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Biomedical subjects

L Sullivan

Publications and source records attributed to L Sullivan.

At least 19 recordsLinked to original sources
PubMed2001

Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial.

CONTEXT: The practice of administering weekly courses of antenatal corticosteroids to pregnant women at risk of preterm delivery is widespread, but no randomized trial has established the efficacy or safety of this practice. OBJECTIVES: To evaluate the efficacy of weekly administration of antenatal corticosteroids compared with a single course in reducing the incidence of neonatal morbidity and to evaluate potential complications of weekly treatment. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled intention-to-treat trial conducted in 13 academic centers in the United States from February 1996 through April 2000. PARTICIPANTS: A total of 502 pregnant women between 24 and 32 completed weeks' gestation who were at high risk of preterm delivery. INTERVENTION: All patients received a complete single course of antenatal corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for 4 doses). Participants who had not delivered 1 week after receipt of the single course were randomly assigned to receive either betamethasone, 12 mg intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks' gestation or delivery, whichever came first (n = 256), or a similarly administered placebo (n = 246). MAIN OUTCOME MEASURE: Composite neonatal morbidity (including severe respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death). RESULTS: Composite morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single-course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59-1.10). Neither group assignment nor the number of treatment courses was associated with a reduction in composite morbidity. CONCLUSIONS: Weekly courses of antenatal corticosteroids did not reduce composite neonatal morbidity compared with a single course of treatment. Weekly courses of antenatal corticosteroids should not be routinely prescribed for women at risk of preterm delivery.

Betamethasone↗
PubMed2001

Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death.

p19, a molecule structurally related to IL-6, G-CSF, and the p35 subunit of IL-12, is a subunit of the recently discovered cytokine IL-23. Here we show that expression of p19 in multiple tissues of transgenic mice induced a striking phenotype characterized by runting, systemic inflammation, infertility, and death before 3 mo of age. Founder animals had infiltrates of lymphocytes and macrophages in skin, lung, liver, pancreas, and the digestive tract and were anemic. The serum concentrations of the proinflammatory cytokines TNF-alpha and IL-1 were elevated, and the number of circulating neutrophils was increased. In addition, ubiquitous expression of p19 resulted in constitutive expression of acute phase proteins in the liver. Surprisingly, liver-specific expression of p19 failed to reproduce any of these abnormalities, suggesting specific requirements for production of biologically active p19. Bone marrow transfer experiments showed that expression of p19 by hemopoietic cells alone recapitulated the phenotype induced by its widespread expression, pointing to hemopoietic cells as the source of biologically active p19. These findings indicate that p19 shares biological properties with IL-6, IL-12, and G-CSF and that cell-specific expression is required for its biological activity.

Acute-Phase Proteins↗
PubMed2001

hprt mutant frequencies, nonpulmonary malignancies, and domestic radon exposure: "postmortem" analysis of an interesting hypothesis.

The hypothesis that exposure to domestic radon raises the risk for leukemia and other nonpulmonary cancers has been proposed and tested in a number of epidemiologic studies over the past decade. During this period, interest in this hypothesis was heightened by evidence of increased frequencies of mutations at the hypoxanthine guanine phosphoribosyl transferase (hprt) gene in persons exposed to domestic radon (Bridges BA et al. [1991]: Lancet 337:1187-1189). An extension of this study (Cole J et al. [lsqb[1996]: Radiat Res 145:61-69) and two independent studies (Albering HJ et al. [1992[: Lancet 340:739; Albering HJ et al. [1994[: Lancet 344:750-751) found that hprt mutant frequency was not correlated with domestic radon exposure, and two well-designed epidemiologic studies showed no evidence of a relation between radon exposure and leukemia in children or adults. In this report, we present additional data from a study of Colorado high school students showing no correlation between domestic radon exposure and hprt mutant frequency. We use reanalyses of previous studies of radon and hprt mutant frequency to identify problems with this assay as a biomarker for domestic radon exposure and to illustrate difficulties in interpreting the statistical data. We also show with analyses of combined data sets that there is no support for the hypothesis that domestic radon exposure elevates hprt mutant frequency. Taken together, the scientific evidence provides a useful example of the problems associated with analyzing and interpreting data that link environmental exposures, biomarkers, and diseases in epidemiologic studies.

