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Biomedical subjects

P O'Regan

Publications and source records attributed to P O'Regan.

17 recordsLinked to original sources

Two formulations of the industrial surfactant, Toximul, differentially reduce mouse weight gain and hepatic glycogen in vivo during early development: effects of exposure to Influenza B Virus.

Previous studies demonstrated that young mice exposed chronically to industrial surfactant (IS) do not exhibit obvious adverse health effects, but do have persistently reduced body weights and compromised hepatic energy metabolism. The present study examined the time course of effects of two formulations of the Toximul (Tox) class of anionic/nonionic IS on body weights and liver glycogen (+/-virus) during early development. Results showed that effects differed in two commonly used strains of mice. In CFW mice, 12 days' exposure to Tox resulted in retardation of weight gain that was most obvious several days after exposure ceased. In this strain effects were greater with Tox 3409F than with Tox MP-A and appeared to be reversible except when the mice were treated with both Tox 3409F and FluB. Weights of the CD-1 mice were not affected by either Tox treatment alone, but were significantly reduced on postnatal day 20 when Tox exposure had been combined with FluB infection. Postnatal replenishment of hepatic glycogen stores during the first three weeks also occurred at different rates in CFW and CD-1 mice. The effects of Tox (+/-FluB) on glycogen also varied with mouse strain and Tox formulation. In CFW mice, exposure to either formulation resulted in significant (55-59%) reductions in glycogen, although reductions were not evident until nine days after Tox exposure stopped. By contrast, hepatic glycogen in CD-1 mice was reduced both during and after dermal exposure to Tox 3409F, whereas no effect was observed with Tox MP-A. Notably, the 3409F effect was reversible in the CD-1 mice, but reversal did not occur in mice also infected with FluB. Tox MP-A+FluB-treated mice exhibited only a transient glycogen reduction. These results illustrate the importance of mouse strain and formulation specificities in assessing biological effects of xenobiotic surfactants. As well, they emphasize that chronic IS exposure can induce changes in growth and energy substrate availability in young mice that may not be evident unless there is a precipitating cofactor such as a viral infection.

Animals↗

Serious lead poisoning in childhood: still a problem after a century.

OBJECTIVE: To describe a series of patients with clinically significant lead poisoning. METHODOLOGY: A case series of nine patients with lead poisoning who required inpatient management, identified through a Clinical Toxicology Service. RESULTS: Nine children presented with clinically significant lead poisoning. The median serum lead was 2.5 micro mol/L (range 1.38-4.83). Eight of the children were exposed to lead-based paint, with seven due to dust from sanded lead paint during house renovations. Serial blood determinations suggested re-exposure in four of the patients, and in one of these patients the re-exposure was from a different source of lead. Eight of the patients required chelation therapy. CONCLUSIONS: Serious lead poisoning continues to occur and there appears to be complacency regarding the hazard posed by lead paint in old houses.

Chelation Therapy↗

Coeliac disease and autoimmune Addison's disease: a clinical pitfall.

BACKGROUND: Coeliac disease has an increased prevalence in a number of autoimmune endocrine conditions. An association between coeliac disease and Addison's disease has been proposed in isolated case reports, but has not been formally studied. AIM: To investigate the extent of this association. DESIGN: Prospective screening of patients with confirmed Addison's disease. METHODS: From central computerized records, we identified all living patients with a diagnosis of autoimmune Addison's disease in the past 30 years and presently attending our affiliated hospitals. After exclusions, 44 were invited to attend for screening. RESULTS: Of 41 patients screened, five (12.2%) had coeliac disease: Three were previously diagnosed coeliacs and this was confirmed on review, including examination of biopsy material. A further two had positive IgA-endomysial antibodies. Histological confirmation was obtained in both cases. Neither had laboratory or clinical evidence of malabsorption. DISCUSSION: In this series of patients with Addison's disease, a higher co-morbidity with coeliac disease was observed than in any previously studied endocrine condition. We recommend that coeliac serology (anti-endomysial and tissue transglutaminase antibody) testing be incorporated routinely into the autoimmune screen for other conditions in patients with Addison's disease.

Addison Disease↗

XRCC2 is a nuclear RAD51-like protein required for damage-dependent RAD51 focus formation without the need for ATP binding.

The human XRCC2 gene was recently identified by its ability to complement a hamster cell line, irs1, which is sensitive to DNA-damaging agents and shows genetic instability. The XRCC2 protein is highly conserved in mammalian species and has structural features, including a putative ATP-binding domain (P-loop), consistent with membership of the RecA/RAD51 family of recombination-repair proteins. We show that a hybrid XRCC2-green fluorescent protein, which was found to be functional by complementation, localizes to the nucleus. We have established a functional link between XRCC2 and RAD51 by looking at damage-dependent RAD51 focus formation in the irs1 cell line. Little or no formation of RAD51 foci occurred in irs1. This effect was specific to the loss of XRCC2 because transfection of the gene into irs1 restored normal levels of focus formation. Surprisingly, XRCC2 genes carrying site-specific mutations in P-loop residues were found to be able to complement the XRCC2-deficient irs1 line for a number of different end points. We conclude that XRCC2 is important in the early stages of homologous recombination in mammalian cells to facilitate RAD51-dependent recombination repair but that it does not make use of ATP binding to promote this function.

