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Biomedical subjects

D Walsh

Publications and source records attributed to D Walsh.

At least 109 records · Page 6Linked to original sources
PubMed1999

No evidence to support the association of the potassium channel gene hSKCa3 CAG repeat with schizophrenia or bipolar disorder in the Irish population.

Anticipation has attracted much interest and has been demonstrated in several neuropsychiatric disorders. For some disorders, this phenomenon has been found to correlate with the repeat number in large and unstable repeats (CAG/CTG). In addition, case control studies have suggested an increase in triplet repeat size in the psychoses. Recently, it was reported that the larger alleles (longer than 19 repeats) of the second potassium channel gene hSKCa3 are associated with schizophrenia in European and American samples. A similar trend, though not statistically significant, was also seen in bipolar disorder samples. This was further supported by an independent UK study.1 In this investigation, we have examined Irish familial schizophrenic patients, bipolar affective disorder patients and ethnically matched controls in an effort to replicate these findings. No significant differences between the patients and the control groups were observed. In addition, linkage analyses in the multiplex schizophrenic families showed no evidence for linkage or linkage disequilibrium. We concluded that the polymorphism of the second CAG repeat of the hSKCa3 gene is not a risk factor in schizophrenia or bipolar disorder, at least in the Irish population.

Bipolar Disorder↗
PubMed1999

Bromodeoxyuridine induces keratin protein synthesis at a posttranscriptional level in human lung tumour cell lines.

Keratin intermediate filaments are formed in epithelial cells in a cell- and tissue-specific manner, but much remains unknown regarding the mechanisms which control the synthesis of these proteins. We examined the effect of the differentiation modulation agent, bromodeoxyuridine (BrdU), on two human keratin-negative (by immunocytochemistry) lung cell lines, DLKP and H82, and showed immunohistochemically that treatment with 10 microM BrdU over 7 days induced K8 and K18 protein synthesis in both lines. Immunoprecipitation and Western blot analyses revealed low levels of K8 and K18 proteins in untreated cell homogenates. These levels increased following treatment with BrdU for 7 days. K8 and K18 mRNAs were detected by Northern blot and reverse transcriptase polymerase chain reaction analyses in both lines before BrdU treatment, but no increase in mRNA levels was observed in either cell line over 21 days of treatment. This suggests, firstly, that keratin synthesis is normally blocked at a posttranscriptional level in DLKP and H82 cells, and secondly, that BrdU can reverse this block. A549 is a human lung cell line which contains K8 and K18 proteins. Treatment with BrdU increased K8 and K18 protein levels in these cells. No corresponding increase in K8 mRNA levels occurred, while an apparent increase in K18 mRNA levels was detected. HL-60 is a leukaemic cell-line of haematopoietic rather than epithelial lineage which contains K8 and K18 mRNA transcripts prior to BrdU treatment, but does not contain keratin proteins. Again, K8 and K18 mRNA levels remained unchanged during BrdU treatment. However, neither K8 nor K18 proteins were detected following treatment, although BrdU is known to alter expression of other genes in HL-60 cells. BrdU thus appears to act at a posttranscriptional level and in an epithelial-specific manner to reverse a block in keratin synthesis in keratin-negative lung cancer cells and increase synthesis in keratin-positive lung cancer cells. This may represent a regulatory step in early lung development or a mechanism whereby tumour cells downregulate expression of a differentiated phenotype.

Antimetabolites, Antineoplastic↗
PubMed1999

Determination of failure of treatment of plasmodium falciparum infection by using polymerase chain reaction single-strand conformational polymorphism fingerprinting.

The inability to distinguish failures of treatment of Plasmodium falciparum infection from new infections is an important impediment to the evaluation of antimalarial drugs. On the basis of a pilot study utilizing polymerase chain reaction (PCR) single-strand conformational polymorphism (SSCP) analysis to genotype P. falciparum isolates, we sought to confirm that PCR SSCP analysis could reliably distinguish infections for which treatment failed from unrelated infections with a sample size adequate to estimate the accuracy of this technique. PCR SSCP analysis of the MSP-1, MSP-2, and GLURP genes was performed on 72 paired isolates recovered from 36 individuals for whom treatment failed in Thailand. In every case (100% [95% confidence interval (CI), 90%-100%]), the PCR SSCP pattern of the recrudescent isolates matched that of the primary isolate. We determined whether PCR SSCP analysis could separate unrelated infections by comparing each recrudescent isolate with each of the unrelated primary isolates. Of 1,260 comparisons, 1,258 (99.8% [95% CI, 99.4%-100%]) were unique. The results indicate that PCR SSCP analysis can be used to differentiate infections for which treatment failed from reinfections.

