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Biomedical subjects

J Feehally

Publications and source records attributed to J Feehally.

At least 37 records · Page 2Linked to original sources
PubMed1999

A quantitative study comparing adjustment and acceptance of illness in adults on renal replacement therapy.

Adjustment and acceptance of illness are major factors influencing quality of life in different modes of renal replacement therapy. A quantitative tool was used to compare adjustment and acceptance of illness in adult patients on maintenance dialysis to those with a functioning renal transplant. A questionnaire incorporating Felton's Acceptance of Illness Scale was sent to 273 patients receiving replacement therapy for end stage renal disease (ESRD) in Leicester, UK. The instrument examined the effects of a variety of clinical and social parameters on the Acceptance of Illness Scale Score (AISS). Patients with a functioning renal transplant had a significantly higher AISS than patients on hemodialysis (HD) or peritoneal dialysis (PD) (P < 0.0001). Patients in employment or full-time education had a higher AISS than other patients (P < 0.01). White/Caucasian ethnic origin had a higher AISS than Asian (P = 0.011). There were weak inverse correlations between age and AISS, and between AISS and perception of 'choice' in treatment modality. Health care professionals need to be aware of all variables that affect patient acceptance of illness in order to administer optimum clinical care.

Adaptation, Psychological↗
PubMed1998

Rate of decline in renal function in Indo-Asians and Whites with diabetic nephropathy.

The incidence of end-stage renal failure (ESRF) is higher in the Indo-Asian ethnic group as compared to the White. To investigate whether this might be associated with faster rates of progression to ESRF in Indo-Asian diabetic patients, we studied a total of 39 Type 2 diabetic patients, using the Department of Nephrology database showing serial serum creatinine measurements from the time of first referral to the clinic until they reached a level of >500 micromol l(-1) or ESRF requiring renal replacement therapy (RRT), either dialysis or renal transplantation. They were grouped into Indo-Asian (n = 24) and White (n = 15). The rate of progression of those who developed ESRF, calculated as the slope of log serum creatinine against time, was not significantly different between the Indo-Asian and White patients, p = 0.73. We conclude that the higher incidence of ESRF in the Indo-Asian Type 2 diabetic patient with nephropathy is therefore not due to a faster rate of deterioration in renal function.

Adult↗
PubMed1998

Correcting impotence in the male dialysis patient: experience with testosterone replacement and vacuum tumescence therapy.

Sexual dysfunction remains a common and often distressing problem in the male dialysis population. Traditionally its management has consisted of correction of anemia, optimization of dialysis, removal of implicated medication, and finally depot injections of a testosterone ester. At a dedicated renal impotence clinic, we studied the effectiveness of testosterone replacement in men with biochemically proven hypogonadism and then vacuum tumescence therapy in those with continued erectile dysfunction. Depot testosterone was given to 27 patients (aged 52.4+/-2.5 years; duration of dialysis, 2.00+/-0.40 years; and duration of sexual dysfunction, 2.92+/-0.49 years): sexual function was fully restored in only three (11.1%), and two gradually lost the response over 18 months. Nineteen patients (70.3%) had partial responses, varying from an increased sense of well-being alone to restored sexual function apart from an impairment of the duration of penile erection. Five patients (18.5%) had no response, and testosterone was contraindicated in another four. Four of the treated patients (14.8%) reported fluid retention. Vacuum tumescence devices were then offered to 32 patients who remained impotent but declined by six. Twenty-six patients (aged 49.6+/-2.2 years; duration of dialysis, 2.50+/-0.58 years; and duration of sexual dysfunction, 3.26+/-0.56 years) used the devices, with 19 (73.1%) having full correction of their erectile dysfunction; six also continued with depot testosterone to maintain their libido. Penile discomfort was described by five patients (19.2%) whose potency was not restored. A further five predialysis patients have used the devices, and all had correction of their erectile dysfunction. The correction of biochemical hypogonadism in the male dialysis population with testosterone rarely restores sexual function to normal, whereas vacuum tumescence therapy corrects penile erection dysfunction in most patients.

