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Biomedical subjects

G H Bock

Publications and source records attributed to G H Bock.

At least 19 recordsLinked to original sources

Improved growth velocity with intensive dialysis. Consequence or coincidence?

Growth failure in children with end-stage renal disease remains a difficult problem. A 2.5-month-old baby in renal failure due to primary hyperoxaluria type I received intensive dialysis aimed at decreasing oxalate tissue accretion. Over 5.5 months, while awaiting transplantation, his growth velocity was 29 cm/year compared with an average 4 cm/year in infants on hemodialysis and 22 cm/year in normal infants of this age. This remarkable growth rate, which could have represented catch-up growth, is hypothesized to be related to the delivered dialysis dose. It is suggested that this relationship be evaluated in a prospective randomized trial.

Growth↗

Cytomegalovirus infections following renal transplantation--effects on antiviral prophylaxis: a report of the North American Pediatric Renal Transplant Cooperative Study.

Post-transplant cytomegalovirus (CMV) infections are a source of significant morbidity. However, the extent of the problem and the benefits of various antiviral prophylactic therapies remain incompletely understood. The North American Pediatric Renal Transplant Cooperative Study registry was screened to identify patients hospitalized for CMV infections during the 1st post-renal transplant year between 1987 and 1993. Using a control group of transplant recipients, we performed a retrospective analysis of risk factors for CMV disease among these hospitalized patients and studied the effects of various viral prophylactic strategies on CMV risk, clinical manifestations, and outcome. We identified 142 patients hospitalized with CMV infections, the majority of which included major organ involvement. A CMV-positive kidney donor was the most significant risk factor for hospitalization [odds ratio (OR) = 5.2, P<0.0001] irrespective of recipient age or CMV immune status. As opposed to antiviral agents (acyclovir, ganciclovir) or pooled IgG, prophylaxis with enriched anti-CMV IgG significantly reduced the risk of CMV hospitalization (OR = 0.31, P = 0.03). The prophylactic use of antiviral agents was associated with a decreased risk of major organ involvement during the CMV infection (OR = 0.34, P<0.005). Among the patients with CMV, the 3-year graft survival was significantly better for those who received any form of prophylaxis compared with those who received none (88% vs. 52%, P<0.001). Our findings suggest a role for combined CMV-enriched IgG and antiviral agent prophylaxis for post-transplant CMV disease. Such an approach could diminish the incidence and severity of CMV infection and appears to have an independent favorable effect on graft outcome.

Adolescent↗

Circulating erythropoietin and interleukin-6 concentrations increase in critically ill children with sepsis and septic shock.

OBJECTIVES: To investigate a possible relationship between plasma erythropoietin and interleukin-6 (IL-6) in critically ill children with sepsis or septic shock. To examine the modulatory effects of plasma from these patients on erythropoietin production in vitro, employing a cell culture system that uses the erythropoietin-producing Hep 3B cell line. DESIGN: A prospective, controlled clinical and laboratory study. SETTING: A pediatric intensive care unit and research laboratory facility at a children's hospital. PATIENTS: Children admitted to the pediatric intensive care unit with the diagnosis of sepsis or septic shock (n = 16), and control patients without infection or anemia (n = 16) were admitted to the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained from 16 children with sepsis or septic shock, and 16 age-matched controls. Plasma erythropoletin and IL-6 concentrations were measured using an enzyme-linked immunoassay. Plasma erythropoietin concentrations were significantly higher in children with sepsis or septic shock (120 +/- 26 mlU/mL) than in controls (10 +/- 2 mlU/mL) (p < .001). Plasma IL-6 concentrations were greater in children diagnosed with sepsis or septic shock (12,405 +/- 6662 pg/mL) than in control patients (7 +/- 1 pg/mL) (p < .001), and higher in septic shock patients (27,469 +/- 13,647 pg/mL) than sepsis patients (688 +/- 258 pg/mL) (p = .03). Hep 3B cells were incubated under hypoxic conditions in media containing plasma from control patients, or patients diagnosed with sepsis or septic shock. Media concentrations of erythropoietin were measured using an enzymelinked immunoassay. Hep 3B cells incubated with plasma from patients diagnosed with sepsis or septic shock produced more erythropoietin (216 +/- 23 mlU/mL) than Hep 3B cells incubated under the same conditions in media containing plasma from control patients (152 +/- 11 mlU/mL) (p = .04). Hypoxic Hep 3B cell erythropoietin production in media incubated with plasma from patients diagnosed with sepsis or septic shock correlated significantly (although weakly) with plasma IL-6 values from these same patients (p = .03, r2 = .28). CONCLUSIONS: Plasma erythropoietin and IL-6 values are increased in critically ill children with sepsis or septic shock in comparison with controls. The data indicate that one or more plasma factors are responsible for stimulation of hypoxia-induced erythropoietin production in the Hep 3B cell line and suggest a possible role for IL-6 in the regulation of erythropoletin production in critically ill children with sepsis or septic shock.

