PubMed Health⌕ Search

Biomedical subjects

A Rangan

Publications and source records attributed to A Rangan.

15 recordsLinked to original sources
PubMed2004

Surgical versus non-surgical treatment for acute anterior shoulder dislocation.

BACKGROUND: Acute anterior shoulder dislocation is the commonest type of shoulder dislocation. Subsequently, the shoulder is less stable and more susceptible to re-dislocation, especially in active young adults. OBJECTIVES: We aimed to compare surgical versus non-surgical treatment for acute anterior dislocation of the shoulder. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (August 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to September week 3 2003), EMBASE (1988 to 2003 week 39), the National Research Register (UK) (Issue 3, 2003), conference proceedings and reference lists of articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing surgical with conservative interventions for treating acute anterior shoulder dislocation. DATA COLLECTION AND ANALYSIS: Selection of the included trials was by all three reviewers. Two reviewers independently assessed methodological quality and extracted data. Where appropriate, results of comparable studies were pooled. MAIN RESULTS: Five studies were included. These involved a total of 239 young (mainly aged around 22 years) active and mainly male people, all of whom had had a primary (first time) traumatic anterior shoulder dislocation. Methodological quality was variable, but notably there was insufficient information to judge whether allocation was effectively concealed in all five trials. Two trials, involving 115 participants, were only reported in conference abstracts.One trial involving military personnel reported that all had returned to active duty. Another trial reported similar numbers in the two intervention groups with reduced sports participation, and a third trial reported that significantly fewer people in the surgical group failed to attain previous levels of sports activity. Pooled results from all five trials showed that subsequent instability, either redislocation or subluxation, was statistically significantly less frequent in the surgical group (relative risk (RR) 0.20; 95%confidence interval (CI) 0.11 to 0.33). This result remained statistically significant (RR 0.32, 95%CI 0.17 to 0.59) for the three trials reported in full. Half (17/33) of the conservatively treated patients with shoulder instability in these three trials opted for subsequent surgery.Different, mainly patient-rated, functional assessment measures for the shoulder were recorded in the five trials. The results were more favourable, usually statistically significantly so, in the surgically treated group. Aside from a septic joint in a surgically treated patient, there were no other treatment complications reported. There was no information on shoulder pain, long-term complications such as osteoarthritis or on service utilisation and resource use. REVIEWER'S CONCLUSIONS: The limited evidence available supports primary surgery for young adults, usually male, engaged in highly demanding physical activities who have sustained their first acute traumatic shoulder dislocation. There is no evidence available to determine whether non-surgical treatment should not remain the prime treatment option for other categories of patient. Sufficiently powered, good quality and adequately reported randomised trials of good standard surgical treatment versus good standard conservative treatment for well-defined injuries are required; in particular, for patient categories at lower risk of activity-limiting recurrence. Long term surveillance of outcome, looking at shoulder disorders including osteoarthritis is also required. Reviews comparing different surgical interventions and different conservative interventions including rehabilitation are needed.

Adult↗
PubMed2004

Optimum configuration of cannulated hip screws for the fixation of intracapsular hip fractures: a biomechanical study.

The radiographs of a sample of patients who had canulated hip screw fixation for intracapsular femoral neck fractures were reviewed in our region. There were six different types of configurations used in these fixations which are divided into two groups: (I) triangular configurations, consisting of two parallel screws with a third screw placed either superiorly, inferiorly, anteriorly or posteriorly; and (II) linear configurations with two or three screws in a vertical line. In our study, we tested the relative strength of each configuration in a laboratory setting using synthetic bone models. Statistical analysis, at 5% significance level, using two-way ANOVA and post-hoc test was carried out to test the differences of the results between the configurations.Our results clearly show that the triangular configurations had a higher peak load, higher ultimate load, less displacement and more energy absorption before failure than other configurations.

Biomechanical Phenomena↗
PubMed2003

Carpal tunnel syndrome - is high-frequency ultrasound a useful diagnostic tool?

This study assessed the clinical use of three ultrasound measurements; median nerve cross-sectional area, median nerve flattening ratio and palmar displacement of the flexor retinaculum, for the diagnosis of carpal tunnel syndrome. The measurements were made in 20 carpal tunnel sufferers and 20 controls. The sensitivity, specificity and predictive values of each were calculated in various clinical settings. Values for each of the three variables were significantly different in the patient and control populations. The differences we recorded were smaller than those found in previous studies. The tests had a sensitivity of 72% and a specificity of 90%. Alterations in the morphology of the carpal tunnel in patients with carpal tunnel syndrome can be measured in the district general hospital setting. The measurements described maybe a useful non-invasive confirmatory test in patients in whom there is a strong clinical suspicion of carpal tunnel syndrome. However, they would be of no benefit in epidemiological surveys of populations with a low incidence of carpal tunnel syndrome.

