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Biomedical subjects

B Sherman

Publications and source records attributed to B Sherman.

At least 19 recordsLinked to original sources

A multicenter, open-label, prospective, randomized, dose-ranging pharmacokinetic study of the anti-TNF-alpha antibody afelimomab in patients with sepsis syndrome.

OBJECTIVE: To investigate the pharmacokinetics and safety of afelimomab, a murine antibody fragment against human tumor necrosis factor (TNF)-alpha in patients with sepsis. DESIGN: Multicenter, randomized, open-label, placebo-controlled phase I/II clinical trial. SETTING: Intensive care units of six academic medical centers in the United States. PATIENTS: Forty-eight patients with a clinical diagnosis of sepsis who received standard supportive care and antimicrobial therapy. INTERVENTIONS: Patients received 0.3, 1.0, or 3.0 mg/kg afelimomab or placebo intravenously over 20 min. Three patients in each dose group received single doses; the remaining nine patients in each group received multiple (nine) doses at 8-h intervals over 72 h. MEASUREMENTS AND MAIN RESULTS: Afelimomab appeared safe and well tolerated. Single- and multiple-dose kinetics were predictable and dose related. The elimination half-life was 44.7 h. Afelimomab treatment resulted in increased serum concentrations of TNF (includes TNF-antibody complexes) and decreased serum interleukin-6 concentrations, whereas no discernible trends were observed in placebo-treated patients. There was no significant treatment effect on 28-day mortality as was expected given the small number of patients. However, overall mortality was significantly (p = 0.001) associated with baseline interleukin-6 concentration. All patients experienced adverse events, but the vast majority were considered unrelated to the study drug and demonstrated no apparent relationship to afelimomab dose. Although 41% of patients developed human anti-murine antibodies, there were no clinical sequelae. CONCLUSIONS: Multidose therapy with afelimomab was safe, well tolerated, and had predictable linear kinetics. A large randomized trial comparing afelimomab to placebo in patients with well defined sepsis has recently been completed.

Adult↗

Assessment of dysphagia with the use of pulse oximetry.

Recent anecdotal literature has shown a relation between arterial oxygen saturation (SpO2), as measured by pulse oximetry, and aspiration during eating. The present study was designed to determine whether bedside pulse oximetry has a role in the assessment of pharyngeal phase dysphagia. Forty-six adult patients with clinically suspected swallowing abnormalities underwent modified barium swallow to evaluate dysphagia. After determining baseline oxygen saturation by pulse oximetry, different consistencies of barium were sequentially ingested. Patients were monitored for radiographic evidence of penetration or aspiration, which was correlated with continuous SpO2 recording. Patients who exhibited aspiration or penetration without clearing had a significant decline in SpO2 compared with those patients who penetrated but cleared or in whom no penetration was observed. These relations were not associated with age, gender, or diagnosis. These preliminary data indicate that bedside pulse oximetry may be a useful tool in the evaluation of patients with dysphagia.

Adult↗

Changes in thyroid hormone levels during growth hormone therapy in initially euthyroid patients: lack of need for thyroxine supplementation.

The occurrence of central hypothyroidism in previously euthyroid children during GH therapy has been reported with widely varying incidence. We monitored the acute effects on the hypothalamic-pituitary-thyroid axis in 15 euthyroid children with classic GH deficiency during the first year of GH therapy. All were initially euthyroid, as assessed by normal baseline TSH, T4, free T4, and T3 levels and negative antithyroid antibodies. A thyroid profile (T4, free T4 index, T3, rT3, and TSH) was performed at baseline and 1, 3, 6, 9, and 12-15 months after GH therapy began; a TRH stimulation test was performed at baseline and after 1, 3, and 9 months of therapy. By 1 month, there were significant decreases in T4, free T4 index, and rT3, and significant increases in T3 and the T3/T4 ratio. The changes from baseline values were greatest at 1 month, were almost universal for all thyroid values, and showed a gradual return to baseline from 3-12 months. There were no clinical signs of hypothyroidism and no change in baseline or TRH-stimulated TSH levels or in cholesterol levels, and all patients grew at velocities expected for the treatment schedule. There is little evidence for the development of clinically significant hypothyroidism in the great majority of initially euthyroid patients after GH therapy is begun. T4 supplementation is seldom needed in such patients.

Child↗

Identification of quantitative trait loci influencing wood specific gravity in an outbred pedigree of loblolly pine.

We report the identification of quantitative trait loci (QTL) influencing wood specific gravity (WSG) in an outbred pedigree of loblolly pine (Pinus taeda L.). QTL mapping in an outcrossing species is complicated by the presence of multiple alleles (> 2) at QTL and marker loci. Multiple alleles at QTL allow the examination of interaction among alleles at QTL (deviation from additive gene action). Restriction fragment length polymorphism (RFLP) marker genotypes and wood specific gravity phenotypes were determined for 177 progeny. Two RFLP linkage maps were constructed, representing maternal and paternal parent gamete segregations as inferred from diploid progeny RFLP genotypes. RFLP loci segregating for multiple alleles were vital for aligning the two maps. Each RFLP locus was assayed for cosegregation with WSG QTL using analysis of variance (ANOVA). Five regions of the genome contained one or more RFLP loci showing differences in mean WSG at or below the P = 0.05 level for progeny as grouped by RFLP genotype. One region contained a marker locus (S6a) whose QTL-associated effects were highly significant (P > 0.0002). Marker S6a segregated for multiple alleles, a prerequisite for determining the number of alleles segregating at the linked QTL and analyzing the interactions among QTL alleles. The QTL associated with marker S6a appeared to be segregating for multiple alleles which interacted with each other and with environments. No evidence for digenic epistasis was found among the five QTL.

