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Biomedical subjects

J Connolly

Publications and source records attributed to J Connolly.

At least 37 records · Page 2Linked to original sources
PubMed2000

Gene delivery from a DNA controlled-release stent in porcine coronary arteries.

Expandable intra-arterial stents are widely used for treating coronary disease. We hypothesized that local gene delivery could be achieved with the controlled release of DNA from a polymer coating on an expandable stent. Our paper reports the first successful transfection in vivo using a DNA controlled-release stent. Green fluorescent protein (GFP) plasmid DNA within emulsion-coated stents was efficiently expressed in cell cultures (7.9% +/- 0.7% vs. 0.6% +/- 0.2% control, p < 0.001) of rat aortic smooth muscle cells. In a series of pig stent-angioplasty studies, GFP expression was observed in all coronary arteries (normal, nondiseased) in the DNA-treated group, but not in control arteries. GFP plasmid DNA in the arterial wall was confirmed by PCR, and GFP presence in the pig coronaries was confirmed by immunohistochemistry. Thus, DNA-eluting stents are capable of arterial transfection, and could be useful as delivery systems for candidate vectors for gene therapy of cardiovascular diseases.

Animals↗
PubMed2000

Controlling the environment to prevent suicide: international perspectives.

BACKGROUND: Suicide and suicidal behaviour are multifaceted events requiring complex solutions. Controlling the environment is a neglected solution, despite strong support for this approach from the World Health Organization (WHO). METHOD: To discuss this approach from a global view, this review is written by authors from various cultures: American, Australian, Canadian, Chinese, Cuban, Dutch, Indian, Irish, Japanese, Lithuanian, Native North American, Russian, and South African. RESULTS: We examine gun control to illustrate the environmental control approach; however, the worldwide diversity of suicide methods calls for diverse responses. Further, controlling the environment encompasses more than restricting the means of suicide, which we illustrate with examples of toned-down media reports and restricted medicine availability. CONCLUSIONS: Controlling the environment may be a viable strategy for preventing suicide, although research shows that few clinicians implement such approaches.

Cross-Cultural Comparison↗
PubMed2000

Dating experiences of bullies in early adolescence.

In this study, 196 young adolescents who reported that they bullied their peers were identified out of a sample of 1,758 students in Grades 5 through 8. After selecting from the total sample a group of nonbullying youth who were matched on gender, school, and grade, a comparison was made of the groups' dating experiences, quality of friend and boyfriend or girlfriend relationships, and acts of physical and social aggression. The results indicated that bullies started dating earlier and engaged in more advanced dyadic dating than comparison adolescents. Bullies were highly relationship oriented, yet their views of their friends and boyfriends or girlfriends were less positive and less equitable than the comparison adolescents. Finally, bullies were more likely to report physical and social aggression with their boyfriends or girlfriends. Although the bullies reported more advanced pubertal development, this factor did not fully account for their dating precocity and negative romantic relationships. The results confirmed our hypotheses that adolescents whose peer relationships are characterized by bullying are at risk in their development of healthy romantic relationships.

Adolescent↗
PubMed2000

Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.

Adult↗
PubMed2000

Prognostic value of thoracic FDG PET imaging after treatment for non-small cell lung cancer.

OBJECTIVE: We determined the prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for patients with treated lung cancer. MATERIALS AND METHODS: We examined patients who underwent FDG PET after first-line treatment for non-small cell lung cancer. FDG PET results were correlated with survival rates to determine whether FDG PET findings were predictive of outcomes. RESULTS: After initial therapy, 113 patients with non-small cell lung cancer underwent FDG PET. One hundred patients had positive FDG PET results and a median survival of 12 months (95% confidence interval, 9.2-15.4). Thirteen patients had negative FDG PET results, and 11 (85%) of these patients are still living at a median follow-up of 34 months. The difference in survival for patients with positive and negative FDG PET results was statistically significant (p = 0.002). CONCLUSION: FDG PET has prognostic value and strongly correlates with survival rates of patients with treated lung cancer. Patients with positive FDG PET results have a significantly worse prognosis than patients with negative results. Additionally, FDG PET may be helpful in guiding therapeutic treatments.

Adult↗
PubMed1999

Developmental delay in P300 production in children at high risk for developing alcohol-related disorders.

