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D Walsh

Publications and source records attributed to D Walsh.

At least 37 records · Page 2Linked to original sources

Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births.

BACKGROUND: Individuals who are small at birth are at increased risk of ischaemic heart disease (IHD) in later life. One hypothesis to explain this association is fetal adaptation to a suboptimum intrauterine environment. We investigated whether pregnancy complications associated with low birthweight are related to risk of subsequent IHD in the mother. METHODS: Routine discharge data were used to identify all singleton first births in Scotland between 1981 and 1985. Linkage to the mothers' subsequent admissions and deaths provided 15--19 years of follow-up. The mothers' risks of death from any cause or from IHD and admission for or death from IHD were related to adverse obstetric outcomes in the first pregnancy. Hazard ratios were adjusted for socioeconomic deprivation, maternal height and age, and essential hypertension. FINDINGS: Complete data were available on 129,920 (95.6%) eligible deliveries. Maternal risk of IHD admission or death was associated with delivering a baby in the lowest birthweight quintile for gestational age (adjusted hazard ratio 1.9 [95% CI 1.5--2.4]), preterm delivery (1.8 [1.3--2.5]), and pre-eclampsia (2.0 [1.5--2.5]). The associations were additive; women with all three characteristics had a risk of IHD admission or death seven times (95% CI 3.3--14.5) greater than the reference category. INTERPRETATION: Complications of pregnancy linked to low birthweight are associated with an increased risk of subsequent IHD in the mother. Common genetic risk factors might explain the link between birthweight and risk of IHD in both the individual and the mother.

Birth Weight↗

Removal of tightly bound endotoxin from biological products.

The method for endotoxin removal described in this paper is useful for separation of tightly bound endotoxin from biological products, particularly those produced in Escherichia coli in the form of inclusion bodies for which a denaturation step is required to solubilise the product. We employed guanidine hydrochloride and ammonium sulphate in combination with hydrophobic interaction chromatography (HIC). These conditions enable binding of the endotoxin to the matrix, giving unbound product in the column flow-through. This makes the method generally applicable to biological products. An endotoxin reduction of about 3.7 logs was achieved; from as much as 1,100,000 EU mg(-1) in the solubilised material to about 200 EU mg(-1) in the product purified by this method. The method was developed for a cervical dysplasia vaccine, a fusion protein comprising L2, E7 and E6 from Human Papilloma Virus type 16, because both conventional and commercially available methods of endotoxin removal were ineffective in removing the tightly bound endotoxin from this product.

Chromatography↗

Analysis of epistasis in linked regions in the Irish study of high-density schizophrenia families.

Epistasis may be important in the etiology of schizophrenia. Analysis of epistasis has been important in the positional cloning of a gene involved in the etiology of type II diabetes mellitus. We investigated the importance of epistasis among six linked regions in 268 multiplex pedigrees in the Irish Study of High-Density Schizophrenia Families (ISHDSF) by computing pairwise correlations between nonparametric linkage scores for narrow, intermediate, and broad diagnostic definitions. The linked regions were on chromosomes 2, 4, 5, 6, 8, and 10. No correlation reached our a priori level of statistical significance. Using this statistical approach, we did not find evidence of important epistatic effects among these six regions in the ISHDSF.

Chromosomes, Human↗

Number of older siblings of individuals diagnosed with schizophrenia.

One of the most consistent epidemiological findings in schizophrenia research is the small excess of late winter/early spring births. There is also evidence that schizophrenia is associated with urban birth and with later birth order. One interpretation of these three findings is that respiratory viral infections brought into the household by children in crowded areas could disrupt foetal brain development and predispose to schizophrenia in later life. To further explore this hypothesis, case register data were used to assess if schizophrenics with a greater number of older siblings are more likely to be born in urban areas and during late winter/early spring months. Data from the Dublin and Three County Case Register were compiled relating to 2969 patients with schizophrenia and 5904 patients with neurosis. We used logistic regression analysis to determine if the number of older siblings differentiated schizophrenia from neurosis after controlling for the effects of gender, urban/rural birth, season of birth and sibship size, and to examine whether any interactions existed. The number of older siblings did not predict a diagnosis of schizophrenia over neurosis. There was no interaction between number of older siblings and urban birth, between number of older siblings and spring birth, or between number of older siblings, season of birth and urban birth. These data do not support the hypothesis that schizophrenia, by comparison with neurosis, is associated with an increased number of older siblings or that there is an interaction between number of older siblings, urban birth or season of birth.