Drug Implants↗
PubMed1998

Renal and haemodynamic effects of amlodipine and nifedipine in hypertensive renal transplant recipients.

BACKGROUND: Immunosuppressive treatment with cyclosporin A (CsA) improves the survival of renal allografts, but is associated with renal vasoconstriction and hypertension. Previous reports suggest that the calcium-channel blockers nifedipine and amlodipine may improve graft function in CsA-treated patients. We have compared the effects of amlodipine (5-10 mg once daily) and nifedipine retard (10-40 mg twice daily) on renal function and blood pressure in renal transplant recipients treated with CsA. METHODS: This was a multicentre, two-way, crossover study in 27 evaluable hypertensive patients with renal insufficiency following renal transplantation, who were maintained on a stable dose of CsA. Patients received either amlodipine (5-10 mg once daily) or nifedipine retard (10-40 mg twice daily) for 8 weeks, and were then crossed over to the other treatment for a further 8 weeks. RESULTS: Trends were seen during amlodipine treatment towards larger improvements, in serum creatinine (by 8% of baseline on amlodipine vs 4% on nifedipine), lithium clearance (13% vs 2%), and glomerular filtration rate 11% vs 7%). Effective renal plasma flow was increased by 11% of baseline on nifedipine vs 9% on amlodipine. There were no significant differences between treatments. Amlodipine and nifedipine lowered systolic blood pressure to a similar extent (21 mmHg vs 15 mmHg respectively, P=0.25), but amlodipine was more effective than nifedipine in lowering diastolic blood pressure (13 mmHg vs 8 mmHg, P=0.006). Both treatments were well tolerated. CONCLUSION: Once-daily amlodipine is at least as effective as twice-daily nifedipine retard in controlling blood pressure and does not adversely affect graft function in hypertensive renal allograft recipients.

Adolescent↗
PubMed1998

Abnormal IgA glycosylation in Henoch-Schönlein purpura restricted to patients with clinical nephritis.

BACKGROUND: Glomerular deposition of IgA1 is a common feature of Henoch-Schönlein purpura, and is indistinguishable from that seen in IgA nephropathy. Serum IgA1 is abnormally O-glycosylated in IgA nephropathy, and this may contribute to mesangial IgA1 deposition and the development of glomerular injury. This altered O-glycosylation of IgA1 can be detected by its increased binding to the lectin Vicia villosa. METHODS: To investigate whether IgA1 is abnormally glycosylated in Henoch-Schönlein purpura, the binding of Vicia villosa lectin to serum IgA1 was studied in the following subject groups: IgA nephropathy; adults and children with Henoch-Schönlein purpura and nephritis; children with clinically diagnosed Henoch-Schönlein purpura but no renal involvement; adults and children with non-IgA associated glomerulonephritis; and matched controls. RESULTS: The abnormality of lectin binding seen in IgA nephropathy was also found in both adults and children with Henoch-Schönlein purpura with nephritis. However, the lectin binding of serum IgA1 from children with Henoch-Schönlein purpura lacking renal involvement did not differ from controls, and similarly, no abnormality of lectin binding was seen in patients with non-IgA associated glomerulonephritis. CONCLUSIONS: These data indicate that the abnormality of IgA1 O-glycosylation seen in IgA nephropathy is also found in Henoch-Schönlein purpura, but only in those subjects with renal involvement, while IgA1 O-glycosylation is normal in patients with other forms of renal disease. These findings lend strong support to a role for altered IgA1 O-glycosylation in the pathogenesis of IgA-associated glomerular disease.

Adolescent↗
PubMed1998

The nucleotide sequence of the IgA1 hinge region in IgA nephropathy.

