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Biomedical subjects

M Durkin

Publications and source records attributed to M Durkin.

At least 19 recordsLinked to original sources
PubMed2006

Elimination of false-positive Histoplasma antigenemia caused by human anti-rabbit antibodies in the second-generation Histoplasma antigen assay.

False-positive Histoplasma antigenemia was reported in solid organ allograft recipients who had received rabbit anti-thymocyte globulin (RATG, RATG) caused by human anti-rabbit antibodies (HARA). A second-generation Histoplasma antigen detection assay was developed to overcome false positivity caused by HARA. With the second-generation assay, false-positive results were eliminated in 18 of 19 cases without reduction in the sensitivity in patients with histoplasmosis. In fact, sensitivity for detection of antigenuria in patients with acquired immunodeficiency syndrome and disseminated histoplasmosis was higher in the second-generation assay. Physicians should be aware of the potential for false-positive results in sandwich immunoassays in specimens from patients who have received RATG.

Antigens, Fungal↗
PubMed2005

Fruit and vegetable intakes in a sample of pre-school children participating in the 'Five for All' project in Bradford.

BACKGROUND: Longitudinal research has shown that eating fruit and vegetables during childhood has a positive impact on long-term health outcome from heart disease and asthma. However, recommendations for fruit and vegetable intakes in pre-school children are not as explicit as those for adults and few data exist on actual intakes of fruit and vegetables in this particular age group. AIMS: To describe fruit and vegetable intakes in the daily diets of a sample of pre-school children in Bradford, West Yorkshire, and to compare the findings with existing national UK data. SUBJECTS: Pre-school children aged 3 and 4 years (n = 207). All subjects attended nurseries in the Airedale and Bradford South and West regions at the time of the study. DESIGN: Dietary data were collected using the pre-validated CADET (Child and Diet Evaluation Tool) diary. All children were also seen individually in order to assess their awareness and preference for a range of fruit and vegetables. RESULTS: Intakes of fruit and vegetables in this sample of pre-school children were below recommended levels. Only 16% of children in this sample were successfully eating fruit and vegetables on five occasions a day and conversely 14% ate no fruit and vegetables at all. Vegetable intakes were far lower than fruit intakes with 39% of the sample consuming no vegetables. There were statistically significant differences in median fruit and vegetable intakes between children with different demographic and lifestyle variables, such as which nursery they attended and what the highest educational qualification in the household was. Children's awareness of and preferences for different fruit and vegetables significantly affected their median intakes of fruit and vegetables. CONCLUSION: Fruit and vegetable intakes in this sample of pre-school children were far lower than the recommended levels of 5 portions a day. A greater diversity of intakes should be encouraged and these data suggest that this may be attained by increasing children's awareness by exposing them to a wider range of fruit and vegetables.

Child Nutritional Physiological Phenomena↗
PubMed2004

False-positive Histoplasma antigenemia caused by antithymocyte globulin antibodies.

False-positive Histoplasma antigen results were identified in two patients who received rabbit antithymocyte globulin (ATG, Thymoglobulin(R)) to prevent allograft rejection. To determine the prevalence of false-positive results following the administration of Thymoglobulin, sequential specimens were tested from a cohort of transplant recipients. Of 107 such patients, 17 (15.9%) demonstrated false-positive tests for Histoplasma antigenemia. False antigenemia peaked at 2-4 weeks after ATG administration and cleared over the next few months. Physicians should be aware of the potential for false-positive results in specimens from patients who have received ATG.

Animals↗
PubMed2003

Effects of CD4 and CD8 T lymphocyte depletion on the course of histoplasmosis following pulmonary challenge.

