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Biomedical subjects

J Fogarty

Publications and source records attributed to J Fogarty.

At least 37 records · Page 2Linked to original sources

Age-related increase in an advanced glycation end product in penile tissue.

Nonenzymatic glycosylation (glycation) of proteins, often referred to as the Maillard reaction, has been proposed to play a role in age and diabetes-related processes by forming protein and DNA adducts and cross-links. These cross-links may contribute to erectile dysfunction by scavenging nitric oxide, which is needed for erection. As the basis for a possible role of the advanced Maillard reaction in age-related erectile dysfunction, we investigated the presence of the specific advanced glycation endproduct (AGE) pentosidine in penile corpus cavernosum tissue and penile tunica albuginea tissue as a function of age. A total of 23 penile tissue specimens were obtained at autopsy, from which 19 samples of tunica albuginea and 21 samples of corpus cavernosum were derived. In addition, 13 penile corporal and tunical specimens were procured at the time of insertion of a penile prosthesis, from which 12 tunica albugineal specimens and 10 samples of corpus cavernosum were derived. Collagen was extracted with acetic acid and pepsin digestion, and the final insoluble collagen product was acid-hydrolyzed with 6 N HCL for 24 h at 110 degrees C. Pentosidine was quantified by high-performance liquid chromatography using a reverse-phase column. The level of pentosidine (expressed in picomoles per milligram of insoluble collagen) was found to increase with age in cadaver as well as living penile corporal and tunical albugineal tissues. Best-fit analysis revealed an exponential increase in both types of cadaver penile tissue, with regression equations of y = 15.29 x 10(9.9e-3x), R2 = 0.79, being obtained in the tunica and y = 13.2 x 10(7.63e-3x), R2 = 0.56, in the corpora. These correspond to 6- and 4-fold increases in pentosidine levels from puberty to the age of 100 years (P < 0.05), respectively. Mean pentosidine levels were higher in the tunica than in the corpora. Comparison of pentosidine levels in the tunica versus the corpora revealed a weakly linear correlation (y = 24.88 + 1.08x, R2 = 0.32). Levels in the tunical and corporal specimens from the living human specimens fell with the predicted confidence intervals of the cadaveric tissue. Tunical specimens from patients who underwent repair or revision of a previously inserted penile prosthesis had very low levels of pentosidine. The exponential age-related increase in pentosidine observed in both types of penile tissue suggests an impairment of collagen turnover, which could be related to the advanced glycation reaction in aging. It is not known whether pentosidine itself is directly associated with erectile dysfunction, but its formation is usually accompanied by extensive tissue modification. Formation of advanced Maillard reaction products, which is greatly accelerated in aging, diabetes, and uremia, could contribute to erectile dysfunction in these syndromes.

Adult↗

The epidemiology of Haemophilus influenzae type b disease in the Republic of Ireland.

A 2-year case-control study was conducted to describe the epidemiology of Haemophilus influenzae type b (Hib) and investigate Hib disease risk factors in the Republic of Ireland. Between October 1991 and September 1993. 149 laboratory confirmed incident cases were matched with community controls. Annual Hib disease incidence was 25.4 per 100,000 children under 5 years, with peak incidence (65.8 per 100,000) in the 6-11 months age-group. Meningitis was the predominant clincial condition. Twenty-four (16.1%) isolates were resistant to ampicillin. Crèche or day-care attendance and the presence of chronic illness emerged as risk factors for Hib disease. Empirical first line treatment for suspected Hib infection warrants alternatives to ampicillin such as cefotaxime. Completed immunization with Hib conjugate vaccine by 6 months of age is required for maximum disease prevention. Until all children are receiving Hib vaccine on schedule, those who are crèche or day-care attendees and those with chronic illness should be prioritized for timely immunization.

Adolescent↗

Illness in a community associated with an episode of water contamination with sewage.

Following an episode of water contamination with sewage in a rural Irish town, a community-wide survey of gastrointestinal-associated illness and health service utilization was conducted. Random sampling of households yielded residents who were surveyed using a self-administered questionnaire. Of 560 respondents from 167 (84%) households, equal proportions lived in areas known to have been exposed and unexposed to the contaminated water, although 65% of subjects reported using contaminated water. Sixty-one percent of subjects met the case definition. The most common symptoms among cases were abdominal cramps (80%), diarrhoea (75%), appetite loss (69%), nausea (68%) and tiredness (66%). Mean duration of illness was 7.4 days. Only 22% of cases attended their general practitioner. Drinking unboiled water from the exposed area was strongly associated with being a case. A substantial degree of community illness associated with exposure to contaminated water was observed. The episode ranks as one of the largest reported water-borne outbreaks causing gastrointestinal illness in recent times.