Adenosine Triphosphate↗

MALTectomy (appendectomy/tonsillectomy) does not influence the occurrence or mode of presentation of adult celiac disease.

OBJECTIVE: Recent reports suggest that appendectomy may protect against the development of ulcerative colitis. Depletion of mucosal helper T-cells is the suggested mechanism. Because mucosal T-cell activity has an even more critical role in the pathogenesis of celiac disease, our objective was to determine whether the development or mode of presentation of this disorder is influenced by appendectomy and/or tonsillectomy. METHODS: One hundred fifty consecutive adult celiac patients were compared with 138 consecutive patients examined at orthopedic clinics. One hundred twenty consecutive patients with ulcerative colitis from the same ethnogeographic population were included as positive disease control. RESULTS: Contrary to the previous findings in ulcerative colitis, which were again confirmed in this study, appendectomy and/or tonsillectomy did not influence the occurrence of celiac disease. In addition, presenting features, predefined in the study protocol, did not differ significantly in the appendectomy and nonappendectomy celiac patients. CONCLUSION: Resection of mucosa-associated lymphoid tissue (MALT) does not influence the occurrence or the mode of presentation of adult celiac disease. Therefore, in this classical example of a T-cell-mediated disorder, the hypothesis that surgical depletion of mucosal T-cells has a protective effect or influences the clinical manifestations cannot be supported.

Adult↗

Melanocytic naevi and melanoma in survivors of childhood cancer.

There is evidence from previous studies of small numbers of children who received cytotoxic therapy for cancer, that they may develop increased numbers of melanocytic naevi (moles), the strongest known risk factors for melanoma. Our aim was to investigate a large number of survivors of childhood cancer in order to test the hypothesis that they have more melanocytic naevi than matched controls. Total-body naevus counts were obtained from 263 oncology patients ascertained in paediatric oncology departments in Queensland, Australia, and from 263 hospital controls matched for age and sex. Additional information was gathered from children's parents about concurrent factors influencing naevus development such as type of complexion and history of sun exposure. Matched analyses, both crude and adjusted for possible confounding factors, revealed no significant difference in overall density of naevi among oncology patients and control subjects, according to diagnosis or to duration or type of chemotherapy. However significantly more oncology patients had atypical naevi (P < 0.05) and acral naevi (P < 0.0001) than controls. One patient developed a malignant melanoma 13 years after chemotherapy and radiotherapy for rhabdomyosarcoma. These findings support an association between treatment for childhood cancer and acral naevi and suggest that atypical naevi may also be associated with chemotherapy in childhood.

Adolescent↗

A provincial hospital C.C.U. after ISIS 2.

A prospective study of admissions to an Irish provincial coronary care unit in the light of reported benefits of streptokinase and oral aspirin as reported in the Isis study was carried out. Of 115 patients admitted with suspected myocardial infarction (M.I.), the diagnosis was confirmed in 41. The average delay from onset of chest pain to admission to C.C.U. was 6.65 hours (0.3-18 hours, median 6 hours). Twenty-six of the 41 patients were given streptokinase after a median time lapse of six hours from the onset of pain. 88% of the M.I. patients were on oral aspirin at discharge but only 12% were on oral beta blockers. These findings are compared with the findings of the Isis 2 study worldwide and in Ireland. The presence of risk factors in the patients with M.I. is analysed, 16 of the 41 had serum cholesterol levels greater than 6 mmols/l. As an index of community risk factor screening, an enquiry was made of the patients and of their family doctor as to whether serum cholesterol had previously been checked, this had been done in only 12 of 41 and in only 2 had it been carried out by the family doctor. Pre-hospital analgesic use was also examined and 36 of the 41 patients had chest pain and were seen by their G.P.s but only 18 were given analgesics of whom 13 received morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Alloimmune neonatal neutropenia in Australian aboriginals: an unrecognized disorder?

Alloimmune neonatal neutropenia (ANN) is reported for the first time in two Australian aboriginals. Both infants displayed the typical clinical features of ANN with profound neutropenia which persisted for 7 weeks and only minor infectious episodes. However, management strategies differed for the two infants because in one case (complicated by uncertain paternity) serological confirmation of ANN was not obtained until after recovery of the infant's neutrophil count. The maternal antibodies could not be assigned to known neutrophil antigen specificities and a new antigen may be involved. The antibodies were reactive with > 99% of neutrophils in a Caucasian population. Aboriginals comprise 1% of the total population of Australia and 1-2% of the obstetric population at our institution. Thus, ANN may be an unrecognized disorder in this ethnic group and a possible cause of neonatal infection and mortality.

