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Biomedical subjects

S G Patel

Publications and source records attributed to S G Patel.

At least 19 recordsLinked to original sources
PubMed2002

Diagnostic and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma.

PURPOSE: Patients with recurrent head and neck squamous cell carcinoma (HNSCC) present a diagnostic and therapeutic challenge. We evaluated the diagnostic accuracy and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography (PET) in this patient population. PATIENTS AND METHODS: We performed a retrospective review of 143 patients with previously treated HNSCC who underwent 181 PET scans at our institution from May 1996 through April 2001 to detect recurrent disease. Disease recurrence within 6 months was used as the gold standard for assessing true disease status at PET. RESULTS: With equivocal sites considered positive, the sensitivity and specificity of PET for detecting recurrence overall were 96% and 72%, respectively. PET was highly sensitive and specific at regional and distant sites. At local sites, sensitivity was high, but specificity was lower because of false-positive findings. One fifth of all false-positive PET scans occurred at sites of known inflammation or infection. The area under the curve for a receiver operator characteristic curve on the basis of standardized uptake value (SUV) was 0.882 +/- 0.025. PET interpretation, SUV, and physical examination were independent predictors of relapse-free and overall survival in a time-dependent, multivariate proportional hazards model. An increase in SUV by one unit increased the relative risk (RR) of relapse by 11% and the RR of death by 14%. A positive PET interpretation increased the RR of relapse by four-fold and the RR of death by seven-fold. CONCLUSION: PET was a highly sensitive method of detecting recurrent HNSCC and provided important prognostic information for relapse-free and overall survival.

Adolescent↗
PubMed2002

Outcome, observer reliability, and patient preferences if CTA, MRA, or Doppler ultrasound were used, individually or together, instead of digital subtraction angiography before carotid endarterectomy.

OBJECTIVES: To evaluate the accuracy of routinely available non-invasive tests (spiral computed tomographic angiography (CTA), time of flight magnetic resonance angiography (MRA), and colour Doppler ultrasound (DUS)), individually and together, compared with intra-arterial digital subtraction angiography (DSA) in patients with symptomatic tight carotid stenosis; and to assess the effect of substituting non-invasive tests for DSA on outcome, interobserver variability, and patient preference. METHODS: Patients referred from a neurovascular clinic were subjected prospectively to DUS imaging. The operator was blind to symptoms. Patients with a tight carotid stenosis on the symptomatic side were admitted for DSA. CTA and MRA were performed during the admission. The CTA, MRA, and DSA films were each read independently by two of six experienced radiologists, blind to all other data. RESULTS: 67 patients were included (34 had all four imaging procedures). DUS, CTA, and MRA all agreed with DSA in the diagnosis of operable v non-operable disease in about 80% of patients. CTA tended to underestimate (sensitivity 0.65, specificity 1.0), MRA to overestimate (sensitivity 1.0, specificity 0.57), and DUS to agree most closely with (sensitivity 0.85, specificity 0.71) the degree of stenosis as shown by DSA. When using any two of the three non-invasive tests in combination, adding the third if the first two disagreed would result in very few misdiagnoses (about 6%). MRA had similar interobserver variability to CTA (both worse than DSA). Patients preferred CTA over MRA and DSA. CONCLUSIONS: DUS, CTA, and MRA all show similar accuracy in the diagnosis of symptomatic carotid stenosis. No technique on its own is accurate enough to replace DSA. Two non-invasive techniques in combination, and adding a third if the first two disagree, appears more accurate, but may still result in diagnostic errors.

Carotid Stenosis↗
PubMed2001

Two distal Sp1-binding cis-elements regulate fibroblast growth factor receptor 1 (FGFR1) gene expression in myoblasts.

