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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 37 records · Page 2Linked to original sources

Nitrogen balance, microbial protein production, and milk production in dairy cows fed fodder beets and potatoes, or barley.

Fourteen multiparous midlactation dairy cows were used in a change-over experiment with 3 periods and 3 diets to evaluate the effects of fodder beets and potatoes on N metabolism, microbial protein production, and milk production. A basal ration of alfalfa/grass silage offered ad libitum, 1 kg of grass hay and 1 kg of heat-treated rapeseed cake was supplemented with 5 kg DM of either rolled barley/raw potatoes 80:20 (BAP), fodder beets/raw potatoes 80:20 (BEP) or rolled barley (BA). Urine and feces were collected quantitatively from 8 cows and ruminal samplings, and evacuations were performed on 4 cannulated cows. Intake and production did not differ between BAP and BA, but the BEP diet lowered intake of both silage and total ration by 0.9 kg DM. Daily yield of energy-corrected milk (ECM) was decreased by 1.7 and 2.3 kg compared with BAP and BA, respectively. Milk urea concentration was 1 mM lower with the BEP diet. The proportion of feed N recovered in milk was 20 to 21% for all diets. With the BEP diet, urinary N amount and proportion were reduced correspondingly to the lower total N intake. Fecal N amount remained unchanged, and hence nitrogen apparent digestibility decreased by 5 percentage units with the BEP diet. Microbial protein production, assessed by allantoin excretion, tended to be highest with the BAP diet. Acetate proportion of VFA was lowered by the BEP diet, while proportions of propionate and butyrate both tended to increase. Different fermentation patterns, probably related to differences in rumen microbiota, could explain why changes in energetic efficiency and milk composition reported in the literature did not occur in the actual experiment when roots replaced barley. Compared with barley, roots appeared to have a greater negative effect on silage intake in conjunction with a prewilted silage with high intake potential allowed ad libitum and this decreased milk production by a magnitude corresponding to the lower intake of ME.

Acetates↗

Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy.

Proton spectroscopy can noninvasively provide useful information on brain tumor type and grade. Short- (30 ms) and long- (136 ms) echo time (TE) (1)H spectra were acquired from normal white matter (NWM), meningiomas, grade II astrocytomas, anaplastic astrocytomas, glioblastomas, and metastases. Very low myo-Inositol ([mI]) and creatine ([Cr]) were characteristic of meningiomas, and high [mI] characteristic of grade II astrocytomas. Tumor choline ([Cho]) was greater than NWM and increased with grade for grade II and anaplastic astrocytomas, but was highly variable for glioblastomas. Higher [Cho] and [Cr] correlated with low lipid and lactate (P < 0.05), indicating a dilution of metabolite concentrations due to necrosis in high-grade tumors. Metabolite peak area ratios showed no correlation with lipids and mI/Cho (at TE = 30 ms), and Cr/Cho (at TE = 136 ms) best correlated with tumor grade. The quantified lipid, macromolecule, and lactate levels increased with grade of tumor, consistent with progression from hypoxia to necrosis. Quantification of lipids and macromolecules at short TE provided a good marker for tumor grade, and a scatter plot of the sum of alanine, lactate, and delta 1.3 lipid signals vs. mI/Cho provided a simple way to separate most tumors by type and grade.

Alanine↗

Effect of anesthesia on voiding function after tension-free vaginal tape procedure.

OBJECTIVE: To determine whether the mode of anesthesia used during the tension-free vaginal tape procedure affects postoperative voiding function. METHODS: A retrospective cohort study was performed using cases in which tension-free vaginal tape placement was the sole procedure performed. Of the 173 cases reviewed, we were able to use the data from 163. Hierarchal linear regression was used to identify independent predictors of our dependent variable: days to complete voiding. In the first block, established predictors of postoperative voiding dysfunction were entered into the model. In the second block, potential confounders of the relationship between anesthesia type and days to complete voiding identified during univariate analysis (P <.15) were entered into the model. In the third block, anesthesia type was entered into the model to determine whether it added any unique variance after controlling for previously established predictors of postoperative voiding dysfunction. RESULTS: The mean days to complete voiding was similar in our local or regional anesthesia (n = 90) and general anesthesia groups (n = 73) (2.3 [0-21] versus 2.3 [0-14], P =.95). Our final regression model (F = 2.74, P =.011) included age, prior pelvic organ prolapse surgery, and preoperative urge symptoms and explained 22.2% of the variance in days to complete voiding. Anesthesia type did not add any predictive improvement after controlling for these variables. CONCLUSION: General anesthesia, and therefore lack of a cough-stress test, does not increase the chance of postoperative voiding dysfunction associated with tension-free vaginal tape.

