Search PubMed⌕ Search

Biomedical subjects

L Daly

Publications and source records attributed to L Daly.

At least 37 records · Page 2Linked to original sources
PubMed1998

Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group.

BACKGROUND: A high plasma homocysteine concentration is a risk factor for atherosclerosis, and circulating concentrations of homocysteine are related to levels of folate and vitamin B6. This study was performed to explore the interrelationships between homocysteine, B vitamins, and vascular diseases and to evaluate the role of these vitamins as risk factors for atherosclerosis. METHODS: In a multicenter case-control study in Europe, 750 patients with documented vascular disease and 800 control subjects frequency-matched for age and sex were compared. Plasma levels of total homocysteine (before and after methionine loading) were determined, as were those of red cell folate, vitamin B12, and vitamin B6. RESULTS: In a conditional logistic regression model, homocysteine concentrations greater than the 80th percentile for control subjects either fasting (12.1 micromol/L) or after a methionine load (38.0 micromol/L) were associated with an elevated risk of vascular disease independent of all traditional risk factors. In addition, concentrations of red cell folate below the lowest 10th percentile (<513 nmol/L) and concentrations of vitamin B6 below the lowest 20th percentile (<23.3 nmol/L) for control subjects were also associated with increased risk. This risk was independent of conventional risk factors and for folate was explained in part by increased homocysteine levels. In contrast, the relationship between vitamin B6 and atherosclerosis was independent of homocysteine levels both before and after methionine loading. CONCLUSIONS: Lower levels of folate and vitamin B6 confer an increased risk of atherosclerosis. Clinical trials are now required to evaluate the effect of treatment with these vitamins in the primary and secondary prevention of vascular diseases.

Adult↗
PubMed1998

Chemotherapeutic drug-induced apoptosis in human leukaemic cells is independent of the Fas (APO-1/CD95) receptor/ligand system.

The potential role of the Fas (CD95/APO-1) receptor/ligand system in chemotherapeutic drug-induced apoptosis was examined in a number of human leukaemic cell lines. Flow cytometric profiles of doxorubicin-treated HL-60, K562, U937 and Jurkat cells failed to show any significant increase in Fas or Fas ligand expression over 24 h, despite the induction of significant levels of apoptosis in these cells. Although preincubation of human leukaemic cells with a neutralizing anti-Fas IgG antibody blocked anti-Fas IgM-induced apoptosis, this strategy failed to inhibit chemotherapeutic drug-induced apoptosis. To determine whether recruitment of the Fas/Fas ligand complex during drug-induced apoptosis was a cell-specific event we utilized the CEM cell line. Doxorubicin treatment of CEM cells over 24 h failed to show any up-regulation in Fas or Fas ligand protein levels as detected by flow cytometry. Furthermore, neutralizing anti-Fas IgG Ab failed to inhibit chemotherapeutic drug-induced apoptosis in CEM cells. The present studies do, however, demonstrate a role for anti-Fas IgM Ab in producing a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs. Low-dose anti-Fas IgM treatment in combination with doxorubicin, methotrexate, camptothecin and etoposide produced an augmented cytoxicity in CEM cells. Taken together these observations demonstrate that although recruitment of the Fas/APO-1/CD95 receptor/ligand system is not a necessary requirement for chemotherapeutic drug-induced apoptosis, combination of anti-Fas IgM and drug treatment produces a synergistic cytotoxic effect which may prove useful in the treatment of human leukaemias.

Antibiotics, Antineoplastic↗
PubMed1998

Coexpression of the HER-2 gene product, p185HER-2, and epidermal growth factor receptor, p170EGF-R, on epithelial ovarian cancers and normal tissues.