Adolescent↗

Current status of pediatric home peritoneal dialysis training in the United States.

There are little aggregate data that examine attributes of peritoneal dialysis (PD) training programs for children. We determined characteristics of pediatric home PD training programs in a sample of 54 centers in the NAPRTCS PD registry by telephone interview. Sixty-seven percent of the programs trained pediatric patients only (P-only); 33% were combined pediatric/adult (P/A) programs; 33 programs had dedicated training rooms. Most programs trained 5 to 8 patients/year; only 2 trained more than 12 patients/year. Forty-eight of 54 programs (89%) taught both automated and manual PD techniques; the preferred type of PD varied. All units preferred to train 2 people. The patient was often one of the trainees, but the minimal eligible age varied greatly. The patients were trained as inpatients (IP) in 38 units (70%) and as outpatients (OP) in 16 units (30%). P-only programs were less likely to train as OP (20%) than P/A programs (50%) (p < 0.01). There was no difference in the mean training time for P-only versus P/A programs. However, training that took more than 6 days occurred more often when done as an IP (79%) than as an OP (56%) (p = 0.057). Furthermore, only 25% of IP units that took more than 6 days to train offered training on the weekend; none of the IP units that took more than 10 days offered weekend training. In conclusion, the structure of PD training programs for children in the United States varies tremendously. OP training is usually shorter in duration and potentially more cost-effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

An assessment of serum and urine soluble interleukin-2 receptor concentrations during renal transplant rejection.

During rejection, renal transplant recipients have increased concentrations of soluble interleukin-2 receptors (sIL-2R) in their serum and urine. However, the clinical application of this measurement in the diagnosis of rejection or the assessment of treatment efficacy is limited by the variance of the measurement in sample populations. We examined the serum and urine sIL-2R concentrations in 20 renal transplant recipients, 12 of whom experienced 13 episodes of allograft rejection. There was no statistical difference in the mean serum sIL-2R concentration at the time of rejection compared with the baseline value (2,817 +/- 801 v 1,943 +/- 255 U/mL). By contrast, the urinary excretion rate, expressed as units of sIL-2R per milligram creatinine, was 26.2 +/- 6.4 compared with 14.2 +/- 2.5 (P < 0.05). Furthermore, when urinary sIL-2R was expressed as a fractional excretion (FE), both the absolute measurement (4.4% +/- 1.7%) and the percent increase (+245%) at the time of rejection provided the greatest degree of discrimination of rejection from those values during allograft stability (1.2% +/- .2% and +2.5%, respectively; P < 0.005). We conclude that (1) serum and urine sIL-2R concentrations are affected by a number of factors during rejection; (2) FE calculations of sIL-2R improve discrimination of rejection from graft stability; and (3) serial measurement of sIL-2R excretion may be a useful adjunct to the diagnosis of rejection and, possibly, the subsequent assessment of response to immunotherapy.

Adult↗

A proposed method for the noninvasive evaluation of renal asymmetry in a living-related donor candidate.

