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Biomedical subjects

C Curry

Publications and source records attributed to C Curry.

At least 19 recordsLinked to original sources
PubMed2004

Long term visual and neurological prognosis in patients with treated and untreated cavernous sinus aneurysms.

OBJECTIVE: To determine the long term visual and neurological outcome of patients diagnosed with cavernous sinus aneurysms (CCAs). METHODS: Prospective follow up for at least five years or until death of 31 retrospectively recruited patients (27 women, 4 men) with treated and untreated CCAs. RESULTS: There were 40 aneurysms in all. Mean age at diagnosis was 60.4 years (range 25 to 86; median 64). The most common symptoms were diplopia (61%), headache (53%), and facial or orbital pain (32%). Fifteen patients (48%) were diagnosed after they developed cranial nerve pareses, four (13%) after they developed carotid-cavernous sinus fistulas (CCFs), and 12 (39%) by neuroimaging studies done for unrelated symptoms. Twenty one patients (68%) had treatment to exclude the aneurysm from circulation, 10 shortly after diagnosis and 11 after worsening symptoms. Immediate complications of treatment occurred in six patients and included neurological impairment, acute ophthalmoparesis, and visual loss. Ten patients (32%) were observed without intervention. Over a mean (SD) follow up period of 11.8 (7.7) years, eight had improvement in symptoms, five remained stable, and eight deteriorated. Among the 10 patients followed without intervention, none improved spontaneously, three remained stable, and seven worsened. CONCLUSIONS: Most treated patients in this series improved or remained stable after treatment, but none improved without treatment. The long term prognosis for treated cases is relatively good, with most complications occurring immediately after the procedure. Endovascular surgery has decreased the morbidity and mortality of treatment so should be considered for any patient with a CCA.

Adult↗
PubMed2002

Uptake of psychosocial referrals in an outpatient cancer setting: improving service accessibility via the referral process.

The object of this study was to identify factors which influence the uptake of psychosocial services in an ambulatory cancer setting and to identify potential barriers to the access of support services in the referral process. To this end, 202 individuals attending outpatient clinics of a cancer hospital were randomised to the intervention arm of a study to assess the impact of providing co-ordinated, targeted psychosocial referrals and interventions. Qualitative and quantitative analysis of the reasons for failure to offer services and for nonacceptance of services was undertaken. Individuals accepted 22% of offered services, refused 38% of offered services, indicated that services were in place in 31% of cases, and were not offered 9% of identified services. The major response from patients refusing services was "not now". Female patients ( P < 0.01), and individuals with a moderate to high level of depression ( P = 0.02), were more likely to accept services. A variety of factors impact on decisions on utilisation of support services. Recommendations on how individuals' access to these services might be improved are offered, based on an analysis of the reasons given by patients for refusal.

Aged↗
PubMed2001

Reversal of experimental diabetic neuropathy by VEGF gene transfer.

The pathogenetic basis for diabetic neuropathy has been enigmatic. Using two different animal models of diabetes, we have investigated the hypothesis that experimental diabetic neuropathy results from destruction of the vasa nervorum and can be reversed by administration of an angiogenic growth factor. Nerve blood flow, as measured by laser Doppler imaging or direct detection of a locally administered fluorescent lectin analogue, was markedly attenuated in rats with streptozotocin-induced diabetes, consistent with a profound reduction in the number of vessels observed. A severe peripheral neuropathy developed in parallel, characterized by significant slowing of motor and sensory nerve conduction velocities, compared with nondiabetic control animals. In contrast, 4 weeks after intramuscular gene transfer of plasmid DNA encoding VEGF-1 or VEGF-2, vascularity and blood flow in the nerves of treated animals were similar to those of nondiabetic control rats; constitutive overexpression of both transgenes resulted in restoration of large and small fiber peripheral nerve function. Similar experiments performed in a rabbit model of alloxan-induced diabetes produced comparable results. These findings support the notion that diabetic neuropathy results from microvascular ischemia involving the vasa nervorum and suggest the feasibility of a novel treatment strategy for patients in whom peripheral neuropathy constitutes a secondary complication of diabetes.

Animals↗
PubMed2001

The N-terminal 17% of apoB binds tightly and irreversibly to emulsions modeling nascent very low density lipoproteins.