Skeletal myoblast cell proliferation and subsequent differentiation are dependent on developmentally regulated expression of the fibroblast growth factor receptor 1 (FGFR1) gene. We have previously reported the isolation and initial characterization of the chicken FGFR1 gene (cek1) promoter. Both distal and proximal regions of the promoter were identified as necessary for developmentally regulated transcriptional activity in proliferating myoblasts, including its down-regulation in differentiated muscle fibers in vitro. Here we report detailed characterization of the molecular mechanism regulating FGFR1 promoter activity via the distal promoter region in proliferating myoblasts. This region was identified as a 242 base pair segment located greater than 1 kilobase upstream from the start of transcription that conferred increased transcriptional activity to a minimal thymidine kinase promoter. This segment contains two Sp1 binding sites. Site directed mutagenesis and transfection studies indicated that both Sp1 sites are functional and both are required for FGFR1 promoter activity. Furthermore, Sp1 binding to the two sites was synergistic enhancing FGFR1 promoter activity. The specificity of Sp1 binding to the two distal promoter cis-elements was verified by electromobility shift and transfection assays employing an Sp1 expression construct. Differences in myoblast versus fibroblast-specific protein-DNA complex formation at these sites correlated with high promoter activity in myoblasts and significantly reduced promoter activity in fibroblasts. These studies for the first time establish a molecular mechanism regulating FGFR1 gene expression during myoblast proliferation.

Animals↗
PubMed2001

Cytokine gene transfer enhances herpes oncolytic therapy in murine squamous cell carcinoma.

Replication-competent, attenuated herpes simplex viruses (HSV) have been demonstrated to be effective oncolytic agents in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the utility of combining these two approaches, two oncolytic HSV vectors (NV1034 and NV1042) were designed to express the murine GM-CSF and murine IL-12 genes, respectively. These cytokine-carrying variants were compared with the analogous non-cytokine-carrying control virus (NV1023) in the treatment of murine SCC VII squamous cell carcinoma. All three viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. SCC VII cells infected by NV1034 and NV1042 effectively produced GM-CSF and IL-12, respectively. In an SCC VII subcutaneous flank tumor model in immunocompetent C3H/HeJ mice, intratumoral injection with each virus caused a significant reduction in tumor volume compared with saline injections. The NV1042-treated tumors showed a striking reduction in tumor volume compared with the NV1023- and NV1034-treated tumors. On subsequent rechallenge in the contralateral flank with SCC VII cells, 57% of animals treated with NV1042 failed to develop tumors, in comparison with 14% of animals treated with NV1023 or NV1034, and 0% of naive animals. The increased antitumor efficacy seen with NV1042 in comparison with NV1023 and NV1034 was abrogated by CD4(+) and CD8(+) lymphocyte depletion. NV1042 is a novel, attenuated, oncolytic herpesvirus that effectively expresses IL-12 and elicits a T lymphocyte-mediated antitumor immune response against murine squamous cell carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of cancer.

Animals↗
PubMed2001

Validating cortical surface analysis of medial prefrontal cortex.

This paper describes cortical analysis of 19 high resolution MRI subvolumes of medial prefrontal cortex (MPFC), a region that has been implicated in major depressive disorder. An automated Bayesian segmentation is used to delineate the MRI subvolumes into cerebrospinal fluid (CSF), gray matter (GM), white matter (WM), and partial volumes of either CSF/GM or GM/WM. The intensity value at which there is equal probability of GM and GM/WM partial volume is used to reconstruct MPFC cortical surfaces based on a 3-D isocontouring algorithm. The segmented data and the generated surfaces are validated by comparison with hand segmented data and semiautomated contours, respectively. The L(1) distances between Bayesian and hand segmented data are 0.05-0.10 (n = 5). Fifty percent of the voxels of the reconstructed surface lie within 0.12-0.28 mm (n = 14) from the semiautomated contours. Cortical thickness metrics are generated in the form of frequency of occurrence histograms for GM and WM labelled voxels as a function of their position from the cortical surface. An algorithm to compute the surface area of the GM/WM interface of the MPFC subvolume is described. These methods represent a novel approach to morphometric chacterization of regional cortex features which may be important in the study of psychiatric disorders such as major depression.

