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Biomedical subjects

A McRae

Publications and source records attributed to A McRae.

At least 37 records · Page 2Linked to original sources
PubMed1995

The role of functional endoscopic sinus surgery in the management of recurrent sinus barotrauma.

Sinus barotrauma occurs when an individual is unable to equilibrate the pressure within his sinuses with atmospheric pressure. Aviators affected by recurrent sinus barotrauma are unfit to fly until the underlying cause is established and treated. While most cases result from intranasal pathology, a significant number are the result of sinus pathology or anatomical abnormalities. This latter group have been difficult to manage in the past but the advent of computerized tomography and the Hopkin's rod endoscope have allowed them to be operated on with precision and safety. Complications of this treatment are uncommon and the aviator has usually been able to resume full flying duties after undergoing a decompression test. In our experience it is rare for an aviator who has passed a decompression test to have further episodes of sinus barotrauma.

Aerospace Medicine↗
PubMed1995

Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 3-hour infusion was combined with carboplatin in a phase I/II study directed to patients with non-small cell lung cancer. Carboplatin was given at a fixed target area under the concentration-time curve of 6.0 by the Calvert formula, whereas paclitaxel was escalated in patient cohorts from 150 mg/m2 (dose level I) to 175, 200, 225, and 250 mg/m2. The 225 mg/m2 level was expanded for the phase II study since the highest level achieved (250 mg/m2) required modification because of nonhematologic toxicities (arthralgia and sensory neuropathy). Therapeutic effects were noted at all dose levels, with objective responses in 17 (two complete and 15 partial regressions) of 41 previously untreated patients. Toxicities were compared with a cohort of patients in a phase I trial of paclitaxel alone at identical dose levels. Carboplatin did not appear to add to the hematologic toxicities observed, and the paclitaxel/carboplatin combination could be dosed every 3 weeks.

Adult↗
PubMed1994

Propentosylline depresses amyloid and Alzheimer's CSF microglial antigens after ischaemia.

In the gerbil hippocampus activated microglial antigens are intensely stained by cerebrospinal fluid from patients with Alzheimer's disease (AD-CSF), OX18 and the amyloid precursor protein (beta-APP) up to 14 days after ischaemia. Propentosylline (PPF), which facilitates the adenosine A2 receptor action, has been shown to be neuroprotective, to depress O2- radical formation in macrophages and to interfere with the generation of phagocytotic macrophages from cultivated microglial cells. In this report we tested in ischaemic gerbils whether PPF treatment influences the potential neurotoxic properties of microglia. Daily post-treatment with PPF, started 24 h after ischaemia, depressed the immunostaining of activated microglia by AD-CSF, OX18 and APP in the hippocampus. Thus, PPF may protect against microglia-related brain damage.

Alzheimer Disease↗
PubMed1994

Transmitter-loaded polymeric microspheres induce regrowth of dopaminergic nerve terminals in striata of rats with 6-OH-DA induced parkinsonism.

Biodegradable controlled-release microspheres made with the biocompatible biodegradable polyester excipient poly (DL-lactide-co-glycolide) represent a new technology for drug delivery to the central nervous system (CNS). A suspension of 3 microliters of dopamine (DA) or NE containing microspheres, or empty microspheres, was implanted in 2 sites of the DA denervated striatum of rats previously unilaterally lesioned with 6-OH-DA. Contralateral rotational behavior induced by apomorphine was used as an index of lesion success. Following implantation of the microspheres, rotational behavior was also used as an index of functional recovery. Both DA and NE microsphere implanted rats displayed a 30-50% reduction in the number of apomorphine induced rotations up to 12 weeks post implantation. Empty microspheres caused no changes in rotational behavior. Implantation of a mixture of DA/NE microspheres resulted in an 80% decrease in the number of apomorphine induced rotations, registered up to 4 weeks. Immunocytochemical examination revealed growth of DA and tyrosine hydroxylase immunoreactive fibers in the striatum of DA and NE microsphere implanted rats. Interestingly, functional behavior correlated with the degree of fiber ingrowth. This method to deliver substances to the CNS will be tested for therapeutic usefulness in patients with Parkinson's disease, in a recently approved clinical trial in Göteborg.

