Biomedical subjects

J Murphy

Publications and source records attributed to J Murphy.

At least 19 recordsLinked to original sources

PubMed1992

In vitro specificity of EcoRI DNA methyltransferase.

The sequence selectivity of enzyme-DNA interactions was analyzed by comparing discrimination between synthetic oligonucleotides containing the canonical site GAATTC and altered DNA sequences with the EcoRI DNA methyltransferase. The specificities (kcat/KmDNA) are decreased from 5- to 23,000-fold relative to the unmodified site. For several substrates the decrease in kcat makes a disproportionate contribution to the specificity difference, suggesting that discrimination is mediated by the placement of critical catalytic residues rather than binding interactions. This is supported by our observation that specificity changes are generally not followed by changes in the stability of the methyltransferase-DNA complexes. Also, base pair substitutions near the site of methylation result in greater decreases in complex stability, suggesting that recognition and catalytic mechanisms overlap.

Base Sequence↗

PubMed1992

Characterization and pharmacological modulation of soluble phospholipase A2 generated during glycogen-induced rat peritonitis.

Soluble phospholipase A2 (PLA2) activity was assessed in rat peritoneal lavage fluid after an intraperitoneal injection of 6% glycogen. Enzyme activity immediately increased 5-fold above basal by 4 h. Activity decreased by only 30% at 18 h and remained at this elevated level through 72 h. The initial rise in PLA2 activity was coincident with protein extravasation but not with polymorphonuclear leukocyte infiltration, suggesting that the early PLA2 activity could be, in part, blood-derived. Mononuclear cell influx occurred later (4 h), peaked by 6-8 h but remained elevated through 72 h possibly contributing to the persistence of PLA2 activity through 20-72 h. The exudate PLA2 measured at 4-6 h (early) and 20-24 h (late), after glycogen administration, were biochemically compared. They were found to be neutral pH active, Ca(2+)-dependent and were similarly inhibited by the inhibitors, p-bromophenacylbromide, ellagic acid, gossypol and luffariellolide. Oral administration of dexamethasone to rats inhibited the appearance of PLA2 activity in the peritoneal lavage fluid as well as cellular influx and protein extravasation. Indomethacin had no effect on these parameters. These studies demonstrate that PLA2 is an integral component of glycogen-induced peritonitis and can be pharmacologically manipulated.

Animals↗

PubMed1992

Estimation of normal lumbar flexion with surface inclinometry. A comparison of three methods.

The purpose of this study was to determine the magnitude and clinical significance of surface measurement error in the determination of lumbar spinal flexion. Intrarater, inter-rater and intermethod reliability estimates were obtained using single inclinometry, double inclinometry and back range-of-motion inclinometry methods. Eight healthy subjects were examined independently by two experienced observers and three replicates of each measurement were obtained by each observer in a random sequence. In addition, three replicates of lumbar flexion angles were obtained for each subject by a single observer using the B-200. Reliability estimates were determined by intraclass correlation coefficients and were further compared by paired t tests between observation series. The median range of error was 8.5 degrees using the single inclinometer, 10.5 degrees using the double inclinometer and 16 degrees using the back range-of-motion. The intrarater reliability was generally higher than inter-rater reliability and intermethod reliability was low in most cases reflecting the poor cross-validity across inclinometry methods and between each inclinometry method and the B-200. In conclusion, significant measurement error in estimating lumbar flexion by inclinometry may be expected to occur even in a "controlled" setting using experienced observers, standard examination techniques and asymptomatic healthy subjects. These findings appear to undermine the expectation that the clinician can reliably apply surface inclinometry to estimate loss of spinal mobility for purposes of impairment determination.

Adolescent↗

PubMed1992

Laparoscopic versus conventional cholecystectomy. Use of biliary scintigraphy.

