Biomedical subjects

L Rees

Publications and source records attributed to L Rees.

At least 19 recordsLinked to original sources

PubMed2006

Perinatal renal venous thrombosis: presenting renal length predicts outcome.

BACKGROUND: Renal venous thrombosis (RVT) is the most common form of venous thrombosis in neonates, causing both acute and long term kidney dysfunction. Historical predisposing factors include dehydration, maternal diabetes, and umbilical catheters, but recent reports highlight associations with prothrombotic abnormalities. STUDY: Twenty three patients with neonatal RVT were analysed over 15 years. Predisposing factors, presentation, and procoagulant status were compared with renal outcome using multilevel modelling. RESULTS: Median presentation was on day 1: 19/23 (83%) had pre/perinatal problems, including fetal distress (14), intrauterine growth retardation (five), and pre-identified renal abnormalities (two); 8/18 (44%) had procoagulant abnormalities, particularly factor V Leiden mutations (4/18). Long term abnormalities were detected in 28/34 (82%) affected kidneys; mean glomerular filtration rate was 93.6 versus 70.2 ml/min/1.73 m2 in unilateral versus bilateral cases (difference 23.4; 95% confidence interval 6.4 to 40.4; p = 0.01). No correlation was observed between procoagulant tendencies and outcome, but presenting renal length had a significant negative correlation: mean fall in estimated single kidney glomerular filtration rate was 3 ml/min/1.73 m2 (95% confidence interval 3.7 to -2.2; p = 0.001) per 1 mm increase, and kidneys larger than 6 cm at presentation never had a normal outcome. CONCLUSIONS: This subgroup of neonatal RVT would be better termed perinatal RVT to reflect antenatal and birth related antecedents. Prothrombotic defects should be considered in all patients with perinatal RVT. Kidney length at presentation correlated negatively with renal outcome. The latter, novel observation raises the question of whether larger organs should be treated more aggressively in future.

Blood Coagulation Disorders, Inherited↗

PubMed2004

The effects of list difficulty and modality of presentation on a computerized version of the Paced Serial Addition Test (PSAT).

The Paced Serial Addition Test (PSAT) presents a series of digits at different speeds with the requirement that the two most recent numbers be added together. Although the PSAT is a relatively difficult test, its level of difficulty may be decreased by changing the number list to make the answers simpler and by presenting the digits visually rather than aurally. In view of this, the present experiment varied both task difficulty (easy vs. hard) and mode of presentation (visual vs. auditory). Task difficulty was manipulated by using two different lists composed of single digits whose answers ranged between 2 and 10 (easy) or 2 and 18 (hard). All stimuli were presented by computer which permitted measurement of response latencies, as well as correctness of responding. The results showed that mode of presentation, but not task difficulty, produced highly significant effects. Additional evidence showed that the ability to compute answers to simple addition problems must be considered as a modulator variable. However, an individual's basic arithmetic ability is not as critical as the modality in which a stimulus is presented. The lower performance associated with the auditory version (i.e., PASAT) was interpreted as an interference effect caused by both the stimulus and the response occurring in a single auditory information processing channel. This interpretation suggests that the PASAT's well documented sensitivity to traumatic brain injury (TBI) may be due, at least in part, to an increased susceptibility to interference effects rather than attributable solely to a decreased rate of information processing.

Acoustic Stimulation↗

PubMed2004

A systematic review of case-control studies of human papillomavirus infection in laryngeal squamous cell carcinoma.

A role for human papillomavirus (HPV) has been suggested in laryngeal squamous cell carcinoma (LSCC). In order to quantitate the available evidence, we reviewed studies examining the risk of laryngeal cancer-associated HPV. PubMed was searched for case-control studies conducted worldwide and published in any language since 1966. Relevant papers were hand-searched and cross-referenced. Six studies met the inclusion criteria. The studies are heterogeneous in the methods used to harvest tissue samples and techniques for detecting the virus within the tissue. HPV-16 positivity among cases ranged from 2.7% to 46.9% and 0-5.7% among controls. Two studies showed a significantly increased risk of LSCC if HPV-16 was present (OR 18.5, 95% CI 2.2-154.8, OR 2.6, 95% CI 1.1-6.0). An increased risk was also observed for glottic versus supraglottic cancer in one study (OR 9.69, 95% CI 1.47-64.04). The direction of effect is towards an increase in risk of LSCC in people with evidence of HPV-16 infection. There is marked heterogeneity in the methods used to detect the virus and frequency with which it is detected. An adequately powered study using a reliable detection technique is required to confirm and quantify this risk and to examine effect modification.