Adolescent↗
PubMed2001

Leukocytes expressing green fluorescent protein as novel reagents for adoptive cell transfer and bone marrow transplantation studies.

Transgenic mice expressing green fluorescent protein (GFP) were generated to provide a source of labeled leukocytes for cell transfer studies. The transgene comprises the GFP coding region under the transcriptional control of the chicken ss-actin promoter and human cytomegalovirus enhancer. Mice expressing this GFP transgene were generated in the B6D2 and in the 129SvEv backgrounds. Flow cytometric analysis of cells from the blood, spleen, and bone marrow of these transgenic mice revealed that most leukocytes, including dendritic cells and memory T cells, express GFP. In allogeneic cell transfers, donor GFP+ splenocytes were detected in the spleen and mesenteric lymph nodes of recipient mice within 2 hours after transfer and for at least 9 days thereafter. In syngeneic experiments using 129-derived GFP+ donor splenocytes, donor cells were detected in multiple tissues of 129 recipients from 2 hours to 3 weeks after transfer. In bone-marrow transplantation experiments using irradiated allogeneic recipients, the percent of GFP+ donor cells in recipients at 3 weeks was comparable to that seen in similar tissues of GFP+ donor mice. These data demonstrate that GFP+ transgenic mice provide a ready source of GFP-expressing primary cells that can be easily monitored after their transfer to recipient animals.

Adoptive Transfer↗
PubMed2001

Incidence of primary opportunistic infections in two human immunodeficiency virus-infected French clinical cohorts.

BACKGROUND: Clinical guidelines for the prevention of opportunistic infections in human immunodeficiency virus (HIV)-infected individuals have been developed on the basis of natural history data collected in the USA. The objective of this study was to estimate the incidence of primary opportunistic infections in HIV-infected individuals in geographically distinct cohorts in France. METHODS: We conducted our study on 2664 HIV-infected patients from the Tourcoing AIDS Reference Centre and the hospital-based information system of the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine enrolled from January 1987 to September 1995 and followed through December 1995. We estimated: (1) CD4-adjusted incidence rates of seven primary opportunistic infections in the absence of prophylaxis for that specific infection or any antiretroviral drugs other than zidovudine; and (2) CD4 lymphocyte count decline. RESULTS: The highest incidence rates for all opportunistic infections studied occurred in patients with CD4 counts < 200/microl. With CD4 counts < 50/microl, the most common opportunistic infections were toxoplasmic encephalitis (12.6 per 100 person-years) and Pneumocystis carinii pneumonia (11.4 per 100 person-years). Mycobacterium tuberculosis was the least common opportunistic infection (< 5.0/100 person-years). Even with CD4 counts > 300/microl, cases of Pneumocystis carinii pneumonia and toxoplasmic encephalitis were reported. The mean CD4 lymphocyte decline per month was 4.6 cells/microl. There was a significant association between HIV risk behaviour and the incidence of cytomegalovirus infection, between calendar year and the incidence of Pneumocystis carinii pneumonia, toxoplasmic encephalitis and Candida esophagitis, and between geographical area and the incidence of Pneumocystis carinii pneumonia and cytomegalovirus infection. CONCLUSIONS: Geographical differences exist in the incidence of HIV-related opportunistic infections. These results can be used to define local priorities for prophylaxis of opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed2001

The pharmacokinetics of epidural ropivacaine in infants and young children.

