Novel effects of sarcopenic osteoarthritis on metabolic syndrome, insulin resistance, osteoporosis, and bone fracture: the national survey.

UNLABELLED: This study compared the effects sarcopenic osteoarthritis on metabolic syndrome, insulin resistance, osteoporosis, and bone fracture. By using national survey data, we suggest that the relationship between sarcopenia and metabolic syndrome or insulin resistance is potentiated by the severity of osteoarthritis and is independent of body weight. INTRODUCTION: Sarcopenia and osteoarthritis are known risk factors for metabolic syndrome. However, their combined effects on metabolic syndrome, insulin resistance and osteoporosis remain uncertain. METHODS: We used data from the fifth Korean National Health and Nutrition Examination Survey using a total of 3158 adults (age >50 years). Sarcopenia was defined as a skeletal muscle index score (appendicular skeletal muscle mass/body weight) within the fifth percentile of sex-matched younger reference participants. Radiographic knee osteoarthritis was defined as a Kellgren-Lawrence (K-L) grade of 2 or greater. Metabolic syndrome was diagnosed using the National Cholesterol Education Program criteria. Insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance index (HOMA-IR). Osteoporosis was defined using the World Health Organization T-score criteria. RESULTS: In multivariable logistic regression analysis, the sarcopenic osteoarthritis group had a higher odds ratio (OR) for metabolic syndrome (OR = 11.00, 95 % confidential interval (CI) = 2.12-56.99, p = 0.013) than the non-sarcopenic osteoarthritis (OR = 1.02, 95 % CI = 0.65-1.62, p = 0.972) and sarcopenic non-osteoarthritis groups (OR = 7.15, 95 % CI = 1.57-32.53, p = 0.027). Similarly, sarcopenic osteoarthritis had a greater OR of highest HOMA-IR quartiles (OR = 8.19, 95 % CI = 2.03-33.05, p = 0.003) than the other groups. Overall, the association between the K-L grade and body mass index was significant; however, this significance was lower in individuals with sarcopenia and was lost in those with sarcopenic osteoarthritis. Additionally, osteoporosis and bone fracture were not associated to sarcopenic osteoarthritis (p > 0.05). CONCLUSIONS: These results suggest that the relationship between sarcopenia and metabolic syndrome or insulin resistance is potentiated by the severity of osteoarthritis and is independent of body weight.

Isoquercetin upregulates antioxidant genes, suppresses inflammatory cytokines and regulates AMPK pathway in streptozotocin-induced diabetic rats.

Lifestyle and genetic factors contribute to the initiation of oxidative stress and inflammation in diabetes mellitus (DM). Oxidative stress and lipid peroxidation worked in an orchestrated manner and reported to be strongly associated with the formation of the hyperlipidemic condition in DM patients. Isoquercetin, a bioactive constituent isolated from guava leaves has attracted considerable attention because of its antidiabetic activity. The antidiabetic activity of guava leaves may be due to the presence of isoquercetin at a significant level. However, how isoquercetin regulates different pathways in DM is insufficiently studied. We have selected versatile regulators of oxidative stress and inflammatory pathways to fully analyze if isoquercetin effectively modulated the genes of these pathways. At the end of our experimental duration, rats were dissected and analyzed for the oxidative stress, lipid peroxidation, inflammatory and lipid markers. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is believed to be the key regulator of expression of various antioxidant enzyme genes and it is directly or indirectly related to nuclear factor Kappa- B (NF-kB) and AMP-activated protein kinase (AMPK) pathways. Therefore, we tend to study the effects of STZ on Nrf2, NF-kB and AMPK pathway and how the isoquercetin treatment performs at a molecular level to overcome the burden of DM. The results of our study provided convincing evidence of significant pharmacological properties of isoquercetin in context of its ability to inhibit the oxidative stress elicited by the STZ through generation of the free radicals and regulation of the expression of Nrf2 pathway-associated proteins and genes and it also reduced the burden of hyperlipidemia and inflammation. By taking the above results into consideration isoquercetin can be studied further to elucidate its antidiabetic effects at various levels.

Environmental degradation of glass-ionomer cements: a depth-sensing microindentation study.

