT scans in patients with deficits from spasm showed that an increase in subarachnoid blood was not associated with a worse neurologic outcome among patients who received nimodipine, unlike the situation in patients given a placebo. There were no side effects from nimodipine. We conclude that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm.

Adolescent↗
PubMed1983

Serotonin-induced contraction of canine basilar artery: mediation by 5-HT1 receptors.

Serotonin and related agonists cause a marked contraction of canine basilar artery segments. These contractions can be inhibited by a variety of serotonergic antagonists. Absolute potencies of both serotonin agonists and antagonists in chamber contraction studies significantly correlate (P less than 0.01) with their potencies for 5-HT1, but not 5-HT2, receptors as defined by central nervous system radioligand binding studies. Serotonin-induced contractions of canine basilar artery segments appear to be mediated by 5-HT1 receptors.

Animals↗
PubMed1983

Calcium channel antagonist binding sites labeled by 3H-nimodipine in human brain.

In vitro binding of 3H-nimodipine to human brain membranes is demonstrated in this study. This binding was specific and saturable, and had an apparent affinity constant (KD) of 0.27 nM. The maximal number of binding sites for 3H-nimodipine was 5.8 pmoles/gm wet weight of human frontal cortex. The binding was shown to be dependent on calcium, with half-maximal stimulation obtained at 3 X 10(-5) M CaCl2. Other 1,4-dihyropyridine calcium antagonists were shown to be competitive antagonists of 3H-nimodipine binding. In contrast, the calcium antagonists, verapamil and diltiazem, had complex interactions with 3H-nimodipine binding. These results represent the first identification of 3H-calcium antagonist binding sites in human brain, and they confirm that various calcium antagonist drugs may differ with respect to both their potency and their molecular site of action.

Binding Sites↗
PubMed1981

Microsurgical endarterectomy of the intracranial vertebral artery for vertebrobasilar transient ischemic attacks.

Two patients who had typical vertebrobasilar transient ischemic attacks (TIAs) that were refractory to anticoagulation with dicumarol and to antiplatelet therapy with aspirin and/or dipyridamole are described. Angiography revealed in both patients a stenotic atherosclerotic plaque of the intracranial vertebral artery between the posterior and anterior inferior cerebellar arteries. At operation, the first patient had an atherosclerotic plaque extending into the basilar artery, and no endarterectomy was attempted. The second patient had a 1-cm localized plaque that was removed successfully from the vertebral artery. Neither patient sustained a neurological deficit as a result of the operation. The patient whose plaque was not removed at operation continues to have vertebrobasilar TIAs and suffered a brain stroke 2 weeks after operation. The patient whose plaque was removed at operation continues to be free of TIAs 8 months later, and angiography performed 3 months after operation showed a widely patent vertebral artery. A portion of the intracranial vertebral artery has now been shown to be accessible to endarterectomy using the operating microscope. Angiography is helpful in determining this accessibility preoperatively.

Aged↗
PubMed1979

Cerebral arterial spasm: part 9. In vitro effects of nifedipine on serotonin-, phenylephrine-, and potassium-induced contractions of canine basilar and femoral arteries.

We performed in vitro experiments with a small volume chamber to determine the inhibitory effect of nifedipine on serotonin-, phenylephrine-, and potassium-induced contractions of canine basilar and femoral arteries. Nifedipine, an inhibitor of the influx of extracellular calcium into smooth muscle cells, was found to be a sensitive inhibitor of contractions of the basilar artery induced by all three agents. In contrast, nifedipine did not significantly inhibit the serotonin- and phenylephrine-induced contractions of the femoral artery but did inhibit potassium-induced contractions of the femoral artery. Calcium-induced contractions of the basilar artery were also inhibited by nifedipine. These experiments demonstrate a relatively selective effect of nifedipine on the basilar artery, and a mechanism to explain this selective effect is postulated.

Animals↗
PubMed1979

Cerebral arterial spasm: part 10. Reversal of acute and chronic spasm in dogs with orally administered nifedipine.

In vivo experiments in dogs demonstrated angiographically that the subarachnoid injection of blood produced cerebral arterial apasm both immediately after the injection of blood and 2 days later. The sublingual adminstration of nifedipine reversed both the acute and the delayed cerebral arterial spasm. In addition, sublingual administration of nifedipine 20 minutes before the subarachnoid injection of blood prevented the acute spasm.

Acute Disease↗
PubMed1979

Sphenoidal pneumosinus dilatans with bilateral optic nerve meningiomas. Case report.