Adult↗
PubMed2001

Left atrial aneurysm.

Aneurysms of the left atrium are rare abnormalities. They can be congenital or acquired. Whereas a true congenital aneurysm presents as isolated pathology, inflammatory or degenerative processes involving the endocardium are associated with the acquired type. The clinical records of 2 patients with the diagnosis of left atrial aneurysm were reviewed, along with the surgical strategies, current literature, and patient outcomes. Because of the risk of life-threatening complications, surgery is recommended even in asymptomatic cases. Resection and mitral valvuloplasty should be the treatment of choice.

Cardiac Catheterization↗
PubMed2001

How epicardial electrodes influence the transmembrane potential during a strong shock.

This paper analyzes a possible artifact that may corrupt experiments studying defibrillation of the heart. Our hypothesis is that surface recording electrodes can influence the transmembrane potential during a shock. In the vicinity of an electrode, current leaves the intracellular space to take advantage of the low resistance of the extracellular path, thereby depolarizing the tissue. We calculate the transmembrane potential induced around a circular electrode when exposed to a uniform electric field. The bidomain model represents the electrical behavior of the cardiac tissue, and we account for electrode polarization impedance. Our results show that adjacent regions of depolarization and hyperpolarization exist around the electrode, and that the induced depolarization is greater than 100 mV for a 0.5 mm radius silver-silver chloride electrode in a 500 V/m electric field. We conclude that surface electrodes may produce artifacts during experiments designed to study defibrillation-strength electrical shocks.

Artifacts↗
PubMed2000

Ectopia cordis and other midline defects.

BACKGROUND: Thoracic ectopia cordis and other midline defects are rare congenital anomalies that often occur with other intracardiac defects. Despite significant improvements in neonatal and infant cardiac surgeries, operations for thoracoabdominal ectopia cordis carry an extremely high mortality with only a few reported survivors of thoracic ectopia cordis. METHODS: The clinical charts of 4 patients with ectopia cordis over a 6-year period were reviewed. Three of the patients showed varying degrees of Cantrell's Pentalogy; thoracic ectopia cordis was found in 1. We have reviewed our surgical strategies and reported the patients' clinical outcomes. RESULTS: All 4 patients are alive at follow-up. Two infants with double-outlet right ventricle have been fully corrected, and extracorporeal membrane oxygenation was necessary in 1 infant for cardiac failure following the cardiac repair. A newborn with thoracoabdominal ectopia cordis underwent primary repair of his diaphragmatic defect, and a silo was used to progressively reduce the omphalocele. He is currently awaiting elective repair of tetralogy of Fallot. Lastly, the patient with thoracic ectopia cordis underwent successful soft tissue coverage, and she is being followed in the clinic with restrictive muscular ventricular septal defects and a left ventricular diverticulum. CONCLUSIONS: Our experience along with other reports in the literature demonstrates that patients with thoracic and thoracoabdominal ectopia cordis can undergo and survive full cardiac, neurologic, and abdominal repair during infancy. Furthermore we advocate different approaches determined by the severity of the presentation and the presence of other complicating factors.

Female↗
PubMed2000

Partial laryngectomy for recurrent laryngeal carcinoma.

