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Biomedical subjects

D Templeton

Publications and source records attributed to D Templeton.

At least 19 recordsLinked to original sources

Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy.

We assessed the antiemetic efficacy and safety of three different oral doses of ondansetron (GR 38032F), a novel serotonin type-3 receptor antagonist, in three consecutive series of 20 breast cancer patients receiving cyclophosphamide-doxorubicin-based chemotherapy for the first time. Patients received oral doses of 8 mg, 4 mg, or 1 mg of ondansetron three times daily for 2 days, with the first dose given 30 minutes before the cyclophosphamide infusion. We then evaluated the efficacy of a conventional antiemetic regimen of intravenous lorazepam, metoclopramide, and diphenhydramine given before chemotherapy and 10 mg prochlorperazine given orally twice on study day 1 and three times on study day 2 in a fourth series of 20 patients with comparable characteristics. The number of emetic episodes, assessment of nausea and appetite, and adverse events were recorded throughout the 2-day study period. Pretreatment and posttreatment clinical laboratory data were also collected. No emesis was observed during the 2-day study period in 17 (85%), 13 (65%), and 11 (55%) patients treated with 8-mg, 4-mg, and 1-mg ondansetron doses, respectively, and in seven (35%) patients who received conventional therapy. The incidence and intensity of nausea were lower with increasing doses of ondansetron and were lower than in the conventional group. Ondansetron-related side effects were generally mild and reversible and did not appear to increase in a dose-dependent manner. These effects included headache, stomach cramps, diarrhea, fatigue, and elevated serum transaminase concentrations. One patient who received three 1 mg doses of ondansetron experienced tremors and muscle twitching. Oral ondansetron is an effective and safe antiemetic for patients receiving noncisplatin cyclophosphamide-doxorubicin-based chemotherapy, and its antiemetic activity appears to be dose-related.

Administration, Oral

Pseudallescheria boydii infection of the central nervous system.

Pseudallescheria boydii is a rare cause of central nervous system infection characteristically presenting as a neutrophilic meningitis or multiple brain abscesses. Factors predisposing to central nervous system infection with this fungus include immunosuppression and near drowning. The organism is infrequently cultured from fluid obtained by lumbar puncture, delaying clinical recognition and appropriate antifungal therapy. All untreated patients with P boydii infection of the central nervous system died. We describe a patient who developed a persistent neutrophilic meningitis with focal neurologic deficits due to P boydii 6 months after a freshwater aspiration pneumonia. We also review the characteristic clinical and pathologic features of previously reported cases and emphasize the importance of early detection and treatment in the management of this frequently intractable disease.

Adult

The relationship of intracellular free calcium activity to amylase secretion in substance P- and isoprenaline-stimulated rat parotid acini.

The relationship between intracellular free calcium activity ([Ca2+]i) and stimulated amylase secretion was investigated in rat parotid acini by measuring the effects of substance P methyl ester and isoprenaline on quin2 fluorescence and amylase release. Although both of these drugs evoked concentration-dependent increases in [Ca2+]i and amylase release, the tachykinin had a greater effect on [Ca2+]i while the catecholamine was the more effective secretagogue. Whereas isoprenaline exerted equipotent effects on amylase secretion and [Ca2+]i, the dose-response relationship for stimulation of secretion by substance P was dissociated by three orders of magnitude to the right of that for elevation of [Ca2+]i by this peptide. It is concluded that these data do not support the hypothesis that substance P-stimulated amylase secretion is mediated solely through an increase in [Ca2+]i and that other second-messengers may be involved in mediation of this secretory response.

Aminoquinolines

Effect of parasympathetic denervation on K+ release by rat parotid slices.

1. By measuring the release of 86Rb, potassium movement was compared in parasympathectomized (Px) and contralateral control parotid gland slices three weeks following surgical denervation. 2. Carbachol and phenylephrine elicited a biphasic increase in 86Rb release that was dose related and could be blocked by atropine and phentolamine respectively. The transient phase was of 2-4 min duration and Ca independent whereas the sustained phase of 86Rb release was greatly reduced by the omission of the external Ca. 3. Denervation caused a shift to the left of the 86Rb efflux dose-response curve to carbachol and phenylephrine (3.75- and 3.37-fold respectively). Pilocarpine had similar action to carbachol but it behaved as a partial agonist. 4. Parasympathectomy (Px) increased the intrinsic activity of the partial agonist pilocarpine and converted it to a full agonist. Results of the present study indicate the possibility of an altered receptor-signal transduction mechanism between the receptor and phospholipid turnover/Ca mobilization in the denervated rat parotid gland.

Animals

Description of an automated assay for measurement of alpha-amylase in vitro from rat parotid gland slices.

1. A modified continuous assay of alpha-amylase is detailed and its usefulness in measuring amylase secretion from rat parotid salivary gland described. 2. The alpha-amylase secretion from the rat parotid gland can be evoked by acetylcholine, substance P and isoprenaline. 3. The secretion of amylase was greatest following isoprenaline stimulation and was of a slower time course than with the other two agonists.

