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Biomedical subjects

J Murphy

Publications and source records attributed to J Murphy.

At least 55 records · Page 3Linked to original sources
PubMed2001

Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group.

OBJECTIVES: We sought to assess plasma concentrations of the amino (N)-terminal portion of pro-brain natriuretic peptide (N-BNP) and adrenomedullin for prediction of adverse outcomes and responses to treatment in 297 patients with ischemic left ventricular (LV) dysfunction who were randomly assigned to receive carvedilol or placebo. BACKGROUND: Although neurohormonal status has known prognostic significance in heart failure, the predictive power of either N-BNP or adrenomedullin in chronic ischemic LV dysfunction has not been previously reported. METHODS: Plasma N-BNP and adrenomedullin were measured in 297 patients with chronic ischemic (LV) dysfunction before randomization to carvedilol or placebo, added to established treatment with a converting enzyme inhibitor and loop diuretic (with or without digoxin). The patients' clinical outcomes, induding mortality and heart failure events, were recorded for 18 months. RESULTS: Above-median N-BNP and adrenomedullin levels conferred increased risks (all p < 0.001) of mortality (risk ratios [95% confidence intervals]: 4.67 [2-10.9] and 3.92 [1.76-8.7], respectively) and hospital admission with heart failure (4.7 [2.2-10.3] and 2.4 [1.3-4.5], respectively). Both of these predicted death or heart failure independent of age, New York Heart Association functional class, LV ejection fraction, previous myocardial infarction or previous admission with heart failure. Carvedilol reduced the risk of death or heart failure in patients with above-median levels of N-BNP or adrenomedullin, or both, to rates not significantly different from those observed in patients with levels below the median value. CONCLUSIONS: In patients with established ischemic LV dysfunction, plasma N-BNP and adrenomedullin are independent predictors of mortality and heart failure. Carvedilol reduced mortality and heart failure in patients with higher pre-treatment plasma N-BNP and adrenomedullin.

Adrenergic beta-Antagonists↗
PubMed2001

Laminin-5 promotes neurite outgrowth from central and peripheral chick embryonic neurons.

Laminin-5 (Ln-5) is an essential component of epithelial basal laminae that is also expressed in the developing nervous system. Here we use a convenient, simple and reproducible in vitro fluorescent assay to assess the neurite outgrowth promoting activity of purified Ln-5. Embryonic chick neurons from dorsal root ganglia, ciliary ganglia, and (to a lesser extent) retina extended neurites on Ln-5, but the neurite outgrowth promoting activity was not as great as that of Ln-1 or Ln-2. Neurons from diencephalon, telencephalon, and spinal cord did not respond to Ln-5.

Animals↗
PubMed2001

Changes in the demographics and perioperative care of stage IA(2)/IB(1) cervical cancer over the past 16 years.

OBJECTIVES: The aim of this study was to determine whether there have been any significant changes in the demographics and perioperative care of FIGO stage IA(2)/IB(1) cervical cancer over the past 16 years and, if so, to quantify them. METHODS: Since July 1984, all patients with FIGO stage IA(2)/IB(1) cervical cancer undergoing radical surgery by members of our division have been entered into a prospective database. Selection for surgery has been unchanged over the past 16 years. Since March 1994 and November 1996, one surgeon has performed radical vaginal trachelectomy and laparoscopic assisted radical vaginal hysterectomy, respectively. Statistical analysis used Spearman's correlation analysis, the proportional hazards regression model of Cox, and the Mantel-Hanzel test was performed. Due to the number of statistical analyses, statistical significance was defined as P < 0.01. RESULTS: Eight hundred sixty-four patients have undergone radical surgery (784 radical hysterectomy, 42 radical vaginal trachelectomy, 32 radical vaginal hysterectomy, 6 radical abdominal trachelectomy) for FIGO stage IA(2)/IB(1) carcinoma of the cervix by members of our division since 1984. There have been no changes in the median age (40 years), tumor size (2.0 cm), incidence of capillary lymphatic space involvement (47%), or positive pelvic lymph nodes (6%) over the past 16 years. The median Quetelet index (24.6), depth of tumor invasion (squamous cell carcinomas only) (6.0 mm), and proportion of patients with comorbid conditions (17%) have increased over time (P = 0.001, P = 0.003, and P < 0.001, respectively). Pathologically, there has been an increase in the proportion of adenocarcinomas (28%) and a decrease in the proportion of grade 3 tumors (28%) (P < 0.001 and P < 0.001, respectively). The median operating time (2.8 h), hospital stay (7.0 days), blood loss (600 cc), allogeneic blood transfusion (23%), postoperative infections (13%), and noninfectious complications (6%) have all decreased (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively). There has been no change in the incidence of positive surgical margins (3%), adjuvant radiation (13%), or recurrence-free survival (2 and 5 years, 94 and 90%, respectively) after a median follow-up of 45 months. CONCLUSION: Despite no substantive changes in the selection criteria for surgery and the small time interval studied (16 years), almost all indices of operative and postoperative morbidity analyzed have decreased significantly. These changes have occurred without an increase in the use of adjuvant radiation or decrease in recurrence-free survival. Although little progress has been made in the cure rates associated with surgical management of FIGO stage IA(2)/IB(1) cervical cancer during this time interval, it appears that the morbidity of surgery has decreased.

