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M Carmody

Publications and source records attributed to M Carmody.

At least 19 recordsLinked to original sources
PubMed2001

FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels.

This study compared the relative levels of ryanodine receptor (RyR) isoforms, inositol 1,4,5-trisphosphate receptor (IP(3)R) isoforms, and calcineurin, plus their association with FKBP12 in brain, skeletal and cardiac tissue. FKBP12 demonstrated a very tight, high affinity association with skeletal muscle microsomes, which was displaced by FK506. In contrast, FKBP12 was not tightly associated with brain or cardiac microsomes and did not require FK506 for removal from these organelles. Furthermore, of the proteins solubilised from skeletal muscle, cardiac muscle and brain microsomes, only skeletal muscle RyR1 bound to an FKBP12-glutathione-S-transferase fusion protein, in a high affinity FK506 displaceable manner. These results suggest that RyR1 has distinctive FKBP12 binding properties when compared to RyR2, RyR3, all IP(3)R isoforms and calcineurin.

Animals↗
PubMed2001

Dysfunctional intracellular calcium homoeostasis: a central cause of neurodegeneration in Alzheimer's disease.

The clinical symptoms of all forms of Alzheimer's disease (AD) result from a slowly progressive neurodegeneration that is associated with the excessive deposition of beta-amyloid (A beta) in plaques and in the cerebrovasculature, and the formation of intraneuronal neurofibrillary tangles, which are composed primarily of abnormally hyperphosphorylated tau protein. The sequence of cellular events that cause this pathology and neurodegeneration is unknown. It is, however, most probably linked to neuronal signal transduction systems that become misregulated in the brains of certain individuals, causing excessive A beta to be formed and/or deposited, tau to become aggregated and hyperphosphorylated and neurons to degenerate. We hypothesize that a progressive alteration in the ability of neurons to regulate intracellular calcium, particularly at the level of the endoplasmic reticulum, is a crucial signal transduction event that is linked strongly to the initiation and development of AD pathology. In this chapter we will discuss the key findings that lend support to this hypothesis.

Alzheimer Disease↗
PubMed1997

Cutaneous abnormalities and metabolic disturbance of porphyrins in patients on maintenance haemodialysis.

Blistering disorders may occur in patients with chronic renal failure. Photoactive medication may account for some, and others may be attributable to porphyria cutanea tarda (PCT), but most appear idiopathic. Seventy haemodialysis patients at the National Renal Transplant Centre were therefore screened to determine the prevalence of cutaneous disease and to establish a reference range for plasma porphyrins in this population. The possible contribution of hepatitis C virus (HCV) infection to increased porphyrin levels in this group was also investigated. Ninety four percent of patients on haemodialysis had dermatoses associated with chronic uraemia, and the plasma porphyrin levels in those patients (mean +/- 2 S.D.: 19.1 +/- 13.5 nmol/L) were significantly higher than those of a normal population (n = 40; mean +/- 2 S.D.: 5.5 +/- 3.2 nmol/L) (p < 0.05). Only 2 patients (2.9%), however, had antibodies to HCV and although three others had blistering on light-exposed skin, none of these had PCT or was on photoactive medication, nor did they differ from the rest of the haemodialysis population with regard to erythropoietin or alcohol ingestion. For patients on haemodialysis, therefore, in whom urinary porphyrin estimation is impossible or unreliable, it is recommended that plasma porphyrin profiles be checked where necessary with reference to the range for a haemodialysis population, in addition to assessment of the faecal porphyrin profile. Abnormal porphyrin levels in this group may not, however, be explained by HCV infection, but the occurrence of blistering on the sun-exposed sites of 3 patients suggests that ultraviolet radiation may be implicated in those instances.

Adolescent↗
PubMed1996

Allele-specific hybridization of lipoprotein lipase and factor-V Leiden missense mutations with direct label alkaline phosphatase-conjugated oligonucleotide probes.