Monoclonal antibodies (MAbs) and immunoconjugates reactive with different antigens expressed by neoplastic cells can inhibit tumor growth. Use of these agents in combination with one another or with chemotherapy can exert additive or synergistic cytotoxicity against tumor cells. An augmented therapeutic activity with favorable therapeutic index might be attained when coexpression is observed on tumor cells, but not in normal tissues. In this study frozen sections of 19 ovarian cancers (2 stage I, 10 stage III, 2 stage IV, and 5 recurrent), as well as 29 normal tissues, were evaluated by immunohistochemistry using 11 distinct MAbs against HER-2/p185 and 2 antibodies against EGF-R/p170 to assess coexpression of these receptors. HER-2/p185 expression was detected in 5 to 100% of ovarian cancers and 0 to 50% of normal ovarian epithelia, depending on the antibody used. EGF-R/p170 expression was detected in approximately 70% of cancers and 40% of normal ovaries by both antibodies. Coexpression of p185 and p170 was observed in 47-68% of ovarian cancers and 9-18% of normal ovarian epithelial specimens depending upon the combination of antibodies used. Staining of 273 specimens from 29 normal tissues indicated that coexpression of HER-2 and EGF-R is rare. Normal tissues that coexpressed both receptors in > or =50% of the cases included cervix, endometrium, esophagus, skin, and prostate. These data confirm that HER-2 and EGF-R are more frequently expressed in advanced ovarian cancers than in normal ovarian epithelium and a significant fraction of these tumors coexpress both HER-2 and EGF-R.

Antibodies, Monoclonal↗
PubMed1998

Residual blood in neonatal oxygenators after drainage.

The objective of this investigation was to measure the quantity of residual blood remaining in neonatal cardiopulmonary bypass (CPB) circuits after they had been drained and to assess the overall significance with regards to total patient blood volume. The residual blood volume left in three infant/neonatal CPB circuits-Medtronic Minimax 3381 (Group MM; n = 5), Polystan Safe Micro (Group SM; n = 6), and Terumo Capiox 308 (Group CX; n = 3)--after they had been drained was determined. This was done by using an electronic scale to weigh the circuit before setup and after CPB when all possible blood was recovered from it. Total priming volume, estimated patient blood volume, residual blood volume, surgical blood loss in theater, and autogeneic blood usage were recorded in each case. Mean residual blood volumes measured were MM = 161 ml (SD 27 ml), SM = 103 ml (SD 19 ml), and CX = 133 ml (SD 15 ml). These volumes were significant, because calculations show that the volume of red cells lost in the circuit is equivalent to fourteen percent of the total patient blood volume. In view of this, neonatal oxygenator design should be minimized to reduce the priming volume and more consideration should be given to ease of residual blood recovery.

Blood Loss, Surgical↗
PubMed1997

Identifying stage B colorectal cancer patients at high risk of tumor recurrence and death.

PURPOSE: This study was designed to determine clinical and pathologic variables associated with poor outcome following resection of Stage B colorectal cancer. METHODS: This was a retrospective study of 117 patients with Stage B cancer who underwent curative surgery and survived the postoperative period. Fourteen clinical and pathologic features were studied. Clinical data were extracted from a prospective colorectal cancer database, and histologic slides were retreived and examined by a pathologist blinded as to clinical details and outcome. RESULTS: After a median follow-up period of 8.2 years, bowel obstruction was significantly related to a poor prognosis (log-rank test; P = 0.03). Extensive necrosis (P = 0.01) and perineural invasion (P = 0.03) were also associated with decreased survival. Vascular invasion was associated with poor long-term outcome in the subgroup of patients with rectal (P = 0.07) but not colonic (P = 0.57) cancer. Multivariate regression analysis identified both tumor necrosis (P = 0.01) and perineural invasion (P = 0.03) as independently related to outcome. CONCLUSION: Further study of prognostic indicators might result in an algorithm to distinguish Stage B cases at high risk of tumor recurrence and death. Such patients could be included in future trials of adjuvant therapies.

Adult↗
PubMed1997

Retinopathy of prematurity screening, stress related responses, the role of nesting.

AIMS/BACKGROUND: In a prospective study the degree of distress caused by retinopathy of prematurity (ROP) screening in a cohort of preterm infants was assessed and the modifying effects of nesting in reducing their discomfort was evaluated. METHODS: 38 preterm infants were included in the study. 19 infants were placed in a nest with boundaries (intervention group) and 19 infants were placed on a cot blanket (control group). Observations were made 2 minutes before, throughout, and 2 minutes after ROP examination. The factors observed were crying responses, neurobehavioural activity, and physiological changes (heart rate, oxygen saturation). Recordings were made using a video camera for crying and neurobehavioural activity and an Oxypleth monitor for heart rate and oxygen saturation. RESULTS: During ROP screening, the total group of 38 infants (nested and non-nested combined) displayed increased neurobehavioural activity (p < 0.01) and crying (p < 0.01). The increased activity and crying coincided with the invasive part of the procedure. The distress caused by ROP screening was significantly less for the nested group compared with the non-nested group for both movement activity (p < 0.01) and crying (p < 0.01). The physiological data, heart rate, and oxygen saturation were not statistically significant. CONCLUSION: ROP screening is distressing for preterm infants. Nesting can significantly reduce this discomfort. The findings in this study are of value in designing more optimal ROP examination schedules for infants.

