Circular posterior-hinged craniotomy malignant cerebral oedema.
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Brain Edema↗
Biomedical subjects
T Blackburn
Publications and source records attributed to T Blackburn.
Studies on the role of 5-HT2C and 5-HT2B receptors in regulating generalised seizure threshold in rodents.
The present studies were conducted to investigate the role of 5-HT2C and 5-HT2B receptors in the generation of pentylenetetrazol and electroshock-evoked seizures. The 5-HT2C/2B receptor-preferring agonist 1-(m-chlorophenyl)-piperazine (mCPP; 2.5-7 mg/kg i.p.) weakly elevated seizure threshold in the mouse (but not the rat) electroshock test and also provided appreciable protection against pentylenetetrazol-induced myoclonic and/or tonic seizures in mice and rats, an action that was inhibited by the 5-HT2C/2B receptor antagonist 5-methyl-1-(3-pyridylcarbomoyl)-1,2,3,5-tetrahydropyrrolo[2, 3-f]indole (SB-206553; 10-20 mg/kg p.o.). In contrast, the 5-HT2B receptor agonist 1-[5-(2-thienylmethoxy)-1H-3-indoyl]propan-2-amine hydrochloride (BW-723C86; 3-30 mg/kg s.c.) had no effect on the threshold for generalised seizures in any of the models employed. These results indicate that the observed anticonvulsant effects of mCPP are likely to be mediated by activation of 5-HT2C receptors. However, blockade of these receptors in mice (or rats) by SB-206553 (5-20 mg/kg p.o.) did not result in the reduced seizure threshold characteristic of mutant mice deficient of 5-HT2C receptors, suggesting that in normal adult animals this receptor subtype may usually be subjected to only a low level of 5-hydroxytryptamine tone.
Animals↗
Treatment of articular cartilage defects of the knee with autologous chondrocyte implantation.
The treatment of focal full thickness articular defects in the knee has continued to present a challenge, with no traditional treatment method providing consistent acceptable long-term clinical results. Patients with significant chondral defects frequently have persistent joint line pain, swelling, and catching in the knee. In contrast to marrow stimulation treatment techniques, such as abrasion arthroplasty, drilling, or microfracture which populate the defect with pluripotential stem cells, the use of cultured autologous chondrocytes fills the defect with cells of a committed pathway to develop hyaline-like cartilage. This hyaline-like cartilage more closely recreates the wear characteristics and durability of normal hyaline cartilage than the fibrous or fibrocartilage repair tissue formed by pluripotential stem cells. The purpose of this paper is to review the efficacy of available treatment options as well as the basic science rationale, indications, technique, postoperative rehabilitation, and clinical results of using cultured autologous chondrocytes in the treatment of focal full thickness chondral defects of the knee.
Arthroscopy↗
An investigation of the mechanism responsible for fluoxetine-induced hypophagia in rats.
The effect of fluoxetine on feeding in p-chlorophenylalanine (PCPA) pretreated rats and the nature of its interaction with 5-HT2C receptors have been investigated. Animals that received 3 days PCPA (150 mg/kg i.p.) pretreatment and vehicle on the test day consumed a similar amount as control, saline pretreated animals under the test paradigm used in this study. Fluoxetine (20 and 30 mg/kg p.o.) significantly reduced food intake in PCPA and control pretreated animals to a similar extent, despite an approximately 90% reduction in the levels of brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the PCPA-pretreated animals. Thus, hypophagia is unlikely to be caused by inhibition of 5-HT reuptake. In the pig choroid plexus in vitro, fluoxetine and norfluoxetine inhibited specific [3H] mesulergine binding with pKI's (+/- S.E.M.) of 6.45 +/- 0.09 (n = 4) and 6.05 +/- 0.05 (n = 3), and slope factors (+/- S.E.M.) of 1.06 +/- 0.14 and 0.99 +/- 0.13, respectively. In slices of piglet choroid plexus fluoxetine (1, 10 and 33 microM) caused a rightward shift in the dose-response curve produced by 5-HT with no effect on the maximal response, and a mean pKB of 5.94 +/- 0.09. Norfluoxetine (10 microM) also produced a rightward shift in the 5-HT dose-response curve with no effect on the maximal response, and a pKB of 6.20. Thus, both compounds acted as surmountable antagonists with no agonist efficacy at 5-HT2C receptors present in choroid plexus. The hypophagic effect of fluoxetine (20 mg/kg p.o.) was also unaffected by the non-specific 5-HT2C receptor antagonist metergoline (2 and 5 mg/kg i.p.). These findings suggest that the hypophagic effect of fluoxetine is not likely to be dependent upon intact brain 5-hydroxytryptaminergic presynaptic function, nor is it mediated by an agonist action at the 5-HT2C receptor, but by an additional, unknown mechanism.
