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Biomedical subjects

K E Meyers

Publications and source records attributed to K E Meyers.

At least 19 recordsLinked to original sources
PubMed2004

Short sirolimus half-life in pediatric renal transplant recipients on a calcineurin inhibitor-free protocol.

Immunosuppression with SRL may provide an opportunity to avoid long-term exposure to the nephrotoxicity of CNI. Thus, we have initiated an experimental protocol of IL-2r antibody induction, prednisone, MMF and SRL in pediatric renal transplant recipients (median age 15.5 yr, IQR 8.5, range 1.3-21.7). The recipients were treated with daclizumab every 2 wk for the first 2 months, prednisone on a tapering schedule, MMF at 1200 mg/m(2)/day and SRL given b.i.d. The SRL was dosed to achieve defined target whole blood 12-h trough levels. We performed 24 SRL PK profiles in 13 stable pediatric renal transplant recipients at 1 and 3 months post-transplant. Half-life (T(1/2)) and terminal T(1/2) were 9.7 (7.1-24.6) and 10.8 (4.4-95.2) hours (median, range) respectively at month 1, and were 9.6 (5-17.8) and 12.1 (4.7-71.0) hours respectively at month 3. SRL trough levels correlated with AUC (r(2) = 0.84, p < 0.001). There was no relationship between SRL and mycophenolic acid (MPA) AUC values (r(2) = 0.04). During the first 3 months post-transplant only one patient experienced severe neutropenia and another patient had subclinical (histologic) evidence of a mild acute rejection episode with no change in renal function. We conclude that the T(1/2) of SRL in pediatric renal transplant recipients not treated with CNI is much shorter than what has been reported for adults, due to rapid metabolism. We conclude that children require SRL dosing every 12 h, higher doses and frequent drug monitoring to achieve target SRL concentrations.

Adolescent↗
PubMed2000

Wegener granulomatosis--an atypical case.

An unusual sequence of the clinical manifestations of microvascular disease is described in a 15 year-old girl. She initially presented with acute renal failure caused by a crescentic glomerulonephritis associated with positive tests for MPO-ANCA. Eighteen months later she had pulmonary hemorrhage and respiratory failure. An open lung biopsy showed granulomas that were diagnostic for Wegener granulomatosis. We discuss the diagnostic dilemmas faced in attempts to distinguish infective causes of pulmonary granulomas, such as tuberculosis or fungi, from granulomas associated with vasculitis, in a patient previously treated with immunosuppressive therapy.

Adolescent↗
PubMed2000

Genitourinary complications of systemic lupus erythematosus.

A 14-year-old African-American girl was diagnosed with antiphospholipid-positive systemic lupus erythematosus (SLE) in July 1994. The course was complicated by nephrotic syndrome, sepsis, hemolytic anemia, acute renal failure, saphenous vein thrombosis, cutaneous vasculitis, mesenteric vasculitis, appendicitis, hemorrhagic cystitis, and avascular necrosis of the hips. In August 1997, she developed ovarian and fallopian tube complications secondary to SLE. Genitourinary complications of SLE, however, are uncommon, and ovarian vasculitis has not previously been reported as a complication of SLE. This report describes the course of an adolescent patient with SLE and focuses specifically on her genitourinary complications.

Acute Kidney Injury↗
PubMed2000

High affinity of anti-GBM antibodies from Goodpasture and transplanted Alport patients to alpha3(IV)NC1 collagen.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) antibody-mediated diseases are characterized by rapidly progressive glomerulonephritis (RPGN) that often results in irreversible loss of renal function and renal failure. Although many factors contribute to the fulminant nature and treatment resistance of this disease, we questioned whether high affinity autoantibody-alpha3(IV) collagen interactions lead to persistent antibody deposition, thereby perpetuating inflammation. To address this hypothesis, the binding kinetics of human anti-GBM antibodies (Ab) to alpha3(IV)NC1 were evaluated using an optical biosensor interaction analysis. METHODS: Polyclonal anti-GBM Abs were purified by alpha3(IV)NC1 affinity chromatography from the sera of patients with anti-GBM AB-mediated diseases, including individuals with Goodpasture syndrome (GS), idiopathic RPGN (N = 7), and Alport syndrome (AL) following kidney transplantation (N = 4). The affinity-binding characteristics of the autoantibodies were determined using a biosensor analysis system, with immobilized bovine alpha3(IV)NC1 dimers. RESULTS: All of the autoantibody preparations bound to alpha3(IV)NC1, whereas none bound to alpha1(IV)NC1 (control). Purified, normal serum IgG did not bind to either antigen. Estimated dissociation constants (Kd) for the purified autoantibodies were 1.39E-04 +/- 7.30E-05 s-l (GS) and 8. 90E-05 +/- 2.80E-05 s-l (AL). Their estimated association constants (Ka) were 2.67E+04 +/- 1.8E+04 (M-ls-l) and 2.76E+04 +/- 1. 70E+04(M-ls-l) for GS and AL patients, respectively. By comparison with other Ab interactions, these Abs demonstrated high affinity, with relatively high on (binding) rates and slow off (dissociation) rates. CONCLUSIONS: The results suggest that anti-GBM Abs bind rapidly and remain tightly bound to the GBM in vivo. This property likely contributes to both the fulminant nature of this disease and its resistance to therapy, because persistent glomerular Ab deposition has the potential to produce continuous inflammation, despite removal of circulating Abs and adequate immunosuppression.

