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Biomedical subjects

D B Allen

Publications and source records attributed to D B Allen.

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

Growth in asthmatic children treated with fluticasone propionate. Fluticasone Propionate Asthma Study Group.

OBJECTIVE: To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma. STUDY DESIGN: In a double-blind, randomized, parallel-group, multicenter study, 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 microg or 100 microg administered twice daily by a breath-actuated device for 1 year. Growth was evaluated monthly, whereas other safety variables and pulmonary function were evaluated periodically. RESULTS: The prepubescent patients showed no statistically significant differences in mean height, mean growth velocity, or mean skeletal age between any of the treatment groups at any time. Over a period of 1 year, mean height (+/- SE) increased 6.15 +/- 0.17 cm in the placebo group, 5.94 +/- 0.16 cm in the fluticasone propionate 50 microg group, and 5.73 +/- 0.13 cm in the fluticasone propionate 100 microg group (p = 0.308, overall). CONCLUSIONS: Prepubescent children treated with fluticasone propionate 50 microg and 100 microg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age.

Administration, Inhalation↗
PubMed1998

Influence of inhaled corticosteroids on growth: a pediatric endocrinologist's perspective.

Given the increasing advocacy for the use of inhaled corticosteroids as a treatment of choice for persistent asthma, growing numbers of children are being exposed to the possible growth-suppressing effects of glucocorticoids. Recent evidence strongly suggests that, when consistently administered at moderate doses, inhaled corticosteroids (IC) are capable of slowing growth in children. Whether such growth suppression would persist and ultimately affect final adult height remains unknown. Therapeutic goals which aim for uninterrupted inflammatory disease control rather than periodic symptom control may increase the occurrence of growth failure in children treated with IC. In this article, current information about the mechanisms of growth suppression by glucocorticoids and the effects of IC on growth is reviewed, and recommendations for designing studies to investigate the effects of drugs on growth are presented.

Administration, Inhalation↗
PubMed1998

Treatment of glucocorticoid-induced growth suppression with growth hormone. National Cooperative Growth Study.

Growth failure is common during long term treatment with glucocorticoids (GC) due to blunting of GH release, insulin-like growth factor I (IGF-I) bioactivity, and collagen synthesis. These effects could theoretically be reversed with GH therapy. The National Cooperative Growth Study database (n = 22,005) was searched for children meeting the following criteria: 1) pharmacological treatment with GC and GH for more than 12 months, 2) known type and dose of GC, and 3) height measurements for more than 12 months. A total of 83 patients were identified. Monitoring of glucose, insulin, IGF-I, IGF-binding protein-3, type 1 procollagen, osteocalcin, and glycosylated hemoglobin levels was performed in a subset of patients. Stimulated endogenous GH levels were less than 10 microg/L in 51% of patients and less than 7 microg/L in 37% of patients. The mean GC dose, expressed as prednisone equivalents, was 0.5 +/- 0.6 mg/kg day. Baseline evaluation revealed extreme short stature (mean height SD score = -3.7 +/- 1.2), delayed skeletal maturation (mean delay, 3.1 yr), and slowed growth rates (mean, 3.0 +/- 2.5 cm/yr). After 12 months of GH therapy (mean dose, 0.29 mg/kg x weeks), mean growth rate increased to 6.3 +/- 2.6 cm/yr, and height SD score improved by 0.21 +/- 0.4 (P < 0.01). During the second year of GH therapy (n = 44), the mean growth rate was 6.3 +/- 2.0 cm/yr. Prednisone equivalent dose and growth response to GH therapy were negatively correlated (r = -0.264; P < 0.05). Plasma concentrations of IGF-I, IGF-binding protein-3, procollagen, osteocalcin, and glycosylated hemoglobin increased with GH therapy, whereas glucose and insulin levels did not change. The following conclusions were reached. The growth-suppressing effects of GC are counterbalanced by GH therapy; the mean response is a doubling of baseline growth rate. Responsiveness to GH is negatively correlated with GC dose. Glycosylated hemoglobin levels increased slightly, but glucose and insulin levels were not altered by GH therapy.