The N-terminal 17% of apolipoprotein B (apoB-17) readily associates with dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV) to form large (240-A diameter) discoidal particles. Because apoB is normally secreted with triacylglycerol (TAG)-rich lipoproteins, we studied the binding of apoB-17 to triolein-rich emulsions modeling nascent TAG-rich very low density-like lipoproteins. Emulsions with the following composition (by weight) were prepared: 85--89% triolein, 1.1--1.4% cholesterol, and 10--14% phosphatidylcholines (PC) including either egg yolk (EY)-, dimyristoyl (DM)-, or dipalmitoyl (DP)-PC representing (at 25 degrees C), respectively, a fluid surface, a surface at transition, and a mainly solid surface. The respective sizes were 1,260 +/- 500, 1,070 +/- 450, and 830 +/- 300 A mean diameter. The emulsions were incubated with conditioned medium containing apoB-17, and then reisolated by ultracentrifugation. Analysis of the emulsion-bound proteins by gel electrophoresis showed that all three emulsions bound primarily apoB-17. The DPPC emulsions bound more apoB-17 than EYPC or DMPC emulsions. Immunoaffinity-purified apoB-17 exhibited saturable, high affinity binding to EYPC and DPPC emulsions. The respective K(d) values were 32 +/- 23 and 85 +/- 27 nM and capacities (N) were 10 and 58 molecules of apoB-17 per particle. When apoB-17 bound to emulsions was incubated with DMPC MLV at 26 degrees C for 18 h, it remained bound to the emulsions, indicating that once bound to these emulsions it is unable to exchange off and solubilize DMPC into discs. In contrast, apoE-3 bound to emulsions dissociated from the emulsions when incubated with DMPC MLV and formed discs.Thus, apoB-17 binds strongly and irreversibly to emulsions modeling nascent lipoproteins. It therefore may play an important role in the stabilization of nascent VLDL and chylomicrons.- Herscovitz, H., A. Derksen, M. T. Walsh, C. J. McKnight, D. L. Gantz, M. Hadzopoulou-Cladaras, V. Zannis, C. Curry, and D. M. Small. The N-terminal 17% of apoB binds tightly and irreversibly to emulsions modeling nascent very low density lipoproteins. J. Lipid Res. 2001. 42: 51;-59.

Animals↗
PubMed2000

Age-dependent defect in vascular endothelial growth factor expression is associated with reduced hypoxia-inducible factor 1 activity.

Previous studies have indicated that advanced age is associated with impaired angiogenesis in part because of reduced levels of vascular endothelial growth factor (VEGF) expression. To investigate potential mechanisms responsible for this age-dependent defect in VEGF expression, aortic smooth muscle cells isolated from young rabbits (ages 6-8 months) or old rabbits (ages 4-5 years) were exposed to normoxic (21% oxygen) or hypoxic (0.1% oxygen) conditions. Hypoxia-induced VEGF expression was significantly lower in old versus young cells. VEGF mRNA stability in hypoxic conditions was similar in both young and old cells. However, transient transfection with a luciferase reporter gene that was transcriptionally regulated by the VEGF promoter revealed a significant defect in VEGF up-regulation following hypoxia in old versus young cells (a 43 versus 117% increase in luciferase activity, p < 0.05); this difference was not seen when a deletion construct lacking the hypoxia-inducible 1 (HIF-1) binding site was used. Moreover, although HIF-1 alpha-mRNA expression was shown to be similar in young and old smooth muscle cells, HIF-1 alpha protein and DNA binding activity were significantly reduced in old versus young smooth muscle cells that were exposed to hypoxia. We propose that age-dependent reduction in hypoxia-induced VEGF expression results from reduced HIF-1 activity and may explain the previously described age-dependent impairment of angiogenesis in response to ischemia.

Aging↗
PubMed2000

Can we improve the diagnostic efficiency and predictive power of prodromal symptoms for schizophrenia?

Prodromal symptoms and other variables for a sample of 200 young people who had experienced a first-onset functional psychosis, were analyzed to examine their diagnostic efficiency and predictive power in relation to a diagnosis of schizophrenia. Two different techniques were utilized to generate optimal cut-off points for a number of prodromal symptoms, and optimal decision rules to maximize diagnostic efficiency. The product of the chance-corrected sensitivity and specificity, or the area under the QROC curve, was used to assess the predictive efficiency of a number of prodromal variables, DSM-III-R prodromal variables, pre-psychotic deterioration, pre-morbid functioning, and prodromal duration. The SPAN technique generated a decision rule that performed equivalently to the single variable 'duration of prodrome'. Implications of these results for future research are discussed.

Adolescent↗
PubMed2000

Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy.