Adult↗
PubMed2002

The value of follow-up of patients with early breast cancer treated with conservative surgery and radiation therapy.

A retrospective study of 438 women with Stage I or II breast cancer who were treated with conservation therapy and followed in accordance with a 'minimal' follow-up programme was conducted to identify a follow-up schedule to optimize detection of salvageable recurrence and/or contralateral new primary breast cancer, and to rationalize cost. Data from 104 women were used to establish the cost of detecting a salvageable event and to model the efficacy of 13 theoretical follow-up schedules. Among women followed for 5 years, 21% relapsed, and 19% of recurrences were salvageable. Only 0.1% of 1294 follow-up visits resulted in the detection of a salvageable event, at an average cost per woman of A $802. A simulated follow-up programme involving monthly visits for 5 years, costing A $3870 per woman, was the most successful in facilitating the detection of a salvageable recurrence but was also prohibitively expensive. Three-monthly visits for 4 years and 12-monthly for 1 year was more efficacious, but a better understanding of the psychosocial impact and patients' preferences for follow-up is required before any programme is implemented.

Journal Article↗
PubMed2001

Selective interactions of cationic porphyrins with G-quadruplex structures.

G-quadruplex DNA presents a potential target for the design and development of novel anticancer drugs. Because G-quadruplex DNA exhibits structural polymorphism, different G-quadruplex typologies may be associated with different cellular processes. Therefore, to achieve therapeutic selectivity using G-quadruplexes as targets for drug design, it will be necessary to differentiate between different types of G-quadruplexes using G-quadruplex-interactive agents. In this study, we compare the interactions of three cationic porphyrins, TMPyP2, TMPyP3, and TMPyP4, with parallel and antiparallel types of G-quadruplexes using gel mobility shift experiments and a helicase assay. Gel mobility shift experiments indicate that TMPyP3 specifically promotes the formation of parallel G-quadruplex structures. A G-quadruplex helicase unwinding assay reveals that the three porphyrins vary dramatically in their abilities to prevent the unwinding of both the parallel tetrameric G-quadruplex and the antiparallel hairpin dimer G-quadruplex DNA by yeast Sgs1 helicase (Sgs1p). For the parallel G-quadruplex, TMPyP3 has the strongest inhibitory effect on Sgs1p, followed by TMPyP4, but the reverse is true for the antiparallel G-quadruplex. TMPyP2 does not appear to have any effect on the helicase-catalyzed unwinding of either type of G-quadruplex. Photocleavage experiments were carried out to investigate the binding modes of all three porphyrins with parallel G-quadruplexes. The results reveal that TMPyP3 and TMPyP4 appear to bind to parallel G-quadruplex structures through external stacking at the ends rather than through intercalation between the G-tetrads. Since intercalation between G-tetrads has been previously proposed as an alternative binding mode for TMPyP4 to G-quadruplexes, this mode of binding, versus that determined by a photocleavage assay described here (external stacking), was subjected to molecular dynamics calculations to identify the relative stabilities of the complexes and the factors that contribute to these differences. The DeltaG(o) for the external binding mode was found to be driven by DeltaH(o) with a small unfavorable TDeltaS(o) term. The DeltaG(o) for the intercalation binding model was driven by a large TDeltaS(o) term and complemented by a small DeltaH(o) term. One of the main stabilizing components of the external binding model is the energy of solvation, which favors the external model over the intercalation model by -67.94 kcal/mol. Finally, we propose that intercalative binding, although less favored than external binding, may occur, but because of the nature of the intercalative binding, it is invisible to the photocleavage assay. This study provides the first experimental insight into how selectivity might be achieved for different G-quadruplexes by using structural variants within a single group of G-quadruplex-interactive drugs.

Cations↗
PubMed2001

G-quadruplex DNA binding by a series of carbocyanine dyes.

We have examined a number of carbocyanine dyes for their ability to bind intramolecular G-quadruplex DNA structures (G4'-DNA) using a Taq polymerase stop assay. Of the five dyes examined, only one, N,N'-diethylthiacarbocyanine iodide (DTC), was found to bind to G4'-DNA. DTC was also the only dye found to inhibit human telomerase at 50 microM concentration.

Binding Sites↗
PubMed2001

Design and synthesis of fluoroquinophenoxazines that interact with human telomeric G-quadruplexes and their biological effects.

