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Biomedical subjects

S M Kumta

Publications and source records attributed to S M Kumta.

At least 19 recordsLinked to original sources
PubMed2003

The effect of hyaluronan on osteoblast proliferation and differentiation in rat calvarial-derived cell cultures.

Hyaluronan (or hyaluronic acid, HA) is an essential component of extracellular matrices. It interacts with other macromolecules and plays a predominant role in tissue morphogenesis, cell migration, differentiation, and adhesion. The cell signaling functions of HA are mediated through the CD-44 receptor and are dependent upon the molecular weight of the polymer. We hypothesized that an HA of appropriate molecular weight alone in optimal concentration may induce osteoblast differentiation and bone formation. Enzyme-digested calvarial-derived mesenchymal cells from 2-day-old newborn rats were cultured with the addition of HA of three different molecular weights (2300, 900, and 60 kDa). We added, 0.5, 1.0, and 2.0 mg/mL HA for each molecular weight to the medium at the first plating of cells. After 7 to 20 days in culture, cell proliferation and differentiation were evaluated by measuring thymidine incorporation, alkaline phosphatase activity, and osteocalcin gene expression. The effects of HA on bone formation were examined by using Alizarin red staining for mineralization. The results showed that low molecular weight HA (60 kDa) significantly stimulated cell growth, increased osteocalcin mRNA expression in a dose-dependent manner, but showed no apparent effects on alkaline phosphatase activity and bone mineralization. On the other hand, high-weight HA (900 and 2,300 kDa) significantly increased all the parameters examined, particularly alkaline phosphatase activity, in a dose-dependent manner and stimulated cell mineralization to 126% and 119% of the controls, respectively, in the 1.0 mg/mL dose. Our findings suggest that HA has a molecular weight-specific and dose-specific mode of action that may enhance the osteogenic and osteoinductive properties of bone graft materials and substitutes due to its stimulatory effects on osteoblasts.

Alkaline Phosphatase↗
PubMed2003

Expression of VEGF and MMP-9 in giant cell tumor of bone and other osteolytic lesions.

This study aims to investigate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in giant cell tumor of bone (GCT) and other osteolytic lesions in bone. By using semi-quantitative RT-PCR, we showed that three major isoforms of VEGF (121, 165 and 189) were expressed in GCTs, with isoform 121 being the most abundant. The expression levels of VEGF and MMP-9 mRNA were significantly higher in advanced GCTs (stage II/III) than in stage I GCTs. We further elucidated the cellular localization of VEGF and MMP-9 gene transcripts in GCT and other osteolytic lesions using an in situ hybridization assay. The results showed that stromal tumor cells and osteoclast-like giant cells of GCT, fibrous stromal cells in anuerysmal bone cysts and fibrous dysplasia, and Langerhans-type giant cells as well as histocytes in eosinophillic granuloma, were all strongly positive for VEGF and MMP-9 mRNA expression. In a prospective study, we performed VEGF and MMP-9 immuno-staining on paraffin sections of pathological tissues harvested from 48 patients (14 GCT, 10 anuerysmal bone cysts, 10 eosinophillic granuloma, 4 fibrous dysplasia, 2 simple bone cyst, 2 osteomyelitis and 6 patients with fractured femoral head as control). The results showed that the differences in VEGF and MMP-9 expression between Stage I and other advanced Stages (II, III and recurrent) were highly significant (p<0.001), with advanced stages showing a higher mean expression. The difference between recurrent and Stage II and III lesions, was also statistically significant (p=0.03 for VEGF, and p=0.01 for MMP-9 expression), with recurrent lesions showing a higher mean expression of both VEGF and MMP-9. In conclusion, VEGF and MMP-9 expression in osteolytic lesions of bone co-relates well with the extent of bone destruction and local recurrence. Their expression may therefore provide some prognostic indication of the possible aggressive behavior of the underlying pathology.

Bone Cysts↗
PubMed2003

Massive intestinal hemorrhage resulting from a polypoid tumor in the sigmoid colon: an unusual complication of a giant cell tumor of the fifth lumbar vertebra.

STUDY DESIGN: Clinicopathologic study of a case of giant cell tumor of the spine. SUMMARY OF BACKGROUND DATA: Giant cell tumors of the spine are uncommon, accounting for 1.3-6.5% of all cases in various series. Because of their location, they may cause neurologic deficits. The treatment consists of excision or curettage and has been claimed to give good results. METHODS: A 33-year-old woman presented with low back pain in 1995; radiologic investigation and biopsy showed features of giant cell tumor involving the fifth lumbar and first sacral vertebrae. Wide excision was performed, but the tumor recurred in 1996 and was curetted. She developed massive intestinal bleeding in 1997 resulting from infiltration of the sigmoid colon by giant cell tumor in the form of a polypoid intraluminal mass. The involved segment of colon was resected, and the patient remained alive, although debilitated, 7 years after initial presentation. RESULTS: Examination of the tumor in the spine and the colon showed typical histology of giant cell tumor with no evidence of malignant transformation. The involved colon was freely mobile and away from the tumor of the spine. CONCLUSION: Giant cell tumor of the spine can result in unusual complication, massive intestinal hemorrhage in our case, which causes considerable morbidity.