Adenocarcinoma↗
PubMed2001

Blunt abdominal aortic trauma in association with thoracolumbar spine fractures.

All patients with blunt abdominal aortic disruption (BAAD) in the trauma registries at the three Regional Trauma Centres were retrospectively reviewed over the last decade. From the 11465 trauma admissions ISS>16,194 sustained aortic injuries. Eight cases of BAAD were identified, six with concurrent thoracolumbar spine (TLS) fractures (mean ISS 42). Patients with BAAD and TLS were subject to a detailed analysis. Clinically, three injury types were seen, hemodynamically unstable (uncontained full thickness laceration), stable symptomatic (intimal dissection with occlusion), and stable asymptomatic (contained full thickness laceration or intimal dissection without occlusion). All spinal column fractures involved a distractive mechanism, one with both distractive and translational fracture components. We propose that a distractive force, applied to the aorta lying anterior to the anterior longitudinal ligament, results in an aortic injury spectrum ranging from an intimal tear to a full thickness laceration, as a related injury. Computed tomography (CT) was an important imaging modality in the stable asymptomatic patients. All intimal dissections without occlusion were managed non-operatively. With distractive TLS fractures, BAAD needs to be considered.

Abdominal Injuries↗
PubMed2001

Assisted reproductive interventions and multiple birth.

OBJECTIVE: To investigate the contributions of ovulation-inducing drugs and assisted reproductive technologies to multiple birth. METHODS: This historic prospective study was conducted in a cohort of 13,151 women who delivered after 20 weeks' gestation between October 1996 and December 1999. The study setting was a Colorado health maintenance organization. Cases were women who were pregnant as a result of exposure to treatment with either assisted reproductive technologies or ovulation induction in the absence of assisted reproductive technologies. The main outcome measure was multiple birth. RESULTS: There was a significant association between assisted conception and multiple birth. Compared with women with naturally conceived pregnancies, there was a 25-fold likelihood (95% confidence interval 18, 35, P <.001) of multiple birth among women exposed to any of those treatments. In the total cohort the proportion of multiple births attributable to those treatments was 33%. After adjusting for the use of assisted conception and other covariates, we found no association between advanced maternal age and multiple birth. CONCLUSION: In this cohort, assisted reproductive interventions were strongly associated with multiple birth. Although a higher proportion of older women sought assisted reproductive technologies, we did not find an independent relationship between advanced maternal age and multiple birth. The increasing number of multiple births attributable to assisted conception raises public health concerns regarding multiple gestation-related maternal and infant morbidities.

Adolescent↗
PubMed2001

Amniotic fluid infection, cytokines, and adverse outcome among infants at 34 weeks' gestation or less.