Use of a pulmonary model of histoplasmosis in CD4/CD8 lymphocyte depleted animals offers an opportunity to study pathogenesis in a setting resembling AIDS. Flow cytometric analysis demonstrated that administration of anti-CD4 and anti-CD8 antibodies reduced CD4 and CD8 T cell subsets in the lungs, lymph nodes and spleen. Depletion of these cells transformed the infection from a self-limited course in normal mice to a progressive, fatal course in CD4/CD8 depleted mice. CD4 depletion alone had a lesser effect on survival, but increased fungal burden, while CD4/CD8 depletion had the greatest effect. Histopathologic studies showed marked differences in the inflammatory response between the dually depleted animals and the non-depleted controls. In conclusion, the course of histoplasmosis in CD4/CD8 depleted animals is progressive and fatal, resembling that observed in immunosuppressed patients. This model appears suitable for investigation of immunity to H. capsulatum, and should be useful for evaluation of treatment in the immunocompromised host.

Animals↗
PubMed2002

Effect of CD40 ligand on the course of murine histoplasmosis.

CD40 ligand-CD40 ligation is important in the development of T-cell-mediated immune responses. The purpose of this study was to examine the role of CD40L in recovery from histoplasmosis using a murine model of intratracheally induced infection. B6C3F1 mice were infected intratracheally with Histoplasma capsulatum yeast and monitored for clearance of the organism from the lungs and spleen. CD40L treatment was begun on either day -2 or +2 post inoculation and continued until day 14 in CD4-depleted animals and from day -2 to day +4 in non-immunosuppressed animals. Amphotericin B treatment was begun four days following inoculation and given every other day for 10 days. CD40L reduced fungal burden by less than one log when started two days before infection but did not act synergistically with low-dosage amphotericin B (0.2 mg kg(-1) qod) in CD4 depleted mice. Low-dose amphotericin B, CD40L, and the combination of the two failed to lower the fungal burden in a second experiment using a more virulent isolate of the same strain of H. capsulatum in CD4-depleted mice. Furthermore, CD40L did not increase the concentrations of IFN-gamma, IL-12 or IL-10 in the lungs or spleens of infected animals. In summary, CD40L had minimal or no effect on the course of infection in this murine model of histoplasmosis.

Animals↗
PubMed2001

Chronic infection and reactivation in a pulmonary challenge model of histoplasmosis.

Reactivation may be a mechanism for the development of histoplasmosis in AIDS. In this study, histoplasmosis was reactivated by the depletion of CD4 and CD8 lymphocytes in mice. CD4 and/or CD8 depletion beginning 1 month after intratracheal infection and continuing for 2 months caused reactivation with a 2.1 log/g increase in the lungs and a 1.5 log increase in the spleen of B6C3F1 mice. Because control animals showed persistent infection, a subsequent experiment sought to determine the long-term outcome in competent mice. Twelve of 32 immunocompetent mice died at weeks 26-52 of infection, and 4 survivors appeared to be clinically ill; all ill mice had high fungus burdens, whereas cultures were sterile in the healthy mice. Eight of the surviving healthy-appearing mice underwent autopsy 2 years after infection, and cultures were sterile. Thus, 16 of 32 immunocompetent mice exhibited progressive infection. CD4 and/or CD8 depletion exacerbated infection, but a chronic progressive and ultimately fatal infection occurred in half the immunocompetent mice.

Analysis of Variance↗
PubMed2001

Urinary tract infections during pregnancy in South Carolina.

This study presents evidence that over 20 percent of pregnant women with a UTI in South Carolina did not have an antibiotic pharmacy claim within 14 days of diagnosis. Untreated maternal UTI in pregnancy was associated with a 22 percent increased risk for MR/DD in the infant compared to the risk for women who had a UTI and a pharmacy claim for an antibiotic and 31 percent increased risk compared to women who did not have a UTI. The importance of medications compliance should be emphasized in the care of pregnant women.

Anti-Infective Agents, Urinary↗
PubMed2000

Comparison of a new triazole, posaconazole, with itraconazole and amphotericin B for treatment of histoplasmosis following pulmonary challenge in immunocompromised mice.

