PubMed Health⌕ Search

Biomedical subjects

J L Nerad

Publications and source records attributed to J L Nerad.

7 recordsLinked to original sources
PubMed1996

A randomized, placebo-controlled trial of combined insulin-like growth factor I and low dose growth hormone therapy for wasting associated with human immunodeficiency virus infection.

Loss of body mass, or wasting, is a major cause of morbidity and a contributor to mortality in human immunodeficiency virus-1 (HIV-1) infection. Dietary supplements and appetite adjuvants have had limited effectiveness in treating this condition. GH and insulin-like growth factor I (IGF-I) have been shown to be anabolic in many catabolic conditions, and limited data suggest similar efficacy in HIV wasting. In addition, it appears that GH and IGF-I may have complementary anabolic effects with opposing glucoregulatory effects. We report results from a 12-week randomized, placebo-controlled trial of combination recombinant human GH (rhGH; Nutropin; 0.34 mg, sc, twice daily) and rhIGF-I (5.0 mg, sc, twice daily) in individuals with HIV wasting and without active opportunistic infection, cancer, or gastrointestinal disease. A total of 142 subjects (140 males and 2 females) were randomized using a 2:1, double blind treatment scheme and assigned to receive either active treatment or placebo injections. Eighty subjects completed the 12-week protocol. Nutritional intake and demographic and clinical characteristics did not differ between the groups at any study time point. At 3 weeks, the treatment group had a significantly larger weight increase (P = 0.0003), but this difference was not observed at any later time point. Similarly, fat-free mass, calculated from skinfold measurements, increased transiently in the treatment group at 6 weeks (P = 0.002). No significant differences in isokinetic muscle strength or endurance testing or in quality of life were observed between the groups. Resting heart rate was significantly higher in the treatment group at each time point post-baseline. GH and IGF-binding protein-3 levels did not change; however, IGF-I levels were higher in the treatment group at 6 and 12 weeks. There were no significant between-group differences in any of the measured biochemical or immunological parameters. rhGH plus rhIGF-I treatment was associated with an increased incidence of peripheral edema and other side-effects, possibly related to fluid retention. We conclude that the combination of rhIGF-I and low dose rhGH used in this study had no significant anabolic effect in HIV wasting.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Nutritional aspects of HIV infection.

Wasting may not be an inevitable consequence of HIV infection but may be a consequence of multiple nutritional insults that are additive without periods of replenishment in between. Protein energy malnutrition in AIDS patients may be consequential to underlying illness and concomitant to death as a result of that illness or may hasten a patient's demise, that is, starvation with fatal loss of body cell mass. Mortality is closely related to weight loss. Malnutrition may be a result of decreased intake, malabsorption, altered metabolism, or any combination of the three. Nutritional strategies to prevent PEM include appetite stimulation, early nutritional supplementation with oral supplements, and the diagnosis and treatment of malabsorption and underlying infections. More aggressive measures such as gastrostomy or jejunostomy tube placement and total parenteral feedings are still being evaluated. Nutritional supplementation to enhance the immune system or manipulate metabolism may be adjunctive to the above strategies. Early intervention and attention to nutritional status may have long-term benefits to patients with this disease.

HIV Infections↗
PubMed1993

Measuring circulating cytokines.

Cytokines, i.e., regulatory proteins derived primarily (but not exclusively) from cells of the immune system, are receiving increasing attention for their influences on physiological processes. This paper outlines several of the unique characteristics of cytokines and discusses the pitfalls encountered when measuring them in biological fluids. At present, each available assay has a combination of advantages and drawbacks; therefore, investigators must be aware of the trade-offs and choose the assay that best addresses their needs. The factors that affect cytokine measurement also influence cytokine activity in vivo; thus they are important from a physiological as well as methodological standpoint. Moreover, the absolute concentration of a single cytokine is probably less important than the balance between that cytokine and its natural antagonists.

Animals↗
PubMed1992

Interleukin-1 beta (IL-1 beta), IL-1 receptor antagonist, and TNF alpha production in whole blood.

The ability of an individual to mount defense responses to infection depend in part on the capacity to produce cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The specialized equipment, labor intensity, and sterile practice required for the standard in vitro evaluation of cytokine production can make such evaluation impractical in some clinical situations. We report a method for stimulating whole blood to produce cytokines that can be implemented in laboratories without tissue culture facilities and requires minimal sample preparation. IL-1 beta and TNF alpha production in whole blood samples was stimulated with endotoxin and/or phytohemagglutinin in standard EDTA-containing vacuum collection tubes. After incubation, plasma was removed and frozen for later assay. Comparison of this whole blood method with isolated mononuclear cell cultures indicated a significant correlation for IL-1 beta production (r = 0.746, P = 0.005). This technique also produced the newly described cytokine, IL-1 receptor antagonist. We conclude that the whole blood method is an acceptable alternative to isolated cell culture methods for measuring IL-1 beta in situations that preclude the standard in vitro approach.

Adult↗
PubMedDate not supplied

Comparison of granulocyte-macrophage colony stimulating factor and interleukin-1 production from human peripheral blood mononuclear cells as measured by specific radioimmunoassays.

Attention has focused on cytokine networks in which gene and protein expression of some cytokines is under the influence of other cytokines. In the present studies, we addressed the relationship between the synthesis of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-1 (IL-1) in human peripheral blood mononuclear cells (PBMC) stimulated with mitogens. Since bioassays for cytokines are sensitive to more than one of these factors, it was necessary to measure the amounts of IL-1 and GM-CSF independent of bioassays. A specific and sensitive (40 pg/ml) radioimmunoassay (RIA) was developed for human GM-CSF. The sensitivity of the RIA was greater when lysine residues were iodinated with Bolton-Hunter reagent than tyrosine residues using chloramine T. After stimulating PBMC with concanavalin A (Con A), the biological activity of GM-CSF was determined in bone marrow cultures and compared to immunoreactive GM-CSF; GM-CSF levels detected by bioassays and RIAs were highly correlated in two separate sets of experiments (r2 = 0.95 and 0.43). Incubation with Con A for 48 h induced more GM-CSF than stimulation by phytohemagglutinin (PHA) despite the fact that PHA stimulates large amounts of IL-1 alpha; indomethacin had no effect on Con A stimulated synthesis of GM-CSF or IL-1 alpha. In two separate studies, PBMC from 14 donors and a second group of 12 donors were incubated with Con A for 48 h and the total amount of immunoreactive IL-1 alpha and GM-CSF was determined in the same cell cultures. There was no correlation of the amount of either cytokines in these cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