Animals↗
PubMed1999

Nephrotic syndrome, microcephaly, and developmental delay: three separate syndromes.

We describe a patient with microcephaly, developmental delay, and nephrotic syndrome who had normal renal function and normal brain imaging studies. She does not have the Galloway-Mowat syndrome. The concurrence of nephrotic syndrome with microcephaly and developmental delay may be coincidental, or may reflect one of at least three syndromes: Galloway-Mowat, a second syndrome of microcephaly, nephrotic syndrome and developmental delay (MNSDD), and a third syndrome of microcephaly, developmental delay, and spondylorhizomelic short stature.

Developmental Disabilities↗
PubMed1999

Selection of specific phage from display libraries: monoclonal antibody against VCS M13 helper phage coat protein III (gIIIp).

Screening of specific phage is often hampered by nonspecific binding either of the VCS M13 helper phage to the solid phase absorbent or to the polyclonal antibodies used for selection. The former is improved by increasing the stringency for selection. However, the available polyclonal anti-VCS M13 antibodies often react with immobilized antigen nonspecifically, making it difficult to distinguish between positive and negative clones. To improve this selection process, a monoclonal antibody (MAb) was produced which recognizes ligand-coat protein three (gIIIp) on the helper phage VCS M13. This MAb is highly sensitive and specific, and it is useful for selecting relevant clones. This reagent should find widespread application in identifying interactive clones from a variety of phage display libraries.

Animals↗
PubMed1998

Human Goodpasture anti-alpha3(IV)NC1 autoantibodies share structural determinants.

To examine the structural relationship among autoantibodies produced by individuals with anti-GBM antibody-mediated disease, a polyclonal anti-idiotype directed against human anti-alpha3(IV)NC1 antibodies was produced and then used to study autoantibodies from other patients. For this purpose, anti-alpha3(IV)NC1 antibodies (anti-GBM), derived from a single patient (LL) with high titer and typical anti-GBM antibody specificity, were isolated using recombinant alpha3(IV)NC1-sepharose affinity chromatography. Following hyperimmunization of rabbits with anti-GBM IgG, irrelevant rabbit anti-human IgG antibodies were removed from the antiserum using a human IgG-sepharose column. The rabbit anti-alpha3(IV)NC1 antibodies (anti-Id GBM) effluent bound to human anti-GBM antibodies, but it did not bind to either normal human IgG or recombinant alpha3(IV)NC1 protein. The Id-anti-Id interaction was conformationally dependent on intact heavy and light chains of the anti-alpha3(IV)NC1 antibodies (ELISA and Western blotting). A competitive immunoassay was developed to evaluate structural and potential genetic relationships among anti-alpha3(IV)NC1 antibodies from different patients. All patients tested (9 of 9) had a substantial fraction (producing > 50% inhibition) of anti-GBM antibodies expressing Id-GBM. The results indicate that shared determinants are expressed by anti-GBM antibodies from different individuals, and they raise the possibility that common genetic elements are used to encode them. These regions are potential targets for design of reagents to regulate autoreactive B cells and/or interfere with pathogenic antibody-GBM interactions, in individuals with anti-GBM antibody mediated diseases.

Animals↗
PubMed1998

Limited evaluation of microscopic hematuria in pediatrics.