This study investigated the effects of various environmental conditions on the hardness and elastic modulus of restorative glass-ionomer cements (GICs). Two resin-modified GICs (RMGICs) (Fuji II LC [FL]; Photac-Fil Quick [PQ]) and three highly viscous GICs (HVGICs) (Fuji IX Fast [FN]; KetacMolar [KM]; KetacMolar Quick [KQ]) were evaluated in this study. Specimens were fabricated according to the manufacturers' instructions and stored under a variety of conditions (n = 7): 100% humidity, distilled water, pH 5 demineralization solution, and pH 7 remineralization solution. The hardness and elastic modulus were measured using a depth-sensing microindentation test after 4 weeks. The results were analyzed using the independent samples T-test and ANOVA/Scheffe's post hoc test (p < 0.05). HVGICs showed significantly higher hardness and elastic modulus than RMGICs under all storage conditions. Storage in distilled water significantly increased the hardness and elastic modulus of FN, but decreased that of PQ. All HVGICs and RMGICs stored in remineralization solution had hardness values and elastic moduli comparable to those stored in water. Compared to remineralization solution, demineralization solution had no significant effects on the modified GICs with the exception of KQ. The results suggest that the mechanical properties of glass-ionomer restoratives are material-type and storage condition dependent. Therefore, the clinical selection of a glass-ionomer material should be based on the oral environment to which it will be subjected.

Characterization of a cathepsin L-like enzyme secreted from human pancreatic cancer cell line HPC-YP.

Spent culture medium from the human pancreatic carcinoma cell line HPC-YP, which can propagate in a protein-free, chemically defined medium without any other supplements, was analyzed for the presence of the cysteine protease, cathepsin L. The secreted form of cathepsin L was distinguished from the lysosomal form by its increased stability at alkaline pH, by its strong thermostability, and by its larger molecular size. HPC-YP cathepsin L was still stable at pH 7.4 and at 56 degrees C after 60-min preincubation. The molecular weight of this enzyme was estimated to be 68,000, compared with a molecular weight of 29,000 for normal liver cathepsin L. By Western blot analysis, HPC-YP enzyme was found to be composed of two components, one with a molecular weight of 37,000 and the other of 31,000. This result suggests that HPC-YP enzyme in the spent medium may be a complex of the proenzyme (in the case of liver proenzyme; Mr 39,000) and the mature enzyme (in the case of liver mature enzyme; Mr 29,000). Interestingly, an intrinsic inhibitor was also separated from the spent medium by gel filtration. The molecular weight of this inhibitor was estimated to be approximately 13,000. The cathepsin L of HPC-YP proved more resistant toward leupeptin than did liver cathepsin L. On the other hand, the former was more sensitive than the latter toward the diazomethane inhibitors, Z-Phe-Phe-CHN2 and Z-Phe-Ala-CHN2. These results indicate that cathepsin L secreted from cancer cell lines may play a role in the destruction of basal lamina, invasion of tissue, and formation of metastasis.

Replication-competent, nonneuroinvasive genetically engineered herpes virus is highly effective in the treatment of therapy-resistant experimental human tumors.

A genetically engineered, nonneurotropic herpes simplex virus (R7020) with a proven safety profile in both animals and humans was found effective in the treatment of large xenotransplanted tumors arising from a radiation- and chemotherapy-resistant human epidermoid carcinoma and a hormone-refractory prostate adenocarcinoma. R7020 replicated to high titer and caused rapid regression of the human tumor xenografts. Tumor destruction was accelerated in animals given both R7020 and fractionated ionizing radiation. Tumors arising from cells surviving one treatment with R7020 were fully susceptible to a second dose of virus. We conclude R7020 is an effective antitumor agent for non-central nervous system tumor xenografts with an excellent safety profile.

Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus.

Malignant gliomas remain incurable with current interventions. Encouraging investigational approaches include the use of genetically modified herpes simplex-1 (HSV-1) viruses as direct cytotoxic agents. Combining attenuated HSV-1 with standard therapy, human U-87 malignant glioma xenografts grown in the hind limb or intracranially in athymic nude mice were exposed to ionizing radiation, inoculated with genetically modified HSV R3616, or received both virus and radiation. The combination of virus with fractionated ionizing radiation suggests a synergistic action and results in reduced tumor volumes and longer survivals when compared with treatment with either modality alone.

