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Biomedical subjects

A C Scott

Publications and source records attributed to A C Scott.

At least 19 recordsLinked to original sources

Feline spongiform encephalopathy: fibril and PrP studies.

The brains from 18 cats were examined for the presence of the fibrils and modified PrP protein which are molecular diagnostic markers for scrapie-like diseases. Thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (FSE). Of these, five had histopathological changes of FSE, five had other lesions of the central nervous system, and in three the brain was normal. The remaining five cats had no clinical neurological signs and were selected as controls. Fibrils and modified PrP protein were found in the brains of the five cats with FSE and in one of the cats with neurological signs but no histopathological changes in the central nervous system. Fibrils were present in the absence of modified PrP in the brains of two cats, one with neurological signs and a histologically confirmed meningioma, and one with no neurological signs and a histologically normal brain.

Animals

Scrapie-like encephalopathy in a greater kudu (Tragelaphus strepsiceros) which had not been fed ruminant-derived protein.

A 19-month-old greater kudu (Tragelaphus strepsiceros), whose dam had died 15 months earlier with spongiform encephalopathy, required euthanasia after developing severe ataxia and depression with an apparently sudden onset. No macroscopic abnormalities were detected on post mortem examination but a scrapie-like spongiform encephalomyelopathy was apparent on histopathological examination of brain and segments of spinal cord. Negative stain electron microscopy of proteinase K-treated detergent extracts of tissue from the brain stem revealed the presence of scrapie associated fibrils, and a 25 to 28 kDa band comparable with that identified as abnormal PrP (prion protein) from the brains of domestic cattle with spongiform encephalopathy was detected using rabbit antiserum raised against mouse PrP. The animal was born nine months after the statutory ban on the inclusion of ruminant-derived protein in ruminant feeds and, as no other possible sources of the disease were apparent, it appears likely that the infection was acquired from the dam.

Animal Feed

Bovine spongiform encephalopathy: detection of fibrils in the central nervous system is not affected by autolysis.

The effect of autolysis on the electron microscopic detection of the characteristic abnormal fibrils, originally called 'scrapie-associated fibrils', was investigated in four different areas of the central nervous system (CNS) from 10 clinically suspect BSE cattle after post mortem delay and compared with the histopathological diagnosis. The tissues for fibril detection were subjected to controlled incubations to simulate autolysis. Fibril detection in all areas sampled from nine animals in which BSE was confirmed by histopathology was not affected by combined post mortem delays and specific controlled treatments. Detection of fibrils from the cervical spinal cord was no less sensitive than from brain areas. Fibrils were not detected in the one suspect case in which histopathology did not reveal lesions of BSE. The study confirms that fibril detection is of diagnostic value in BSE when post mortem autolysis renders CNS material unsuitable for histopathology.

Animals

Isolation of a Lelystad virus-like agent from British pigs and scanning electron microscopy of infected macrophages.

Six, one-week-old gnotobiotic piglets were inoculated with tissues or sera collected from field cases of porcine reproductive and respiratory syndrome. The piglets showed little or no illness, and two that were necropsied at 8 and 9 days post infection appeared grossly normal. However, a Lelystad virus-like agent was isolated from most of the inoculated pigs using porcine alveolar macrophage cultures. Seroconversion to the Lelystad virus was observed and some animals developed microscopically detectable interstitial pneumonias. Scanning electron microscopy was used to study the in vitro cytopathic effect of the Lelystad virus on porcine alveolar macrophages.

Abortion, Veterinary

An evaluation of the Thermafil endodontic obturation technique.

The purpose of this study was to evaluate the Thermafil endodontic obturation technique and to compare it with laterally condensed gutta-percha. Thirty-seven maxillary central incisors were similarly prepared and divided into groups. Seventeen were obturated with Thermafil and 17 with lateral condensation. Three served as controls. After vacuum staining, all teeth were cleared and apical dye penetration was evaluated by two independent observers. Average leakage values were 0.24 mm and 1.32 mm for Thermafil and 0.47 mm and 1.18 mm for lateral condensation. There was no significant difference between the techniques, although a difference between evaluators was noted. Final results point to the relative subjectivity of in vitro leakage studies. When comparing the obturation times of both techniques, the Thermafil technique averaged 2 min 56 s while lateral condensation took 3 min 26 s. Statistical analysis showed no significant difference in obturation times.

Analysis of Variance

Membrane conductances involved in amplification of small signals by sodium channels in photoreceptors of drone honey bee.