OBJECTIVE: The purpose was to determine the value of the standard laboratory and radiologic evaluation of microscopic hematuria in children, and to determine the prevalence of idiopathic hypercalciuria in those children referred for evaluation of unexplained microscopic hematuria. METHODS: This was a retrospective study of 325 children referred from 1985 to 1994 for the evaluation of asymptomatic microscopic hematuria. The diagnostic studies reviewed included serum creatinine, blood urea nitrogen, serum electrolyte studies, serum complement concentration, antinuclear antibody, urinalysis, urine calcium to creatinine ratios, urinary protein to creatinine ratio and/or 24-hour urinary protein excretion, renal ultrasounds, intravenous pyelograms, voiding cystourethrograms, and historical information. RESULTS: All creatinine and electrolyte values were normal for age, and none of the biochemical tests obtained in the children with hypercalciuria was abnormal. Of the 325 patients with idiopathic microscopic hematuria, only 18 had abnormal renal ultrasound examinations and 9 voiding cystourethrograms showed low-grade reflux. Hypercalciuria was found in 29 patients. The family history was positive for urolithiasis in 16% of patients without hypercalciuria compared with 14% of patients with hypercalciuria. A positive family history of hematuria was reported in 25% of patients; 62 patients did not have hypercalciuria and 4 of the patients had hypercalciuria. Microscopic hematuria in children is a benign finding in the vast majority of children. CONCLUSIONS: Our data demonstrate that a renal ultrasound, voiding cystourethrogram, cystoscopy, and renal biopsy are not indicated in the work-up of microscopic hematuria, and microhematuria in the otherwise healthy child is a minimal health threat, rarely indicative of serious illness.

Adolescent↗
PubMed1997

Blood glucose control and compliance of diabetic children.

AIM OF STUDY: Non-compliance is an important factor hindering good control in diabetics. The aim of this study was to identify areas of poor compliance with the diabetes management regimen in the children attending our clinic. DESIGN: A questionnaire was administered to 57 patients who attend the Paediatric Diabetes Clinic. It was designed to elicit socio-demographic data and information about the diabetic regimen. Prior to the administration of the questionnaire, patients were classified as being well, satisfactorily or poorly controlled, based on their average glycosylated Haemoglobin results over the past year. RESULTS: All the patients used home blood glucose monitoring (HBGM)-79% of the poorly controlled children tested twice daily or less whereas 53% of the well controlled children tested three times or more daily. The timing of injections was frequently incorrect. 42% of all patients had been admitted to hospital after diagnosis and more than 60% of them never tested their blood glucose in relation to exercise. The patients' knowledge about their disease was generally good. The mean age of the poorly controlled group was almost 19 months older than that of the well controlled group. Poorly controlled children had also had diabetes for longer and they lived significantly further from the hospital. A higher percentage of poorly controlled patients were in charge of their own treatment while those in the well controlled group were less reliant on doctors for insulin dose adjustments.

Adolescent↗
PubMed1996

Noncompliance in children and adolescents after renal transplantation.

This study assesses the perceptions, knowledge, and attitudes of patients and parents attending the Pediatric Transplant Unit at the Johannesburg Hospital. Fifty-six children with renal transplants accompanied by their parents were assessed by means of a questionnaire. The children's ages were 2.53 to 20.85 years. Eleven of twelve in the noncompliant group were male and nine were Black. The ages of the two groups of patients and distance traveled to the transplant center were similar. The noncompliant group of patients more often missed clinic visits (50% vs. 14%), P=0.0201; forgot to take their medications (50% vs. 23%); and took more medications (10.3 +/- 3.0 vs. 7.5 +/- 2.0) and remembered fewer of their names (4.0 +/- 3.5 vs. 6.5 +/- 2.5), P=0.0001 than the compliant group. The noncompliant patients knew less about their disease (50% vs. 8.3%) P=0.0141, allograft (53% vs. 33%), and immunosuppression (66% vs. 200%) P=0.0217, than the compliant patients. A total of 9% of the patients (5/56) were concerned about immunosuppressive side-effects, and indicated that this affected their compliance. Families wanted additional information, both pretransplant (52%) and posttransplant (45.5%). In addition, 85% wanted ongoing in-house education concerning transplantation and medications. Pediatric renal transplant patients and their families require ongoing education, support, medication evaluation, and compliance surveillance. Patients at high risk of noncompliance require directed additional intervention.

Adolescent↗
PubMed1996

Discordant renal histopathologic findings and complement profiles in membranoproliferative glomerulonephritis type III.

Patients with membranoproliferative glomerulonephritis (MPGN) type III and a low serum C3 concentration tend to have evidence for a nephritic factor of the terminal complement pathway (Nft). Complement profiles were studied in three patients with MPGN type III and low serum C3 concentrations. Serum C3 concentrations were 52, 21, and 14 mg/dL (normal range, 83 to 177 mg/dL). Serum Clq, C2, C4, properdin, and C5 concentrations were normal in all patients, whereas two had a slight decrease of C7 or C8. This pattern of complement activation resembles that seen with MPGN type II in which a nephritic factor activates the amplification loop (NFa). We conclude that in patients with MPGN type III the previously reported profile/presence of Nft is not always found, at least in the chronic stage of the disease, despite a low C3 value.

