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Biomedical subjects

J Fogarty

Publications and source records attributed to J Fogarty.

At least 19 recordsLinked to original sources

Boston naming test short forms: a comparison of previous forms with new item response theory based forms.

Two new short forms of the Boston Naming Test (BNT) were developed using item response theory (IRT) with data from 206 elderly outpatients. We evaluated the diagnostic ability of 12 short forms among the full sample and in a sub-sample of 69 patients diagnosed with mild Alzheimer's disease (AD) either alone or in combination with vascular dementia (VD). The full BNT (reliability alpha = .90) identified 44% of the AD/VD patients as abnormal on naming. Our 30 item short form (alpha = .90) also identified 44% of the AD/VD patients as abnormal, with 93% agreement with the full BNT on abnormal AD/VD patient classifications. Our 15 item short form (alpha = .84) identified 48% of the AD/VD patients as abnormal, with 90% agreement with the full BNT's abnormal classifications. An adaptive 30/15 item version equaled the performance of the full 30 item test while requiring only 15 items for 75% of the patients with normal naming ability. This study illustrates the utility of IRT for developing neuropsychological assessment tools.

Adult↗

Comparison of symptoms related to positioning of double-pigtail stent in upper pole versus renal pelvis.

PURPOSE: This study was a comparison of the symptomatology associated with placement of the upper coil of a double-pigtail stent in the upper pole or the renal pelvis. PATIENTS AND METHODS: A prospective study with 40 patients was performed. In 20 patients, the stent was placed in the upper pole (Group A) and in another 20 patients (Group B) in the renal pelvis. A questionnaire was addressed to all patients before the removal of the stent concerning the presence and severity of flank pain (using a standardized 10-point scale), the presence and severity of urinary urgency (using a standardized 10-point scale), the presence of dysuria, and quality of life with the stent in place. RESULTS: Flank pain was present in 17 (85%) and 15 (75%) patients in Groups A and B, respectively. The average severity of flank pain was 4.3 (range 0-7) and 4.5 (range 0-10) in Group A and B, respectively (p = 0.764). Urinary urgency was present in 13 (65%) and 15 (75%), patients in Group A and B, respectively. The average severity of urgency was 3.1 (range 0-7) and 5.3 (range 0-10) in Group A and B, respectively (p = 0.037). Dysuria was present in 4 (20%) and 13 (65%), and the average quality of life score was 2.5 and 3.05 in Group A and B, respectively (p = 0.04). CONCLUSION: Positioning of the proximal end of the double-pigtail stent in the upper pole of the kidney appears to be better tolerated by patients than is the standard insertion in the renal pelvis.

Adult↗

In vitro bactericidal effect of a modified thermal Nitinol electrode.

PURPOSE: A standard electrode surgical generator connected to a Nitinol coil was used in vitro to evaluate whether the generated electromagnetic energy had any bactericidal effect on Escherichia coli. MATERIALS AND METHODS: The ATCC 259222 E. coli strain was used. We mixed 135 mL of a 1.5% non-nutritive agar with 15 mL of a 10(6) CFU/mL inoculum and transferred it to gas-sterilized plastic containers lined with aluminium foil. A 22F cylindrical shape was cut from the center of the agar, and a Nitinol coil was placed in that space and connected to a standard electrode surgical generator. Electrical energy was then applied from 5 to 25 V at 5-V increments. Temperatures were measured with two thermocouples placed in the middle and periphery of each agar. The treatment was stopped when the temperature at the middle thermometer reached 50 degrees C. The control group was not treated and was embedded in a water bath at 45 degrees C. Three 3 x 7-mm pieces were sliced from the inner to the outer part of the agar and processed, and colony counts were performed. RESULTS: We observed statistically significant deleterious effects on E. coli in all three zones when the treatment voltage was 15 and 20. When the potential was raised to 25 V, we observed a significant result only in the core zone. The treatment duration was 50 minutes for 5 and 10 V, 45 minutes for 15 V, 15 minutes for 20 V, and 10 minutes for 25 V. CONCLUSION: The bactericidal effect was mainly in the central area, decreasing linearly toward the periphery, and was related to the temperature reached during activation of the electrical generator. These results were disappointing with regard to the utility of Nitinol stents to treat bacterial prostatitis.

