Inhibition of REM sleep by fluoxetine, a specific inhibitor of serotonin uptake.
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Biomedical subjects
Publications and source records attributed to G T Jones.
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We have compared the sleep-producing effects of thalidomide and pentobarbital. In a dose range that did not produce ataxia, thalidomide increased slow wave sleep and rapid eye movement sleep in cats (2-8 mg/kg p.o.) and rats (16 mg/kg p.o.). Pentobarbital had hypnotic activity in the same dose range but produced ataxia also at these doses. Thalidomide reduced spontaneous activity of both mice and rats. This occurred over a dose range of 8 to 1000 mg/kg p.o., but plateaued at a level of activity well above the complete inactivity of anesthesia that occurred with pentobarbital at well above the complete inactivity of anesthesia that occurred with pentobarbital at doses (greater than or equal to 32 mg/kg p.o.) above the hypnotic range. Several simple screens for thalidomide-like activity have been described which, together, could facilitate the search for thalidomide-like hypnotics. Pentobarbital, at doses 3 to 10 times the hypnotic range, prevented audiogenic seizures in physically dependent rats withdrawn from sodium barbital but thalidomide did not substitute for barbiturates even at doses 30 times those that increased sleep. Thalidomide, but not pentobarbital, enhanced the sleep-producing effect of electrical stimulation of basal forebrain in cats. The latter two findings suggest that thalidomide probably has a mechanism of action different from that of pentobarbital and that this may involve the activation of a sleep center in the forebrain.
Nisoxetine, a potent and specific inhibitor of norepinephrine uptake, suppressed REM sleep in cats. Oral doses as small as 0.1 mg/kg were effective during the first 2 1/2 hours of a recording session; 0.25 mg/kg, for 5 hours. The amount of slow wave sleep increased in cats that received 0.1-1.0 mg/kg of nisoxetine. These changes in sleep pattern resemble those reported after treatment with somewhat higher doses of tricylic antidepressants.
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Nineteen patients with 28 dislocated hips treated in a Pavlik harness for > 8 weeks with no evidence of hip reduction were identified. After discontinuation of the harness use, reduction was often difficult to obtain and maintain. Thirteen of these patients (17 hips) required operative intervention to obtain stable located hips. In this group of patients, we attempted to identify factors that led to an unusually high number of failures of closed management techniques. Prolonged positioning of the dislocated hip in flexion and abduction potentiates dysplasia, particularly of the posterolateral acetabulum, and increases the difficulty of obtaining a stable closed reduction. Confirmation of satisfactory reduction during treatment with the Pavlik harness is mandatory. Such treatment should be discontinued promptly if reduction is unobtainable.
In this study, phenotypic expression of spontaneous elastic laminae defects within the rat abdominal aorta was examined. Lesions in Brown Norway (BN) rats were compared with those of New Zealand genetically hypertensive (GH) rats. BN and GH rats were cross-bred to determine the phenotypic expression of these lesions in successive F(1) and F(2) generations. Lesions were assessed by distribution, number and a semiquantitative index of severity. All BN aortae contained numerous elastic tissue defects. In comparison, GH aortae contained only occasional elastic tissue lesions. F(1) aortae contained lesions in numbers similar to those of the parental BN strain; however, F(1) lesions were of significantly greater severity. Within the F(2) generation, a wide range in both lesion numbers and severity indices was observed, with approximately a quarter of animals having lesion numbers analogous to the GH parental strain. In conclusion, this study indicates that the spontaneous elastic tissue lesions observed within BN rats are consistent with an autosomal dominant, possibly single gene, effect. Moreover, epistatic effects, derived from the GH strain, may influence the severity of these lesions. The gene(s) responsible may be important in the development of conditions such as arteriosclerosis and aneurysms in humans.