OBJECTIVE: We examined the hypothesis that amniotic fluid (AF) infection and elevated cytokine concentrations may cause neonatal injury beyond that expected solely from prematurity. METHODS: The effects of exposure to AF infection and elevated cytokine concentrations were measured in 151 infants born to afebrile women in preterm labor with intact membranes at less than or equal to 34 weeks' gestation. Amniotic fluid was collected by amniocentesis for culture and determination of tumor necrosis factor-alpha and interleukin-6. Cytokine concentrations, stratified by AF infection, were compared for three gestational age groups. We then examined the associations between a positive AF culture or elevated AF tumor necrosis factor-alpha concentration and adverse neonatal outcomes, adjusted for birth weight. RESULTS: Amniotic fluid from 45 (30%) of 151 pregnancies had microorganisms, an elevated tumor necrosis factor-alpha concentration, or both. Amniotic fluid cytokine concentrations were significantly higher among women in preterm labor at less than or equal to 30 weeks, compared with 31-34 weeks. Nine of 11 infants who died at less than or equal to 24 hours of age had AF infection or elevated AF tumor necrosis factor-alpha. For the 140 surviving infants, AF infection and/or an elevated AF tumor necrosis factor-alpha was associated with respiratory distress syndrome (adjusted odds ratio [OR] 1.7), grade 3-4 intraventricular hemorrhage (adjusted OR 2.2), necrotizing enterocolitis (adjusted OR 1.8), and multiple organ dysfunction (adjusted OR 3.0). CONCLUSION: Among infants born at less than or equal to 34 weeks to women who have intact membranes and are initially afebrile, those exposed to AF bacteria or cytokines have more adverse neonatal outcomes than unexposed infants of similar birth weight.

Adolescent↗
PubMed2001

Impaired bioavailability of vitamin A in adults and children with persistent diarrhoea in Zambia.

BACKGROUND: We have previously demonstrated a strong relationship between low serum retinol concentration and mortality in Zambian AIDS patients with diarrhoea, but were unable to detect any benefit from oral micronutrient supplementation. AIM: To test the hypothesis that this is related to impaired availability of vitamin A, we analysed serum retinol concentration changes over 6 h following oral mega-dose therapy (60, 120 or 180 mg retinol). METHODS: Twenty-four men without diarrhoea, 15 adults with persistent diarrhoea and 11 children (six girls, five boys) with persistent diarrhoea were studied. RESULTS: Men with persistent diarrhoea had lower baseline serum retinol concentrations (median 0.39 micromol/L, interquartile range 0.21-0.56) than controls (median 1.16 micromol/L, interquartile range 0.84-1.47; P=0.0003). After 60 mg retinol, the rise in serum retinol in HIV seropositive controls (median 0.63 micromol/L, interquartile range 0.35-0.77) did not differ significantly from that observed in HIV seronegative controls (median 0.35 micromol/L, interquartile range - 0.04-0.56; P=0.20). Increasing the dose to 120 mg or 180 mg retinol did not enhance the increase in serum retinol concentration. The increase in serum retinol was less in adults with persistent diarrhoea (median 0.25 micromol/L, interquartile range 0.04-0.35) and in children (median 0.11 micromol/L, interquartile range 0.04-0.46) than in men without diarrhoea (median 0.44 micromol/L, interquartile range 0.26-0.74; P=0.03). Adults and children with diarrhoea had greater losses of retinol in urine over a 24-h period than controls, but less than 1% of the ingested dose was excreted. CONCLUSIONS: These results suggest that persistent diarrhoea in this population is associated with reduced bioavailability of retinol. Further work is required to determine the metabolic fate of therapeutic doses of retinol and to determine appropriate replacement strategies for HIV infected individuals.

Administration, Oral↗
PubMed2001

Screening of a HUVEC cDNA library with transplant-associated coronary artery disease sera identifies RPL7 as a candidate autoantigen associated with this disease.

A HUVEC cDNA library was screened with sera from two patients who had developed transplant-associated coronary artery disease (TxCAD) following cardiac transplantation. A total of six positive clones were isolated from a primary screen of 40 000 genes. Subsequent DNA sequence analysis identified these to be lysyl tRNA synthetase, ribosomal protein L7, ribosomal protein L9, beta transducin and TANK. Another gene whose product could not be identified showed homology to a human cDNA clone (DKFZp566M063) derived from fetal kidney. Full-length constructs of selected genes were expressed as his-tag recombinant fusion proteins and used to screen a wider patient base by ELISA to determine prevalence and association with TxCAD. Of these ribosomal protein L7 showed the highest prevalence (55.6%) with TxCAD sera compared to 10% non-CAD.

Adult↗
PubMed2001

The role of serial transrectal ultrasonography in a 'watchful waiting' protocol for men with localized prostate cancer.