Disease Outbreaks↗

Intestinal mucosal mononuclear cell chimaerism after sex-mismatched allogeneic bone marrow transplantation.

The contribution of haemopoietic cell chimaerism to the pathogenesis of GVHD after BMT is unclear. This report raises the possibility that donor lymphocyte-recipient macrophage chimaerism may occur shortly after allogeneic marrow engraftment and hence might contribute to the development of GVHD. Immunohistological studies of intestinal mucosa in an allogeneic BMT patient, who did not engraft, revealed an almost complete absence of lymphocytes 30 days after transplant, but preservation of mucosal macrophage numbers. Subsequently, combined immunohistology-Y chromosome in situ hybridization studies were performed in two female BMT recipients of male donor marrow. These studies revealed that between 25 and 40% of macrophages and between 25 and 40% of T lymphocytes were of donor origin during the first 6 months after transplant. In conclusion, whilst the immunohistological studies of intestinal mucosa from a patient who failed to engraft suggest that donor lymphocyte-recipient macrophage ('split') chimaerism may occur shortly after marrow engraftment, the subsequent in situ hybridization studies revealed 'mixed' chimaerism in the two sex-mismatched BMT recipients.

Adult↗

Meningococcal disease in childhood--a regional study in Ireland.

A retrospective study of microbiology laboratory records of culture-confirmed cases of meningococcal disease in children under 14 years of age, admitted to four Dublin hospitals, was conducted for the period 1981-1991 inclusive. The study aimed to describe the epidemiology of meningococcal disease in childhood and to assess the potential of meningococcal group A and C vaccine in preventing disease. There were 406 cases of meningococcal disease of which 319 (78.6%) were in children under 5 years of age. The meningitis to septicaemia ratio was almost 4:1 (320 vs. 86 cases). Of the 406 cases, 216 (53.2%) cases occurred during the period November to March. The age-specific annual incidence rates for the Eastern Health Board region served was 64.2 per 100,000 under 1 year of age and 24.6 per 100,000 under 5 years of age. A relative increase in disease caused by meningococcal serogroup C was observed during the period of the study. Only 15% all cases could have been prevented by a policy of universal meningococcal group A and C immunisation at 2 years of age. Such a policy, therefore, is not recommended. A vaccine for preventing disease caused by meningococcal group B is urgently required.

Adolescent↗

Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM.

Pentosidine is an advanced glycosylation end product and protein cross-link that results from the reaction of pentoses with proteins. Recent data indicate that long-term glycation of proteins with glucose also leads to pentosidine formation through sugar fragmentation. In this study, the relationship between the severity of diabetic complications and pentosidine formation was investigated in collagen from skin-punch biopsies from 25 nondiabetic control subjects and 41 IDDM patients with diabetes duration greater than 17 yr. Pentosidine was significantly elevated in all IDDM patients versus control subjects (P less than 0.0001). It correlated strongly with age (P less than 0.0001) and weakly with duration (P less than 0.082). Age-adjusted pentosidine levels were highest in grade 2 (severe) versus grade 1 and 0 complication in all four parameters tested (retinopathy, proteinuria, arterial stiffness, and joint stiffness). Significant differences were found for retinopathy (P less than 0.014) and joint stiffness (P less than 0.041). The highest degree of association was with the cumulative grade of individual complication (P less than 0.005), determined by summing indexes of all four parameters. Pentosidine also was significantly elevated in the serum of IDDM patients compared with control subjects (P less than 0.0001), but levels were not significantly correlated with age, diabetes duration, complication, or skin collagen pentosidine (P greater than 0.05). A high correlation between pentosidine levels and long-wave collagen-linked fluorescence also was observed, suggesting that pentosidine is a generalized marker of accelerated tissue modification by the advanced glycosylation/Maillard reaction, which is enhanced in IDDM patients with severe complications.

Adult↗

Chromatographic quantitation of plasma and erythrocyte pentosidine in diabetic and uremic subjects.

