Biomedical subjects

J Currie

Publications and source records attributed to J Currie.

At least 73 records · Page 4Linked to original sources

PubMed1993

Selective impairment of express saccade generation in patients with schizophrenia.

When a temporal gap is introduced between the offset of a central fixation point and the onset of a peripheral saccadic target, normal subjects generate an increased number of short latency (90-150 ms) saccades, termed express saccades, and the profile of express saccade frequency across different gap sizes for any individual subject, even if untrained in the task, shows a high test-retest reliability. In patients with schizophrenia, the generation of express saccades was also normal for gap sizes of 200-300 ms or in an overlap task (gap = 0 ms). However, for temporal gaps of 50-150 ms, the generation of express saccades was significantly impaired in the schizophrenic subjects. This selective deficit appeared to be independent of the patients' neuroleptic medication status and did not correlate with the severity of schizophrenic symptoms. It is postulated that the successful execution of an express saccade requires that the cognitive operations of disengagement of visual attention and selection of the appropriate motor command to generate a saccade both be commenced or completed during the temporal gap between fixation offset and peripheral target onset. Our results suggest that, in schizophrenia, there is an impairment in the cortical/subcortical neural network that generates express saccades and controls these cognitive operations. Potential sites for such dysfunction in schizophrenia include the parietal cortex and the GABA-ergic function of the superior colliculus.

Adult↗

PubMed1992

Inhalation of carbon monoxide does not accelerate arteriosclerosis in cockerels.

The effects of chronic exposure to moderate levels of carbon monoxide (CO) upon the augmentation of arteriosclerotic plaque development were investigated in a series of in vivo studies. Cockerels were exposed to carefully regulated CO levels in dynamic exposure chambers. The plaque volume percentage in the aortic walls of experimental and control animals was determined by point-counting. Chronic CO inhalation, at levels up to 200 ppm, did not stimulate arteriosclerotic plaque development (at 200 ppm CO, carboxyhemoglobin (COHb) levels 10 min after exposures ended were 11-12%). When administered concomitantly with cholesterol feeding, CO did not augment plaque development. When administered after either carcinogen-associated or diet-promoted plaque size increases had occurred, CO elicited no further plaque size increases. Thus, in this animal model, daily exposures to moderately high CO levels were without discernable effect upon arteriosclerotic plaque development, although high COHb levels were attained.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

An abnormality of plasma amyloid protein precursor in Alzheimer's disease.

beta A4 amyloid deposition in the brain, which is characteristic of Alzheimer's disease (AD), may result from either overexpression of the amyloid protein precursor (APP) or failure of APP to be correctly processed. A blood marker reflecting this abnormal metabolism would be of diagnostic value and would provide a means of monitoring the efficacy of therapeutic interventions. We analyzed immunoblots of plasma APP enriched by heparin-Sepharose chromatography from patients with moderate to severe AD dementia (n = 34) and control subjects (n = 77) and found an approximately 50% increase in the proportion of 130-kd APP species in patients with AD (p less than 0.001), no difference in the 110-kd form, a 15 to 30% decrease in the 65-kd form (p less than 0.001), and a 20 to 35% decrease in the proportion of 42-kd APP (p less than 0.001). These species of APP were soluble, lacked the carboxyl terminus, and the 110- and 42-kd species were shown to be consistent with degradation products derived from the 130-kd species. A comparison of levels of 130-kd plasma APP from moderately to severely demented patients with AD and control subjects distinguished the two groups with a specificity of 87.0% and a sensitivity of 79.4%.

Alzheimer Disease↗

PubMed1992

Gaucher patients with oculomotor abnormalities do not have a unique genotype.

Sixteen non-Ashkenazic American children with Gaucher disease who demonstrate slowing of the horizontal saccades are described. Attempts to correlate this specific clinical phenotype with a unique genotype were unsuccessful. Focusing on the three most common mutations, at least five different genotypes were present in these patients. Children with this isolated oculomotor abnormality generally had a diffusely slowed background on EEG, but an otherwise normal neurologic examination, and exhibited earlier and more severe systemic manifestations and mortality. This study emphasizes the need for careful sequential neuro-ophthalmologic examinations in Gaucher patients and the need for caution in attempting to make clinical predictions regarding the course of Gaucher disease on the basis of current DNA mutational analysis.