1. Voltage signals of about 1 mV evoked in photoreceptors of the drone honey bee by shallow modulation of a background illumination of an intensity useful for behaviour are thought to be amplified by voltage-dependent Na+ channels. To elucidate the roles of the various membrane conductances in this amplification we have studied the effects of the Na+ channel blocker tetrodotoxin (TTX) and various putative K+ channel blockers on the membrane potential, Vm. 2. Superfusion of a slice of retina with 0.5-10 mM-4-aminopyridine (4-AP) depolarized the membrane and, in fifty of sixty-three cells induced repetitive action potentials. Ionophoretic injection of tetraethylammonium produced similar effects. 3. In order to measure the depolarization caused by 4-AP, action potentials were prevented by application of TTX: 4-AP was applied when the membrane was depolarized to different levels by light. 4-AP induced an additional depolarization at all membrane potentials tested (-64 to -27 mV). We conclude that there are 4-AP-sensitive K+ channels that are open at constant voltage over this range. 4. 4-AP slowed down the recovery phase of the action potential induced by a light flash by a factor that ranged from 0.51 to 0.16. This reduction could be accounted for by the reduction in a voltage-independent K+ conductance estimated from the steady-state depolarization. 5. After the voltage-gated Na+ channels had been blocked by TTX, exposure to 4-AP further changed the amplitude of the response to a small (approximately 10%) decremental light stimulus. The change was an increase when the background illumination brought Vm to potentials more negative than about -40 mV; it was a decrease when Vm > -40 mV. The data could be fitted by a circuit representation of the membrane with a light-activated conductance and a K+ conductance (EK = -66 mV) that was partly blocked by 4-AP. The voltage range studied was from -52 to -27 mV; neither conductance in the model was voltage dependent. 6. The responses to small changes in light intensity in the absence of TTX were mimicked by a model. We conclude that a voltage-dependent Na+ conductance described by the Hodgkin-Huxley equations can amplify small voltage changes in a cell membrane that is also capable of generating action potentials; the magnitude of the K+ conductance is critical for optimization of signals while avoiding membrane instability.

4-Aminopyridine

Natural scrapie: detection of fibrils in extracts from the central nervous system of sheep.

Extracts from the cervical spinal cord and from the medulla, thalamus, cerebellum and cerebral cortex of the brains of 10 sheep, histopathologically confirmed as cases of scrapie, were examined by electron microscopy for the presence of scrapie-associated fibrils. Characteristic fibrils were observed in all the extracts except for that from the thalamus of one sheep. No fibrils were found in any extracts from three control sheep. A comparison of these results with a similar study of 22 cases of bovine spongiform encephalopathy (BSE) suggests that in cases of scrapie the area of the brain chosen for the detection of fibrils is less critical than in cases of BSE, in which fibrils are more readily extracted from areas of the brain stem.

Animals

A comparison of morphine-perphenazine and midazolam on preoperative sedation and arterial oxygen saturation.

The effectiveness of midazolam and a mixture of morphine-perphenazine premedication to produce sedation and their effects on preoperative oxygen saturation (SaO2) were examined. Eighty-five patients whose SaO2 measured with a pulse oximeter was greater than 90% and who were not receiving narcotic sedatives or oxygen were randomized to three groups. Each patient had his SaO2 recorded before premedication with placebo (saline), midazolam 0.08 mg.kg-1 or morphine 0.15 mg.kg-1 with perphenazine 2.5-5.0 mg im. From 30-90 min later, prior to anaesthesia SaO2 was repeated, and a sedation score was obtained by a blinded observer using a seven point scale. Median sedation scores were greater for midazolam (4) than for morphine-perphenazine (2) and placebo (1) (P less than 0.0001). As well, there was a decrease in the SaO2 in the morphine-perphenazine group (1.7 +/- 2.7%, P less than 0.001) but not in the midazolam and placebo groups (0.1 +/- 2.3%, -0.8 +/- 2.1%). In conclusion midazolam produced greater sedation than morphine-perphenazine and placebo without effect on SaO2 whereas morphine-perphenazine showed a decrease in SaO2 preoperatively.

Adult

Bovine spongiform encephalopathy: detection and quantitation of fibrils, fibril protein (PrP) and vacuolation in brain.

Bovine spongiform encephalopathy (BSE) is a new disease of cattle which has considerable homology with scrapie, the archetype of the transmissible spongiform encephalopathies. Abnormal brain fibrils, called scrapie associated fibrils (SAF), are specific ultrastructural markers for these diseases. Fibril detection was compared with histopathological diagnosis in the brains of 167 cattle; 157 clinically suspect BSE and 10 clinically normal. Fibrils were detected in samples of pooled brain regions of 67/144 in which vacuolar changes of BSE were confirmed, but absent in the remaining 23 brains, in which no vacuolation was found, including those from the clinically normal cattle and 13 with alternative neuropathological diagnoses. When eight defined anatomic regions from the brains of another 22 affected cows were examined, the sensitivity of fibril detection was greater than 90% for the brain stem areas. Fibril prevalence in these areas approximated to severity of vacuolar changes. When the same defined regions from four of the affected cows were assayed for fibril protein (PrP) by western blotting, the density of immuno-labelling generally correlated with the fibril prevalence. This study confirms the specificity of fibril detection for BSE, shows that the ease of fibril detection depends on anatomic region sampled and suggests an association between PrP accumulation and vacuolar changes in certain neuroanatomic areas.