From July 1975 to January 1998, 33 patients underwent partial laryngeal resection for residual or recurrent tumour after primary radical radiotherapy. Sixteen patients had T1 tumours on presentation, 14 were T2 and three were T3. Six patients underwent a supraglottic (horizontal) laryngectomy, 24 had a vertical partial laryngectomy, two had an endoscopic laser resection and one had an endoscopic laser resection followed by a vertical partial laryngectomy. The median time interval between radiotherapy and salvage surgery was 10 months (range 2-188 months). The median follow-up period was 41 months (range 12-185 months). There were five major postoperative complications (15%); two patients developed a pharyngeal fistula and three required further surgery for laryngo-tracheal stenosis. Twenty-five patients (76%) retained their larynx with satisfactory speech and swallowing. Eight patients (24%) had to be converted to a total laryngectomy, seven for recurrent disease and one for laryngeal stenosis. Of the eight patents converted, seven had normal swallowing and six developed good tracheo-oesophageal speech. Seven patients (21%) developed recurrent tumour after partial laryngectomy and were subjected to total laryngectomy; six of these seven were salvaged. Only one of the 33 patients died with recurrent tumour, giving an ultimate disease-related survival of 97%. Conservation laryngeal surgery for salvage of selected patients who fail radical radiation therapy is safe, effective, and results in reasonable preservation of laryngeal function.

Adult↗
PubMed2000

How electrode size affects the electric potential distribution in cardiac tissue.

We investigate the effect of electrode size on the transmembrane potential distribution in the heart during electrical stimulation. The bidomain model is used to calculate the transmembrane potential in a three-dimensional slab of cardiac tissue. Depolarization is strongest under the electrode edge. Regions of depolarization are adjacent to regions of hyperpolarization. The average ratio of peak depolarization to peak hyperpolarization is a function of electrode radius, but over a broad range is close to three.

Animals↗
PubMed1999

Regulation of avian fibroblast growth factor receptor 1 (FGFR-1) gene expression during skeletal muscle differentiation.

Myogenic cell proliferation and differentiation are regulated by a fibroblast growth factor (FGF) signal transduction cascade mediated by a high-affinity fibroblast growth factor receptor (FGFR). Exogenous FGF added to myogenic cultures has a mitogenic effect promoting myoblast proliferation while repressing differentiation. We have examined the regulation of the FGFR-1 gene (cek-1) in avian myogenic cultures by immunocytochemistry and Northern blot analysis. FGFR-1 protein was readily detected in undifferentiated myoblast cultures and was significantly reduced in differentiated muscle fiber cultures. Similarly, FGFR-1 mRNA was 2.5-fold more abundant in myoblast cultures than in differentiated cultures. To define the molecular mechanism regulating FGFR-1 gene expression in proliferating myoblasts and post-mitotic muscle fibers, we have isolated and partially characterized the avian FGFR-1 gene promoter. Transfection of FGFR-1 promoter-chloramphenicol acetyltransferase gene constructs into myogenic cultures identified two regions regulating expression of this gene in myoblasts. A distal region of 2226 bp conferred a high level of expression in myoblasts. This region functioned in an orientation-dependent manner and interacted with a promoter element(s) in a proximal 1058 bp promoter region to direct transcription. Deletion analysis revealed a 78 bp region that confers a high level of cek1 promoter activity in myoblasts. This DNA segment also contains Spl binding sites and interacts with a component in myoblast nuclear protein extracts. The proximal promoter region alone demonstrated no activity in directing transcription in either myoblasts or muscle fibers. Using the full-length promoter, gene expression was significantly decreased in differentiated muscle fibers relative to undifferentiated myoblasts indicating that the promoter-reporter gene constructs contain elements regulating expression of the endogenous FGFR-1 gene in both myoblasts and muscle fibers.

Animals↗
PubMed1999

Radiation induced sarcoma of the head and neck.