Alleles↗

Recombinant growth hormone treatment of amyotrophic lateral sclerosis.

Based on the known trophic effects of growth hormone (GH) on nerve and muscle 75 patients with ALS were treated for up to 18 months with synthetic human growth hormone (Protropin) or a placebo. The course of ALS was assessed serially using a quantitative (TQNE) neuromuscular and manual exam (MRC) and laboratory chemistries. Average insulin-related growth factor (IGF-I) values increased from 1.2 to 2.3 U/mL in the treated group. Surprisingly, serum insulin levels did not increase. Hyperglycemia was noted in only 2 patients of the 38 patients receiving hGH, and this resolved with cessation of treatment. Over the 12 months of treatment there were 11 deaths (6 controls, 5 treated). Survival analysis, performed approximately 12 months following cessation of treatment, did not reveal a difference between the treatment and placebo group. The TQNE scores declined inexorably in both the control and treated group. Retrospective analysis of the TQNE data indicated a poor prognosis for patients who lost arm strength early. A correlation between the TQNE and MRC scores was evident at early stages of motor unit loss, less so when muscle weakness was advanced.

Adult↗

Serum levels of tumor necrosis factor-alpha and interleukin-6 in ocular cicatricial pemphigoid.

PURPOSE: These studies examined regulation of the cytokines interleukin-6 and tumor necrosis factor-alpha in ocular cicatricial pemphigoid (OCP), a systemic autoimmune disease. METHODS: Serum levels of interleukin-6 and tumor necrosis factor-alpha in sera collected from 35 patients with OCP, 29 normal persons and 17 patients with ocular inflammatory diseases were determined using an enzyme-linked immunosorbent assay. RESULTS: Levels of interleukin-6 were significantly decreased in sera of patients with OCP (median, 28.9; range, 7.5 to 136.7 pg/ml, P < 0.001) compared with sera from normal subjects (median, 65.2; range, 21.1 to 303.9 pg/ml). Sera from patients with non-OCP, extraocular inflammatory diseases and uveitis, showed no such decrease. In contrast, tumor necrosis factor-alpha levels were significantly elevated in OCP patients (median, 22.5; range, 8.3 to 44.4 pg/ml, P < 0.001), whereas no such increase was observed in sera from patients with extraocular inflammatory disease or uveitis, compared to normal sera controls (median, 17.4; range, 5 to 27.2 pg/ml). CONCLUSIONS: These results suggest that elevated serum tumor necrosis factor-alpha levels and decreased serum interleukin-6 levels can be added to the increasing list of systemic immunologic correlates of active OCP, again emphasizing that OCP is a systemic disease whose primary manifestation is ocular.

Adult↗

Urinary growth hormone and insulin-like growth factor I. Effects of growth-hormone injection schedule.

Urinary growth hormone (GH) and insulin-like growth factor I (IGF-I) excretion profiles were compared in children receiving biosynthetic GH. Group 1 included 18 healthy controls. Group 2 included nine children given biosynthetic GH three times a week. Group 3 included 14 children given daily GH injections. Overnight urine samples were collected for three consecutive nights in all groups. No significant day-to-day variation in urinary GH output was observed in group 1. In group 2, urinary GH output was significantly higher on day one following injection than on days two and three. Urine GH outputs in group 2 were significantly lower on days two and three than the values observed on all days in group 3. Throughout the three-day study, subjects in group 3 excreted similar amounts of GH significantly higher than those of controls. Urinary IGF-I output (nmol/kg) was similar on all three study days in groups 1 and 3. Group 2 had significantly lower urinary IGF-I output on day three compared with day one. Urinary IGF-I output on day three was also significantly lower in group 2 than in group 3. We conclude that urinary GH and IGF-I outputs are influenced by the frequency of GH administration.

Adolescent↗

Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone.

Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 +/- 0.3 versus 3.4 +/- 0.2 micrograms/L); group 2 had significantly lower GH concentrations (1.6 +/- 0.2 micrograms/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 +/- 2.6 nmol/L, p less than 0.001) than in groups 2 and 3 (2.6 +/- 0.5 and 5.5 +/- 0.7 nmol/L, respectively). Urinary GH (mean +/- SEM) standardized for body weight (micrograms/kg) in group 1 (0.31 +/- 0.02) was significantly greater than in group 2 (0.14 +/- 0.01) and group 3 (0.20 +/- 0.01). However, when expressed as microgram/mol creatinine, the output of GH was similar in group 1 (4.0 +/- 0.3) and group 3 (3.4 +/- 0.3); both groups had significantly greater output compared to group 2 (1.3 +/- 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 +/- 0.02) was significantly greater than in group 2 (0.12 +/- 0.01) or group 3 (0.07 +/- 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p less than 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure.

Adolescent↗

Sex differences in cognitive processing in children treated with CNS prophylaxis for acute lymphoblastic leukemia.

Evaluated cognitive processing in 51 children (27 female, 24 male) who had been treated for acute lymphoblastic leukemia (ALL) with CNS prophylaxis (cranial radiation in combination with intrathecal chemotherapy) and were continuously disease-free for 5 to 12 years. The control group comprised 15 children treated for Wilm's tumor. Functions assessed included visuoperceptual skills, generation of organizational strategies, sensitivity to organizational structure, and attention. The ALL group showed performance deficits relative to the solid tumor controls in appreciating the organization inherent in complex visuospatial material and alertness, with females more severely affected than males. Sex differences favoring males on IQ and academic achievement were related to these cognitive processes.

Adolescent↗