This report proposes an adjunctive technique for the evaluation of asymmetry of renal size and function of undetermined etiology, discovered during the assessment of two living-related donor candidates. The method utilizes the observation of renal functional reserve measurement as demonstrated by oral protein loading in patients with normal and diseased kidneys. Renal function was measured as timed Ccr and estimation of differential GFR by technetium-99m diethylenetriaminepentaacetic acid (99mTcDTPA) scintigraphy. A comparison of renal function before and after protein loading in two such patients demonstrated the anticipated increase in GFR. No change in differential GFR as determined by renal scan in one patient was interpreted as supportive evidence for bilaterally normal parenchymal function. Follow-up of both donors shows continued normal renal function.

Adolescent↗

Serum and urine soluble interleukin-2 receptor in idiopathic nephrotic syndrome.

Although a cellular immune pathogenesis is suspected in idiopathic nephrotic syndrome of childhood (INS), there is scant direct evidence of in vivo immune activation. In order to investigate cytokine cascade activation in INS, soluble interleukin-2 receptor (sIL-2R) in plasma and urine was characterized and its levels measured in INS patients during relapse. Immunochemically detectable sIL-2R had a molecular mass of 35-46 kDa in both serum and urine and the molecule appears to be excreted intact; the pI was 5.05. INS patients had elevated serum sIL-2R levels compared with adult normal controls (845 +/- 97 vs. 373 +/- 47 U/ml, P = 0.001) and were significantly higher than previously published age-matched controls. Urinary excretion of sIL-2R was 47.2 +/- 13 U/mg creatinine in patients. Both the sIL-2R excretion rate and the fractional excretion of sIL-2R were positively correlated with the excretion of albumin (P = 0.02 and 0.002, respectively). These increased serum and urine levels occurred whether relapse was or was not associated with an intercurrent illness. We conclude that: (1) despite increased sIL-2R excretion during INS relapse, serum levels are significantly elevated; (2) while the elevated urinary levels could result from enhanced intrarenal production, they more likely reflect the increased serum levels; (3) the elevated sIL-2R levels support an immune pathogenesis in INS.

Adolescent↗

Characterization of a new IL-6-dependent human B-lymphoma cell line in long term culture.

We have established a cell line (DS-1) of B-cell lineage in long-term culture. It was derived from an immunodeficient patient with intestinal lymphangiectasia and lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(-). Cell proliferation was poor in medium and exhibited an eight-fold, dose-dependent increase of proliferation in response to rIL-6 of human but not murine origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced by rIL-6. While constitutive production of IL-6 was not detected by bioassay using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%) and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies arising in patients with AIDS and other immunodeficiency diseases. Despite constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell line may also facilitate development of strategies for diagnosis and treatment of B-cell lymphomas in immunocompromised patients.

Adult↗

Accelerated growth rates in children treated with growth hormone after renal transplantation.

To determine the usefulness of growth hormone treatment among children with renal allografts, we treated nine children with functioning renal transplants who were less than 16 years of age and had poor growth. The nine children, who were aged 12.6 +/- 4.0 years, had (1) heights greater than 2.5 SD less than the mean for age, (2) growth rates less than or equal to 5 cm/yr, and (3) additional growth potential, as assessed by bone age (8.9 +/- 2.8 year). Insulin-like growth factor I, thyrotropin, and thyroid hormone levels were normal for age in all children. Growth hormone treatment increased growth rates from 1.9 +/- 1.1 cm/yr to 7.2 +/- 1.8 cm/yr without accelerating skeletal maturation and without advancing pubertal status. During growth hormone treatment, serum creatinine concentration rose from 140 +/- 50 to 190 +/- 80 mumol/L (1.6 +/- 0.6 to 2.1 +/- 0.9 mg/dl) (p less than 0.05), and creatinine clearances decreased from 0.79 +/- 0.37 to 0.58 +/- 0.30 ml/sec per 1.73 m2 (47 +/- 22 to 35 +/- 18 ml/min per 1.73 m2) (p less than 0.05) but then remained stable. Growth rates of two patients returned to pretreatment rates when growth hormone treatment was discontinued after 5 and 7 months because of increased serum creatinine values. Growth hormone treatment may be useful as adjunctive therapy for increasing growth rates in selected children with renal allografts who have poor growth; however, serum creatinine concentrations should be closely monitored during such treatment.

