Bone Growth Retardation Research Articles

Rhegmatogenous Retinal Detachment in Labrador Retrievers

We used clinical and pathologic methods to examine ten Labrador retrievers with ocular and skeletal abnormalities. The major ocular findings were axial myopia; cataract; vitreous abnormalities, including liquefaction, detachment, and vitreoretinal traction; retinal tears; rhegmatogenous retinal detachment; and proliferative vitreoretinopathy. The appendicular skeleton showed retarded bone growth, bone dysplasia, and degenerative arthropathy. Vitreoretinal traction appeared to be the cause of the retinal tears because (1) formed vitreous was always attached near the anterior edge of the tear, and (2) vitreous traction caused a retinal ridge adjacent to a retinal tear in a dog that had not yet developed retinal detachment. The pathogenetic sequence of spontaneous vitreous abnormalities, retinal tears, and retinal detachment observed in these dogs has not previously been described in animals, to the best of our knowledge, and mimicked human rhegmatogenous retinal detachment, particularly those associated with giant retinal tears.

Retardation of finger growth after injury to the flexor tendons

The absence of any part of the total mechanical force (i.e., flexor tendons) may be responsible for retardation of bone growth during a child's growth phase. The cause of retardation may be dedifferentiation of cartilage cells at the epiphyseal plate. Four cases in which unrepaired flexor tendons in digits caused retardation of growth illustrate this possible phenomenon. We feel that this is not a well recognized problem and thus deserves mention to stimulate further study. We believe that meticulous primary repair in children is desirable not only to preserve function, but also to prevent growth disturbances.

Biomaterials-Associated Pathology of Cardiac Valve Prostheses: Clinical Explant Analysis and Studies of Tissue Valve Calcification

ABSTRACTStudies of the pathology of explanted clinical and experimental valve specimens were done to determine the role of biomaterials in the failure of heart valve prostheses. From 7/80 through 12/84, 129 patients had valve prostheses removed at our hospital. Thrombosis/thromboembolism was the most frequent cause of the 39 mechanical valve failures (23%). Structural failure (poor durability) caused 12%. In contrast, with tissue-derived bioprostheses (90 patients), primary tissue degenerative failure was frequent (70%), and was usually associated with calcification (CALC). Infection caused 19% of all valve failures with a frequency not differing among valve types. Other causes of failure were not biomaterials-related. Thus, although frank materials degradation necessitates only a minority of mechanical valve removals, the suboptimal biologic properties of contemporary heart valve biomaterials contribute to some frequent complications (such as thrombosis/thromboembolism). Furthermore, degeneration due to mineralization is the overwhelming mode of failure of bioprosthetic valves.To understand and potentially eliminate bioprosthetic valve CALC, the kinetics, morphology and host and implant determinants of this process were studied using subcutaneous implants in rats. In this model, in which the pathologic features were similar to those of actual experimental and clinical valve replacements, CALC of glutaraldehyde-treated porcine aortic valve and bovine pericardium began within 48 hours following implantation; mineral levels were comparable to those in failed clinical valves after 84–126 days. Calcific deposits were initially associated with connective tissue cells, but later involved collagen. Systemically-administered ethane-hydroxy-diphosphonate (EHDP), a drug used to treat some forms of metabolic bone disease, inhibited CALC by 97%, but caused significant bone growth retardation. However, EHDP given by site-specific controlled-release largely mitigated CALC at only 1% of the total effective systemic dose, but without adverse effects.

Management of children with progressive renal failure.

The strategy of management in childhood renal failure is to integrate available therapeutic modalities with the natural history of the disease in such a manner that linear growth is preserved. Attention to psychosocial growth is necessary for full rehabilitation. Treatment is ordered to provide hope and confidence to family and patient. Conservative medical therapy provides chemical stabilization and prophylaxis against bone disease and growth retardation. Planned progression to replacement of renal function by dialysis or renal transplant is made when growth or control of bone disease is no longer possible, but before complications occur. Therapy is effective; 90% of patients survive 5-10 years with 65% retaining a functioning allograft. Full rehabilitation is attained in 85-90% of post-transplant and 50% of dialysis patients. Technical advances now allow safe dialysis for all age groups. Although growth maintenance remains a major problem, it is possible that earlier metabolic control and transplantation to protect growth in the critical early years, together with improved control of rejection, may allow close approximation to optimal growth potential.