Beds↗
PubMed1997

Evaluation of quantitative CT vertebral bone mineral density measurement and the Singh index in elderly females with hip fractures--a case control study.

This study aims to evaluate the ability of quantitative computed tomography (QCT) bone mineral density (BMD) measurement of vertebral bodies to predict risk of hip fracture. We also examine the predictive value of the radiographic Singh index and its relationship to the vertebral BMD. The vertebral BMD (using a QCT protocol) and radiographic Singh index were evaluated in 86 white females who had sustained a hip fracture after minor trauma. 86 age-matched female controls were also studied. All patients were post-menopausal, the age range was 52-95 years. BMD values were found to be low in both the study group and controls; there was no statistically significant difference between the groups. A low Singh index did not correlate with hip fracture, nor did it correlate with low vertebral BMD measurement. We conclude that vertebral BMD and radiographic Singh index are not reliable predictors of hip fracture in the elderly female.

Age Factors↗
PubMed1997

Comparison of two methods of bedside blood glucose screening in the NICU: evaluation of accuracy and reliability.

Bedside whole blood glucose screening in the NICU has been an accepted method of care for several years. Meters or visually read reagent strips are used in bedside screening, but the reliability and accuracy of these methods are not always established before they are implemented as routine practice in the NICU. A study was conducted to determine which method of bedside whole blood glucose screening was the more accurate: visually read Chemstrip bG reagent strips or the One Touch II meter method. The values obtained were compared with lab analysis of serum glucose, and a correlation study was performed to compare the accuracy and reliability of the values produced by the two methods. One hundred samples were obtained from 38 NICU infants; 63 percent of the 100 samples were compared with lab values. Results revealed that the One Touch II method was more reliable (r = .92) than the Chemstrip bG method (r = .87). Furthermore, the One Touch II results correlated better with lab values when the meter was not operated in the neonatal mode. This study revealed that the One Touch II method appears to provide safe and accurate screening of bedside blood glucose in a high-risk neonatal population.

Blood Glucose↗
PubMed1995

Combinations of multiple serum markers are superior to individual assays for discriminating malignant from benign pelvic masses.

To determine whether measurement of the levels of multiple tumor markers in the preoperative serum of women presenting with a pelvic mass distinguished benign from malignant disease better than the assay of CA 125 alone, sera from 429 patients, 192 of whom had malignant histology, were assayed for 8 different markers: CA 125, macrophage colony-stimulating factor, OVX1, lipid-associated sialic acid (LASA), CA15-3, CA72-4, CA19-9, and CA54/61. The sensitivity and specificity of CA 125 alone (> 35 U/ml) was 78.1 and 76.8%, respectively. A panel consisting of CA 125, OVX1, LASA, CA15-3, and CA72-4 had a sensitivity of 83.3% and specificity of 84.0% when two or more markers were elevated. Using the concentrations of these five markers, logistic regression analysis had a sensitivity of 85.4% and a specificity of 83.1%. Considering the values of markers in different sequences, classification and regression tree analysis substantially improved the sensitivity to 90.6% and the specificity to 93.2%. When applied in clinical practice this approach could improve the management of women presenting with a pelvic mass and may also have application in screening for ovarian cancer.

Biomarkers, Tumor↗
PubMed1995

Cardiovascular risk factor changes in the Kilkenny Health Project. A community health promotion programme.