Adolescent↗

PubMed1992

Management of diabetes in surgery: a survey of current practice by anaesthetists.

A questionnaire survey of anaesthetists, based at the three main hospitals in Bristol, was undertaken to determine what methods are currently being used by anaesthetists to manage diabetes in patients for surgery. Replies were received from 56 of the 90 anaesthetists (62%). Surgical procedures were defined as minor, moderate, and major. Two areas were identified where considerable differences in management between anaesthetists occurred, namely insulin-treated patients requiring minor surgery, and non-insulin-treated patients requiring moderate surgery. In addition, no consensus view was apparent for the preferred intra-operative blood glucose range or for the threshold blood glucose level at which to postpone an operation. It was apparent that anaesthetists preferred to administer intravenous insulin by a syringe pump rather than by a drip bag containing insulin, potassium, and glucose, particularly if more severe metabolic upset was anticipated. No difference in management was apparent between different hospital grades or between the three hospitals.

Anesthesiology↗

PubMed1991

Validation of a clinical antisaccadic eye movement test in the assessment of dementia.

The ability to generate antisaccades (eye movements deliberately made in the direction opposite to that of a visual stimulus) may be used to assess central nervous system function in a variety of neurologic and psychiatric disorders. However, the usefulness of this paradigm in clinical practice is limited by the need for an oculographic laboratory. We describe a clinical version of such an antisaccadic task and present normative data from 332 subjects. We also examined clinical antisaccades and cognitive performance in 30 patients with Alzheimer's disease, five patients with Huntington's disease, and 12 patients with pseudodementia. In Alzheimer's disease, error rates in the clinical antisaccadic test correlated well with those from a laboratory-based antisaccadic task measured on the same day by infrared oculography, confirming that the clinical antisaccadic test is a valid analog of the more sophisticated laboratory paradigms. Clinical antisaccadic error rates correlated strongly with the severity of dementia in Alzheimer's disease, and correlations with cognitive performance suggested that the clinical antisaccadic test may have some specificity for frontal lobe dysfunction. Patients with pseudodementia had normal clinical antisaccadic error rates, and the test may therefore be of use in differentiating dementia from pseudodementia. This clinical antisaccadic test provides a simple, reliable, and inexpensive quantitative clinical tool that is of value in the assessment of disturbances of higher cortical function.

Adolescent↗

PubMed1991

The incidence of abnormal morphology and nucleocytoplasmic ratios in 2-, 3- and 5-day human pre-embryos.

Human cleaving pre-embryos at 2 and 3 days and cavitated pre-embryos at 5 days post-insemination have been examined for cell number and the incidence of mononucleated cells. At least 60% of polynucleate or anucleate cells have been detected at all these stages and regardless of morphological grading at day 2. It is concluded that even by the time at which pre-embryo replacement would occur therapeutically, the majority of pre-embryos are unlikely to have full developmental potential. The possible origins of the abnormalities of nucleocytoplasmic ratios are discussed.

Blastocyst↗

PubMed1991

Intraretinal gray lesions as a sign of reversible visual loss following prolonged ophthalmic artery hypoperfusion.

A 49-year-old woman developed severe unilateral visual loss following carotid artery ligation for a carotid-cavernous fistula. The pathophysiology was presumed to be an ophthalmic artery steal caused by the fistula. This was confirmed when visual acuity was restored by a subsequent ligation of the ophthalmic artery, despite 2 weeks of profound visual loss and ocular ischemia. Superficial cotton-wool spots and deep gray intraretinal lesions developed in the retina during the period of ocular ischemia. We postulate that the deep intraretinal lesions are clinical manifestations of a zone of retinal microvascular watershed ischemia, and that their presence may be an important diagnostic guide to the presence of reversible ocular ischemia.

Blindness↗

PubMed1990

The amyloid precursor protein of Alzheimer's disease is released by human platelets.

