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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 55 records · Page 3Linked to original sources
PubMed2001

Depression in the community dwelling elderly: do clinical and sociodemographic factors influence referral to psychiatry?

BACKGROUND: Little is known about the reasons why depressed elderly patients are referred to the old age psychiatric services. Reasons for referral of depressed younger patients have been clarified however they may not be generalisable to an older population. OBJECTIVES: The purpose of this study is to examine which clinical and sociodemographic factors influence referral of patients with late life depression from primary care. METHODS: Twenty-eight people were identified with depression in a day hospital referred by their general practitioner. These were compared with fifty-two people with depression in the community who had not been referred to the psychiatric services. RESULTS: Having a more severe depression (p = 0.0016) and having co-morbid anxiety (p = 0.0017) meant you were more likely to be referred to the day hospital. Gender did not appear to influence referral from general practitioners. CONCLUSIONS: It appears that severity of depression and having higher levels of anxiety make it more likely that you will be referred by your general practitioner to the old age psychiatry services.

Aged↗
PubMed2001

Rainbow trout (Oncorhynchus mykiss) recombinant IL-1beta and derived peptides induce migration of head-kidney leucocytes in vitro.

The present work provides the first information concerning the chemoattractant activity of trout recombinant IL-1beta and its derived peptides, referred to as P1, P2 and P3. The predicted rainbow trout mature interleukin-1beta peptide was produced as a recombinant protein in Escherichia coli. The first peptide, P1, corresponded to fragment 146-157 (YVTPVPIETEAR) of the trout sequence and had an MW of 137 kDa. It was equivalent to a region known to be part of the receptor binding domain from the mammalian crystal structure of IL-1beta complexed to its receptor. P2 was used as control peptide, consisting of the same 12 amino acids as P1, but arranged in a random sequence (VVEEYIRAPPTT). P3 was synthesised to complex with an adjacent region of the IL-1 receptor, and corresponded to fragment 207-216 (YRRNTGVDIS) of the trout sequence, with an MW of 1.18 kDa. Migration was stimulated when leucocytes were exposed to concentrations of > or = 10 ng ml(-1) rIL-1beta. Peptide P3 also induced leucocyte migration, with an optimal dose of 0.25 mM being recorded. While P1 had no effect on cell migration when used alone, synergism was evident as a consequence of combining P1 with a suboptimal dose (0.01 mM) of P3. No synergism occurred when cells were exposed to a combination of P3 and the control peptide P2.

Amino Acid Sequence↗
PubMed2001

Toxicity assessment of intratumoral injection of the herpes simplex type I thymidine kinase gene delivered by retrovirus in patients with refractory cancer.

Introduction of the herpes simplex type I thymidine kinase (HSV-TK) gene into tumor tissue, followed by ganciclovir, initiates a phosphorylation cascade that induces formation of a toxic ganciclovir triphosphate. Animal trials suggest that this ganciclovir triphosphate has antitumor activity. Here we report application of the HSV-TK transfection approach using a retroviral construct. Sixteen patients (median age 61.5 years) with refractory carcinoma (13 melanoma, 1 breast cancer, 1 nonsmall-cell lung cancer, and 1 osteogenic sarcoma) received intratumoral injection of HSV-TK retroviral vector at escalating doses (0.2x10(7) cfu per injection x 5 daily doses) and we evaluated them for toxicity and activity. We observed grade III pain associated with cellulitis in one patient following injection. Analysis of blood samples drawn between 3 and 28 weeks from 14 patients for replication-competent retrovirus by PCR analysis of the amphotrophic envelope revealed no replication-competent retrovirus. We injected 21 lesions. We identified no tumor responses of the injected lesions. Of 13 patients with advanced melanoma, 6 survived over one year. Thus, injection of retroviral delivered HSV-TK in patients with refractory cancer was well-tolerated.

Adult↗
PubMed2001

Cloning and sequencing of caspase 6 in rainbow trout, Oncorhynchus mykiss, and analysis of its expression under conditions known to induce apoptosis.