The authors report a case of bilateral progressive visual loss in a patient with a radiological diagnosis of sphenoidal pneumosinus dilatans. At craniotomy, bilaterally symmetrical meningiomas of the optic nerve sheaths were found at the intracranial optic foramina. Reported cases of sphenoidal pneumosinus dilatans as well as bilateral meningiomas of the optic nerve sheaths are reviewed. The possible mechanisms of visual loss in pneumosinus dilatans and the management of nerve sheath and planum sphenoidale meningiomas are discussed.

Adolescent↗
PubMed1976

Cerebral arterial spasm. Part 4: in vitro effects of temperature, serotonin analogues, large nonphysiological concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery.

In vitro experiments were performed using a small volume chamber to study serotonin-induced contractions of the canine basilar artery. Temperature was found to have a profound effect on the artery's response to serotonin. Raising the temperature to 40 degrees C (104 degrees F) increased the maximum response by 20% and lowering the temperature by 10 degrees C caused a 40% reduction in the maximum contraction. Cumulative log-dose response curves for analogues of serotonin demonstrated a high degree of specificity for the serotonin receptor and large nonphysiological concentrations of serotonin caused relaxation of the contracted artery. Extracellular calcium was shown to be an absolute requirement for serotonin-induced contractions. Extracellular magnesium, in contrast, was shown to inhibit serotonin-induced contractions.

Animals↗
PubMed1976

Cerebral arterial spasm. Part 5: in vitro contractile activity of vasoactive agents including human CSF on human basilar and anterior cerebral arteries.

In vitro experiments were performed with a small volume chamber to determine the contractile activity of various vasoactive agents on human basilar and anterior cerebral arteries. Cumulative log-dose response curves were obtained for most of the agents tested including serotonin and three different prostaglandins; many of these curves were found to be similar to curves previously obtained with canine cerebral arteries. It was concluded from these similarities that canine cerebral arteries are a good in vitro model for studying human cerebral arterial spasm. It was also demonstrated that human cerebrospinal fluid, collected up to 17 days after a subarachnoid hemorrhage from patients with clinical and angiographic evidence of cerebral arterial spasm, would cause large, dose-dependent contractions in human anterior cerebral arteries.

Adolescent↗
PubMed1976

Cerebral arterial spasm. Part 7: In vitro effects of alpha adrenergic agents on canine arteries from six anatomical sites and six blocking agents on serotonin-induced contractions of the canine basilar artery.

In vitro experiments were performed using a small volume chamber to determine the contractile activity of several adrenergic agents on arteries from six locations of the canine vascular bed. Cumulative log-dose response curves were obtained for epinephrine, norepinephrine, phenylephrine and dopamine. It was found that the basilar and internal carotid arteries responded much less to these agents than did the mesenteric, renal and femoral arteries. Six blocking agents including nitroprusside were tested to determine their effect on the response of the canine basilar artery to log-dose additions of serotonin, prostaglandin F2alpha and KC1. Another chamber was developed to study the differential effect of nitroprusside and papaverine when placed on the luminal side versus the adventitial (cerebrospinal fluid) side of the basilar artery during a sustained contraction with serotonin. A theoretical treatment of cerebral arterial spasm following a subarachnoid hemorrhage is presented.

Adrenergic alpha-Agonists↗
PubMed1976

Cerebral arterial spasm. Part 8: The treatment of delayed cerebral arterial spasm in human beings.

Three patients who had neurological deficits from delayed cerebral arterial spasm following rupture of posterior communicating artery aneurysms were treated with continuous, simultaneous, intravenous injections of phenylephrine and nitroprusside. The results were determined by cerebral angiography before and after treatment. A dramatic increase in the cross-sectional area of the large cerebral arteries was found after treatment. The clinical implications of this treatment are discussed.

Adolescent↗
PubMed1975

Modulation by acetylcholine of adrenergic transmission in the rabbit ear artery.

1. Low concentrations of acetylcholine (4 times 10(-11) and 1 times 10(-10) M) increase the vasoconstrictor response of the isolated ear artery of the rabbit to stimulation of the periarterial sympathetic nerves. Higher concentrations (4 times 10(-8) M and greater) decrease the response. 2. Low concentrations of acetylcholine (1 times 10(-11) and 1 times 10(-10) M) increase the stimulation-induced efflux of radioactivity from artery segments previously incubated with [3H]-noradrenaline. Higher ocncentrations (3 times 10(-8) M and greater) decrease the efflux. 3. Neither atropine nor hexamethonium affects the facilitatory action of low concentrations of acetylcholine on adrenergic transmission in the rabbit ear artery. 4. Atropine antagonizes the inhibitory effect of higher concentrations of acetylcholine on adrenergic transmission.

Acetylcholine↗