Carcinoma, Squamous Cell↗

PubMed2004

The Adjusting-Paced Serial Addition Test (Adjusting-PSAT): thresholds for speed of information processing as a function of stimulus modality and problem complexity.

A modified computer version of the PASAT (Adjusting-PSAT; ) is described that measures speed of information processing and working memory by means of a temporal threshold rather than number of correct responses. This is accomplished by making the duration of the interval between numbers depend on the correctness of responding-a correct response decreases the interval between digits and an incorrect response increases the interval. Modality of presentation (visual and auditory) was factorially combined with problem difficulty (answers between 2-10 or 2-18). Performance of 60 healthy student volunteers on the Adjusting-PSAT was compared to that obtained on several traditional neuropsychological measures (Digit Span, Trail Making Test, and Symbol Digit Modality Test) and on a test of basic addition skills. The visual version of the test produced a lower threshold than did the auditory version, but problem difficulty did not produce a significant effect. Of the neuropsychological tests, Trails-B (TMT-B) was most highly correlated with thresholds. However, regression analyses revealed that math ability accounted for more variance than did TMT-B. The clinical implications of these finding are discussed.

Acoustic Stimulation↗

PubMed2003

The significance of a defect on DMSA scan in children with renal transplants.

Since December 1995, pediatric renal transplant recipients in our unit have received a DMSA scan as soon as possible post-transplant in order to provide a baseline for comparison in the event of subsequent complications. We retrospectively reviewed the case notes and DMSA scans of the 45 patients who underwent a scan within 9 wk of their transplant to see if pre or peri-transplant factors or post-transplant complications were associated with defects on scanning. Forty percentage of scans had defects. The presence of defects was not associated with potential predisposing factors such as patient or donor age, cadaveric or live donation, cold ischemia time, multiple donor vessels, the use of non-heart beating donors, the mean time to scan, the serum creatinine, or the presence of structural renal tract anomalies predisposing to UTI. However, 87% of patients had complications before the scan, including UTI, rejection, acute tubular necrosis, transplant biopsy and drug toxicity. Children with no clinical complications had a significantly reduced risk of a defect (p = 0.035), while biopsy was associated with the presence of defects (p = 0.0034). Twenty patients had one or more follow up DMSA scans: one patient developed a new focal defect. In conclusion, renal transplant defects are frequently found on DMSA scanning even early after transplantation and are non-specifically associated with many different complications.

Adolescent↗

PubMed2002

Epstein-Barr virus monitoring in paediatric renal transplant recipients.

Prospective Epstein-Barr virus (EBV) surveillance post transplant was undertaken by qualitative polymerase chain reaction testing for EBV DNA in plasma so as to detect EBV viremia as early as possible and thereby attempt to pre-empt post-transplant lymphoproliferative disease by reduction of immunosuppression. Forty-three children (46 transplants) were followed for a median (range) of 15.5 (3-25) months. Thirty-one children (67%) were EBV seropositive pre transplant. Twenty children (44%) developed EBV viremia; of these 9 (60%) were seronegative and 11 (36%) seropositive recipients. Primary infection developed later (median difference 14.2 weeks, P=0.009), was more likely to be symptomatic (odds ratio 2.91, 95% confidence interval 0.95-4.88) and associated with a rise in serum creatinine (odds ratio 6.13, 95% confidence interval 4.13-8.13) than reactivation disease. There was a higher incidence of EBV disease in children receiving quadruple therapy and tacrolimus (odds ratio 13.2, 95% confidence interval 11.5-14.9) compared with those given cyclosporin-based immunosuppression. Immunosuppression was reduced when EBV infection was detected. All children became asymptomatic and renal function returned to normal by a median (range) of 17 (6-52) days, although mild relapses occurred in 3 children. Regular EBV surveillance allowed prompt reduction of immunosuppression and was associated with a good outcome in this group of children.

Adolescent↗

PubMed2002

Does oral folic acid lower total homocysteine levels and improve endothelial function in children with chronic renal failure?