Adolescent↗

Glucose tolerance in children with renal allografts and effect of growth hormone treatment.

We performed oral glucose tolerance tests (oGTTs) on 15 children who had functioning renal allografts received greater than or equal to 18 months previously, had adequate renal function, and had heights greater than 2.5 SD below the mean height for age. Three of the children had impaired glucose tolerance; their mean glucose levels during the last 2 hours of the oGTT were higher (p less than 0.05) than published control values. Integrated glucose concentrations correlated inversely with the prednisone dose on the first day of an alternate-day dosage schedule (R2 = 0.383) and directly with adiposity (partial R2 = 0.322). The integrated insulin concentration correlated directly with the prednisone dose on day 1 of an alternate-day regimen (R2 = 0.355) and with age (partial R2 = 0.163). In 10 children with renal transplants who had been treated with growth hormone for greater than or equal to 6 months, the mean fasting glucose concentration, integrated glucose concentration, and integrated insulin concentration during the oGTTs obtained after 6 months or 12 months of growth hormone treatment were not significantly different (p greater than 0.05) from values measured before the treatment. We conclude that increased integrated concentrations of both glucose and insulin during oGTTs in children with renal allografts correlate with the dose of prednisone administered on the first day of an alternate-day schedule, with age, and with adiposity index. Growth hormone treatment of children with renal allografts who are growing poorly does not significantly affect glucose metabolism as assessed by oGTT.

Adolescent↗

Restoration of kidney function after prolonged renal artery occlusion.

An 11-month-old child developed renal artery occlusion (RAO) and anuric renal failure following an unsuccessful transluminal renal artery angioplasty of a solitary kidney. Despite the prolonged period of anuria, kidney viability was suspected based upon preservation of kidney length and the absence of glomerulosclerosis. At 19 months of age, revascularization of the kidney was performed. During the 7 months following revascularization, renal function gradually improved so that dialysis was no longer necessary. This improvement occurred in spite of significant tubular atrophy. Kidney viability may have been preserved, despite prolonged ischemia, as a result of the decreased renal oxygen consumption that existed during subfiltration glomerular perfusion pressures. The low normal blood erythropoietin level may have reflected the lack of renal hypoxia. The ability of the kidney to adapt to chronic ischemia underscores the importance of considering vascular reconstruction in all patients with RAO despite a long period of non-function.

Humans↗

Feeding disorders and gastroesophageal reflux in infants with chronic renal failure.

Twenty-two infants (mean age 7.5 months) with chronic renal failure (CRF) were studied for their nutrition, growth, and upper gastrointestinal function. Most infants had a history of poor caloric intake and 7 had received supplemental feeding (SF) prior to the investigation. All infants were undergrown, underweight, and malnourished. The infants were characterized as having only a fair interest in food, refusing feedings, and vomiting excessively. Sixteen of 22 infants (73%) had significant gastroesophageal (GE) reflux demonstrated by 24-h esophageal pH monitoring. Gastroesophageal scintiscans were less sensitive and specific in detecting the reflux. Infants with GE reflux were significantly younger and more often required SF than those without GE reflux. There were no significant differences in the degree of renal failure, growth failure, caloric intake, protein intake, or nutritional status between the infants with and without GE reflux. From these studies we conclude that GE reflux should be considered as one of the factors contributing to the feeding problems of infants with CRF.

Energy Intake↗

Renovascular hypertension in children: current concepts in evaluation and treatment.