Animals↗
PubMed1999

Palliative management of dyspnea in advanced cancer.

Dyspnea is a common and devastating symptom of life-threatening disease. Approximately 90% of non-small cell lung cancer patients experience moderate to severe dyspnea by death. Currently, the pathology is ill-defined and measurement of this subjective symptom is imprecise. The treatment is directed at the underlying cause when appropriate. When specific therapies no longer exist, palliative interventions are necessary. This article outlines the current state of knowledge and standards of care for palliative interventions in dyspnea. These include nonpharmacologic interventions, oxygen supplementation, and medications. Further research is needed to clarify the role of each and to develop better pathophysiologic understanding.

Dyspnea↗
PubMed1999

Is the emergency readmission rate a valid outcome indicator?

OBJECTIVES: The principal aim was to determine whether the emergency readmission rate varies between medical specialties, and to identify whether differences in emergency readmission rates between hospital trusts can be reduced by standardising for specialty. Possible factors influencing emergency readmission were also investigated, including frequency of previous admission and cause of readmission. DESIGN: Emergency readmission rates were obtained from the Scottish Morbidity Record scheme (SMR1) using record linkage, standardised for age and sex. Rates throughout Scotland were analysed by specialty, and rates for general medicine compared among teaching hospital trusts. Cause of emergency readmission was determined from hospital records in a random sample (177 patients). SETTING: Medical specialties throughout Scotland. SUBJECTS: All patients readmitted as an emergency within 28 days of discharge (October 1990 to September 1994). RESULTS: Emergency readmissions varied markedly between medical specialties, with highest rates in nephrology (24.2%, 95% CI 23.5 to 24.8) and haematology (20.4%, 95% CI 19.9 to 20.9), and the lowest in homeopathy (2.2%, 95% CI 1.6 to 2.7) and metabolic diseases (3.5%, 95% CI 2.4 to 4.5). The largest number of emergency readmissions was in general medicine, accounting for 63% of the total. Restricting emergency readmission rates to general medicine significantly altered previous rates. In the year preceding the emergency readmission, 59% of all patients had been admitted to hospital at least once, and most emergency readmissions (73.3%) resulted from a chronic underlying condition. CONCLUSIONS: Significant variations in emergency readmission rates occurred between medical specialties, suggesting that differences between hospital trusts are influenced by differences in specialties and thus case mix. The majority of emergency readmissions occurred in patients with an underlying chronic condition, and many had a history of multiple previous hospital admissions. The emergency readmission rate is therefore unlikely to be a valid outcome indicator reflecting quality of care until routine data are available for standardisation by case mix.

Diagnosis-Related Groups↗
PubMed1999

Pseudoaneurysm of the lateral malleolar artery after an ankle sprain: case report and review of the literature.

A pseudoaneurysm of the peroneal artery or one of its branches is rare after trauma. The diagnosis is frequently delayed, resulting in substantial morbidity to the patient. The infrequent occurrence of this condition has resulted in a lack of diagnostic and treatment guidelines. However, when recognized, prompt attention involving either surgical ligation or embolization of the injured arterial branch is the most reliable method of treatment. Presented is a report of a patient who developed a lateral malleolar arterial pseudoaneurysm after an ankle sprain, which was treated successfully with aneurysmal excision and surgical ligation of the injured arterial branch. A review of the literature and treatment recommendations follow.

Adult↗
PubMed1999

Acute care palliative medicine: psychosocial assessment of patients and primary caregivers.

This paper describes the application of an empirically-derived psychosocial assessment for use in advanced cancer. The patient population selected for this study was those patients no longer pursuing aggressive antitumour treatment, and the focus of care was on management of major symptoms and complications, and psychosocial support of the patient and family. The physical, cognitive, social and emotional dimensions were the framework for the assessment of both patient and caregiver functioning. Through this assessment of all patients admitted to our inpatient palliative medicine unit, care needs were identified and psychosocial interventions planned. The results of 150 assessments are reported, as well as observations of the process, implications for psychosocial care and modifications of the assessment based on this experience.

Adult↗
PubMed1999

Pseudoautosomal gene: possible association with bipolar males but not with schizophrenia.