Ostertagia circumcincta infection of lambs, the effect of different intakes of larvae on skeletal development

Six groups of 8 4-month-old cross-bred lambs were used to investigate the effect of daily intakes of Ostertagia larvae on skeletal growth. One group was killed at the onset as control. The remaining groups were offered a complete ruminant ration ad libitum and dosed with zero (group ALC control), 1000 (group 1), 3000 (group 2), 5000 (group 3) and 5000 (group 4) larvae of Ostertagia circumcincta per day for 12 weeks. Group 4 also received a single dose of anthelmintic (fenbendazole) on days 21, 42, 63 and 84 of infection. All sheep were killed after 14 weeks and selected bones removed for histological and chemical evaluation. None of the sheep showed obvious clinical signs of infection and mean worm egg counts were less than 400 e.p.g. Deposition of calcium in the carcase of Ostertagia infected sheep was reduced by 11, 35, 57 and 27 per cent in groups 1, 2, 3 and 4, respectively. Phosphorus deposition was similarly affected. Growth in volume of the tibia, rib and vertebra was reduced in groups 2, 3 and 4, compared to controls (ALC). There was also a reduction in the amount of ash per unit volume of bone in groups 2 and 3, mainly due to a decrease in bone matrix, although in the more severely affected animals mineralization of bone matrix was slightly reduced. Anthelmintric treatment did not prevent retardation of bone growth but it did improve the quality of the skeleton. Intakes of 1000 Ostertagia larvae per day did not significantly affect any of the bone parameters.

Symptomatic Splenic Hamartoma: A Report of Two Cases and Review of the Literature

Two cases of large, multiple splenic hamartomas in children with pancytopenia, bone marrow hyperplasia, lymphadenopathy, hepatosplenomegaly, frequent infections, growth retardation, and fever are reported. These symptoms were relieved by splenectomy, and have not recurred during follow-up periods of one year and nine years. The sharply circumscribed lesions comprised large portions of the resected spleens and were composed of dilated vascular channels filled with mononuclear cells and immunoblasts. The lesions lacked splenic cords or trabeculae, lymphoid follicles, Reed-Sternberg cells, and granulomas or other evidence of infection. Splenic hamartomas are usually single small lesions found incidentally at necropsy or laparotomy. Splenic hamartomas associated with symptoms and hypersplenism are large, and often confluent multiple tumors. Recognition of their benign nature is important in light of the current practice of laparotomy for staging and diagnosis of malignant conditions.

Mandibular growth retardation in corticosteroid-treated juvenile mice.

Juvenile mice were treated for up to eight weeks with weekly doses of a synthetic analogue of cortisol:triamcinolone hexacetonide. The mandibular condylar cartilage was studied histologically and histochemically at regular intervals. Morphometric measurements were performed along the mandibular posterior vertical dimension (condylar process and ramus). By the second injection significant morphological changes were noted in the condylar cartilage, followed by retardation of bone growth. The most distinctive feature in the cartilage of triamcinolone-treated mice was a marked increase in the dimension of its mineralized zone concomitant with a significant increase in the number of hypertrophic chondrocytes. The role of condylar cartilage in mandibular growth is discussed.

Decreased response to calcitonin in osteopetrotic microphthalmic mouse bone.

OSTEOPETROSIS is an autosomal recessive disease characterised by an increase in skeletal mass, often associated with retarded bone growth and a deficiency of marrow cavity development, which is related to a failure of bone resorption to keep pace with bone formation1,2. The disease has been studied in man and in several genetic mouse and rat mutants1. These mutants generally have diminished osteoclast function in the skeleton based on a lack of ruffled borders1,3, lowered acid phosphatase activity4 and a lower level of parathormone-induced resorption in vivo3,5 and in vitro6. It seems that osteo-petrosis has a cellular basis as it can be cured by parabiosis with a normal littermate7 or by administration of spleen or bone marrow cells8. However, the only report examining bone cell metabolism in osteopetrosis indicates that in the calvarium of the osteopetrotic incisor-absent rat, parathormone affects adenylate cyclase activity and lactic acid production to the same extent as in the bone from normal littermates9. Recently, specific hormone-sensitive biochemical activities in intact bone in culture10,11 or in cultured bone cells12,13 have been associated with the functions of osteoclasts and osteoblasts. Based on these biochemical parameters we show here that in osteopetrotic (micropthalmic) bone there is a defect in calcitonin response attributable to osteoclast function whereas osteoblast activity is apparently normal.

