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Biomedical subjects

D McGrath

Publications and source records attributed to D McGrath.

At least 19 recordsLinked to original sources
PubMed2003

Is there a role for microorganisms in the pathogenesis of sarcoidosis?

Sarcoidosis is a granulomatous disease that has the immunopathological features of being antigen-driven. It is a complex disease that appears to arise from the interaction of one or more triggers with an immunologically predisposed host. Previous reports of familial clustering and varying prevalence of sarcoidosis in different populations could reflect differences in ethnic predisposition or differences in local environmental exposures. This review focuses specifically on these areas that have been the subjects of intensive investigation recently. Specific focus is provided on the issue of an infective trigger and highlights popular candidates. It is concluded that microbes are a likely trigger (but not as an infection) in a genetically predisposed individual and that this initial event culminates in the sarcoidosis granulomatous response.

Bacterial Infections↗
PubMed2001

High beryllium-stimulated TNF-alpha is associated with the -308 TNF-alpha promoter polymorphism and with clinical severity in chronic beryllium disease.

Beryllium (Be)-antigen stimulates tumor necrosis factor-alpha (TNF-alpha) from bronchoalveolar lavage (BAL) cells in chronic beryllium disease (CBD). This study tested the hypothesis that high concentrations of Be-stimulated TNF-alpha are related to polymorphisms in the TNF-alpha promoter and clinical markers of disease severity in CBD. Demographic and clinical information was obtained from patients with CBD (n = 20). TNF-alpha concentrations were measured in BAL cell culture supernatant by ELISA. A priori, we categorized CBD subjects as either high or low TNF-alpha producers using a cutoff of 1,500 pg/ml. The TNF-alpha promoter sequence, +64 to -1045, was determined by direct sequencing. Human leukocyte-associated antigen (HLA)-DPB1 and -DRB1 genotyping was determined by polymerase chain reaction (PCR). High Be-stimulated TNF-alpha was associated with TNF2 alleles, Hispanic ethnicity, presence of HLA-DPB1 Glu69, and absence of HLA-DR4. Be-stimulated TNF-alpha concentrations correlated with markers of disease severity, including chest radiograph, beryllium lymphocyte proliferation, and spirometry. We found no novel TNF-alpha promoter polymorphisms. These data suggest that the TNF2 A allele at -308 in the TNF-alpha promoter region is a functional polymorphism, associated with a high level of Be-antigen-stimulated TNF-alpha and that these high TNF-alpha levels indicate disease severity in CBD.

Antigens↗
PubMed2001

Disinfection efficacy of contact lens care solutions against ocular pathogens.

PURPOSE: Three commercially available products labeled as multi-purpose contact lens solutions, one multi-purpose disinfecting solution, and a hydrogen peroxide system were evaluated for antimicrobial activity according to the current International Organization for Standardization (ISO) and the U.S. Food and Drug Administration (FDA) stand-alone procedure for disinfecting products. One multi-purpose solution was selected to assess its antimicrobial activity against two human corneal isolates of Pseudomonas aeruginosa. METHODS: Products were challenged with bacteria and fungi, and following a specified period, aliquots of inoculated test solution were neutralized and plated on validated recovery media. After incubation the number of viable microorganisms was enumerated and mean log reductions determined. RESULTS: ReNu MultiPlus (Bausch & Lomb, Rochester, NY), AOSEPT (CIBA Vision Corporation, Duluth, GA), and Opti-Free Express with Aldox (Alcon Laboratories, Ft. Worth, TX) were the only lens care products that met the stand-alone criteria for all required microorganisms within their minimum recommended disinfection time. Of these, ReNu MultiPlus provided the greatest overall antimicrobial activity. ReNu MultiPlus demonstrated a significantly higher mean log reduction of Staphylococcus aureus and Serratia marcescens than Opti-Free Express. ReNu MultiPlus also gave a higher mean log reduction of S. aureus and S. marcescens than AOSEPT, and a higher mean log reduction of Candida albicans and Fusarium solani than AOSEPT, Complete Comfort Plus (Allergan, Irivine, CA), and Solo-Care (CIBA Vision Corp.) (at 4 hours). Both Complete Comfort Plus and Solo-Care (at 4 hours) met the primary acceptance criteria for bacteria; however, neither product possessed enough antimicrobial activity to meet the minimum criteria for yeast or mold. ReNu Multiplus was effective against corneal isolates of P. aeruginosa. CONCLUSION: ReNu MultiPlus, AOSEPT, and Opti-Free Express met the requirements of the stand-alone primary criteria for disinfecting solutions. ReNu MultiPlus demonstrated the greatest overall disinfection efficacy, as well as excellent activity against clinical strains of P. aeruginosa.

