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Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 19 recordsLinked to original sources

Morphologic and histologic comparisons between in vivo and nuclear transfer derived porcine embryos.

Nuclear transfer (NT) is an inefficient but invaluable tool of the biotechnology industry. This study looked at abnormalities associated with peri-implantation NT porcine embryos. Four experimental groups were examined: nonpregnant animals, in vivo pregnant animals, NT recipients, and manipulation control embryos (MC). Embryos (Day 10, 12, or 14) were evaluated for embryonic disc diameter, gross morphology, nucleoli density, and mitotic figure index. Day 12 (P < or = 0.03) and Day 14 (P < or = 0.01) NT embryos had increased numbers of nucleoli, and Day 14 NT embryos had an increased (P < or = 0.03) mitotic index compared to in vivo and MC embryos. In vivo produced Day 14 embryos had increased (P < or = 0.01) disk diameters when compared to other embryos except for MC Day 14, which also showed increases (P < or = 0.01) in disk diameter except when compared to in vivo produced Day 12 and Day 14 embryos. In vivo produced Day 12 had greater (P < or = 0.03) disk diameters when compared to NT and MC embryos except for MC Day 14, and in vivo produced Day 14 embryos, which had a significantly increased (P < or = 0.01) disk diameter. In vivo produced Day 14 embryos were morphologically more advanced (P < or = 0.01) than Day 14 NT and MC counterparts. NT embryos develop at a slower rate than their in vivo produced counterparts. The increase in nucleoli and mitotic index of NT embryos suggest the cell cycle may be affected or the NT embryos are employing other means to compensate for slow development. The techniques used during NT also appear to compromise embryo development.

Animals↗

Analysis of veterinary drug residues in fish and shrimp composites collected during the Canadian Total Diet Study, 1993-2004.

Thirty shrimp, marine fish, freshwater fish, and canned fish composite samples collected and prepared as part of the Canadian Total Diet Study were analysed for 39 different veterinary drug residues. The analyses were undertaken to obtain baseline data that could be used to estimate the dietary exposure of Canadians to these residues. The most frequently observed residue was AOZ (four out of 30 samples), the metabolite of furazolidone, at a range of 0.50 to 2.0 ng g(-1) wet weight. Other residues detected included enrofloxacin (three samples; 0.3-0.73 ng g(-1)), leucomalachite green (three samples; 0.73-1.2 ng g(-1)), oxolinic acid (two samples; 0.3-4.3 ng g(-1)), AMOZ (the metabolite of furaltadone; one sample; 0.40 ng g(-1)), chloramphenicol (one sample; 0.40 ng g(-1)), and SEM (the metabolite of nitrofurazone; one sample; 0.8 ng g(-1)). The results of this survey indicate that Canadians are exposed to low ng g-1 concentrations of some banned and unapproved veterinary drug residues via the consumption of certain fish and shrimp.

Animals↗

Preliminary antiproliferative effects of some species of Terminalia, Combretum and Pteleopsis collected in Tanzania on some human cancer cell lines.

Methanolic extracts (25 microug/ml) of species belonging to the genera of Combretum, Terminalia and Pteleopsis, collected during a field expedition in Tanzania in 1999, were screened for their antiproliferative and cytotoxic effects against three human cancer cell lines (HeLa, cervical carcinoma; T 24, bladder carcinoma; and MCF 7, breast carcinoma). A leaf extract of Combretum fragrans and a fruit extract of C. zeyheri gave the strongest antiproliferative and cytotoxic effects of all the twenty-four extracts screened in this investigation. In contrast to the highly powerful leaf extract of C. fragrans, the root extract of this species gave no cytotoxic effects against the investigated cancer cell lines at a concentration of 25 microg/ml. The other investigated species of Combretum and Terminalia differed greatly in their cytotoxic potential. Root extracts of Terminalia sambesiaca and T. sericea gave the strongest cytotoxic effects of the five species of Terminalia used in this study. Eight of the twenty-four investigated plant extracts showed pronounced cytotoxic effects (<30% proliferation compared to the control) against the T 24 bladder cancer cells, seven against the HeLa cells and four against the MCF 7 cells.

