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Biomedical subjects

J Sampath

Publications and source records attributed to J Sampath.

13 recordsLinked to original sources
PubMed2006

Treatment of idiopathic club foot using the Ponseti method. Initial experience.

We report our initial experience of using the Ponseti method for the treatment of congenital idiopathic club foot. Between November 2002 and November 2004 we treated 100 feet in 66 children by this method. The standard protocol described by Ponseti was used except that, when necessary, percutaneous tenotomy of tendo Achillis were performed under general anaesthesia in the operating theatre and not under local anaesthesia in the out-patient department. The Pirani score was used for assessment and the mean follow-up time was 18 months (6 to 30). The results were also assessed in terms of the number of casts applied, the need for tenotomy of tendo Achillis and recurrence of the deformity. Tenotomy was required in 85 of the 100 feet. There was a failure to respond to the initial regimen in four feet which then required extensive soft-tissue release. Of the 96 feet which responded to initial casting, 31 (32%) had a recurrence, 16 of which were successfully treated by repeat casting and/or tenotomy and/or transfer of the tendon of tibialis anterior. The remaining 15 required extensive soft-tissue release. Poor compliance with the foot-abduction orthoses (Denis Browne splint) was thought to be the main cause of failure in these patients.

Casts, Surgical↗
PubMed2006

Is secondary radiological follow-up of infants with a family history of developmental dysplasia of the hip necessary?

The practice of regular radiological follow-up of infants with a positive family history of developmental dysplasia of the hip is based on the widespread belief that primary acetabular dysplasia is a genetic disorder which can occur in the absence of frank subluxation or dislocation. We reviewed all infants who were involved in our screening programme for developmental dysplasia of the hip, between November 2002 and January 2004, and who had a normal clinical and ultrasound examination of the hip at six to eight weeks of age, but who, because of a family history of developmental dysplasia of the hip, had undergone further radiography after an interval of 6 to 12 months. The radiographs of 89 infants were analysed for signs of late dysplasia of the hip and assessed independently by three observers to allow for variability of measurement. There were 11 infants (11%) lost to follow-up. All the patients had normal radiographs at the final follow-up and none required any intervention. We therefore question the need for routine radiological follow-up of infants with a positive family history of developmental dysplasia of the hip, but who are normal on clinical examination and assessment by ultrasound screening when six to eight weeks old.

Acetabulum↗
PubMed2005

Functional treatment of acute metatarsal fractures: a prospective randomised comparison of management in a cast versus elasticated support bandage.

A randomised controlled trial was performed in 50 patients with acute isolated minimally displaced lesser metatarsal fractures in order to compare plaster immobilisation with elasticated support bandage treatment. Patients treated with elasticated support bandage had significantly higher AOFAS mid-foot scores at 3-months follow-up and complained of less pain throughout the treatment period. There was no difference between the two groups in time to independent mobility, mid-foot circumference, analgesic requirements and radiological union at 3 months. As plaster casts are associated with serious complications, which were encountered in these studies, we conclude that minimally displaced metatarsal fractures are better treated without a cast.

Adolescent↗
PubMed2005

Operative treatment for hip subluxation in spinal muscular atrophy.

Subluxation of the hip is common in patients with intermediate spinal muscular atrophy. This retrospective study aimed to investigate the influence of surgery on pain and function, as well as the natural history of subluxed hips which were treated conservatively. Thirty patients were assessed clinically and radiologically. Of the nine who underwent surgery only one reported satisfaction and four had recurrent subluxation. Of the 21 patients who had no surgery, 18 had subluxation at the latest follow-up, but only one reported pain in the hip. We conclude that surgery for subluxation of the hip in these patients is not justified.

Adolescent↗
PubMed2004

[Highlighting some clinical aspects of the association of myoma with pregnancy].