Elastic modulus of resin-based dental restorative materials: a microindentation approach.

This research aimed to determine the elastic modulus of resin-based dental composite restoratives using the microindentation test method. Results were then compared with those obtained with the ISO three-point bending test method. Five materials from the same manufacturer (3M ESPE) were selected for the study. They included microfill (A110), minifill (Z100 and Filtek Z250), poly-acid modified (F2000), and flowable (Filtek Flowable [FF]) composites. The indentation moduli of the composites were determined using a custom-designed microindentation test set up after conditioning in water at 37 degrees C for 1 week and 1 month. The indentation test was carried out at peak load of 10 N and Oliver & Pharr's method was used to determine the maximum projected contact area. Data was analyzed using ANOVA/post-hoc Scheffe's test at significance level 0.05 and Pearson's correlation at significance level 0.01. The mean indentation modulus ranged from 5.80 to 15.64 GPa and 5.71 to 15.35 GPa at 1 week and 1 month, respectively. At both time periods, the indentation modulus of Z100 was significantly higher than all other materials. F2000 was significantly higher than Z250, which was significantly stiffer than A110 and FF. The rankings were in good agreement with the ISO flexural test. A significant, positive, and strong correlation (r = 0.93 and 0.94 at 1 week and 1 month, respectively) in modulus between ISO three-point bending and microindentation test methods was observed. In view of the small specimen size and good reproducibility, the microindentation reflects a potential test method for determining the elastic properties of dental composite restoratives.

Effects of surface finish on indentation modulus and hardness of dental composite restoratives.

OBJECTIVES: The depth-sensing micro-indentation testing was recently introduced for the characterization of dental composites. One of the critical issues raised was the possible influence of surface finish on material properties. The aim of this study was to investigate the effects of surface finish on the indentation modulus and micro-hardness of resin-based dental composite materials. METHODS: The materials used included minifill (Z100, 3M ESPE), microfill (A110, 3M ESPE) and poly-acid modified (F2000, 3M ESPE) composites. The specimens were polished successively using SiC grinding papers of different grit size and diamond suspensions to achieve varying surface roughness. The arithmetic mean of the roughness (R(a)) was measured using profilometry. In the depth-sensing micro-indentation test, specimens (n=7) were indented to 10N with Vickers indenter and the load-displacement (P-h) data was obtained using a universal testing system. The indentation modulus (E(in)) and hardness (H) were then computed using the developed analytical solutions. Data was analyzed using ANOVA/post-hoc Scheffe's test at significance level 0.05. RESULTS: The polished specimens had surface roughness ranging from 0.02 to 0.81 microm. The roughness of F2000 was significantly higher than A110 and Z100. The E(in) and H for Z100 ranged from 14.02 to 14.83GPa and 1.18 to 1.27 GPa, respectively. E(in) for F2000 and A110 ranged from 12.25 to 13.82 GPa and 5.26 to 5.52 GPa and hardness ranged from 0.89 to 0.98 GPa and 0.52 to 0.55 GPa, respectively. SIGNIFICANCE: The indentation modulus and hardness of dental composite restoratives were independent of the surface finish provided indenter penetration is sufficiently deep (h(max)/R(a)>30).

Influence of dietary solvents on strength of nanofill and ormocer composites.

The objective of this study was to determine the influence of dietary solvents on the shear punch strength of nanofill (Filtek Supreme [FS], 3M-ESPE) and ormocer (Admira [AM], Voco) composites. The strength of these materials was also compared to a minifill composite (Z250 [ZT], 3M-ESPE), a compomer (F2000 [FT], 3M-ESPE) and a highly viscous glass ionomer cement (Ketac Molar Quick [KM], 3M-ESPE). Thirty-two specimens (8.7 mm diameter and 1-mm thick) of each material were made, randomly divided into four groups of eight and conditioned for one week as follows-Group 1 (control): distilled water at 37 degrees C; Group 2: 0.02M citric acid at 37 degrees C; Group 3: 50% ethanol-water solution at 37 degrees C and Group 4: heptane at 37 degrees C. After conditioning, the specimens were restrained with a torque of 2.5 Nm and subjected to shear punch strength testing using a 2-mm diameter punch at a crosshead speed of 0.5 mm/minute. The shear punch strength of the specimens was computed and data subjected to ANOVA/Scheffe's tests at significance level 0.05. With the exception of AM, the strength of all materials was not significantly influenced by dietary solvents. For AM, conditioning in heptane resulted in significantly higher shear strength values. The strength of the nanofill and ormocer composites was lower than the minifill composite but higher than the compomer and highly viscous glass ionomer cement investigated.

