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Biomedical subjects

J Ahern

Publications and source records attributed to J Ahern.

At least 19 recordsLinked to original sources
PubMed2006

Alcohol drinking problems among New York City residents after the September 11 terrorist attacks.

Recent studies have shown an increase in alcohol use in New York City in the months after the September 11 terrorist attacks; thus far there have been no studies documenting changes in drinking problems. In 2002, a random digit dial phone survey was conducted of residents of New York City. This study provided us with estimates of the prevalence of alcohol drinking problems among residents of New York City 6 months after September 11 compared with the 6 months before September 11. Among 1,570 adults, the prevalence of drinking problems was 3.7% in the 6 months before September 11 and 4.2% in the 6 months after September 11. The incidence of drinking problems among those without drinking problems before September 11 was 2.2%. Persons with incident drinking problems were more likely than those without to report symptoms consistent with posttraumatic stress disorder (17.4% vs. 0.4% in those without drinking problems and 1.4% in nondrinkers), and depression (23.5% vs 5.6% vs. 4.9%, respectively) after September 11. After a disaster, a link between drinking problems and posttraumatic stress disorder or depression should be assessed.

Adolescent↗
PubMed2005

The urban built environment and overdose mortality in New York City neighborhoods.

Accidental drug overdose continues to be a substantial cause of mortality for drug users. Characteristics of the neighborhood built environment may be important determinants of the likelihood of drug overdose mortality independent of individual-level factors. Using data from the New York City Office of the Chief Medical Examiner, we conducted a multilevel case control study using data on accidental overdose deaths as cases and non-overdose accidental deaths as controls. We used archival data from the New York City Housing and Vacancy Survey and the Mayor's Office of Operations to assess characteristics of neighborhood external (e.g. dilapidation of buildings) and internal (e.g. quality of utilities in houses) built environment. Multilevel analyses were used to assess the relations between the neighborhood built environment and the likelihood of overdose death. Six out of the eight characteristics of the external environment studied and three out of the six characteristics of the internal environment studied were significantly associated with the likelihood of fatal drug overdose in multilevel models after adjusting for individual-level (age, race, sex) and neighborhood-level (income, drug use) variables. Deterioration of the built environment, particularly the external environment, is associated with an increased likelihood of fatal accidental drug overdose. Disinvestment in social resources, psychosocial stressors, neighborhood differences in response to a witnessed overdose, and differences in vulnerability to the adverse consequences of drug use in different neighborhoods may explain the observed associations.

Adolescent↗
PubMed2003

Preterm birth among African American and white women: a multilevel analysis of socioeconomic characteristics and cigarette smoking.

STUDY OBJECTIVE: Research shows that neighbourhood socioeconomic factors are associated with preterm delivery. This study examined whether cigarette smoking and individual socioeconomic factors modify the effects of neighbourhood factors on preterm delivery. DESIGN: Case-control study. SETTING: Moffit Hospital in San Francisco, California. PARTICIPANTS: 417 African American and 1244 white women, including all preterm and a random selection of term deliveries 1980-1990, excluding non-singleton pregnancies, congenital anomolies, induced deliveries, and women transported for special care. US census data from 1980 and 1990 were used to characterise the women's neighbourhoods, defined as census tracts. RESULTS: Cigarette smoking increased the risk of preterm delivery among both African American (OR=1.77, 95% confidence intervals (CI) (1.12 to 2.79)) and white women (OR=1.25, 95% CI (1.01 to 1.55)). However, cigarette smoking did not attenuate or modify the association of neighbourhood factors with preterm delivery. Among African American women, having public insurance modified the relation between neighbourhood unemployment and preterm delivery; among women without public insurance, the risk of preterm delivery was low in areas with low unemployment and high in areas with high unemployment, while among women with public insurance the risk of preterm delivery was highest at low levels of neighbourhood unemployment. CONCLUSIONS: Cigarette smoking was associated with preterm delivery, especially among African Americans. Adverse neighbourhood conditions had an influence on preterm delivery beyond that of cigarette smoking. The effects of some neighbourhood characteristics were different depending on individual socioeconomic status. Examining socioeconomic and behavioural/biological risk factors together may increase understanding of the complex causes of preterm delivery.