The aortic expression of endothelin-1 (ET-1) was examined in three species of rat using a novel en face immunohistochemical technique. A genetically hypertensive strain was compared to two normotensive strains, one of which is known to develop spontaneous lesions within the abdominal aorta. ET-1-positive staining was increased about the major aortic branch ostia and over the dorsal abdominal aortic wall in all three species indicating a flow-related expression pattern. Mitotic and hyperchromatic endothelial cells stained strongly for ET-1 as did occasional multi-nucleated endothelial cells. The aortic-lesion-prone normotensive strain developed transverse tears of the internal elastic lamina with a corresponding endothelial cell response. Endothelium at the edge of these lesions was strongly stained for ET-1 and appeared to be associated with increased leucocyte adhesion as did other strongly ET-1-stained areas in all three species. This study indicates that increased ET-1 expression is anatomically localised within the rat aorta, possibly by haemodynamic stress. This may have implications for maintaining endothelial cell confluence, aortic smooth muscle cell reparative processes and possibly eventual pathophysiological conditions such as atherosclerosis.
The purpose of this retrospective study was to evaluate clinically, functionally, and objectively our initial experience using free, autogenous middle third patellar tendon for anterior cruciate ligament reconstruction without extraarticular augmentation in 62 of 75 patients (80% followup) who were available for clinical review at a minimum 2-year followup. Subjective, clinical, functional, Cybex dynamometer, and KT-1000 arthrometer tests were performed along with modified tests of the Hospital for Special Surgery, Noyes Cincinnati, Tegner, and Lysholm knee rating scales. Ninety-two percent had a negative pivot shift at followup. The mean Cybex dynamometer extension deficits postoperatively were 9% and 7% at 180 and 240 deg/sec. Mild patellar pain symptoms were noted in 18%. The reoperation rate was 10% with a mild flexion contracture as the most common reason. The Hospital for Special Surgery scoring scale postoperatively was 88; Noyes, 86; Lysholm, 88; and Tegner, 6. Mean postoperative single-legged and vertical jump indices were 88% and 87%, respectively. The KT-1000 arthrometric evaluation postoperatively revealed a mean maximum manual difference of 0.3 mm; 92% of the patients had a maximum manual difference of < or = 3 mm. Subjectively, 95% indicated that they would undergo the procedure again. Early results demonstrate excellent stability, preservation of motion, and encouraging evaluations by scoring scales and arthrometric evaluation.
Sixty-two patients who underwent arthroscopically assisted anterior cruciate ligament reconstruction with the middle-third patellar tendon autograft without extraarticular augmentation were retrospectively reviewed at a minimum 2-year (mean, 37-month) followup. A postoperative KT-1000 arthrometric evaluation revealed a mean maximum manual difference of 0.3 mm (range, -6 to +16). Ninety percent of the patients had a mean maximum difference of < or = 3 mm. Three patients had a > or = 5 mm mean maximum difference; positive pivot shifts were noted in two of these patients. Despite an early range of motion, early weightbearing protocol without an extraarticular backup, the pivot shift (92% negative) was reliably eliminated at postoperative followup. Arthrometric parameters were statistically reduced (P < 0.0001) from preoperative status and were consistent with the diagnostic criteria established for normal knees. There was no relationship established in the "tighter" knees (those with negative side-to-side arthrometric differences) and the incidence of knee flexion contractures, patellar pain symptoms, Cybex extension deficit (> 20%), functional indices, or postoperative rating scales.
Eighty-nine consecutive patients were followed for twelve to twenty-four months after carotid thromboendarterectomy. Forty-seven underwent operations using a standard carotid closure; a second group of forty-two patients had a saphenous vein patch graft applied in closure. The patients were evaluated with carotid duplex scans at regular intervals to evaluate the incidence of early restenosis. Patients with positive duplex scans underwent arterial angiography or digital subtraction angiography. Operative mortality was zero. Twelve late deaths occurred; eleven due to cardiac disease. In the unpatched group, 19.1% of the patients developed significant restenosis (a luminal narrowing of greater than 50%) with only a 2.4% incidence occurring in the patched group, a statistically significant difference (p less that 0.05). There was a higher incidence of symptomatic restenosis in the unpatched group, though the results were not considered significant. Venous patch rupture was seen in three patients who have not been included in the study group. All of these had venous patches harvested from a distal greater saphenous vein site at the ankle. The authors recommend venous patch closure with a thicker patch taken from the proximal saphenous vein at the groin to reduce the incidence of early restenosis and to avoid venous patch rupture. Regular non-invasive evaluation is recommended to detect restenosis with careful clinical follow-up to evaluate neurologic complications.