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Biomedical subjects

S L Cheng

Publications and source records attributed to S L Cheng.

At least 55 records · Page 3Linked to original sources

Single versus double arterial anastomoses in combined second- and third-toe transplantation.

Combined second and third toe transplantation is one good option for reconstruction of multiple digit amputation. However, the use of one or two arteries for pedicle anastomoses, which may influence the vascular complication and success rate, has never been addressed in the literature. This study includes a retrospective review of 57 combined second and third toe transplantation in 54 patients performed from February of 1983 through December of 1996. Group I, composed of 41 transplantations, underwent one arterial anastomosis, and group II, composed of 16 transplantations, underwent double arterial anastomoses during surgery if there were two recipient arteries available or whenever the second and third toes showed inadequate blood perfusion after one arterial anastomosis. In group I, 10 transplantations (24.4 percent) required re-exploration with a success rate of 92.7 percent (38 out of 41 transplantations). In group II, only one transplantation (6.2 percent) required re-exploration with successful flap salvage. The success rate was 100 percent for group II. Because the re-exploration and success rates between groups I and II were not statistically significant according to two-tailed Fisher's exact test, the combined second and third toe transplantation is a reliable procedure using either single or double arterial anastomoses.

Adolescent↗

Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2-induced osteogenic differentiation.

Direct cell-cell interactions are fundamental for tissue development and differentiation. We have studied the expression and function of cadherins in human osteoblasts during in vitro differentiation. Using reverse transcription-polymerase chain reaction and mRNA hybridization, we found that human trabecular bone osteoblasts (HOBs), osteoprogenitor marrow stromal cells (BMCs), and the osteogenic sarcoma lines, SaOS-2 and MG-63, expressed mRNA for cadherin-11 (C11) and N-cadherin (N-cad). HOBs and BMCs also expressed low levels of cadherin-4 (C4) mRNA. C11 was the most abundant cadherin protein present in human osteoblasts, and its expression was unaffected by bone morphogenetic protein-2 (BMP-2) treatment of either BMCs or HOBs. Likewise, N-cad mRNA did not change during BMP-2 incubation. Conversely, C4 protein, undetectable in transformed cell lines, was down-regulated by BMP-2 treatment of normal cells. Both C11 and C4 were localized to sites of cell-cell contact in both HOBs and BMCs, colocalized with beta-catenin, and bands corresponding to cadherins were coimmunoprecipitated by a beta-catenin antibody, findings indicative of functional cadherins. A decapeptide containing the HAV motif of human N-cad partially inhibited Ca2+-dependent cell-cell adhesion and completely prevented BMP-2-induced stimulation of alkaline phosphatase activity by BMCs. Thus, human osteoblasts and their progenitor cells express a repertoire of multiple cadherins. Cadherin-mediated cell-to-cell adhesion is critical for normal human osteoblast differentiation.

Bone Morphogenetic Protein 2↗

Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2.

We have examined the effects of BMP-2 on the expression of bone matrix proteins in both human bone marrow stromal cells (HBMSC) and human osteoblasts (HOB) and their proliferation and mineralization. Both HBMSC and HOB express BMP-2/-4 type I and type II receptors. Treatment of these two cell types with BMP-2 for 4 weeks in the presence of beta-glycerophosphate and ascorbic acid results in mineralization of their matrix. BMP-2 increases the mRNA level and activities of alkaline phosphatase and elevates the mRNA levels and protein synthesis of osteopontin, bone sialoprotein, osteocalcin, and alpha 1(I) collagen in both cell types. Whereas the mRNA level of decorin is increased, the mRNA concentration of biglycan is not altered by BMP-2. No effect on osteonectin is observed. The effect of BMP-2 on bone matrix protein expression is dose dependent from 25 to 100 ng/ml and is evident after 1-7 days treatment. In the presence of BMP-2, proliferation of HBMSC and HOB is decreased under either serum-free condition or in the presence of serum. Thus, BMP-2 has profound effects on the proliferation, expression of most of the bone matrix proteins and the mineralization of both relatively immature human bone marrow stromal preosteoblasts and mature human osteoblasts.

Adult↗

The effect of tenidap on cytokines, acute-phase proteins, and virus load in human immunodeficiency virus (HIV)-infected patients: correlation between plasma HIV-1 RNA and proinflammatory cytokine levels.