Adult↗
PubMed2003

Receptor activator of NF-kappaB ligand (RANKL) is expressed in chondroblastoma: possible involvement in osteoclastic giant cell recruitment.

AIMS: Chondroblastoma is a rare, locally aggressive bone tumour that causes osteolytic destruction at the epiphyseal end of the affected bone. It is possible that tumour cells may stimulate osteoclastogenesis and osteolytic destruction through the production of receptor activator of NF-kappaB ligand (RANKL), which is a key molecule essential for regulating osteoclast formation and activity. Therefore, the expression of RANKL at both the mRNA and the protein level was investigated in chondroblastoma tumour tissue obtained from patients. METHODS: The expression of RANKL gene transcripts was analysed by the reverse transcription-polymerase chain reaction (RT-PCR), and the cellular localisation of RANKL mRNA and protein was demonstrated by means of in situ hybridisation and immunohistochemistry. RESULTS: RT-PCR analysis indicated that RANKL mRNA was present in all chondroblastoma specimens and normal cancellous bone samples, but not in normal articular cartilage and chondrosarcoma tissues. In contrast, gene transcripts of osteoprotegerin (OPG), the decoy receptor of RANKL, were detected in all types of tissues. The chondroid origin of neoplastic mononuclear cells in chondroblastoma was confirmed by positive S-100 immunohistochemical staining. Both RANKL mRNA and protein were exclusively expressed in these neoplastic mononuclear cells. CONCLUSIONS: These findings suggest that RANKL may be involved in the tumour cell induced recruitment of osteoclast-like cells and consequent osteolytic bone destruction in chondroblastoma.

Adolescent↗
PubMed2003

Local flap coverage for soft tissue defects following open repair of Achilles tendon rupture.

The authors assessed the long term clinical and functional results following local flap coverage (medial plantar flap, peroneal reverse flow island flap, posterior tibial reverse flow flap) in 11 patients who developed wound complications after open repair of a ruptured Achilles tendon. At the latest follow-up, seven patients had achieved a good result, having returned to their pre-injury activities. All patients were able to stand on tiptoes unaided, and were able to walk without aid. In our hands, local flaps are a reliable means of treating skin defects following open repair of subcutaneous ruptures of the Achilles tendon.

Achilles Tendon↗
PubMed2002

Closed retrograde nailing of pathological humeral fractures.

We treated 19 patients with 21 pathological humeral fractures secondary to metastatic disease. All patients were stabilized using retrograde Ender's nails. Open reduction was required in one patient and mean operative time was 40 min (range 30-65 min). All patients retained satisfactory elbow and shoulder function while 16 patients reported good pain relief. Functional recovery was rated as good in 15 patients, fair in three, and poor in one. In our experience the retrograde technique using Ender's nails provides secure stabilization with minimal morbidity, minimal blood loss, and short operative time, and is well suited for this category of patients.

Adult↗
PubMed2002

Pseudoaneurysm complicating osteochondromas: symptom relief with embolization.

Pseudoaneurysm is a recognized vascular complication of osteochondromas. The diagnosis is confirmed by various imaging techniques including ultrasound, magnetic resonance imaging, and conventional angiography. Surgical repair and excision of the adjacent osteochondroma is considered the treatment of choice. The authors report a case of successful transarterial embolization using helical microcoils in the treatment of osteochondroma-related pseudoaneurysm of the superficial femoral artery. It resulted in complete obliteration of blood flow to the pseudoaneurysm and good symptomatic relief before subsequent semielective surgery. No complication was encountered during the procedure. Transarterial embolization is a safe mode of treatment in experienced hands. In patients with contraindications to surgery, embolization may be considered a definitive treatment.

Adolescent↗
PubMed2001

Gene expression of glucocorticoid receptor alpha and beta in giant cell tumour of bone: evidence of glucocorticoid-stimulated osteoclastogenesis by stromal-like tumour cells.