Acetylcholine

The role of dopamine in salivation in the rat parotid gland.

The ability of dopamine to evoke secretion from the rat parotid gland has been investigated. The actions of dopamine were investigated alone and during carbachol mediated secretion. Dopamine increased flow rate and protein secretion in both experimental models. The increase in protein secretion is mediated via beta 1-adrenoceptors whereas the increase in flow rate may be due to activation of specific dopamine receptor.

Animals

The spinal origin of the sympathetic nerve fibres to the vascular and secretory components of the rat submaxillary salivary gland.

The spinal origin of the sympathetic vasoconstrictor and secretory fibres to the submaxillary gland of the rat was identified in the pithed rat preparation by means of selective stimulation of small segments of the spinal outflow. Secretory and vascular responses were similar following stimulation in pithed rats to those following stimulation of the isolated superior cervical nerve trunk in anaesthetized rats. The spinal origin of the secretory and vascular fibres was coincident and it is concluded that if a separate control of blood flow and secretion by sympathetic fibres does exist that it must occur at the level of C.N.S. but that the nerves share a common pathway to the gland.

Animals

Secretory, motor and vascular effects in the sublingual gland of the rat caused by autonomic nerve stimulation.

The influence of the autonomic nerves on sublingual glands of rats was studied. Stimulation of the chorda-lingual nerve evoked a lively flow of saliva and was also thought to contract the myoepithelial cells in the gland. Sympathetic nerve stimulation, on the other hand, usually evoked no secretion and did not cause any motor responses in the sublingual gland. The glandular blood flow was increased by chorda-lingual nerve stimulation, and this vasodilatation persisted also when atropine had been administered. Sympathetic nerve stimulation decreased the sublingual blood flow; this vasoconstrictor effect was mediated via activation of alpha-adrenoceptors.

Animals

Difference in sensitivity of parotid glands brought about by disuse and overuse.

The sensitivity to methacholine of the parotid glands in rats maintained on a liquid diet (aiming at sensitization) for a period of 2 weeks or 3-4 weeks was compared with that of the parotid glands in rats on a pelleted bulk diet (aiming at desensitization). In the rats on the liquid diet, it was found that the dose needed to evoke a just perceptible secretion of saliva was smaller, that the secretion started earlier and continued over a longer time period, and further that the amount of saliva secreted expressed per gland weight in response to submaximal doses of the sialogogue drug was bigger when compared with the rats on the pelleted bulk diet. These findings are interpreted as signs of a higher degree of sensitivity of the glands in the rats on the liquid diet than of those in the rats on the pelleted bulk diet.

Acetylcholine

Effect of electrical stimulation of the autonomic nerves on the levels and synthesis of cyclic nucleotides in the rat salivary glands: relationship to enhanced growth.

Electrical stimulation of either the parasympathetic or the sympathetic nerve supply to the parotid and submaxillary glands increases the intracellular level of cyclic GMP and the rate of DNA synthesis and cell division while only sympathetic stimulation raises cyclic AMP levels. The periods of electrical stimulation inducing hyperplasia also raise the cyclic GMP concentration but there is no similar correlation with changes in cyclic AMP levels. However, the extent of hyperplasia induced by parasympathetic and sympathetic stimulation is not directly related to the size of the increase in cyclic GMP concentration that these treatments produce. Changes in cyclic AMP levels are reflected in altered in vitro adenylate cyclase activity. This activity is raised after 2 min sympathetic stimulation and markedly decreased with 30 min sympathetic or parasympathetic stimulation. Guanylate cyclase activity shows no such changes with nerve stimulation.

Adenylyl Cyclases

The role of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in the ability of sympathetic nerve stimulation to enhance growth and secretion in rat salivary glands in vivo.

1. The cyclic AMP content of the rat salivary glands was measured after sympathetic and parasympathetic nerve stimulation, and after the administration of isoprenaline and phenylephrine. 2. Stimulation of the sympathetic nerves (20 Hz, 1 msec supramaximal voltage for 30 sec of every min) initially raised the cyclic AMP level in both the parotid and submaxillary glands. The rise, which was blocked by propranolol, was not maintained and declined during stimulation from the maximum (reached after 3 min stimulation) to control levels after approximately 15 min. Stimulation of the parasympathetic nerves for 5 min did not raise the cyclic AMP levels. 3. Isoprenaline and phenylephrine raised the cyclic AMP level in both glands. 4. Theophylline enhanced the growth of the parotid and submaxillary glands as measured either by an increase in the wet and dry weights or in acinar axes lengths. N6O2-dibutyryl cyclic monophosphoric acid (dibutyryl cyclic AMP), did not enhance the growth of the glands. 5. It is concluded that cyclic AMP does not directly control cell growth in the rat salivary glands but may be a 'trigger' for events leading eventually to increased growth.

Animals