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Biomedical subjects

S L Watkins

Publications and source records attributed to S L Watkins.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cholelithiasis following Escherichia coli O157:H7-associated hemolytic uremic syndrome.

Sequelae of Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) 2-3 years following an outbreak in Washington State have been prospectively studied to identify predictors of adverse sequelae. Logistic regression analysis was used to examine associations between findings in the acute course and long-term renal and gastrointestinal outcomes. Twenty-one percent of patients had gastrointestinal sequelae, which included cholelithiasis resulting in cholecystectomy (3/29), persistent pancreatitis (2/29), late colon stricture (1/29), and/or glucose intolerance (1/29). Logistic regression analysis found long-term gastrointestinal sequelae were higher in patients who, during HUS, had hypertension [odds ratio (OR) = 21.2, 95% confidence interval (CI) = 1.9-164.4, P = 0.01] or gastrointestinal complications (OR = 21.2, 95% CI = 1.9-164.4, P = 0.01). Renal sequelae were seen in 35% of patients. One patient (4%) had persistent hypertension and 9 (31%) had minor urinary findings (hematuria or proteinuria). Thrombocytopenia lasting longer than 10 days during the acute illness was associated with a risk for subsequent renal sequelae (OR = 15.0, 95% CI = 1.98-1,703.0, P = 0.009). We conclude a high incidence of gastrointestinal sequelae, especially cholelithiasis presenting long after the acute illness, may be seen with HUS. The short follow-up period may underestimate the extent and severity of eventual renal sequelae.

Child↗
PubMed1998

The insulin-like growth factor axis and growth in children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Children with chronic renal failure (CRF) are often growth recarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF serum contribute to CRF growth failure. This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP-3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150-kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.

Child↗
PubMed1998

Current advances in the therapy of chronic renal failure and end stage renal disease.

The improved outcomes recently experienced by children with chronic renal failure and end stage renal disease (ESRD) does not obviate the need to strive to better the quality of their physical, mental and emotional well-being. This article reviews some of the recent advances in the care of these children that are intended to achieve that goal. Dialysis topics include prescription, novel solutions, adequacy measures, management of anemia, and access. Transplantation areas covered include graft and patient survival, growth, organ availability, opportunistic infections and immunity, immunosuppressive agents, and transplant-related malignancies. The care of the pre-ESRD patient is discussed with a review of new data that are being compiled in this patient population.

Child↗
PubMed1997

Improved outcome of young children on nightly automated peritoneal dialysis.

We reviewed our center's experience with nightly automated peritoneal dialysis (APD) as maintenance renal replacement therapy (RRT) for infants and children under the age of 5 years and compared it with national dialysis and transplant data. A retrospective chart review of 19 consecutive patients with the onset of end-stage renal disease (ESRD) before 5 years of age (mean = 1.8 years) between June 1988 and June 1994 was performed. All patients received nightly APD, supplemental feedings, calcitriol, erythropoietin, and 10 of 19 were on growth hormone (rhGH) therapy. The growth of our patients was maintained or improved during the study period, with the 10 of 19 on rhGH gaining a mean of one standard deviation in height when followed for 2 years. Our school-age children were all in age-appropriate classes. There were no deaths in our group; the incidence of peritonitis was lower than in national data. We conclude that APD is a realistic option for the treatment of ESRD in the 0- to 5-year-old child. Because of the improved graft and patient survival in older children, APD in a specialized center might be the RRT of choice in this age group, allowing good growth and development while maximizing the chances of an eventual and successful renal transplant.

Child, Preschool↗
PubMed1997

Modulation of growth factors by growth hormone in children with chronic renal failure. The Southwest Pediatric Nephrology Study Group.

Anthropometric measurements and circulating growth factors were studied serially in 44 prepubertal children with growth failure and chronic renal failure (GFR = 10 to 40 ml/min/1.73 m2) who were randomized to receive either recombinant human growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as Nutropin, 0.05 mg/kg/day, and the studies were carried out at baseline and after 3 and 12 months. At baseline, serum insulin-like growth factor binding protein (IGFBP)-1 and -2 levels were, while IGFBP-3 levels were not, higher than those of children with normal renal function. In addition, height SDS at baseline correlated inversely with serum IGFBP-2 levels (r = -0.461, P = 0.0016), but did not correlate significantly with any other factor. After 12 months of study, the 30 children receiving rhGH showed: (i) greater increase in height (9.1 +/- 2.8 vs. 5.5 +/- 1.9 cm, P < 0.0001); (ii) increases in serum levels of IGF-I, IGF-II, free IGF-I, IGFBP-3 and acid labile subunit (ALS); (iii) a greater decrease in serum IGFBP-1 levels; and (iv) no significant difference in serum IGFBP-2 levels, when compared to the 14 control patients. The change in height SDS after 12 months of rhGH (+0.8) in the 30 treated children correlated significantly and positively with serum ALS, IGFBP-3, total IGF, IGF-I, IGF-II and free IGF-I levels measured during treatment. These observations suggest that, in children with growth failure associated with chronic renal failure: (i) IGFBP-2, and not IGFBP-3, is likely to be a growth inhibitor; (ii) rhGH stimulates catch-up growth in part by increasing serum levels of IGF peptides; and (iii) linear growth is influenced by the balance between growth stimulating IGFs and growth inhibitory IGFBPs.