Anesthesia, General↗

The effect of head position, electrode site, movement and smoothing window in the determination of a reliable maximum voluntary activation of the upper trapezius muscle.

Quantitative measures derived from raw myoelectric signal (MES) data must be normalized to allow for comparisons both within and between subjects. The most common method of normalization involves dividing the root mean square (RMS) amplitude of the MES recorded during a given activity by the RMS of the MES elicited during a maximal voluntary isometric contraction (MVIC) of that particular muscle. The objective of this study was to use surface-recorded MES amplitude to determine the combination of electrode site, test position, head posture, and smoothing window that elicits the highest and most reliable MES amplitudes during an MVIC of the upper trapezius (UT) muscle. Ten volunteers had surface electrodes positioned at five sites on the UT of their dominant side. Three trials of each of three MVIC test positions were performed both with the head in neutral and rotated 45 degrees to the contralateral side. A repeated-measures ANOVA was used for statistical hypothesis testing. Coefficients of variation were used to quantify the between-factor variability introduced in each case. In addition, the data were re-analyzed using moving windows of 100 to 500 ms in length, and an ANOVA was used to determine the effect of window length on both the amplitude and variability of the estimates of maximum voluntary activation (MVE). Head position had no significant effect on RMS amplitude of the MVIC in any of the test positions. There was a significant electrode site by test position interaction effect. Bonferroni post-hoc analyses were performed on this interaction by fixing test position and testing electrode site, revealing that Sites 1 (2 cm lateral to the midpoint between C7 spinous process and the posterolateral border of the acromion) and 4 (2 cm posterior to Site 1) recorded significantly higher RMS values for all test positions, and were not significantly different from each other. Fixing electrode site, the test position analysis revealed that abduction of the humerus, and abduction with external rotation of the humerus produced significantly higher RMS values than shoulder elevation at both Sites 1 and 4, and that abduction produced a significantly higher RMS amplitude than abduction in external rotation at Site 1. The results confirmed that Sites 1 and 4 consistently produced the highest MES amplitudes for all movements. Pure abduction consistently elicited maximal RMS values; however there is concern regarding supraspinatus cross talk during this movement. Site 1 was found to produce the most reliable data. A moving window of 100 ms was found to generate MVE estimates that were significantly higher than windows ranging from 200 ms to 500 ms in length. There was no effect of window length on the reliability of the MVEs. Based on this study, it was concluded that abduction or abduction with the arms in lateral rotation should be used as normalization contraction positions for the upper trapezius muscle. During this movement, Site 1 data smoothed with a moving window of 100 ms produces the highest amplitude MVE data but window lengths greater than 200 ms produce more stable estimates in terms of being able to compare studies in which moving windows are used to compute RMS.

Adult↗

Heparan sulphate sulphotransferase expression in mice and Caenorhabditis elegans.

Heparan sulphate (HS) acts as a multifunctional cell regulator, with specific sulphated saccharide sequences designed for selective interactions with many proteins. Functionally, these interactions result in regulation of the protein activities, and there is growing evidence that cells can dynamically alter the structure of HS sequences that they display. HS biosynthesis involves the action of a complex set of enzymes with polymerase, epimerase and sulphotransferase (ST) activities. In higher organisms, multiple isoforms of STs decorate the nascent HS chains with specific patterns of sulphation that confer selective biological functions. The study of HSSTs in model organisms provides a valuable opportunity to examine the expression of these enzymes in relation to the structure and activities of the HS produced. Here we describe that, in mice, there are stage-specific combinations of HSST isoenzymes that underlie the synthesis of different HS species at different times in the developing brain. This differential expression of HSSTs results in the synthesis of structurally variant HS species that form functional signalling complexes with specific fibroblast growth factors and their receptors. Regulated synthesis of specific HS species could be a mechanism for the regulation of proliferation and differentiation in the developing brain. We also describe evidence that a Caenorhabditis elegans orthologue of the mammalian 2OST enzyme, called HST-2, is essential for the normal development of this nematode. Together, these studies emphasize the importance of HSSTs in the biosynthesis of functionally variant HS proteoglycans, and demonstrate the importance of these complex regulatory molecules in developmental processes.

Animals↗

A randomized, placebo-controlled, double-blind trial of ondansetron in renal itch.