Anti-Bacterial Agents↗
PubMed2000

Atovaquone and azithromycin for the treatment of babesiosis.

BACKGROUND: Babesiosis is a tick-borne, malaria-like illness known to be enzootic in southern New England. A course of clindamycin and quinine is the standard treatment, but this regimen frequently causes adverse reactions and occasionally fails. A promising alternative treatment is atovaquone plus azithromycin. METHODS: We conducted a prospective, nonblinded, randomized trial of the two regimens in 58 subjects with non-life-threatening babesiosis on Nantucket, on Block Island, and in southern Connecticut. The subjects were assigned to receive either atovaquone (750 mg every 12 hours) and azithromycin (500 mg on day 1 and 250 mg per day thereafter) for seven days (40 subjects) or clindamycin (600 mg every 8 hours) and quinine (650 mg every 8 hours) for seven days (18 subjects). RESULTS: Adverse effects were reported by 15 percent of the subjects who received atovaquone and azithromycin, as compared with 72 percent of those who received clindamycin and quinine (P<0.001). The most common adverse effects with atovaquone and azithromycin were diarrhea and rash (each in 8 percent of the subjects); with clindamycin and quinine the most common adverse effects were tinnitus (39 percent), diarrhea (33 percent), and decreased hearing (28 percent). Symptoms had resolved three months after the start of therapy in 65 percent of those who received atovaquone and azithromycin and 73 percent of those who received clindamycin and quinine (P=0.66), and after six months no patient in either group had symptoms. Three months after the completion of the assigned regimen, no parasites could be seen on microscopy, and no Babesia microti DNA was detected in the blood of any subject. CONCLUSIONS: For the treatment of babesiosis, a regimen of atovaquone and azithromycin is as effective as a regimen of clindamycin and quinine and is associated with fewer adverse reactions.

Adult↗
PubMed2000

The copper transport protein Atox1 promotes neuronal survival.

Atox1, a copper transport protein, was recently identified as a copper-dependent suppressor of oxidative damage in yeast lacking superoxide dismutase. We have previously reported that Atox1 in the rat brain is primarily expressed in neurons, with the highest levels in distinct neuronal subtypes that are characterized by their high levels of metal, like copper, iron, and zinc. In this report, we have transfected the Atox1 gene into several neuronal cell lines to increase the endogenous level of Atox1 expression and have demonstrated that, under conditions of serum starvation and oxidative injury, the transfected neurons are significantly protected against this stress. This level of protection is comparable with the level of protection seen with copper/zinc superoxide dismutase and the anti-apoptotic gene bcl-2 that had been similarly transfected. Furthermore, neuronal cell lines transfected with a mutant Atox1 gene, where the copper binding domain has been modified to prevent metal binding, do not afford protection against serum starvation resulting in apoptosis. Therefore, Atox1 is a component of the cellular pathways used for protection against oxidative stress.

Amino Acid Sequence↗
PubMed2000

Impact of laparoscopic staging in the treatment of pancreatic cancer.

HYPOTHESIS: Staging laparoscopy in patients with pancreatic cancer identifies unsuspected metastases, allows treatment selection, and helps predict survival. DESIGN: Inception cohort. SETTING: Tertiary referral center. PATIENTS: A total of 125 consecutive patients with radiographic stage II to III pancreatic ductal adenocarcinoma who underwent staging laparoscopy with peritoneal cytologic examination between July 1994 and November 1998. Seventy-eight proximal tumors and 47 distal tumors were localized. INTERVENTIONS: Based on the findings of spiral computed tomography (CT) and laparoscopy, patients were stratified into 3 groups. Group 1 patients had unsuspected metastases found at laparoscopy and were palliatedwithout further operation. Group 2 patients had no demonstrable metastases, but CT indicated unresectability due to vessel invasion. This group underwent external beam radiation with fluorouracil chemotherapy followed in selected cases by intraoperative radiation. Patients in group 3 had no metastases or definitive vessel invasion and were resection candidates. MAIN OUTCOME MEASURE: Survival. RESULTS: Staging laparoscopy revealed unsuspected metastases in 39 patients (31.2%), with 9 having positive cytologic test results as the only evidence of metastatic disease (group 1). Fifty-five patients (44.0%) had localized but unresectable carcinoma (group 2), of whom 2 (3.6%) did not tolerate treatment, 20 (36.4%) developed metastatic disease during treatment, and 21 (38.2%) received intraoperative radiation. Of 31 patients with potentially resectable tumors (group 3), resection for cure was performed in 23 (resectability rate, 74.2%). Median survival was 7.5 months for patients with metastatic disease, 10.5 months for those receiving chemoradiation, and 14.5 months for those who underwent tumor resection (P = .01 for group 2 vs. group 1; P<.001 for group 3 vs group 1). CONCLUSIONS: Staging laparoscopy, combined with spiral CT, allowed stratification of patients into 3 treatment groups that correlated with treatment opportunity and subsequent survival. Among the 125 patients, laparoscopy obviated 39 unnecessary operations and irradiation in patients with metastatic disease not detectable by CT. Laparoscopic staging can help focus aggressive treatment on patients with pancreatic cancer who might benefit.

