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Biomedical subjects

D McCarty

Publications and source records attributed to D McCarty.

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

Limited entry of adenovirus vectors into well-differentiated airway epithelium is responsible for inefficient gene transfer.

Investigations of the efficiency and safety of human adenovirus vector (AdV)-mediated gene transfer in the airways of patients with cystic fibrosis (CF) in vivo have demonstrated little success in correcting the CF bioelectrical functional defect, reflecting the inefficiency of AdV-mediated gene transfer to the epithelial cells that line the airway luminal surface. In this study, we demonstrate that low AdV-mediated gene transfer efficiency to well-differentiated (WD) cultured airway epithelial cells is due to three distinct steps in the apical membrane of the airway epithelial cells: (i) the absence of specific adenovirus fiber-knob protein attachment receptors; (ii) the absence of alphavbeta3/5 integrins, reported to partially mediate the internalization of AdV into the cell cytoplasm; and (iii) the low rate of apical plasma membrane uptake pathways of WD airway epithelial cells. Attempts to increase gene transfer efficiency by increasing nonspecific attachment of AdV were unsuccessful, reflecting the inability of the attached vector to enter (penetrate) WD cells via nonspecific entry paths. Strategies to improve the efficiency of AdV for the treatment of CF lung disease will require methods to increase the attachment of AdV to and promote its internalization into the WD respiratory epithelium.

Adenoviridae↗
PubMed1998

Complications of diabetes in the hospitalized population in Victoria, 1993-95.

A retrospective analysis of computerized data from the Victorian Inpatient Minimum Database (VIMD) was undertaken in order to describe the prevalence of diabetes and its associated complications in the hospitalized population over a 2-year period. While diabetes was rarely recorded as a principal cause of hospitalization (less than 0.5% of admissions), this condition was present in 4% (95,091) of the hospitalized population with a slight male excess. Cardiovascular disease was present in 60% of these diabetes-related admissions and was the principal diagnosis in a quarter of all cases. The prevalence of hypertension was 28%. Cardiovascular disease (CVD) was the principal diagnosis in 40% of in-hospital deaths, and in women, the risk of CVD death was 22% greater than it was for men. Diabetes-related complications were noted in 22%; 3.3% recorded renal disease, 2.7% peripheral vascular disease, and ophthalmic and neurological complications were recorded in 2.1% and 1.4%, respectively. Of all lower limb amputations carried out in Victoria over the period, 40% (1281) were in people with diabetes. Eye surgery was carried out on (6.8%) 6463 diabetes-related separations. There are recognized limitations of using routinely collected computerized data. Nevertheless, data relating to number of amputations and eye surgery in those with diabetes can be used as indicators of the success of diabetes care and national strategies for prevention.

Adult↗
PubMed1997

Managed care of substance abuse disorders. Implications for generalist physicians.

Given the rapidly changing landscape of both private and public health plan programs, it is foolhardy to suggest that a definitive characterization of managed care and substance abuse issues can be made. Among other topics, this article discusses goals of managed care organizations, managed care models, and physicians' roles in managed care.

Cost Control↗
PubMed1997

Replication-deficient adenoviral vector for gene transfer potentiates airway neurogenic inflammation.

Human trials for the treatment of cystic fibrosis lung disease with adenoviral vectors have been complicated by acute inflammatory reactions of unknown etiology. Because replicating respiratory viruses can potentiate tachykinin-mediated neurogenic inflammatory responses in airways, we studied whether the endotracheal administration of a replication-deficient adenoviral vector potentiated this response. The vector Ad5CMVLacZ was administered endotracheally to rats and the leakage of Evans blue dye was used to measure the capsaicin-induced neurogenic albumin extravasation. These studies show that neurogenic albumin extravasation is significantly potentiated in the airways of rats after administration of Ad5CMVLacZ. This inflammatory response can be blocked by selective antagonists of the substance P receptor or by glucocorticoids. Therefore, (1) the acute airway inflammation observed in patients after exposure to adenoviral vectors may exhibit a neurogenic component, which can be blocked pharmacologically, and (2) preclinical adenoviral vector safety studies of other organs innervated by the tachykinin system, e.g., coronary arteries and gastrointestinal tract, should include assessment of neurogenic inflammation.

