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Biomedical subjects

R T Jackson

Publications and source records attributed to R T Jackson.

144 records · Page 8Linked to original sources
PubMedDate not supplied

Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine.

OBJECTIVE: Sumatriptan hemisulfate nasal spray may provide a useful therapeutic option for patients with migraine who find injectable medications inconvenient or uncomfortable and for patients whose migraine-associated nausea and vomiting preclude the use of oral medication. This study was the first US trial to evaluate the effects of sumatriptan nasal spray administered for multiple migraine attacks. DESIGN/INTERVENTIONS: Sumatriptan nasal spray (5, 10, or 20 mg) was administered via a 1-shot nasal applicator into either nostril for up to 3 migraine attacks occurring over 6 months in a randomized, double-blind, parallel-group, placebo-controlled study. SETTING: Fifty-six outpatient clinical centers in the United States. PATIENTS: A total of 1086 men and women diagnosed with migraine with or without aura per International Headache Society criteria. MAIN OUTCOME MEASURES: Percentage of patients with headache relief (moderate or severe predose pain reduced to mild or none); percentage of patients with no or mild (vs moderate or severe) clinical disability; percentage of patients with nausea, vomiting, photophobia, or phonophobia; adverse events; clinical laboratory test results. RESULTS: Across attacks, headache relief in the 20-, 10-, and 5-mg drug and placebo groups was experienced 120 minutes postdose by 60%, 54%, 44%, and 32% of patients, respectively (P<.05 for each sumatriptan nasal spray group vs placebo, for the 10-mg vs 5-mg drug group, and for the 20-mg vs 5-mg drug group). Two thirds of the 20-mg patients treating 3 attacks experienced relief at 2 hours postdose for at least 2 of 3 attacks. Clinical disability scores at 120 minutes in the 20-, 10-, and 5-mg drug and placebo groups reflected no or mild impairment in 70%, 67%, 57%, and 50% of patients, respectively (P<.05 for the 10- or 20-mg drug group vs placebo group, and for the 20-mg vs 5- mg drug group). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. For all parameters, individual-attack efficacy rates did not differ from across-attack rates. The incidence of adverse events was not dose related. The most frequently reported adverse event in the active treatment groups was taste disturbance (bad, bitter, or unpleasant). CONCLUSIONS: Sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) is effective and well tolerated in the treatment of multiple migraine attacks. The 20-mg dose was associated with the highest efficacy rates across the greatest number of parameters.

Administration, Intranasal↗
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Nasal-cardiopulmonary reflexes: a role of the larynx.

A brief review of the literature from otorhinolaryngology and the basic sciences shows the existence and role of nasal-cardiopulmonary reflexes in animals and man. There is ample evidence that odors, fluids and mechanical stiumlation of the nasal mucosa will induce changes in the lungs and cardiovascular system. The proposition that nasal obstruction also produces cardiopulmonary changes is briefly reviewed. The suggestion is made that one of the functions of the nose is to act as an expiratory brake. the removal of this brake could result in changes in laryngeal resistance that lead to poor ventilation.

Airway Obstruction↗
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Vidian nerve and the eustachian tube.

The vidian nerve was stimulated electrically in the dog and this resulted in a reduced patency of the Eustachian tube. The effect was atropine resistant. This physiological evidence in the dog corresponds to anatomical evidence in man of a parasympathetic, vasodilator nerve bundle passing through the vidian to the sphenopalatine ganglion and then via the pharyngeal nerve to the Eustachian tube mucosa. Additional parasympathetic routes to the tube may exist.

Animals↗
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Autonomic stimulation, osmolarity and prostaglandin effects in the Eustachian tube.

Stimulation of the vidian nerve in the dog induced an apparent vasodilation in the mucosa of the Eustachian tube. It is presumed that these parasympathetic fibers course from the greater petrosal nerve through the vidian to the sphenopalatine ganglion. The pharyngeal nerve arises from the ganglion and innervates the mucosa of the tube. Perfusion of the dog's Eustachian tube with solutions of various osmolarities caused a shrinking or swelling of the tube mucosa. Ten percent alterations in the concentration of saline, Ringer's or isotonic KCl produced a hypo- or hypertonic effect. Systemic administration of osmotic diuretics was shown to remove water from normal and edematous tubal mucosa. An agent in human middle ear effusions was found to contract smooth muscle. The behavior of this agent in pharmacological tests suggested the presence of prostaglandins (PG). The effusions were tested for the presence of other inflammatory mediators such as bradykinin, acetylcholine and histamine. These were felt to be absent or present in small amounts. A radioimmune assay of pooled samples of middle ear effusions revealed the presence of several PG, notably PGF2alpha and PGE2. There appeared to be a higher concentration of PG in mucoid effusions than serous effusions. The inflammatory capabilities of these agents are mentioned.

Animals↗
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Evidence for presynaptic parasympathetic receptors on nasal blood vessels.