Age Determination by Skeleton↗
PubMed1997

Insulin-like growth factor-binding protein-6 levels are elevated in serum of children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

Adolescent↗
PubMed1996

A comparison of the renal and hepatic microsomal glucose-6-phosphatase enzymes.

The liver glucose-6-phosphatase enzyme has been extensively characterized and relatively little is known about the renal microsomal glucose-6-phosphatase enzyme. The reason for lack of study of the renal glucose-6-phosphatase enzyme is that it has been assumed to be the same as the liver enzyme. Immunoblotting with antibodies raised against the liver enzyme revealed differences in apparent molecular weight and antigenicity between the liver and kidney glucose-6-phosphatase enzyme proteins. Characterization of the activity of the renal glucose-6-phosphatase enzyme also showed that it is regulated differently to the liver enzyme in some metabolic states. This implies that the renal and liver glucose-6-phosphatase enzymes may have different roles.

Animals↗
PubMed1996

Is severe renal osteodystrophy a contraindication for recombinant human growth hormone treatment?

Recent extension of the use of recombinant growth hormone (rhGH) to non-growth hormone-deficient patients necessitates close attention to possible complications in these patients, including effects on bone. Recent studies on the use of rhGH in children with chronic renal failure (CRF) provide some early data. No significant differences in radiographic osteodystrophy scores, serum calcium, phosphorus, or parathyroid hormone (PTH) levels were found between treated and untreated groups. Alkaline phosphatase increased transiently. The effect of renal osteodystrophy on growth response has not yet been reported. Animal models demonstrate that GH stimulates chondrocyte proliferation. Experimental data further suggest that GH can weaken the epiphyseal plate. Slipped capital femoral epiphysis has been reported in GH-deficient patients, before, during, and after GH therapy. In CRF patients treated with GH, slipped capital femoral epiphysis has also been reported. As renal osteodystrophy and hypocalcemia are risk factors for this condition, the relationship to GH therapy is unclear in these patients. Avascular necrosis, known to be associated with slipped capital femoral epiphysis and CRF, has also been reported in patients receiving GH, although the relationship to the therapy is unknown. Children with CRF treated with rhGH should be serially monitored for renal osteodystrophy, slipped capital femoral epiphysis, and avascular necrosis with serial radiographs and serum calcium, phosphorus, alkaline phosphatase, and PTH levels.

Child↗
PubMed1996

Progress in renal transplantation for children.

Renal transplantation continues to be the goal of therapy for children with end-stage renal disease. Patient age, primary renal disease, psychosocial status, living versus cadaver donor allograft, optimal immunosuppressive therapy, urologic status, and maximization of growth and development must be considered in determining the optimal time for transplantation. Immunizations should be up to date, and the immune status of both the donor and the recipient with regard to Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, and hepatitis A, B, and C must be known. Prednisone, imuran, cyclosporine, and T cell antibodies remain the mainstay of immunosuppression. However, new therapies, such as FK-506, rapamycin, mofetil, brequinar, leflunomide, and human leukocyte antigen-derived peptides, are under investigation for use in transplantation. Complications, including infection, rejection, and malignancy, continue to be problematic in pediatric renal transplantation. Although patient and graft survival has improved over time, outcomes in pediatric renal transplantation continue to lag behind those in young adults.

Child↗
PubMed1996

Association of elevated umbilical cord blood creatine kinase and myoglobin levels with the presence of cocaine metabolites in maternal urine.