Laparoscopic cholecystectomy has become a popular alternative to traditional open cholecystectomy for uncomplicated, acute cholecystitis. At some centers, laparoscopic cholecystectomy is already the more frequently performed procedure. The presence or suspicion of common bile duct (CBD) stones or obstruction may necessitate conventional surgery or additional procedures. This report describes a patient with acute cholecystitis for whom the surgical management changed based on biliary scintigraphy. The demonstration of an unsuspected CBD obstruction by biliary imaging allowed the surgeon to change the initial plan for laparoscopic cholecystectomy to conventional open surgery. Stones in the common bile duct were removed.

Acute Disease↗

PubMed1992

Hemodialysis intravascular hemolysis and kinked blood lines.

Between May 29 and September 13, 1991, 4 patients developed acute intravascular hemolysis during hemodialysis with Monitral-S delivery systems and Hospal BSM A77 blood lines. All had malaise, nausea and headache; 3 had severe abdominal pain and 2 became very ill. Plasma hemoglobins were 3-21 g/l and LDH 542-3,300 IU in the 4 patients. Hepatoglobin became unmeasurable in 3 and was 0.09 g/l in the 4th patient. Soon afterwards, we found the arterial blood line tightly kinked at the dialyzer inlet port in the 4th patient and released it; he developed abdominal pain, hemolysis was present. We then found these lines had an extra long pump segment, and the rest was short and fitted poorly. When put in the first tubing organizer, severe kinking could occur just after the pump segment, causing back pressure but no alarm. We produced early visible hemolysis in a 1-liter circulating closed loop blood system with the blood line kinked either at the dialyzer inlet or just below the first arterial line tubing organizer with 40 g/l free plasma hemoglobin by 30 min. We excluded reported causes of intravascular hemolysis during hemodialysis. No hemolysis occurred before or during the 9 months after we discarded BSM A77 lines. The evidence indicates that kinked blood lines caused the hemolysis.

Hemolysis↗

PubMed1992

Abnormal intracellular calcium ion concentration in platelets and lymphocytes of bipolar patients.

The authors measured intracellular Ca2+ concentrations in four manic and five bipolar depressed patients and seven comparison subjects. Platelet and lymphocyte intracellular Ca2+ concentrations were comparable. The patients' mean intracellular Ca2+ concentrations were higher than those of the comparison subjects and demonstrated more interindividual variation. These findings suggest a diffuse abnormality in mechanisms affecting intracellular calcium homeostasis in bipolar disorder.

Adult↗

PubMed1992

The calcium second messenger system in bipolar disorders: data supporting new research directions.

Studies of aberrations in second messenger function may help to elucidate some of the multiple complex neurobiological alterations in bipolar affective disorders. The phosphatidylinositol and calcium ion (Ca2+) second messengers are of particular interest because of evidence of hyperactivity of these signaling mechanisms in both mania and bipolar depression and of their normalization by lithium and other mood-stabilizing treatments. Because the intracellular Ca2+ signal has a biphasic action, a single aberration could explain diverse clinical manifestations of the same illness, and a single action on the messenger could explain the biphasic actions of many treatments for bipolar disorders.

Bipolar Disorder↗

PubMed1992

para-amino benzoic acid in the assessment of completeness of 24-hour urine collections from hospital outpatients and the effect of impaired renal function.

Eighteen (29%) of 24-h urine collections made by 63 hospital outpatients attending a gastroenterology clinic were incomplete, as judged by 24 h urine recovery of an oral marker, para-amino benzoic acid (PABA), despite more than the usual efforts to obtain complete collections. Incomplete collections contained significantly less sodium, urea and total nitrogen than full collections. Average outputs were 134 mmol and 103 mmol per day for sodium (P less than 0.02); 301 mmol and 223 mmol for urea (P less than 0.001); and 10.1 g and 8.3 g nitrogen (P less than 0.01) in the complete and incomplete collections respectively. In renal outpatients with a plasma creatinine in excess of 125 mumol per litre, urine recoveries of PABA were reduced, but within the expected range in renal patients whose plasma creatinine was normal.

4-Aminobenzoic Acid↗

PubMed1992

DES clinic--the first six months.