A murine model of intratracheally induced histoplasmosis in immunocompromised B6C3F(1) mice was used to evaluate a new triazole antifungal agent, posaconazole. This compound was previously shown to be comparable to amphotericin B and superior to itraconazole for the treatment of histoplasmosis in immunocompetent mice. The current study used mice that were depleted of T lymphocytes by intraperitoneal injection of anti-CD4 and anti-CD8 monoclonal antibodies beginning 2 days before infection and continuing at 5-day intervals until completion of the study. Groups of B6C3F(1) mice that were depleted of CD4 and CD8 T cells were infected with an inoculum of 10(4) Histoplasma capsulatum yeasts. All mice receiving posaconazole at 1 or 0.1 mg/kg of body weight/day, amphotericin B at 2 mg/kg every other day (qod), or itraconazole at 75 mg/kg/day survived to day 29. Only 60% of mice receiving itraconazole at 10 mg/kg/day and none receiving amphotericin B at 0.2 mg/kg qod survived to that date. Fungal burdens were determined at day 14 of infection, 1 day after discontinuation of therapy. Quantitative colony counts and Histoplasma antigen levels in lung and spleen tissues declined following treatment with amphotericin B at 2 mg/kg qod, posaconazole at 5 and 1 mg/kg/day, and itraconazole at 75 mg/kg/day but not in mice treated with amphotericin B at 0.2 mg/kg qod or itraconazole at 10 mg/kg/day. Posaconazole at 0.1 mg/kg/day reduced fungal colony counts and antigen levels in spleens but not in lungs. This study shows posaconazole activity for the treatment of histoplasmosis in immunosuppressed animals.

Amphotericin B↗
PubMed2000

Comparison of nikkomycin Z with amphotericin B and itraconazole for treatment of histoplasmosis in a murine model.

Nikkomycin Z was tested both in vitro and in vivo for efficacy against Histoplasma capsulatum. Twenty clinical isolates were tested for susceptibility to nikkomycin Z in comparison to amphotericin B and itraconazole. The median MIC was 8 microg/ml with a range of 4 to 64 microg/ml for nikkomycin Z, 0.56 microg/ml with a range of 0.5 to 1.0 microg/ml for amphotericin B, and < or =0.019 microg/ml for itraconazole. Primary studies were carried out by using a clinical isolate of H. capsulatum for which the MIC of nikkomycin Z was greater than or equal to 64 microg/ml. In survival experiments, mice treated with amphotericin B at 2.0 mg/kg/dose every other day (QOD) itraconazole at 75 mg/kg/dose twice daily (BID), and nikkomycin Z at 100 mg/kg/dose BID survived to day 14, while 70% of mice receiving nikkomycin Z at 20 mg/kg/dose BID and none of the mice receiving nikkomycin Z at 5 mg/kg/dose BID survived to day 14. All vehicle control mice died by day 12. Fungal burden was assessed on survivors. Mice treated with nikkomycin Z at 20 and 100 mg/kg/dose BID had significantly higher CFUs per gram of organ weight in quantitative cultures and higher levels of Histoplasma antigen in lung and spleen homogenates than mice treated with amphotericin B at 2.0 mg/kg/dose QOD or itraconazole at 75 mg/kg/dose BID. Studies also were carried out with a clinical isolate for which the MIC of nikkomycin Z was 4 microg/ml. All mice treated with amphotericin B at 2.0 mg/kg/dose QOD; itraconazole at 75 mg/kg/dose BID; and nikkomycin Z at 100, 20, and 5 mg/kg/dose BID survived until the end of the study at day 17 postinfection, while 30% of the untreated vehicle control mice survived. Fungal burden assessed on survivors showed similar levels of Histoplasma antigen in lung and spleen homogenates of mice treated with amphotericin B at 2.0 mg/kg/dose QOD; itraconazole at 75 mg/kg/dose BID; and nikkomycin Z at 100, 20, and 5 mg/kg/dose BID. The three surviving vehicle control mice had significantly higher antigen levels in lung and spleen than other groups (P<0.05). The efficacy of nikkomycin Z at preventing mortality and reducing fungal burden correlates with in vitro susceptibility.

Aminoglycosides↗
PubMed2000

Comparison of the echinocandin caspofungin with amphotericin B for treatment of histoplasmosis following pulmonary challenge in a murine model.