Antineoplastic Agents, Phytogenic↗

Outcome of clinical pregnancies after ovulation induction using metformin.

The objective of this study was to review the first 50 clinical pregnancies of women with polycystic ovarian syndrome (PCOS) who had ovulation induced either with metformin alone, or in combination with clomifene. The study was confined to women with PCOS attending our infertility service. A register of clinical pregnancies was maintained of women who conceived after metformin therapy. The metformin was continued throughout the first trimester. The outcome of pregnancy was determined by individual chart review. Of the 50 women, 21 conceived with a combination of clomifene and metformin, and 29 with metformin alone. Seven women had a first trimester loss and 43 had a live birth. There were no perinatal deaths, no neonatal seizures and no congenital malformations. There were also no multiple pregnancies. The overall caesarean rate was 37%, and none of the babies had an Apgar score less than 7, at 5 min. This study found no evidence of any adverse clinical effects when metformin is continued in the first trimester of women with PCOS following ovulation induction. There was also no evidence of an increase in the rate of miscarriage or multiple pregnancy.

Adult↗

Environmental survival mechanisms of the foodborne pathogen Campylobacter jejuni.

Campylobacter spp. continue to be the greatest cause of bacterial gastrointestinal infections in humans worldwide. They encounter many stresses in the host intestinal tract, on foods and in the environment. However, in common with other enteric bacteria, they have developed survival mechanisms to overcome these stresses. Many of the survival mechanisms used by Campylobacter spp. differ from those used by other bacteria, such as Escherichia coli and Salmonella spp. This review summarizes the mechanisms by which Campylobacter spp. adapt to stress conditions and thereby increase their ability to survive on food and in the environment.

Adaptation, Physiological↗

Intravenous immunoglobulin for resistant Clostridium difficile infection.

Clostridium difficile (CD)-associated diarrhoea and colitis may relapse in up to 20% of treated patients. We present a patient who failed to respond over a 6-month period to treatment either singly or in combination with metronidazole, vancomycin, rifampicin, cholestyramine and probiotics. Her diarrhoea rapidly resolved after a 3-day course of intravenous immunoglobulin. This treatment may compensate for a failed immune response to CD toxin and should be considered for relapsing CD-associated diarrhoea where there is no response to conventional treatment strategies.

Clostridioides difficile↗

Studies on LXR- and FXR-mediated effects on cholesterol homeostasis in normal and cholic acid-depleted mice.

As previously reported by us, mice with targeted disruption of the CYP8B1 gene (CYP8B1-/-) fail to produce cholic acid (CA), upregulate their bile acid synthesis, reduce the absorption of dietary cholesterol and, after cholesterol feeding, accumulate less liver cholesterol than wild-type (CYP8B1+/+) mice. In the present study, cholesterol-enriched diet (0.5%) or administration of a synthetic liver X receptor (LXR) agonist strongly upregulated CYP7A1 expression in CYP8B1-/- mice, compared to CYP8B1+/+ mice. Cholesterol-fed CYP8B1-/- mice also showed a significant rise in HDL cholesterol and increased levels of liver ABCA1 mRNA. A combined CA (0.25%)/cholesterol (0.5%) diet enhanced absorption of intestinal cholesterol in both groups of mice, increased their liver cholesterol content, and reduced their expression of CYP7A1 mRNA. The ABCG5/G8 liver mRNA was increased in both groups of mice, but cholesterol crystals were only observed in bile from the CYP8B1+/+ mice. The results demonstrate the cholesterol-sparing effects of CA: enhanced absorption and reduced conversion into bile acids. Farnesoid X receptor (FXR)-mediated suppression of CYP7A1 in mice seems to be a predominant mechanism for regulation of bile acid synthesis under normal conditions and, as confirmed, able to override LXR-mediated mechanisms. Interaction between FXR- and LXR-mediated stimuli might also regulate expression of liver ABCG5/G8.