BACKGROUND: Reduction of P300 amplitude in children and adolescents at high risk for developing alcoholism has frequently been reported. It has been hypothesized that this reduction represents a developmental delay in reaching age-appropriate levels in P300 amplitude. Using latent growth analysis of longitudinal data obtained at yearly intervals, this study seeks to define normal growth, and determine if the pattern seen in high-risk children differs from that obtained in normal low-risk controls. METHODS: A total of 156 children from either high or low-risk families have been assessed multiple times (two-thirds more than 4 times) using both a clinical assessment (K-SADS) and ERP evaluation performed on the same day. A total of 635 separate assessments were available for modeling. RESULTS: Quadratic growth curves revealed a slower rate of change in P300 amplitude in high-risk than low-risk males. High-risk girls showed reduced visual P300 amplitude only when the presence of a K-SADS diagnosis was considered. No differences were seen for P300 latency. CONCLUSIONS: This study confirms the hypothesis that when reduction of P300 amplitude is seen in males at high risk for developing alcoholism, it is due to a developmental delay.

Adolescent↗
PubMed1999

Psychopathology and achievement in children at high risk for developing alcoholism.

OBJECTIVE: To compare rates of psychopathology and academic achievement in children who were either at high or low risk for developing alcoholism and to determine whether academic deficits would predict prospectively the presence of psychopathology occurring within the next year. METHOD: Children and adolescents, aged 8 to 18 years, were evaluated as part of a longitudinal follow-up. Diagnoses obtained by using the Schedule for Affective Disorders and Schizophrenia for School-Age Children and grade-equivalent scores from the reading, spelling, and arithmetic sections of the Wide Range Achievement Test were determined at yearly intervals. RESULTS: High-risk offspring were more likely to have a diagnosable disorder. In addition, analyses using the mother's and father's diagnosis of alcoholism as a covariate showed higher hazard ratios for selected disorders (depression, affective disorder, attention-deficit/hyperactivity disorder, and conduct disorder), some of which were gender-dependent. Logistic regression analysis of achievement test scores demonstrated that reading and math scores predicted the presence of childhood psychopathology at the following annual evaluation. CONCLUSIONS: Children from pedigrees with a high density of alcoholism are at greater risk for developing psychopathology. Furthermore, observed deficits in academic performance may be considered an indicator of a developing diagnosable illness.

Adolescent↗
PubMed1998

Maternal-fetal tolerance is maintained despite transgene-driven trophoblast expression of MHC class I, and defects in Fas and its ligand.

During mammalian pregnancy, one or more semiallogeneic fetuses gestate in direct contact with the maternal circulation and uterine tissue. However, a damaging maternal immune response is not normally provoked. We studied two possible mechanisms for this maternal-fetal tolerance, alone and in combination. First, we directly tested the hypothesis that the striking absence of MHC class I molecules on most placenta trophoblasts protects the fetus from maternal immune attack, by creating transgenic mice which express Ld in giant cell trophoblasts. Second, because Fas ligand (FasL) may contribute to immune privilege, we tested whether functional FasL expression by the fetus, or Fas expression by the mother, contributes to successful reproduction in a fully allogeneic breeding. Our data indicate that neither abnormal expression of MHC class I in giant cells, nor disruption of the Fas-FasL system, nor a combination of these two defects, has an adverse effect on pregnancy outcome. These results suggest that during healthy allogeneic pregnancy, down-regulation of MHC class I and expression of FasL on placenta are not critical events, and other factors must prevent a harmful maternal immune response.

Adoptive Transfer↗
PubMed1998

Quantitation of progesterone receptor mRNA in breast carcinoma by branched DNA assay.

Expression of progesterone receptor (PR) mRNA is indicative of a normal gene regulation mechanism mediated by functional estrogen receptor (ER). A simple assay which can reliably detect and quantitate PR mRNA levels in a small amount of tissue will be of value for studying functional status of ER. We have developed a quantitative nucleic acid hybridization assay for PR mRNA in breast carcinoma. The assay, which is based on the branched DNA (bDNA) technology, is simple, highly specific, and reproducible, requires 20 mg of tissue, and correlates reasonably well (r = 0.86) with an established methodology. The assay has a dynamic range of 3 x 10(3)-6 x 10(7) copies of PR mRNA per well. PR message as high as 3.9 x 10(5) copies per well could be detected in normal breast tissues. Thus a sensitivity of 3 x 10(3) PR copies per well was sufficient for testing clinical samples. In the present studies, accurate measurement of tissue weight enabled direct reporting of the PR mRNA values as the end point results. The bDNA assay provides a useful tool for the detection and quantitation of PR mRNA in research and routine clinical laboratories.

Animals↗
PubMed1998

The familial aggregation of adolescent suicide attempts.