The rainbow trout caspase 6 gene has been cloned and sequenced. The open reading frame consisted of 906bp, which translated into a protein of 302 amino acids, containing the caspase active site pentapeptide (QACRG) and the caspase family signature (HADADCFVCVFLSHG). Amino acids involved in catalysis and those known to form the P1 carbohydrate binding pocket were conserved. Phylogenetic tree analysis showed a tight grouping with other known caspase 6 genes. Conserved aspartic acid residues at positions 33, 191 and 202 suggested that this molecule is produced as a proenzyme that is subsequently cleaved to release active subunits, with the region between Asp-191 and Ala-203 acting as a linker that is cleaved out. RT-PCR analysis revealed that the trout caspase 6 gene was expressed in brain, blood, gill, liver, head kidney and spleen. Addition of LPS or cortisol to head kidney leucocyte cultures had no effect upon caspase 6 expression. However, addition of LPS after preincubation with cortisol increased expression relative to control cultures. Incubation with RU486 abrogated this effect, confirming it was mediated via glucocorticoid receptors. Lastly, a confinement stress in vivo increased caspase 6 expression. The data are discussed with respect to the immunoregulatory role of apoptosis in fish immune responses.

Amino Acid Sequence↗
PubMed2001

Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity.

Although genetically engineered adenoviruses hold promise for the treatment of cancer, clinical trial reports have utilized intratumoral injection to date. To determine the feasibility of intravenous delivery of ONYX-015, an E1B-55kD gene-deleted replication selective adenovirus with demonstrated clinical safety and antitumoral activity following intratumoral injection, we performed a clinical trial in patients with metastatic solid tumors. ONYX-015 was infused intravenously at escalating doses of 2 x 10(10) to 2 x 10(13) particles via weekly infusion within 21-day cycles in 10 patients with advanced carcinoma metastatic to the lung. No dose-limiting toxicity was identified. Mild to moderate fever, rigors and a dose-dependent transient transaminitis were the most common adverse events. Neutralizing antibody titers significantly increased within 3 weeks in all patients. IL-6, gamma-IFN, TNF-alpha and IL-10 increased within 24 h following treatment. Evidence of viral replication was detectable in three of four patients receiving ONYX-015 at doses > or = 2 x 10(12) particles and intratumoral replication was confirmed in one patient. In conclusion, intravenous infusion of ONYX-015 was well tolerated at doses up to 2 x 10(13) particles and infection of metastatic pulmonary sites with subsequent intratumoral viral replication was seen. The intravenous administration of genetically altered adenovirus is a feasible approach.

Adenocarcinoma↗
PubMed2001

Constipation in very-low-birth-weight children at 10 to 14 years of age.

BACKGROUND: The authors documented that very-low-birth-weight children (less than 750-g) when compared with 750-to 1,499-g birth-weight and normal-birth-weight-matched controls have higher than normal rates of neurosensory and cognitive impairments at school age. In this population, the authors found a higher rate of constipation than expected among 19 of 59 (32%) less-than-750-g-birth-weight children. The authors therefore wanted to evaluate in greater detail the problem of constipation and associated toileting problems in this population. METHODS: Nineteen less-than-750-g-birth-weight children with constipation were matched to the next less than 750-g-birth-weight child of comparable age, sex, and race who did not have constipation. A telephone questionnaire was administered to 15 of 19 parents of the less-than-750-g-birth-weight children who had constipation. RESULTS: The 15 children with constipation had significantly higher rates of neurosensory impairment (7 [47%] vs. 1 [7%]) and lower mean WISC III IQ scores (72 +/- 22 vs. 89 +/- 13) when compared with birth-weight-matched controls without constipation (P < 0.05). The constipated children also had significantly higher rates of associated toileting problems, including encopresis (8[53%] vs. 1 [7%])and stool withholding (9 [60%] vs. 2 [13%]; P < 0.05). CONCLUSION: The higher incidence of constipation among less-than-750-g-birth-weight children is associated with neurodevelopment impairment. Awareness of this problem and preventive intervention to ensure regular stools could possibly decrease the high rate of constipation and associated toileting problems.