Adenoviruses, Human↗
PubMed1994

De novo synthesis of an intron by the maize transposable element Dissociation.

The mechanisms by which introns are gained or lost in the evolution of eukaryotic genes remain poorly understood. The discovery that transposable elements sometimes alter RNA splicing to allow partial or imperfect removal of the element from the primary transcripts suggests that transposons are a potential and continuing source of new introns. To date, splicing events that precisely restore the wild-type RNA sequence at the site of insertion have not been detected. Here we describe alternative RNA splicing patterns that result in precise removal of a Dissociation (Ds) insertion and one copy of its eight-nucleotide host site duplication from an exon sequence of the maize shrunken2-mutabe1 (sh2-m1) mutant. In one case, perfect splicing of Ds was associated with aberrant splicing of an intron located 32 bp upstream of the insertion site. The second transcript type was indistinguishable from wild-type mRNA, indicating that Ds was spliced like a normal intron in about 2% of the sh2-m1 transcripts. Our results suggest that the transposition of Ds into sh2 in 1968, in effect, marked the creation of a new intron in a modern eukaryotic gene. The possibility of precise intron formation by a transposable element demonstrated here may be a general phenomenon of intron formation, since consensus intron splice sites can be explained by insertions that duplicate host sequences upon integration. A model is presented.

Alleles↗
PubMed1994

National diabetes programs. Application of capture-recapture to count diabetes?

OBJECTIVE: To evaluate the utility of capture-recapture methods using multiple, routinely collected, computerized data sources to estimate the numbers and prevalence of diabetes. Methods employed for regional and national monitoring of diabetes have been too inaccurate or too expensive. RESEARCH DESIGN AND METHODS: A survey was undertaken that used four sources of ascertainment to identify prevalent cases of known diabetes in community of Northern Italy: diabetic clinic and family physicians, hospital discharges, prescriptions, and reagent strips and insulin syringes. Capture-recapture methods were employed to estimate the number of missing cases and to adjust for undercount to accurately estimate the number of people who had diabetes. RESULTS: We identified 2,069 unique prevalent cases of known diabetes with the intensive case-finding procedure. The diabetic clinic and family physicians data source identified the largest number of cases. The evaluation of the two sample capture-recapture estimates showed that they were all biased downward because of dependencies between sources. Log-linear modeling was employed to take into account the dependence among all data sources and the heterogeneity of diabetic patients. This method estimated that 2,586 cases existed, resulting in an ascertainment-adjusted prevalence of 2.77% (95% confidence interval, 2.44-3.10). Thus, despite the active case identification, approximately 20% could not be identified. However, the number of cases and rates could easily be adjusted using capture-recapture. CONCLUSIONS: The study shows that a two-sample capture-recapture estimate could be very biased if the investigator is not assured that the sources are independent. However, if at least three data sources are employed, log-linear models allow estimation of the number and prevalence rate adjusted for the degree of undercount (in spite of both the dependence of data sources and the heterogeneity of the diabetic population). The critical factor, however, is that the application of multiple sources with capture-recapture methods could be applied across broad geographical areas and across time to have cost-effective monitoring of diabetes at local and national level.

Adolescent↗
PubMed1993

The use of shelters as substance abuse stabilization sites.

The feasibility of providing postdetoxification residential substance abuse programming (stabilization) in large emergency shelters was examined as part of a demonstration project funded by the National Institute on Alcohol Abuse and Alcoholism under Section 613 of the Stewart B. McKinney Act (Public Law 100-71). The program completion rates of 773 homeless/near-homeless substance-abusing individuals assigned to two large shelters (71% and 62%) and two traditional substance abuse treatment agencies (68% and 54%) were comparable. These data support the expansion of shelter services to include substance abuse programming and intervention. Shelters represent windows of opportunity into the lives of homeless substance-abusing men and women, and full advantage of this opportunity should be taken to impact this subgroup of the homeless.

Adult↗
PubMed1993

Counting diabetes in the next millennium. Application of capture-recapture technology.