Twenty clinical isolates of Histoplasma capsulatum were tested for their in vitro susceptibilities to caspofungin in comparison to those to amphotericin B by following National Committee for Clinical Laboratory Standards guidelines for yeasts. The mean MICs were 16.6 microgram/ml (range, 8 to 32 microgram/ml) for caspofungin and 0.56 microgram/ml (range, 0.5 to 1.0 microgram/ml) for amphotericin B. Survival experiments used a 10(5) dose in a pulmonary challenge model with B6C3F(1) mice. All mice that received amphotericin B at 2 mg/kg of body weight every other day (q.o.d.), 30% of mice that received caspofungin at 8 mg/kg/day, and 20% of mice that received caspofungin at 4 mg/kg/day survived to day 15, while mice that received caspofungin at 2 mg/kg/day and all control mice that received the vehicle died by day 14. Amphotericin B at 2 mg/kg q.o.d. markedly reduced the fungal burden in the lungs and spleens, as measured by Histoplasma antigen detection techniques and quantitative cultures, for each comparison. Caspofungin at 10 mg/kg twice a day (b.i.d.) did not reduce the fungal burden, as measured by antigen detection techniques, but slightly reduced the levels of fungi in both the lungs and spleens, as determined by quantitative cultures. Caspofungin at 5 mg/kg b.i.d. did not affect fungal burden. Overall, caspofungin had only a slight effect on survival or fungal burden.

Amphotericin B↗
PubMed1999

Comparison of a new triazole antifungal agent, Schering 56592, with itraconazole and amphotericin B for treatment of histoplasmosis in immunocompetent mice.

A murine model of intratracheally induced histoplasmosis was used to evaluate a new triazole antifungal agent, Schering (SCH) 56592, for treatment of histoplasmosis. MICs were determined for SCH 56592, amphotericin B, and itraconazole by testing yeast-phase isolates from 20 patients by a macrobroth dilution method. The MICs at which 90% of the isolates are inhibited were for 0.019 microgram/ml for SCH 56592, 0.5 microgram/ml for amphotericin B, and < or = 0.019 microgram/ml for itraconazole. Survival studies were done on groups of 10 B6C3F1 mice with a lethal inoculum of 10(5). All mice receiving 5, 1, or 0.25 mg of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every other day (qod), or 75 mg of itraconazole per kg per day survived to day 29. Only 44% of mice receiving 5 mg of itraconazole/kg/day survived to day 29. Fungal burden studies done in similar groups of mice with a sublethal inoculum of 10(4) showed a reduction in CFUs and Histoplasma antigen levels in lung and spleen tissue in animals treated with 2 mg of amphotericin B/kg qod, 1 mg of SCH 56592/kg/day, and 75 mg of itraconazole/kg/day, but not in those treated with lower doses of the study drugs (0.2 mg of amphotericin B/kg qod, 0.1 mg of SCH 56592/kg/day, or 10 mg of itraconazole/kg/day). Serum drug concentrations were measured 3 and 24 h after the last dose in mice (groups of five to seven mice), each treated for 7 days with SCH 56592 (10 and 1 mg/kg/day) and itraconazole (75 and 10 mg/kg/day). Mean levels measured by bioassay were as follows: SCH 56592, 10 mg/kg/day (2.15 micrograms/ml at 3 h and 0.35 microgram/ml at 24 h); SCH 56592, 1 mg/kg/day (0.54 microgram/ml at 3 h and none detected at 24 h); itraconazole, 75 mg/kg/day (22.53 micrograms/ml at 3 h and none detected at 24 h); itraconazole, 10 mg/kg/day (1.33 micrograms/ml at 3 h and none detected at 24 h). Confirmatory results were obtained by high-pressure liquid chromatography assay. These studies show SCH 56592 to be a promising candidate for studies of treatment of histoplasmosis in humans.

Amphotericin B↗
PubMed1999

Prevention of youth injuries.