Animals

Oral ciprofloxacin in the treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis.

Oral ciprofloxacin in doses of 0.75 to 2 g daily for 8-16 (median 10) days was given as first-line treatment of 33 unselected episodes of CAPD-associated peritonitis in 20 patients. Treatment was well tolerated and effective, curing 25 episodes. Treatment was withdrawn in five episodes, four because of resistant organisms and in the other because of vomiting. Infection relapsed twice in one patient during follow-up and one patient had persistence of the infecting organism (Pseudomonas aeruginosa) despite clinical improvement. Plasma and dialysate ciprofloxacin levels ranged from 1 to 8 mg/l. Assay between days 2 and 4 of treatment indicated the ciprofloxacin steady state concentration. If this proves to be greater than 7 mg/l the dose may be reduced and if less than 2 mg/l the dose should be increased. Overall a single course of oral ciprofloxacin was 76% successful as a first-line treatment for CAPD-associated peritonitis, caused by a wide range of organisms.

Administration, Oral

Indium-111 leukocyte scanning and fracture healing.

This study was undertaken to determine the specificity of indium-111 leukocyte scans for osteomyelitis when fractures are present. Midshaft tibial osteotomies were performed in 14 New Zealand white rabbits, seven of which were infected postoperatively with Staphylococcus aureus per Norden's protocol. All 14 rabbits were scanned following injection with 75 microCi of indium 111 at 72 h after osteotomy and at weekly intervals for 4 weeks. Before the rabbits were killed, the fracture sites were cultured to document the presence or absence of infection. The results of all infected osteotomy sites were positive, whereas no positive scans were found in the noninfected osteotomies. We concluded from this study that uncomplicated fracture healing does not result in a positive indium-111 leukocyte scan.

Animals

Recovery room oxygenation: a comparison of nasal catheters and 40 per cent oxygen masks.

One hundred and sixty-one ASA physical status I-III patients undergoing elective surgery were evaluated using nasal catheters versus 40 per cent O2 venturi masks. Twenty-one per cent of the patients arrived in the recovery room with hypoxia as measured with a pulse oximeter (SaO2 less than 90 per cent). Fifteen minutes later all patients who arrived hypoxic were well oxygenated on their chosen oxygen therapy. Only one patient that arrived normoxic became hypoxic using a nasal catheter 15 minutes later. There was no statistical difference between patients given 40 per cent O2 by mask versus patients given oxygen by nasal catheter. The mean SaO2 for the group given 40 per cent O2 at 15 minutes was 96.7 +/- 2.15 per cent versus 96.6 +/- 2.48 per cent for nasal catheters. Nasal catheters are as effective as 40 per cent O2 masks for treating hypoxia in the recovery room. Obesity and age were statistically significant risk factors in the patients that arrived hypoxic. Patients were 47.4 +/- 15.6 years in the hypoxic group versus 38.3 +/- 15.6 years in the non-hypoxic group (p less than 0.001). Patients having an endotracheal tube with intermittent positive pressure ventilation or having a premedication were more apt to be hypoxic on arrival. These last two factors were closely associated and may reflect bias. The patient's gender, history of smoking, presence of obstructive lung disease, not including asthma, location of incision, or type of anaesthetic were not statistically significant risk factors.

Adolescent

Fibrils from brains of cows with new cattle disease contain scrapie-associated protein.

During the past two years, more than 1,000 cases of a neurological disorder of cattle, bovine spongiform encephalopathy (BSE), have been confirmed from farms throughout Great Britain. The neurological signs and brain pathology of BSE resemble those produced in other species by the pathogens of scrapie and related disorders. The discovery of fibrils similar to scrapie-associated fibrils in detergent extracts o BSE-affected brain supported the clinical and pathological diagnosis of the disease, but has been controversial. Scrapie-associated fibrils are found in brain extracts of all species affected by scrapie and diseases caused by related pathogens. They are pathological aggregates of a neuronal membrane protein termed PrP and a protease-resistant form of PrP is a molecular marker of scrapie-associated fibrils. In this report, we show the major protein of BSE fibrils is the bovine homologue of PrP as judged by its size, protease resistance, immunoreactivity, lectin binding and partial N-terminal protein sequence. This confirms that BSE is a scrapie-like disease.

Amino Acid Sequence