Black or African American↗
PubMed2001

Needle exchange programs and experience of violence in an inner city neighborhood.

OBJECTIVE: To assess the association between proximity to a needle exchange program (NEP) and experience of violence in an inner city neighborhood. METHODS: A cross-sectional survey of residents of Harlem, New York City provided data for this study. We used geocoding to obtain the distance between respondents and the nearest NEP. Respondents reported violence they were aware of or had personally experienced in their neighborhood. Multiple logistic regression analyses assessed the relation between violence and distance from the nearest NEP. RESULTS: Among 220 respondents, 50.1% were African American, 39.0% were Latino, 44.7% were male, and the mean age was 44.5 years. In separate age-, race-, sex-, and income-adjusted logistic regression models, there was no significant association between (1) reporting a fight and distance from the nearest NEP (odds ratio [OR] = 1.05, p =.89); (2) robbery in the neighborhood in the previous 6 months and distance from the nearest NEP (OR = 1.13, p =.71); (3) ever having experienced violence and distance from the nearest NEP (OR = 0.72, p =.52); or (4) ever having been robbed by drug users and distance from the nearest NEP (OR = 1.05, p =.91). CONCLUSIONS: There was no consistent association between living close to NEPs and violence reported by residents of Harlem in this study. This study suggests that NEPs do not adversely affect rates of violence in their vicinity.

Adolescent↗
PubMed2001

Prevalence, incidence, and correlates of chlamydia and gonorrhea among young adult injection drug users.

PURPOSE: To measure prevalence, incidence, and correlates of chlamydia and gonorrhea among injection drug users (IDUs). METHODS: Participants (n = 2129; 63% male, 52% white, ages 18-30 years) in five US cities were tested for chlamydia and gonorrhea by urine LCR assay and completed a standardized questionnaire about demographics and recent sexual behavior. Logistic regression identified correlates of prevalent infection; incidence rates were calculated from 6-month follow-up data. RESULTS: Chlamydia prevalence was 5.2% and did not differ by gender. Gonorrhea prevalence was 0.2% among men and 2.0% among women, P < .001. Among men, younger age [OR (95% CI): 0.89 (0.83-0.96)], age at sexual debut [0.91 (0.83-0.99)], and African American race [2.92 (1.53-5.59)] were associated with chlamydia. Among women, age at sexual debut [1.16 (1.02-1.31)] and commercial sex [1.96 (1.03-3.74)] were associated with chlamydia, and with gonorrhea [1.27 (1.04-1.56)] and [5.17 (1.66-16.11)], respectively. At 6 months, the cumulative incidence of chlamydia was 1.7% among men and 4.4% among women, P = .03; no men and 1.3% of women tested positive for gonorrhea, P = .01. IMPLICATIONS: Prevalence and correlates of chlamydia and gonorrhea were similar to other samples, suggesting that screening criteria need not be modified for IDU populations. The number of behavioral correlates identified was limited; perhaps unmeasured sexual-network-level factors play a role in determining sexually transmitted disease (STD) prevalence.

Adolescent↗
PubMed2001

Multicenter phase II study of gemcitabine in previously untreated patients with advanced epithelial ovarian cancer.