UNLABELLED: The pharmacokinetic variables of ropivacaine were characterized after epidural bolus injection in pediatric patients. The subjects, 7 infants (aged 3-11 mo) and 11 young children (aged 12-48 mo), received 1.7 mg/kg of ropivacaine via a lumbar epidural catheter. Total plasma concentrations of ropivacaine measured over 24 h were assayed by high-pressure liquid chromatography, and pharmacokinetic modeling was performed by Nonlinear Mixed Effects Modeling analysis. The median peak venous plasma concentrations (C(max)) in infants and young children were 610 microg/L (interquartile range [IQR], 550-725 microg/L) and 640 microg/L (IQR, 540-750 microg/L), respectively. The median times to maximum plasma ropivacaine concentration (T(max)) were 60 min (IQR, 60-120 min) in infants and 60 min (IQR, 30-90 min) in young children. There were no statistical differences between median values of C(max) and T(max) between infants and young children. The calculated clearance (CL) in infants was 4.26 mL x min(-1) x kg(-1) (9% coefficient of variation), and in young children it was 6.15 mL x min(-1) x kg(-1) (11% coefficient of variation). The CL for infants was significantly less than the CL for young children (P < 0.01). The volume of distribution was estimated to be 2370 mL/kg (9% coefficient of variation) for both young children and infants. No systemic toxicity was observed in either group. IMPLICATIONS: This study revealed that the pharmacokinetic variables of lumbar epidural bolus ropivacaine in pediatric patients aged 3 to 48 mo are similar to those of adults, except that drug clearance was less in infants compared with older children.

Algorithms↗
PubMed2001

A comparison of different depth ablations in the treatment of painful bullous keratopathy with phototherapeutic keratectomy.

AIM: To study the efficacy of phototherapeutic keratectomy (PTK) for pain relief for patients with painful bullous keratopathy and poor visual potential. METHODS: Patients with painful bullous keratopathy and poor visual potential were treated with superficial PTK (8-25 microm), intermediate (50-100 microm) or deep PTK (25% stromal thickness) using the Nidek EC5000 excimer laser after manual epithelial debridement. Follow up ranged from 1 to 24 months (mean 6.5 months). Outcome measures included symptomatic relief and need for further treatment. RESULTS: In the superficial PTK group five of eight (62%) patients improved symptomatically after treatment. The three (38%) who did not improve went on to have penetrating keratoplasty for pain relief. In the intermediate depth group only two of five (40%) patients had symptom alleviation. The three others (60%) required further procedures. 20 of 24 (83%) patients treated with deep PTK had significant or total alleviation of symptoms. Of these, one developed acute anterior uveitis 9 months after PTK and two required botulinum ptosis for persistent corneal epithelial defects, one of whom had three consecutive episodes of microbial keratitis. Three of 24 suffered occasional discomfort and one patient required a penetrating keratoplasty for continued pain. CONCLUSION: PTK can be a useful therapeutic measure in painful bullous keratopathy with poor visual potential. Deep PTK appears to be more successful in pain management than superficial treatment.

Adult↗
PubMed2001

Ventricular septal defect in the 9th decade.

This case reports the oldest patient with a large, unoperated, isolated, congenital ventricular septal defect in the literature. Issues related to the natural history of the disease and its management are discussed.

Age Factors↗
PubMed2000

Physical and sexual abuse in women infected with the human immunodeficiency virus: increased illness and health care utilization.

BACKGROUND: A history of physical or sexual abuse is associated with increased health care utilization and possibly an increase in illness based largely on self-reported data. OBJECTIVE: To examine whether victimization experience is associated with increases in documented medical disease and health care utilization among women infected with the human immunodeficiency virus (HIV). METHODS: We interviewed and reviewed medical record data of 50 women seeking initial primary care for HIV infection at 2 urban hospitals. Women with and without a history of physical and sexual abuse were compared. Using multiple regression analysis, 2 periods were examined: entire life before study entry and the subsequent 2 years. The characteristics examined included episodic disease, chronic disease, sexually transmitted disease, chronic pain syndrome, opportunistic infections, obstetrical history, and number of injuries, surgical procedures, hospitalizations, ambulatory care visits, and emergency department visits. RESULTS: Evidence of physical or sexual abuse was found in 34 (68%) of the 50 women, of whom 16 (32%) did not disclose during the interview that they were abused. At entry, the rates of episodic disease, chronic pain syndrome, and sexually transmitted disease were greater among those women with histories of abuse. At 2 years, episodic disease, chronic disease, injuries, emergency department visits, and hospitalizations were all more likely in abused women. CONCLUSION: Physical and sexual abuse are common and associated with increased medical disease and health care utilization among HIV-infected women.