BACKGROUND: Mesangial IgA1 deposition is characteristic of IgA nephropathy (IgAN). Structural abnormalities of the IgA1 glycoprotein may play a key role in its mesangial deposition, particularly the recently described abnormalities of O-glycosylation of the IgA1 hinge region. The mechanism of abnormal O-glycosylation has not yet been elucidated; it is not clear whether there is an alteration in the amino acid sequence of the hinge region, modifying the number of O-glycosylation sites available, or whether there is a post-translational defect in the glycosylation process. METHODS: The O-glycosylation of serum IgA1 from a series of patients with IgAN and matched controls was assessed by lectin binding assay. We then used dideoxy-sequencing of the PCR-amplified hinge region of the alpha1 heavy chain gene to compare the hinge region nucleotide sequence in IgAN and controls. We also compared cDNA transcripts of alpha1 hinge region mRNA to look for evidence for a transcriptional abnormality in IgAN. RESULTS: Lectin binding assays confirmed that the IgAN subjects used in this study did indeed display the previously reported abnormality of IgA1 O-glycosylation. However, the hinge region nucleotide sequence of the alpha1 gene was identical in IgAN and controls. There was also no difference in the sizes of cDNA transcripts of hinge region mRNA from patients with IgAN and controls. CONCLUSIONS: We found no evidence for any nucleotide sequence alteration or transcriptional abnormality of the alpha1 hinge region in IgAN, and we conclude that the O-glycosylation defect is post-translational.

Adolescent↗
PubMed1997

Henoch-Schönlein purpura with immunoglobulin A nephropathy and abnormalities of immunoglobulin A in a Wiskott-Aldrich syndrome carrier.

Abnormalities of immunoglobulin A1 (IgA1) glycosylation have been described in patients with IgA nephropathy (IgAN), whether primitive or secondary to Henoch-Schönlein purpura. The Wiskott-Aldrich syndrome, an X-linked recessive disorder, is associated with abnormalities of IgA. Renal involvement with mesangial IgA deposition identical to that found in IgAN has been reported during this affection. We report the case of a female carrier of the Wiskott-Aldrich syndrome presenting with Henoch-Schönlein purpura and abnormalities of IgA glycosylation, as previously reported in patients with IgAN. The galactosylation abnormalities of IgA could be linked to the patient's status as carrier of the Wiskott-Aldrich syndrome and could contribute to the pathogenesis of IgAN.

Adult↗
PubMed1997

Expression of the mucosal gamma delta T cell receptor V region repertoire in patients with IgA nephropathy.

IgA nephropathy (IgAN) is characterized by the deposition of IgA in the glomerular mesangium and often leads to progressive renal dysfunction and kidney failure. We have previously shown that the mesangial IgA is likely to derive from the bone marrow plasma cells, and suggested that a primary abnormality within the mucosal immune system may underly the pathogenesis of IgAN. This study has analyzed the T cell receptor (TCR) variable (V) region expression by gamma delta T cells in the intestinal mucosa of patients with IgAN. The V gamma and V delta usage of TCR transcripts was determined using a semiquantitative reverse transcriptase-PCR protocol. Primers specific for the four human V gamma and six V delta subfamilies were used each with a constant (C) gamma or C delta specific primer, and the PCR-amplified TCR transcripts were detected by Southern blotting and oligonucleotide hybridization. gamma delta TCR V region expression was determined in gut biopsies and peripheral blood of 11 patients with IgAN, and the TCR V gamma and V delta repertoires were compared to those in gut and peripheral blood of 11 control individuals. gamma delta T cells in normal blood predominantly expressed V gamma 2 (V gamma 9 gene) and V delta 2 gene segments whereas those in normal gut mainly expressed V gamma 3 and V delta 3. In IgAN patients, V delta 2 was also the predominant V delta gene utilized by peripheral blood gamma delta T cells, however, we observed a predominance of V gamma 3 and reduced V gamma 2 usage by these cells. gamma delta T cells in the gut of IgAN patients mainly used V gamma 3 and V delta 1. While the gamma and delta TCR V region repertoires did not differ significantly between the peripheral blood of patients and controls, there were significant differences in V gamma and V delta repertoire expression between IgAN and control gut biopsies. V gamma 3 gene expression was significantly decreased in IgAN gut compared to control gut (P = 0.023). In addition, there was a significant decrease in V delta 3 gene expression in IgAN gut compared to control gut (P = 0.043). These findings indicate that a subpopulation of gamma delta T cells, which represent the majority of gamma delta T cells in normal gut mucosa, are significantly diminished in the gut of patients with IgAN. This suggests that a "hole" in the mucosal gamma delta T cell repertoire may play a fundamental role in contributing to the pathogenesis of IgAN.