Ischemic peripheral neuropathy is a frequent, irreversible complication of lower extremity vascular insufficiency. We investigated whether ischemic peripheral neuropathy could be prevented and/or reversed by gene transfer of an endothelial cell mitogen designed to promote therapeutic angiogenesis. Intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor (VEGF) simultaneously with induction of hindlimb ischemia in rabbits abrogated the substantial decrease in motor and sensory nerve parameters, and nerve function recovered promptly. When gene transfer was administered 10 days after induction of ischemia, nerve function was restored earlier and/or recovered faster than in untreated rabbits. These findings are due in part to enhanced hindlimb perfusion. In addition, however, the demonstration of functional VEGF receptor expression by Schwann cells indicates a direct effect of VEGF on neural integrity as well. These findings thus constitute a new paradigm for the treatment of ischemic peripheral neuropathy.

Animals↗
PubMed1999

Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay.

BACKGROUND: Ventricular pacing can improve hemodynamics in heart failure patients, but direct effects on left ventricular (LV) function from varying pacing site and atrioventricular (AV) delay remain unknown. We hypothesized that the magnitude and location of basal intraventricular conduction delay critically influences pacing responses and that single-site pacing in the delay-activated region yields similar or better responses to biventricular pacing. METHODS AND RESULTS: Aortic and LV pressures were measured in 18 heart failure patients (mean+/-SD: LV ejection fraction, 19+/-7%; LV end-diastolic pressure, 25+/-8 mm Hg; QRS duration, 157+/-36 ms). Data under normal sinus rhythm were compared with ventricular pacing (VDD) at varying sites and AV delays (randomized order). Right ventricular (RV) apical or midseptal pacing had negligible contractile/systolic effects. However, LV free-wall pacing raised dP/dtmax by 23.7+/-19.0% and pulse-pressure by 18.0+/-18.4% (P<0.01). Biventricular pacing yielded less change (+12.8+/-9.3% in dP/dtmax, P<0.05 versus LV). Pressure-volume analysis performed in 11 patients consistently revealed minimal changes with RV pacing but increased stroke work and lower end-systolic volumes with LV pacing. Optimal AV intervals averaged 125+/-49 ms, and within this range, AV delay had less influence on LV function than pacing site. Basal QRS duration positively correlated with %DeltadP/dtmax (P<0.005), but pacing efficacy was not associated with QRS narrowing. Conduction delay pattern generally predicted pacing sites with most effect. CONCLUSIONS: VDD pacing acutely enhances contractile function in heart failure patients with intraventricular conduction delay. Single-site pacing at the site of greatest delay achieves similar or greater benefits to biventricular pacing in such patients. These data clarify pacing-effect mechanisms and should help in candidate identification for future studies.

Adult↗
PubMed1999

Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2.

Deficiency of the GM2 activator protein, encoded by GM2A, results in the rare AB-variant form of GM2 gangliosidosis. Four mutations have been identified, but the human gene structure has been only partially characterized. We report a new patient from a Laotian deme whose cells are deficient in both GM2-activator mRNA and protein. However, reverse transcription (RT)-PCR detected some normal-sized cDNA and a smaller cDNA species, which was not seen in the RT-PCR products from normal controls. Sequencing revealed that, although the patient's normal-sized cDNA contained a single nonsense mutation in exon 2, his smaller cDNA was the result of an in-frame deletion of exon 2. Long PCR was used to amplify introns 1 and 2 from patient and normal genomic DNA, and no differences in size, in 5' and 3' end sequences, or in restriction-mapping patterns were observed. From these data we developed a set of four PCR primers that can be used to identify GM2A mutations. We use this procedure to demonstrate that the patient is likely homozygous for the nonsense mutation. Other reports have associated nonsense mutations with dramatically reduced levels of mRNA and with an increased level of skipping of the exon containing the mutation, thus reestablishing an open reading frame. However, a recent article has concluded that, in some cases, the latter observation is caused by an artifact of RT-PCR. In support of this conclusion, we demonstrate that, if the competing, normal-sized cDNA is removed from the initial RT-PCR products, from both patient and normal cells, by an exon 2-specific restriction digest; a second round of PCR produces similar amounts of exon 2-deleted cDNA.

Base Sequence↗
PubMed1999

Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach.