BACKGROUND: Renal itch is a relatively common and distressing problem for patients with chronic renal failure. Ondansetron, a serotonin type 3 receptor antagonist was developed for relief of chemotherapy induced nausea. Recently, anecdotal reports describe relief of renal itch with ondansetron. OBJECTIVES: We performed a double-blind randomized placebo-controlled trial to objectively assess the effectiveness of ondansetron in renal itch. PATIENTS AND METHODS: With approval from the local ethical committee, 24 patients on haemodialysis were enrolled in the trial. On a random basis 14 patients were blindly allocated to the ondansetron-placebo sequence and 10 to the placebo-ondansetron sequence. Baseline values for itch were obtained for 7 days before the treatment period and there was a 7-day washout between the treatment periods. During the treatment patients received either 8 mg of ondansetron three times a day or a placebo tablet three times a day for 2 weeks. Patients were asked to record the severity of their pruritus on a visual analogue scale (VAS) twice a day. At the end of the study patients were asked blindly which treatment they had preferred. RESULTS: Seventeen patients completed the trial. Pruritus decreased by 16% (95% CI: 0.5-32%) during active treatment and by 25% (95% CI: 9-41%) during treatment with placebo. The change in VAS scores during treatment with ondansetron (P = 0.04) and placebo (P = 0.01) were both significant. Eleven patients expressed a preference, seven for placebo and four for ondansetron. CONCLUSIONS: Our results show that ondansetron is no better than placebo in controlling renal itch.

Antipruritics↗

Tracing blood units to their recipients: results of a two-centre study.

An important principle of the use of blood components is the ability to trace them from the donor to the recipient. This study set out to establish whether there was sufficient documentation in patient case notes to confirm the transfusion of blood components in a sample of computer blood bank records at two large teaching hospitals in UK. The criteria for verification of transfusion were taken from guidelines from the British Committee for Standards in Haematology (Transfusion Medicine 1999, 9, 227-238). The blood bank computer records indicated that 486 units of blood components were issued and not returned to the blood bank for 80 patients during a 2-month period. Of the 486 units, transfusion of 409 units (84%) was verified against patient notes, but 77 units (16%) could not be verified as received by the patient. The study showed that documentation of transfusions was variable. For example, written prescriptions were only found for 204 units (42%). These results have implications for 'lookback studies' involving blood transfusion. Further efforts are required to educate those involved in transfusing blood about the need for accurate documentation.

Blood Banks↗

Characteristics of Type 1 diabetes of over 50 years duration (the Golden Years Cohort).

BACKGROUND: Type 1 diabetes mellitus is associated with high levels of premature morbidity and mortality. Prolonged survival is possible, however, and some patients appear to be protected from the long-term complications of this condition. METHODS: Diabetes UK awards medals to patients who have had Type 1 diabetes for 50 years or more. By examining medal-holders, we have established the clinical and biochemical features of a group of 400 subjects (54% male) with Type 1 diabetes of long duration. RESULTS: Mean age of the subjects was 68.9 years and mean age-at-onset of diabetes 13.7 years. Features of long duration diabetes in this cohort include normal body mass (mean BMI 25.0 kg m-2), low insulin dose (mean 0.52 units kg-2) and greatly elevated HDL-cholesterol (mean 1.84 mmol/l). Mean HbA1c was 7.6% (normal range 3.8-5.0%) and no patient had a normal HbA1c at the time of venesection. As a group, they have long-lived parents and consume moderate amounts of alcohol. Medical contact has often been sporadic. A significant proportion (29%) were taking anti-hypertensive medication. Screening for micro- and macroalbuminuria was positive in 35.7%. CONCLUSIONS: Patients with long-duration (> 50 years) Type 1 diabetes are relatively protected from clinical diabetic nephropathy and large vessel disease; our data are consistent with protection possibly being genetically determined in part via elevated HDL-cholesterol levels. An abnormal urinary albumin/creatinine ratio is common in these patients, despite their low risk of significant renal deterioration; this may have implications for microalbuminuria screening programmes.

Aged↗

Patients' decision-making for migraine and chronic daily headache management. A qualitative study.