Adolescent↗
PubMed1997

Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms.

BACKGROUND: "Respiratory burst" activity, ie, O2- production, is dependent on PO2, temperature, pH, and glucose concentrations within the physiologic range. OBJECTIVES: To determine whether environmental conditions characteristic of wounds may limit human neutrophil respiratory burst metabolism and to clarify the degree to which bactericidal oxidant production depends on local PO2. METHODS: Human blood and wound neutrophils were stimulated with phorbol myristate acetate. Oxygen consumption and superoxide production were measured over a range of 30 to 300 mm Hg PO2, 0 to 40 mmol/L glucose, pH 6.0 to 8.0, and 30 degrees C to 37 degrees C. The apparent Michaelis Menten constant for oxidant production with respect to PO2 was calculated. RESULTS: Oxygen consumption and O2- production were dependent on PO2 throughout the range tested. Half-maximal oxidant production occurred in the range of 45 to 80 mm Hg PO2 and maximal at PO2 higher than 300 mm Hg. These data agree with the highest previous estimates. Oxidant generation was also dependent on pH, temperature, and glucose concentration, but to a lesser extent. CONCLUSIONS: Leukocyte bacterial killing capacity as measured by oxygen consumption and superoxide production are substantially impaired at the low oxygen tensions often found in wounds. Changes in pH, temperature, and glucose concentration have lesser but nonetheless significant consequences. The data provide a plausible mechanism for the vulnerability of some wounds to infection and for the previous finding that increasing oxygen tension at wound sites enhances bactericidal function. Thus, the data serve as a basis for future studies on prevention of wound infection.

Acidosis↗
PubMed1997

Risk of leukemia in children treated with human growth hormone: review and reanalysis.

BACKGROUND: Data have suggested that any increased incidence of leukemia in growth-hormone (GH)-treated patients was limited to those with known risk factors for leukemia. However, previous studies may have overestimated the numbers of patient-years of risk by not excluding data from "positive-risk-factor" patients. This risk was reanalyzed by using data on children in the National Cooperative Growth Study (NCGS), with correction for this possible confounding factor. METHODS: The risk of leukemia in GH-treated patients without known risk factors was determined by using patient-years of GH therapy and patient-years since first exposure to GH therapy and the values obtained were compared with values from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. RESULTS: Three cases of leukemia in patients without known risk factors were found in the NCGS database; 3.42 cases would be expected in the 119,846 patient-years in the analysis using time since GH exposure. Two of these cases of leukemia occurred during GH therapy (67,773 patient-years); 2.13 cases would be expected. CONCLUSION: Excluding data on patients with known risk factors for leukemia provides a more accurate estimate of the risks in GH-treated patients. The incidence of leukemia in these patients is comparable to that in the general population of age-matched children.

Adolescent↗
PubMed1997

Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels.