Birth Order↗

Relationship between positive and negative symptoms of schizophrenia and schizotypal symptoms in nonpsychotic relatives.

BACKGROUND: Continuous rather than categorical measures of psychopathology may provide greater statistical power to detect susceptibility loci for schizophrenia. However, it has not been established that the dimensions of schizophrenic symptomatology and personality traits in nonpsychotic individuals share etiological factors. We therefore sought to clarify the relationship between positive and negative symptoms of schizophrenic probands and dimensions of schizotypy in their first-degree relatives. METHODS: In the Roscommon Family Study, we examined the ability of positive and negative symptoms in probands to predict 7 factors of schizotypy in nonpsychotic relatives using regression analysis. These consisted of positive, negative, and avoidant symptoms; odd speech; suspicious behavior; social dysfunction; and symptoms of borderline personality disorder. We examined 3 proband groups: schizophrenia (n = 127); schizophrenia, simple schizophrenia, and schizoaffective disorder (n = 178); and all nonaffective psychoses (n = 216), and their nonpsychotic relatives (n = 309, 477, and 584, respectively). RESULTS: Positive symptoms in all nonaffective psychoses probands predicted positive schizotypy (beta = 0.1972, P =.0004), social dysfunction (beta = 0.0719, P =.0489), and borderline personality disorder symptoms (beta = 0.1327, P =.0084) in relatives, while negative symptoms predicted negative schizotypy (beta = 0.2069, P =.0002), odd speech (beta = 0.2592, P =.0001), suspicious behavior (beta = 0.2749, P =.0001), and social dysfunction (beta =.2398, P =.0002). Proband negative symptoms and borderline personality disorder symptoms in relatives in the schizophrenia, simple schizophrenia, and schizoaffective disorder group were inversely related (beta = -0.1185, P =.05). CONCLUSIONS: Positive and negative symptoms in schizophrenia predict corresponding schizotypal symptoms in relatives. This provides evidence that these schizophrenic symptom factors (1) are etiologically distinct from each other and (2) occur on an etiological continuum with their personality-based counterparts.

Borderline Personality Disorder↗

The gastrointestinal symptoms of advanced cancer.

The commonest gastrointestinal (GI) symptoms in advanced cancer are reviewed with reference to definition, pathophysiology, etiology, prevalence, severity, and management. Observation or reporting of such symptoms must lead to consideration of the multi-faceted pathophysiology. Careful assessment and an analytical detailed approach are the keystones of effective management.

Age Factors↗

Methadone for relief of cancer pain: a review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration.

Methadone, a synthetic opioid, has unique pharmacodynamics and pharmacokinetics, which contribute to its unique ability to relieve pain unresponsive to other potent opiates and its unique dosing and drug interactions. Several guidelines of administration have been established. Physicians who are involved in pain management should have a fundamental understanding of methadone's unique properties.

Analgesics, Opioid↗

Hydromorphone: pharmacology and clinical applications in cancer patients.

Hydromorphone is a more potent opioid analgesic than morphine and is used for moderate to severe pain. It can be administered by injection, by infusion, by mouth, and rectally. Oral bioavailability is low. The kidney excretes hydromorphone and its metabolites. Some metabolites may have greater analgesic activity than hydromorphone itself but are unlikely to contribute to the pharmacological activity of hydromorphone. With the exception of pruritus, sedation and nausea and vomiting, which may occur less after hydromorphone than after morphine, the side-effects of these drugs are similar. On a milligram basis hydromorphone is five times as potent as morphine when given by the oral route, and 8.5 times as potent as morphine when given intravenously.

Analgesics, Opioid↗

Music therapy in palliative medicine.

A partnership between The Cleveland Clinic Foundation and The Cleveland Music School Settlement has resulted in music therapy becoming a standard part of the care in our palliative medicine inpatient unit. This paper describes a music therapy program and its impact on patients, their families, and staff. A service delivery model is suggested for implementation and integration of music therapy within palliative medicine. Specific music therapy interventions, evaluation and documentation techniques are also mentioned. A description of patient and family responses to music therapy, staff satisfaction, and effectiveness of interventions is presented.