Glucocorticoids have been shown to increase bone resorption in vitro and in vivo, however, the mechanism(s) of this action are not fully understood. Given that human giant cell tumour of bone (GCT) is considered to arise from mesenchymal stromal cells and has the capacity to recruit and harbour macrophages and multinucleated osteoclasts, we have used GCT as a model for studying the effect of glucocorticoids on osteoclast formation. We have demonstrated, by RT-PCR and fluorescence in-situ hybridisation, that both glucocorticoid receptor alpha and beta (GRalpha and GRbeta) gene transcripts were present in the stromal-like tumour cells, macrophage-like cells (putative osteoclast precursors) and multinucleated osteoclast-like cells. Moreover, in the presence of 1,25(OH)(2)D(3), dexamethasone dose-dependently stimulated the formation of osteoclast-like cells from GCT-derived co-culture system of stromal-like tumour cells and macrophage-like cells. The stimulation of osteoclastogenesis by dexamethasone was coincident with the up-regulation of receptor activator of NF-kappaB ligand (RANKL) but down-regulation of osteoprotegerin (OPG) gene expression in stromal-like tumour cells. These data are consistent with the hypothesis that glucocorticoids increase bone resorption by promoting osteoclastogenesis which is at least in part due to the stimulation of RANKL and inhibition of OPG production in bone stromal cells.

Cells, Cultured↗
PubMed2001

Alveolar soft-part sarcoma: a rare soft-tissue malignancy with distinctive clinical and radiological features.

Alveolar soft-part sarcoma (ASPS) is a rare tumour. Certain distinctive clinical and radiological features suggest the correct diagnosis. There is moderate predilection for young women. ASPS almost always arises in skeletal muscle and occurs most frequently in the lower limbs. There is often a long clinical history and a large mass at presentation. Two young females with ASPS presented with very vascular tumours in the thigh, with prominent intra- and extra-tumoural blood vessels. The imaging findings and the existing literature are reviewed.

Adolescent↗
PubMed2001

Clinical significance of P-glycoprotein immunohistochemistry and doxorubicin binding assay in patients with osteosarcoma.

In 45 osteosarcoma patients, mean age 18 (4-61) years and followed for 14 (5-48) months, we studied the sensitivity to doxorubicin as well as P-glycoprotein expression, and compared these with the extent of tumour necrosis following chemotherapy. Doxorubicin assay was positive in 37 patients in whom necrosis induced by chemotherapy was good in 20 and poor in 17. Metastases developed in nine patients. In eight patients in whom doxorubicin assay indicated tumour resistance, chemonecrosis was poor and all developed pulmonary metastases. P-glycoprotein was studied in pre-treatment biopsies and post-treatment resection specimens. Its expression was positive in 16 patients in whom the necrosis induced by chemotherapy was good in four and poor in 12. In 29 patients with negative P-glycoprotein expression, necrosis was good in 16 and poor in 13. The doxorubicin sensitivity had a high correlation with chemonecrosis (P=0.006) and the incidence of metastases (P<0.001). However, P-glycoprotein expression at the time of diagnosis did not correlate statistically with chemonecrosis (P=0.066). Doxorubicin sensitivity prior to treatment is a better determinant of the response to chemotherapy and clinical outcome than is the P-glycoprotein expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Kaposiform hemangioendothelioma: five patients with cutaneous lesion and long follow-up.

Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor of the skin, deep soft tissue, and bone in children, characterized by infiltrating nodules and sheets of spindle cells, and unmistakable resemblance to Kaposi's sarcoma. More than 60 patients with such tumor have been reported so far, and while many have died as a result of extensive disease and severe coagulopathy, the long-term biologic behavior of this tumor remains undetermined. We describe five patients with kaposiform hemangioendothelioma and a mean follow-up of 19 years, ranging from 8 to 35 years. This report emphasizes on the importance of cutaneous lesions being the most commonly affected site, but also for its clinical diversity. Early diagnosis is possible even for a small skin lesion, which may be critical for the treatment of a potentially fatal deep-seated extensive tumor. All five patients are well, and three of them with persistent vascular tumor, which has carried two patients from childhood to adult. Although the behavior of this tumor might have been modified by radiation or interferon in three patients, this series indicates that kaposiform hemangioendothelioma is incapable of metastasis, despite a protracted course of many decades with no tendency for spontaneous regression.

Adult↗
PubMed2000

Monostotic fibrous dysplasia of the spine: report of a case involving the lumbar transverse process and review of the literature.

Monostotic fibrous dysplasia of the spine is rare. We report its clinical, radiologic and histologic features affecting a 47-year-old housewife. She presented with low-back pain of 1-year's duration, and radiographs showed a diffuse expansile lesion in the left transverse process of the fourth lumbar vertebra. The lesion was excised and histologically confirmed to be fibrous dysplasia. The patient remained well 8 years after operation. Including the present case, a total of 22 cases of monostotic fibrous dysplasia of the spine were found in the literature. Combining these reported cases, we found that the condition affects either sex with equal frequency and presents at any age, the mean being 32 years. There is no predilection for any part of the spinal column, though sacral or coccygeal involvement is distinctly rare. It most commonly involves the body and adjacent pedicle, although no part of the vertebra is spared. It is worth noting that a propensity for progressive enlargement, even to the extent of causing graft destruction, exists if the lesion is left untreated or incompletely treated. Complete removal of all involved bone, together with stabilization, should therefore be the treatment of choice for this condition.