The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma.

To test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity.

Clinical results of 24 pituitary macroadenomas with linac-based stereotactic radiosurgery.

PURPOSE: To determine the impact of stereotactic radiosurgery (SRS) on the clinical course, hormonal status, and follow-up CT/MRI scan of pituitary macroadenomas. METHODS AND MATERIALS: From July 1988 to March 1996, 24 pituitary macroadenomas had been treated using 6 MV linear accelerator based SRS. They consisted of 11 (45.8%) prolactinomas, 2 (8.3%) growth hormone (GH)-secreting tumors, 1 (4.2%) Cushing's disease, 8 (33.3%) nonsecreting (nonfunctioning: NF) tumors, and 2 (8.3%) mixed prolactin-growth hormone (PRL-GH)-secreting tumors (M:F = 12:12; aged 21-61 years). Postoperative irradiation was performed in all cases except for the instance of Cushing's disease. The prescribed dose to tumor center varied from 10 to 27 Gy (mean 21.1 Gy) using a collimator size of 0.5 to 2.5 cm. The follow-up duration ranged from 13 to 89 months (mean 49.2 months). Results from these patients were compared to our results using conventional radiation. RESULTS: Visual acuity and field defect were improved or became normal in 19 (79.2%) cases. Four (16.7%) remained unchanged after the treatment. One (4.1%) progressed 6 years after SRS and subsequently had repeat surgery with conventional boost irradiation. Of the 13 (46.4%) prolactinomas, including two mixed PRL-GH secreting tumors, 11 (84.1%) revealed normal hormonal levels within 1 year after SRS. In contrast, it took 2 years to become normal after conventional radiation therapy. In four GH-secreting tumors including two mixed PRL-GH secreting tumors, SRS and conventional methods showed similar responses. On follow-up imagings of the 21 patients, the mass was completely resolved in 4 (16.7%), including 3 PRLs and one NF, decreased in 11 (45.8%), and unchanged in 5 (16.7%) with central necrosis or cysts. One (4.2%) progressed and was reoperated 6 years after treatment. The complications related to SRS were comparable to those from conventional method. CONCLUSION: Radiosurgery can be used effectively in patients with pituitary adenoma. In this study, a more rapid hormonal and clinical response was achieved with radiosurgery than with conventional pituitary irradiation treatment.

Cholinergic stimulation of phosphatidic acid formation by rat cornea in vitro.

The cornea has one of the highest acetylcholine (ACh) concentrations of any tissue but the function of the ACh has remained enigmatic. During studies on corneal arachidonic acid metabolism, we observed that ACh stimulates formation of labeled phosphatidic acid in rat corneas whose phospholipids were prelabeled with [14C]arachidonate. ACh did not affect the metabolism of free [14C]arachidonate. [14C]Arachidonyl-phosphatidic acid formation was doubled after 10 min of incubation in the presence of ACh concentrations of 10(-4) M or greater. The stimulation by ACh could be completely blocked by atropine and scopolamine and partially blocked by d-tubocurarine. These studies suggest that intact rat cornea has muscarinic cholinergic receptors and that the enzymes of the inositol phospholipids pathway are present since phosphatidic acid is an obligatory intermediate in that cycle of reactions.

Ocular neuromyotonia in Graves dysthyroid orbitopathy.