BACKGROUND: Accelerated vascular disease is common in chronic renal failure (CRF) and accounts for significant mortality and morbidity. Elevated homocysteine levels may contribute by an effect on endothelial function. METHODS AND RESULTS: We performed a double-blind placebo-controlled randomized crossover trial of folic acid at 5 mg/m2 in 25 normotensive children 12+/-3 (7 to 17) years of age with CRF (glomerular filtration rate 26.8+/-13.2 mL/min per 1.73 m2) of noninflammatory etiology. Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period. The effect of folic acid on homocysteine levels, LDL oxidation, and both endothelial-dependent and -independent vascular function were measured. After oral folic acid, serum folate levels rose from 11.7+/-4.25 to 635+/-519 microg/L (P=0.001), red cell folate levels rose from 364+/-195 to 2891+/-2623 microg/L (P<0.001), and total homocysteine levels fell from 10.28+/-4.16 to 8.62+/-2.32 micromol/L (P=0.03). In addition, there was a significant improvement in flow-mediated dilatation (FMD) (endothelial-dependent dilatation) from 7.21+/-2.8% to 8.47+/-3.01% (P=0.036) with no change in response to glyceryl trinitrate (endothelial-independent dilatation). There was no significant change in FMD or glyceryl trinitrate during the placebo phase. There was, however, no significant difference in final FMD after placebo or folic acid. Lag times for LDL oxidation were prolonged during the treatment phase (58.4+/-18.7 to 68.1+/-25.9 minutes, P=0.01). CONCLUSION: Folic acid supplementation in children with CRF may improve endothelial function with an increased resistance of LDL to oxidation.

Administration, Oral↗

PubMed2002

Immunodeficiency-related lymphoproliferative disorders: prospective data from the United Kingdom Children's Cancer Study Group Registry.

Clinical data and biological samples were prospectively collected in 42 children with lymphoproliferative disease (LPD) secondary to organ/bone marrow transplant-related immunosuppression (30: 11 liver, 10 heart/lung, 8 kidney and 1 bone marrow), other drug-induced immunosuppression (2), congenital immunodeficiency (8) or human immunodeficiency virus (HIV)-related immune dysfunction (2). Ages ranged from 10 months to 17 years and there were 15 girls. Pathology was centrally reviewed and showed polymorphic features in 5 cases, monomorphic in 23, mixed pattern in 5 patients and 9 other types. Using the Revised European-American Classification of Lymphoid Neoplasms, 5 were B lymphoblastoid, 24 were high-grade B and 14 were other subtypes. Using the Pittsburgh classification, 9 were lymphadenopathic, 10 were systemic, 25 were lymphomatous and, with the Murphy grouping for non-Hodgkin's lymphoma (NHL), 10 were localized and 32 non-localized. Twenty-four out of 38 evaluable cases were Epstein-Barr virus positive. Thirty-five patients were evaluable for clonality; 24 were monoclonal and 11 were polyclonal. Reduced immunosuppression in solid organ transplant patients resulted in resolution of disease in 14/24, which was sustained in 11. Nineteen patients received chemotherapy, 14/18 evaluable responded, which was sustained in 8 cases. Seven out of 29 solid organ transplant and 10/13 other immune-deficient patients died. In the largest group of patients, solid organ transplants, no significant clinical or biological characteristics that predicted outcome were identified. In the transplant group close monitoring of response during reduction in immunosuppression is essential and the early use of B NHL chemotherapy may be effective.

Adolescent↗

PubMed2002

Early treatment with allopurinol in familial juvenile hyerpuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease.

BACKGROUND: The efficacy of allopurinol in autosomal dominant familial juvenile hyperuricaemic nephropathy (FJHN) has been disputed. AIM: To address this question, in the absence of controlled trials. DESIGN: Retrospective long-term follow-up study. METHODS: All kindreds were biochemically screened. Measurements included uric acid clearance, creatinine clearance, serum creatinine, and glomerular filtration rate (GFR). We used five siblings who had died or progressed to transplantation, ten other deceased relatives, and two index cases (one untreated, one non-compliant) as controls to assess the effects of allopurinol. RESULTS: Of eight families with FJHN, six had a strong history of renal disease and early parental death (mean age 41 years, n=10). Of 27 patients started immediately on allopurinol and treated uninterruptedly, 21 responded well, including three children born subsequently. Eight siblings (mean age 19 years) with a normal plasma creatinine at start (<120 micromol/l, mean GFR 80 ml/min/1.73 m(2)) retained stable renal function (mean 14.5 years, mean age 34 years, GFR 85 ml/min/1.73 m(2)). Of the 13 other responders, treated for up to 34 years, 10 with a creatinine <200 micromol/l at diagnosis (mean age 28 years, mean creatinine 137 micromol/l at start) now have a mean creatinine of 210 micromol/l. In contrast, five patients (mean age 26 years) with a creatinine >200 micromol/l (GFR <35 ml/min/1.73 m(2)) when allopurinol commenced, plus one untreated index case, all progressed rapidly (mean 6 years) to end-stage renal failure. In two others (one non-compliant, one initially untreated), GFR fell by >50% in 7 years. Introduction of allopurinol in the latter has stabilized GFR. DISCUSSION: Allopurinol reduced the morbidity and mortality from renal failure seen in untreated siblings and previous generations of these families. Early diagnosis of FJHN is important, so that treatment can begin before irreversible renal damage has developed.