ATP Binding Cassette Transporter 1↗

Similar endometrial development in oocyte donors treated with either high- or standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in natural cycles.

BACKGROUND: This descriptive study evaluates the impact on endometrial development of standard and high doses of a GnRH antagonist in stimulated cycles compared with GnRH agonist and natural cycles. METHODS: Thirty-one oocyte donors were treated with a combination of rFSH and 0.25 mg/day ganirelix (standard dose), 2 mg/day ganirelix (high dose) or 0.6 mg/day buserelin (long protocol). Vaginal progesterone (200 mg/day) was administered in the luteal phase. Endometrial biopsies were performed 2 and 7 days after HCG administration. Additional biopsies were carried out in a subset of 12 subjects, 2 and 7 days following the LH peak of their previous natural cycle. Biopsies were evaluated histologically and by scanning electron microscopy. Gene expression profiles were also studied. RESULTS: At HCG +2, all the parameters studied were similar in all the groups and comparable to those observed in the natural cycle. At HCG +7, endometrial dating, steroid receptors and the presence of pinopodes were comparable in both GnRH antagonist groups and in the natural cycle. In buserelin group, endometrial dating and pinopode expression suggested an arrested endometrial development. For window of implantation genes, expression patterns were closer to those in the natural cycle following standard- or high-dose ganirelix than after buserelin administration. CONCLUSION: No relevant alteration was observed in the endometrial development in the early and mid-luteal phases in women undergoing controlled ovarian stimulation for oocyte donation following daily treatment with a standard- or high-dose GnRH antagonist. In addition, the endometrial development after GnRH antagonist mimics the natural endometrium more closely than after GnRH agonist.

Adolescent↗

Use of confocal immunofluorescence microscopy to localize viral nonstructural proteins and potential sites of replication in pigs experimentally infected with foot-and-mouth disease virus.

Replication of foot-and-mouth disease virus in infected pig epithelium has been studied by immunofluorescence labeling of the viral nonstructural protein 3ABC and confocal microscopy. The results were correlated with viral RNA copy numbers in tissue samples from adjacent sites determined by reverse transcription-PCR (RT-PCR). Lesion formation was seen in the tongues and coronary band epithelia of infected pigs 2 days after infection. Viral replication was observed in cells of the epithelium of the tongue and coronary band but not in the associated stromal cells. Infected epithelial cells were present in the stratum spinosum, away from the lesion, with small lesions formed above the basement membrane. Viral replication was markedly reduced in tongue epithelium by day 3 postinfection but remained apparent in the coronary band tissue up to 5 days postinfection. These results were confirmed by the RNA copy number determined by RT-PCR.

Animals↗

Anosmia is very common in the Lewy body variant of Alzheimer's disease.

BACKGROUND: Olfactory abnormalities are reported in Alzheimer's disease and Parkinson's disease. Anosmia appears to be common in dementia with Lewy bodies but not in pure Alzheimer's disease. OBJECTIVE: To determine whether anosmia improves discrimination between the Lewy body variant (LBV) of Alzheimer's disease and "pure" Alzheimer's disease. METHODS: 106 cases of necropsy confirmed pure Alzheimer's disease (n = 89) or LBV (n = 17) were reviewed. All had received butanol odour threshold testing. Anosmia was defined as a score < or = 1.0 on a 0-9 point scale. Logistic regression analysis was used to model potential predictors (for example, parkinsonism, smoking, hallucinations) of neuropathological diagnosis and anosmia. RESULTS: LBV cases had an increased prevalence of anosmia (65%) compared with Alzheimer's disease (23%; odds ratio (OR) = 6.3, p = 0.00045), or normal elderly people (6.7%). Within the dementia cases, the negative predictive value (92%) and specificity (78%) of anosmia were both good; sensitivity for detecting LBV was 65%, but the positive predictive value (PPV) was only 35%. Logistic regression models showed anosmia (OR = 5.4, p = 0.005) and visual hallucinations (OR = 7.3, p = 0.007) were strong independent predictors of Lewy body pathology. When anosmia was added as a core feature to consensus diagnostic criteria for probable Lewy body dementia, five additional cases of LBV were detected (29% increased sensitivity), but with four additional false positives (1% increased discrimination, 4% decreased specificity, 33% decreased PPV). CONCLUSIONS: Anosmia is very common in LBV. Adding anosmia as a core feature improved sensitivity for detecting LBV, but did not improve discrimination between Alzheimer's disease and LBV owing to a concomitant increase in false positives.