UNLABELLED: Leiomyoma is a benign tumor, with mesenchymal embryonal cell origin. During pregnancy 0.1 to 4% of cases are diagnosed. MATERIAL, METHODS AND RESULTS: During the period of 1999-2003, 59 pregnant and delivering women were registered with the diagnosis of Leiomyoma (0.5%) at the ObGyn complex, University Hospital, Pleven. In the observed group, were encountered significantly more often primary sterility, pathological positions of the fetus and placental pathologies. CONCLUSIONS: Leiomyoma frequently complicates the progress of pregnancy and delivery necessitating operative intervention by the means of Caesarean Section.

Adult↗
PubMed2002

Impaired 2',3'-dideoxy-3'-thiacytidine accumulation in T-lymphoblastoid cells as a mechanism of acquired resistance independent of multidrug resistant protein 4 with a possible role for ATP-binding cassette C11.

Cellular factors may contribute to the decreased efficacy of chemotherapy in HIV infection. Indeed, prolonged treatment with nucleoside analogues, such as azidothymidine (AZT), 2',3'-deoxycytidine or 9-(2-phosphonylmethoxyethyl)adenine, induces cellular resistance. We have developed a human T lymphoblastoid cell line (CEM 3TC) that is selectively resistant to the antiproliferative effect of 2',3'-dideoxy-3'-thiacytidine (3TC) because the CEM 3TC cells were equally sensitive to AZT, as well as the antimitotic agent, vinblastine. The anti-retroviral activity of 3TC against HIV-1 was also severely impaired in the CEM 3TC cells. Despite similar deoxycytidine kinase activity and unchanged uptake of nucleosides such as AZT and 2'-deoxycytidine, CEM 3TC had profoundly impaired 3TC accumulation. Further studies indicated that CEM 3TC retained much less 3TC. However, despite a small overexpression of multidrug resistance protein (MRP) 4, additional studies with cells specifically engineered to overexpress MRP4 demonstrated there was no impact on either 3TC accumulation or efflux. Finally, an increased expression of the MRP5 homologue, ATP-binding cassette C11 (ABCC11) was observed in the CEM 3TC cells. We speculate that the decreased 3TC accumulation in the CEM 3TC might be due to the upregulation of ABCC11.

ATP-Binding Cassette Transporters↗
PubMed2002

Role of MRP4 and MRP5 in biology and chemotherapy.

Nucleotide efflux (especially cyclic nucleotides) from a variety of mammalian tissues, bacteria, and lower eukaryotes has been studied for several decades. However, the molecular identity of these nucleotide efflux transporters remained elusive, despite extensive knowledge of their kinetic properties and inhibitor profiles. Identification of the subfamily of adenosine triphosphate (ATP) binding cassette transporters, multidrug resistance protein (MRP) subfamily, permitted rapid advances because some recently identified MRP family members transport modified nucleotide analogs (ie, chemotherapeutic agents). We first identified, MRP4, based on its ability to efflux antiretroviral compounds, such as azidothymidine monophosphate (AZT-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA), in drug-resistant and also in transfected cell lines. MRP5, a close structural homologue of MRP4 also transported PMEA. MRP4 and MRP5 confer resistance to cytotoxic thiopurine nucleotides, and we demonstrate MRP4 expression varies among acute lymphoblastic leukemias, suggesting this as a factor in response to chemotherapy with these agents. The ability of MRP4 and MRP5 to transport 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) suggests they may play a biological role in cellular signaling by these nucleotides. Finally, we propose that MRP4 may also play a role in hepatic bile acid homeostasis because loss of the main bile acid efflux transporter, sister of P-glycoprotein (SPGP) aka bile-salt export pump (BSEP), leads to a strong compensatory upregulation in MRP4 expression. Cumulatively, these studies reveal that the ATP-binding cassette (ABC) transporters MRP4 and MRP5 have a unique role in biology and in chemotherapeutic response.

Animals↗
PubMed2002

Correction of hammer toe with an extended release of the metatarsophalangeal joint.