Alloys↗

What did we learn about leadership in medical education? Effecting institutional change through the Interdisciplinary Generalist Curriculum Project.

The Interdisciplinary Generalist Curriculum (IGC) Project required significant collaboration and cooperation at many levels of leadership to accommodate early clinical experiences in the curriculum. Three elements of institutional change are discussed: the context for desired early clinical experiences in medical education, structural elements required of the IGC Project schools, and leadership within the demonstration schools. Lessons learned from these interdisciplinary projects include the importance of supportive leadership from the top levels, establishing broad buy-in across sectors of the school, creating a team administrative structure that fosters participation by all groups, and central (rather than departmental) administration. The processes needed to establish collaborative leadership and full participation by the generalist departments and cooperation of diverse constituencies, such as basic science faculty, were labor-intensive and required more time to ensure successful program implementation. Uniformly, strong support at the highest levels of the organization, especially the medical schools' deans, was cited as a key element in the success of the IGC Project. An interesting unanticipated outcome of the project was the movement of the interdisciplinary course administration into a central location (dean's office) by the end of the project for all schools. This change may reflect a practical advantage for administration of interdisciplinary programs located at the level of the school or college, rather than housed within departments.

Administrative Personnel↗

The Interdisciplinary Generalist Curriculum Project at the University of Vermont College of Medicine: The Vermont Generalist Curriculum (VGC) Experience.

The University of Vermont College of Medicine received its Vermont Generalist Curriculum (VGC) subcontract as one of the second-cycle Interdisciplinary Generalist Curriculum (IGC) Project schools from 1995 to 1998. The Vermont program was jointly codirected by the chairs of family practice and pediatrics and the program director for internal medicine on a rotating basis and was overseen by a multidisciplinary steering committee that included generalists, basic scientists, specialists, and students. This committee provided guidance and support in recruitment of preceptors, continuous assessment and improvement of the courses, development of a clinical correlation manual for students in clinical offices, and cooperation around a jointly sponsored annual primary care meeting that included a joint scientific program, a research forum, and a faculty development workshop. The VGC has provided a pilot for many innovative curricular changes that have served as models for the school-wide curriculum redesign process currently under way at VERMONT: While the funding for this project ended in 1998, the changes, innovations, and collaboration born out of the project are valuable enough for the dean's office to maintain the VGC's funding and its steering committee for the future.

Curriculum↗

Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era.

BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib) disease caused by the widespread use of conjugate vaccines, non-type b H. influenzae will become a more important cause of H. influenzae (Hi) disease. Characterization of the clinical and epidemiologic features of non-b Hi disease is needed in the Hib vaccine era. METHODS: A prospective active surveillance study of invasive Hi disease involving pediatricians in the United Kingdom and Republic of Ireland. For the first phase of the study (October 1, 1992, to October 31, 1995) pediatricians were asked to report any child who had invasive Hi disease and who had received Hib conjugate vaccine. For the second phase of the study (November 1, 1995. To December 31, 1998) pediatricians were asked to report any child with invasive Hi disease regardless of vaccination status. RESULTS: During the study period 102 cases of invasive non-type b Hi disease and 106 cases of invasive Hib disease were reported in children who had been fully vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22 months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than children with type b disease. For the last 2 years of the study invasive Hi disease occurring in a fully vaccinated child was more likely to be caused by a non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi is a rare cause of disease in children, but in the Hib vaccine era it has become more common than type b as a cause of Hi disease in fully vaccinated children.

Age Factors↗

Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood.

Haemophilus influenzae type b (Hib) conjugate vaccines have proved extremely efficacious in healthy children. True Hib vaccine failures are rare. Hib conjugate vaccines were introduced for routine immunization in the United Kingdom and the Republic of Ireland in 1992. Coincident with this, active prospective and national surveillance via pediatricians, microbiologists, and public health physicians was commenced to assess the clinical and immunological factors associated with vaccine failure. During the 6 years of the study, 115 children with true vaccine failure were reported. Of the children who were vaccinated before 12 months of age, a clinical risk factor was detected in 20%, an immunological deficiency was detected in 30%, and one or both were detected in 44%. Children who were vaccinated after 12 months of age were more likely to have one or both factors (67%). Thirty percent (33 of 105) of children with true vaccine failure had a low Hib antibody response (concentration, <1.0 microg/mL) after disease, but the majority then responded to a further dose of Hib vaccine. Children who develop Hib disease despite vaccination deserve further clinical and immunological evaluation.