Aged↗
PubMed1998

Adenovirus infection in adult orthotopic liver transplant recipients: incidence and clinical significance.

Adenovirus infection occurs in 10% of pediatric orthotopic liver transplant recipients; however, no cases have been described in adult liver transplant recipients. A retrospective review of 191 adults who underwent liver transplantation from January 1988 through October 1995 was done to describe the incidence and clinical significance of adenovirus infection in this population. There were 11 (5.8%) patients with 16 cultures positive for adenovirus. Sites of isolation were urine (9), blood (2), liver biopsy (2), colonic biopsy (1), lung biopsy (1), and stool (1). Adenovirus infection was classified as either disease or asymptomatic infection. There were 7 cases of adenovirus disease (2 definite, 1 probable, and 4 possible). Disease was disseminated in 3 patients: All had pneumonia and 2 died. Of the 3 patients with pneumonia, 2 had evidence of multiorgan involvement. Adenovirus disease occurs in adult orthotopic liver transplant recipients and may be associated with significant morbidity and occasional mortality.

Adenoviridae↗
PubMed1998

Débridement and closed packing for the treatment of necrotizing pancreatitis.

OBJECTIVE: To evaluate the results of débridement and closed packing for necrotizing pancreatitis and to determine the optimal timing of surgical intervention based on patient outcomes. METHODS: Between February 1990 and November 1996, 64 consecutive patients with necrotizing pancreatitis were treated with necrosectomy followed by closed packing of the cavity with stuffed Penrose and closed suction drains. The mean APACHE II score immediately before surgery was 9, and 31% of the patients had organ failure. Patients were stratified with an outcome score based on death and major complications; this was correlated with the timing of surgical intervention. The data were then subjected to cut-point analysis by sequential group comparison. RESULTS: Patients underwent surgery a median of 31 days after diagnosis. Fifty-six percent had infected necrosis. The mortality rate was 6.2% and was no different in infected or sterile necrosis. Eleven patients required a second surgical procedure and 13 required percutaneous drainage; a single surgical procedure sufficed in 69%. Enteric fistulae occurred in 16% of patients. The mean hospital stay after surgery was 41 days, and the interval until return to regular activities was 147 days. A significant negative correlation between duration of pancreatitis and outcome scores was found, and sequential group comparison demonstrated that the change point at which significantly better outcomes were encountered was day 27. CONCLUSION: Débridement of pancreatic necrosis followed by closed packing and drainage is accomplished with a low mortality rate and reduced rates of complications and second surgical procedures. Although intervention is best deferred until the demarcation of necrosis is complete, delay beyond the fourth week confers no additional advantage.

APACHE↗
PubMed1996

Improving the copy numbers of antibody fragments expressed on the major coat protein of bacteriophage M13.

BACKGROUND: Antibody fragments have been expressed on the major coat protein of filamentous phage using a gene VIII expression system, but with low copy numbers (averaging 0.2 Fab/phage). OBJECTIVES: As a general strategy to increase copy number, the phage vector was optimized by site directed mutagenesis. STUDY DESIGN: One mutation was the introduction of a random six amino acid tether between the heavy chain and pseudo gene VIII to form a phage library. The other mutation was the removal of two cysteine residues which form a disulfide bond between the heavy and light chains. An assay was developed to measure Fab concentrations and used to calculate the average number of copies displayed on phage. RESULTS: Phage libraries containing random tethers were panned, and clones containing a proline rich motif were extracted. Removing the interchain disulfide had a greater effect on copy number and soluble Fab concentrations in the periplasmic space of the bacterial cultures. CONCLUSION: A tenfold increase in the copy number was achieved using the optimized vector. Incorporation of these vector mutations may be a general strategy for optimizing Fab display on the major coat protein of bacteriophage M13.

Bacteriophage M13↗
PubMed1996

Rollerblading in children: the Edinburgh experience.