Adult↗
PubMed2000

Analysis of 'natural' and vaccine-induced haemophilus influenzae type B capsular polysaccharide serum antibodies for 3H1, a V3-23-associated idiotope.

The variable (V-) region repertoire of antibodies (Abs) to Haemophilus influenzae capsular polysaccharide (Hib PS) has been extensively studied in individuals vaccinated against the microbe, but to a lesser extent in subjects who generated such Abs in response to a 'natural' encounter with this microbe or its antigenic mimics. To gain an insight into the repertoire of Hib PS-reactive Abs in vaccinated and non-vaccinated individuals, we used a monoclonal Ab, 3H1, which detects an idiotypic marker associated with an Ab V-region gene, V3-23. We show here that Hib PS-reactive Abs with detectable 3H1 idiotope can be quantified by an indirect inimunoezymatic assay in serum samples of non-vaccinated healthy adults as well as of recently vaccinated healthy infants. The percentage of Abs that was simultaneously Hib PS-reactive and 3H1-positive ranged widely (from 0 to 68%) among individual serum samples from both groups of subjects. No dramatic differences in the expression of 3H1 idiotope on Hib PS-reactive Abs were found between vaccinated and non-vaccinated individuals. Our results are consistent with the hypothesis that the utilization of V-region genes in Hib PS-reactive Abs that individuals generate after a 'natural' encounter with Hib PS or its mimics is similar to that in these Abs elicited by Hib PS conjugate vaccines.

Adult↗
PubMed2000

Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi's sarcoma.

Human herpesvirus 8 (HHV8, also known as Kaposi's sarcoma [KS]-associated herpesvirus) has been implicated as an etiologic agent for KS, an angiogenic tumor composed of endothelial, inflammatory, and spindle cells. Here, we report that transgenic mice expressing the HHV8-encoded chemokine receptor (viral G protein-coupled receptor) within hematopoietic cells develop angioproliferative lesions in multiple organs that morphologically resemble KS lesions. These lesions are characterized by a spectrum of changes ranging from erythematous maculae to vascular tumors, by the presence of spindle and inflammatory cells, and by expression of vGPCR, CD34, and vascular endothelial growth factor. We conclude that vGPCR contributes to the development of the angioproliferative lesions observed in these mice and suggest that this chemokine receptor may play a role in the pathogenesis of KS in humans.

Animals↗
PubMed2000

Management of alkali burns : an 11-year retrospective review.

OBJECTIVE: To review the spectrum of patients with alkali burns admitted over an 11-year period and to assess the clinical outcomes after the introduction of a standard alkali burn treatment protocol. DESIGN: Retrospective nonrandomized comparative study. PATIENTS AND INTERVENTIONS: A total of 121 patient records with alkali burns (n = 177 eyes) admitted to a tertiary hospital between 1987 and 1998 were reviewed. Eyes treated with a standard alkali burn treatment protocol, which included intensive topical steroids, ascorbate, citrate, and antibiotics, were compared with eyes treated by conservative management with antibiotics, and a short course of steroids. MAIN OUTCOME MEASURES: Time to corneal reepithelialization, final best-corrected visual acuity, and time to visual recovery, length of hospital stay, and complications were analyzed. RESULTS: The standard protocol tended to delay corneal reepithelialization by one day (P: = not significant) in eyes with grade 1 burns (n = 76) and by 2 days (P: = 0.04) in grade 2 burns (n = 52), with no difference in final visual outcome. There were 37 eyes with grade 3 burns. Those treated with the standard protocol showed a trend toward more rapid corneal reepithelialization. Twenty-seven of 29 (93%) eyes with grade 3 injuries achieved a final best-corrected visual acuity of 20/40 or better compared with 3 of 6 (50%) eyes not treated according to the standard protocol (P: = 0.02). Eyes with grade 4 burns (n = 12), whether treated with the standard protocol or not, required 10 to 12 weeks for corneal reepithelialization. There was no statistically significant difference in final visual acuity. CONCLUSIONS: On the basis of our findings, a number of recommendations can be made for the management of alkali injuries. Patients with a grade 1 or 2 injury do not require routine admission and do not benefit from the use of intensive treatment with ascorbate and citrate. A trend toward more rapid healing and a better final visual outcome were apparent in grade 3 burns, but our standard protocol made no difference in grade 4 burns.