1-Butanol↗

Reduced osmolarity oral rehydration solution for treating cholera.

BACKGROUND: Oral rehydration solution (ORS) is used to treat dehydration caused by diarrheal diseases including cholera. Reduced osmolarity formulations are safe and more effective than standard ORS for treating non-cholera diarrhea. As cholera causes rapid electrolyte loss, it is important to know if these benefits are similar for people with cholera. OBJECTIVES: To compare the safety and efficacy of reduced osmolarity oral rehydration solution (ORS) with standard ORS for treating diarrhea due to cholera. SEARCH STRATEGY: We searched the Cochrane Infectious Disease Group Specialized Register (January 2004), CENTRAL (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1974 to January 2004), and LILACS (1982 to January 2004). We also contacted organizations and searched reference lists. SELECTION CRITERIA: Randomized controlled trials comparing reduced osmolarity ORS with standard ORS for treating adults and children with acute diarrhea due to cholera. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria, assessed trial quality, and extracted data. We pooled binary data using relative risks (RR), continuous data using weighted mean difference (WMD) or the standardized mean difference (SMD), and presented the results with 95% confidence intervals (CI). MAIN RESULTS: For glucose-based reduced osmolarity ORS, seven trials (718 participants) met the inclusion criteria. Biochemical hyponatremia (serum sodium < 130 mmol/L) was more common with reduced osmolarity ORS (RR 1.67, CI 1.09 to 2.57; 465 participants, 4 trials); for severe biochemical hyponatremia (serum sodium < 125 mmol/L) this was not significant (RR 1.58, CI 0.62 to 4.04; 465 participants, 4 trials). No trials reported symptomatic hyponatremia or death. We found no statistically significant difference in the need for unscheduled intravenous infusion. Analyses separating children and adults showed no obvious trends. Two trials also examined rice-based ORS. In the reduced osmolarity group, duration of diarrhea was shorter (WMD -16.85 hours, CI -21.22 to -12.48; 102 participants, 2 trials). REVIEWERS' CONCLUSIONS: In people with cholera, reduced osmolarity ORS is associated with biochemical hyponatremia when compared with standard ORS, although there are similar benefits in terms of other outcomes. Although this risk does not appear to be accompanied by serious consequences, the total patient experience in existing trials is small. Under wider practice conditions, especially where patient monitoring is difficult, caution is warranted.

Adult↗

Demographic profile of the elderly population in Dublin accident and emergency hospital catchment areas.