The phenomenon of anticipation has been demonstrated in several neuropsychiatric disorders and suggested for schizophrenia and bipolar affective disorder. Many conditions exhibiting anticipation have been shown to be caused by trinucleotide repeat (CAG/CTG) expansions. Some evidence suggests that these expansions also exist in individuals with schizophrenia and bipolar affective disorder. In this investigation, we analysed a polymorphic CAG repeat in the interleukin receptor gene (IL9R), mapped to the pseudoautosomal region Xq28 and Yq21 (a candidate region for schizophrenia and affective disorder). Two common alleles, differing by one repeat unit and two rare alleles were found in cases and controls. Allele frequencies of this repeat were investigated in Irish schizophrenic, bipolar disorder and ethnically matched control samples. We found no evidence of an increased frequency of larger CAG repeats in either the schizophrenic or bipolar affective disorder samples as a whole when compared to the controls. However, dividing the samples by sex demonstrated a significant association between bipolar affective disorder males and the larger allele (allele 2) (patients 54.8% vs controls 40.1%, chi2 = 6.7, P = 0.009). In addition, a decreased frequency of this allele has been observed in the female patients, but did not attain statistical significance (patients 37% vs controls 46%, chi2 = 2.1, P = 0.14). This provides preliminary evidence that this locus or a closely mapped DNA variant (in linkage disequilibrium with the CAG repeat) may be involved in the genetic susceptibility to bipolar affective disorder in males.

Bipolar Disorder↗
PubMed1999

The role of heat shock proteins in mammalian differentiation and development.

Heat shock proteins (HSPs) have been identified in all cells, prokaryotic and eukaryotic, to protect the cells from harmful insults and stress. Increased HSP synthesis can also result during normal cellular functions and also respond to exposure from environmental stress and infection. Although the molecular mechanisms responsible for HSP cellular protection are still not fully understood, their expression is critical for cellular survival and can be modified by cell signal transducers such as intracellular pH, cyclic AMP, Ca2+ Na+, inositol [correction of inostitol] triphosphate, protein kinase C, and protein phosphates. Most HSPs interact, assemble, fold, unfold, bind, transport, translocate and 'chaperone' other proteins in the cell and alter their function.

Animals↗
PubMed1998

Seasonal influences on admissions in schizophrenia and affective disorder in Ireland.

Although the seasonal patterns of admissions of affective disorder have been extensively studied, less attention has been given to the seasonal admission patterns of schizophrenia. The traditional method of aggregating the data over a study period, rather than analysing by year of admission may obscure potentially relevant fluctuations in the seasonal pattern. We examined the year-to-year variation in the admission patterns of schizophrenia and affective disorder in Ireland. Using the National Psychiatric Inpatient Reporting System (NPIRS), individuals admitted with an ICD-9/10 diagnosis of a first episode of schizophrenia or affective disorder during the 6-year period 1989-1994 were identified. Seasonal variations in their admission patterns were examined statistically and graphically. There was a significant seasonal variation in the monthly admission patterns of both schizophrenia and affective disorder. This pattern was more marked for individuals with affective disorder. However, the seasonal pattern was not constant from year to year, particularly for schizophrenia.

Humans↗
PubMed1998

No linkage or linkage disequilibrium between brain-derived neurotrophic factor (BDNF) dinucleotide repeat polymorphism and schizophrenia in Irish families.

There is increasing evidence that a neurodevelopmental process is accountable for at least a proportion of schizophrenic cases. Brain-derived neurotrophic factor (BDNF), a member of a group of proteins that includes neurotrophin-3/4/5 and nerve growth factor (NGF), is an attractive candidate gene. We have performed a case control association study using the BDNF dinucleotide repeat polymorphism in a sample of familial schizophrenic individuals and in healthy, ethnically matched control subjects. We also performed a linkage analysis on 265 multiplex families using the same marker. We found no differences in allele frequencies between the patient and control groups nor any evidence for transmission disequilibrium or linkage with the multiply affected families. We conclude that DNA variation at or near the BDNF gene is unlikely to contribute to the genetic predisposition to schizophrenia.

Alleles↗
PubMed1998

A schizophrenia locus may be located in region 10p15-p11.