Administration, Topical↗
PubMed1999

Small cell carcinoma of the bladder: long term outcome with integrated chemoradiation.

BACKGROUND: Small cell carcinoma of the bladder (SCCB) is an uncommon tumor with approximately 8% 5-year survival reported in the literature for patients with disease confined to the pelvis. It exhibits biologic behavior similar to that of small cell carcinoma of the lung (SCLC). The authors sought to determine whether etoposide and cisplatin chemotherapy integrated with local irradiation is associated with improved survival in SCCB, as has been shown in SCLC. METHODS: The authors performed a retrospective analysis of stage, treatment, disease free survival (DFS), and overall survival (OS) among 14 British Columbia Cancer Agency (BCCA) patients treated between 1985 and 1996 for SCCB. RESULTS: When multiagent chemotherapy was combined with local irradiation, the authors observed a 70% 2-year and 44% 5-year actuarial OS among 10 patients without contraindications to systemic chemotherapy. Actuarial DFS was 70% at 2 and 5 years. The mean survival was 47 months (95% confidence interval, 18.5-76.1 months) and the median survival was 41 months. Nine of these patients had disease confined to the pelvis, and one had metastases to retroperitoneal lymph nodes. Five patients were alive and disease free an average of 82 months following diagnosis. Two patients had died of other causes without evidence of disease at 34 and 48 months following diagnosis. The incidence of second primary transitional cell bladder neoplasms following successful treatment was 60% at 2 years (3 of 5 long term survivors). CONCLUSIONS: Integrated chemoradiation for patients with limited stage SCCB generates a realistic expectation of long term survival. Prospective trials to confirm these findings are warranted.

Adult↗
PubMed1999

Patient satisfaction with Department of Veterans Affairs health care: do women differ from men?

This study compared the patient satisfaction of female and male veterans using Department of Veterans Affairs health care and examined the relationship between sociodemographic characteristics and satisfaction in men and women. Using data from the Department of Veterans Affairs Women's Health Project (N = 719) and the Veterans Health Study (N = 600), we examined women's and men's unadjusted and adjusted mean scores on three dimensions of satisfaction: location of health care facility, access to health care, and prescription services. Although the unadjusted results indicated that women were less satisfied with both location and access, there were no differences in satisfaction with prescription services. After adjusting for age and then for both age and a recent physician visit, women remained less satisfied with location but were more satisfied with prescription services; there were no differences on access ratings. In an exploratory analysis, we examined the relationships between sociodemographic, military experience, and health characteristics and satisfaction within each sample. Older age was the only characteristic consistently positively associated with each dimension of satisfaction among both women and men. General health perceptions were positively associated with all three dimensions of women's satisfaction but with only the location dimension for men. Although other characteristics were associated with satisfaction within each sample, these differed for women and men. The results suggest that although there were not consistent differences in mean satisfaction ratings by gender, the characteristics associated with satisfaction differed for men and women.

Cross-Sectional Studies↗
PubMed1998

Butyrate analogue, isobutyramide, inhibits tumor growth and time to androgen-independent progression in the human prostate LNCaP tumor model.