Proinflammatory cytokines may be important in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) disease. Tenidap decreases interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF) production by peripheral blood mononuclear cells and decreases IL-6 plasma levels in rheumatoid arthritis patients. In this randomized double-blind study, 43 HIV-1-infected patients received tenidap (120 mg) or placebo daily for 6 weeks and then crossed over to the alternative therapy for an additional 6 weeks. Mean entry CD4 cell count was 140/microL. Analyses were performed on cytokines, acute-phase proteins, virus load, and CD4 cell counts. With the exception of small differences in plasma TNF levels, tenidap had no significant effect on these indices. Significant correlations of plasma IL-6 and TNF levels with HIV-1 RNA were noted. Six patients discontinued tenidap due to rash. The effects of tenidap in HIV-1 infection contrast to results in arthritis patients, in whom tenidap decreased plasma levels of IL-6 and acute-phase proteins.

Acute-Phase Proteins↗

Lack of autocrine effects of IL-6 on human bone marrow stromal osteoprogenitor cells.

Interleukin-6 (IL-6) produced by osteoblastic cells plays an important role in the regulation of bone remodeling, mainly by stimulating osteoclast action. Although the IL-6 receptor is also found in osteoblastic cells, whether IL-6 exerts autocrine effects on osteoblastic cells is a matter of debate. This led us to study the effects of IL-6 on proliferation, osteoblastic activity as well as mRNA expression of various osteoblastic proteins in human bone marrow stromal osteoprogenitor cells (hBMSC). IL-6 did not affect cell proliferation assessed by [3H]-thymidine incorporation and osteoblastic activity determined by alkaline phosphatase activity and 45Ca incorporation. The expression of mRNAs for alkaline phosphatase, alpha 1 (I)-collagen, osteopontin and decorin also did not change significantly by IL-6 treatment. These results show that IL-6 does not have a significant autocrine role in regard to proliferation and osteoblastic activity of hBMSC.

Alkaline Phosphatase↗

Management of complex dislocations of the distal radioulnar joint.

The authors reviewed their experience in the treatment of complex dislocations of the distal radioulnar joint. Six cases of complex dislocations were treated between 1990 and 1993. An algorithm for the treatment of these injuries has been developed. In most cases, complex dislocations are associated with an avulsion fracture of the ulnar styloid. The authors prefer to treat these by fixation of the ulnar styloid using a tension band wiring technique. Cases in which the ulnar styloid fragment is small, or in which there is no styloid fracture, are treated with open reduction and repair of the triangular fibrocartilage complex if the distal radioulnar joint is irreducible, or by ulnoradial transfixion pinning if the distal radioulnar joint is reducible but unstable. Good results were obtained in five of six cases using this algorithm.

Adolescent↗

Induction of early growth response-1 gene by interleukin-1 beta and tumor necrosis factor-alpha in normal human bone marrow stromal an osteoblastic cells: regulation by a protein kinase C inhibitor.

The early growth response-1 (Egr-1) gene has been identified as a nuclear transcriptional factor and implicated in the regulation of growth and differentiation of osteoblastic cells. In the present study, we investigated whether Egr-1 mRNA is expressed and induced by interleukin-1 beta, (IL-beta) and tumor necrosis factor-alpha (TNF-alpha) in normal human bone marrow stromal (HBMS) and osteoblastic (HOB) cells. Results demonstrate a very low basal expression of Egr-I mRNA which is induced by IL-1 beta, and TNF-alpha in a time- and dose-dependent manner. Egr-1 mRNA induction was detectable within 15 min, reached maximal by 60 min and thereafter declined to basal levels by 120 min. Induction of Egr-1 mRNA by IL-1 beta and TNF-alpha was completely inhibited by H-7 suggesting the mediation of protein kinase C. The induction by IL-1 beta and TNF-alpha of Egr-1 mRNA was independent of de novo protein synthesis since this induction was also observed in the presence of protein synthesis inhibitor cycloheximide. Fetal bovine serum and cycloheximide also independently induced the Egr-1 mRNA. Actinomycin D experiments demonstrated that Egr-1 mRNA is degraded very rapidly with a half-life of 30 min. Our results demonstrate the expression of Egr-1 gene and its induction by IL-1 beta, and TNF-alpha in normal human bone marrow stromal (osteoprogenitor) and osteoblastic cells in primary cultures. Data also reveal that the expression of Egr-1 gene is inhibited by protein kinase C inhibitor H-7 suggesting that the activation of protein kinase C or other protein kinases resulting in the phosphorylation of specific transcription factor(s) is the first immediate early step in the induction of immediate-early Egr-1 gene by IL-1 beta, and TNF-alpha. Results also suggest that Egr-1 is an important mediator of IL-1 beta and TNF-alpha action in normal human osteoblastic cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Expression of bone matrix proteins during dexamethasone-induced mineralization of human bone marrow stromal cells.