STUDY OBJECTIVE: To determine whether an association exists between antenatal cocaine exposure and elevated levels of creatine kinase (CK) and myoglobin in umbilical cord blood collected upon delivery. STUDY POPULATION: 105 anonymous maternal urines with corresponding infant umbilical cords bloods. METHODS: Maternal urines were screened for cocaine metabolites by the Syva EMIT assay, with positive specimens confirmed by gas chromatography/mass spectrometry. For all 8 positives, plus the first 47 of the negatives collected, matched infant cord blood specimens were analyzed for myoglobin by radioimmunoassay and CK by kinetic enzyme activity assay. Cord bloods matched to the remaining 50 cocaine-negative urines were not analyzed. A two-tailed Mann-Whitney test was used to evaluate the significance of differences in CK and myoglobin levels between the two groups. RESULTS: CK levels were evaluated twofold in the cocaine-positive group as compared to the cocaine negative group (mean 383 +/- 260 vs. 189 +/- 68 IU/L, p = 0.005). Myoglobin levels were twofold higher in the cocaine-positive group compared to the cocaine negative group (mean 55.9 +/- 37.1 vs. 33.3 +/- 26.8 ng/mL, p = 0.077). CONCLUSION: Antenatal cocaine exposure is associated with elevated cord blood CK, and possibly with elevated cord blood myoglobin. Additional studies, using larger study populations and more sensitive methods of detecting antenatal cocaine exposure, along with detailed follow-up examination of infants, are indicated.

Cocaine↗
PubMed1996

Human fetal testis endoplasmic reticulum glucose-6-phosphatase enzyme protein.

Microsomal glucose-6-phosphatase (EC 3.1.3.9) is an enzyme system traditionally thought to be present only in gluconeogenic tissues. We have used microassay techniques, immunohistochemistry using monospecific antibodies to the liver enzyme, and specific DNA probes and primers to examine whether glucose-6-phosphatase is present in human and rat testis. Microsomal glucose-6-phosphatase activities in human fetal testis (weeks 15-20 of gestation) are approximately 25% of corresponding liver values. Localization is predominantly in Leydig cells, with variable and weak immunoreactivity in developing seminiferous tubules. Kinetic analysis of glucose-6-phosphatase in intact and disrupted microsomes and Southern blot analysis of polymerase chain reaction products indicated that the specific glucose-6-phosphatase enzyme system was also present in rat testis. We have shown for the first time that specific microsomal glucose-6-phosphatase activity, protein, and mRNA are present in testis, and that the predominant site of expression is the Leydig cell in human fetal testis.

Animals↗
PubMed1996

Continuous venovenous hemofiltration with and without dialysis in pediatric patients.

Peritoneal dialysis (PD) is often the preferred modality in dialyzing the pediatric patient in acute renal failure. However, PD may be contraindicated in the presence of the acute surgical abdomen, respiratory compromise, or diaphragmatic disruption. The child's size and cardiovascular instability may also render hemodialysis undesirable. The use of continuous arteriovenous hemofiltration (CAVH) has been an option for the acutely ill child but requires arterial and venous access as well as adequate blood pressure to drive the CAVH circuit. Another option is continuous venovenous hemofiltration (CVVH), which obviates the need for arterial access and provides blood flow via an external pump. This article presents a retrospective of 20 acutely ill pediatric patients who received continuous venovenous hemofiltration with and without dialysis (CVVH/D) during the period covering Fall 1992 through Fall 1993 at Children's Hospital in Seattle. The children ranged in age from 1 day to 12 years (mean age 4 years) and weights ranged from 1.7 kg to 76 kg (mean 15.8 kg). Seventeen of the 20 patients were started on CVVH/D due to hemodynamic instability, 1 for PD complications, and 2 for metabolic disorders. Fluid and solute removal were achieved efficiently and metabolic imbalances were easily corrected. Patients received 1-25 days (mean 7.7 days) of CVVH/D.

Acute Kidney Injury↗
PubMed1996

Bone disease in patients receiving growth hormone.

Recent expansion of the use of recombinant growth hormone (GH) to non-GH-deficient patients demands close attention to possible complications in these patients, including effects on bone, recent studies on the use of GH in children with chronic renal failure (CRF) provide some early data. Animal models demonstrate that GH stimulates chondrocyte proliferation. Experimental data further suggest that GH can weaken the epiphyseal plate. Slipped capital femoral epiphysis (SCFE) has been reported in GH-deficient patients, having been detected before, during and after GH therapy. In CRF patients treated with GH SCFE has also been reported. As renal osteodystrophy (ROD) and hypocalcemia are risk factors for this condition, the relationship to GH therapy is unclear in this type of patient. Avascular necrosis (AVN) of the femoral head has been reported in children with congenial structural renal abnormalities and GH deficient patients treated with GH. In recent studies in over 200 children with CRF, 15 cases of AVN have been identified in treated patients. Eight were present prior to treatment; the other 7 patients were not examined radiographically prior to their treatment, and thus the relationship to GH is unknown. In several studies of GH in CRF no significant differences in radiographic osteodystrophy scores, serum calcium, phosphorus or parathyroid hormone (PTH) levels between treated and untreated groups have been found. Alkaline phosphatase increases transiently. The effect of ROD on growth response has not yet been reported. Children with CRF treated with GH should be serially monitored for AVN, SCFE and ROD with serial radiographs and serum calcium, phosphorus, alkaline phosphatase and PTH levels.

Bone Diseases↗