Humans↗

Quality of life measurement in the palliative management of advanced cancer.

A 4-week quality of life (QOL) study was conducted in 157 consecutive advanced cancer patients to compare five QOL measures and to assess changes in QOL during the course of the study. The study patients were representative of the advanced cancer population in the USA, and were similar to the advanced cancer population with respect to age and gender. Global QOL measures appear to be as effective as multidimensional measures in assessing QOL in patients with advanced cancer. Generally, QOL was rated as satisfactory and did not change markedly during the study period.

Aged↗

Terminal sedation in palliative medicine--definition and review of the literature.

This paper reviews the reported use of nonopioid medications for terminal sedation. To provide a summary of the available literature, an electronic database search was performed. Thirteen series and 1 4 case reports were identified. Various symptoms, including agitation, pain, and confusion, required terminal sedation. Eleven drugs were used in 342 patients. Most patients were also treated with concurrent opioids and received terminal sedation in an inpatient hospice unit. Midazolam was the most common sedative employed. A good response--defined as adequate sedation--ranged between 75% and 100%. The median time to death following the introduction of terminal sedation was greater than 1 day. No agent appears to have superior efficacy or limiting toxicity.

Analgesics, Non-Narcotic↗

Evaluation and treatment of cancer-related fluid deficits: volume depletion and dehydration.

Fluid deficits should be divided into two categories (dehydration and volume depletion) according to pathophysiology and into 3 categories (hyponatremic, hypernatremic, and isotonic) according to the plasma sodium concentration. Dehydration (total water deficit especially intracellular) is always hypernatremic, while volume depletion (intravascular water and sodium deficit) is either hyponatremic, hypernatremic, or isotonic. There are no clear clinical differences among the various categories, but a delay of capillary refill, tachycardia, and orthostatic hypotension are more common with early volume depletion. An Evans blue and mannitol test can be used to distinguish between hypernatremic volume depletion and dehydration. Careful clinical assessment and laboratory tests (especially serum sodium) are the key to diagnosis and effective management. According to the type (hypernatremic, hyponatremic, or isotonic), severity of fluid deficit, and associated symptoms, oral or parenteral fluid should be given along with treatment of the underlying cause. In hemodynamically compromised individuals with orthostatic hypotension and oliguria, replacement with isotonic saline until hemodynamic stabilization is crucial. Terminal hydration is still controversial. Important ethical principles govern clinical decision-making about hydration at the end of life.

Dehydration↗

Important drugs for cough in advanced cancer.

Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management.

Antitussive Agents↗

Preparation of porous composite implant materials by in situ polymerization of porous apatite containing epsilon-caprolactone or methyl methacrylate.

Biodegradable and biostable composite foams were formed from porous apatite cement infiltrated with epsilon-caprolactone (CL) or methylmethacrylate (MMA) using a high over vacuum. For CL composites in situ polymerization was induced using trace water as an initiator and heating at 120 degrees C for up to 10 days or at 80 degrees C for 60 days. MMA composites were polymerized using AIBN initiator at 70 degrees C for 8 h. CL preparations gave composites with a polycaprolactone (PCL) number average of molecular weight (Mn) up to the maximum of 7.1 x 10(3) g/mol after 10 days and 16.8 x 10(3) g/mol after 60 days. The PCL and PMMA contents were close to 50 and 40 wt%, respectively, polymer was present as a thin coating on the apatite crystal plates and was evenly distributed throughout the samples. Re-evacuation of apatite saturated with monomer during preparation ensured that the upwards of 200 nm microchannels within the apatite cement were largely free of polymer, and the overall macroporous structure of the apatite foams was partly retained. Maximum compressive strengths increased from 9 MPa to 37 and 64 MPa for PCL and PMMA composites, respectively. The water drop contact angle of the PCL composite was 64 degrees, and therefore suitable for cell attachment. PMMA composite surfaces were more hydrophobic. Composites were subjected to corona discharge to induce suitable moderate hydrophilicity at the surface.

Apatites↗

Preparation of a bone-like apatite foam cement.