The Kilkenny Health Project was a community research and demonstration programme which aimed to reduce risk of cardiovascular disease in a county in the south-east of Ireland with a total population of approximately 70,000. The health promotion programme was carried out in Kilkenny from 1985 to 1992. Outcome evaluation was by means of population surveys of independent samples of men and women aged 35 to 64 years in Kilkenny (n approximately 800) and in the reference county (n approximately 600) in 1985/1986 and in 1990/1991. Survey methods for health behaviour questionnaires and risk factor measurements were similar to those of the WHO MONICA Project. Mean systolic blood pressure (SBP) declined significantly (P < 0.01) in men and women in both counties, from 144.0 by 5.4 mmHg and from 143.2 by 5.4 mmHg in men and from 139.5 by 7.7 mmHg and from 136.5 by 6.6 mmHg in women in the intervention and reference counties. The prevalence of hypertension declined from 23.1% by 2.8% and from 26.1% by 6.0% in men in the two counties. Prevalence declined from 24.1% by 6.2% (P < 0.05) in women in the intervention county but was unchanged, increasing by 0.5% from 17.5%, in women in the reference county. Mean serum total cholesterol declined from 6.04 mmol.l-1 by 0.09 mmol.l-1 and from 6.00 by 0.44 mmol.l-1 (P < 0.01) in men and from 6.01 by 0.36 (P < 0.01) and from 5.90 by 0.31 (P < 0.01) in women in the intervention and reference counties, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

DARPP-32 promoter directs transgene expression to renal thick ascending limb of loop of Henle.

DARPP-32, a dopamine- and adenosine 3',5'-cyclic monophosphate (cAMP)-regulated inhibitor of protein phosphatase-1, is highly colocalized with neuronal and nonneuronal D1-type receptors. DARPP-32 concentration is enriched in the renal outer medulla and in the medium-size spiny neurons of the brain. In the ascending limb of the loop of Henle, DARPP-32 is phosphorylated following stimulation by dopamine and other first messengers, and in this form inhibits the activity of the Na(+)-K(+)-adenosinetriphosphatase pump. For functional analysis of the DARPP-32 promoter in the kidney, we characterized the murine gene. There are two groups of transcription start sites utilized in the brain, but the proximal set appears to be preferentially used in the kidney. In four of four lines of mice carrying a DARPP-32/lacZ transgene with 2.1 kb of 5'-flanking DNA, adult kidney lacZ transgene expression mimicked that of endogenous DARPP-32. There was no ectopic expression in peripheral organs. We conclude that the sequences necessary for direction of DARPP-32 expression to the medullary thick ascending limb are contained within this 2.1-kb fragment.

Animals↗
PubMed1994

OVX1 as a marker for early stage endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is generally diagnosed only after the onset of postmenopausal bleeding. Although most patients with Stage I disease can be cured, the prognosis worsens significantly when the tumor is no longer confined to the uterine corpus. Serum CA 125 is elevated in only 10-20% cases of Stage I and II endometrial carcinoma. A serum tumor marker that can detect early stage endometrial cancer might aid in management of the disease. METHODS: An OVX1 double-determinant radioimmunoassay was used to detect an epitope on a high-molecular-weight mucinlike glycoprotein found in the sera of 45 patients with endometrial cancer. RESULTS: Apparently healthy persons had serum OVX1 antigen levels of 2.23 plus or minus 2.48 U/ml (mean +/- standard deviation). Elevated levels of OVX1 antigen (> 7.2 U/ml) were found in 5% of 184 healthy persons and in 64% of 45 patients with endometrial cancer. OVX1 antigen was elevated in 64% of 36 patients with Stage I, 50% of 2 patients with Stage II, 60% of 5 patients with Stage III, and each of 2 patients with Stage IV endometrial cancer, but only 8.6% of 58 patients with endometriosis. Elevation of serum OVX1 was found more frequently in patients with deep myometrial invasion and with poorly differentiated tumors (P < 0.01). CONCLUSIONS: The OVX1 antigen deserves further evaluation as a marker for early detection of endometrial cancers and as a prognostic factor for women with apparent early stage disease.

Antigens, Neoplasm↗
PubMed1994

Folic acid metabolism and mechanisms of neural tube defects.

Folate acts as a cofactor for enzymes involved in DNA and RNA biosynthesis. Folate is also involved in the supply of methyl groups to the so-called methylation cycle, which uses methionine and makes homocysteine. The folate cofactor, N5-methyltetrahydrofolate, donates its methyl group to a vitamin B12-dependent enzyme, methionine synthase, which recycles homocysteine back to methionine. The cell's ability to methylate important compounds such as proteins, lipids and myelin will be compromised by deficiency of folate or vitamin B12, resulting in impaired cellular function. Methionine synthase plays another role: it converts circulating N5-methyltetrahydrofolate into tetrahydrofolate. The latter but not the former can act as a substrate for polyglutamate synthase, thereby becoming retained in the cell as polyglutamate. Interruption of DNA biosynthesis or methylation reactions could prevent the proper closure of the neural tube. Such inhibition could be caused by simple deficiency of either folic acid or vitamin B12. Studies comparing serum folate and vitamin B12 status in women who have had an affected pregnancy to those in control women indicate no difference between the two groups and show that most cases are not clinically deficient in either vitamin. A small number of studies using the level of folate in red blood cells, which is a better reflection of tissue stores, confirm this, suggesting instead a metabolic impairment in the biochemical functions of one of these vitamins. The trials using folic acid to prevent neural tube defects thus seem to be effectively overcoming a metabolic block rather than treating folate deficiency.