OBJECTIVE: To evaluate the efficacy and efficiency of weight-adjusted threshold levels for 17-hydroxyprogesterone (17-OHP) in screening newborn infants for 21 hydroxylase deficiency-congenital adrenal hyperplasia (21-OH-D-CAH). DESIGN: Analysis of the number of false-positive reports and diagnoses in infants, of 21-OH-D-CAH with the use of two strategies. Before October 1993, separate criteria for definite abnormal 17-OHP levels were established and implemented for 41,846 infants on the basis of birth weight: either less than 2200 gm (17-OHP level, 90 ng/ml) or 2200 gm or more (40 ng/ml). To reduce the burden of follow-up testing in low birth weight infants, criteria for definite abnormal 17-OHP results were statistically determined for four, rather than two, birth weight divisions: 1299 gm or less (17-OHP level > or = 165 ng/ml), 1300 to 1600 gm (> or = 135 ng/ml), 1700 to 2200 gm (> or = 90 ng/ml), and more than 2200 gm (> or = 40 ng/ml). These criteria were applied to the next 149,684 infants screened, and rates of false-positive test results and of false-positive diagnoses of 21-OH-D-CAH were compared. RESULTS: Before implementation of four-tiered weight-adjusted 17-OHP criteria, 205 definite abnormal reports yielded four confirmed cases of 21-OH-D-CAH (positive predictive value = 2%; incidence of 21-OH-D-CAH = 1 in 10,461). With the revised criteria, 61 of 149,684 infants had definite abnormal results and 14 cases of 21-OH-D-CAH were confirmed (positive predictive value, 20%; incidence of 21-OH-D-CAH, 1 in 10,692). No undetected severe cases of 21-OH-D-CAH have been subsequently reported. CONCLUSIONS: Weight-adjusted criteria for 17-OHP levels in screening for 21 -OH-D-CAH markedly reduced the number of false-positive results requiring immediate follow-up testing, particularly among low birth weight infants. Increased specificity afforded by these criteria was not accompanied by diminished sensitivity in detecting severe cases. Long-term follow-up of this screened cohort will determine whether the goals of newborn screening for 21-OH-D-CAH are adequately and efficiently fulfilled by this approach.

17-alpha-Hydroxyprogesterone↗
PubMed1996

Safety of human growth hormone therapy: current topics.

Current data on patients treated with human growth hormone (GH) were analyzed for the following safety topics. New leukemia. Thirteen of 46 new cases of leukemia were in non-Japanese patients without risk factors for leukemia (compared with at least 13 new cases expected). A possible increased occurrence of leukemia with GH treatment appears to be limited to patients with risk factors. Nonleukemic extracranial neoplasms. The number of cases reported (10) does not differ significantly from the number expected. Acute pancreatitis. In five of the seven cases reported risk factors (renal failure, valproic acid use, insulin-dependent diabetes mellitus) were present. The available data do not indicate a clear cause-and-effect relation between GH therapy and pancreatitis. Prepubertal gynecomastia. Of 15 possible cases, two were pubertal, eight resolved or improved with continued GH therapy, and two resolved with the cessation of GH therapy. An effect of GH treatment on prepubertal gynecomastia remains unknown. Scoliosis. Scoliosis is reported in fewer than 1 percent of the patients in the National Cooperative Growth Study (general-population prevalence, 1.5% to 3%). Curvature progression can occur during growth acceleration, and a causal association with GH treatment is not substantiated. Pigmented nevi. Nevi growth may be increased with GH treatment. Biopsies have detected no neoplasia or premalignant nevi transformations.

Adolescent↗
PubMed1996

Growth suppression by glucocorticoid therapy.

Glucocorticoids exert multiple growth-suppressing effects, interfering with endocrine (e.g., endogenous GH secretion) and metabolic (e.g., bone formation, nitrogen retention, collagen formation) processes essential for normal growth. Relatively small oral doses of daily exogenous GC, alternate-day oral GC therapy, and even IC are capable of slowing growth in some children. These growth-inhibiting and catabolic effects of GC can be variably counterbalanced by GH therapy. With regard to linear growth, GH responsiveness depends on the GC dose and severity of underlying GC-dependent disease. Short-term risks of combined GH and GC therapy are low; longer term risks (e.g., reduced allograft function, survival, or both; increased underlying disease activity; oncologic risk) require further study. GH therapy in GC-dependent children remains experimental; children considered for such treatment should be enrolled in studies that facilitate careful monitoring and collective data analysis.

Administration, Inhalation↗
PubMed1996

Safety of recombinant deoxyribonucleic acid-derived growth hormone: The National Cooperative Growth Study experience.