Since 1981, we have evaluated and treated 22 children with renovascular hypertension (RVH). Seventeen patients had stenosis of their native renal arteries, and five had stenosis of the artery in a transplanted kidney. RVH was caused by fibromuscular dysplasia in 13 patients, by trauma in 2 patients, and by arteritis in 2 patients. Among the patients who had transplanted kidneys, three had technical causes for stenosis and two had stenosis due to rejection. The disease was unilateral in 10 patients, bilateral in 5, and present in a solitary kidney in 7, including the five renal transplants. Diagnostic studies that strongly suggested the presence of renovascular disease were an initial diastolic blood pressure greater than 100 mm Hg, an elevated peripheral vein renin activity level, and an abnormal renal scan if the patient's hypertension was being controlled with an angiotensin-converting enzyme inhibitor (ACEI). Only the renal arteriogram was 100% accurate in confirming the presence of RVH. Percutaneous angiographic correction was attempted in 13 patients and resulted in lasting improvement of the hypertension in five (38%). Surgical revascularization was attempted in 17 children, including the 8 with failed angioplasty, with improvement or cure of the hypertension in 15 patients (88%). Combining percutaneous transluminal angioplasty (PTA) and surgical results gave 20 of 22 patients (91%) with cure or improvement of their hypertension. Four of 27 affected kidneys (15%) could not be revascularized and were removed. We conclude from this series of patients that despite improvements in noninvasive studies, renal arteriogram remains the only study that is 100% accurate in evaluating children for RVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Disturbances of brain maturation and neurodevelopment during chronic renal failure in infancy.

Fifteen infants with moderate to severe congenital renal disease were prospectively studied by serial renal, neurodevelopmental, neurophysiologic, and anthropometric assessments. The observation period ranged from 3 to 25 months (mean = 10.9). Eight patients maintained a Mental Development Index (MDI) above the 16th percentile (greater than -1 SD) and comprised group 1. Of the remaining seven patients (group 2), three had an MDI less than 16th percentile when first studied and four had serial decreases of the MDI to less than 16th percentile. Although motor development was more delayed in group 2 at study entry, there were no significant changes of motor performance levels for either group during the study period. Group 2 patients had smaller length (p less than 0.05) and head circumference (p less than 0.05) standard deviation scores in comparison with group 1, and they had higher serum creatinine values (mean = 3.8 vs 1.3 mg/dl, respectively; p less than 0.01). By spectral electroencephalography, the expected progressive increase of the frequency of cerebral cortical background activity with age was demonstrated in group 1 but was not seen in group 2 (multivariate analysis of variance p less than 0.03). This increase of faster-frequency activity was primarily manifested in the left cerebral hemisphere of group 1 patients (p less than 0.01), a finding that was also absent in group 2. The frequent occurrence of neurodevelopmental abnormalities in infants with renal failure is possibly a consequence of impaired dominant hemispheric maturation in the first several years of life, which is clinically manifested as deterioration of cognitive function.

Cephalometry↗

Hyponatremia in the very young chronic peritoneal dialysis patient.

Two anuric infants had recurrent hyponatremia during chronic peritoneal dialysis (PD). This occurred because at normal serum sodium concentrations ([Na]), Na losses from ultrafiltration (UF) were greater than the Na ingested from infant formula. Hyponatremia was corrected with increased oral Na intake or with increased dialysis solution [Na]. Anuric infants undergoing PD have hyponatremia because of their high UF requirements/body weight and the low Na content of proprietary infant formulas.

Body Weight↗

Relief of respiratory distress with leukapheresis in a child with chronic myelocytic leukemia.

Therapeutic leukapheresis of a 10-year-old girl with adult-type chronic myelocytic leukemia is described. The efficiency of WBC removal was noted to improve significantly after addition of hydroxyethyl starch to the anticoagulant infusion. In fact, the percentage of white cells removed more than doubled (39% vs. 16%) when comparing procedures of similar duration, with and without the sedimenting agent. Of particular interest was the relief of the patient's respiratory distress concomitant with the decline in her leukocyte count, a finding that has not previously been documented in pediatric patients. The arterial oxygen pressure remained greater than 95 mmHg after the procedure with hydroxyethyl starch compared with 70 mmHg after the procedures without it. In addition, her respiratory rate decreased from 70 on admission to the low 20s after the final procedure. Leukapheresis with hydroxyethyl starch was shown to be a safe procedure, and the use of hydroxyethyl starch was shown to be of particular benefit for prevention of prolonged apheresis procedures.

Child↗