Gemcitabine has activity in advanced ovarian cancer, with responses in platinum-resistant disease. This study assessed the activity of gemcitabine in previously untreated patients with advanced epithelial ovarian cancer. All patients had histologically verified invasive epithelial ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease and no prior chemotherapy. Patients received gemcitabine 1250 mg/m(2) on days 1, 8 and 15 of a 28-day cycle. Radiological response was assessed after two cycles. Between December 1992 and October 1995, 35 patients were enrolled. Of 33 evaluable patients, there was one complete response and five partial responses, for an overall response rate of 18% (95% confidence interval 7-36%). Forty-two percent of patients had a greater than 50% decrease in their CA-125 levels. Of the 25 patients who received platinum-based chemotherapy following treatment with gemcitabine, 12 achieved an overall response rate of 48%. Toxicity was mild, with two episodes of WHO grade 4 neutropenia (not associated with fever) and two episodes of grade 4 thrombocytopenia (not associated with bleeding). Gemcitabine has single-agent activity for poor-prognosis patients with advanced ovarian cancer. Similar results with subsequent platinum-based therapy indicate a lack of cross-resistance. This, combined with gemcitabine's favorable toxicity profile, warrants testing in comparative trials.

Adult↗
PubMed1999

Elevated ambulatory blood pressure in 20 subjects with Williams syndrome.

Previous studies report conflicting frequencies of hypertension in cohorts of patients with Williams syndrome (WS). We studied blood pressure (BP) in WS using 24-hour ambulatory BP monitoring. This technique reliably measures day- and nighttime BP in a subject's natural environment and provides better prognostic information on long-term risks of hypertension than casual BP determinations. Twenty WS subjects evaluated through a multidisciplinary WS clinic and 35 age and gender-matched controls were studied. We found that WS subjects had significantly higher ambulatory BP than controls. After controlling for age, sex, and weight, the diagnosis of WS added approximately 10 mmHg to mean daytime and nighttime BPs. Hypertension, as defined by elevated mean daytime BP, was present in 40% of WS subjects versus 14% of controls (P < 0.05); among the children studied this difference was even more dramatic with 46% of WS children versus 6% of control children classified as hypertensive (P = 0.01). We also demonstrated normal diurnal BP variation but no evidence of a "white coat" effect or increased BP variability. Interestingly, parental reporting of a history of infantile hypercalcemia was strongly associated with the presence of hypertension (P = 0.008). Our data demonstrate that both children and adults with WS have higher mean BP and higher frequency of hypertension than healthy controls. Thus, elevated BP readings in the office setting should not be dismissed but require more thorough assessment.

Adolescent↗
PubMed1999

Designing compliance programs that foster ethical behavior.

The federal government continues to expand its initiatives to uncover healthcare fraud, waste, and abuse. It is therefore more important than ever that healthcare organizations have an effective compliance program in place. The organization should have a compliance officer with adequate authority and staff to carry out the compliance program's functions. The program should include an ethics code, an internal hotline that employees can use to report compliance concerns, and education and training for all employees. In addition, the program should be audited periodically to ensure its viability. To be successful, a compliance program also needs the support of the healthcare organization's senior management.

Communication↗
PubMed1997

Implications and results of the Diabetes Control and Complications Trial.

After almost 60 years of debate, the DCCT demonstrated that intensive management that is able to lower blood glucose and HbA1c to levels that are close to normal markedly lowers the risk for and progression of the microvascular and neuropathic complications of IDDM. The challenge to pediatricians and other clinicians is to achieve and maintain such stringent treatment goals in children and adolescents, who are especially difficult to manage, without causing an unacceptably high rate of severe hypoglycemia. Translation of DCCT recommendations into clinical practice is best accomplished by multidisciplinary teams who are experienced in the management of young patients with IDDM and are willing to use the variety of unconventional treatment regimens that may be required. Patients and families must be instructed on ways to reduce the risk for hypoglycemia and be able to recognize and treat hypoglycemic events that require assistance. New agents, such as insulin lispro, may enhance the ability to achieve strict glycemic control, but the treatment remains a burden. Nevertheless, in patients in whom treatment is successful, the improvement in long-term prognosis more than justifies the investment in time, effort, and resources.

Adolescent↗
PubMed1997

Cloning and mutagenesis of the p110 alpha subunit of human phosphoinositide 3'-hydroxykinase.