Soft-tissue effects following 224Ra injections into humans.

Following the Second World War, repeated intravenous injections of 224Ra (ThX) were given to German children and adults for the intended treatment of tuberculosis, ankylosing spondylitis, and a few other diseases. We have ascertained the health status of 204 juveniles and 612 adults for whom both dosage and injection span are known. 224Ra is known as a “skeletal-seeker”, and has induced malignant bone sarcomas, benign exostoses, tooth breakage, and growth retardation. But because of its short 3.62-day half-life, 224Ra also decays to an appreciable extent in soft tissues, as do the injected atoms of its decay products. In the present article we present evidence suggesting that some, but certainly not all, of the observed cases of soft-tissue neoplasms, kidney diseases, liver cirrhosis, and cataracts may be related to the 224Ra therapy. Of particular interest are the 8 cases of cataracts reported at 14–46 years of age (33 yr average) among the 204 patients injected with 224Ra as juveniles. Due to the rarity of “naturally-occurring” cataracts at young ages, perhaps all of these 8 cases can be regarded as induced.

The effect of lead on mouse brain development

Nursing C57 black or Swiss-Webster albino mother mice were given doses ranging from 0.08 to 2% of lead in food (PbCO 3) or 0.5% in drinking water (PbAc 2) and the pups were maintained on the lead diet through 60 days of age. Daily measurements of food intake, body weight, and neurological status were performed. Pups were killed at 30, 42, and 60 days of age, and the dams were killed 2 weeks after weaning. The highly inbred C57 mice only rarely raised their litters if given 0.8% lead but the less inbred albino mice accepted up to 2% lead. The dams remained well on diets of 1% and less. A dose-related retardation as high as 50% of controls in body growth, brain development, and sexual and behavioral maturation was found. Although dams fed 0.4% or more of lead ate less than control mice, retardation at the various lead doses was better correlated with lead concentration in the diet than with food consumption. Undernutrition is probably not the major cause of the retardation since varying the litter size did not greatly affect the detrimental effect of the diet. The lead mice were weaned approximately 2 weeks later than the controls. Small brain size, marked retardation of brain maturation, and retardation of bone growth characterized the lead-fed animals.

Delay in bone age in children with cyanotic congenital heart disease.

Of 110 children with congenital heart disease evaluated for bone age, 61 were cyanotic and 49 had normal systemic saturation. Cyanotic children had a much higher incidence (22∕61) of retarded bone age than did the acyanotic group (3∕49) (p < 0.001). The correlation between resting systemic oxygen saturation and bone age retardation was significant (r = +.733) and an oxygen saturation of 75% at rest appeared critical. All laboratory values were within normal limits except for the finding of polycythemia. Hypoxemia appears to be a significant factor in bone age and growth retardation when resting systemic oxygen saturation is 75% or less. It is postulated that this retardation in bone age reflects a local cellular response to hypoxemia.

Bone metabolism and composition in the protein-deprived rat.

1. Bone and calcium metabolism in protein-deprived 5-week-old male rats who exhibited no biochemical or histological features of rickets were compared with age-and weight-matched control animals. 2. Intestinal calcium absorption was significantly lower in protein-deprived rats. This was associated with a smaller exchangeable calcium pool and lower bone formation as measured by calcium accretion and proline incorporation into hydroxyproline. However, calcium resorption from bone barely changed in this group and a disproportionately high fraction of the calcium pool continued to be excreted. 3. As a consequence, retarded bone growth occurred in the protein-deprived rat, leading to bones which were shorter and lighter than those of age-matched control animals, the epiphyseal regions appearing to bear the brunt of the growth retardation. This was not accompanied by a change in quality of bone, as the percentage ash content of extirpated bone remained normal. 4. Though alternative hypotheses are possible, the data are consistent with a primary disturbance of intestinal, and possibly renal tubular, calcium transport, perhaps associated with impaired synthesis of calcium-binding protein. An independent depression of collagen synthesis is likely.

