Scientific misconduct.
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Ethics, Research↗
Biomedical subjects
M Sundaram
Publications and source records attributed to M Sundaram.
Heterotopic ossification: a review.
Heterotopic ossification is the formation of bone in the soft tissues. Soft tissue bone deposition may range from the minimal and inconsequential to massive and clinically significant. In some clinical settings it is a predictable finding with an unpredictable course and in other settings it may be diagnostically confounding. Heterotopic ossification may be encountered in clinically disparate disease processes and circumstances. We review the genetic, neurogenic, post-traumatic, post-surgical and "reactive" causes of heterotopic ossification and discuss some current concepts of its pathogenesis.
Arthroplasty, Replacement, Hip↗
Calcific myonecrosis: a unique presentation in the upper extremity.
Calcific myonecrosis is a rare and latent condition characterized by a dystrophic calcified lesion that can present 10-64 years following initial trauma. Of the 25 cases documented in English world literature, all have occurred in the lower extremity exclusively. We report a case of a 60-year-old man with a painless enlarging left forearm mass that was subsequently diagnosed as calcific myonecrosis. Awareness of this lesion arising outside of the lower extremity is important to avoid unnecessary surgical intervention and patient reassurance.
Calcinosis↗
Microscopic correlation of radiographically disparate appearing well differentiated osteosarcoma.
Well differentiated (low grade) osteosarcomas are often unrecognized and inadequately treated. We report on a patient with a well differentiated osteosarcoma of the tibia that radiographically presented with two strikingly dissimilar appearing juxtaposed lesions. Proximally, the lesion was sclerotic, and distally, osteolytic. The distal lytic half of the lesion showed focal cortical disruption on MR imaging. Microscopic correlation of the resected specimen suggested that the sclerotic component of the lesion had more fibrous dysplasia-like tissue with fewer features of well differentiated osteosarcoma, and the lytic component, features suggestive of well differentiated osteosarcoma. We believe this microscopic interpretation explains the disparate radiographic appearance as all belonging to well differentiated osteosarcoma with varying amounts of fibrous dysplasia-like tissue rather than the development of well differentiated osteosarcoma in fibrous dysplasia.
Bone Neoplasms↗
Acral synovial chondrosarcoma.
Acral chondrosarcoma is rare. Synovial chondrosarcoma is even rarer. Synovial chondrosarcoma arising without evidence of pre-existing or concurrent synovial chondromatosis is exceedingly rare. We present a case of acral synovial chondrosarcoma involving both sides of the metacarpophalangeal joint of the thumb in a 69-year-old man. Radiographically, the lesion mimicked gout. On MR imaging, the lobulated contours of the soft tissue mass suggested synovial chondromatosis. Histological examination revealed a chondrosarcoma, which on the basis of imaging findings we present as having arisen from the synovium. The tumor invaded a portion of the cartilage of the metacarpophalangeal joint and equally destroyed the bones of the distal metacarpal and base of the proximal phalanx of the thumb, while sparing the bony joint surfaces.
Aged↗
Effect of RH-5992 on adult development in the spruce budworm, Choristoneura fumiferana.
The effect of RH-5992 (tebufenozide), a non-steroidal ecdysone agonist, on adult development of the spruce budworm, Choristoneura fumiferana, was investigated by administering the compound intrahemocoelically to pupae on days 1-6 after pupal ecdysis. At concentrations of 200ng/pupa there was significant mortality but at doses of 50-100ng/pupa, the emerging adults displayed wing deformities which reduced their ability to mate and oviposit. Light microscopy of the pupal wings revealed that there was degeneration of the epithelial cells, reduction in the number of veins, precocious cuticle formation and inhibition of growth of normal wing scales. Injection of RH-5992 into pupae resulted in a dose dependent induction of mRNA for ecdysone-induced transcription factor, Choristoneura hormone receptor 3 (CHR3). These results suggest that the pupae respond to RH-5992 in a manner similar to larvae. However, the effects are not expressed overtly and are camouflaged by the pharmacological effects.
Animals↗
Topology of a human equilibrative, nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter (hENT1) implicated in the cellular uptake of adenosine and anti-cancer drugs.
The human equilibrative nucleoside transporter hENT1, the first identified member of the ENT family of integral membrane proteins, is the primary mechanism for the cellular uptake of physiologic nucleosides, including adenosine, and many anti-cancer nucleoside drugs. We have produced recombinant hENT1 in Xenopus oocytes and used native and engineered N-glycosylation sites in combination with immunological approaches to experimentally define the membrane architecture of this prototypic nucleoside transporter. hENT1 (456 amino acid residues) is shown to contain 11 transmembrane helical segments with an amino terminus that is intracellular and a carboxyl terminus that is extracellular. Transmembrane helices are linked by short hydrophilic regions, except for a large glycosylated extracellular loop between transmembrane helices 1 and 2 and a large central cytoplasmic loop between transmembrane helices 6 and 7. Sequence analyses suggest that this membrane topology is common to all mammalian, insect, nematode, protozoan, yeast, and plant members of the ENT protein family.