Adolescent↗

Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial.

The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).

Adolescent↗

Invasive Haemophilus influenzae in the Republic of Ireland.

Prior to the general availability of Haemophilus influenzae type b vaccine in the Republic of Ireland, a two-year study of the epidemiology of invasive Haemophilus influenzae disease was carried out. Of 137 invasive strains of Haemophilus influenzae examined in a central laboratory, 94.2% were serotype b and 90.5% were biotype I. Seventeen percent of serotype b strains produced beta-lactamase, and 2.3% were resistant to both ampicillin and chloramphenicol. The majority of serotype b strains were electrophoretic types of the electrophoretic 12 clone family, principally 12.5. Meningitis was the most common infection caused by serotype b. The study data extend the current knowledge of strains of Haemophilus influenzae causing invasive disease in the Republic of Ireland.

Anti-Bacterial Agents↗

Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS.

OBJECTIVES: We hypothesized that advanced glycation end product (AGE) formation contributes to erectile dysfunction (ED) by quenching nitric oxide. Our first goal was to identify the specific AGE pentosidine in the diabetic human penis. Because AGE-mediated effects may involve inducible nitric oxide synthase (iNOS), we performed immunohistochemical and Western blot analysis of diabetic and nondiabetic human penile tissue for iNOS. Finally, because AGEs may act intracellularly to affect proteins, we set out to identify endothelial NOS (eNOS) in the human penis as an initial step in examining a possible intracellular interaction between eNOS and AGEs. METHODS: We performed high-performance liquid chromatographic analysis of diabetic human penile corpus cavernosum and serum for pentosidine and performed immunohistochemical, electron microscopic (EM), and Western blot analysis of the diabetic and nondiabetic penile corpus cavernosum and tunica for pyrraline, iNOS, and eNOS (and neural NOS [nNOS] for comparative purposes) via standard methods. RESULTS: We found a significant elevation of pentosidine in the penile tissue but not the serum of diabetic patients (average age 55.6 +/- 2.3 years) compared with that of nondiabetic patients (average age 61.8 +/- 3.6 years). Pentosidine was 117.06 +/- 9.19 pmol/mg collagen in the diabetic tunica versus 77.58 +/- 5.5 pmol/mg collagen in the nondiabetic tunica (P < 0.01) and 74.58 +/- 8.49 pmol/mg collagen in the diabetic corpus cavernosum versus 46.59 +/- 2.53 pmol/mg collagen in the nondiabetic corpus cavernosum (P < 0.01), suggesting a tissue-specific effect of the AGEs. We localized the site of deposition of the specific AGE pyrraline to the human penile tunica and the penile corpus cavernosum collagen. Immunohistochemical and EM analysis localized eNOS and iNOS to the cavernosal endothelium and smooth muscle. Western blot analysis in 6 patients revealed the following: iNOS, but no eNOS, in penile tissue from 1 insulin-dependent diabetic man; eNOS only in 1 man after radical prostatectomy; both eNOS and iNOS in 2 men with Peyronie's disease, as well as in 2 other men with impotence and hypertension. Finally, the specific iNOS inhibitor PNU-19451A significantly augmented relaxation of precontracted human cavernosal tissue, from 64.7% +/- 5.58 to 80.03% +/- 4.55 at 10 microM acetylcholine and 65.06% +/- 2.84 to 86.16% +/- 3.96 at 0.1 mM acetylcholine (n = 4, P < 0.002 and P < 0.02, respectively). CONCLUSIONS: AGEs are elevated in diabetic human penile tissue, but not in serum, and are localized to the collagen of the penile tunica and corpus cavernosum. We identified eNOS and iNOS in the human penile cavernosal smooth muscle and endothelium. The augmentation of cavernosal relaxation with a specific iNOS inhibitor, combined with the identification of iNOS protein, but not eNOS, in a patient with severe diabetes and ED, allows for speculation of a pathophysiologic mechanism for AGE-mediated ED via upregulation of iNOS and downregulation of eNOS. These data provide further insight into the mechanisms of advanced glycation end product-mediated ED and provide a foundation for further study.