Preliminary Study of Inhibitory Effects of Tetracyclines on Membranous Bone Growth in Rhesus Monkeys

Various doses and forms of tetracycline were administered to young monkeys that received multiple injections of lead acetate as a vital marker of the calcification sites. The effects of these tetracyclines on membranous bone growth were assessed histologically ; retarded bone growth occurred under some conditions.

METABOLISM: Lysosmal bone disease

For normal bone growth, matrix must be laid down and resorbed. The process of remodeling could be altered if the activity of a single lysosomal hyrolase was deficient since compounds catabolized by the enzyme might then accumulate within bone cells and matrix with resultant abnormalities in bone architecture and growth retardation. We have studied a 9 year old dwarfed white male with normal intelligence whose disease appears limited to bone. He shows no corneal infiltration, visceromegaly or mucopolysacchariduria. His radiological diagnosis is spondyloepiphysealmetaphyseal dysplasia. Chemical studies of cultured skin fibroblasts from the patient showed decreased enzyme activity of α-L-fucosidase (controls 2.67 ± .75 vs patient 0.25 ± .05 n-moles/min/mg protein) with accumulation of fucose in his cells (controls 5.42 ± 1.52 vs patient 27 γ/mg protein). Fibrobalst enzyme activities for α-L-mannosidase, acid phosphatase, β-D-galactosidase and n-acetyl glucosaminidase were comparable to normal controls. A bone specimen from the patient was compared to 7 control specimens for hydrolase activity. Fucosidase activity was decreased in the patient (controls 3.2 ± .38 vs patient 0.36 n-moles/hr/mg wet wt.) as were several other acid hydrolyses. Compositional analyses of bone are in progress to define the character of the stored material. Thus far, the data in this patient is consistent with the hypothesis that his bone disease is due to a deficiency of lysosomal hydrolase, α-L-fucosidase. Since lysosomes in bone cells contain a variety of acid hydrolyses, the chemical bases for other chondrodystrophies may be related to the altered activity of one or more of these enzymes.

Short-leg syndrome.

Short-leg syndrome, or asymmetry of length in the lower extremities, is a common orthopedic problem in children. It is vital to recognize normal bone function, bone growth, and potential growth when evaluating this syndrome. Classification of this problem is either structural or functional. Structural (real) short legs usually have trauma or congenital growth inequality as their etiology. Functional (apparent) short legs usually result from soft tissue contractures or foot function aberrations. The child's age determines the extent of our examination. The lower extremity should be segmented during examination to help determine the location of pathology. Measuring the deformity requires precise scientific procedures. The level of compensation must be determined. Foot, pelvic, and spinal compensations should be evaluated. Scanograms or orthoroentgenograms are useful in diagnosing, quantifying, and prognosing short-leg syndrome. Prediction of the projected discrepancy is accomplished by the Anderson et al. remaining growth charts. Common etiologic considerations include congenital, neuromuscular, infection, trauma-induced, and tumor-caused disorders. Treatment of short-leg syndrome is determined by classification. Structural problems may need heel elevation or a combination of heel elevation and orthotic control on a conservative basis. Functional problems may require neutral position control of the feet with orthotics and correction of soft tissue contractures. Resin foam or orthopedic shoe adjustment may be used in moderate discrepancies. Structural leg inequalities may be corrected by surgical epiphysiodesis. This bone growth retardation procedure is normally performed on the long limb in pediatric patients. Therapy is directed at correcting pelvic obliquity, gait and postural aberration. The end result should be a child with cosmetically acceptable and normal functioning lower extremities.

CUTIS GYRATUM, ACANTHOSIS NIGRICANS AND OTHER CONGENITAL ANOMALIES A NEW SYNDROME

SUMMARY. A boy with a complex combination of physical features is reported. These include an unusual fades with hypertelorism, cutis gyratum, acanthosis nigricans, abnormal genitalia, cleft of the soft palate, bifid uvula, premature eruption of teeth, partial anodontia, retardation of bone growth and functional pyloric obstruction. These features are compared with those of leprechaunism, Seip's syndrome, and a case of “leprechaunism” in a male described by Patterson and Watkins (1962). The aetiology is unknown.