Animals↗
PubMed1993

Cerebrospinal fluid microglial antibodies: potential diagnostic markers for immune mechanisms in Alzheimer's disease.

Hallmark lesions of Alzheimer's disease (AD) are filled with reactive immunocompetent microglia, suggesting that immunological aberrations may participate in the pathophysiology of this disorder. Microglia may participate in the initial stages of neurodegeneration before the onset of dementia. If immune mediated processes are closely linked to neuronal breakdown it would be of importance to have a reliable means to detect these processes. Serum and cerebrospinal fluid (CSF) antibodies are discussed as such potential sources. The serendipitous use of the developing rat central nervous system (CNS) to screen CSF antibrain antibodies produced some unexpected findings. Firstly, CSF antibodies of AD and other dementia patients recognized distinctly different neuronal structures in the developing rat brain. Secondly, some AD CSF recognized fiber networks whereas others recognized amoeboid microglial cells. The same AD CSF which recognized amoeboid microglia cells also specifically marked activated microglia and neural macrophages in experimentally induced lesions. AD CSF microglial antibodies appear to be significant in view of the increasing association between microglia and neurogenerative processes in AD. In addition, CSF microglial antibodies are present in numerous at-risk descendants of familial AD patients. Some have subsequently developed the disorder. These findings together with the fact that microglial antibodies are usually found in the early stages of AD suggest that AD CSF microglial antibodies could be of value in detecting neurodegenerative processes before the onset of dementia. These findings add further support to the concept that inflammation and similar immune mechanisms may contribute to AD pathogenesis.

Aged↗
PubMed1993

Growth factors and carcinoid tumours.

The presence of growth factors and their receptors in human midgut carcinoids and in gastric carcinoids of Mastomys have been investigated. Human midgut carcinoid tumours produce IGF-I as demonstrated by immunocytochemistry and radioimmunoassay. IGF-I receptors were detectable in half of the tumours and stimulation of cultured tumour cells with IGF-I enhanced DNA synthesis. IGF-I may therefore act as an autocrine stimulator of carcinoid tumour growth. Expression of TGF-alpha and EGF-receptors could also be demonstrated in midgut carcinoids by immunocytochemistry and Northern analysis, suggesting that TGF-alpha participates in the autocrine modulation of carcinoid growth. Co-culture of human midgut carcinoid tumours and rat fetal cholinergic neurons demonstrated secretion of a potent neuronotrophic factor by cultured tumour cells. IGF-I and TGF-alpha may account for these neuronotrophic effects, but carcinoid tumours may also secrete an as yet unidentified growth factor. Gastric (ECL cell) carcinoids developed rapidly in Mastomys during hypergastrinemia due to histamine2-receptor blockade, suggesting that gastrin is an essential growth factor for these carcinoids.

Animals↗
PubMed1992

Studies of activated microglial cells and macrophages using Alzheimer's disease cerebrospinal fluid in adult rats with experimentally induced lesions.

Previous investigations have shown that cerebrospinal fluid from Alzheimer's disease patients contains antibodies that recognize the amoeboid microglia--a nascent and active form of microglia in the developing rat brain [McRae et al. (1991) Neuroscience 41, 739-752]. The present study extended this to show that the same cerebrospinal fluid from Alzheimer's disease patients also labeled the activated microglia and macrophages induced experimentally in adult central nervous system. Thus, in the spinal cord, activated microglia were elicited following the destruction of the motor neurons by the toxic lectin, Ricinus communis agglutinin, injected into the sciatic nerve. The activated microglia which were closely associated with the soma of the degenerating neurons were intensely immunostained with the cerebrospinal fluid from Alzheimer's disease patients. The labeling pattern was comparable to some known monoclonal antibodies including OX-42, OX-18 and OX-6 that mark microglia. The microglia cells on the contralateral normal side remained unstained. In the cerebrum, activated microglia and neural macrophages were induced following an epidural application of the excitotoxin, kainic acid or cryolesion. Immunoelectron microscopy of these cells showed that the immunoreactivity was localized at the plasma membrane and its derivatives suggesting that these are the sites where the antigens are associated. The results obtained in this investigation suggest that these experimental models may be a means to gain further insight to antigens recognized by antibodies in the cerebrospinal fluid of Alzheimer's disease patients.

