Bacteria/blood/material interactions. I. Injected and preseeded slime-forming Staphylococcus epidermidis in flowing blood with biomaterials.

Blood-material interactions were studied using in vitro recirculation with human blood, slime-forming Staphylococcus epidermidis, and cardiovascular materials. Staphylococcus epidermidis, under preseeded or injected conditions, adhered to nonsmooth materials and elevated plasma levels of fibrinopeptide A (FpA) and C3a in the presence of all materials. Increased white blood cell (WBC) and platelet adhesion and thrombospondin and platelet factor 4 (PF4) release were noted for respective materials in the presence of injected bacteria. Materials that adhered significant quantities of injected S. epidermidis exhibited low levels of adsorbed proteins. Materials with high levels of preseeded S. epidermidis showed high levels of adsorbed proteins. Adhesion of preseeded bacteria and blood plasma elevations of C3a and FpA were lowest on semicrystalline polymer substrates, intermediate on halogenated substrates, and highest on amorphous substrates. In the presence of injected bacteria, WBCs and platelets adhered at earlier recirculation times to amorphous substrates than to semicrystalline substrates.

Human plasma alpha 2-macroglobulin promotes in vitro oxidative stress cracking of Pellethane 2363-80A: in vivo and in vitro correlations.

It is hypothesized in this study that the phenomenon of environmental stress cracking (ESC) in polyetherurethane is caused by a synergistic action of biological components in the body fluids, oxidative agents, and stress. An in vitro system is designed to mimic the in vivo system; human plasma contains certain biological components that can act as a stress cracking promoter, while H2O2 (Co) solution provides an oxidative reaction comparable to that observed in the respiratory burst of adherent macrophages and foreign-body giant cells. It is demonstrated that the phenomenon of in vivo stress cracking in Pellethane 2363-80A is duplicated by an in vitro system that involves a pretreatment of prestressed specimens with human plasma at 37 degrees C for 7 days followed by oxidation in 10% hydrogen peroxide with 0.10M cobalt chloride at 50 degrees C for 10 days. The pretreatment with plasma has a synergistic effect with the oxidation by H2O2 (Co) treatment to produce ESC. A plasma component responsible for promoting stress cracking in Pellethane polyurethane is identified to be alpha 2-macroglobulin (alpha 2M).

Adrenal activation and the prolactin response to exercise in eumenorrheic and amenorrheic runners.

Adrenocorticotropic hormone (ACTH), cortisol, and prolactin responses following maximal and submaximal (40 min at 80% maximal O2 consumption) running were studied in eumenorrheic (ER; n = 8, 29.0 +/- 1.5 yr) and amenorrheic (AR; n = 8, 24.5 +/- 2.0 yr) runners. ER were studied in the early follicular and midluteal phases of the menstrual cycle. Physical, training, and gynecological characteristics were similar, and cardiorespiratory and metabolic responses to the exercises were indistinguishable in the groups. ACTH, cortisol, and prolactin data from the follicular luteal phases in ER were combined for comparison to AR, because no differences were noted between the menstrual phases at rest. Similar preexercise ACTH levels and responses following exercise occurred in both groups, but preexercise cortisol levels were elevated (ER = 293.1 +/- 46.3, AR = 479.6 +/- 42.4 nmol/l) and cortisol responses blunted in AR. Adrenal sensitivity was blunted in AR compared with ER after submaximal (ER = 121.9 +/- 17.4, AR = 51.7 +/- 13.6) and maximal exercise (ER = 27.9 +/- 9.2, AR = 12.1 +/- 3.8). Preexercise prolactin levels were reduced (ER = 16.4 +/- 2.7, AR = 10 +/- 2.3 micrograms/l), and prolactin responses to maximal exercises were blunted in AR, despite high lactate levels (11.4 +/- 0.4 mmol/l). We conclude that 1) control for menstrual phase in ER is important in studies of prolactin responses following exercise but not in studies of ACTH and cortisol responses following exercise, 2) cortisol responses following submaximal and maximal exercise in AR are blunted at the adrenal level, 3) prolactin responses following submaximal and maximal exercise are also blunted in AR, and 4) prolactin responses following exercise may be mediated by adrenal activation.

Effects of menstrual phase and amenorrhea on exercise performance in runners.