Monitoring diabetes is critical for our understanding of the etiology and natural history of disease and for public health actions. However, traditional methods for monitoring are either too expensive (e.g., IDDM registries, NIDDM-OGTT prevalence surveys) or too inaccurate (routinely collected data or passive surveillance) for broad accurate, national programs for monitoring the incidence and prevalence of disease. We suggest that one technology called capture-recapture would considerably increase our ability to "count" diabetes, both nationally and globally. Implementation of this approach could lead to accurate inter- and intracountry data on rates of disease. Moreover, such tracking of diabetes could serve as the model for the monitoring of all disease in the 21st century and beyond.

Animals↗
PubMed1992

Substance abuse treatment management information systems: balancing federal, state, and service provider needs.

There is increased interest in documenting the characteristics and treatment outcomes of clients served with Alcohol, Drug Abuse, and Mental Health Block Grant funds. The evolution of federal client-based management systems for substance abuse treatment services demonstrates that data collection systems are important but require continued support. A review of the Massachusetts substance abuse management information system illustrates the utility of a client-based data set. The development and implementation of a comprehensive information system require overcoming organizational barriers and project delays, fostering collaborative efforts among staff from diverse agencies, and employing considerable resources. In addition, the need to develop mechanisms for increasing the reliability of the data and ongoing training for the users is presented. Finally, three applications of the management information system's role in shaping policy are reviewed: developing services for special populations (communities of color, women, and pregnant substance abusers, and injection drug users), utilizing MIS data for evaluation purposes, and determining funding allocations.

Computer Communication Networks↗
PubMed1992

Monitoring the incidence of myocardial infarctions: applications of capture-mark-recapture technology.

It is critical to monitor the incidence of myocardial infarction. Typically, death certificates have been used as a proxy for incidence, however, these have been found to be crude as they lag behind changes in incidence. In the last decade several myocardial infarction registries have been established, however, these registries are still too limited in geographical spread to assess either national or global trends of heart attack. Here we suggest that employing an alternate approach, that of capture-mark-recapture, would be helpful to provide accurate monitoring both within and between countries. This method would complement existing registries by providing a simple and inexpensive means to provide accurate heart attack data across broad geographical areas and time.

Cohort Studies↗
PubMed1991

Alcoholism, drug abuse, and the homeless.

Credible estimates of the prevalence of alcohol and drug abuse suggest that alcohol abuse affects 30% to 40% and drug abuse 10% to 15% of homeless persons. A review of policies that address substance abuse among the homeless finds that interventions alternate between control and rehabilitation. However, the unique needs of a changing homeless population require an integration of alcoholism and drug abuse recovery services with programs for women, adolescents, and the mentally ill. Alcohol- and drug-free housing is essential to support and maintain recovery. Psychology can contribute in the development of effective programs for homeless individuals struggling with addiction and alcoholism.

Alcoholism↗
PubMed1990

Risk factors for postvitrectomy fibrin formation.

We prospectively studied 194 patients undergoing vitrectomy between July 1988 and April 1989 to determine the incidence of postvitrectomy intraocular fibrin formation and the association of a variety of preoperative and intraoperative variables with the formation of severe postvitrectomy fibrin. Overall, 62 (32%) patients developed postvitrectomy fibrin; 25 (13%) had mild fibrin formation, 13 (6.5%) had moderate fibrin formation, and 24 (12.4%) had severe fibrin formation. By logistic multivariate analysis, preoperative factors that were independently predictive of severe fibrin formation included severe flare (P = .004), the presence of a previously placed scleral buckle (P = .001), and poor preoperative visual acuity (P = .007). Anterior epiretinal membrane dissection was the only intraoperative factor that was independently associated with an increased fibrin risk (P = .0003). A risk score derived from the multivariate analysis effectively categorized patients according to their likelihood of developing severe postvitrectomy fibrin. Results of this study may be useful in designing prophylactic interventions to decrease postvitrectomy fibrin formation.

Adult↗
PubMed1990

Clinical evaluation of an acetaminophen meter for the rapid diagnosis of acetaminophen intoxication.