Animals↗
5-HT2 receptor subtypes: a family re-united?
The current classification for 5-HT2 receptors accommodates three subtypes. In addition to the originally defined 5-HT2 receptor, sanctuary is now provided for the structurally related 5-HT1c receptor (now 5-HT2c) and at least one atypical 5-HT receptor subtype. The strong functional union of this family is reflected in the paucity of ligands that will discriminate between its subtypes and prompts some re-evaluation of the activities of compounds which may now be regarded as nonselective for the receptor subtypes in this class. In this article, Gordon Baxter and colleagues examine the pharmacology of both officially recognized and atypical 5-HT2 receptor subtypes. A number of novel selective agents are highlighted, some of which may prove useful for 5-HT2 receptor classification and, ultimately, clarify the mechanistic basis for current and future therapeutic strategies which target this receptor family.
Animals↗
Embryonic fat-cell lineage in Drosophila melanogaster.
The Drosophila adipose tissue, or fat body, and the bodywall muscle are two major tissues derived from the mesoderm. Although much is known about the lineage of muscle cells, little is known about the development of the fat body. Using known genes and an enhancer trap (29D), we have begun to trace the lineage of the cells comprising the fat body. The genes Adh (alcohol dehydrogenase) and DCg1 (type IV collagen) code for gene products involved in fat-cell metabolism and therefore serve as terminal fat-cell differentiation markers. The expression of these genes was used to identify the fat body at stage 17 and to identify the start of terminal fat-cell differentiation at stage 15. We found that the steroid-hormone receptor gene, svp (seven-up), was expressed transiently within the fat-cell lineage from stages 12 to 14. We suggest that stage 12 marks the beginning of early fat-cell differentiation and that the svp-positive cells within the mesoderm are early precursor fat cells. To confirm the identity of these cells and to establish the role of svp in the developing fat cell, we examined svp mutant embryos for alterations in the expression of the two terminal fat-cell differentiation markers, Adh and DCg1. Loss of svp function resulted in the loss of Adh transcript and a reduction of DCg1 expression specifically in the fat body. Thus, svp plays a role in fat-body-specific expression of at least two terminal fat-cell differentiation genes. In contrast to svp, we found no evidence that the steroid receptor HNF-4(D) gene was expressed in the fat body nor that it was involved in the development of this tissue. Using an enhancer-trap line (29D), we further traced the fat-cell lineage to nine bilateral clusters of cells within the mesoderm at germ-band extension. We suggest these 29D-positive cells represent the progenitor fat cells. In stage-12 embryos, the 29D-positive cell clusters can be identified within the mesoderm internal to nautilus-expressing cells. These data suggest that the precursor fat cells may be derived from the inner mesoderm, or spanchnopleura. Embryos deficient for the DNA region surrounding the site of the 29D enhancer trap lack most, if not all, of the cells in the fat-cell lineage. These embryos exhibit the loss of svp-positive precursor fat cells and concomitant loss of fat-body-specific expression of Adh and DCg1.(ABSTRACT TRUNCATED AT 400 WORDS)
Alcohol Dehydrogenase↗
Anticoagulant treatment of atrial fibrillation in the elderly.