OBJECTIVE: Early intervention research is examining whether reducing the duration of untreated psychosis (DUP) leads to improved outcome from first-episode psychosis. Another key influence may be the quality of treatment after initiation of care. This study examined the effect of phase-specific treatment on 12-month outcome for different categories of DUP. METHOD: A total of 250 first-episode psychosis cases were followed up 12 months after stabilization. The sample consisted of two historically sequential cohorts treated in the same region within different service models, one of which was more intensive and phase-specific. Outcome was compared according to four predefined categories of DUP. RESULTS: Only patients with a mid-range DUP of 1-6 months who were treated within the phase-specific model experienced significantly better outcomes than patients treated within the previous model. CONCLUSION: These data suggest that there may be a limited window of opportunity in which to influence outcome. However, the complexity of this relationship is emphasized.

Acute Disease↗
PubMed1998

Acute mountain sickness in the Southern Alps of New Zealand.

AIM: To assess the incidence and impact of acute mountain sickness in the Southern Alps of New Zealand. METHODS: Over a 22 month period, mountaineers in the Mount Cook region were asked to complete a questionnaire at the completion of their climbing excursions. The questionnaire recorded demographic data and incorporated the Lake Louise scoring system to assess the presence of acute mountain sickness. RESULTS: Of the 114 subjects who completed the questionnaire, 30 (26%) developed acute mountain sickness. The incidence was higher amongst those who slept above 2500 m (50%). Of those with acute mountain sickness, 33% reported that their symptoms resulted in no reduction in activity, while 13% reported a moderate or severe reduction in activity. CONCLUSION: Mountaineers climbing in New Zealand's Southern Alps should be aware of the risk of acute mountain sickness, especially for those sleeping above 2500 m.

Adolescent↗
PubMed1998

Juvenile rheumatoid arthritis and del(22q11) syndrome: a non-random association.

Del(22q11) is a common microdeletion syndrome with an extremely variable phenotype. Besides classical manifestations, such as velocardiofacial (Shprintzen) or DiGeorge syndromes, del(22q11) syndrome may be associated with unusual but probably causally related anomalies that expand its phenotype and complicate its recognition. We report here three children with the deletion and a chronic, erosive polyarthritis resembling idiopathic cases of juvenile rheumatoid arthritis (JRA). Patient 1, born in 1983, initially presented with developmental delay, facial dysmorphism, velopharyngeal insufficiency, and severe gastro-oesophageal reflux requiring G tube feeding. From the age of 3 years, he developed JRA, which resulted in severe restrictive joint disease, osteopenia, and platyspondyly. Patient 2, born in 1976, had tetralogy of Fallot and peripheral pulmonary artery stenosis. She developed slowly, had mild dysmorphic facial features, an abnormal voice, and borderline intelligence. JRA was diagnosed at the age of 5 years. The disorder followed a subacute course, with relatively mild inflammatory phenomena, but an extremely severe skeletal involvement with major osteopenia, restrictive joint disease (bilateral hip replacement), and almost complete osteolysis of the carpal and tarsal bones with phalangeal synostoses, leading to major motor impairment and confinement to a wheelchair. Patient 3, born in 1990, has VSD, right embryo-toxon, bifid uvula, and facial dysmorphism. She developed JRA at the age of 1 year. She is not mentally retarded but has major speech delay secondary to congenital deafness inherited from her mother. In the three patients, a del(22q11) was shown by FISH analysis. These observations, and five other recently published cases, indicate that a JRA-like syndrome is a component of the del(22q11) spectrum. The deletion may be overlooked in those children with severe, chronic inflammatory disorder.

Adult↗
PubMed1998

Analysis of the initial treatment phase in first-episode psychosis.

BACKGROUND: The Early Psychosis Prevention and Intervention Centre (EPPIC) commenced operation in Melbourne, Australia, in 1992. It offers a model for management of first-episode psychosis, utilising principles of early detection, low-dose medication and comprehensive psychosocial interventions within the least restrictive setting. METHOD: Data were examined from the first three months of treatment for all consecutive people with first-episode psychosis (n = 231) accepted in the programme in 1995-1996. A subsample of patients (n = 120) was assessed comparing clinical ratings with variables of gender, diagnosis, hospitalisation, and medication. RESULTS: Hospitalisations were brief, and avoided for a third of the people. Low-dose antipsychotic medication was maintained in both in-patient and community settings. Those people with manic psychosis were more likely to be hospitalised. Hospitalised people received higher antipsychotic dosages, and had a greater rate of reduction in Brief Psychiatric Rating Scale psychotic subscale scores at three months follow-up. Eighty per cent of a representative subsample had responded to treatment and 63% were in remission by the end of the three months. CONCLUSION: This naturalistic study suggests that the feasibility of implementing the EPPIC model in a range of clinical settings is promising and applicable in practice.

Adult↗