Adenosine↗
Equilibrative nucleoside transporters: mapping regions of interaction for the substrate analogue nitrobenzylthioinosine (NBMPR) using rat chimeric proteins.
The rat equilibrative nucleoside transporters rENT1 and rENT2 belong to a family of integral membrane proteins with 11 potential transmembrane segments (TMs) and are distinguished functionally by differences in sensitivity to inhibition by nitrobenzylthioinosine (NBMPR). Structurally, the proteins have a large glycosylated extracellular loop between TMs 1 and 2 and a large cytoplasmic loop between TMs 6 and 7. In the present study, we have generated chimeras between NBMPR-sensitive rENT1 and NBMPR-insensitive rENT2, using splice sites at rENT1 residues 99 (end of TM 2), 171 (between TMs 4 and 5), and 231 (end of TM 6) to identify structural domains of rENT1 responsible for transport inhibition by NBMPR. Transplanting the amino-terminal half of rENT2 into rENT1 rendered rENT1 NBMPR-insensitive. Domain swaps within the amino-terminal halves of rENT1 and rENT2 identified two contiguous regions, TMs 3-4 (rENT1 residues 100-171) and TMs 5-6 (rENT1 residues 172-231), as the major sites of NBMPR interaction. Since NBMPR is a nucleoside analogue and functions as a competitive inhibitor of zero-trans nucleoside influx, TMs 3-6 are likely to form parts of the substrate translocation channel.
Affinity Labels↗
Identification of Cys140 in helix 4 as an exofacial cysteine residue within the substrate-translocation channel of rat equilibrative nitrobenzylthioinosine (NBMPR)-insensitive nucleoside transporter rENT2.
The human and rat equilibrative nucleoside transporter proteins hENT1, rENT1, hENT2 and rENT2 belong to a family of integral membrane proteins with 11 potential transmembrane segments (TMs), and are distinguished functionally by differences in transport of nucleobases and sensitivity to inhibition by nitrobenzylthioinosine (NBMPR) and vasoactive drugs. In the present study, we have produced recombinant hENT1, rENT1, hENT2 and rENT2 in Xenopus oocytes and investigated uridine transport following exposure to the impermeant thiol-reactive reagent p-chloromercuriphenyl sulphonate (PCMBS). PCMBS caused reversible inhibition of uridine influx by rENT2, but had no effect on hENT1, hENT2 or rENT1. This difference correlated with the presence in rENT2 of a unique Cys residue (Cys(140)) in the outer half of TM4 that was absent from the other ENTs. Mutation of Cys(140) to Ser produced a functional protein (rENT2/C140S) that was insensitive to inhibition by PCMBS, identifying Cys(140) as the exofacial Cys residue in rENT2 responsible for PCMBS inhibition. Uridine protected wild-type rENT2 against PCMBS inhibition, suggesting that Cys(140) in TM4 lies within or is closely adjacent to the substrate-translocation channel of the transporter. TM4 has been shown previously to be within a structural domain (TMs 3-6) responsible for interactions with NBMPR, vasoactive drugs and nucleobases.
Amino Acid Sequence↗
Mode of action of the ecdysone agonist tebufenozide (RH-5992), and an exclusion mechanism to explain resistance to it.
Spruce budworm larvae (Choristoneura fumiferana) upon ingesting tebufenozide (RH-5992) stop feeding and go into a precocious, incomplete molt, leading eventually to death. Like 20-hydroxyecdysone (20E), tebufenozide also acts at the receptor level and transactivates the expression of up-regulated genes but, because of its persistence, the down-regulated genes that are normally expressed in the absence of 20E are not expressed. While tebufenozide is lepidopteran-specific, an analog, RH-5849, is effective on dipterans. This is reflected in the respective effects of the two compounds on Cf-203 (C. fumiferana--203), a lepidopteran cell line and Dm-2 (Drosophila melanogaster--2), a dipteran cell line. Cf-203 cells accumulated [14C]tebufenozide and expressed CHR3 (Choristoneura hormone receptor 3), but Dm-2 cells excluded the material and did not express DHR3 (Drosophila hormone receptor 3). Using yeast ABC (ATP binding cassette) transporter mutants, we determined that PDR5 (pleiotropic drug resistance 5) was responsible for the exclusion. We discovered recently that older instars of the white-marked tussock moth (Orgyia leucostigma) are resistant to tebufenozide, perhaps as a result of such an exclusion system. We are currently cloning PDR5 (pleiotropic drug resistance 5), which is an essential step in studying the resistance mechanism.