Pentosidine is a fluorescent advanced Maillard/glycosylation product and protein cross-link present in elevated amounts in skin from diabetic and uremic subjects. A high-performance liquid chromatographic (HPLC) assay was developed to quantitate pentosidine in plasma and erythrocytes and other tissue proteins with low levels of pentosidine. High protein content and presence of basic amino acids and O2 during acid hydrolysis led to the formation of fluorescent artifacts that could be separated from true pentosidine through combined reverse-phase ion-exchange HPLC. No true pentosidine was formed during acid hydrolysis of ribated protein, suggesting that Amadori products do not generate artifactual pentosidine during hydrolysis. With the combined reverse-phase ion-exchange chromatographic assay, we found a 2.5-fold (P less than 0.001) and a 23-fold (P less than 0.001) elevation of mean +/- SD plasma protein pentosidine in diabetic (2.4 +/- 1.2 pmol/mg) and uremic (21.5 +/- 10.8 pmol/mg) subjects compared with healthy (0.95 +/- 0.33 pmol/mg) subjects. Pentosidine in hemolysate was normal in diabetes but dramatically elevated in uremia (0.6 +/- 0.4 pmol/mg hemoglobin, P less than 0.001). Although the precise nature of the pentosidine precursor sugar is unknown, plasma pentosidine may be a useful marker for monitoring the biochemical efficacy of trials with aminoguanidine or other treatment modalities. Furthermore, pentosidine in plasma proteins may act as a signal for advanced glycosylation end product-mediated receptor uptake by macrophages and other cells and contribute to accelerated atherosclerosis in diabetes and uremia.

Analysis of Variance↗

Assessment of the nutritional status of rural and urban elderly living at home.

Assessment of nutritional status was conducted on a selected sample of 46 rural and 24 urban elderly people living at home in Galway. Nutrient intake was assessed by the 24 hour dietary recall method. Blood tests and anthropometric measurements were also carried out. Both subject groups, but particularly the rural elderly were discovered to have deficient intake of many nutrients when compared to 80% of the Irish Recommended Dietary Allowances. Blood tests of nine haematological and biochemical parameters with values below the lower limit of the adult laboratory references range were rarely found. Anthropometric values below recognized standards were common. Sub-optimal nutritional status was present to a greater degree in subjects living in the geographically isolated rural area but inadequate nutrition was also detected in the city-dwelling elderly. Education of these elderly people on better dietary intake should be conducted and increased social contact encouraged. Provision of improved transport and communication facilities for the rural elderly studied may aid improvement in their nutritional status. While results of this study suggest that undernutrition is a problems in this group, a more representative sample of elderly people needs to be studied to ascertain the true prevalence of undernutrition in the elderly.

Aged↗

Pentosidine: a molecular marker for the cumulative damage to proteins in diabetes, aging, and uremia.

Collagen undergoes progressive browning with age and diabetes characterized by yellowing, fluorescence, and cross-linking. The present research was undertaken in order to investigate the nature of the collagen-linked fluorescence. Human collagen was exhaustively cleaved into peptides by enzymatic digestion. Upon purification, a highly fluorescent chromophore was identified and purified from old human collagen. Structure elucidation revealed the presence of an imidazo [4,5-b] pyridinium-type structure acting as a cross-link between arginine, lysine, and a pentose. This advanced glycosylation end-product and protein cross-link results from the reaction of pentoses with proteins and was named pentosidine. Further work indicated that long-term glycosylation of proteins with hexoses also leads to pentosidine formation through sugar fragmentation. The proposed mechanism of pentosidine formation involves the dehydration of the pentose-derived Amadori compound to form an intermediate which is attacked under base catalysis by the guanido group of arginine. The strict requirement for the Amadori rearrangement is uncertain. However, oxidation is definitely involved since pentosidine is not formed in the absence of oxygen. Five-carbon sugars contributing to pentosidine formation could be formed from larger sugars by oxidative fragmentation or from trioses, tetroses, and ketoses by condensation and/or reverse aldol reactions. Pentosidine increases exponentially in human skin at autopsy. Mean age-adjusted skin levels were significantly increased in subjects with uremia and especially in type 1 diabetics with uremia vs. controls. In skin biopsy, levels were significantly elevated in all diabetic (type 1) vs. control subjects. The highest degree of association was with the cumulative grade of diabetic complication (retinopathy, nephropathy, arterial stiffness, and joint stiffness). Pentosidine also forms in various proteins other than collagen, although to a much lesser extent. In blood, pentosidine is mainly associated with plasma proteins and is highly elevated during uremia. In the lens, it is associated with both water-soluble and -insoluble protein fractions and is especially elevated during brunescent cataract formation. The origin of pentosidine in vivo is uncertain. Evidence suggests that the pentoses are the most reactive sugars in pentosidine formation in vitro; however, the origin and importance of free pentoses in vivo, especially during the diabetic state, are not certain. Possible origins include hemolysis and/or a defect in the primary pentose metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Behavioural risk factors among young adults in small areas with high mortality versus those in low-mortality areas.