OBJECTIVE: To determine the value of serial 6-monthly transrectal ultrasonography (TRUS) in a cohort of men with localized prostate cancer who consented to a programme of watchful waiting with selective delayed intervention. PATIENTS AND METHODS: Since November 1995, 180 men were accrued into an ongoing prospective study of watchful waiting with selective delayed intervention; 174 patients enrolled before 31 December 1999 comprised the cohort for the present study. The prospectively collected clinical data, including the TRUS reports, were reviewed systematically. Twenty-eight men met the arbitrarily predefined criteria of disease progression and required definitive treatment. The TRUS findings were scored as being consistent with the clinical scenario (i.e. clinical, biochemical or histological progression) if they reported a new or enlarging hypoechoic peripheral zone lesion, or a > or = 30% increase in overall prostate volume at the time of progression. In 136 men who had undergone two or more serial TRUS examinations the relationships between the rate of change of prostate-specific antigen (PSA) and changes in both gland volume and the number of hypoechoic lesions were also examined. RESULTS: The group of 28 men who progressed to require radical intervention underwent 83 TRUS examinations (median number per patient, three). Two men underwent TRUS only once at baseline because of progression within 6 months. Of these 28 men, only seven had changes on TRUS that were regarded as being consistent with progression; all seven consisted of the growth of an existing nodule or the appearance of a new nodule. In only one case was this accompanied by an increase of > or = 30% in gland volume. In the 136 men who underwent two or more serial TRUS examinations (median three, maximum nine), there was no correlation between the rate of change of PSA and changes in either gland volume or the number of peripheral zone hypoechoic lesions. CONCLUSION: The use of serial TRUS in men with known but untreated prostate cancer is of limited value as a determinant of disease progression.

Clinical Protocols↗
PubMed2001

Occult carcinoma in prophylactic oophorectomy specimens: prevalence and association with BRCA germline mutation status.

Prophylactic oophorectomy (PO) is an option for women at increased risk for ovarian carcinoma. In this study the value of intensive pathologic examination of PO specimens and accompanying resected tissues in the identification of occult carcinoma and any association of occult carcinoma with BRCA germline mutation status were ascertained. Specimens from 60 consecutive PO patients, who were not suspected of having any ovarian tumor at the time of surgery, were subjected to standardized, complete pathologic examination in a prospective study over an 8-year period. Extra-ovarian tissues were examined as well, but they were not subject to the same standardized protocol. Any occult carcinoma of the ovaries or fallopian tubes was noted. The BRCA status and follow-up of patients were obtained, if available. Fifty-five of the 60 PO specimens did not show any evidence of malignancy. Of the 32 patients in this group followed for >1 year, all are alive and well. The remaining five patients, all BRCA1 mutation positive, showed occult carcinoma of the ovaries and/or in situ or invasive carcinoma of a fallopian tube. One of these five patients has died of abdominal carcinomatosis; four continue to be well, but follow-up is <4 years in all cases. Occult carcinoma is present in a small proportion of BRCA-positive or unknown PO patients and may be of prognostic significance. The entire ovaries and tubes from PO patients should be submitted for histologic examination to identify malignancy.

Cystadenocarcinoma, Papillary↗
PubMed2001

Genetic counselling for schizophrenia in the era of molecular genetics.

OBJECTIVE: To review the role of genetic counselling for individuals with psychiatric illnesses. METHOD: Using schizophrenia as an example and including updated information about a genetic subtype (22q deletion syndrome), we discuss the value of the genetic counselling process in psychiatry, with support from the literature and our clinical experience. RESULTS: Genetic counselling, the process through which knowledge about the genetics of illnesses is shared, provides information on the inheritance of illnesses and their recurrence risks; addresses the concerns of patients, their families, and their health care providers; and supports patients and their families dealing with these illnesses. For comprehensive medical management, this service should be available to all individuals with schizophrenia and their families. CONCLUSIONS: New findings in the genetics of psychiatric illness may have important clinical implications for patients and their families.

Chromosome Deletion↗
PubMed2001

The varicella-autoantibody syndrome.