Western blots of normal human platelets, employing a monoclonal antibody raised against the full-length amyloid precursor protein of Alzheimer's disease (APP695), revealed major bands of 100-110 and 120-130 kDa in both cytosolic, membrane, and released fractions. These species were similar in size to forms seen in brain preparations and in plasma. There was no difference in Western blots of platelet preparations from Alzheimer patients compared with controls. Purified platelet amyloid precursor proteins were sequenced and shown to be amino terminally homogeneous. Immunohistochemistry localized the antigen to the platelet and megakaryocyte and demonstrated weak immunostaining of some lymphocytes. Immunoprecipitation of material released from platelets demonstrated that sedimentable full-length APP with the carboxyl-terminal epitope, and soluble APP lacking the carboxyl-terminal epitope, may exist in the circulation. Western blots and carboxyl-terminal and amino-terminal APP radioimmunoassay of material released by platelets in response to stimulation revealed that platelets release APP during degranulation. The function of platelet APP is yet to be determined, but the present studies suggest a role in regulation of the coagulation cascade or in platelet aggregation.

Alzheimer Disease↗

PubMed1990

Acid Tyrode's solution can stimulate parthenogenetic activation of human and mouse oocytes.

Fresh and aged (24 hours after ovulation) human oocytes and recently ovulated mouse oocytes may be activated by exposure to acidified Tyrode's solution. No activation of either type of human oocyte was observed after exposure to hyaluronidase or pronase, but significant numbers of fresh mouse oocytes were activated after exposure to pronase but not to chymotrypsin. The implications of these results for the manipulation of human and mouse eggs in vitro are discussed.

Animals↗

PubMed1990

Transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in the human oocyte.

The effect on the microtubule system of human oocytes of cooling to room temperature for either 10 or 30 minutes has been investigated. Changes in spindle organization were found in all oocytes cooled for 30 minutes compared with control oocytes kept at 37 degrees C throughout. These changes included reduction in spindle size, disorganization of microtubules within the spindle itself, and sometimes a complete lack of microtubules. In some oocytes, chromosome dispersal from the metaphase plate was associated with these changes. Cooling the oocyte to room temperature for only 10 minutes produced a similar pattern of disruption to spindle structure in many cases. The spindles in oocytes that were cooled for either 10 or 30 minutes and then allowed to recover at 37 degrees C for either 1 or 4 hours were found to resemble those in noncooled control oocytes in less than one half of the cases examined, although in only a few cases did the chromosomes remain dispersed. The significance of these findings for the handling of oocytes during gamete intrafallopian transfer and in vitro fertilization procedures is discussed in relation to the levels of aneuploidy detected in early human embryos.

Chromosomes↗

PubMed1990

[Paraneoplastic retinopathy simulating cone dystrophy with achromatopsia].

A 72-year-old woman developed recurrent blindness on exposure to bright light (sunlight). Examination revealed total achromatopsia; bilateral central scotomas, predominant suppression of the cone response by electroretinography, and narrowing of the retinal arteries on ophthalmoscopy. The general examination revealed a pelvic tumor that later proved to be a pleomorphic carcinoma of presumed uterine origin. The patient died of metastatic disease 9 months after the ocular symptoms developed. Histopathologic examination of the eyes revealed loss of the photoreceptors, most extensive in the macular regions, and selective loss of the cones from the rest of the retinas. No ocular metastases of inflammation were found. The changes described are interpreted as paraneoplastic retinopathy of autoimmune origin.

Aged↗

PubMed1990

Rate-controlled analgesia: a laboratory evaluation of a new infusion device.

We report an evaluation of the Bard Harvard Mini Infuser, one of a new generation of agent-specific intraoperative infusion pumps which are designed for use by the anaesthetist. This pump permits potent intravenous anaesthetic agents to be used in pharmacokinetically designed dosage regimens. The controls are calibrated directly in kg body weight and micrograms per minute rather than the usual settings of ml of solution per hour. The performance was assessed by measuring the volume delivered over given time intervals and all safety functions were tested at least three times. This device was found to be acceptably safe and accurate. Two points to note are that it must be purged every time before it is connected to the intravenous infusion and if an occlusion is suddenly relieved, the patient can receive an 'accidental bolus' of up to 1.18 ml of drug. The main advantage of this pump is that it uses undiluted drug direct from the ampoule and does not require any calculations or dilutions prior to use. However, this restricts its use to drugs with a concentration of 500 mcg/ml and in effect means that it is suitable mainly for infusion of alfentanil.