Antibody Specificity↗

Cerebral astrocytoma as a complication of acute lymphoblastic leukaemia.

A boy who developed acute lymphoblastic leukaemia at the age of two years and 10 months had several central nervous system relapses, and received two courses of cranial irradiation, each of 24 Gy, in addition to systemic and intrathecal chemotherapy. Nearly 10 years after the onset of his leukaemia he developed a brain stem astrocytoma from which he died. This appears to be a rare occurrence, and the role of the treatment in the induction of his second tumour is discussed. The need for the long-term follow-up of cancer patients after apparent cure is emphasized.

Astrocytoma↗

Captopril for refractory hypertension in patients with impaired renal function.

The use of captopril in 19 patients with renal parenchymal disease and refractory hypertension was studied for a mean period of 12 months. There was a significant reduction in the systolic and diastolic blood pressures, with a reduction in the mean arterial pressure of 29 mmHg. The mean maintenance dose of captopril was 142 mg daily in three divided doses. All but one of the patients required a diuretic for satisfactory blood pressure control and 3 patients were also given a beta-blocker. In all patients a simplification of the previous therapeutic regimen was achieved. A significant rise in serum creatinine was noted in 2 patients, one of whom had to be withdrawn from the study. Despite the presence of renal functional impairment, proteinuria did not occur de novo nor did established proteinuria increase. Leukopenia was noted in any of the patients in this group.

Blood Pressure↗

Successful renal transplantation in primary hyperoxaluria.

A successful live related renal transplant in a 29-year-old male patient with Type 1 primary hyperoxaluria, who remains well 32 months postoperatively, is described. The plasma oxalate and exchangeable oxalate pool before transplantation were 160 mumol/1 and 4429 mumol respectively. Since the transplant these have been greatly reduced although they remain elevated above the normal by a factor of 2. Pyridoxine therapy and the avoidance of oxalate-rich foods have been effective in maintaining these reduced levels and the 24-hr urinary oxalate excretion has also been maintained close to normal levels on this regime. After review of the previously reported transplants in patients with well documented primary hyperoxaluria and from the experience with this patient, the following guidelines for successful renal transplantation in primary hyperoxaluria are suggested: transplants should only be carried out in those who have shown a response to adequate pyrodoxine therapy; frequent haemodialysis pre-operatively and during periods of oliguria postoperatively is necessary; oxalate-rich foods should be avoided and a high fluid intake should be maintained after transplantation. If these guidelines are followed there is no contra-indicatin to live related renal transplants in primary hyperoxaluric patients.

Adult↗

Plasma level and renal clearance of oxalate in normal subjects and in patients with primary hyperoxaluria or chronic renal failure or both.

1. Plasma oxalate has been measured by a radioisotopic method applicable to all concentrations of plasma oxalate and renal function, and also by an enzymatic method which was only applicable to raised concentrations of plasma oxalate. 2. Where the two methods could be applied simultaneously, the agreement between them was good. 3. Plasma oxalate was 86% ultrafiltrable at concentrations of up to 44 micromol/l. 4. Oxalate clearance and the exchangeable oxalate pool were also measured. The ratio of oxalate clearance to creatinine clearance was greater than unity in most normal subjects and patients. 5. These methods were used in normal subjects and in patients with primary hyperoxaluria and/or chronic renal failure. A raised plasma oxalate concentration was found in both conditions. Chronic renal failure is probably the most common cause of a raised plasma oxalate.

Adult↗

Uncensored open access gastroscopy--limited resources--unlimited demand.

In the first 3 yr of an uncensored open access gastroscopy service in a County Hospital, 891 patients attended for first gastroscopy. The data on these patients is presented and compared with a randomly selected group who attended for gastroscopy in the yr prior to the establishment of the service having come to the normal Consultant clinics. In the open access group the gastroscopy examination was normal in 29 per cent (32 per cent comparator group), 31 per cent had major abnormalities (33 per cent comparator group) and 40 per cent had minor abnormalities (35 per cent comparator group). Delay time from referral to endoscopy was 37 days for open access patients (45 days comparator group). Only 6 per cent of open access patients were brought back to O.P.D. (47 per cent comparator group) and 72 per cent of open access patients returned directly to their family doctor (28 per cent comparator group). A comparison of the Clonmel findings with British centres reporting their results shows a broadly similar picture. It is concluded that almost 1,300 unnecessary clinic visits were avoided by the provision of the open access service, some reduction in delay time to gastroscopy was achieved, the family doctor maintained control of patient management in the great majority of patients, the pattern of referral was not inappropriate and compared very well with the comparator group. Over the 3 yr there was a large increase in the number of gastroscopies performed which caused resource difficulties. It is recommended that adequate planning of these requirements should be carried out before an open access service is started. At least 1 additional dedicated gastroscopy only endoscopy service per week would be required.

Gastroscopy↗