Animals↗
Florid reactive periostitis and bizarre parosteal osteochondromatous proliferation: pre-biopsy imaging evolution, treatment and outcome.
OBJECTIVE: To report on the imaging evolution of florid reactive periostitis (FRP) and bizarre parosteal osteochondromatous proliferation (BPOP) of the phalanges of the hands from prospective diagnosis to operation and on postsurgical outcome. DESIGN AND PATIENTS: Three patients (2 female, 1 male; age range 11-34 years) presented with a swollen digit of the hand. Following presumptive radiographic diagnosis of FRP, they were closely observed both clinically and radiographically until operation. All three patients had radiographs of the involved digit, and one patient had an MR imaging examination. The interval between presumptive diagnosis and operation ranged from 2 to 8 months. Following operation, the patients have been clinically followed for 9-13 months (mean 10 months). RESULTS: In each of the patients, maturing of periosteal reaction without bone destruction was observed within 1-2 weeks of the presumptive diagnosis of FRP. Periosteal reaction was initially minimal in relation to the extent of soft tissue swelling and subsequently became more florid. In one patient, the lesion ossified, became adherent to the phalanx, and had an "osteochondromatous" appearance. In another patient, periosteal reaction was seen on both sides of the phalanx with an intact phalanx. In the sole patient who had MR imaging, edema was seen in the phalanx distal to the symptomatic site and the metacarpal proximal to the symptomatic site. CONCLUSIONS: Close clinical and radiographic correlation permits an accurate pre-biopsy diagnosis of FRP. The first follow-up radiograph taken within 2 weeks usually provides re-assurance of the accuracy of the diagnosis. FRP may progress to BPOP. Arbitrary antibiotic treatment can be avoided, and a planned surgical approach can be adopted.
Adult↗
Focal fibrocartilaginous dysplasia: curettage as an alternative to conservative management or more radical surgery.
We describe two cases of focal fibrocartilaginous dysplasia, one treated conservatively while the other underwent curettage of the lesion. Resolution of tibia vara and healing of the focal fibrocartilaginous dysplasia was noted at 6 months in the patient who underwent curettage while the conservatively managed patient required 8 years of follow-up. Of the 17 cases of conservatively followed tibial focal fibrocartilaginous dysplasia described in the literature, 11 showed complete recovery after a median interval of 57 months. We believe that curettage may result in rapid healing by removing the persistent mesenchymal anlage which can interfere with the normal growth of the tibia.
Age Factors↗
T1-weighted MR imaging for distinguishing large osteolysis of Paget's disease from sarcomatous degeneration.
OBJECTIVE: To report five symptomatic patients, four with unequivocal Paget's disease and large areas of osteolysis and one patient with presumed osteolytic Paget's disease, evaluated by MR imaging to confirm or exclude a sarcoma. DESIGN AND PATIENTS: Four men and one woman (median age 74 years) presented with new symptoms of pain. Four of these patients had unequivocal Paget's disease with large areas of osteolysis; one patient presented with large focal osteolysis and no other finding. MR imaging was performed in each case to exclude malignancy in the area of osteolysis. RESULTS: Two patients whose MR images showed a low signal abnormality on the T1-weighted sequence corresponding to osteolysis on the radiograph were found to have malignant degeneration. Three patients with osteolytic lesions on T1-weighted MR imaging showed preservation of fat signal in the areas of osteolysis, were not biopsied and have been free of malignant disease for from 12 months to 2 1/2 years. One patient had one area of osteolysis in the iliac bone which showed malignancy and another area of osteolysis which showed preservation of fat signal on the T1-weighted sequence. CONCLUSIONS: The information obtained from T1-weighted MR imaging sequences performed on patients with Paget's disease who have new symptoms and large areas of osteolysis could reliably be used in the clinical decision-making process between conservative follow-up and biopsy.
Aged↗
Severe toxic osteoblastoma of the humerus associated with diffuse periostitis of multiple bones.
Toxic osteoblastoma is a rare variant of an uncommon primary bone tumour that has been described only once before in the world medical literature. It is characterised by systemic features including fever, weight loss and a striking diffuse periostitis in association with an osteoblastoma, resulting in delayed diagnosis. Early recognition of this condition could prevent inappropriate therapies and reduce morbidity.