In October 1990 a DES (Diethylstilbestrol) clinic was established at the National Maternity Hospital, Dublin. We describe the results of the first six months of the clinic. During this time, 172 inquiries were received; 95 women were seen at the clinic, 16 were deemed to be DES--exposed and eight were classified as possibly DES exposed. Classical cervicovaginal signs of DES exposure were noted in 15 women, a further eight women showed cervical epithelial abnormalities at colposcopy, the history of in utero DES exposure was confirmed in eight cases. No cases of cervical intraepithelial neoplasia or vaginal clear-cell adenocarcinoma were detected. Pregnancy related problems possibly attributable to DES exposure were documented in six women.

Adenocarcinoma↗

PubMed1991

Serotonergic sprouting is induced by dopamine-lesion in substantia nigra of adult rat brain.

We have previously extracted a serotonin (5-HT) neurotrophic supernatant from the 5,7-DHT lesioned hippocampus. The current study shows that a new 5-HT neurotrophic signal was monitored in the striatum and nigra after DA-denervation. Such a signal may be involved in the heterotypic sprouting. Dopaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), was injected directly into the substantia nigra of adult rats. Two months after surgery, immunocytochemical staining showed that tyrosine hydroxylase (TH)-positive cell bodies had mostly disappeared in the substantia nigra, and TH-positive terminals in the striatum were almost completely depleted. Meanwhile, the 5-HT fibers, which exist in the same areas with low density, sprouted in the nigra as well as in the striatum and became dense. Normally 5-HT fibers innervate the striatum sparsely and the globus pallidus densely with sharp delineation (in the control side), and become dense across both areas with no appreciable delineation (in the lesion side). The increase of 5-HT fibers was more prominent in the posterior than in the anterior striatum. A significant increase in 5-HT and 5-HIAA levels was also evident in the posterior striatum when the decrease in DA level exceeded 90% in the nigra and striatum. In addition, we found that induction of 5-HT sprouting requires a greater than 90% decrease of DA level. Current data support that 6-OHDA injection in the substantia nigra of adult rats triggered a trophic signal or removed an inhibition for the growth of 5-HT neurons which responded with sprouting in the nigra as well as in the striatum.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition.

Left ventricular dysfunction can be improved with angiotensin-converting-enzyme inhibition started 1 week after myocardial infarction or later. To see whether earlier intervention may confer greater benefit, a double-blind study was carried out in which 100 patients with Q wave myocardial infarction, but without clinical heart failure, were randomly allocated treatment with captopril 50 mg twice daily or placebo starting 24-48 h after onset of symptoms. Left ventricular volumes were measured regularly during 3 months of treatment and after a 48 h withdrawal period by means of two-dimensional echocardiography. The placebo group showed significant increases in left ventricular end-diastolic (LVEDVI) and end-systolic (LVESVI) volume indices, with the ejection fraction unchanged. By contrast, the captopril group showed a slight but not significant rise in LVEDVI and a significant reduction in LVESVI with ejection fraction increased significantly. At 3 months there was a 4.6% difference in the change in ejection fraction from baseline between the groups (p less than 0.0001). Most of the treatment benefit was evident at 1 month and there were no changes in left ventricular volumes after 48 h withdrawal of treatment at 3 months. Heart failure requiring treatment with frusemide developed in 7 patients in each group during the study period; 3 of these (1 captopril-treated, 2 placebo-treated) had to be withdrawn from the trial with severe heart failure requiring open treatment. Thus early treatment with captopril is effective in preventing the ventricular dilatation that can occur after Q wave myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1991

Elevated platelet intracellular calcium concentration in bipolar depression.

Baseline and thrombin-stimulated free intracellular calcium concentrations in blood platelets were significantly higher in untreated depressed bipolar patients than in untreated unipolar depressed patients or controls. Platelet intracellular calcium ion concentrations in euthymic-treated bipolar patients were equivalent to control values, suggesting but not proving a state-dependent change in intracellular calcium ion dynamics in bipolar depression. Unipolar and some subsets of bipolar patients appear not to exhibit this change.

Adult↗

PubMed1991

Use of Tc-99m MAA in determining the etiology of increasing cyanosis following SVC-PA anastomosis for the hypoplastic left heart syndrome.