STUDY OBJECTIVES: To test the accuracy of a newly developed meter that determines serum acetaminophen concentration after a 30-second analysis of one drop of whole blood. DESIGN: Sixty-six blood samples from patients with known or suspected drug overdose were analyzed for the presence of acetaminophen. In all cases determination of serum acetaminophen concentration was performed simultaneously with the meter and by a reference laboratory. SETTING: Eligible patients were those who presented during a nine-month period to the emergency departments of two tertiary care hospitals (including a pediatric hospital). RESULTS: Thirty-one specimens had a laboratory-confirmed detectable acetaminophen concentration. The meter identified these toxic specimens in all cases; there were no false-negatives (sensitivity, 100%). Among the 35 specimens not containing acetaminophen, the meter invariably confirmed a nondetectable serum acetaminophen concentration (specificity, 100%). Acetaminophen measurements by the meter correlated strongly with laboratory determinations (r = .985, P less than .001). Repeated testing of one specimen documented the precision and reproducibility of the meter's analysis; mean coefficient of variation was .08 in measuring toxic acetaminophen concentrations. Drug coingestion had no significant effect on the accuracy of the meter. Instrument accuracy was maintained after more than 100 uses without recalibration. CONCLUSIONS: This meter identifies the possibility of rapid and accurate determinations of serum acetaminophen concentration. The instrument is ideally suited for patients with acetaminophen poisoning in whom expeditious and appropriate administration of antidotal therapy is desired.

Acetaminophen↗
PubMed1988

Rearrest following residential treatment for repeat offender drunken drivers.

Multiple offenders are at high risk for continued drunken driving. Massachusetts, therefore, mandated that individuals convicted of a second drunken driving offense either be committed for a minimum of 7 days in a house of correction or enter a 14-day residential alcoholism treatment program for second offenders. A 2-year follow-up study of arrest rates assessed the impact of the two sentencing options on subsequent arrests for driving under the influence of liquor (DUIL). The incarcerated sample (N = 190) was slightly younger, had more prior DUIL charges and exhibited greater criminality than those who entered treatment (N = 199). Offenders admitted to the 14-day program were significantly less likely to be rearrested for drunken driving (10 vs 20%). A summary odds ratio suggested that when adjusted for differences in prior arrests, the risk of rearrest was 1.9 times greater among incarcerated offenders. Although a 2-year follow-up is insufficient to assess the complete impact of the 14-day program, the two-fold difference in the risk of rearrest suggests that mandated short-term residential treatment may provide an effective intervention among repeat offender drunken drivers.

Adult↗
PubMed1985

Criminality among individuals arraigned for drinking and driving in Massachusetts.

Criminal record searches of 1406 randomly selected driving under the influence of liquor (DUIL) offenders in Massachusetts revealed a history of prior court arraignments in 76.5% of the cases. Half (51.2%) had been arraigned for criminal offenses other than or in addition to traffic and DUIL, and one-fourth (27.7%) had been previously arraigned for DUIL. Among those with prior DUIL arrests, 68% also had criminal arrests. A 3-year follow-up indicated that 63% of those rearrested for DUIL had prior criminal arrests. Eight subgroups of offenders were created by categorizing the sample according to the presence or absence of criminal, traffic and prior DUIL offenses. Rates of recidivism differed among the subgroups and illustrated the utility of using criminal history data to differentiate DUIL offenders. The need to develop alternative court management-rehabilitation strategies responsive to subgroup differences is discussed.

Adult↗
PubMed1985

Legislated policies and recidivism for driving under the influence of liquor in Massachusetts.

Legislation on driving under the influence of liquor was changed significantly in Massachusetts on 1 December 1975; it permitted courts to continue cases without a finding if defendants were place probation and assigned to driver alcohol education. The effect of the revisions on the incidence of rearrest was assessed. The 3-yr arrest records of 522 individuals arrested for drunken driving 2 yr before the changes (1973) were compared with 716 and 690 offenders arrested 1 (1976) and 2 (1977) yr post-law modification. Sample participants were selected randomly. The legislation strongly affected court dispositions. Over 70% of the 1976-1977 cases were continued without findings and more offenders were sanctioned. The proportion found not guilty dropped from 1973 to 1976-1977. Absolute rearrest rates were similar for each cohort. Probability of arrest, however, rose substantially between 1973 and 1980. Relative to the increased arrest rate, there was a significant decline in rearrests 2 and 3 yr after a drunken driving arrest during the post-law period. The legislation apparently contributed to an amelioration of the drunken driving problem by encouraging judicial reforms and educational interventions.

Accidents, Traffic↗