This cross-sectional study was conducted to determine the incidence of autoantibodies to phospholipids and coagulation proteins in children with acute varicella zoster virus (VZV) infection. Study groups included children with VZV alone or complicated by purpura fulminans and/or thromboembolism. VZV naïve children and children who had VZV >1 y before sample collection formed a control group. Blood was assayed for the following: free protein S (PS), protein C, antithrombin, and prothrombin; antibody binding to these proteins; lupus anticoagulant; anticardiolipin antibody; antiphospholipid antibodies; and prothrombin fragment 1+2. Data regarding coinfections was collected. Forty-three VZV-infected children showed an increased frequency of lupus anticoagulant, anticardiolipin antibody, antiphospholipid antibodies, and autoantibodies to PS, protein C, prothrombin, and antithrombin in comparison to 52 children without acute VZV (p < 0.0001). Seventeen children with VZV and purpura fulminans and/or thromboembolism showed a statistically significant decrease in free PS, significantly increased PS IgG antibody, and significantly increased prothrombin fragment 1+2 (p < 0.0001) compared with the group without acute VZV and the group with uncomplicated VZV. Twenty-six children with uncomplicated VZV showed increased PS IgG antibody (p < 0.001) compared with the children without acute VZV. For all groups combined, elevated PS IgG antibody showed negative correlation with free PS (p < 0.0001) and positive correlation with prothrombin fragment 1+2 (p = 0.0002). Autoantibodies were transient. Transient antiphospholipid and coagulation protein autoantibodies were common with VZV infection, but were not predictive of thrombotic complications.

Adolescent↗
PubMed2001

Perineural cysts presenting as complex adnexal cystic masses on transvaginal sonography.

OBJECTIVE: This study describes the sonographic features of sacral perineural cysts that initially presented as adnexal complex cystic masses on transvaginal sonography. CONCLUSION: Perineural cysts may have a complex cystic appearance, including septation and internal debris, on transvaginal sonography. The extraovarian, extraperitoneal, and posterior location on real-time sonography are suggestive features.

Adnexal Diseases↗
PubMed2001

The quality of physician-patient relationships. Patients' experiences 1996-1999.

BACKGROUND: Our objective was to examine how patients of primary care physicians are responding to a changing health care environment. The quality of their relationship with their primary care physicians and their experience with organizational features of care were monitored over a 3-year period. METHODS: This was a longitudinal observational study (1996-1999). Participants completed a self-administered questionnaire at baseline and at follow-up. The questionnaires included measures of primary care quality from the Primary Care Assessment Survey (PCAS). We included insured adults employed by the Commonwealth of Massachusetts who remained with one primary care physician throughout the study period (n=2383). The outcomes were unadjusted mean scale score changes in each of the 8 PCAS over the 3 years and associated standardized difference scores (effect sizes). The 8 PCAS scales measured relationship quality (4 scales: communication, interpersonal treatment, physician's knowledge of the patient, patient trust) and organizational features of care (4 scales: financial access, organizational access, visit-based continuity, integration of care). RESULTS: There were significant declines in 3 of the 4 relationship scales: communication (effect size [ES] = -0.095), interpersonal treatment (ES = -0.115), and trust (ES = -0.046). Improvement was observed in physician's knowledge of the patient (ES = 0.051). There was a significant decline in organizational access (ES = -0.165) and an increase in visit-based continuity (ES = 0.060). There were no significant changes in financial access and integration of care indexes. CONCLUSIONS: The declines in access and 3 of the 4 indexes of physician-patient relationship quality are of concern, especially if they signify a trend.

Adult↗
PubMed2001

Switching doctors: predictors of voluntary disenrollment from a primary physician's practice.

BACKGROUND: Our objective was to evaluate 8 interpersonal and structural features of care as predictors of patients' voluntary disenrollment from their primary care physician's practice. METHODS: We performed a longitudinal observational study in which participants completed a validated questionnaire at baseline (1996) and follow-up (1999). The questionnaire measured 4 elements of the quality of physician-patient relations (communication, interpersonal treatment, physician's knowledge of the patient, and patient trust) and 4 structural features of care (access, visit-based continuity, relationship duration, and integration of care). Study participants were insured adults who reported having a regular personal physician at baseline and who completed both baseline and follow-up questionnaires (n=4108). The outcome measured was voluntary disenrollment from the primary physician's practice between baseline and follow-up. RESULTS: One fifth of the patients voluntarily left their primary physician's practice during the study period. When tested independently, all 8 scales significantly predicted voluntary disenrollment (P <.001), with somewhat larger effects associated with the 4 relationship quality measures. In multivariable models, a composite relationship quality factor most strongly predicted voluntary disenrollment (odds ratio [OR]=1.6; P<.001), and the 2 continuity scales also significantly predicted disenrollment (OR=1.1; P<.05). Access and integration did not significantly predict disenrollment in the presence of these variables. CONCLUSIONS: These findings highlight the importance of relationship quality in determining patients' loyalty to a physician's practice. They suggest that in the race to the bottom line medical practices and health plans cannot afford to ignore that the essence of medical care involves the interaction of one human being with another.

Adult↗