Biopsy↗
Destructive spondyloarthropathy of the cervical spine in long-term hemodialyzed patients: a five-year clinical radiological prospective study.
OBJECTIVE: To describe the radiographic features and progression of cervical spine destructive spondyloarthropathy (DSA) in hemodialyzed patients, and to evaluate the relationship between this disease and patient characteristics, biochemical values, and hemodialysis duration. DESIGN AND PATIENTS: Standard radiographs, and lateral flexion and extension views of the cervical spine, were performed annually for 5 years in 31 hemodialyzed patients who were divided into three groups at the commencement of the study: those showing (I) DSA, (II) vertebral rim erosions (VRE) without DSA, and (III) absence of DSA and VRE. Magnetic resonance (MR) imaging and computed tomography (CT) were performed in seven and two patients respectively. The imaging features were evaluated for the presence and progression of spondyloarthropathy and correlated with clinical and biochemical variables. Statistical analysis was performed using one-way analysis of variance. RESULTS: The duration of hemodialysis appeared to be the main predictive factor (P=0.0003) for DSA, which was found in six patients (19%). DSA was found to correlate with higher levels of beta2-microglobulin (P<0.00001), parathyroid hormone (P<0.05), and alkaline phosphatase (P<0.05). Clinical symptoms were minimal. In two patients, MR imaging revealed changes mimicking spondylodiscitis. In another patient, CT of the craniocervical junction showed bone resorption due to a pseudotumor, and basilar invagination. CONCLUSIONS: DSA of the cervical spine is often clinically silent. Pathogenesis of DSA may be multifactorial but its progression is most influenced by the duration of hemodialysis. On MR imaging, DSA may mimic spondylodiscitis.
Adult↗
Imaging findings in pseudocystic osteosarcoma.
OBJECTIVE: Our purpose was to describe four female patients with osteosarcoma whose clinical and imaging findings primarily suggested either simple or aneurysmal bone cyst. All lesions were osteolytic, intracompartmental, and expanded bone without periosteal reaction. None of the patients presented during the peak age incidence for osteosarcoma. From imaging to histologic diagnosis, the discovery of osteosarcoma ranged from 1 week to 3 years. CONCLUSION: Atypical osteosarcoma may rarely mimic simple or aneurysmal bone cyst radiologically and may show a nonmalignant rate of growth. It may be more frequently encountered in females and may not present during the peak age incidence for osteosarcoma. Microscopically, the tumors were not cystic, necrotic, or telangiectatic but were conventional osteosarcoma and osteoclast-rich osteosarcoma.
Adult↗
Periosteal chondroid tumors: radiologic evaluation with pathologic correlation.
OBJECTIVE: The purpose of this study was to determine whether the imaging features of periosteal chondroid tumors correlate with histopathology. MATERIALS AND METHODS: Twenty-two patients (nine women and 13 men; mean age, 33 years) with pathologically proven periosteal chondroid lesions were retrospectively reviewed. The imaging modalities included conventional radiography (n = 17), CT (n = 10), and MR imaging (n = 14). The images were reviewed by two osteoradiologists, with agreement by consensus. Evaluation criteria included lesion location, mineralization, and size; periosteal reaction; and cortical response. Intramedullary extension, adjacent intramedullary edema, soft-tissue edema, and intrinsic characteristics were also evaluated on MR imaging. After the evaluation, a radiologic diagnosis of chondroma or chondrosarcoma was obtained. An experienced osteopathologist who was unaware of the patient's medical history and radiologic findings reviewed all histopathology. Agreement between the radiologic and the histopathologic diagnosis was tested using the kappa analysis. Imaging features were correlated with the pathologic findings, and a statistical analysis was performed. RESULTS: Using strict pathologic criteria, we diagnosed 11 chondromas and 11 chondrosarcomas (nine, grade I; two, grade II). Moderate agreement was reached between the radiologic and the pathologic diagnosis (kappa = 0.55). The size of periosteal chondrosarcomas (range, 3-14 cm; median, 4 cm) was considerably larger than the size of the chondromas (range, 1-6.5 cm; median, 2.5 cm; p < 0.05). Other imaging features did not significantly correlate with benign versus malignant disease at pathology (all p > 0.05). CONCLUSION: A variable overlap existed in the imaging appearances of benign and malignant periosteal chondroid lesions, with size being the most reliable indicator in distinguishing the two lesions. This and the fact that histologic differentiation of the entities can be difficult, suggests that surgical wide excision may be the most appropriate procedure in treating patients with lesions greater than 3 cm.
Adult↗
Myositis of the quadriceps muscle group including vastus lateralis, vastus medialis, and rectus femoris.
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Diabetes Complications↗