OBJECTIVES: To describe 2 patients with ocular neuromyotonia in association with Graves orbitopathy and to consider the possible underlying mechanisms. DESIGN: Description of the clinical findings in 2 patients with these conditions. SETTING: Neuro-ophthalmology referral centers. PATIENTS: Two patients, aged 55 and 52 years, had episodic, involuntary periods of vertical diplopia and dysthyroid orbitopathy. INTERVENTION: Treatment with carbamazepine in one patient and external beam radiation therapy in the second patient. MAIN OUTCOME MEASURES: Frequency and duration of episodic spasms of the extraocular muscles. RESULTS: Although radiation therapy is the most common association with ocular neuromyotonia, it cannot explain the involuntary contractions of extraocular muscles in all affected patients. Other mechanisms must be involved, such as those discussed in this article. CONCLUSION: Ocular neuromyotonia is described in 2 patients with dysthyroid orbitopathy, confirming previous findings. Possible mechanisms are given.

Association of quinone-induced platelet anti-aggregation with cytotoxicity.

Various anti-platelet drugs, including quinones, are being investigated as potential treatments for cardiovascular disease because of their ability to prevent excessive platelet aggregation. In the present investigation 3 naphthoquinones (2,3-dimethoxy-1,4-naphthoquinone [DMNQ], menadione, and 1,4-naphthoquinone [4-NQ]) were compared for their abilities to inhibit platelet aggregation, deplete glutathione (GSH) and protein thiols, and cause cytotoxicity. Platelet-rich plasma, isolated from Sprague-Dawley rats, was used for all experiments. The relative potency of the 3 quinones to inhibit platelet aggregation, deplete intracellular GSH and protein thiols, and cause cytotoxicity was 1,4-NQ > menadione >> DMNQ. Experiments using 2 thiol-modifying agents, dithiothreitol (DTT) and 1-chloro-2,4-dintrobenzene (CDNB), confirmed the key roles for GSH in quinone-induced platelet anti-aggregation and for protein thiols in quinone-induced cytotoxicity. Furthermore, the anti-aggregative effects of a group of 12 additional quinone derivatives were positively correlated with their ability to cause platelet cytotoxicity. Quinones that had a weak anti-aggregative effect did not induce cytotoxicity (measured as LDH leakage), whereas quinones that had a potent anti-aggregative effect resulted in significant LDH leakage (84-96%). In one instance, however, p-chloranil demonstrated a potent anti-aggregative effect, but did not induce significant LDH leakage. This can be explained by the inability of p-chloranil to deplete protein thiols, even though intracellular GSH levels decreased rapidly. These results suggest that quinones that deplete GSH in platelets demonstrate a marked anti-aggregative effect. If this anti-aggregative effect is subsequently followed by depletion of protein thiols, cytotoxicity results.

Purification of human pancreatic gamma-glutamyltranspeptidase by lectin affinity chromatography.

Two types of pancreatic gamma-glutamyltranspeptidase (GGTP) (EC 2.3.2.2), sialic acid poor and sialic acid rich, were purified by the following: anion-exchange chromatography, wheat germ agglutinin (WGA)-Sepharose chromatography, gel filtration chromatography, phenyl-Superose chromatography, and hydroxylapatite chromatography. Among these, WGA-Sepharose chromatography helped to increase the specific activity of the GGTPs by approximately 20-30-fold in one effort. On dodecyl sulfate polyacrylamide gel electrophoresis, the two pancreatic GGTPs had different molecular weights. Sialic acid-rich GGTP had two subunits of Mr 67,000 and 27,000; however, the sialic acid-poor type had two subunits of Mr 72,000 and 29,000. The pI value of the sialic acid-poor GGTP was 5.9, and that of the sialic acid-rich GGTP 3.6.

Characterization of variant gamma-glutamyl transpeptidase produced by pancreatocholangiocarcinoma cell lines in a protein-free, chemically defined medium.