There is now adequate clinical evidence that the most appropriate treatment of elderly patients with non-valvular atrial fibrillation is with low dose warfarin. Patients may have contraindications to therapy with this agent, but should not be denied treatment based on age alone. Withholding treatment based on age places patients at unwarranted risk for severely disabling thromboembolic complications.
Aged↗
Optical differences in multiple personality disorder. A second look.
The study was designed as a replication of a study reported in this Journal (Miller S [1989] Optical differences in cases of multiple personality disorder. J. Nerv Ment Dis 177:480-486) which found that subjects with multiple personality disorder (MPD) experienced significantly more changes in visual functioning between alter personalities than a control group simulating the disorder. In the present study, data from 20 patients diagnosed with MPD and 20 control subjects role playing MPD were analyzed for statistical and clinical significance. The findings from the present study appear to confirm results from the earlier study that individuals with MPD experience differences in some aspects of visual functioning between alter personalities. The results further confirm that MPD subjects experience more differences across visual measures than control subjects simulating the disorder. However, the findings from the present study are not entirely consistent across the various visual measures or with findings from previous studies.
Adult↗
5-hydroxytryptamine antagonistic effects of ICI 169,369, ICI 170,809 and methysergide in human temporal and cerebral arteries.
ICI 169,369 and ICI 170,809 are two chemically novel 5-HT antagonists that have high affinity for the 5-HT2 binding site in rat cortex (Ki 1.79 x 10(-8)M and 6.6 x 10(-10)M, respectively). In human temporal artery preparations ICI 169,369 was shown to cause a progressive rightward shift of the 5-HT-response curve over the range 10(-7)-10(-5)M, while ICI 170,809 in these concentrations shifted the curve to the same degree (no dose dependency). In human cerebral vessels no effect was observed until a high concentration (10(-5)M) was used for either compounds. The mixed 5-HT1/5-HT2 antagonist, methysergide, induced a non parallel rightward shift of the 5-HT-induced concentration-effect curve with a depression of the maximum achievable response in both the temporal and cerebral artery. The mode of effect of ICI 169,369 and ICI 170,809 to block the 5-HT-induced contractions in human temporal vessels resembles that of the pure 5-HT2 antagonist ketanserin, thus suggesting that the two ICI compounds are mainly 5-HT2 antagonists. In high concentrations both ICI 169,369 and ICI 170,809 have vasorelaxant properties, explaining the reduction in maximum 5-HT-induced contraction seen at high antagonist concentrations.
Cerebral Arteries↗
Cystocerebral syndrome. Acute urinary retention presenting as confusion in elderly patients.
The diagnosis of acute mental status changes in the elderly patient is often very difficult. Many causes are possible, and there is often little history obtainable. The physical examination occasionally provides the essential clues needed to discover the source of the sudden deterioration. We have recently evaluated four episodes of acute delirium in three elderly patients who presented with no readily apparent cause for these changes. On further evaluation, the patients were found to have marked bladder distention associated with acute urinary retention. None of these patients complained of discomfort, and none had any awareness or recollection of their deterioration. Each patient had rapid resolution of symptoms on bladder decompression. To our knowledge, this "cystocerebral syndrome" has not been previously described, and we suggest that it be considered in the evaluation of acute confusional states in elderly men.
Aged↗
Pacemaker-induced superior vena cava syndrome: consideration of management.
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Brachiocephalic Veins↗
Abdominal mass and non-functioning left kidney in the neonate.
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Humans↗
Prevention of ankle sprains.
Ankles are sprained when supported on an unstable foundation, while too rididly fixed to the playing surface, or when forced into unnatural positions by extrinsic muscle tightness. The unstable foundation may be the shoe itself, a chuck-hole, or another player's foot. Undue fixation may be by 1-inch mud cleats, baseball spikes, or a modern wrestling mat. When these circumstances occur, heel cord tightness may alter the ankle's response. Thus, prevention of ankle sprains may be by modification of any of these factors.
Ankle Injuries↗