Stimulation of collagen synthesis and linear growth by growth hormone in glucocorticoid-treated children.

Impaired linear growth and skeletal maturation associated with chronic glucocorticoid therapy may result from (1) inhibited insulin-like growth factor 1 (IGF-1) activity; (2) impaired type 1 collagen synthesis; or (3) suppressed growth hormone (GH) secretory response to growth hormone-releasing hormone. Each mechanism could potentially be improved by exogenous GH treatment. Seven slowly growing glucocorticoid-treated children received recombinant DNA human GH (0.3 mg/kg/per week) for 6 to 21 (mean 13.1 +/- 4.9) months. Height, weight, IGF-1 activity, glycosylated hemoglobin level, and C-terminal type 1 procollagen level were measured every 3 months and growth velocity was calculated. Skeletal maturation and 2-hour postprandial serum glucose and insulin levels were assessed every 6 months. All patients showed increased growth velocity during treatment with GH. Mean growth velocity increased from 3.43 +/- 0.65 cm/y to 6.72 +/- 0.84 cm/y with GH therapy (P less than .005). Growth velocity standard deviation scores corrected for bone age (P less than .005), IGF-1 levels (P less than .05), and C-terminal type 1 procollagen levels (P less than .005) also increased with GH therapy. C-terminal type 1 procollagen levels correlated well with growth velocity (r = .652) while IGF-1 levels did not (r = .17). Glycosylated hemoglobin levels remained unchanged, but 2-hour postprandial glucose levels rose during GH treatment. Slowly growing glucocorticoid-treated children receiving GH therapy increased growth velocity for 6 to 21 months. Initially diminished C-terminal type 1 procollagen levels rose with GH therapy, a change which corresponded with growth acceleration.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of collagen propeptides as growth markers in children with inflammatory bowel disease.

The serum concentrations of the carboxy-terminal propeptide of type I procollagen and the amino-terminal propeptide of type III procollagen as biochemical markers of growth activity were compared in 46 children and adolescents with inflammatory bowel disease. Significant correlations were noted between growth velocity and type I procollagen (r = 0.65; P less than 0.001) and type III procollagen concentrations (r = 0.64; P less than 0.001). Although the serum concentration of type I procollagen was generally about 15 times greater than that of type III, the respective serum concentrations were highly correlated (r = 0.66; P less than 0.001) at all growth velocities. The use of daily corticosteroid therapy was associated with significantly lower concentrations of both propeptides (P less than 0.01) than was alternate-day or no corticosteroid therapy, respectively. Children with growth arrest (0.0 cm/mo) had type I and type III procollagen concentrations similar to those found in adults. These observations indicate that the serum concentrations of both collagen propeptides reflect growth activity in children with inflammatory bowel disease and suggest that routine measurement of collagen propeptides may have clinical value in monitoring normal and abnormal growth. The data suggest that the measurement of one propeptide does not offer an advantage over the other.

Longitudinal assessment of type I procollagen in children with inflammatory bowel disease subjected to surgery.

Using radioimmunoassay we have measured the serum concentrations of the C-terminal propeptide of type I procollagen (pColl-I-C) in 12 Tanner I-II subjects (aged 9-16 years) with severe Crohn's disease (8 patients) or ulcerative colitis (4 patients) and markedly decreased growth velocity who were subjected to surgery and 50 similarly aged children with either ulcerative colitis (20 patients) or Crohn's disease (30 patients) and normal growth. Prior to operation, the mean growth velocity and pColl-I-C concentration in the former group of 12 children were 0.03 +/- 0.02 cm/month (normal greater than or equal to 0.5 cm/month) and 14.1 +/- 1.9 micrograms/dl, respectively. This pColl-I-C concentration is comparable with that previously reported for adults (5-17 micrograms/dl) and significantly lower than found in the 50 normally growing children with inflammatory bowel disease (IBD) (46.9 +/- 2.0 micrograms/dl) (p less than 0.001). All 12 children subjected to surgery had a marked increase in growth velocity and pColl-I-C concentration to 0.73 +/- 0.08 cm/month and 59.1 +/- 5.6 micrograms/dl, respectively (p less than 0.001 compared with preoperative values). Changes in pColl-I-C concentrations antedated measurable changes in linear growth. These data suggest that pColl-I-C concentrations can reflect growth velocity in children with IBD subjected to surgery and may provide a rapidly available measure of current "growth activity."

Breast-feeding attitudes and practices among adolescents.

Breast-feeding attitudes of 128 low-income, pregnant adolescents were assessed using a questionnaire developed for this population. Teens who had been breast-fed as infants had more positive attitudes than bottle-fed teens (p less than 0.002); no differences in attitudes were found by race or age. Pregnant teens who planned to breast-feed their infants had higher attitude scores than those who planned to bottle feed or who were uncertain (p less than 0.001). Of the sample, 32.4% subsequently breast-fed their baby; these teen mothers had more positive attitude scores than the teen mothers who bottle fed (p less than 0.001). The prenatal infant feeding plans of these pregnant teens were significantly related to their postnatal feeding practices (p less than 0.001). Selected implications of these data for health care professionals are discussed.