Four pancreatocholangiocarcinoma cell lines (HPC-Y1, HPC-YT, MIA PaCa-2, and HChol-Y1) were established to propagate in a protein-free, chemically defined medium. High gamma-glutamyl transpeptidase (GGTP) activities were showed in their spent media (designated as the secreted (GGTP). Their GGTP activities in the spent media were 125, 85, 110, and 153 IU/L/mg of lyophilized spent media, whereas GGTP activities extracted from their cancer cell lines with bromelain were 105, 37, 86, and 112 IU/L/1 x 10(6) cells, respectively. The chemical characteristics of the GGTPs in the spent media from these cell lines resembled one of the GGTPs, sialic acid-rich GGTP, extracted from normal human pancreas with bromelain treatment as follows: the GGTPs secreted from the cancer cell lines bound to an anion exchange column moved fast on electrophoresis and then showed decreased electrophoretic mobility with neuraminidase treatment, showed a high affinity for concanavalin A and lentil lectin columns, and had an acidic isoelectric point. However, the elution patterns of erythroagglutinating phytohemagglutinin (E-PHA) column chromatography and thermostability tests demonstrated clear differences between the carcinoma GGTPs both in the spent media and cell lines and the sialic acid-rich GGTP of normal pancreas, namely the carcinoma GGTPs treated with neuraminidase showed affinity to E-PHA columns, and, in addition, the GGTPs in the spent media showed an apparent heat resistance at 56 degrees C. These findings indicate that the carcinoma GGTPs have a different oligosaccharide structure from that in normal pancreatic GGTPs.

Menadione induces endothelial dysfunction mediated by oxidative stress and arylation.

Our previous studies showed that menadione causes endothelial dysfunction which results in decreased relaxation and increased contraction of blood vessels. This investigation examined the role of two possible mechanisms (oxidative stress and arylation) in menadione-induced endothelial dysfunction. Menadione increased superoxide anion generation in aortic rings in a dose-dependent manner. Superoxide dismutase (SOD), reversed the inhibitory effects of menadione on vascular relaxation. The relaxation induced by the NO donor, sodium nitroprusside, was inhibited by menadione pretreatment in a dose-dependent manner. Endothelial nitric oxide synthase activity (eNOS) was suppressed by menadione. Menadione resulted in a dose-dependent reduction of cGMP levels accumulated by acetylcholine. This reduction of cGMP levels was blocked by SOD treatment, suggesting that superoxide anion generated by menadione could play a role in the inhibition of the nitric oxide pathway. Evidence supporting a possible role for arylation in impaired vascular relaxation was suggested by the observation that benzoquinone, which does not induce oxidative stress in aortic rings, inhibited acetylcholine-induced vascular relaxation to the same extent as menadione. Collectively, these results suggest that menadione can cause endothelial dysfunction in blood vessels by the inhibition of the nitric oxide pathway via superoxide anion generation and that arylation activity may also be another important mechanism.

The arterial supply of the developing proximal end of the human femur.

By means of perfusion studies, an analysis was made of the arterial supply to the proximal end of the femur in 150 specimens from autopsied fetuses and children, aged from twenty-six weeks of gestation to fourteen years and eight months old. All died of diseases which did not involve the hip joint. Two anastomotic rings were found: an extracapsular one formed by the medial and lateral femoral circumflex arteries, and a subsynovial intra-articular ring at the articular cartilage-neck junction. The intra-articular rings in males were discontinuous more often than in females. A three-plane analysis of totally-cleared specimens demonstrated that the epiphyseal plate constituted an absolute barrier to blood flow between the epiphysis and metaphysis in all but two of the 124 barium sulphate-perfused specimens examined. A smaller number of ascending cervical arteries crossed the anterior and medial surfaces of the mid-neck in the specimens from three to ten-year-old white children than in those from newborn to two-year-old white and black children. This finding may be important for the etiology of Legg-Perthes disease. No differences with respect to age, sex, or race were found in the arteries of the ligamentum teres.

Long-term results in the treatment of femoral-shaft fractures in young children by immediate spica immobilization.

Manual traction reduction without anesthesia and immediate immobilization in a spica cast were used to treat eighty-five children ranging in age from birth to ten years old who had closed femoral-shaft fractures and no associated injuries. Up to two centimeters of overriding, 30 degrees of anterior angulation, and 15 degrees of medial angulation were accepted. Any angulation in excess of these amounts, or lateral or posterior angulation, was corrected by wedging the cast at the fracture site. Further telescoping of the fracture fragments in the case was attributed to the child pressing the foot against the bottom of the cast and was prevented by removing the sole of the cast. Of the seventy-five children examined two to eighteen years after fracture, none had any residual skeletal deformity or joint stiffness. The length discrepancies of the fractured limbs ranged from 1.7 centimeters of shortening to 0.9 centimeter of overgrowth.