Adolescent↗
PubMed2001

Mastery motivation in children with Down syndrome.

Mastery motivation refers to the intrinsic motivation children have to interact with their environments in order to learn about them. It appears early in life, and has been regarded by many researchers as a key motivator for development. It has also been suggested that young school age children with Down syndrome show lowered motivation to perform tasks. It is important to know if this low motivation is present from the start, or develops as a result of environmental experiences; studies of mastery motivation have been one way of investigating this issue. However definitions of mastery motivation, and hence empirical studies, have varied. Thus this paper starts by revisiting the issues surrounding definition and measurement. There is general agreement on some issues: that mastery motivation is intrinsic, that it is manifest in different behaviours as the child develops, that there are individual differences in mastery behaviour, and that these are affected by environmental factors. There is also current agreement that it is essential to remove the confound of differing levels of developmental competence by using individualized measurement. However there is disagreement about which behaviours best index mastery motivation. Some empirical work with infants with Down syndrome is reviewed, and results from a recent longitudinal study on the development of mastery motivation are presented. The results concurred with most others in the recent literature, suggesting that low mastery motivation is not inevitable in infancy in Down syndrome. Infants with Down syndrome showed similar patterns of development as typically developing children, with slight delays. It is argued that longitudinal studies are needed to demonstrate such patterns of development. As the children developed from 6 to 24 months mental age there was no evidence for decreasing levels of mastery motivation. Thus there was no support for the view that more failure experiences impact on levels of mastery motivation. In contrast caregivers did see their young children with Down syndrome as less object mastery oriented than did caregivers of typically developing children. The caregivers of children with Down syndrome were also significantly more directive in their interactions with their children, and there was some suggestion that individual differences in mastery behaviours were related to levels of mastery behaviours in their children. The final section speculates on reasons for these results, and makes suggestions for future work.

Child↗
PubMed2001

Potential clinical application of antioncogene ribozymes for human lung cancer.

Non-small-cell lung cancer frequently contains oncogenetic defects (mutations in ras, retinoblastoma, and p53 genes) that contribute to disease pathophysiology. Recent studies and clinical trials have focused on gene therapy approaches that either replace the function of defective tumor-suppressor genes such as p53 or inactivate mutant oncogenes such as ras. Ribozymes are RNA molecules with highly specific intrinsic enzymatic activity against target RNA sequences, which can discriminate mutant sequences that differ by a single base from their wild-type counterparts. Following binding to the RNA substrate by base-pair complementation, the ribozyme cleaves the target RNA irreversibly, then releases itself for new rounds of subsequent cleavage, resulting in significantly improved target:effector stoichiometry as compared with antisense oligonucleotides of the same specificity. Transcript-specific ribozymes have been used extensively for experimental oncogene inactivation. Ribozymes are effective for targeting mutant ras, p53, or the multidrug-resistant gene product for lung cancer cells in vitro. However, their in vivo effect is not well defined against this malignancy. We recently characterized the antitumor properties of an anti-K-ras ribozyme specific for the K-ras codon 12 mutation (GGT-->GTT). When delivered as a transgene by an adenoviral vector (ADV), the K-ras ribozyme (KRbz) suppressed growth of lung tumor xenografts expressing the relevant mutation, whereas the corresponding antisense sequence lacking catalytic activity did not. Multiple intratumoral (3-5) injections of KRbz-ADV were effective in producing complete tumor regressions of preexisting tumor xenografts. Clinical trials are under consideration to examine the applicability of this anti-K-ras ribozyme for treatment of non-small-cell lung cancers expressing the relevant mutation.

Journal Article↗
PubMed2001

The effects of age on accident severity and outcome in Irish road traffic accident patients.

