Biomedical subjects
Publications and source records attributed to K R Spencer.
The indications and operative technique of various procedures commonly used to provide or increase access to the central skull base, anterior and middle cranial fossae, nasopharynx, infratemporal fossa and retromaxillary space are discussed with illustrative cases.
This paper focuses on how patients with oral squamous cell carcinoma (SCC) are assessed and managed once they have been referred for specialist care. Current and future treatment options are presented and basic management principles are discussed. It is our hope that this will enable the general dental practitioner to gain insight into the process and reasoning behind the multidisciplinary treatment of these complex cases.
A series of 21 patients, who were selected for primary mandibular stabilisation with titanium plates following excision of advanced malignant tumours, is reported. Success was defined as a plate that did not have to be removed due to fracture, exposure or infection. The overall success rate was 71%, with follow-up ranging from 7-53 months. The majority of plate losses were experienced when either anterior or large lateral defects which included the condyle were bridged and when patients were subjected to either pre- or postoperative radiotherapy.
Odontogenic myxoma is a benign but locally aggressive neoplasm. The present case documents the resective and reconstructive management of a patient with a moderately large myxoma of the mandible.
Non-peptide receptor ligands with differential affinity for the angiotensin II-1 (AII-1) receptor (EXP3312, EXP3880) or the AII-2 receptor (PD123177) and an angiotensin converting enzyme (ACE) inhibitor captopril were evaluated for the ability to protect against a renin-induced performance deficit in a passive avoidance (PA) task in rats. The ability to retain a PA response was shown to decrease as the dose of intracerebroventricularly (i.c.v.) administered renin increased with maximal retention deficits occurring at 1.0 micrograms/5 microliters i.c.v. EXP3312 (1-100 micrograms/5 microliters i.c.v.) and EXP3880 (1-100 micrograms/5 microliters i.c.v.) produced dose-dependent increases in retention latencies when co-administered with renin. The peak effect dose (PED) for EXP3312 and EXP3880 was 3 and 30 micrograms i.c.v., respectively. In contrast, PD123177 was not effective in preventing the renin-induced decrease in retention across a broad range of doses (0.1-100 micrograms/5 microliters i.c.v.). Captopril (1-100 micrograms/5 microliters i.c.v.) also prevented the renin-induced performance deficit with a PED of 30 micrograms/5 microliters i.c.v. These results suggest that renin given i.c.v. produces a deficit in performance of a PA response in rats and that this effect can be attenuated by an ACE inhibitor, AII-1 receptor ligands, but not AII-2 receptor blocker.
DuP 996 and ketanserin have previously been shown to protect against experimentally induced passive avoidance (PA) deficits. In the present experiment the potential interaction between DuP 996 and ketanserin on hypoxia-induced amnesia was evaluated. Exposure to hypoxia (6.5% oxygen) produced a reliable deficit in PA retention which was attenuated by posthypoxia treatment with DuP 996 (0.01-0.1 mg/kg SC). Similar effects were found with ketanserin at 1.0 and 3.0 mg/kg SC. Coadministration of ketanserin, at a dose that did not protect against hypoxia (0.3 mg/kg SC), and DuP 996 (at doses of 0.005, 0.1, 0.03, 0.1, 0.3 and 1.0 mg/kg SC) revealed a potentiation of both previously inactive doses of DuP 996 (e.g., 0.005, 0.3, and 1.0 mg/kg SC) and an increase in the protective effect of previously active doses of DuP 996 (0.01, 0.03, 0.1 mg/kg SC). These results suggest that combined administration of DuP 996, a neurotransmitter release enhancer, with ketanserin, a serotonin (5HT) antagonist, may provide a useful treatment for dementia.
DuP 996, 3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, physostigmine (PH), tetrahydroaminoacridine (THA) and 3,4-diaminopyridine (3,4-DAP) were compared for their ability to protect against hypoxia-induced performance deficits in a passive avoidance (PA) task. The ability to retain PA response was found to decrease as the oxygen concentration decreased with the largest retention deficit occurring at 6.5% oxygen. DuP 996 (0.01-0.1 mg/kg SC), 3,4-DAP (0.1-10.0 mg/kg SC), THA (0.3-5.0 mg/kg SC) and PH (0.001-0.1 mg/kg SC) administered one minute after PA training produced dose-dependent increases in retention latencies following exposure to 6.5% oxygen. In comparing each compound for side effects, DuP 996 induced tremor and mortality at 10 and 40 mg/kg SC, respectively, and PH at 0.3 and 0.8 mg/kg SC, respectively. With PH the 0.3 mg/kg SC dose also produced hypersalivation and a decrease in lift strength. THA produced tremor and mortality at 6.0 and 40 mg/kg SC, respectively, and 3,4-DAP at 50 and 200 mg/kg SC, respectively. 3,4-DAP also produced chromodacryorrhea and hypersalivation at 50 mg/kg SC. Dividing the dose necessary to produce mortality by the highest effective dose active in the hypoxia test yielded a safety ratio for DuP 996 of 400, for 3,4-DAP 20, for PH 8, and for THA 8, showing a greater safety margin for DuP 996 than the other cholinergic agents. These results suggest that DuP 996 may be of use in the treatment of diseases associated with cognitive impairment and may have a greater safety margin than other cholinergic agents.
The 5-HT antagonists ketanserin, mianserin, methysergide, and cyproheptadine and the 5-HT uptake inhibitors fluoxetine and zimeldine were evaluated for their ability to protect against an hypoxia-induced performance deficit in a passive avoidance (PA) task. The ability to retain a PA response was found to decrease as the oxygen concentration decreased with the largest retention deficit occurring at 6.5% O2. The 5-HT2 selective antagonists ketanserin (0.01-10.0 mg/kg SC) and mianserin (0.05-10.0 mg/kg SC) administered one minute after PA training produced dose-dependent increases in retention latencies following exposure to a 6.5% oxygen environment. Peak effective doses (PED) for ketanserin and mianserin were 3.0 mg/kg SC and 0.05 mg/kg SC, respectively. In contrast, methysergide (0.05-30.0 mg/kg SC) and cyproheptadine (0.05-7.0 mg/kg SC), antagonists that show less affinity for the 5-HT2 receptor subtype, were not effective in preventing the hypoxia-induced amnesia. Inhibition of 5-HT reuptake by fluoxetine (0.01-1.0 mg/kg SC) produced dose-dependent increases in retention latencies with a PED of 0.05 mg/kg SC while zimeldine (0.1-10.0 mg/kg SC), another 5-HT reuptake inhibitor, had no effect on the amnesia. The results of this study suggest that modification of 5-HT after exposure to hypoxia can ameliorate a performance deficit in an animal model of learning and memory.
A drug interaction involving thiamylal sodium and a proprietary antidiarrheal preparation caused fatal ventricular fibrillation in a dog. Trials involving 4 dogs were conducted to recreate the interaction, and 1 of the 4 dogs died after ventricular fibrillation developed. The nature of the interaction was hypothesized to be mediated through the anticholinergic drug diphemanil methylsulfate, producing an autonomic imbalance.