PIP: Breastfeeding attitudes of 128 low-income, pregnant adolescents were assessed using a questionnaire developed for the urban population attending the Teen Pregnancy Service of Milwaukee, Wisconsin. The sample was between 13 and 20 years of age (mean age = 17.7 years). There were 14 adolescents 15 years of age or less, 81 teens 16-18 years, and 31 19-20 years. 68% were black, 6% hispanic, 24% white and 2% other. 100% were enrolled in the Special Supplemental Food Program for Women, Infants, and Children (WIC) 84% were receiving Title 19 benefits. Most were having their 1st child (72%); 21 had 1 other child; 6 had 2, and 2 mothers had 4. Teens who had been breastfed as infants had more positive attitudes than bottle-fed teens (p0.002); no differences in attitudes were found by race or age. Pregnant teens who planned to breastfeed their infants had higher attitude scores than those who planned to bottle feed or who were uncertain (p0.001). Of the sample, 32.4% subsequently breastfed their baby; these teen mothers had more positive attitude scores than the teen mothers who bottle fed (p0.001). The prenatal infant feeding plans of these pregnant teens were significantly related to their postnatal feeding practices (p0.001). Health care professionals could use the breastfeeding questionnaire, combined with information about a pregnant teen's plans for infant feeding, to provide baseline data regarding a pregnant adolescent's breastfeeding attitudes. Such information can be efficiently obtained during an early prenatal visit. Subsequent prenatal visits could correct teen misconceptions about breastfeeding (e.g. results in obesity) and emphasize the positive benefits to the infant and mother. It may be useful to invite the teen's boyfriend and mother, given the impact of these individuals on the teen's breastfeeding attitudes. Once a teen decides to breastfeed, significant support is required following delivery to ensure a positive experience. Studies show a "lactation support team" may make significant changes in increasing the use of breastfeeding.

Relationship of type I procollagen to corticosteroid therapy in children with inflammatory bowel disease.

We determined the serum concentration of the C-terminal propeptide of type I procollagen (pColl-I-C) in 60 children and adolescents (ages 4 to 17 years) with inflammatory bowel disease (24 ulcerative colitis, 36 Crohn disease) and in seven children (ages 2 to 15 years) with nongastrointestinal disease (asthma) during varying regimens of corticosteroid therapy. Patients with inflammatory bowel disease were grouped according to disease severity (mild, and moderate to severe). Significantly lower pColl-I-C concentrations and growth velocities were found in each severity group among those subjects receiving daily corticosteroid therapy compared with those receiving alternate-day or no corticosteroid therapy (P less than 0.01). When daily corticosteroid therapy was initiated and then maintained for 7 to 14 days in 11 patients with exacerbation of inflammatory bowel disease clinical improvement resulted, but mean procollagen concentrations decreased significantly (P less than 0.001). In seven children with asthma receiving methylprednisolone intravenously, significant decreases in pColl-I-C concentrations were noted within 24 to 48 hours of therapy (P less than 0.001). These data indicate that serum procollagen values decrease during both short- and long-term daily administration of corticosteroid therapy. Longitudinal assessment of procollagen concentrations may provide rapid assessment of the effects of different corticosteroid regimens on growth.

Prenatal education for pregnant adolescents.

Providing services to pregnant adolescents poses a unique challenge for health professionals. Several programs have emerged tailored specifically to this special population. Prenatal education is an integral component of these programs. This paper describes prenatal education classes offered at Teen Pregnancy Service, including special modifications required to meet the learning needs of participants. Outcome data provided for 66 pregnant teens show significant changes in prenatal knowledge following the class series. Information is included about the teens' backgrounds, their perceptions regarding potential problems infants may experience, and how they remembered being reared by their parents.

Type 1 procollagen as a biochemical marker of growth in children with inflammatory bowel disease.

Using radioimmunoassay, we measured the levels of the C-terminal propeptide of type I procollagen (pColl-I-C) in sera from 69 children with functional bowel disease (control population), 18 children with ulcerative colitis, and 35 children with Crohn disease. Sexually mature fully grown adolescents from all three patient groups had mean pColl-I-C concentrations (12.0 +/- 0.8 micrograms/dl) similar to those previously reported for adults (5 to 17 micrograms/dl). Children with functional bowel disease and normal growth had significantly higher concentrations (32.8 +/- 1.7 micrograms/dl) (P less than 0.001) than did the fully grown adolescents. In patients with inflammatory bowel disease a significant relationship between growth velocity and pColl-I-C concentrations was noted (P less than .001). Lower pColl-I-C concentrations were found in patients receiving daily prednisone therapy compared with those receiving alternate-day therapy (P less than 0.01) or those not taking the drug (P less than 0.01). These data suggest that pColl-I-C concentrations reflect growth activity in children. Repeated determinations may allow rapid assessment of the effects of various therapeutic modalities on growth in children with inflammatory bowel disease.