The hypoplastic left heart syndrome, which characteristically presents in the first few hours of life with cardiovascular collapse, is treated by reconstructive surgery (Norwood's procedure) beginning in the neonatal period. If untreated, more than 95% of infants with this malformation die within the first month of life. The case described involves the development of increasing cyanosis 7 weeks following bilateral superior vena caval-pulmonary artery (SVC-PA) anastomosis in an infant born with a hypoplastic left heart (including aortic and mitral valve stenosis) and an anatomic variant of bilateral superior vena cavae. The use of Tc-99m MAA proved efficacious in quantitating the differential perfusion to each lung, establishing the site of a postoperative stenosis in an anastomotic channel, and documenting systemic perfusion, thus confirming the right-to-left shunt from the superior vena cava to the systemic circulation that resulted in increasing cyanosis.

Anastomosis, Surgical↗

PubMed1991

Twenty-four-hour ambulatory blood pressure in men and women aged 17 to 80 years: the Allied Irish Bank Study.

In order to determine reference values for ambulatory blood pressure, a sample of 815 healthy bank employees (399 men and 416 women), aged 17-79 years, were investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 30-min intervals. Blood pressure was also measured by trained observers in the clinic. Ambulatory blood pressure in the 815 subjects averaged 118/72 mmHg over 24 h, 124/78 mmHg during the day (1000-2259 h) and 106/61 mmHg at night (0100-0659 h). Office blood pressure, measured by an observer, was 4/2 mmHg lower (p less than 0.0001) than daytime ambulatory pressure. The 95th centiles for the daytime ambulatory pressure in men were: 114/88 mmHg for the age group 17-29 years (n = 107); 143/91 mmHg from 30-39 years (n = 123); 150/98 mmHg from 40-49 years (n = 109); and 155/103 mmHg in 50-79 year old men (n = 60); for the corresponding age groups in women, the 95th centiles of the daytime pressure were: 131/83 mmHg (n = 174); 132/85 mmHg (n = 149); 150/94 mmHg (n = 55); and 177/97 mmHg (n = 38).

Adult↗

PubMed1991

The relation of dizziness to functional decline.

OBJECTIVE: to assess the effect of dizziness on the probability that an older person will die or become functionally disabled within 2 years. Dizziness is a common symptom for which the prognosis is uncertain. This report compares the prognoses for dizzy and not-dizzy older people in order to assist clinicians who diagnose and treat these patients. DESIGN: a prospective study of a representative sample of elderly (70+) non-institutionalized Americans. Elderly subjects (n = 3,798) in the Longitudinal Study of Aging (LSOA) were asked questions about the presence of dizziness, medical conditions, and functional disability in 1984. The cohort was reinterviewed about functional disability in 1986. OUTCOME MEASURE: transition from functional ability to disability after 2 years. RESULTS: Bivariate analyses showed that dizziness predicts functional decline but not mortality. Multivariate models revealed that age, race, sensory impairment, vascular disease, and other morbidity are independent predictors of becoming disabled. Controlling for these potential confounders, dizziness does not predict an increased probability of becoming disabled. CONCLUSION: Elderly people who are dizzy should be evaluated for the presence of these related conditions.

Aged↗

PubMed1991

Ventricular pacing threshold and time to capture postdefibrillation in patients undergoing implantable cardioverter-defibrillator implantation.