Between March 1995 and January 2000 we reviewed retrospectively 84 patients with hammer-toe deformity (99 feet; 179 toes) who had undergone metatarsophalangeal soft-tissue release and proximal interphalangeal arthroplasty. The median follow-up was 28 months. Patients were assessed by the American Orthopaedic Foot and Ankle Society Scores (AOFAS) and reviewed by independent assessors. The median AOFAS score was 83, with 87% of patients having a score of more than 60 points; 83% were satisfied and 17% were dissatisfied with the procedure. Pain at the metatarsophalangeal joint was the commonest cause of dissatisfaction, with 14% having moderate or severe pain. Only 2.5% had instability and 9% had formation of callus. There was no statistical difference for the age and gender of the patients, the number of toes operated on, associated surgery for hallux valgus or length of follow-up. Our study was based on an anatomical model and shows good results with no recurrence of deformity.

Adult↗
PubMed2001

Mutant p53 cooperates with ETS and selectively up-regulates human MDR1 not MRP1.

The most frequently expressed drug resistance genes, MDR1 and MRP1, occur in human tumors with mutant p53. However, it was unknown if mutant p53 transcriptionally regulated both MDR1 and MRP1. We demonstrated that mutant p53 did not activate either the MRP1 promoter or the endogenous gene. In contrast, mutant p53 strongly up-regulated the MDR1 promoter and expression of the endogenous MDR1 gene. Notably, cells that expressed either a transcriptionally inactive mutant p53 or the empty vector showed no endogenous MDR1 up-regulation. Transcriptional activation of the MDR1 promoter by mutant p53 required an Ets binding site, and mutant p53 and Ets-1 synergistically activated MDR1 transcription. Biochemical analysis revealed that Ets-1 interacted exclusively with mutant p53s in vivo but not with wild-type p53. These findings are the first to demonstrate the induction of endogenous MDR1 by mutant p53 and provide insight into the mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype.

Stem cells from bone marrow, skeletal muscle and possibly other tissues can be identified by the 'side-population' (SP) phenotype. Although it has been assumed that expression of ABC transporters is responsible for this phenotype, the specific molecules involved have not been defined. Here we show that expression of the Bcrp1 (also known as Abcg2 murine/ABCG2 human) gene is a conserved feature of stem cells from a wide variety of sources. Bcrp1 mRNA was expressed at high levels in primitive murine hematopoietic stem cells, and was sharply downregulated with differentiation. Enforced expression of the ABCG2 cDNA directly conferred the SP phenotype to bone-marrow cells and caused a reduction in maturing progeny both in vitro and in transplantation-based assays. These results show that expression of the Bcrp1/ABCG2 gene is an important determinant of the SP phenotype, and that it might serve as a marker for stem cells from various sources.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Dislodgement of the locking cap from the AO unreamed intramedullary nail: a case report.

We report on the dislodgement of the proximal locking cap from an AO solid femoral intramedullary nail with spiral blade. The pathologic femoral fracture subsequently went on to heal, and the spiral blade did not back out of the femoral neck. Meticulous intraoperative attention to detail is required to select the correct offset for the proximal cap, because the turning moments of the hip abductor muscles are sufficient to unscrew a prominent cap.

Bone Nails↗
PubMed1998

Identification of a DNA cytosine methyltransferase gene in conjugative transposon Tn5252.

The nucleotide sequence of the 3.5-kb right junction fragment of the streptococcal conjugative transposon Tn5252 was obtained. The DNA fragment was found to carry four putative genes one of which displayed a high degree of similarity to prokaryotic 5C-cytosine methyltransferases carrying multiple sequence specificities. No cognate endonuclease gene was detected in the sequenced DNA. Purified methylase polypeptide synthesized in a T7 promoter-controlled overexpression system was found to lack methylase activity while the cell extracts of host cells containing the recombinant plasmid carrying the methylase gene were active. In vivo mutations in the methylase gene did not seem to affect the transferability of the element.

Amino Acid Sequence↗