The Dublin metropolitan area is now divided into a number of clearly defined accident and emergency (A & E) catchment areas since the closing of the smaller inner city hospitals and the opening of newer hospitals on the periphery of the city. We examined the demographic profile of the elderly population in Dublin city and county served by each of the new catchment areas. Whilst the elderly population make up 9.9% (105,188) of the Dublin population (1996 census) they make up over 20% of the A & E attendances and up to over 40% of the A & E admissions in major Dublin hospitals. There is a wide variation in the percentage elderly population in each hospital catchment area with inner more settled city areas having a much higher percentage elderly population over those hospital catchment areas that serve newer housing areas. We also looked at the level of deprivation. Combining the two most deprived levels St James's Hospital had the largest absolute number and the highest percentage of deprived elderly 12,736 (51.1%) followed by the Mater 6,919 (32.9%), Beaumont 5371 (31.5%), James Connolly 2,983 (38.1%), Tallaght 2012 (22.3%) and St Vincent's Hospital 1987 (7.7%). Hospitals with high numbers of elderly and serving deprived catchment areas face particular resource problems in meeting the needs of the population that they serve. A significant increase in the provision of publicly funded community facilities and long stay accommodation is required to meet the needs of the large number of deprived elderly in the inner city area. Failure to respond to these demographic challenges will have a profound effect on the ability of hospital emergency services to meet the increasing pressures posed by the high volume of acutely sick economically deprived elderly presenting to hospital accident and emergency departments.

Aged↗

Studies of quantitative parameters of virus excretion and transmission in pigs and cattle experimentally infected with foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) can be spread by a variety of mechanisms and the rate of spread, the incubation period and the severity of disease depend on a multitude of parameters, including the strain of virus, the dose received, the route of introduction, the animal species and the husbandry conditions. More knowledge with regard to these parameters is urgently needed to improve resource-efficient disease control. This report describes detailed studies of FMDV load, excretion and transmission in pigs infected with FMDV O UKG 2001, O TAW 1997 and C Noville virus and in cattle infected with the O UKG 2001 virus to facilitate use of a "FMDV load framework" for the assessment of transmission risks. Virus replicated rapidly in pigs and cattle exposed by direct contact. The mean incubation period was around 3-4 days for cattle-to-cattle and 1-3 days for pig-to-pig transmission, depending on the intensity of contact. The results confirmed that a strong relation exists between dose and length of incubation period. Clinical disease was severe in pigs but relatively mild in inoculated cattle; contact infection of cattle appeared to increase the severity of lesions. FMDV RNA was recovered in nasal and mouth swabs from inoculated animals soon after they developed a viraemia and probably reflected the early production and excretion of virus. FMDV RNA in nasal and mouth swabs from contact animals could be detected several days before they showed other signs of infection, indicating the possibility of detecting exposed animals during the incubation period. FMDV RNA could also be detected in swab samples after the viraemic phase. This may have represented background environmental virus that had been trapped in the respiratory tract and mouth. Alternatively, it may have indicated a somewhat slower clearance or half-life of viral RNA or an extended low level of FMDV replication at these sites. The pattern of FMDV RNA concentrations in pigs was closely similar to that in cattle, but the amounts of FMDV RNA were higher.

Animals↗

Comparison of the effects of two intrathecal anaesthetic techniques for transurethral prostatectomy on haemodynamic and pulmonary function.

BACKGROUND AND OBJECTIVE: Transurethral prostatectomy is routinely performed under spinal anaesthesia. This technique can cause hypotension, which is particularly undesirable in the elderly. The objective was to compare spinal anaesthesia for transurethral prostatectomy using hyperbaric bupivacaine 15 mg (control group) and hyperbaric bupivacaine 10 mg (limiting spread by maintaining the upright position for 15 min) and fentanyl 25 microg (fentanyl group) in terms of haemodynamic and pulmonary function. METHODS: Thirty ASA I-III patients were randomly selected and underwent spinal anaesthesia with either hyperbaric bupivacaine 15 mg (immediately positioned supine) or hyperbaric bupivacaine 10 mg (upright for 15 min) and fentanyl 25 microg. RESULTS: The greatest changes in mean arterial pressure (P = 0.9), ephedrine requirements (P = 0.8) and mean maximum change in forced vital capacity (P = 0.5) were similar in both groups. CONCLUSIONS: The addition of fentanyl 25 microg to bupivacaine 10 mg and limiting the spread of the block does not improve either haemodynamic or pulmonary function compared with bupivacaine 15 mg in patients undergoing transurethral prostatectomy.