The National Cooperative Growth Study has monitored the safety of recombinant human GH (rhGH) since 1985. Data have been collected from more than 19,000 children representing over 47,000 patient-years of rhGH treatment. Children receiving GH for renal disease were more likely to develop problems such as intracranial hypertension than those with GH deficiency (P < 0.01). Children with idiopathic short stature were less likely to develop slipped capital femoral epiphysis than those with GH deficiency or Turner's syndrome (P < 0.01). There was no evidence of an increased recurrence of leukemia or central nervous system tumors. There were 3 new cases of leukemia in children without known risk factors for developing leukemia and 5 cases in children with known risk factors. Growth deceleration associated with high affinity, high capacity antibodies to GH was found in only 2 of 5039 subjects tested (0.04%). Major adverse events in association with rhGH treatment have been rare, and preexisting medical conditions such as renal insufficiency may affect their frequency.

Adolescent↗
PubMed1995

Canine laryngeal transplantation: preliminary studies and a new heterotopic allotransplantation model.

While transplantation of the larynx may eventually be useful in post-laryngectomy reconstruction, three criteria must first be met before human transplants can be attempted: transplant viability must be high, immunosuppression must be safe and effective and functional recovery of the larynx must occur. To study these first two criteria, a total of 11 canine larynx transplants were performed: 3 autografts, 6 orthotopic allografts and 2 heterotopic allografts. The rationale and technical performance of these different transplant procedures are reviewed in detail. Orthotopic transplant recipients received cyclosporin A (CsA) while the heterotopic allograft recipients received RS-61443 and methylprednisolone in addition to CsA. Overall, 9 of 11 of the transplants remained viable. In contrast, all 3 autografted animals developed esophageal-cutaneous fistulas; 2 developed sepsis and were sacrificed on post-operative days (POD) 5 and 28, respectively. The third survived for 91 days and demonstrated a high degree of regeneration in the recurrent and superior laryngeal nerves of the transplant. Orthotopically transplanted dogs also had a high morbidity and perioperative mortality (5 of 6 animals). The single "long-term" survivor was treated with CsA alone, but developed complete transplant rejection on POD 33. The two heterotopic transplant recipients had no perioperative morbidity and the combination of CsA, RS-61443 and methylprednisolone given these latter animals was effective in the long-term prevention of rejection. One of these heterotopic recipients died of sepsis on POD 68 while the other remained alive and well on POD 168. Our present findings show that currently available microsurgical techniques allow experimental canine laryngeal transplantation to be done with significantly high transplant viability rates. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Lack of increased risk for extracranial, nonleukemic neoplasms in recipients of recombinant deoxyribonucleic acid growth hormone.

This report describes cases of new extracranial nonleukemic neoplasms in recombinant human GH (rhGH) recipients. The data are largely from the National Cooperative Growth Study (NCGS), with over 51,000 patient-years at risk from 12,209 patients treated with Protropin rhGH. In addition to case reports of extracranial tumors from the NCGS enrollees, there have been reports from non-NCGS patients. Ten cases of new extracranial neoplasms have been reported from this total study population, and there have been eight cases whose second neoplasms were extracranial in nature. For the new cases, the number of observed cases is compared with the number of expected cases, as derived from incidence rates published by the National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) Program. The standard morbidity ratio (SMR), defined as the number of observed cases/expected cases, is calculated for males and females separately, with further subgroup analysis based upon age. For the NCGS population, the SMRs were not statistically distinguishable from unity (i.e. 1). When the number of non-NCGS Protropin patients is estimated and SMRs are calculated for the total Protropin-treated group, the SMRs remain statistically indistinguishable from one. At present, these data suggest that rhGH does not increase the risk for developing nonleukemic extracranial neoplasms. Because a small number of additional cases could significantly alter the SMR calculations, meticulous reporting and continued surveillance must continue.

Adolescent↗
PubMed1995

The use--and misuse--of growth hormone.

Recombinant growth hormone is an effective treatment for many children with short stature, but certainly not for all of them. The approach outlined here will help you make the right choices.

Adolescent↗