There are few well controlled studies in terms of subject selection, menstrual classification, and exercise protocol that have examined both maximal and submaximal exercise responses during different phases of the menstrual cycle in eumenorrheic runners and compared these runners to amenorrheic runners. Thus, the purpose of this study was to measure selected physiological and metabolic responses to maximal and submaximal exercise during two phases of the menstrual cycle in eumenorrheic runners and amenorrheic runners. Eight eumenorrheic runners (29.0 +/- 4.2 yr) and eight amenorrheic runners (24.5 +/- 5.7 yr) matched for physical, gynecological, and training characteristics were studied. The eumenorrheic runners performed one maximal and one submaximal (40 min at 80% VO2max) treadmill run during both the early follicular (days 2-4) and midluteal (6-8 d from LH surge) phases. The amenorrheic runners performed one maximal and one submaximal (40 min at 80% VO2max) treadmill run. Cycle phases were documented by urinary luteinizing hormone and progesterone assays and by plasma estradiol and progesterone assays. No differences were observed in oxygen uptake, minute ventilation, heart rate, respiratory exchange ratio, rating of perceived exertion, time to fatigue (maximal), and plasma lactate (following the maximal and submaximal exercise tests) between the follicular and luteal phases in the eumenorrheic runners and the amenorrheic runners. We conclude that neither menstrual phase (follicular vs luteal) nor menstrual status (eumenorrheic vs amenorrheic) alters or limits exercise performance in female athletes.

Malignant osteoporosis and defective immunoregulation.

The linkage between immune cells and the osteoclast has become partially understood in the laboratory, but the full spectrum of clinical disorders of this relationship remain to be elucidated. We report a 29-month-old girl with recurrent infections and multiple fractures. Immune evaluation showed normal quantitative serum immunoglobulins but absent antibodies to the respiratory viruses and tetanus toxoid and decreased in vitro polyclonal-induced immunoglobulin production. Further analysis in vitro with separated lymphocyte populations showed normal B cell function but markedly increased suppressor T cell activity. The bone evaluation showed diffuse osteopenia on x-ray. Serum calcium, phosphorus, PTH, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal for age. Urinary calcium excretion (24 h) was, however, two times normal. An iliac crest biopsy confirmed the presence of extreme osteopenia with normal mineralization and numerous small atypical osteoclasts resorbing the bone. No circulating plasma resorptive activity was demonstrated. Calcitonin therapy markedly diminished the patient's hypercalciuria. We speculate that this patient's increased bone resorption, decreased bone formation, and suppressor activity may be linked by a common pathway involving the abnormal function of immune cells. Since no similar constellation of findings has been previously reported, this case may represent a new congenital disorder: severe osteopenia associated with increased osteoclast activity in association with a defect in T cell immunoregulation.

Relationship of somatomedin-C concentration to bone age in boys with constitutional delay of growth.

Serum somatomedin-C (Sm-C) levels increase sharply during puberty, leading to difficulty in the interpretation of Sm-C values obtained from children who exhibit a discrepancy between chronological age (CA) and pubertal development. To evaluate the utility of assessing Sm-C levels on the basis of bone age (BA), we measured serum Sm-C levels in 44 boys with constitutional delay of growth (CDG). Levels of Sm-C were compared with the normative data of the Nichols Institute Reference Laboratories (NIRL), Los Angeles, by age category, substituting BA for CA. We found the mean Sm-C level in boys with CDG to be lower than that for NIRL normal subjects in each age category for both CA and BA, but the regression curve for Sm-C levels based on BA more closely approximated the NIRL regression curve than did the curve based on CA. The rise in Sm-C levels observed in NIRL normal subjects between CA 13 to 14 years is delayed in boys with CDG until CA 15 to 17 years only when a correction for BA is not made. We conclude that in boys with CDG, Sm-C levels should be interpreted on the basis of BA rather than CA, especially during the peripubertal period. The observation of blunted Sm-C levels in all age categories, even when BA was used, suggests that short children with presumed CDG may be at high risk for a "nonclassic" form of growth hormone deficiency.

Radioimmunoassay for type I procollagen in growth hormone-deficient children before and during treatment with growth hormone.

Type I procollagen concentrations were measured by radioimmunoassay in sera from 14 growth hormone-deficient children before and during 12 months of treatment with human growth hormone. Basal procollagen levels were lower than those of control children and comparable to those of normal adults. With treatment, the mean procollagen level increased into the range of the control children and was significantly greater than the baseline level at 1, 2, 3, and 12 months (p less than 0.01; p less than 0.05). Although there was no significant statistical correlation between the growth velocity during treatment and the serum procollagen level, there was a suggestion that a high basal procollagen may be predictive of a less than optimal response to human growth hormone.