Alzheimer Disease↗
PubMed1991

Antibody in the CSF of patients with multiple system atrophy reacts specifically with rat locus ceruleus.

Idiopathic chronic autonomic dysfunction may occur as pure autonomic failure (PAF) or in association with multiple system atrophy (MSA). CSF immunoreactivity to rat locus ceruleus occurred in a significantly greater number of samples from MSA patients compared to control subjects or patients with PAF. Other brain regions infrequently showed immunoreactivity. These findings suggest that degeneration in MSA may release antigen(s) that induce antibodies against locus ceruleus neurons. Further studies are required to determine whether immune abnormalities play a pathogenetic role in MSA. Lack of CSF immunoreactivity in PAF is consistent with primarily peripheral involvement.

Adult↗
PubMed1991

Antibodies in the cerebrospinal fluid of some Alzheimer's disease patients recognize amoeboid microglial cells in the developing rat central nervous system.

Previous investigations have demonstrated that the cerebrospinal fluid from Alzheimer's disease patients contains antibodies that recognize specific neuronal populations in the adult rat central nervous system. These findings suggest a pathogenic role for immunological aberrations in this disorder. In the present report the investigation of antibodies in the cerebrospinal fluid of Alzheimer's disease patients was extended to developing rat central nervous system. The antibody in cerebrospinal fluid from Alzheimer's disease patients recognized entirely different types of antigens in the developing rat central nervous system as compared to adult rat central nervous system. One of the most remarkable differences was the recognition of amoeboid microglial cells. Diverse morphological forms of amoeboid microglial cells were observed, located mainly in the cavum septum pellucidum and in the corpus callosum. Electron microscopy revealed that the cerebrospinal fluid antibody from the Alzheimer's disease patients recognized specific membrane receptors in the macrophagic microglia. The unexpected recognition of amoeboid microglia by antibodies in Alzheimer's disease-cerebrospinal fluid is particularly interesting since these cells proliferate in response to nervous system disease and also engulf debris. The results add further support to the concept that inflammation and similar immune mechanisms may contribute to Alzheimer's disease pathogenesis.

Adult↗
PubMed1991

Tracheo-oesophageal puncture: a review of problems and complications.

Tracheo-oesophageal puncture now has a well established role and in several units is now the principal means of speech rehabilitation following laryngectomy. Although not a difficult procedure, there are a number of problems and complications that may be encountered. With proper management these can usually be overcome and a useful voice achieved. This study looks at those problems in a series of 119 patients and discusses their management.

Deglutition Disorders↗
PubMed1991

Production of transferable neuronotrophic factor(s) by human midgut carcinoid tumour cells; studies using cultures of rat fetal cholinergic neurons.

A co-culture system was established between human midgut carcinoid tumour cells and rat fetal cholinergic neurons. In monocultures in serum-free media, only tumour cells survived, while neurons deteriorated. In serum-free co-cultures, neurons displayed outgrowth of neuritic processes. Neurons of neuronal serum-free monocultures thrived if supplemented with conditioned media from tumour cell cultures grown serum-free. This indicates that tumour cells produce transferable growth factor(s) with potent neuronotrophic actions. Immunocytochemical studies indicate that this growth factor resembles nerve growth factor immunologically, since tumour cells were strongly immunoreactive after incubation with a rabbit anti-nerve growth factor antiserum, and furthermore expressed immunoreactive nerve growth factor receptors.