Road traffic accidents (RTA's) are the leading cause of fatal trauma in Ireland. Although older drivers are the safest group of drivers in the population, once involved in a crash they are more likely to sustain a severe injury or death. The experiences of Irish elderly RTA victims has not been previously documented. We studied older RTA patients admitted to two Irish trauma centres in 1995. Of 525 patients, 39 (7%) were aged over 65. We compared 38 patients aged 16-64 years for comparison and reviewed the notes in detail. Elderly patients were mostly pedestrians (23/38 - 61%) though 21% (8/38) were drivers with 8% (3/38) on public transport. Younger patients were mostly drivers (14/37 - 38%), cyclists (9/37 - 24%) or motorcyclists (7/37 - 19%). Older patients had a higher median Injury Severity Score, p < 0.05, were more likely to be female (p<0.01), involved in RTA's between 9am-5pm (p<0.05) and have pre-existing medical conditions (p<0.01). The following were significantly increased in older patients (p values): surgical (<0.01), medical (<0.01) and therapist workload (p<0.05), complications (<0.0001), length of stay (<0.01). Less elderly were discharged directly to home (p<0.001). Strategies to reduce the mortality and morbidity associated with RTA in the elderly should emphasise a) older pedestrians during daytime hours, b) attention to safety in public transport. Treatment must ensure adequate medical and therapist input to anticipate higher complication rates.

Accidents, Traffic↗
PubMed2001

Venous thromboembolism prophylaxis used by consultant general surgeons in Scotland.

BACKGROUND: Venous thromboembolism (VTE) is a common source of morbidity and mortality in general surgical patients. Guidelines have been produced to help guide doctors through the complex issue of VTE prophylaxis. This study intended to examine the use of VTE prophylaxis amongst general surgeons in Scotland, with reference to nationally produced guidelines. METHOD: A postal questionnaire was sent to all consultant general surgeons in Scotland. They were asked to give their opinion on the best means of VTE prophylaxis in six different clinical scenarios. The responses were evaluated with reference to the guidelines from the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: A 69% response rate was achieved. There was a wide variance in the suggested prophylaxis in each of the scenarios. With reference to SIGN guidelines, 35% of responses represented undertreatment, 16% overtreatment and 49% appropriate treatment. CONCLUSION: Despite the publication of VTE guidelines, there is still a wide variety of opinions amongst consultant general surgeons with regards to VTE prophylaxis. Many of the responses were not consistent with such guidelines and represent suboptimal prophylaxis for patients.

Attitude of Health Personnel↗
PubMed2000

Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with cardiac syndrome X.

Chest pain with normal coronary angiograms is often associated with chronic sympathetic activation, anxiety, and depression, and is resistant to conventional antianginal treatment. The practice of transcendental meditation, a standard relaxation method for 3 months twice daily, significantly improved exercise tolerance, angina episodes, and quality of life in 9 women; the positive findings in this study warrant further research.

Aged↗
PubMed2000

Elevated levels of Ca(II) modulate the activity and inhibition of serine proteases: implication in the mechanism of apoptosis.

Elevated levels of intracellular Ca(II) are a prominent feature of apoptosis, a natural form of cell death involved in many physiological and pathological processes. Serine proteases play crucial roles in apoptosis and have been implicated in the genomic DNA degradation and the massive protein degradation that occur during apoptosis. In this study, the effects of the elevated level of Ca(II) on the activity and inhibition of serine proteases were examined by spectrophotometric methods. The effects of the elevated levels of Ca(II), Mg(II), K(I), and Na(I) on the activity and inactivation of three representative members of serine proteases were determined. The level of serine protease activity in CEM-C7-14 leukemic cells was also evaluated in the presence and absence of dexamethasone-induced apoptosis, and also in the presence of A23187, a Ca(II)-ionophore. Among the four metal-ions studied, only Ca(II) was found to significantly enhance the activity of mammalian serine proteases. Ca(II) was also found to significantly protect the enzymes from inhibition, while the other three metal-ions showed no significant effect on the inactivation of the enzymes. Compared to the control sample, the enzymic activity was found to be higher during apoptosis, and in the presence of the Ca(II)-ionophore. Results of this study indicate that Ca(II) can significantly enhance the catalytic efficiency of serine proteases during apoptosis.

Apoptosis↗
PubMed2000

CT measurement of medial temporal lobe atrophy in Alzheimer's disease, vascular dementia, depression and paraphrenia.