Biopsy↗
PubMed1995

Paediatric renal transplantation non-compliance.

The aim of this study was to quantify and where possible objectively confirm the magnitude of non-compliance (NC) in our paediatric renal transplant recipients. A total of 94 paediatric transplants were performed between 1984 and 1989; 17 were excluded due to graft loss (2), death (3), oxalosis (2) and transfer to the adult unit (10). NC was assessed as missed clinic visits plus medication shortages or actual admission of NC. NC was found in 22% (17/77) of transplanted patients. NC showed no correlation with parental marital status, sex, distance lived from the hospital, pre-emptive transplant status or total lymphoid irradiation. Most NC was peripubertal with a smaller NC in the late teenager group. Social class correlated positively with NC; 82.3% of NC was from social classes III and IV, who formed 52.4% of the patients. NC in social class II (3/26) was significantly different from social class IV (12/24) (P = 0.01); 91% of black patients with NC were from social class IV. Race, corrected for social class, failed to reach significance (P > 0.05). Confirmation of compliance was sought from retrospective cyclosporin A (CsA) trough levels (twice daily dosage). Concomitant phenytoin therapy and CsA given as a daily dosage were excluded as significant confounding variables. The CsA dosage was not significantly different between the compliant (C) and patients with NC. Patients with NC were 8 times more likely to have a CsA level < 10 ng/ml (P = 0.0026) than C patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Gallium scintigraphy in the diagnosis and total lymphoid irradiation of Takayasu's arteritis.

Takayasu's arteritis (TA) in children causes appreciable morbidity and mortality, predominantly as a result of the complication of renovascular hypertension (RVH). Ten children with TA, complicated by RVH, were treated at our centre over the past decade. An initial raised erythrocyte sedimentation rate (ESR) and a purified protein derivative greater than 15 mm were present in every case. More recently, gallium scintigraphy has been used to demonstrate sites of active inflammation in affected vessels (3/4 patients) which became negative after total lymphoid irradiation (TLI). The latter was used in the last 6 children, and appeared to be effective in controlling disease activity as evinced in the normalisation of their ESRs and negative findings on gallium scintigraphy (in all 3 patients with prior active inflammation). Because of vascular damage caused by the vasculitic process, surgical intervention is often required to improve organ perfusion, particularly of the kidney/s. Renal autografting (or allografting) seems preferable (6/11 kidneys functional) to renal bypass grafting (5/5 kidneys clotted). Patient survival improved when TLI was used in addition to standard surgical and medical therapy; this included steroids and antituberculous therapy with TLI, and steroids and cyclophosphamide in the two relapses. Five of 6 patients treated with TLI were alive after 32-54 months' follow-up, while 4 patients who received standard medical and surgical therapy but not TLI all died within 18 months of diagnosis. Gallium scintigraphy is a helpful diagnostic tool in assessing vasculitic activity in TA; TLI is an important mode of immunosuppression, but still needs to be compared with cyclophosphamide as the major immunosuppressive.

Child↗
PubMed1994

Renal allograft preservation: a comparison of University of Wisconsin solution and of hypothermic continuous pulsatile perfusion.

A study was performed to compare early allograft function in kidneys preserved with University of Wisconsin (UW) solution to kidneys preserved by hypothermic pulsatile perfusion. The study consisted of two sets of data. The first set was a donor-paired study (matched data) of 30 heart-beating, hemodynamically stable donors. After removal from the donor each cooled kidney was individually prepared for preservation. One kidney was flushed with +/- 500 ml of UW solution and stored in UW solution on slushed ice. The other kidney was continuously perfused with cooled (4-6 degrees C) cryoprecipitated plasma. The kidneys were transplanted into suitable recipients in a random sequence. Twelve donors were excluded from the study because one or both kidneys were transplanted into recipients who had previously been transplanted. The remaining 36 kidneys were implanted into two similar groups after a mean of 19 hours in the pulsatile perfusion group and 18 hours in the UW solution group. The second set of data consisted of all the kidneys preserved in UW solution (n = 62) at our institution and of 57 kidneys preserved by hypothermic continuous pulsatile perfusion during the same period (mixed data) and was used to evaluate the effect of prolonged preservation (longer than 24 hours) on delayed graft function. Both of these groups were also comparable. Acute tubular necrosis (ATN) was defined as the need for dialysis during the 1st week after transplantation, and delayed function as the delayed clearance of creatinine during the early post-operative phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