Activation of phosphoinositide 3'-hydroxykinase (P13K) is required for mitogenic signal transduction by several growth factors and oncogenes. P13K is a heterodimer consisting of a p85 regulatory subunit and a p110 catalytic subunit. In the current study, we report the cloning and characterization of the p110 alpha catalytic subunit of human P13K. This clone is highly homologous (> 99% amino acid identity) to bovine brain p110 alpha, but contains 10 amino acid differences from the human p110 alpha sequence previously reported. Comparison of this sequence with known Ser/Thr kinases and p110 homologs highlighted several conserved residues within the putative kinase domain. Mutational analysis of these residues (Asp915, (Asp933 + Phe934)) yielded P13K mutants with virtually complete loss of phosphoinositide phosphorylating activity. Expression of the wild-type p110 alpha protein in CHO cells is sufficient to activate the serum response element derived from the promoter of c-fos, an immediate early gene product. In contrast, the catalytically impaired p110 alpha mutants as well as the p85 alpha subunit of P13K were inactive in the fos assay. These studies suggest that the mitogenic signal transduction pathway mediated by P13K is dependent upon the enzymatic activity of the p110 alpha subunit of P13K.

Amino Acid Sequence↗
PubMed1997

A randomized controlled trial of enhanced Social Service occupational therapy for stroke patients.

OBJECTIVE: To determine whether stroke patients referred to the Social Service occupational therapy service would benefit from an enhanced service compared to the usual service. DESIGN: Randomized controlled study allocating patients to the enhanced service or the usual service. SUBJECTS: Stroke patients discharged home from hospital and referred to Social Service occupational therapy department. OUTCOME MEASURES: The sections and total score from the Nottingham Extended Activities of Daily Living Scale (EADL), the Barthel Index, the General Health Questionnaire (GHQ) and the number of pieces of equipment provided were analysed. RESULTS: One hundred and eleven stroke patients were recruited to this study. Fifty-three were randomly allocated to the enhanced service and 58 to the usual service. Patients receiving the enhanced service were seen more quickly after referral, for longer, and received significantly more visits (p < 0.01) than those receiving the usual service. Three months after entry to the study the enhanced service group had better EADL (p < 0.01) than the usual service group. This benefit remained significant in only the mobility section of the EADL at six months. Careers of the stroke patients in the enhanced group had lower GHQ scores (p < 0.05) than those in the usual group at six months. CONCLUSIONS: This trial supports the use of domiciliary occupational therapy for stroke patients after discharge from hospital in terms of improvements in functional outcomes in the short term, but the long-term benefits remain unclear.

Activities of Daily Living↗
PubMed1996

Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture.

N1-guanyl-1,7-diaminoheptane (GC7) is a potent inhibitor of deoxyhypusine synthase (DHS), the enzyme that catalyzes the first step in the hypusination of eukaryotic translation initiation factor 5A (eIF-5A). Since eIF-5A is the only known cellular substrate for DHS and GC7 has been reported to block the proliferation of CHO cells, it has been suggested that DHS may be a novel target for anti-cancer therapy. In the present study we investigated the antiproliferative effect of GC7 on several tumorigenic cell lines under various growth conditions. We found that this compound inhibits the proliferation of H9 cells in suspension culture and the growth of HeLa cells and v-src-transformed NIH3T3 cells under both anchorage-dependent and anchorage-independent conditions. Moreover, studies with NIH3T3 cells and v-src-transformed NIH3T3 cells show that GC7 inhibits the growth of both cell lines in monolayer culture with similar potency and could not reverse the transformed phenotype. In addition, the v-src-transformed cells grown under both anchorage-dependent and anchorage-independent conditions showed similar sensitivity toward GC7. These data indicate that GC7 acts as a general antiproliferative agent and does not appear to preferentially target tumorigenic cell types. Cell cycle analysis show that GC7 reduces the CHO-K1 cell population in the G1-phase of the cell cycle by 42% and increases the number of cells in the S-phase by 44%. This cell cycle distribution profile strikingly resembles the distribution of cells treated with puromycin. This result supports the hypothesis that the synthesis of a subset of proteins important for the S-phase progression of CHO-K1 cells might be dependent upon hypusinated eIF-5A. Thus the antiproliferative effect of GC7 appears to be related to its interference with the progression of cell cycle, which also provides a possible explanation for the lack of selectivity of GC7 between nontransformed and transformed cell types tested in this study.