Adult↗

Ten-year survival of Down syndrome births.

OBJECTIVE: To determine the survival status of children with Down syndrome (DS), and to document factors influencing survival. DESIGN: Follow-up study of cases identified from the Dublin European Register of Congenital Anomalies and Twins (EUROCAT) Register. Follow-up was attempted for each case until death or 1992 or until the date last known to be alive. SETTING: Eastern Health Board, Dublin. SUBJECTS: In all, 389 DS children, born between 1 January 1980 and 31 December 1989 were followed up. RESULTS: Survival rates of 88% at one year and 82% at 10 years were found. There was a non-significant improvement in survival between the cohort born in 1980-1984 and that born in 1985-1989. Congenital heart defects reduced survival to 72% and complete atrio-ventricular canal defects (CAVD) had the poorest prognosis (58% survival at 10 years). Cases with CAVD showed a trend towards improved survival when surgically treated. Maternal age mother's county of residence, sex of infant, season of birth and presence of additional non-cardiac congenital anomalies had no impact on survival. CONCLUSIONS: Four out of five DS children now survive at least 10 years. Adequate educational and health service provision needs to be made for them, especially those with congenital heart defects. The need for studies which compare survival and quality of life in DS children with CAVD who undergo cardiac surgery versus those who do not, taking account of various selection factors, is identified.

Child↗

Screening of patients with iron overload to identify hemochromatosis and porphyria cutanea tarda.

OBJECTIVE: To assess the importance of iron overload as a risk factor for porphyria cutanea tarda (PCT). DESIGN: Prospective study during a 4-month period. SETTING: Departments of emergency care, gastroenterology, and dermatology in a tertiary referral center. PATIENTS: Patients were deemed eligible for inclusion in the study if serum ferritin levels were greater than 500 micrograms/L (normal range: females, < 125 micrograms/L; males, < 325 micrograms/L). MAIN OUTCOME MEASURES: Porphyrin excretion profiles were analyzed on all patients included in the study, where clinically relevant. A diagnosis of PCT was confirmed biochemically in all cases. The HLA typing was then performed on newly diagnosed cases of PCT. RESULTS: Of 4127 patients tested, 240 patients with an elevated serum ferritin level were identified, of whom 74 had an elevated serum ferritin level of more than 500 micrograms/L. Of the latter group, 17.5% had hemochromatosis and 6.7% had PCT. The incidence of PCT in the hemochromatosis group was 23%; HLA typing revealed the presence of at least 1 of the hemochromatosis markers. CONCLUSIONS: A high serum ferritin level in the absence of evident cause should prompt investigation for both hemochromatosis and PCT. The HLA heterozygosity for hemochromatosis in some patients with PCT may be a cause of hepatic siderosis.

Adult↗

Porphyrin metabolism in hepatitis C infection.

Hepatitis C virus has been implicated as a major precipitating factor in porphyria cutanea tarda (PCT). To determine whether hepatitis C infection alone is sufficient to induce PCT, we screened two groups of patients with hepatitis C infection. The first group comprised women who had become HCV positive secondary to immunization with anti-D immunoglobulin (group 1). Group 2 included males and females who were HCV positive but HIV negative secondary to intravenous drug abuse. Though both groups had very abnormal liver function tests, we found no significant abnormalities in porphyrin metabolism in these groups of patients. Therefore, in this study population, we conclude that HCV infection alone is insufficient to cause porphyrin metabolic derangement.

Adolescent↗

Evidence of a glycemic threshold for the formation of pentosidine in diabetic dog lens but not in collagen.