Glucocorticoids have been shown to induce the differentiation of bone marrow stromal osteoprogenitor cells into osteoblasts and the mineralization of the matrix. Since the expression of bone matrix proteins is closely related to the differentiation status of osteoblasts and because matrix proteins may play important roles in the mineralization process, we investigated the effects of dexamethasone (Dex) on the expression of bone matrix proteins in cultured normal human bone marrow stromal cells (HBMSC). Treatment of HBMSC with Dex for 23 days resulted in a significant increase in alkaline phosphatase activity with maximum values attained on day 20 at which time the cell matrix was mineralized. Northern blot analysis revealed an increase in the steady-state mRNA level of alkaline phosphatase over 4 weeks of Dex exposure period. The observed increase in the alkaline phosphatase mRNA was effective at a Dex concentration as low as 10(-10) M with maximum values achieved at 10(-8)M. In contrast, Dex decreased the steady-state mRNA levels of both bone sialoprotein (BSP) and osteopontin (OPN) over a 4 week observation period when compared to the corresponding control values. The relative BSP and OPN mRNA levels among the Dex treated cultures, however, showed a steady increase after more than 1 week exposure. The expression of osteocalcin mRNA which was decreased after 1 day Dex exposure was undetectable 4 days later. Neither control nor Dex-treated HBMSC secreted osteocalcin into the conditioned media in the absence of 1 ,25(OH)(2)D(3) during a 25-day observation period. The accumulated data indicate that Dex has profound and varied effects on the expression of matrix proteins produced by human bone marrow stromal cells. With the induced increment in alkaline phosphatase correlating with the mineralization effects of Dex, the observed concomitant decrease in osteopontin and bone sialoprotein mRNA levels and the associated decline of osteocalcin are consistent with the hypothesis that the regulation of the expression of these highly negatively charged proteins is essential in order to maximize the Dex-induced mineralization process conditioned by normal human bone marrow stromal osteoprogenitor cells.

Adolescent↗

Lipid peroxidation in rats administrated with mercuric chloride.

Parenteral administration of mercuric chloride (HgCl2) to rats enhanced lipid peroxidation in liver, kidney, lung, testis, and serum (but not in heart, spleen, or muscle), as measured by the thiobarbituric acid reaction for malondialdehyde (MDA) in fresh tissue homogenates and body fluids. After sc injection of HgCl2 (5 mg/kg body wt), MDA concentrations in liver and kidney became significantly increased by 9 h and reached peak values at 24 h. Dose-response studies were carried out with male albino rats of the Fisher-344 strain (body wt 170-280 g) injected with 1, 3, 5 mg Hg/kg as HgCl2 and sacrificed after 24 h. In time-response studies, animals were administered 5 mg Hg/kg as HgCl2 and sacrificed after 3, 9, 18, 24, and 48 h. Studies in the authors' laboratory have shown that (1) concentrations of MDA are increased in targets (liver, kidney, lung, and testis) of HgCl2-treated rats; (2) severity of hepatotoxicity and nephrotoxicity is generally consistent with the elevation of Hg and MDA concentrations, based upon the time-course and dose-effect relationships observed after administration of HgCl2 to rats; and (3) concentrations of MDA are reduced in target tissues after pre-treatment with antioxidants and chelators to HgCl2-treated rats. The results of this study implicate that the lipid peroxidation is one of the molecular mechanisms for cell injury in acute HgCl2 poisoning.

Animals↗

Salvage of superficial palmar avulsion.

Avulsion injuries of the hand caused by moving rollers usually create a distally or, less commonly, a laterally based skin flap. Progressive necrosis in the distant part of the flap usually occurs because of arterial insufficiency and venous stasis over the next 2 to 3 weeks. From 1991 to 1994, we applied the concept of the "arterialized venous flap" to salvage the palmar tissue by revascularizing the superficial palmar venous network with an arterial anastomosis in eight patients. Six of the flaps survived completely and two had a small strip of marginal necrosis which healed secondarily. When compared with conventional methods, this method can remarkably improve the circulation of the flap and provide a better cosmetic and functional result for the highly specialized palmar tissue.

Accidents, Occupational↗

Management of large infected tibial defects with radical debridement and staged double-rib composite free transfer.