3T3 Cells↗
PubMed1995

Interfacial catalysis by phosphoinositide 3'-hydroxykinase.

Phosphorylation of phosphoinositides by phosphoinositide 3'-hydroxykinase (PI3K) occurs at a lipid/water interface. We have determined that highly purified recombinant human P13K binds tightly to vesicle interfaces composed primarily of phosphatidylinositol (PI) or 1,2-dimyristoyl-sn-glycero-3-phosphomethanol (DMPM). The rate of desorption of PI3K from the vesicle interface is slow and does not significantly affect the observed product formation kinetics. Observations which demonstrate that PI3K is tightly bound to the vesicle lipid/water interface include the following: (1) product formation plateaus rapidly, even in the presence of active enzyme and excess substrate; (2) total product formation is proportional to the amount of PI3K; (3) initial product formation rates are unaffected by bulk lipid concentration but are dependent on the interfacial substrate concentration; and (4) PI3K partitions with lipid vesicles in sedimentation gradients. This enzymatic profile has been referred to as catalysis in the "scooting" mode (Berg et al., 1991). A kinetic analysis of PI3K catalysis in the scooting mode is presented. The interfacial Km,app for PI was determined to be approximately 6.0 mol % in PI/DMPM vesicles. The ratio of specificity constants (kcat/Km) for PI, phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-diphosphate (PIP2) utilization was determined to be near unity. These results provide a rigorous enzymological framework for the kinetic analysis of PI3K inhibitors.

Adenosine Triphosphate↗
PubMed1993

Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in postmenopausal patients with advanced breast cancer.

A phase I study was performed of CGS 20267, an oral nonsteroidal, highly potent, and selective aromatase inhibitor, in 21 postmenopausal patients with advanced breast cancer. The patients were recruited in 3 successive groups of 7, receiving 0.1, 0.5, and 2.5 mg p.o./day, respectively. All patients had received at least one prior endocrine treatment (range, 1-4), and six patients had received prior chemotherapy. The treatment was very well tolerated, and no toxicity was seen at any of the three doses. There was a statistically significant suppression of estradiol (E2) and estrone (E1) levels by 74% and 79% from baseline levels, respectively (P < 0.0001). Suppression occurred in all three patient groups, with many patients having serum concentrations of estradiol and estrone, which were below the limit of detection of the assays (3 and 10 pM, respectively), which corresponds to a maximum measurable estrogen suppression of 86%. CGS 20267 had no significant effect on serum levels of follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, cortisol, 17 alpha-hydroxyprogesterone, androstenedione, and aldosterone. Seven (33%, 95% confidence interval, 15-57%) of the 21 patients have responded to treatment (one complete remission, 6 partial remissions according to criteria of the Union Internationale contre le Cancer), and 6 are still responding to CGS 20267 (duration of response; 4+, 6+, 6+, 9+, 9, 12+, and 12+ months). Five have had stable disease for more than 3 months, and 9 had progressive disease. These results suggest that CGS 20267 is a very potent and specific aromatase inhibitor, and phase II studies are now required to confirm its clinical efficacy.

Aromatase Inhibitors↗
PubMed1993

Response to third-line endocrine treatment for advanced breast cancer.

In a retrospective analysis we have identified 55 patients who have received three endocrine treatments for advanced breast cancer. 42% of these patients have benefitted from third-line endocrine treatment in terms of disease stabilisation, symptom relief or objective response and this was translated into statistically significant (P < 0.01) improved median survival of these patients (34 months) compared with those with progressive disease on third-line treatment (14 months). This suggests that third-line endocrine treatment might be of benefit to a number of patients with advanced breast cancer.

Adult↗