Adjuvants, Anesthesia↗

Patients' health-related quality-of-life and health state values for motor neurone disease/amyotrophic lateral sclerosis.

Motor neurone disease (MND) has a severe impact on patient quality of life, especially in later stages of the disease. This study assesses the health-related quality of life (HRQL) of MND patients, and for the first time elicits health state values from patients for their present health state. A structured interview was conducted with 77 patients. Patients completed a disease specific health status measure (ALSAQ-40), a generic health status measure (EuroQol EQ-5D), a visual analogue scale (VAS) and a standard gamble (SG) exercise. The ALSAQ-40 was sensitive to disease severity. Patients' mean VAS rating of their own health ranged from 0.74 for stage 1 (early) disease severity (n = 15), to 0.37 for stage 4 (late stage) disease severity (n = 19). Utilities elicited via SG varied from a mean of 0.79 for stage 1 disease severity to a mean of 0.45 for stage 4 disease severity. The EQ-5D derived single index ranged from a mean of 0.63 for stage 1 disease severity to a mean of -0.01 for stage 4 disease severity. This study demonstrates that it is feasible and practical to obtain health state values from MND patients and it provides evidence that patients place a high value on their HRQL, even in cases where health status is very poor.

Adult↗

Identification of a novel stress resistance mechanism in Campylobacter jejuni.

AIM: To study stress resistance mechanisms in Campylobacter spp. METHODS AND RESULTS: Campylobacter strains were grown to the appropriate phase in Brucella broth. The cells were diluted into either cell-free spent medium (obtained by filtration of a grown culture) or a freshly prepared medium and the pH reduced to 4.5, a lethal pH value. At suitable time intervals survivors were enumerated on Campylobacter blood free selective agar base. The cell-free spent medium from mid-exponential and stationary phase had a protective effect on acid and thermal stress in Campylobacter jejuni CI 120, a natural isolate. The protective effect of the extracellular compound was not significantly inactivated by boiling, but was inactivated by proteinase. CONCLUSIONS: The present study suggests that a protein (or proteins) accumulated by C. jejuni CI 120 during growth may play an active role in the induction of stress responses and that this protein is heat stable. SIGNIFICANCE AND IMPACT OF THE STUDY: The results indicate that C. jejuni CI 120, a natural isolate, has the ability to use extracellular signalling mechanisms to induce tolerance to stress factors. This is a major advancement in the understanding of the physiological basis for survival of C. jejuni in the environment.

Animals↗

A Scandinavian adaptation of the Multi-Clinic Smell and Taste Questionnaire: evaluation of questions about olfaction.

OBJECTIVE: A Scandinavian adaptation of the Multi-Clinic Smell and Taste Questionnaire (MCSTQ-Sc) was evaluated with respect to comprehension and test-retest reliability for responses to questions about olfactory dysfunction (abnormal sensitivity, parosmia and phantosmia) and related questions about medical history and consequences of olfactory dysfunction. MATERIAL AND METHODS: Comprehension was evaluated in a first study in 20 patients with chief complaints of olfactory dysfunction by comparing questionnaire- and interview-based responses. Test-retest reliability was evaluated in a second study in 30 other patients with olfactory complaints. RESULTS: Data from the two studies suggest that the vast majority of the questions evaluated from the MCSTQ-Sc are comprehensible and generate responses with very good reliability. Distinct exceptions were poor agreement between the questionnaire- and interview-based responses for questions about the number of cigarettes smoked and the pleasantness and typical episode length of phantosmia; the test-retest reliability regarding the nostril side of phantosmia also showed poor agreement. The results suggest the importance of probing these areas further in the clinical interview. CONCLUSION: The findings imply that, with a few caveats, the MCSTQ-Sc is a useful tool for the clinical assessment of olfactory dysfunction and its consequences.

Female↗