There are four categories of causes responsible for the majority of injuries in youth 10-19 years of age: 1) motor vehicle traffic; 2) violence (intra-familial, extra-familial, self, pregnancy-related); 3) recreational; and 4) occupational. This article presents data from the National Center for Health Statistics mortality data and the National Pediatric Trauma Registry morbidity data. Nationwide, the pediatric injury death rate is highest among adolescents 15-19 years of age. Motor vehicle-related deaths account for 41% and firearm-related deaths account for 36% of injury deaths in this age group. For youths aged 10-14 years, motor vehicle-related deaths account for 38% and; firearm-related deaths account for 26% of injury deaths. For both age groups, occupant motor vehicle-related deaths account for the majority of deaths and underscore the need for seat belt use. Using theoretical principles based on the Haddon matrix and a knowledge of adolescent development, proposed interventions to decrease injuries and deaths related to motor vehicles and firearms include graduated licensing, occupant restraint, speed limits, conflict resolution, and gun control. Occupational injuries, particularly injury associated with agricultural production, account for an estimated 100,000 injuries per year. Preventive strategies include OSHA regulations imposing standards for protective devices and further study for guidelines for adolescent work in agriculture. Injuries related to recreation include drowning and sports injuries. Preventive strategies may include proper supervision and risk reduction with respect to use of alcohol/drugs. The data presented support the use of primary prevention to achieve the most effective, safe community interventions targeting adolescents.

Accidents, Occupational↗
PubMed1998

Multiple cases of life-threatening adenovirus pneumonia in a mental health care center.

Eighteen cases of pneumonia developed during an outbreak of adenovirus infection in a chronic psychiatric care facility. The six patients most severely affected were admitted to the intensive care unit (ICU) at our institution. Four of these patients developed septic shock. We report the presentation, disease progression, and response to treatment of these patients. Clinical features consisted of high fever, nonproductive cough, and dense lower lobe infiltrates. Laboratory abnormalities included transient fall in white blood cell and platelet counts, and elevations of transaminases, lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK). Five patients were intubated for hypoxemia and four developed the acute respiratory distress syndrome (ARDS) and septic shock (mean cardiac output, 14.1 +/- 1.3 L/min; cardiac index, 6.4 +/- 0.4 L/min/min2; systemic vascular resistance, 326 +/- 107 dyne cm/s2). All patients recovered and were discharged back to the chronic care facility except for one patient with chronic renal failure who died 2 mo after admission. Adenovirus (serotype 35) was isolated from the respiratory secretions of five patients and antibody titers increased 6-fold in the other. These patients constitute the largest series of patients with ARDS and septic shock caused by adenovirus pneumonia and the first outbreak of multiple cases of adenovirus pneumonia in immunocompetent civilian adults occurring from a single source.

Adenoviridae Infections↗
PubMed1997

Impact of risperidone on the use of mental health care resources.

OBJECTIVE: The effects of risperidone treatment on health care utilization and treatment costs were examined among patients with treatment-refractory schizophrenia or schizoaffective disorder. METHODS: Data from the Santa Clara County Mental Health Department were used to measure inpatient and ambulatory services and outpatient medications related to the treatment of mental disorders. Data for 139 patients were analyzed for periods before and after initiation of risperidone treatment. A mean +/- SD of 14 +/- 2.1 months of data were available in both the before and after periods, for a mean total study period of 28 months. RESULTS: The patients' mean age was 40 years (range, 18 to 78 years), and 46 percent were women. After the start of risperidone treatment, days in acute care inpatient facilities were reduced by 26 percent, and days in residential treatment were reduced by 57 percent. These reductions were accompanied by an increase in the use of lower-cost services, such as community living, treatment planning, and partial hospital-day treatment. There was a 3.4 percent increase in total psychiatric health care costs after initiation of treatment with risperidone. CONCLUSIONS: Overall, risperidone treatment resulted in a shift or resource utilization from provider-delivered services to pharmaceutical care without a significant change in total health care cost.

Adolescent↗
PubMed1995

Children who are shot: a 30-year experience.