OBJECTIVE: Measurement of medial temporal lobe atrophy (MTL) by computerised tomography (CT) may be a useful adjunct to the diagnosis of AD. The aim of this study was to assess the sensitivity, specificity, predictive values and diagnostic accuracy of CT measurement of MTL thickness for patients with probable AD, compared with a 'diseased' control group, and to correlate the measure with neuropsychological test scores. DESIGN: Cross-sectional. METHODS: One hundred subjects were prospectively recruited: 60 with probable AD (mean age 73.7 years, mean Mini-Mental State Examination [MMSE] 19.6), 17 with probable vascular dementia (VaD) (mean age 77.9 years, mean MMSE 20.9), 14 with depression (mean age 73.2 years, mean MMSE 25.7) and nine with paraphrenia (mean age 74 years, mean MMSE 25.4). Axial and temporal lobe-oriented CT brain was performed and the minimum MTL thickness was measured electronically. RESULTS: The mean minimum MTL thickness was significantly smaller in AD subjects compared to VaD (p<0.0001) and psychiatric subjects (p<0.0001). For the clinical diagnosis of probable AD, the sensitivity of the measure was 0.75, specificity 0.9, and diagnostic accuracy 0.81. For the mildest cases of AD (CDR 0.5), the sensitivity of the measure was 0.61, specificity 0.91, and diagnostic accuracy 0.81. No significant correlations with neuropsychological test scores were found. CONCLUSIONS: Temporal lobe-oriented CT imaging is a non-invasive test with good discrimination for AD. Potential uses of this technique include as an aid to diagnosis and possibly as a means of monitoring disease progression.

Aged↗
PubMed2000

Three monoclonal antibodies to the VHS virus glycoprotein: comparison of reactivity in relation to differences in immunoglobulin variable domain gene sequences.

Three monoclonal antibodies (MAbs) to the VHSV G protein were compared in different immunoassays and the variable domain cDNA sequences from the respective immunoglobulin (Ig) genes were determined. One MAb (IP1H3) was non-neutralising and recognised different virus isolates equally well in ELISA. The other two were neutralising and recognised the same or closely related epitopes. One of these two MAbs (3F1H10) was more restricted in its ability to neutralise heterologous VHSV isolates than the other (3F1A2). A semi-quantitative relationship between binding of the two neutralising MAbs in ELISA and their neutralising activity was evident. Binding kinetic analyses by plasmon resonance identified differences in the dissociation rate constant (kd) as a possible explanation for the different reactivity levels of the MAbs. The Ig variable heavy (VH) and light (V kappa) domain gene sequences of the three hybridomas were compared. The inferred amino acid sequence of the two neutralising antibody VH domains differed by three amino acid residues (97% identity) and only one residue difference was evident in the V kappa domains. In contrast, IP1H3 shared only 38 and 39% identity with the 3F1A2 and 3F1H10 VH domains respectively and 49 and 50% identity with the 3F1A2 and 3F1H10 V kappa domains respectively. The neutralising antibodies were produced by hybridomas originating from the same fusion and the high nucleotide sequence homology of the variable Ig gene regions indicated that the plasma cell partners of the hybridomas originated from the same virgin B lymphocyte. The few differences observed in the VH and V kappa amino acid sequences were probably due to somatic mutations arising during affinity maturation and might explain the observed reactivity differences between the two MAbs.

Amino Acid Sequence↗
PubMed2000

Genes for three different isoforms of transforming growth factor-beta are present in plaice (Pleuronectes platessa) DNA.

Although transforming growth factor-beta (TGF-beta) genes have been described in several species of fish, whether an individual fish possesses more than one member of this multigene family has yet to be established. During this study, three DNA fragments were isolated from the plaice (Pleuronectes platessa) by homology cloning. Sequence analysis revealed that each fragment closely resembled a distinct member of the TGF-beta family. Each putative plaice TGF-beta clustered individually with a different TGF-beta subgroup during phylogenetic analysis suggesting that these may be the plaice homologues of vertebrate TGF-beta 1/4/5, -beta 2 or -beta 3. The first direct evidence for the presence of multiple TGF-beta genes in a single fish species is presented.

Alleles↗