To assess the effect of defibrillation and amiodarone on ventricular pacing threshold and time to capture in patients undergoing automatic implantable cardioverter-defibrillator (AICD) implantation, 28 patients were prospectively evaluated. The patients were entered into one of two protocols: Ia--epicardial ventricular pacing threshold measured at baseline (preventricular fibrillation induction) and 10 and 60 seconds postdefibrillation with 20 J, or Ib--two fibrillation-defibrillation sequences were performed 3 minutes apart and ventricular pacing thresholds were measured for each sequence at baseline and at 10 and 60 seconds postdefibrillation with 20 J. Ten patients also underwent asynchronous pacing at 1.1 times baseline threshold during ventricular fibrillation with measurement of time to capture postdefibrillation. All patients were randomly assigned to receive either amiodarone or no antiarrhythmic drug therapy. Ventricular fibrillation was induced with AC (applied for 1-2 seconds), and standard epicardial bipolar and epicardial patch electrodes of the AICD were used for pacing and defibrillation, respectively. Ventricular pacing threshold at baseline, 10 seconds, 60 seconds, and 3 minutes postdefibrillation did not differ significantly. There were no significant differences in patients with or without amiodarone therapy. Furthermore, there was no transient loss of ventricular capture postdefibrillation or significant difference in time to capture with amiodarone (less than or equal to 2 seconds). We conclude that following internal defibrillation with 20 J: (1) ventricular pacing threshold at 10 seconds, 60 seconds, and 3 minutes were not significantly different from baseline with one or two fibrillation-defibrillation sequences, (2) time to capture was short, and (3) there was no significant difference in no drug versus amiodarone. These findings have direct clinical importance in considering device therapy with both pacing and defibrillating capabilities.

Amiodarone↗

PubMed1991

Respiratory rate: measurement of variability over time and accuracy at different counting periods.

The respiratory rates/minute of 97 children were monitored every 10-15 minutes over one hour, by an observer and by pneumogram, at which times two 30 second and one 60 second counts were obtained. The children were under 5 years of age with lower respiratory tract infections (n = 20), upper respiratory tract infections (n = 34), or controls without acute respiratory infection (n = 43). The difference between respiratory rate count determined simultaneously by observation and pneumogram in relation to their mean count was analysed for the 60 second counting period, 30 plus 30 second period, and the 30 second period doubled. The mean difference for the 60 second period was 1.79, for the 30 plus 30 second period 1.42, and for the 30 second period doubled 1.72. The variability between respiratory rate counts determined by observation and pneumogram was significantly lower in counts obtained when the subject was sleeping and higher when agitated compared with obtaining a count when the subject was awake and calm or feeding. The variability was also significantly lower in subjects with lower respiratory tract infections compared with those with upper respiratory tract infections and control subjects without respiratory symptoms. In the same patient, over the one hour, 50% of the 60 second counts varied by up to 14 breaths/minute and 75% by up to 21 breaths/minute. The least variability was seen in children with a lower respiratory tract infection, who tended to maintain their rapid breathing in contrast to those with an upper respiratory tract infection and controls without respiratory symptoms. About 10% of initial 30 second counts, 12% of 60 second, and 16% of initial and repeat 30 second attempts to obtain accurate counts failed. Failures occurred more frequently in children <2 months of age and those agitated. The data from this study suggest that one minute's counting either at a stretch or in two blocks of 30 second intervals is better than counting the respiratory rate for 30 seconds, when the child is either awake and calm or when asleep.

Child, Preschool↗

PubMed1991

Hyperlipidemia in stable renal transplant recipients.

Hyperlipidemia is a major risk factor for atherosclerosis and probably contributes to the increased cardiovascular mortality following renal transplantation. We studied the lipid profiles of 62 adults (29 males) with stable renal function (mean plasma creatinine 0.14 mmol/l, SD 0.07), 7 months to 21 years after renal transplantation. Fifteen patients (24%) were above the age- and sex-adjusted 95th percentile for total triglyceride and 10 (16%) for total cholesterol concentrations when compared with a local reference population. The most common lipoprotein abnormalities were type IIa (19%) and type IIb (13%). Multiple regression analysis demonstrated that the use of diuretics and angiotensin-converting enzyme inhibitors were significant factors determining plasma triglyceride concentrations. There were significant bivariate associations between plasma triglyceride concentration and duration since transplantation, plasma creatinine concentration and the use of ciclosporin and diuretics. Duration since transplantation and ciclosporin use were significant factors determining lower plasma cholesterol concentrations. The use of ciclosporin and diuretics was associated with a significantly higher apolipoprotein (apo) B concentration. The cholesterol/HDL cholesterol risk ratio correlated poorly with the apo B/apo A-1 ratio. The value of these ratios as predictors of coronary artery disease need to be established in renal transplant recipients.

Adult↗