In this study we have identified a new structural motif for a ligand with G-quadruplex interaction that results in biological effects associated with G-quadruplex-interactive compounds. Fluoroquinolones have been reported to possess weak telomerase inhibitory activity in addition to their better known bacterial gyrase poisoning. Starting with a fluoroquinobenzoxazine, which has modest potency in a human topoisomerase II assay, we have designed a more potent inhibitor of telomerase that has lost its topoisomerase II poisoning activity. This fluoroquinophenoxazine (FQP) interacts with G-quadruplex structures to inhibit the progression of Taq polymerase in a G-quadruplex polymerase stop assay. In addition, we demonstrate by 1H NMR studies that this compound interacts with telomeric G-quadruplex structures by external stacking to the G-tetrad with both the unimolecular fold-over and the parallel G-quadruplex structures. A photocleavage assay confirms the FQP interaction site, which is located off center of the external tetrad but within the loop region. Molecular modeling using simulated annealing was performed on the FQP-parallel G-quadruplex complex to determine the optimum FQP orientation and key molecular interactions with the telomeric G-quadruplex structure. On the basis of the results of these studies, two additional FQP analogues were synthesized, which were designed to test the importance of these key interactions. These analogues were evaluated in the Taq polymerase stop assay for G-quadruplex interaction. The data from this study and the biological evaluation of these three FQPs, using cytotoxicity and a sea urchin embryo system, were in accord with the predicted more potent telomeric G-quadruplex interactions of the initial lead compound and one of the analogues. On the basis of these structural and biological studies, the design of more potent and selective telomeric G-quadruplex-interactive compounds can be envisaged.

Animals↗
PubMed2000

Cationic porphyrins promote the formation of i-motif DNA and bind peripherally by a nonintercalative mechanism.

Telomeric C-rich strands can form a noncanonical intercalated DNA structure known as an i-motif. We have studied the interactions of the cationic porphyrin 5,10,15,20-tetra-(N-methyl-4-pyridyl)porphine (TMPyP4) with the i-motif forms of several oligonucleotides containing telomeric sequences. TMPyP4 was found to promote the formation of the i-motif DNA structure. On the basis of (1)H NMR studies, we have created a model of the i-motif-TMPyP4 complex that is consistent with all the available experimental data. Two-dimensional NOESY data prompted us to conclude that TMPyP4 binds specifically to the edge of the intercalated DNA core by a nonintercalative mechanism. Since we have shown that TMPyP4 binds to and stabilizes the G-quadruplex form of the complementary G-rich telomeric strand, this study raises the intriguing possibility that TMPyP4 can trigger the formation of unusual DNA structures in both strands of the telomeres, which may in turn explain the recently documented biological effects of TMPyP4 in cancer cells.

DNA↗
PubMed2000

Induction of duplex to G-quadruplex transition in the c-myc promoter region by a small molecule.

A major control element of the human c-myc oncogene is the nuclease-hypersensitive purine/pyrimidine-rich sequence. This double-stranded DNA fragment, corresponding to the 27-base pair segment in the nuclease-hypersensitive element of the c-myc promoter region, forms a stable Watson-Crick double helix under physiological conditions. However, this duplex DNA can be effectively converted to G-quadruplex DNA by a small molecular weight ligand. Both intermolecular and intramolecular G-quadruplex forms can be induced by this ligand. Similar transitional changes are also observed with the duplex telomeric sequence from the Oxytricha species. These results provide additional support to the idea that G-quadruplex structures may play structural roles in vivo and also provide insight into novel methodologies for rational drug design. These structurally altered DNA elements might serve as regulatory signals in gene expression or in telomere dynamics and hence are promising targets for drug action.

Animals↗
PubMed2000

The treatment of isolated ulnar fractures in adults: a systematic review.

The treatment of isolated ulnar fractures remains controversial, with different authors recommending both surgical and non-surgical management. We undertook a systematic review of the current literature in order to assess whether any conclusions can be drawn. A total of 33 series involving 1876 patients were identified as suitable for analysis. Data from these papers were combined by method of treatment. The results of the non-operative treatment of minimally displaced ulnar fractures with a stable configuration were uniformly good. Below elbow plaster cast, functional brace and early mobilisation all produced similar results. An above elbow cast was unnecessarily restrictive. To preserve forearm rotation, widely displaced or unstable fractures are best treated by open reduction and internal fixation. Guidelines based on cadaveric and clinical studies exist to predict fracture stability and the extent of acceptable displacement. However, these have not been verified in clinical studies. Compression plate fixation gave reliable results in these cases. Other methods lacked sufficient published data to be recommended.

Adult↗
PubMed1999

Early mobilisation versus immobilisation of surgically treated ankle fractures. Prospective randomised control trial.

In a randomised prospective controlled trial of 52 patients aged 16 to 65 we compared early non-weightbearing ankle mobilisation with ankle immobilisation following surgical treatment of bimalleolar ankle fractures. At 3 months there was no significant difference between the two groups in the range of ankle movements or pain. There was however a significant difference in the gait pattern with a higher proportion of cases in the early ankle mobilisation group having a symmetrical gait (P = 0.0001).

Adolescent↗