Evaluation of atrial natriuretic peptide and brain natriuretic peptide in atrial granules of rats with experimental congestive heart failure.

The natriuretic peptides are believed to play an important role in the pathophysiology of congestive heart failure (CHF). We utilized a quantitative cytomorphometric method, using double immunocytochemical labeling, to assess the characteristics of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in atrial granules in an experimental model of rats with CHF induced by aortocaval fistula. Rats with CHF were further divided into decompensated (sodium-retaining) and compensated (sodium-excreting) subgroups and compared with a sham-operated control group. A total of 947 granules in myocytes in the right atrium were analyzed, using electron microscopy and a computerized analysis system. Decompensated CHF was associated with alterations in the modal nature of granule content packing, as depicted by moving bin analysis, and in the granule density of both peptides. In control rats, the mean density of gold particles attached to both peptides was 347.0 +/- 103.6 and 306.3 +/- 89.9 gold particles/microm2 for ANP and BNP, respectively. Similar mean density was revealed in the compensated rats (390.6 +/- 81.0 and 351.3 +/- 62.1 gold particles/microm2 for ANP and BNP, respectively). However, in rats with decompensated CHF, a significant decrease in the mean density of gold particles was observed (141.6 +/- 67.3 and 158.0 +/- 71.2 gold particles/microm2 for ANP and BNP, respectively; p<0.05 compared with compensated rats, for both ANP and BNP). The ANP:BNP ratio did not differ between groups. These findings indicate that the development of decompensated CHF in rats with aortocaval fistula is associated with a marked decrease in the density of both peptides in atrial granules, as well as in alterations in the quantal nature of granule formation. The data further suggest that both peptides, ANP and BNP, may be regulated in the atrium by a common secretory mechanism in CHF.

Developmental dysplasia of the hip: a new approach to incidence.

OBJECTIVE: The controversy over the incidence of developmental dysplasia of the hip (DDH) stems mainly from an ambiguity of criteria for defining a genuinely pathologic neonatal hip. In this study, we evaluate an algorithm we devised for the treatment of DDH, for its ability to identify those neonatal hips which, if left untreated, would develop any kind of dysplasia and, therefore, are to be included in the determination of DDH incidence. METHODS: Clinical and ultrasonographic examinations for DDH were performed on 18 060 consecutive neonatal hips at 1 to 3 days of life. Newborns with skeletal deformities, neurologic/muscular disorders, and neural tube defects were excluded. Hips that featured any type of sonographic pathology were reexamined at 2 or 6 weeks, depending on the severity of the findings. Only hips in which the initial pathology was not improved or had deteriorated were treated; all others were examined periodically until the age of 12 months. RESULTS: Sonographic screening of 18 060 hips detected 1001 instances of deviation from normal, indicating a sonographic DDH incidence of 55.1 per 1000. However, only 90 hips remained abnormal and required treatment, indicating a true DDH incidence of 5 per 1000 hips. All the others evolved into normal hips, and no additional instances of DDH were found on follow-up throughout the 12 months. CONCLUSIONS: The implementation of our protocol enables us to distinguish two categories of neonatal hip pathology: one that eventually develops into a normal hip (essentially sonographic DDH); and another that will deteriorate into a hip with some kind of dysplasia, including full dislocation (true DDH). This approach seems to allow for a better-founded definition of DDH, for an appropriate determination of its incidence, for decision-making regarding treatment, and for assessment of the cost-effectiveness of screening programs for the early detection of DDH.

Prevention of overtreatment of neonatal hip dysplasia by the use of ultrasonography.

The use of sonography for the neonatal screening of developmental dysplasia of the hip (DDH) results in the overdiagnosis of this entity. In 1994, we examined sonographically and clinically 8,642 hips belonging to 4,321 neonates and found 8,150 hips clinically and sonographically normal, 398 stable but with various sonographic pathology, and 81 unstable with a variety of sonographic pathology. Using an algorithm we proposed for follow-up, and treatment if necessary, we found that 90.4% of hip joints with DDH were spared unnecessary overtreatment.

Differential effects of hypothyroidism on the cartilage and the osteogenic process in the mandibular condyle: recovery by growth hormone and thyroxine.

Hypothyroidism was induced in young female Sprague-Dawley rats by the addition of methimazole (50 mg/kg BW.day) to drinking water for a period of 7 weeks (7-14 weeks of age). Replacement therapies of 0.7 U/kg BW human GH (hGH), 15 micrograms/kg BW L-T4 (T4), and a combination of hGH and T4 at the same doses were introduced during the last 2 weeks of the experiment. The responses of the cartilage and subchondral spongiosa of mandibular condyles were assessed by morphological and morphometric parameters. In addition, immunohistochemical localization of the GH receptor and insulin-like growth factor-I was determined by the streptavidin-biotin-peroxidase technique. In the hypothyroid rats, the trabecular bone volume of the subchondral spongiosa increased by 49%, indicating osteopetrosis. Along the ossification front, bone trabeculae occupied 18% and vascular elements 82% in mandibular condyles of control rats, whereas in hypothyroid rats, the percentage occupied by bone trabeculae increased to 89%. The cellularity of the cartilage in hypothyroid condyles was markedly reduced and was fully restored by T4, but not by GH replacement. Immunohistochemistry revealed the presence of GH receptors throughout the condyle regardless of the thyroid state of the animal. On the other hand, insulin-like growth factor-I immunohistochemical localization revealed the peptide to be present at all maturational stages of the cells in condyles from control and T4-treated rats, but to be lacking in young chondrocytes of hypothyroid and hGH-treated rats. This result demonstrates that the hypothyroid cartilage is compromised in its response to hGH.