Adult↗
PubMed1997

Leucocyte beta 1,3 galactosyltransferase activity in IgA nephropathy.

BACKGROUND: Reduced galactosylation of the O-linked glycans of the IgA1 hinge region in IgAN has recently been described. To investigate the underlying defect resulting in this abnormality, we have measured the activity of beta 1,3 galactosyltransferase, the enzyme responsible for galactosylation of O-linked sugars. METHODS: A galactose-acceptor substrate was prepared from degalactosylated hinge region fragments of normal IgA1, and incubated with the T cell, B cell, and monocyte lysates from patients with IgAN and controls for acceptor regalactosylation. The extent of acceptor galactosylation was then measured with biotinylated Vicia villosa lectin (VV), which is specific for ungalactosylated moieties. Lectin binding of serum IgA from the same subjects was also measured. RESULTS: T cell and monocyte beta 1,3 galactosyltransferase activities did not differ between IgAN and control, but B cell lysates in IgAN showed significantly lower beta 1,3 galactosyltransferase activity than control (6.2 +/- 0.71 vs. 9.5 +/- 1.03 AU/microgram, P = 0.018). Furthermore, B cell beta 1,3 galactosyltransferase activity showed a negative correlation (r = -0.87, P = 0.002) with VV lectin binding of serum IgA in IgAN, but not controls. CONCLUSIONS: These data indicate that altered IgA1 O-galactosylation in IgAN results from a B cell-restricted reduction of beta 1,3 galactosyltransferase activity. This enzyme defect may be a fundamental pathogenic abnormality in IgAN.

Adult↗
PubMed1997

Erythropoietin and sexual dysfunction.

BACKGROUND: Erythropoietin (rHuEpo) therapy has been shown to improve sexual function in the male dialysis population, with several studies suggesting a direct effect upon endocrine function, as well as correction of anaemia. Nevertheless many male dialysis patients receiving rHuEpo continue to complain of sexual dysfunction. METHODS: At a dedicated renal impotence clinic, 65 male dialysis patients were screened for endocrine disturbances. Baseline serum sex hormones were compared between those receiving and not receiving rHuEpo, using either the two-sample t test or the Mann-Whitney U test, after assessing for normality. Results from four patients were excluded on account of either medications (antiemetic phenothiazines), hepatic dysfunction, or carcinomatosis. RESULTS: Twenty-five patients (41.0%) were receiving rHuEpo, the recipients and non-recipients being well matched for haemoglobin (10.19 +/- 0.29 vs 10.55 +/- 0.25 g/dl, n.s.), age (51.1 +/- 1.9 vs 53.6 +/- 2.1 years, n.s.) and duration of sexual dysfunction (median, 3.0 vs 3.0 years, n.s.). The rHuEpo recipients had a higher median creatinine (1090 vs 972 micromol/l, P < 0.02), but similar nutritional status to the non-recipients (albumin 41.0 vs 39.0 g/l, n.s.). The total duration of rHuEpo therapy was 0.85 +/- 0.14 years. Prolactin levels were similar in both the rHuEpo recipients and non-recipients (440 vs 541 mu/l, n.s.), as were LH (11.0 vs 10.5 iu/l, n.s.) and FSH (8.0 vs 6.5 iu/l, n.s.). However, there were significant elevations of testosterone (19.8 +/- 1.3 vs 16.1 +/- 1.1 nmol/l, P < 0.05) and sex hormone binding globulin (SHBG) (40.5 vs 26.0 nmol/l, P < 0.01), with a trend toward elevated oestradiol (304 vs 248 pmol/l, P = 0.095) in the rHuEpo-treated group. Forty-eight subjects (78.7%) received peritoneal dialysis (PD), with the 19 rHuEpo recipients (39.6%) demonstrating increased serum testosterone (21.0 +/- 1.5 vs 16.6 +/- 1.3 nmol/l, P < 0.05), SHBG (40.5 vs 26.5 nmol/l, P < 0.01), LH (15.0 vs 10.0 iu/l, P < 0.01) and FSH (12.0 vs 5.3 iu/l, P < 0.05). These differences were not demonstrated in the 13 haemodialysis (HD) subjects. CONCLUSIONS: Male dialysis patients complaining of sexual dysfunction after correction of anaemia with rHuEpo are characterized by higher levels of serum testosterone and SHBG, but not suppression of hyperprolactinaemia or hyperoestrogenism. Male PD subjects receiving rHuEpo also demonstrated increased LH and FSH.