Animals↗
PubMed1991

Microencapsulated dopamine (DA)-induced restitution of function in 6-OHDA-denervated rat striatum in vivo: comparison between two microsphere excipients.

Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly [DL lactide-co-glycolide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microspheres encapsulated within two different polymer excipients into denervated-striatal tissue assures a prolonged release of the transmitter in vivo. Moreover, in this regard, the results show that there were clear cut temporal differences in the effect of the two DA microsphere formulations compared in this study, probably reflecting variations in the actual composition (i.e., lactide to glycolide ratio) of the two copolymer excipients examined. This technology has considerable potential for basic research with possible clinical application.

Animals↗
PubMed1991

The potential use of a dopamine neuron antibody and a striatal-derived neurotrophic factor as diagnostic markers in Parkinson's disease.

The cerebral spinal fluid (CSF) of patients with Parkinson's disease (PD) contains an antibody that immunocytochemically reacts with dopamine (DA) neurons in the substantia nigra (SN). This antibody was found in 78% of the CSF samples taken from patients with clinical PD. In contrast, only 3% of the CSF samples taken from control patients or patients with neurologic symptoms other than PD possessed this antibody. The production of this antibody might contribute to disease progression but does not appear to be the etiologic factor responsible for PD. In other experiments, concentrates of the CSF of patients with PD enhanced growth of mesencephalic cultures relative to control CSF. Both the antibody and the growth-promoting activity found in CSF are associated with degeneration of the SN and might therefore be useful as potential diagnostic markers for PD.

Adrenal Medulla↗
PubMed1990

Investigations on auto-antibodies in Alzheimer's and Parkinson's diseases, using defined neuronal cultures.

In immunocytochemical studies, the CSF from Parkinson disease (PD) patients and from Alzheimer disease (AD) patients were investigated for the presence of neuron specific antibodies using dopaminergic and cholinergic neuronal cultures from embryonic rat brain, respectively. Dopamine containing cell bodies were labelled by Parkinsonian CSF-IgG, while cholinergic neurons, identified with a-NGF-receptor antibodies, were recognized by CSF from AD-patients. The CSF from PD-patients was investigated after autologous adrenal transplantation. CSF was removed 7 d, 5 months and 1 year after operation. When added to 18 d neuronal cultures for 3 d, the 7 d CSF caused neuronal cell and a glial reaction. The 4 months CSF caused cell death, but markedly less than the 7 d CSF. One year after transplantation the CSF had no toxic effects; these cultures were similar to control cultures. It is concluded that CSF from PD patients may contain aggressive IgG-species specific for DA neurons, and that the amount of such antibodies decrease after adrenal transplant operations. It is suggested that neurodegenerative diseases may become aggravated by autoimmune reactions.

Alzheimer Disease↗
PubMed1990

Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

Animals↗
PubMed1987

The acute orbit. Preseptal (periorbital) cellulitis, subperiosteal abscess and orbital cellulitis due to sinusitis.

The clinical picture of an acute orbit, as manifest by preseptal cellulitis, subperiosteal abscess or orbital cellulitis, is still frequently seen in ENT practice. The commonest cause is sinusitis and the authors advocate early surgical intervention in acute orbits due to sinusitis. Clinically, it can be difficult to distinguish between a subperiosteal abscess and orbital cellulitis and a CAT scan may be helpful. Surgically, a subperiosteal abscess is the more important (and probably more frequent) entity as it may require drainage. It may be suspected in an acute orbit which progresses rapidly or fails to settle on treatment and it may require drainage to allow the condition to resolve and avoid potentially damaging sequelae. A classification of the stages of the inflammatory processes seen in the acute orbit is given and the management of 34 cases due to sinusitis is discussed. The other causes of acute orbits are discussed and the further complications that may occur are also mentioned. Blindness, cavernous sinus thrombosis and cerebral involvement are still frequently recorded and death may still occur.

Abscess↗