Female↗
PubMed2000

Repair of muscle and musculotendinous junction injuries with an autogenous fascial patch.

We have used an autogenous fascia lata patch to repair muscle and musculotendinous junction injuries affecting 99 individual muscles in 23 patients with multiple incised wounds to the upper limbs. All patients were followed up for at least 2 years. Two patients with severe dystrophic changes following nerve injuries were excluded from the final analysis. Satisfactory grip strength was restored 6 months following the repair in 19 of the 21 patients we evaluated. Complete active and passive range of wrist and digital motion was seen in 18 of these 21 patients. Tightness of the flexor pollicis longus was seen in 2 patients, one of whom had a deformity of the interphalangeal joint of the thumb that was passively stretched and subsequently reduced. Scar adhesions were noted in 4 other patients, but this did not affect wrist or finger motion, except in one. The autogenous fascial patch repair technique provides strong and good apposition of muscle fibres simply by distributing the force and tension over a large area of the muscle, thereby allowing early mobilization and functional restoration of the extremity.

Arm Injuries↗
PubMed2000

Gene expression of vascular endothelial growth factor in giant cell tumors of bone.

The production of vascular endothelial growth factors (VEGF), a major cause of neoangiogenesis, is a prerequisite for tumor growth and invasion. VEGF have also been shown to be important for the formation of osteoclasts. Because giant cell tumors of bone (GCT) are frequently hypervascular and have the ability to recruit macrophages and multinucleated osteoclast-like giant cells, we evaluated the levels of VEGF gene transcript in several of these tumors using Northern blot analyses, semiquantitative reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry. Our results showed that three major isoforms of VEGF (121, 165, and 189) were expressed in all cases of GCT investigated, with isoform 121 transcripts the most abundant. By both FISH and immunohistochemistry, we have shown that VEGF was present in spindle-shaped stromal-like tumor cells, round macrophage-like cells, and osteoclast-like multinucleate giant cells. Moreover, we have shown that the levels of VEGF gene expression but not microvessel density correlated with Enneking's clinical stage of GCT. There were higher levels of VEGF gene expression in stage III GCT than in stage I/II GCT (P < .0357). In conclusion, our results indicate that overexpression of VEGF may be associated with the advanced stage of the neoplasm.

Adult↗
PubMed2000

Vascularised bone grafting for fibrous dysplasia of the upper limb.

We describe our experience with vascularised bone grafting for the treatment of fibrous dysplasia of the upper limb in eight patients, five men and three women, aged between 17 and 36 years. The site was in the humerus in six and the radius in two. Persistent pain, progression of the lesion and pathological fracture with delayed union were the indications for surgical intervention. We used a vascularised fibular graft after curettage of the lesion. Function and radiological progress were serially monitored. Early radiological union of the graft occurred at periods ranging from 8 to 14 weeks. The mean period for reconstitution of the diameter of the bone was 14 months (12 to 18) predominantly through inductive formation of bone around the vascularised graft, which was a prominent feature in all patients. There were no recurrences and none of the grafts sustained a fracture or failed to unite. After operation function was excellent in three patients and good in five. Vascularised bone grafts provide a safe and reliable means of ensuring good continuity of bone with little risk of recurrence and failure.

Adolescent↗
PubMed1999

Imaging following allograft reconstruction in children with malignant bone tumours.

PURPOSE: To determine the nature of the imaging findings following reconstructive surgery using massive allografts in children with malignant bone tumours. MATERIALS AND METHODS: A retrospective review of the imaging studies and medical charts of 25 consecutive children who received an allograft as part of the management of a malignant bone tumour. RESULTS: Uncomplicated allografts were sclerotic relative to native bone on radiographs and showed a typical 'tramline' appearance on bone scintigraphy. On MR, the medullary canal of the allograft showed low signal, similar to or greater than skeletal muscle, but less than subcutaneous fat, on 91 % of T1-weighted images. On short-tau inversion recovery images, the medullary canal was inhomogeneous and hyperintense to subcutaneous fat in 70 % and hyperintense to muscle in the remainder. Complications occurred in 68 % of patients and included allograft fractures (36 %), recurrent tumour (20 %), infection (8 %), and non-union or delayed union (8 %). The radiographic findings alone permitted accurate diagnosis of most serious complications. Infection and rejection were difficult to distinguish with any technique. All complications were suspected on clinical and/or radiological grounds before being shown by MR or scintigraphy. CONCLUSIONS: Allografts, whether normal or complicated, have characteristic imaging findings, except that infection and bone resorption related to rejection and revascularisation are difficult to distinguish. Routine MR and bone scintigraphy appear to contribute little to the management of these patients.

Adolescent↗