The relationship between long-term glycemic control and the advanced Maillard reaction was investigated in dura mater collagen and lens proteins from dogs that were diabetic for 5 years. Diabetic dogs were assigned prospectively to good, moderate, and poor glycemic control and maintained by insulin. Biochemical changes were determined at study exit. Mean levels of collagen digestibility by pepsin decreased (NS) whereas collagen glycation (P < 0.001), pentosidine cross-links (P < 0.001), and collagen fluorescence (P = 0.02) increased with increasing mean HbA1 values. Similarly, mean levels of lens crystallin glycation (P < 0.001), fluorescence (P < 0.001), and the specific advanced lens Maillard product 1 (LM-1) (P < 0.001) and pentosidine (P < 0.005) increased significantly with poorer glycemic control. Statistical analysis revealed very high Spearman correlation coefficients between collagen and lens changes. Whereas pentosidine cross-links were significantly elevated in collagen from diabetic dogs with moderate levels of HbA1 (i.e., 8.0 +/- 0.4%), lens pentosidine levels were normal in this group and were elevated (P < 0.001) only in the animals with poor glycemic control (HbA1 = 9.7 +/- 0.6%). Thus, whereas protein glycation and advanced glycation in the extracellular matrix and in the lens are generally related to the level of glycemic control, there is evidence for a tissue-specific glycemic threshold for pentosidine formation, i.e., glycoxidation, in the lens. This threshold may be in part linked to a dramatic acceleration in crystallin glycation with HbA1 values of > 8.0% and/or a loss of lens membrane permeability. This study provides support at the molecular level for the growing concept that glycemic thresholds may be involved in the development of some of the complications in diabetes.

Animals↗

Porphyrin abnormalities in acquired immunodeficiency syndrome.

OBJECTIVE: To examine prospectively porphyrin metabolism in a human immunodeficiency virus (HIV)-positive population. SETTING: Specialist referral unit at the Department of Genitourinary Medicine, St James's Hospital, Dublin, Ireland. PATIENTS: Twenty-eight men and 5 women (age range, 18-35 years). Twenty-nine were current or previous intravenous drug abusers. Four were thought to have sexually acquired HIV infection. All had a history of acquired immunodeficiency syndrome-defining illnesses. The patients were selected as a consecutive sample from the inpatient department. Eligibility criteria were cooperation with urine and stool collection and confirmed HIV seropositivity. The patients were matched to 2 groups: 1 with normal results of porphyrin studies and the other with abnormal findings from porphyrin studies. INTERVENTION: None. MAIN OUTCOME MEASURES: Plasma, urine, and stool porphyrin excretion patterns. RESULTS: Of the 33 patients in the study, 13 (40%) had increased urinary porphyrin excretion. All but 2 of these patients were seropositive for hepatitis C virus. No study patient had clinical evidence of porphyria. Four patients (12%), however, had urine and stool porphyrin excretion patterns that were classic for porphyria cutanea tarda. All 4 of these patients were hepatitis C virus-positive. Patients with porphyrinuria had a greater degree of immunosuppression (P = .002) than those with normal porphyrin metabolism, and they were more likely to be taking zidovudine (P = .009). CONCLUSIONS: Commonly, porphyrin metabolism is abnormal in persons with established HIV infection. Hepatitis C may contribute to abnormal porphyrin metabolism. An unexpected number of patients studied had porphyrin excretion patterns that were characteristic of porphyria cutanea tarda, and all of these were hepatitis C virus-positive. A diagnosis of porphyria cutanea tarda, especially in a young patient, should prompt investigation for underlying HIV and hepatitis C virus infections. Dermatologists should be aware of the infectious risk associated with the vesicles and erosions in these patients. Porphyrin studies should be performed in any patient with HIV and photosensitivity.

Acquired Immunodeficiency Syndrome↗

The risk of hepatitis A from sewage contamination of a water supply.

The drinking water supply of a town became contaminated with sewage. The town's population was surveyed to determine the baseline prevalence of hepatitis A antibodies and to establish whether an associated outbreak of hepatitis A had occurred. Samples of saliva were obtained from 540 people in 200 randomly selected households, and tested for IgG and IgM antibodies to hepatitis A. Fifty-six per cent (279/495) were susceptible to hepatitis A and 43% (213/495) immune as a result of previous infection. Immunity was directly related to age; those who were immune were significantly older than those who were susceptible (mean ages: 43.5 years and 19.0 years; p < 0.0001). Six people were found to have had a recent infection with hepatitis A, but exposure to hepatitis A during the water pollution incident was possible in only one case. The results offer no evidence that this incident caused an outbreak of hepatitis A, but the study has provided useful epidemiological data on hepatitis A.

Adolescent↗