Progression to androgen independence remains the main obstacle to improving survival and quality of life in patients with advanced prostate cancer. Induction of differentiation may serve as a rational basis for prevention of progression to androgen independence by modulating gene expression activated by castration or upregulated during androgen-independent progression. The objectives of this study were to characterize the in vitro effects of sodium butyrate on human prostate cancer cell growth, PSA gene expression, and differentiation in the LNCaP tumor model and to determine whether tumor progression in vivo is delayed by isobutyramide, an orally bioavailable butyrate analogue with a longer half-life. The effects of isobutyramide on LNCaP tumor growth and serum PSA levels in both intact and castrate male mice were compared to controls. At concentrations >1 mM, butyrate induced dose-dependent changes towards a more differentiated phenotype, G1 cell cycle arrest, and an 80% decrease in LNCaP cell growth rates. PSA gene expression was increased threefold by butyrate, indicative of differentiation-enhanced gene expression. The half-life of isobutyramide in athymic mice was determined by gas chromatography to be 4 h. During a 4 week period in intact-placebo mice, tumor volume and serum PSA increased 4.1- and 6.6-fold, respectively, compared to twofold and 2.7-fold increases in tumor volume and serum PSA in intact-treated mice. During a 7 week period in castrate-placebo mice, tumor volume and serum PSA levels increased 2.4-fold and fourfold, respectively, compared to a 50% reduction in tumor volume and a twofold increase in serum PSA above nadir levels in castrate mice treated with adjuvant isobutyramide. Isobutyramide treatment induced pronounced morphological changes in LNCaP tumor cells, with loss of defined nucleoli and dispersion of chromatin distribution. LNCaP tumor PSA mRNA levels actually increased threefold, indicative of differentiation-enhanced gene expression. This study demonstrates that butyrate causes LNCaP cell cycle arrest and increased PSA gene expression, both indicative of differentiation. The combination of castration and adjuvant isobutyramide was synergistic in delaying tumor progression. Decreased tumor cell proliferation and increased PSA gene expression induced by isobutyramide results in disconcordant changes in serum PSA and tumor volume and reduces the utility of serum PSA as a marker of response to therapy.

Administration, Oral↗
PubMed1998

Trillion virion delay: time from testing positive for HIV to presentation for primary care.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals' initial presentation to medical care frequently occurs at a point of advanced immunosuppression. OBJECTIVES: To investigate the time between HIV testing and presentation to primary care. Also to examine factors associated with delayed presentation. METHODS: One hundred eighty-nine consecutive outpatients without prior primary care for HIV infection were assessed at 2 urban hospitals: Boston City Hospital, Boston, Mass, and Rhode Island Hospital, Providence. Sociodemographics, alcohol and drug use, social support, sexual beliefs and practices, and HIV testing issues were examined in bivariate and multivariate analyses for association with delay in presentation to primary care after positive test results for HIV. RESULTS: Of 189 patients, 74 (39%) delayed seeking primary care for more than 1 year, 61 (32%) delayed for more than 2 years, and 35 (18%) for more than 5 years after an initial positive HIV serologic evaluation. The median CD4+ cell count of subjects was 0.28 x 10(9)/L (range, 0.001-1.71 x 10(9)/L). In multiple linear regression analysis the following characteristics were found to be associated with delayed presentation to primary care after HIV testing: history of injection drug use (P<.001); not having a living mother (P=.01); not having a spouse or partner (P=.08); not being aware of HIV risk before testing (P<.001); and being notified of HIV status by mail or telephone (P=.002). An interaction effect between sex and screening for alcohol abuse was significant (P=.03) and suggested longer delays for men with positive screening test results (CAGE [an alcoholism screening questionnaire containing 4 structured questions], 2+) compared with men without positive screening test results or women. CONCLUSIONS: Patients with positive HIV test results often delay for more than a year before establishing primary medical care. Information readily available at the time of HIV testing concerning substance abuse, social support, and awareness of personal HIV risk status is useful in identifying patients who are at high risk of not linking with primary care. Patients who were notified of their HIV status by mail or telephone delayed considerably longer than those notified in person. Efforts to ensure primary care linkage at the time of notification of positive HIV serostatus are necessary to maximize benefits for both individual and public health and should be an explicit task of posttest counseling.

Alcohol Drinking↗