The objective of this study was to determine whether the familial aggregation of suicidal behaviour is explained by the familial aggregation of personality disorder and aggression. The relatives of 62 clinically referred adolescent suicide attempters were compared with 70 never-suicidal psychiatric controls. The first-degree relatives of the suicide attempters had a higher rate of suicide attempts/completion than those of the psychiatric controls. This rate remained significantly higher after controlling for Axis I and II differences in the probands and the relatives, but familial personality disorder was significantly associated with suicidal risk in probands. Among the adolescent attempters, high scores on a measure of assaultiveness were associated with significantly higher familial rates of suicide attempts/completion. Our results support the hypothesis that suicidal behaviour may be transmitted as a trait independent of Axis I and II psychopathology but that, in addition, personality disorder has a role in the transmission of suicidal behaviour. An interrelationship between proband assaultiveness and the familial aggregation of suicidality was noted.

Adolescent↗
PubMed1998

Home-based versus hospital-based care for serious mental illness. Controlled cost-effectiveness study over four years.

BACKGROUND: The Daily Living Programme (DLP) offered intensive home-based care with problem-centred case management for seriously mentally ill people facing crisis admission to the Maudsley Hospital, London. The cost-effectiveness of the DLP was examined over four years. METHOD: A randomised controlled study examined cost-effectiveness of DLP versus standard in/out-patient hospital care over 20 months, followed by a randomised controlled withdrawal of half the DLP patients into standard care. Three patient groups were compared over 45 months: DLP throughout the period, DLP for 20 months followed by standard care, and standard care throughout. Bivariate and multivariate analyses were conducted (the latter to standardise for possible inter-sample differences stemming from sample attrition and to explore sources of within-sample variation). RESULTS: The DLP was more cost-effective than control care over months 1-20, and also over the full 45-month period, but the difference between groups may have disappeared by the end of month 45. CONCLUSIONS: The reduction of the cost-effectiveness advantage for home-based care was perhaps partly due to the attenuation of DLP care, although sample attrition left some comparisons under-powered.

Adolescent↗
PubMed1998

Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer.

PURPOSE: To evaluate the safety and efficacy of breast-conserving therapy for young women with a family history (FH) suggestive of inherited breast cancer susceptibility. MATERIALS AND METHODS: A total of 201 patients aged 36 or younger at diagnosis treated with breast-conserving surgery and radiation therapy (> or = 60 Gy) for early-stage breast cancer were categorized by FH. FH was considered positive in 29 patients who, at the time of diagnosis, had a mother or sister previously diagnosed with breast cancer before age 50 or ovarian cancer at any age. Clinical, pathologic, and demographic variables; sites of first failure; disease-free survival; and overall survival (OS) were compared between FH-positive and -negative groups. Median follow-up time was 11 years. RESULTS: Patient and tumor features were similar between those with and without an FH. Regression analysis of sites of first failure at 5 years demonstrated a risk ratio (RR) of 5.7 for opposite breast cancer for FH-positive patients. Rates of local, regional, and distant failure and disease-free survival or OS did not differ between FH-positive and -negative patients. Age at diagnosis and Ashkenazi heritage were not significantly predictors of patterns of failure. CONCLUSION: Breast-conserving surgery combined with radiation therapy is not associated with a higher rate of local recurrence, distant failure, or second (non-breast) cancers in young women with an FH suggestive of inherited breast cancer susceptibility compared with young women without an FH. However, their increased risk of opposite breast cancer should be taken into account when considering breast conservation as a treatment option.

Adult↗
PubMed1997

Familial aggregation of psychiatric disorders in a community sample of adolescents.

OBJECTIVE: To determine whether specific psychiatric disorders and suicide attempts ascertained in a community sample of adolescents show evidence of familial aggregation. METHOD: Fifty-eight adolescent probands recruited from the community and their relatives were assessed as to the presence of specific DSM-III Axis I disorders and suicide attempt, using a combination of family study and family history methodology. RESULTS: In first-degree relatives, there was evidence for specific familial aggregation of suicide attempt (odds ratio [OR] = 12.1 95% confidence interval [CI] = 1.3 to 111.0), substance abuse (OR = 2.7, 95% CI = 1.1 to 6.7), and any Axis I disorder (OR = 2.5, 95% CI = 1.3 to 4.6), even after demographic confounders and familial comorbidity were controlled. Similarly, among second-degree relatives, in analyses controlling for potentials confounders, the disorders-specific aggregation of suicide attempt (OR = 12.3, 95% CI = 1.2 to 130.0), substance abuse (OR = 2.8, 95% CI = 1.6 to 4.8), and any Axis I disorder (OR = 1.5, 95% CI = 1.0 to 2.2) persisted. CONCLUSIONS: The familial aggregation of suicide attempts and psychiatric disorders, particularly of substance abuse and any Axis I disorder, occurs in community samples and is not primarily attributable to referral status.

Adolescent↗
PubMed1997

Paracetamol poisoning in the north east of England: presentation, early management and outcome.

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.

Acetaminophen↗