Direct label alkaline phosphatase (AP) conjugated oligonucleotide probes (AP-DNA) were prepared to assess their utility for allele-specific detection of single base substitutions. Oligonucleotide conjugates were designed to detect point mutations in the genes for lipoprotein lipase (LPL) and coagulation factor-V (FV). Genomic DNA samples, including ones known to harbor point mutations in the genes for LPL and FV, were prepared from whole blood and subjected to polymerase chain reaction (PCR). PCR products were analyzed by Southern hybridization with the allele-specific AP-DNA probes and restriction endonuclease analysis. Thermal profiles for hybridization indicate optimal allele-specific selectivity was achieved with temperatures ranging from 45 degrees C to 55 degrees C at a total Na divided by concentration of 150 mM. Under these conditions the base changes studied were easily discriminated with allele specific hybridization signals in excess of 200:1 as estimated by scanning densitometry. Complete concordance was observed between hybridization and restriction analyses for 175 LPL and 201 FV clinical and reference samples. The total time for analysis of the PCR products was less than 2 h with a dot blot hybridization protocol.

Alkaline Phosphatase↗
PubMed1996

Effect of hydrochlorothiazide on the pharmacokinetics of enalapril in hypertensive patients with varying renal function.

An open, randomised, cross-over study was performed to investigate the pharmacokinetics of enalaprilat, administered as 20 mg enalapril both as monotherapy and in combination with hydrochlorothiazide (HCTZ 12.5 mg). Three groups of 6 hypertensive patients were enrolled [untreated diastolic blood pressure (DBP) 90-115 mm Hg]; normal renal function [glomerular filtration rate (GFR) > 81 ml min-1 1.73 m-2], mild renal impairment (GFR 51-80 ml min-1 1.73 m-2), and moderate renal impairment (GFR 31-50 ml min-1 1.73 m-2). The pharmacokinetics of enalaprilat and enalaprilat plus HCTZ correlated predictably with renal impairment with increased plasma concentrations and decreased urinary elimination at lower values of GFR. The coadministration of HCTZ had no significant effect on the pharmacokinetics of enalaprilat in any group. We conclude that although the pharmacokinetics of both enalaprilat and HCTZ are related to renal function, HCTZ has no significant effect on the pharmacokinetics of enalaprilat and that dosage adjustment for both regimens should be based on renal function.

Adult↗
PubMed1995

Glomerulonephritis after ventriculo-atrial shunt.

We describe five patients with glomerulonephritis (GN) associated with cerebrospinal fluid shunt insertion to relieve hydrocephalus. A ventriculo-atrial (V-A) shunt had been placed on average 12.5 years prior to the diagnosis of nephritis (range 0.5-21 years). Four patients developed membranoproliferative glomerulonephritis (MPGN) with associated hypocomplementaemia. A single patient developed focal proliferative glomerulonephritis. Coagulase-negative staphylococci were cultured in four patients, either from blood or from the shunt. Four patients had their shunts removed, two of whom also received antibiotics. The other patient received antibiotics alone for infective endocarditis due to staphylococcal bacteraemia which originated in the shunt. All patients had substantial renal impairment at the time of diagnosis (GFR, glomerular filtration rate, 20-45 ml/min). There was significant improvement in renal function after appropriate treatment; four of the five patients doubled their GFRs and two patients regained normal function.

Adolescent↗
PubMed1994

Antiglomerular basement membrane disease: the long-term pulmonary outcome.

We have evaluated long-term pulmonary function in 14 patients who were treated for anti-glomerular basement membrane disease at our institution during the last 17 years. Eight of these patients had evidence of pulmonary involvement, as manifested by hemoptysis, pulmonary infiltrates on chest x-ray film, or anemia. These patients were compared with a control group of 15 patients who had renal disease and who were matched for degree and duration of renal disease, age, smoking history, and method of renal replacement. The following variables were measured in each patient: forced vital capacity, forced expiratory volume in 1 minute, vital capacity, total lung capacity, residual volume, functional residual capacity, single-breath carbon monoxide transfer factor, and single-breath carbon monoxide transfer factor corrected for alveolar volume (KCO). These patients also participated in a graded exercise test and measurements of oxygen uptake, carbon dioxide production, minute ventilation, and oxygen saturation were taken. Patients with anti-glomerular basement membrane disease and a prior history of pulmonary hemorrhage had a significantly reduced KCO (46% +/- 10% v 68.7% +/- 14.7%) compared with the control group. There was no difference in any of the other measured parameters.

Adult↗
PubMed1993

Lower prevalence of anti-hepatitis C antibody in dialysis and renal transplant patients in Ireland.