OBJECTIVE: To determine the incidence and severity of injuries sustained by children who present to an accident and emergency (A&E) department following rollerblading accidents. DESIGN: A prospective case-control study. SETTING: The A&E department of a city centre paediatric teaching hospital. METHODS: Data were collected on a specially designed proforma on each child presenting with an injury sustained while rollerblading. The injury severity score was calculated for each patient and details were taken of the length of admission or outpatient follow up where appropriate. RESULTS: Seventy four children (37 male; 37 female) presented with injuries over a three month period. The age range was 6-13 years in both groups. Half the injuries occurred at weekends. Fractures (n = 37) and soft tissue injuries (n = 28) were the most prevalent; 89% of injuries involved the limbs. Sixty eight children (92%) required treatment in A&E. Four (3%) were admitted to hospital and required operative procedures under general anaesthetic. The injury severity score ranged from 1 to 9 with a mean of 2.8. The length of hospital stay for admissions was 1-3 days; 47 children required follow up in the outpatient department (1-3 visits). Average length of outpatient contact was 18 days. CONCLUSIONS: This study shows a greater incidence of rollerblading injuries than has been reported elsewhere. No figures are at present available for the United Kingdom as a whole.

Adolescent↗
PubMed1994

The measurement of alcohol dependence and impaired control in community samples.

The concept of the Alcohol Dependence Syndrome has been influential in the field of alcohol studies in the 1980s. The Severity of Alcohol Dependence Questionnaire (SADQ) is one of a generation of alcohol problem scales developed to measure degree of dependence rather than presence or absence of 'alcoholism'. This paper describes the development of a form of the SADQ for community samples of drinkers (SADQ-C) and its relationship to a brief scale designed to measure impaired control over drinking. In a sample of 52 problem drinkers, SADQ and SADQ-C correlated almost perfectly (r = 0.98). In a larger sample of 197 attenders at a controlled drinking clinic, Principal Components Analysis revealed one major factor accounting for 71.7% of the total variance. High internal reliability was indicated with a Cronbach's Alpha of 0.98. Application of this instrument in a random survey of Western Australian households is then described. It was necessary to remove items relating to 'reinstatement of dependence' for this sample. A single major factor was identified by principal components analysis, accounting for 69.1% of the total variance. In both the clinic and the community samples SADQ-C scores correlated highly with Impairment of Control scores. The findings are interpreted as supporting the view that there is a single dimension of alcohol dependence upon which all persons who drink alcohol with any regularity may be located.

Adolescent↗
PubMed1994

Clival marrow changes in AIDS: findings at MR imaging.

PURPOSE: To determine the prevalence and clinical significance of marrow changes in the clivus identified at magnetic resonance (MR) imaging in patients with the acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: MR images of the head of 119 patients with AIDS and 119 control subjects were retrospectively reviewed. Marrow signal intensity patterns in the clivus of each patient were evaluated and scored as type 1 (homogeneous high signal intensity on T1-weighted images [normal]), type 2 (heterogeneous low signal intensity on T1-weighted images [abnormal]), or type 3 (homogeneous low signal intensity on T1-weighted images [abnormal]) and correlated with clinical parameters including CD4 counts, evidence of previous systemic disease, and presence of coexistent disease on corresponding MR head images. RESULTS: Abnormal clival signal intensity (type 2 and 3) was observed in 64 (54%) patients with AIDS and nine (7.5%) control subjects (P < .001), correlating with both a marked decrease in CD4 count (P < .001) and the presence of systemic disease (P < .001). CONCLUSION: Clival marrow signal abnormality is commonly identified in patients with AIDS and may be a marker of advanced disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Analysis of a measles outbreak in Kent County, Michigan in 1990.

New recommendations from the Immunization Practices Advisory Committee call for a second dose of measles vaccine for school age children. The purpose of this paper is to demonstrate the need for additional measures for the protection of preschool age children. A hospital-based measles outbreak of 25 cases in Kent County, MI, in 1990 provided an opportunity to study measles transmission to preschool age children. Twenty-two (88%) were people who had never received measles vaccine. Twelve of the cases were unvaccinated preschoolers, seven of whom were older than 15 months. Three nonvaccinated, but eligible people (one philosophic exemption and two vaccine-eligible preschoolers) were the source of most of the other cases. One school age unvaccinated child died of measles pneumonitis. A telephone survey indicated that improved public education regarding indications and contraindications to vaccination might encourage vaccination of children according to public health recommendations.

Adolescent↗
PubMed1992

Meaning of craving in research on addiction.

The meaning of the word craving varies as illustrated by Kozlowski and Wilkinson's reports of ambiguities in use amongst cigarette smokers. We extended this line of investigation to problem drinkers who sought a goal of controlled drinking versus abstinence, to professionals involved in the addictions area, and to university students. Significant differences in meaning were noted particularly among the problem drinkers (N = 256 between 17 and 60 years of age). Reasons for this are offered.

Adolescent↗