In our genomic scan of 265 Irish families with schizophrenia, we have thus far generated modest evidence for the presence of vulnerability genes in three chromosomal regions, i.e., 5q21-q31, 6p24-p22, and 8p22-p21. Outside of those regions, of all markers tested to date, D10S674 produced one of the highest pairwise heterogeneity lod (H-LOD) scores, 3.2 (P = 0.0004), when initially tested on a subset of 88 families. We then tested a total of 12 markers across a region of 32 centimorgans in region 10p15-p11 of all 265 families. The strongest evidence for linkage occurred assuming an intermediate phenotypic definition, and a recessive genetic model. The largest pairwise H-LOD score was found with marker D10S2443 (maximum 1.95, P = 0.005). Using multipoint H-LODs, we found a broad peak (maximum 1.91, P = 0.006) extending over the 11 centimorgans from marker D10S674 to marker D10S1426. Multipoint nonparametric linkage analysis produced a much broader peak, but with the maximum in the same location near D10S2443 (maximum z = 1.88, P = 0.03). Based on estimates from the multipoint analysis, this putative vulnerability locus appears to be segregating in 5-15% of the families studied, but this estimate should be viewed with caution. When evaluated in the context of our genome scan results, the evidence suggests the possibility of a fourth vulnerability locus for schizophrenia in these Irish families, in region 10p15-p11.

Chromosome Mapping↗
PubMed1998

The structure of psychosis: latent class analysis of probands from the Roscommon Family Study.

BACKGROUND: The nosologic structure of psychotic illness, still influenced as much by historical as empirical perspectives, remains controversial. METHODS: Latent class analysis was applied to detailed symptomatic and outcome assessments of probands (n=343) with broadly defined schizophrenia and affective illness ascertained from a population-based psychiatric registry in Roscommon County, Ireland. First-degree relatives (n=942) were assessed by personal interview and/or review of hospital record. RESULTS: Six classes were found, all of which bore substantial resemblance to current or historical nosologic constructs. In order of decreasing frequency, they were (1) classic schizophrenia, (2) major depression, (3) schizophreniform disorder, (4) bipolar-schizomania, (5) schizodepression, and (6) hebephrenia. These classes differed on many historical and clinical variables not used in the latent class analysis. Compared with relatives of controls, significantly increased rates of major depression were seen in relatives of depressed and schizodepressed probands. Significantly increased rates of bipolar illness were restricted to relatives of bipolar-schizomanic probands. The risks for schizophrenia and schizophrenia spectrum disorders were significantly increased in relatives of all proband classes except major depression. This increase was moderate for bipolar-schizomanic probands, substantial for schizophrenic, schizophreniform, and schizodepressed probands, and marked for hebephrenic probands. CONCLUSIONS: These results suggest a relatively complex typology of psychotic syndromes consistent neither with a unitary model nor with a Kraepelinian dichotomy. The familial vulnerability to psychosis extends across several syndromes, being most pronounced in those with schizophrenialike symptoms. The familial vulnerability to depressive and manic affective illness is somewhat more specific.

Adolescent↗
PubMed1998

Analysis of the D1S80 locus by capillary electrophoresis.

We have demonstrated in a systematic manner that the capillary electrophoresis (CE) method of genotyping the human D1S80 locus is an effective replacement for the commonly used gel electrophoresis method. The CE method is fast, with a total run time of less than 22 min per sample. Separation has been optimized so that resolution for all pairs of alleles from 14 through 41 is greater than 1, providing unambiguous identification. The method utilizes run buffer containing 0.30% hydroxyethyl cellulose as the sieving polymer in a 50 microm internal diameter (ID) column coated with a 0.1 microm DB-17 film. Laser-induced fluorescence (LIF) with YO-PRO-1 intercalating dye is used for detection. Internal standards of 300 and 1000 bp bracket the D1S80 region in the electropherogram. Two typing procedures were evaluated: matching of the normalized migration times of sample alleles to ladder alleles; and software alignment of sample and ladder electropherograms using the internal standard peaks as references. Using the first procedure, 91.5% of the D1S80 genotypes were unambiguous, while 100% were unambiguous using the second procedure. Seventy-nine routine samples were analyzed in a side-by-side comparison of the CE and slab gel methods, with complete agreement of the results. Twenty-two samples were selected from a large database previously analyzed by the slab gel method to demonstrate that all alleles from 14 through 41 were typed correctly, including samples containing adjacent alleles. Additionally, 43 samples containing alleles greater than the 41 repeat number were typed correctly.

Automation↗