It is well recognised that haemodialysis and renal transplant patients are at increased risk of developing non-A, non-B hepatitis. Recently the genome of hepatitis C virus (HCV), the major causative agent for non-A, non-B hepatitis, has been isolated. Anti-HCV seroprevalence was assessed in all haemodialysis patients (266) in Ireland who in March 1990 had been dialysed for at least 6 months. For comparative purposes, 272 patients who had functioning renal transplants for greater than 6 months were also studied. Potential risk factors such as age, number of blood transfusions and time on dialysis were evaluated. The prevalence of HCV infection as evidenced by antibody detection was only 1.1% for transplant and 1.7% for haemodialysis patients. This compares to a reported incidence of between 10% and 50% found elsewhere. Two of the 5 anti-HCV positive haemodialysis patients and 2 of the 3 transplant patients had biochemical evidence of liver disease. From stored sera it was possible to ascertain when patients acquired HCV. Whether the very low prevalence of anti-HCV in Irish patients is due to the low prevalence of the virus in the general population, the policy of non reimbursement of blood donors, genetic or other factors, remains to be determined.

Adult↗
PubMed1993

The use of recombinant human erythropoietin in end stage renal disease.

We treated 57 patients who suffered from end stage renal disease (ESRD) with recombinant human erythropoietin (EPO) for a mean period of 56 weeks. Patients were aged between 18 and 81 years. Forty three patients were on haemodialysis and 14 on continuous ambulatory peritoneal dialysis (CAPD). Despite regular transfusions, the mean haemoglobin prior to EPO therapy was 7.4 g/dl +/- 1.7. The target haemoglobin of 10 g/dl was reached at a mean of 12 weeks for the CAPD patients and at 14 weeks for the haemodialysis population. Patients were noted during the study to have a progressive rise in mean red cell volume, and this appeared to be related to their level of iron stores. The mean dose EPO used to reach the target haemoglobin was 8,700 u/week (125 u/kg/week) for the haemodialysis patients and 7,200 u/week (102 u/kg/week) for the CAPD patients. Three patients (7%) developed thrombosis of their A/V fistula. Hypertension was exacerbated in 28% of the patients. We conclude that EPO is a very effective but not inexpensive therapy for the anaemia of ESRD.

Adolescent↗
PubMed1993

Sequential Tc 99m mercaptoacetyl-triglycine (MAG3) renography as an evaluator of early renal transplant function.

A prospective study was carried out to evaluate the role of sequential Tc 99m MAG3 renography in assessing transplant function in the early post-operative period. Twenty patients were included in the study. Studies were performed on all patients at intervals of 48-72 hours until discharge. There were 11 clinically diagnosed episodes of rejection, 9 of which were correctly diagnosed using MAG3 renography. Six episodes of rejection were diagnosed prior to the onset of clinical symptoms. Two patients with graft infarction were correctly diagnosed. Six patients had evidence of transient renographic abnormalities in the immediate post-operative phase which were not associated with clinical symptoms, all of these resolved spontaneously on subsequent examinations and were presumed to be related to resolving acute tubular necrosis (ATN). The perfusion index was of no discriminatory value in this study. Sequential Tc 99m MAG3 renography is highly sensitive but entirely nonspecific in the evaluation of pathology in the transplant kidney. Rejection in an uncomplicated transplant can be readily detected in many cases well in advance of clinical manifestations. This study demonstrates that Tc 99m MAG3 renography is certainly equal to Tc 99m DTPA renography or Iodine 131 renography in assessing early transplant function. However, Tc 9m MAG3 exposes the patient to considerably less radiation and the images are of superior quality.

Adolescent↗
PubMed1992

Paediatric renal transplantation in Ireland: 1980-1990.

Between 1980 and 1990, 862 renal transplants were performed at our unit. Forty-six of these were given to 38 children. The mean age of the children was 8.6 years. Reflux nephropathy accounted for 39% of the primary renal diseases, followed by congenital disorders (30%), and glomerulonephritis (16%). Seventy percent of the grafts were from cadaveric donors. The one year patient survival was 90%, and the one year graft survival 61%. Seven children received a second graft with a one year graft survival of 71%.

Adolescent↗
PubMed1992

Skin cancer in an Irish renal transplant population.

One hundred and forty-nine renal transplant patients attending 2 centres in Dublin were examined. Twelve patients (8.1%) were found to have cutaneous malignancy while dysplastic lesions (premalignant and/or malignant) were identified in 34 (22.8%). The prevalence of cutaneous malignancy in this study is substantially greater than that of previous Irish studies. The introduction of cyclosporin A (CyA) as a new and more effective immunosuppressive agent in renal transplantation may in part explain this increase.

Adult↗