Seven patients with tibial fractures complicated by large infected tibial defects were treated with a two-stage protocol. In the first stage, antibiotic-impregnated polymethylmethacrylate (PMMA) bead chains were used to obliterate the debrided osseous defect, and a meshed porcine skin was used for temporary wound coverage. In the second stage, the bead chains were removed, and the defects were reconstructed with a microvascularized double-rib and serratus anterior muscle composite free transfer. The interval between the first and second operations was 2 to 4 weeks. The bone defects ranged from 6 to 9 cm, and the skin defect areas ranged from 20 to 40 cm2. Wound healing and bony union was achieved in all seven cases. Minor pin track infection was seen in one patient. Stress fractures in two cases were successfully managed with patellar tendon short-leg bracing for 6 months in one case and a plate internal fixation in the other case. Within 2 years, all seven patients returned to light work without any external support, and all of their most recent radiographs showed good consolidation and hypertrophy of grafted rib bones. No occurrence of osteomyelitis was observed during an average follow-up of 37 months (out of a range of 24 to 50 months). We conclude that this treatment protocol provides rapid recovery from osteomyelitis and the double-rib graft is a useful, durable alternative for large tibial defect management.

Adult↗

Comparison of 22-oxacalcitriol and 1,25(OH)2D3 on bone metabolism in young X-linked hypophosphatemic male mice.

Using a mouse model (Hyp) of human hypophosphatemic vitamin D-resistant rickets [X-linked hypophosphatemia (XLH)], we compared the effects of 22-oxa-1,25-dihydroxyvitamin D3 (OCT) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on restoring defects in mineral and skeletal metabolism. Hyp/Y mice received OCT or 1,25(OH)2D3 at doses of 0.05-0.25 micron.kg-1.day-1 for 4 wk. OCT normalized serum calcium levels, whereas 1,25(OH)2D3 produced hypercalcemia in Hyp/Y. OCT and 1,25(OH)2D3 also normalized serum phosphate levels and increased urinary calcium levels. Additionally, OCT and 1,25(OH)2D3 reduced elevated urinary pyridinoline levels and suppressed urinary adenosine 3',5'-cyclic monophosphate levels to normal. Bone ash content was low in Hyp/Y, and OCT was more effective than 1,25(OH)2D3 in reversing this defect. Histomorphometric analysis of bone turnover, mineralization rate, and osteoid content demonstrated comparable responses with OCT and 1,25(OH)2D3, although the highest dose of 1,25(OH)2D3 resulted in increased osteoid content and delayed mineralization. OCT appears to be more effective and definitely less toxic than 1,25(OH)2D3 in reversing skeletal lesions in Hyp/Y mice and may prove to be the drug of choice in the treatment of childhood XLH.

Animals↗

Fatal hemorrhage caused by vascular injury associated with an acetabular fracture.

We present a case of a widely displaced double-column acetabular fracture associated with lacerations of the ipsilateral common iliac artery and vein, resulting in a fatal hemorrhage. This case illustrates the importance of considering the possibility of a concomitant vascular injury in the assessment of a patient with an acetabular fracture and otherwise unexplained hemorrhage.

Acetabulum↗

"Splint-top" fracture of the forearm: a description of an in-line skating injury associated with the use of protective wrist splints.

Upper extremity injuries are commonly seen in the sport of in-line skating. The use of protective equipment, including wrist splints, has been advocated as a means to decrease both the incidence and severity of upper extremity injuries in this sport. We report on four cases of open forearm fractures in the in-line skaters that occurred adjacent to the proximal border of the wrist splints. The unusual nature of these injuries and the location of the fractures in relation to the location of the splints suggest that the two may be mechanistically related. The splint and distal forearm may act as a single unit to convert the impact from the level of the wrist to a torque moment, with the fulcrum located at the proximal border of the splint. The energy from the fall is then dissipated by the fracturing of the forearm bones at this level. These cases suggest that the use of wrist splints may be associated with their own specific set of injury patterns.

Adult↗

X-linked hypophosphatemic rickets and the murine Hyp homologue.