Three data sets describe the pattern of gunshot injuries to children from 1960 to 1993: The Harlem Hospital pediatric trauma registry (HHPTR), the northern Manhattan injury surveillance system (NMISS) a population-based study, and the National Pediatric Trauma Registry (NPTR). A small case-control study compares the characteristics of injured children with a control group. Before 1970 gunshot injuries to Harlem children were rare. In 1971 an initial rise in pediatric gunshot admissions occurred, and by 1988 pediatric gunshot injuries at Harlem Hospital had peaked at 33. Population-based data through NMISS showed that the gunshot rate for Central Harlem children 10 to 16 years of age rose from 64.6 per 100,000 in 1986 to 267.6 per 100,000 in 1987, a 400% increase. The case fatality for children admitted to Harlem Hospital (1960 to 1993) was 3%, usually because of brain injury, but the majority of deaths occurred before hospitalization. During the same period, felony drug arrests in Harlem increased by 163%. The neighboring South Bronx experienced the same increase in gunshot wound admissions and felony arrests from 1986 to 1993. The NPTR showed a similar injury pattern for other communities in the United States. In a case-control analysis. Harlem adolescents who had sustained gunshot wounds were more likely to have dropped out of school, to have lived in a household without a biological parent, to have experienced parental death, and to have known of a relative or friend who had been shot than community adolescents treated for other medical or surgical problems.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Injury prevention in an urban setting: challenges and successes.

The Harlem Hospital Injury Prevention Program (HHIPP) was established in 1988 with the goal of reducing injuries to children in central Harlem by providing safe play areas, supervised activities, and injury prevention education. To achieve this goal, a broad-based coalition was formed with state and local governmental agencies interested in injury prevention and with community groups, schools, parents, and hospital staff. An evaluation of the program in terms of both process and outcome formed a critical element of this effort. Since 1988 the HHIPP, as the lead agency for the Healthy Neighborhoods/Safe Kids Coalition, developed or participated in two types of programs: injury-prevention education programs and programs that provide safe activities and/or environments for children. The educational programs included Window Guards campaign; Safety City Program; Kids, Injuries and Street Smarts Program (KISS); Burn Prevention Curriculum and Smoke Detector Distribution; Harlem Alternative to Violence Program; Adolescent Outreach Program; and Critical Incident Stress Management Teams. The safe activities and environmental programs included the Bicycle Safety Program/Urban Youth Bike Corps; Playground Injury Prevention Program; the Greening of Harlem Program; the Harlem Horizon Art Studio; Harlem Hospital Dance Clinic; Unity through Murals project; baseball at the Harlem Little League; winter baseball clinic; and the soccer league. Each program was conceived using injury data, coupled with parental concern and activism, which acted as catalysts to create a community coalition to respond to a specific problem. Data systems developed over time, which monitored the prevalence and incidence of childhood injuries in northern Manhattan, including central Harlem, became essential not only to identify specific types of childhood injuries in this community but also to evaluate these programs for the prevention of injuries in children.

Accident Prevention↗
PubMed1994

Computed tomography or endoscopic ultrasonography in preoperative staging of gastric and esophageal tumors.

BACKGROUND: Accurate preoperative staging of tumors of the esophagus and stomach is important in selecting treatment and determining prognosis. To date, no exact preoperative test has been useful in assessing stage of these tumors. Until recently, computed tomographic (CT) scanning has been the most frequently used examination to predict operative findings. Endoscopic ultrasonography (EUS) is a relatively new modality used by some centers to assess extramural anatomy of tumors in these two locations. METHODS: We described 28 patients with tumors involving the esophagus and gastroesophageal junction, and the stomach, who underwent both EUS and CT before surgical exploration. We compared these two tests with the final pathologic interpretation and paid particular attention to presence of lymph nodes and wall penetration by primary tumor. RESULTS: For wall penetration by an esophageal-gastroesophageal junction carcinoma, EUS was 85% accurate versus 15% for CT. For absence of nodal spread by these tumors, EUS was 100% accurate versus 67% for CT. In the presence of nodal spread EUS was 60% accurate versus 50% for CT. For wall penetration by a gastric carcinoma, EUS was 71% accurate versus 0% for CT. In the absence of nodal spread EUS and CT were both 100% accurate. In the presence of nodal spread EUS was 50% accurate versus 25% for CT. CONCLUSIONS: EUS is more accurate than CT in the preoperative staging of upper gastrointestinal malignancies.

Aged↗