The carboxyl fragment released by bacterial collagenase from human type I procollagen: antibodies to the propeptide determinants.

A protocol is offered for the isolation of the carboxyterminal propeptides of human type I procollagen and the development of an antibody specific for these propeptides. Type I procollagen was harvested from the media of cultured human fibroblasts. Digestion with bacterial collagenase released a carboxyterminal fragment that was isolated by ion-exchange chromatography. The fragment contained telopeptides joined to propeptides and could be cleaved by a carboxyl procollagen peptidase. Rabbit antibodies raised to the collagenase-generated fragment were sequentially adsorbed on affinity columns of the reference antigen and human type I collagen. The antibody obtained was shown by sensitive radioimmunoassays to recognize conformational carboxyl propeptide determinants and not to react with triple helical and telopeptide determinants of human type I collagen. Indirect immunofluorescence and indirect immunoperoxidase staining of cultured fibroblasts localized the antigen in the cytoplasm, at the cell surface, and in the extracellular matrix. A radioimmunoassay with the same antibody has reported altered concentrations of the antigen in the sera of patients with diseases affecting collagen metabolism (Taubman, et al., 1976; Savolainen et al., 1984; Carey et al., 1985).

Ultrastructural immunocytochemical localization of type I procollagen in cultured human fibroblasts.

An immunoelectron microscopic study of cultured human fibroblasts was performed with antibody specific for the carboxyl propeptides of human type I procollagen (Goldberg et al., 1985). In cells permeabilized with detergent, the unlabeled antibody peroxidase-antiperoxidase method localized the antigen in the rough endoplasmic reticulum, in the Golgi complex, and upon the plasma membrane. Immunostained thread-like periodic fibrillar aggregates within cytoplasmic vacuoles were not apparent. Extracellular fibrils 20-80 nm in thickness were diffusely and heavily stained. Immunostaining also defined a thin extracellular periodic fibril (diameter 10-20 nm; axial period 53.7 nm +/- 6.5 S.D.). These data are discussed in terms of current views of procollagen secretion and collagen fibrillogenesis.

Binding of soluble type I collagen to fibroblasts: effects of thermal activation of ligand, ligand concentration, pinocytosis, and cytoskeletal modifiers.

Efficient binding of native, soluble 125I-labeled type I rat collagen to mouse 3T3 fibroblast monolayers requires prior warming of the ligand to 35-37 degrees C for 10-30 min. Decreased binding at high ligand concentrations is ascribed to ligand-ligand interactions rather than to negative cooperativity. Addition of bacterial collagenase to monolayers labeled with the 125I-ligand releases a constant fraction (80%) of the bound ligand over a 2-h interval at 37 degrees C, indicating that little of the ligand becomes inaccessible by pinocytosis. Colchicine (10(-7) M) and vinblastine (5 X 10(-8) M) do not inhibit binding by morphologically intact monolayers. Cytochalasins and concanavalin A show dose-related inhibition of binding by intact monolayers that is due to a reduction in the number of available binding sites rather than to a change in binding site affinity. The collagen binding site on the fibroblast surface is proposed as an organizing center for the assembly of periodic type I collagen fibrils.

Binding of soluble type I collagen to fibroblasts: specificities for native collagen types, triple helical structure, telopeptides, propeptides, and cyanogen bromide-derived peptides.

Unlabeled collagenous proteins were quantified as inhibitors of binding of native, soluble, radioiodinated type I collagen to the fibroblast surface. Collagen types IV, V a minor cartilage isotype (1 alpha 2 alpha 3 alpha), and the collagenlike tail of acetylcholinesterase did not inhibit binding. Collagen types II and III behaved as competitive inhibitors of type I binding. Denaturation of native collagenous molecules exposed cryptic inhibitory determinants in the separated constituent alpha chains. Inhibition of binding by unlabeled type I collagen was not changed by enzymatic removal of the telopeptides. Inhibitory determinants were detected in cyanogen bromide-derived peptides from various regions of helical alpha 1 (I) and alpha 1(III) chains. The aminoterminal propeptide of chick pro alpha 1(I) was inhibitory for binding, whereas the carboxyterminal three-chain propeptide fragment of human type I procollagen was not. The data are discussed in terms of the proposal that binding to surface receptors initiates the assembly of periodic collagen fibrils in vivo.

A modern definition of death?

Throughout the ages, man has struggled to define exactly when death takes place. Common law dictated that the presence or absence of a heartbeat indicated whether or not a person was alive. In more recent years, this definition has changed to include brain activity as an important criterion. However, legislation resulting from this changed definition has only brought about more questions--such as what criteria shall be used to decide brain death.