The objective of this study was to gain insight into the patients' decision-making for migraine and chronic daily headache management. Patients were recruited by theoretical sampling in Surrey (UK). Semi-structured and tape-recorded interviews (n = 13) were conducted, transcribed verbatim, coded and analysed according to the grounded theory methodology. Thirteen patients (8 migraine and 5 chronic daily headache) described their management. All patients employed multiple behaviours to manage their headaches. From the patients' descriptions emerged their decision-making. Based on experience, perceptions and new information, the decision-making process involved four stages: headache severity, evaluation, decision making and behaviours. Although the participants were passive with regards to certain management strategies, overall they were actively involved in treating and preventing their headaches. Furthermore, they were active decision-makers in choosing appropriate management. Migraine and chronic daily headache patients are actively involved in managing their headaches. They are key decision-makers and should not be overlooked as a resource for effective management.

Adult↗

Mortality study of 18 000 patients treated with omeprazole.

BACKGROUND: The long term safety of potent gastric acid suppressive therapy has yet to be established. METHOD: General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993-1995. Death rates were compared with general population rates. RESULTS: Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34-1.55); p<0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 (95% CI 1.58-2.08); p<0.0001), circulatory diseases (1.27 (95% CI 1.13-1.43); p<0.0001), and respiratory diseases (1.37 (95% CI 1.12-1.64); p<0.001). Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87-3.43); p<0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 (95% CI 2.60-6.04); p<0.0001), colon and rectum (1.40 (95% CI 0.84-2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19-2.19); p<0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20-10.09) (p<0.0001) in year 1; 2.88 (95% CI 1.62-4.79) (p<0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett's disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 (95% CI 2.17-4.80)). Six deaths occurred in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37-2.22)) and five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25-1.80)). No relationships were detected with numbers of omeprazole scripts received. CONCLUSIONS: Increases in mortality associated with treatment are due to pre- existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration.

Adolescent↗

Amygdala volumetry in "imaging-negative" temporal lobe epilepsy.

OBJECTIVE: Although amygdala abnormalities are sometimes suspected in "imaging-negative" patients with video EEG confirmed unilateral focal epilepsy suggestive of temporal lobe epilepsy (TLE), amygdala asymmetry is difficult to assess visually. This study examined a group of "imaging-negative" TLE patients, estimating amygdala volumes, to determine whether cryptic amygdala lesions might be detected. METHODS: Review of video EEG monitoring data yielded 11 patients with EEG lateralised TLE and normal structural imaging. Amygdala volumes were estimated in this group, in 77 patients with pathologically verified hippocampal sclerosis (HS), and in 77 controls. RESULTS: Seven of 11 "imaging-negative" cases had both significant amygdala asymmetry and amygdala enlargement, concordant with seizure lateralisation. Although significant amygdala asymmetry occurred in 35 of 77 HS patients, it was never attributable to an abnormally large ipsilateral amygdala. Compared with patients with HS, patients with amygdala enlargement were less likely to have suffered secondarily generalised seizures (p<0.05), and had an older age of seizure onset (p<0.01). CONCLUSION: Abnormal amygdala enlargement is reported in seven cases of "imaging-negative" TLE. Such abnormalities are not observed in patients with HS. It is postulated that amygdala enlargement may be attributable to a developmental abnormality or low grade tumour. It is suggested that amygdala volumetry is indicated in the investigation and diagnosis of "imaging-negative" TLE.

Adult↗

Cerebral palsy and juvenile-onset bipolar disorder. A preliminary report.

Cerebral palsy refers to a heterogeneous group of congenital and early acquired brain disorders. Children with cerebral palsy and other brain disorders have an increased rate of psychiatric disorder. The pattern of disorder is not particularly distinctive and no specific association has been found. We report two cases of spastic diplegia of prematurity comorbid with juvenile onset bipolar disorder, which highlight some of the diagnostic difficulties in these cases. An interesting association between the periventricular leucomalacia as an aetiological factor in cerebral palsy and the white matter lesions seen on magnetic resonance imaging in cases of bipolar disorder is noted.

Adolescent↗

An innovative approach to the determination of safety for a dietary ingredient derived from a new source: case study using a crystalline lutein product.