Adolescent↗

PubMed2001

Integrated medicine.

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Complementary Therapies↗

PubMed2001

Effect of chronic renal failure and prednisolone on the growth hormone-insulin-like growth factor axis.

Abnormalities of the growth hormone (GH)/ insulin-like growth factor (IGF) axis have been reported in children with chronic renal failure (CRF) and post-transplant, and are thought to contribute to poor growth. This study examined the effect of CRF and steroid therapy (given post-transplant and to children with normal renal function) on the GH-IGF axis in children with normal and abnormal growth. Thirty-one children with CRF, ten on dialysis, 26 with renal transplants and ten taking steroid therapy but with normal renal function, were studied. IGF-I, measured by radioimmunoassay, was normal but IGF bioactivity was low in groups with a decreased glomerular filtration rate (P<0.05). Transplanted children growing at a subnormal growth rate had lower IGF bioactivity than those growing at a normal rate (P=0.03), but there was no such difference in bioactivity in children with CRF. There was no correlation between IGF bioactivity and prednisolone treatment. There was no correlation between IGF binding proteins 1, 2 or 3 and growth.

Adolescent↗

PubMed2000

Growth over 10 years following a 1-year trial of growth hormone therapy.

The growth of short children with chronic renal failure (CRF) and renal transplants was assessed over 10 years following entry into a 1-year trial of recombinant human growth hormone (rhGH) therapy. Patients were divided into three groups: 6 prepubertal patients with CRF (group 1), mean (range) age at start of trial 7.7 (5.0-10.4) years; 6 prepubertal patients with renal transplants (group 2), age 11.9 (9.5-14.6) years; and 6 pubertal patients with renal transplants (group 3), age 15.6 (14.1-18.3) years. In group 1, the mean (range) height standard deviation score (Ht SDS) increased from -2.9 (-3.7 to -2.2) to -1.9 (-2.9 to -0.5) over 4.0 (0.3-9.1) years of rhGH (P=0.04), and was -1.6 (-2.9 to -0.4) after 10 years of follow-up (NS). In group 2 Ht SDS increased from -3.3 (-4.5 to -1.9) to -2.9 (-5.4 to -0.5) over 2.7 (1.0-6.0) years and was -3.0 (-6.3 to -0.1) at final height (NS). In group 3 Ht SDS increased from -3.4 (-4.3 to -2.6) to -3.0 (-3.4 to -2.2) over 1.4 (0.2-2.3) years (NS) and was -2.5 (-3.0 to -1.9) at final height (P=0.03 from stopping rhGH to final height). Final height was attained in 13 patients, in whom Ht SDS increased from -3.2 (-4.3 to -1.9) to -2.6 (-3.9 to -0.5) on rhGH (P=0.004) and to -2.2 (-4.4 to -0.1) after stopping treatment (P=0.04). Four patients died, 2 have chronic hepatitis C, and 1 has had surgery for parathyroid adenomata. In conclusion, the majority of patients had an improvement in Ht SDS while on rhGH, which was maintained after stopping treatment.

Adolescent↗

PubMed2000

Spontaneous clinical improvement in dense deposit disease.

The clinical course and 3-year follow-up of a female patient aged 11 years who presented with nephrotic syndrome and renal failure is described. The renal biopsy revealed type II membranoproliferative glomerulonephritis or dense deposit disease. She was treated with penicillin prophylaxis, frusemide and captopril, and was not given immunosuppression, anticoagulation or antiplatelet therapy. Despite poor prognostic clinical and pathological features, she had spontaneous resolution of her renal failure and proteinuria, although her proteinuria recurred 17 months post presentation. Her unusual progress, with improvement in her disease activity and normalisation of her glomerular filtration rate, is described.

Acute Kidney Injury↗

PubMed2000

Recurrent focal segmental glomerulosclerosis in grafts treated with plasma exchange and increased immunosuppression.