Noradrenergic synapses in the heart and several blood vessels have been shown to possess prejunctional receptors that modulate the release of norepinephrine from the synapse. The present experiment attempted to find evidence for presynaptic receptors for acetylcholine that modulated norepinephrine release. From the evidence obtained, it appears that the acetylcholine released from nasal parasympathetic fibers does not directly affect the smooth muscle of nasal blood vessels. Acetylcholine does, however, appear to inhibit the release of norepinephrine from nasal sympathetic nerve terminals. It appears that any nasal vasodilation produced by nasal parasympathetic fibers is caused by acetylcholine acting on an inhibitory, presynaptic, muscarinic receptor on the sympathetic nerve terminals. Acetylcholine would exert its control over nasal vessels by regulating the degree of sympathetic neurotransmitter release.

Acetylcholine↗
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Effects of lidocaine and procaine on canine nasal blood vessels.

The effects of lidocaine and procaine on contractile responses of isolated canine nasal mucosal blood vessels to field stimulation and methoxamine were investigated. Analysis of cumulative dose-response curves showed that the two local anesthetics antagonized methoxamine and inhibited the field-stimulation response. The latter effect was interpreted as due to the blockade of Na+ channels. This would inhibit nerve conduction induced by field stimulation. The former effect on methoxamine is probably caused by the effect of these anesthetics on the mobilization of Ca++ needed for smooth muscle contraction. Preincubation of the nasal mucosa with low doses of procaine or lidocaine shifts the methoxamine dose-response curve to the right. With higher doses, the maximal response is also reduced. The shift of the dose-response curve showed that procaine or lidocaine can change the alpha-adrenergic receptor affinity. Commercial 1% lidocaine with 1:100,000 epinephrine also inhibits field stimulation and antagonizes methoxamine contractions. Lidocaine can increase the basal tone of nasal mucosa, while procaine cannot. From these results, we conclude that procaine and lidocaine have common mechanisms in blocking Na+ channels but differ in their ability to modify Ca++ stores or channels.

Animals↗
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H1 and H2 histamine receptors in the in vitro nasal mucosa.

The effect of histamine was studied on canine nasal blood vessels with an in vitro muscle tension measuring technique. Observations suggest that histamine has at least four different effects: 1) inhibits the contraction induced by nerve terminal stimulation, 2) relaxes the smooth muscle under sustained contraction, 3) contracts the smooth muscle, 4) enhances (nor)epinephrine-induced contraction. Both H1 and H2 histamine receptors were identified in the mucosal blood vessels of the canine nasal septum. H1 receptors were present at the surface of vascular smooth muscle and mediated the contractile response (3) due to opening calcium influx channels. H2 receptors existed at both sympathetic nerve terminals and the muscle cell membrane. Stimulation of either H2 receptor caused muscle relaxation. The presynaptic H2 receptors mediated vasodilation through the inhibition of norepinephrine release from the nerve endings. Postsynaptic H2 receptors caused direct muscle relaxation possibly through an increase in cyclic AMP. Both H1 and H2 antagonists worked well, whereas agonists did not properly produce theoretically expected results in these specimens.

Animals↗
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Hemoglobin levels and anemia-associated symptoms in pregnant Liberian women.

An epidemiological study was conducted of 515 pregnant Liberian women. The purposes of the study were to 1) assess the prevalence of anemia in Liberian women during the last trimester of pregnancy (when latent deficiencies are more apt to become clinically manifest), 2) ascertain which physician-obtained symptoms are related to low hemoglobin (Hb) levels and anemia, and 3) determine the sensitivity and specificity of symptoms commonly associated with anemia. The results indicated that the prevalence of anemia (defined as Hb < 11.0 g/dl) was 79.8%. Women who had headache as a symptom had significantly lower mean Hb values than women who did not have this symptom. The socioeconomic status of women with and without symptoms was not statistically different. The sensitivity of headache as an indicator of anemia and low Hb values was 83%, but the specificity of this symptom was low (27%). The utility of signs and symptoms as indicators is discussed in relation to the economic means of lesser-developed societies and their cultural practices.

Adolescent↗
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Unusual effects of histamine antagonists on canine nasal blood vessels.

This paper documents some of the lesser-known effects of antihistamines on nasal blood vessel smooth muscle. An in vitro muscle tension detecting technique was utilized. Three different H1 receptor antagonists (pyrilamine maleate, chlorpheniramine maleate, promethazine hydrochloride), and the H2 antagonist metiamide were used. Besides their basic antihistaminic effect, H1 antagonists (classical antihistamines) induced a contraction, enhanced norepinephrine- and epinephrine-induced contractions, and relaxed the sustained contraction induced by methoxamine hydrochloride or high concentrations of potassium. Although these effects were quite similar to those induced by histamine, the mechanism of each effect was apparently different. Metiamide did not produce these effects except for the relaxation of the sustained contraction. The actions of histamine antagonists seem to be much more complicated than expected.

Animals↗
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An in vitro technique for testing nasal vasodilating agents.

An in vitro method for testing vasoactive drugs on nasal blood vessels is described. Isolated dog nasal mucosa contracts when treated with nasal decongestant or stimulated electrically. Vasodilating drugs inhibit this contraction. Atropine blocks the effects of acetylcholine on this tissue.

Acetylcholine↗