A community-based cross-sectional survey of behavioural risk factors for premature mortality was carried out on a group of 354 adults aged 25-44 from previously identified high-mortality 'black-spots' in Dublin who were compared with 333 others from low-mortality areas. In the black-spot areas, 50.9% of respondents were current smokers versus 28.5% in low-mortality areas and 14.6% took 'sufficient' exercise versus 31.4% in low-mortality areas. People living in black spots were also less likely to make 'healthy' dietary choices than those in low-mortality areas. There is a higher prevalence of behavioural risk factors for premature mortality among young adults living in electoral wards/district electoral divisions (DEDs) with high standardized mortality ratios (SMRs) from all causes than among those in areas with low SMRs. A health promotion programme aimed at increasing exercise levels, reducing smoking and encouraging healthy eating should be aimed at young adults in DEDs with high SMRs.

Adult↗

Knowledge about AIDS among Leaving Certificate students.

A self-administered anonymous questionnaire on knowledge about acquired immunodeficiency syndrome (AIDS) was administered to 2,614 Leaving Certificate students in 50 Galway second-level schools. Levels of knowledge regarding routes of human immunodeficiency virus (HIV) transmission and non-transmission were assessed together with student opinion on related lifestyle issues and awareness of local services. Although 91% had heard of HIV infection only 61% knew that there is a difference between this and AIDS. Over 95% of respondants were aware of the epidemiologically proven means of transmission and between 73% and 98% understood that no transmission risk existed in a range of ordinary social contact situations. Fifty-one per cent of students believed in a HIV transmission risk from receiving blood transfusions in Ireland and 24% doubted the safety of blood donation. Seventy-four per cent of students indicated the media as their main information source on AIDS. Preference for further AIDS information were Health Education sources (30%) and teachers (20%). Only 22% and 23% of respondants respectively were aware of the local Sexually Transmitted Diseases Clinic and AIDS telephone information service. These data indicate areas in which information on AIDS should be improved by education in the school setting.

Acquired Immunodeficiency Syndrome↗

Impact of crime on the rural elderly.

Two hundred and seven persons over 65 years of age were interviewed to determine the impact of crime on their lives. The setting was during a much publicized series of assaults on the rural elderly in their homes. Seventy two per cent were upset, 40% of the total were moderately upset and 26% suffered a major upset. Females and those over 75 years old were most upset. Some aspect of change of lifestyle was found in the vast majority.

Age Factors↗

Complication of prolonged transpyloric feeding: formation of an enterocutaneous fistula.

Enteral feeding tubes have been associated with perforations of the gastrointestinal tract, usually requiring surgical repair. A neonate with centronuclear myopathy developed an enterocutaneous fistula from the duodenum following prolonged placement of a transpyloric catheter. He did not require surgery and died later of unrelated complications.

Duodenal Diseases↗

A new surgical approach to fractures of the lateral tibial plateau.

We are reporting on a previously undescribed surgical approach and postoperative protocol for the treatment of fractures of the lateral tibial plateau in which there is a split pattern and depression of the articular surface. In this approach the anterior horn of the lateral meniscus is incised and detached so that the split fragment can be opened like a book. Detachment and incision of the anterior horn minimizes the need to free the lateral meniscus from its tibial attachment. The postoperative protocol includes continuous passive motion followed by non-weight-bearing in a toe-to-groin plaster cast for three months. Our preliminary results have been encouraging, and arthroscopic examination in the seven knees so studied indicated a healed fracture, restoration of the tibial articular surface, and a healed lateral meniscus.

Adult↗

Can self-administered questionnaires supplant objective testing of erectile function? A comparison between the International Index Of Erectile Function and objective studies.

To determine whether the results of the self-reported International Index of Erectile Function (IIEF) to assess erectile function can overestimate the degree of erectile impairment. A total of 32 consecutive patients seeking treatment for erectile dysfunction (ED) at a urologist's office were evaluated by completion of the erectile function domain of the IIEF. Nocturnal penile tumescence testing using the Rigiscan (Timm Medical Technologies Inc., USA) was performed in these patients after completion of the IIEF. The median IIEF-6 score was 9 of 30 (range, 1-25; mean, 11/30). Rigiscan results were abnormal in six patients (19%), normal in 25 patients (78%), and unable to interpret in one patient (3%). IIEF-6 scores were subdivided by severity along with Rigiscan results. There was no correlation between age, IIEF score, or Rigiscan results. In conclusion, the IIEF is a useful tool and is helpful for follow-up of a patient to evaluate efficacy of treatments for ED, but should not replace objective testing to diagnose the quality of ED.

Adult↗