Anesthesia, Intravenous↗

PubMed1989

Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease.

Immunocytochemical staining with monoclonal antibodies to the beta-protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the beta-protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word "plaques" does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto- and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.

Aged↗

PubMed1989

Neurologic findings in men with isolated hypogonadotropic hypogonadism.

We studied the neurologic abnormalities in 41 men with isolated hypogonadotropic hypogonadism. Findings included anosmia, hyposmia, mirror movements, ocular motor abnormalities, cerebellar dysfunction, and pes cavus foot deformity. One-third of the subjects had a family history of delayed sexual maturation. Patients with a family history of delayed sexual maturation had a significantly higher incidence of olfactory dysfunction, mirror movements, and pes cavus foot deformity. Our data suggest that isolated hypogonadotropic hypogonadism and its accompanying neurologic abnormalities may arise from a genetically linked developmental abnormality of CNS structures.

Adult↗

PubMed1989

[High-resolution eye movement recording in the assessment of neurologic complications in HIV-1 infection].

HIV-1 related brain disease gives rise to widespread eye movement abnormalities that include impairment of fixation, saccadic speed and accuracy, antisaccadic generation and smooth pursuit function. Quantitative high resolution recording of eye movements is a valuable, non-invasive technique both for measuring the severity and progression of the AIDS dementia complex and the early detection of neurologic dysfunction in asymptomatic HIV-seropositive subjects or in patients with AIDS. In particular, it may be of use in neurologically at-risk patients requiring antiviral therapy and in monitoring the neurologic responses to such treatment.

AIDS Dementia Complex↗

PubMed1988

Receptor binding of guinea pig and pig vasoactive intestinal peptides by rat lung.

Guinea pig vasoactive intestinal peptide (gpVIP) differs from other mammalian VIPs in four of its 28 amino acid residues. In the present study, the gpVIP displaced 125I-labelled pig VIP (pVIP) binding by rat lung membranes with 7.7-fold lower potency than pVIP. Degradation of gpVIP by rat lung membranes, assessed by radioimmunoassay and h.p.l.c., was 1.9-fold greater than that of pVIP. This difference in degradation of the two peptides was not large enough to account for the lower receptor-binding potency of gpVIP. The amino acid residues that distinguish pVIP from gpVIP are likely to contribute to the interaction of VIP with receptors and peptide hydrolases in lung membranes.

Animals↗

PubMed1988

Intraperitoneal chromic phosphate therapy after second-look laparotomy for ovarian cancer.

Between 1973 and 1985, 118 patients in clinical remission after initial surgery and postoperative chemotherapy for epithelial ovarian carcinoma underwent second-look laparotomy at the University of North Carolina. No evidence of disease (NED) was found in 57 of these patients; 43 patients received 15 mCi of radioactive chromic phosphate (32P) suspension given intraperitoneally in the immediate postoperative period. In 29 other patients, only microscopic or minimal residual disease (nodules less than 2 cm in size) was found, seven received 32P alone, ten received 32P and further chemotherapy, and 12 received chemotherapy alone. The 4-year postsecond-look survival of the patients with NED at second-look was 89% for those receiving 32P and 67% for those who had not. The respective figures for patients with minimal residual disease at second-look are 59% versus 22%. Irrespective of treatment, a group at high risk for failure after negative second-look laparotomy has been identified; those with an initial International Federation of Gynecology and Obstetrics (FIGO) stage greater than I and histologic grade greater than 1. A comparison of our data with 18 previously published series, indicates that use of postsecond-look intraperitoneal 32P can improve the progression-free interval, and possibly overall survival, of patients with NED or minimal residual disease without adding significant complications.

Carcinoma↗