Aged↗
PubMed1997

A comparative study of digoxigenin, 2,4-dinitrophenyl, and alkaline phosphatase as deoxyoligonucleotide labels in non-radioisotopic in situ hybridisation.

AIM: To determine the optimum form of labelling and the most efficient reporter molecule for non-radioisotopic in situ hybridisation (ISH). METHODS: Nine deoxyoligonucleotides complementary to histone mRNA were synthesised and labelled either enzymatically or during solid-phase synthesis with the reporter molecules digoxigenin, 2,4-dinitrophenyl (DNP), or alkaline phosphatase. Pooled deoxyoligonucleotide cocktails were then used in non-radioisotopic ISH detection of histone mRNA in human tonsil. Hybrid detection was by nitroblue tetrazoleum/5-bromo-4-chloro-3-indolyl phosphate colorimetric development. RESULTS: The use of a spacer in 3' enzymatic labelling and when labelling with alkaline phosphatase significantly increased ISH signal. The 3' and 5' labelling of oligonucleotides with triple DNP groups during solid-phase synthesis produced the strongest signal as determined by the highest cell signal intensity and shortest development time. CONCLUSIONS: 3' and 5' solid-phase labelling with triple DNP groups produced the best labelling for non-isotopic ISH using deoxyoligonucleotide cocktails.

2,4-Dinitrophenol↗
PubMed1997

Isolated microscopic haematuria in the genitourinary clinic: the value of renal biopsy.

Isolated microscopic haematuria is a common finding in the genitourinary clinic. The conventional approach to investigation includes urological referral for cystourethroscopy if renal imaging is normal. However the diagnostic yield is very low; in particular urothelial malignancy at age < 40 years is rare. Glomerular disease is increasingly recognized as a common cause of microscopic haematuria. In this study 50 patients with persistent microscopic haematuria detected at a genitourinary clinic underwent renal biopsy. Twelve (24%) had an abnormal biopsy--IgA nephropathy 6 (12%), thin membrane nephropathy 3 (6%), other glomerulonephritis 3 (6%). In 7 others no abnormality was found but information was incomplete as electron microscopy was unavailable. It is important to establish these diagnoses since some patients will develop progressive renal disease. In this clinical setting renal biopsy will give diagnostic and prognostic information, protects from repeated urological investigation, and allows reassurance if renal histology is normal. Renal biopsy is recommended for patients age < 40 years with persistent microscopic haematuria. An algorithm for the investigation of microscopic haematuria is presented.

Adult↗
PubMed1996

Early measurement of interstitial fibrosis predicts long-term renal function and graft survival in renal transplantation.

This study investigated the relationships between renal allograft interstitial fibrosis, renal function and graft survival. A total of 107 consecutive renal transplant recipients immunosuppressed with cyclosporin were studied. Needle core transplant biopsies were performed before operation and at 1, 6 and 12 months after transplantation. Allograft fibrosis was assessed by histomorphometric analysis of graft interstitial volume fraction. Renal function was measured by isotopic glomerular filtration rate (GFR) measurement at the same time points. Interstitial volume fraction was already high in preperfusion biopsies, significantly increased with time but stabilized at 6 months after transplantation. GFR correlated negatively with interstitial volume fraction at 6 months (P = 0.05). Interstitial volume fraction at 1 month was not a useful predictor of subsequent graft survival but for allografts surviving to 6 months an interstitial volume fraction above 25 per cent predicted significantly poorer survival (P = 0.04). It provides an objective measure of chronic allograft damage and may prove to be a useful surrogate endpoint in the study of therapeutic intervention.

Biopsy, Needle↗