The preparation of a porous bone-like calcium deficient apatite implant material was investigated. A novel cement system composed of an equimolar mixture of Ca4(PO4)2O, Ca(HPO4)2 . H2O, and CaCO3 was used. At a liquid/powder ratio of 0.83 ml/g low density open framework foam cements were formed due to the rapid evolution of CO2. The initial product of the reactants was CaHPO4 . H2O which then reacted with Ca4(PO4)O, forming a calcium deficient carbonated apatite, upon soaking of the cement blocks in SBF. Foam-like cements were composed of a plate-like apatite due to epitaxial overgrowth and conversion of the brushite plate precursor. Cylinders of the foam cement were reinforced with an outer layer of a solid apatite cement to form a material suitable for application as a bone-section implant.

Journal Article↗

NAC Manchester Asthma and Allergy Study (NACMAAS): risk factors for asthma and allergic disorders in adults.

Asthma and atopic disorders are the most common chronic diseases in the developed countries. Knowledge of the risk factors for these disorders may facilitate the development of preventive strategies aimed at reducing prevalence rates. To investigate the risk factors for asthma and allergic diseases in a large number of adults who are the parents of children in the National Asthma Campaign Manchester Asthma and Allergy Study. All pregnant women and their partners attending "Booking" antenatal clinics were invited to take part in the study. Questionnaire data were collected including the history of asthma and other atopic diseases, pet ownership and smoking habits, and skin prick tests were performed. The prevalence of atopy and the risk factors for asthma and allergic disorders were investigated in all subjects who completed the questionnaire and underwent skin testing. Statistical analysis was carried out using logistic regression. Initially, risk factors were assessed by univariate analysis to see how each potential explanatory variable affected the probability of having allergic disease. Variables were then tested in a forward stepwise multivariate analysis. In 5687 adult subjects there was a very high (48.2%) prevalence of atopy, and 9.7% of subjects had a diagnosis of asthma. In a multivariate regression analysis sensitization to dust mite, cat, dog and mixed grasses were all independently associated with asthma. The odds ratios for current asthma increased with the increasing number of positive skin tests (any two allergens - OR 4.3, 95% CI 3.3-5.5; any three allergens - OR 7.0 95% CI 5.3-9.3; all four allergens - OR 10.4, 95% CI 7.7-14; P < 0.00001). Dog ownership (OR 1.31, 95% CI 1.10-1.57; P = 0.003) and current smoking (OR 1.36, 95% CI 1.15-1.62; P = 0.0004) were significantly and directly associated with "asthma ever". Thirteen per cent of participants reported a history of eczema. In the multivariate analysis the strongest independent associate of eczema was sensitization to dog (OR 1.37, 95% CI 1.14-1.63, P < 0.0001). Apart from dog, the strength of the association between sensitization to common allergens and eczema appeared to be much lower than in the case of asthma. The prevalence of hay fever was high (20.6%), and in the multivariate analysis the association between sensitization to pollen and hay fever was extremely strong (OR 13.6, 95% CI 11.3-16.3; P < 0.0001). The results of the current study emphasize the importance of sensitization to indoor allergens in asthma. However, evidence of a possible direct role of allergen exposure in asthma causation remains unclear.

Adult↗

Antibiotic resistance among Listeria, including Listeria monocytogenes, in retail foods.

AIMS: In the past eight to 10 years, reports of antibiotic resistance in food-borne isolates in many countries have increased, and this work examined the susceptibility of 1001 food isolates of Listeria species. METHODS AND RESULTS: Susceptibility/resistance to eight antibiotics was determined using the Bauer-Kirby disc diffusion assay, and 10.9% of the isolates examined displayed resistance to one or more antibiotics. Resistance to one or more antibiotics was exhibited in 0.6% of Listeria monocytogenes isolates compared with 19.5% of Listeria innocua isolates. Resistance was not observed in Listeria seeligeri or Listeria welshimeri. Resistance to tetracycline (6.7%) and penicillin (3.7%) was the most frequently observed, and while resistance to one antibiotic was most common (9.1%), isolates resistant to two or more antibiotics (1.8%) were also observed. CONCLUSION: While resistance to the antibiotics most commonly used to treat human listeriosis was not observed in L. monocytogenes, the presence of such resistance in other Listeria species raises the possibility of future acquisition of resistance by L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: The higher level of resistance in L. innocua compared with L. monocytogenes suggests that a species-related ability to acquire resistance to antibiotics exists.

Ampicillin↗