Lutein and zeaxanthin are antioxidant carotenoids that occur naturally in the diet. A new source of these carotenoids, a crystalline lutein product, is an extract from the marigold flower (Tagetes erecta) that contains approximately 86% by weight of the carotenoids lutein and zeaxanthin. The safety of consumption of a crystalline lutein product used as an ingredient in food is determined by evaluating the safety of ingestion of the whole product, as well as safety of ingestion of the major constituents, lutein and zeaxanthin. The approach to evaluating the safety of increased lutein and zeaxanthin intake from consumption of crystalline lutein product is based on an evaluation of the incremental increase this ingestion will produce in lutein and zeaxanthin and in total carotenoids, compared to background exposure. In addition, bioavailability of lutein+zeaxanthin from crystalline lutein product, when added to food, is determined and used to adjust the estimated daily intake of lutein and zeaxanthin from this new source and standardize it to the bioavailable dose of these carotenoids from food sources. The proposed level of ingestion of lutein and zeaxanthin from the crystalline lutein product would increase intake of lutein zeaxanthin in the generally vegetable-poor American diet to a level comparable to the mean intake of individuals consuming the recommended number of servings of vegetables per day and is therefore determined to be both prudent and safe. Safety of consumption of the whole product is determined by evaluating the source of the product, production process, nature and quantity of impurities, and product specifications. Corroboration of safety is provided by animal toxicology studies of the crystalline lutein product, as well as human and epidemiologic studies of lutein and zeaxanthin intake. It can be concluded that crystalline lutein is a safe and GRAS source of lutein for its proposed uses in food.

Animals↗

The expression of p53, p21, Bax and induction of apoptosis in normal volunteers in response to different doses of ultraviolet radiation.

BACKGROUND: Ultraviolet radiation (UVR) damages keratinocytes. Direct DNA damage may undergo enzymatic repair followed by resumption of the normal cell cycle. Cells may also be eliminated without inflammation by the error-free process of programmed cell death or apoptosis. Necrosis of cells can occur after overwhelming damage. Failure of apoptosis leads to retention of cells with persistent mutations. OBJECTIVES: This study investigates p53-dependent apoptotic responses in normal skin following solar-simulated radiation (SSR). METHODS: Sun-protected buttock skin from normal volunteers with no history or clinical evidence of skin cancer was exposed to graded doses of SSR, 0.5, 1, 2 and 3 times the minimal erythema dose (MED). Biopsies taken at a range of time points (4.5, 9, 24, 33, 48 and 72 h) after UVR, quantified the time course and dose-response of apoptosis and the expression of the relevant proteins, p53, p21waf1/Cip1 and Bax, by single and double labelling techniques. RESULTS: Apoptosis was upregulated in a dose-dependent manner as was the expression of p53, p21waf1/Cip1 and Bax in response to SSR. Following exposure to 3 MEDs it was found that: (i) the maximum number of apoptotic cells occurred at 48 h; (ii) p53 protein expression was upregulated from 4 to 72 h preceding peak p21waf1/Cip1 protein expression (9-48 h) and peak Bax protein expression (33 h). CONCLUSIONS: These results suggest that, following SSR, normal human skin induces apoptosis by the p53, p21waf1/Cip1, Bax pathway in vivo. In addition, induction of apoptosis and expression of p53, p21waf1/Cip1 and Bax occurs in a dose-dependent manner.

Aged↗

The intergenerational transmission of fertility in contemporary Denmark: the effects of number of siblings (full and half), birth order, and whether male or female.

Using the Danish Fertility Database, we investigate intergenerational fertility transmission, including the relationship between the number of children born to those aged 25 and 26 years in 1994 and the number of their full sibs and half-sibs. We find that the fertility behaviour of parents and their children is positively correlated, and that half-sibs and full sibs have broadly similar effects. We do not find, in this complete national population, the strong birth order effects reported in some earlier studies. Nor do we find evidence of a weakening of intergenerational fertility transmission over time, perhaps because the greater flexibility of lifestyles in this post-transitional phase provides the extended social space within which intergenerational continuities can manifest themselves. We show that members of large families are over-represented in subsequent generations - that they have far more kin than those from smaller families - and that intergenerational continuities in fertility behaviour play a substantial role in keeping fertility higher than it would be in the absence of such transmission.

Birth Rate↗

The contribution of proton magnetic resonance spectroscopy (1HMRS) to clinical brain tumour diagnosis.

Proton magnetic resonance spectroscopy (1HMRS) provides biochemical information from tissue non-invasively, and has an evolving role in brain tumour diagnosis and management. We present 100 consecutive patients with brain tumours who had single voxel 1HMRS as part of their preoperative investigations. We report the histopathological findings and the diagnostic contribution of spectroscopy in an adjunctive role. On the basis of clinical and radiological information the preoperative diagnosis was unclear or inaccurate in 26 out of 100 cases. The discrepancy was of lesion grade in 17 cases and lesion type in 9 cases. In 6 of 100 patients with brain tumours 1HMRS could have made a significant contribution to the preoperative diagnosis if used as part of the routine assessment. There is therefore a useful role for 1HMRS in the evaluation of intracranial mass lesions.

Adolescent↗