The effect of single doses of x-radiation on mandibular growth.

The short-term effects of localised X radiation applied in single doses of 110, 550 and 1,100 R on mandibular growth in the rat were examined. Intravital staining with the fluorochrome alizarin red S had labelled the bone mineralised immediately before irradiation and permitted recognition of that level in subsequent examinations. Microscopic measurements were taken from the labelled line to the periphery of the bone at the lingual alveolar plate, the inferior border and the condyle. Gross measurements taken were from the gnathion to condyle and gnathion to gonion. Analysis of results revealed a marked reduction in growth in every area examined in animals receiving 1,100 R of X radiation. The greatest reductions were in the lingual alveolus (63 per cent) and the condyle (36 per cent). The lowest dose to produce any significant retardation of bone growth was 550 R where reductions of 12 per cent in the inferior border and 9 per cent in the condyle were recorded for male animals. At the 110 R level there wa...

Age and Dose Dependence of Bone Growth Retardation Induced by X-Irradiation

Abstract : The quantitative aspects of bone growth retardation in rats after x-irradiation were determined with respect to radiation dose and exposure age. The deficits in femur and tibia growth at 60 days after irradiation increased exponentially with a linear increase in dose. The growth deficits were also a function of exposure age, increasing exponentially with the reciprocal of exposure age. The information obtained from the dose-response and ageresponse relationships was used to derive an equation which could be used to predict the bone growth decrement on the basis of the age at exposure and the dose administered. The general equation for bone growth retardation was found to give a good estimation of effect within the dose range of 100 to 680 rads for exposure ages of 24 to 58 days. (Author)

Pathology of skull, radius and rib in hypervitaminosis A of young calves.

In an experiment to produce hypervitaminosis A, twenty-two Holstein calves, 3 months of age and with a plasma vitamin A of 10 μg/100 ml or less, were fed vitamin A levels of 18, 54, 4000, 12,000 or 16,000 μg/lb of body weight per day for a 12-week period, except for the 16,000 μg group which was terminated in 8 weeks. The long bones and skulls were examined by X-rays and histologically. The roentgenologic changes were a slowing of growth and remodeling processes in all calves on the 3 highest levels resulting in diminution of the overall size, thinning of the cortical bone and a marked decrease in the amount of spongious bone. Serial radiographs at weekly intervals of the radii of the calves on the highest level of vitamin A demonstrated changes as early as 2 weeks after administration of the vitamin supplement was begun. The gross pathologic changes correlated well with the radiographic findings, except that failure of the internal bony plates of the frontal sinuses to form was not detected in the radiographs. The lack of bony separation of the brain from the frontal sinuses and the expansion of the cerebrum into these sinuses may explain the decreased cerebrospinal fluid pressure which accompanied the dilated cerebral ventricles. Histologically, the essential change was retarded osteogenesis with poor differentiation of the mesenchymal cells into osteoblasts. As a result, the compacta was thin, osteoporotic and, at the 2 higher levels of vitamin A administration, contained large amounts of fibrous bone. As demonstrated in calves, the effect of excessive vitamin A on bone appears to be retardation of bone growth due to a defect in osteoid production resulting in osteoporosis.

Nephroblastoma (Wilms' tumor). Prognosis more favorable in infants under one year of age.

Nephroblastoma was treated in 42 children (25 girls, 17 boys) under the age of 9 years. The standard treatment, used in 26 cases, consisted of immediate nephrectomy and postoperative roentgenotherapy. The entire group of 42 patients was followed up for at least three years, and of the 20 who died postoperatively 17 died of metastases (9 the first year and 8 the second). Irradiation caused the disappearance of lung metastases in one patient but visibly retarded bone growth. Because of the ill-effects of unnecessary radiotherapy, preoperative irradiation for suspected malignant conditions of the kidneys is unsafe. The survival rate of 45% in this series of 42 patients since 1934 is gratifying by comparison with the rate of 9% found in a similar series before 1934.