We report on three children with severe, recurrent focal segmental glomeruloscerosis (FSGS) in their first allografts, treated with methylprednisolone, plasma exchange and cyclophosphamide. This protocol is based on a previous publication showing its successful use in three children. Our patients were 2 girls and 1 boy, aged 14.5, 14.6 and 13.2 years, respectively, at transplant. Concomitant immunosuppression included cyclosporin A and prednisolone. Recurrence occurred in all three patients within 24 h, and specific treatment was commenced within 48 h. All patients developed anuria and were dialysed. The boy stopped dialysis after 4 weeks, and has stable chronic renal failure (CRF) and no proteinuria 3 years later. One girl required dialysis for 4 months, and 3 years later has CRF with non-nephrotic range proteinuria. The other girl remained dialysis-dependent and died from septic complications. We conclude that even anuric patients treated with this protocol may have an improvement in renal function and reduction of proteinuria, which can last for over 3 years. However, treatment may need to be prolonged and carries the substantial risks of heavy immunosuppression.

Adolescent↗

PubMed2000

Growth hormone and markers of immune function in children with renal transplants.

Lymphocyte subsets and T cell activation markers were measured in ten children with renal transplants for up to 1 year before and during their 1st year of recombinant human growth hormone (rhGH) treatment. The number of lymphocytes, helper or cytotoxic T cells or natural killer cells, and the T cell expression of CD25, CD26 and HLA-DR antigens were not altered by rhGH. B cell numbers declined both before and during treatment. There was no difference in lymphocyte subset numbers between children with and without rejection episodes.

Adolescent↗

PubMed2000

Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?

Dysfunction of the Wilms' Tumour gene (WT1), a transcription factor critical for normal development and function of the urogenital tract, can result in both tumourigenesis [corrected] and urogenital abnormalities. The association of WT1 gene mutations with most cases of Denys-Drash syndrome is well described. More recently WT1 mutations have also been described in a related condition, Frasier syndrome. We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3' alternative splice donor site in intron 9. The case provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. In addition, it illustrates the increasing significance of genetic investigation within clinical practice for diagnostic, prognostic and therapeutic purposes and the importance of karyotype analysis in phenotypically normal girls with renal disease.

Adolescent↗

PubMed2000

Outcome and growth of infants with severe chronic renal failure.

BACKGROUND: We aimed to assess the outcome and growth of infants with severe chronic renal failure (CRF). One hundred and one children presented between January 1, 1986, and December 12, 1998, with a glomerular filtration rate (GFR) of <20 mL/min/1.73 m2. The median (range) age at presentation was 0.3 (0 to 1.5) years, and follow-up was 7.6 (1.5 to 13) years. One- and five-year survival rates were 87 and 78%, respectively. The growth of the 81 children who survived over two years was evaluated. Eighty-one percent were enterally fed from age 0.7 (0 to 4.5) years for 1.9 (0.1 to 6.8) years. Forty-six percent had a gastrostomy, and 22% a Nissen fundoplication. Twenty-five were managed conservatively. Twenty were transplanted without dialysis at age 4 (1.7 to 8.5) years, and 36 were dialyzed at age 1.1 (0 to 9.8) before transplantation at age 2. 4 (1.3 to 10) years. RESULTS: The mean (SD) height standard deviation score increased from -2.16 (1.34) at 6 months (N = 63) to -1.97 (1.37) at 1 year (N = 75), -1.79 (1.29) at 2 years (N = 75), -1.33 (1.29) at 3 years (N = 68, P = 0.0006), -1.27 (1.04) at 5 years (N = 47, P = 0.0001), and -0.85 (0.82) at 10 years (N = 18, P = 0.001). The body mass index was in the normal range in the majority of patients. CONCLUSION: Mortality in infants with CRF occurs mainly in the first year of life. With early enteral feeding, the mean height standard deviation score is within the normal range from one year of age.

Body Height↗

PubMed1999

Renal transplantation in children under 5 years of age.

Between March 1987 and December 1997, 59 renal transplants [49 cadaveric, 10 live related (LRD)], were performed in 54 children aged 5 years and younger. Six children required a second transplant. The median (range) age of the recipients was 2.9 (1.4-5.0) years; mean weight was 12.6 kg (7.4-23) and donor age 11 (2-50) years. Immunosuppression was cyclosporin or FK506, prednisolone, and azathioprine. Antithymocyte globulin was given as induction therapy for second transplants. Patient survival was 98.3%; 1 patient died from upper gastrointestinal haemorrhage. Graft survival was 67.7% at 1 year, 57.4% at 5 years, and 45.2% at 10 years. No LRD graft was lost during 7 years of follow-up. Thrombosis was the main cause of graft loss (10 cases) followed by vascular rejection (2 cases). There was no significant difference in graft survival between recipients aged less than 2, 2-3, and 3-5 years. The height standard deviation score (+/-SD) improved from -2.1+/-1.3 at transplantation to -1.0+/-1.3 at 1 year, -1.1+/-1.5 at 5 years, and to -0.14+/-1.1 at 10 years.

Adolescent↗