Female↗
PubMed1994

Prognosis of elderly patients with large bowel cancer.

The effect of age on the presentation, diagnosis, management and survival of patients with colorectal cancer was studied prospectively in 512 patients admitted to a single institution. In all, 225 patients were aged 70 years or more and 287 less than 70 years. Older patients had a significant excess of emergency presentations (18 versus 11 per cent). Methods of diagnosis, proportion of curative operations performed, stage and histological grade were similar in the two age groups. The postoperative mortality rate was 6 per cent in the elderly group and 3 per cent in younger patients. The postoperative mortality rate rose to 15 and 12 per cent respectively in those undergoing emergency surgery. The relative 5-year survival rate standardized for age and sex was 52 per cent for older patients and 45 per cent for younger patients; for those undergoing curative surgery it was 68 and 59 per cent respectively. The behaviour of colorectal carcinoma changes little with age and, allowing for population mortality, age has no effect on the long-term survival of elderly patients with large bowel cancer.

Adult↗
PubMed1994

Treatment with coumarin to prevent or delay recurrence of malignant melanoma.

Both coumarin (1,2-benzopyrone) and warfarin (4-hydroxycoumarin) have been shown to prevent the recurrence of malignant melanoma. Their action is macrophage-dependent and the dosage is critical. In 1984 a multicentre, prospective, randomised, double-blind trial of coumarin, given as a daily 50-mg dose for 2 years after surgery in patients with high-risk melanoma, was started. the patients had lesions greater than 1.70 mm thick and TNM stage IB or stage II disease. To date there are 4 recurrences in the coumarin-treated group of 13 patients, and 10 recurrences in the placebo-treated group of 14 patients (P < 0.01). There were no toxic effects.

Chemotherapy, Adjuvant↗
PubMed1994

Hip and ankle walking strategies: effect on peak plantar pressures and implications for neuropathic ulceration.

Treatment of neuropathic plantar ulcers often is directed at reducing excessive, repeated peak plantar pressures (PPP). The purposes of this study were to determine whether instructing a subject to walk using a hip strategy would reduce forefoot PPP and change the kinematics of walking during a single session of testing. Thirteen subjects, 7 with peripheral neuropathy and a history of a recent plantar ulcer, and 6 controls participated. PPPs were measured with an in-shoe pressure monitoring system. Kinematics were measured with a computer-assisted motion analysis system. After data were collected as subjects walked using their normal walking pattern, subjects were instructed to walk using the hip strategy by decreasing their push-off, pulling their leg forward from their hips, decreasing step length, and maintaining their normal walking velocity. Compared with using the normal (ankle) strategy, using the hip strategy showed a significant 27% decrease in forefoot PPP and a 24% increase in heel PPP. Kinematic changes were decreased plantar flexion angular velocity, hip extension range-of motion (ROM), and step length, increased dorsiflexion ROM, and hip flexion ROM, but no change in walking velocity. These findings indicate that a change in walking pattern can result in lower forefoot PPP during a single session. Assuming patients can maintain the alterations in their walking pattern, these adaptations may help to heal plantar ulcers in some patients with peripheral neuropathy.

Adult↗
PubMed1994

Deriving a useful packed cell volume estimate from haemoglobin analysis.

A method is described whereby the packed cell volume (PCV) of a blood sample can be estimated from the haemoglobin concentration. The method defines the relation existing between haemoglobin concentration and the PCV of blood samples and uses the mathematical formula thus obtained to estimate an unknown PCV value for a sample by extrapolation from the known haemoglobin value of the same sample. The method could be used in large scale field studies where haematological services are not available and where an evaluation of red cell status of vitamins such as folate is required.

Erythrocyte Indices↗