Recent studies have reported the cloning of several sodium-dependent phosphate cotransport proteins from the apical membrane of proximal tubules of several species. The human proximal tubule apical sodium-phosphate cotransport protein maps to chromosome 5 in the 5q35 region, indicating that this gene is not a candidate for the genetic defect leading to X-linked hypophosphatemia (XLH). Studies in what is thought to be the murine XLH homologue, Hyp, also indicate that the proximal tubular phosphate cotransporter gene does not map to the X chromosome. In Hyp, message levels for the apical membrane sodium cotransport protein are reduced by approximately 50%, similar to the reductions in the apical membrane protein levels of the transporter. This indicates a potential transcriptional defect in Hyp, leading to underexpression of the sodium-dependent phosphate transport protein. Recent studies in the Hyp osteoblast have characterized the intrinsic abnormalities of the cell leading to the osteomalacia characteristic of both Hyp and XLH. These studies demonstrate that the Hyp osteoblast expresses normal rates of phosphate transport, but altered gluconeogenesis similar to the proximal tubule, and that there is an underphosphorylation of an important matrix protein, osteopontin. Since osteopontin is involved in matrix mineralization, defective posttranslational modification of the protein could be a factor in producing the osteomalacia of the Hyp. Other recent studies have demonstrated improved modalities of treatment for Hyp and potentially for XLH. These involve the use of phosphate and nonhypercalcemic analogues of 1 alpha,25-dihydroxyvitamin D3. Thus, although the detection of the genetic defect producing XLH and Hyp is awaited, significant advances in the characterization of the phenotype and the bone abnormalities continue.

Animals↗

Production of interleukin-6 in human osteoblasts and human bone marrow stromal cells: evidence that induction by interleukin-1 and tumor necrosis factor-alpha is not regulated by ovarian steroids.

Studies in murine models of osteoporosis have suggested the hypothesis that ovarian steroids may control osteoclastic bone remodeling by limiting the production of interleukin-6 (IL-6) from osteoblasts and bone marrow stromal cells. To investigate this hypothesis in a human model, we have examined 12 separate strains of normal human osteoblasts (HOB) and 11 separate strains of human bone marrow stromal cells (HBMSC) and determined whether ovarian steroids regulate the induction of IL-6 by interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) or IL-1 + TNF. Treatment with IL-1, TNF or IL-1 + TNF resulted in the induction of IL-6 from both cell types with IL-1 + TNF inducing a synergistic induction of IL-6 in HOB (24- to 324-fold) and HBMSC (35-288 fold). Addition of 17 beta-estradiol or progesterone did not significantly alter IL-6 messenger RNA or protein levels in either HOB or HBMSC cultures stimulated with IL-1, TNF or IL-1 + TNF. Cultures incubated up to 96 h with the steroids did not affect IL-6 expression. Furthermore ovarian steroids did not affect IL-6 production in either HBMSC cultures representative of preosteoblasts or HOB cultures representative of highly differentiated osteoblasts. Specific chloramphenicol acetyl transferase assays and reverse transcriptase-polymerase chain reaction studies also demonstrated that the lack of an estrogen effect was not due to the failure of HOB to express functional estrogen receptors. Therefore, we conclude that the regulation of human osteoclastic bone remodeling by ovarian steroids does not occur through the direct regulation of IL-6 gene transcription or protein secretion in either early stages of osteoblast differentiation or the differentiated osteoblast.

Adolescent↗

The effect of the medial collar in total hip arthroplasty with porous-coated components inserted without cement. An in vivo canine study.

We performed an in vivo study in a canine model to compare the results of the use of a porous-coated collared femoral component with those of the use of a porous-coated collarless femoral component in total hip arthroplasties without cement. Our study focused on the comparative proximal strain pattern, bone ingrowth, and cortical porosity of the two types of prostheses. We used a trochanteric wire marker to measure subsidence. The use of the limb was assessed with gait analysis. Twelve weeks after the operation, the collarless components had significantly greater bone ingrowth proximally (p = 0.003) and were associated with significantly lower cortical porosity (p = 0.006). There were no differences between the groups with regard to either axial or hoop strain. While the group that had a collarless prosthesis had significantly less proximal-medial radiolucency (p = 0.03), there were no differences between the groups with regard to subsidence.

Animals↗

Knee arthrodesis using a short locked intramedullary nail. A new technique.

This article reports on the use of a new intramedullary nail designed specifically for fixation of knee fusions. The nail is a short locked stainless steel nail that is inserted through a single anterior knee incision and uses an outrigger targeting rod to guide the insertion of the locking screws. The successful use of this technique is illustrated in two cases. The advantages of this nail compared with previously reported techniques of fixation for knee fusions are that the short locked nail avoids the second incision required for the insertion of long knee fusion nails, the bulkiness of the double plating technique in the relatively subcutaneous anterior knee area, and the difficulties inherent with the prolonged use of pins for external fixation.

Adult↗