BACKGROUND: Radiation-induced sarcoma of the head and neck (RISHN) is a long-term complication of treatment. The rarity of this tumour is reflected in the very few series reported in the English language medical literature. The incidence of RISHN is, however, likely to increase due to progressive aging of the population combined with improved survival in head and neck cancer patients resulting from better treatment regimes. Diagnosis and management of this problem can be extremely challenging and the overall outlook has been reported to be very bleak. As survival data from isolated case reports cannot be expected to provide reliable information on outcome, we have reviewed 69 cases reported in the English medical literature since 1966 and pooled this information with our experience in treatment of RISHN. PATIENTS AND METHODS: Ten patients with features of a RISHN were treated at the Royal Marsden Hospital between 1944 and 1997. The features of RISHN, treatment, and outcome were analysed in these patients. Additionally, 61 eligible patients with RISHN reported in the literature between 1966 and 1997 were pooled with nine of our patients to form the RISHN group (n = 70). This group was then compared for survival with 124 patients with a diagnosis of head and neck sarcoma registered on the Head and Neck Sarcoma database at the Royal Marsden Hospital (SHN group). Lifetables were constructed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: There was no site of predilection for RISHN, but malignant fibrous histiocytoma (MFH) was the commonest pathological diagnosis. The period of latency between initial radiation therapy and diagnosis of RISHN ranged from 9 to 45 years with a median of 17 years. Surgery was the mainstay of treatment and follow-up ranged from 6 months to 15 years with a median of 48 months. The actuarial five-year disease free survival in these patients was 60%. CONCLUSION: There is at present little or no prospect for effective prevention of RISHN and therefore, a high index of suspicion based on the patient's symptoms assumes great importance in the outcome of these patients. Although surgical management of RISHN is challenging because of the close proximity of the tumour to important regional structures and the technical difficulties of operating in an irradiated area, complete surgical excision appears to offer the best means for palliation and the only realistic chance for long-term survival.

Adolescent↗
PubMed1999

Management of the N0 neck in early cancer of the oral tongue.

Elective treatment of the clinically negative neck in the management of early oral tongue cancers remains controversial. A retrospective review of 71 patients with T1, 2 N0M0 squamous cell carcinoma of the oral tongue treated at the Royal Marsden Hospital was carried out. Cervical nodal recurrence at 2 years was 17% in the group of patients who received elective neck treatment as compared to 43% in the group who had observation of the neck and the difference is statistically significant (P = 0.025). The difference in 5-year survival between the group who had elective neck treatment and the group who did not (75% versus 65%) was not statistically significant. Until future research allows us to be more selective on the basis of a reliable panel of histological and/or biological markers for propensity to nodal metastases, elective neck treatment should be considered in the initial management of the patients with early oral tongue cancer.

Carcinoma, Squamous Cell↗
PubMed1999

Use of apron flap incision for neck dissection.

Neck dissection is one of the most commonly performed surgical procedures in the management of head and neck cancer. Different skin incisions with various modifications have been described in the literature. Three commonly used but conceptually different incisions were compared with respect to the incidence of wound dehiscence in a retrospective review. There were 166 patients with 184 neck dissections carried out using a triradiate (n = 85), modified MacFee (n = 25), or an apron flap incision (n = 74). The incidence of wound dehiscence in the three groups was 11 percent, 8 percent, and 0 percent for the triradiate, modified MacFee, and apron flap incisions, respectively. There was a statistically significant difference in the incidence of wound dehiscence between the apron flap incision and the triradiate incision groups (p = 0.004). The difference in wound dehiscence was not statistically significant between the apron flap incision and the modified MacFee incision groups (p = 0.06). Overall, there was a significant increase in the incidence of wound dehiscence in previously irradiated necks (p = 0.02), but this was significant only for the triradiate incision (p = 0.005) when analyzed individually. Comparison of triradiate, apron, and MacFee incisions did not show a statistically significant difference between the incisions with regard to other postoperative complications in terms of seroma, hematoma, wound infection, and fistula formation. The apron flap incision is the recommended approach in the presence of previous neck irradiation as it gives easier access than the MacFee incision. The robustness of the flap is because of the absence of a trifurcate point as well as a good vascular supply arising from arterial territory of the external carotid artery.

Female↗
PubMed1999

Atherosclerotic plaque at the carotid bifurcation: CT angiographic appearance with histopathologic correlation.

BACKGROUND AND PURPOSE: The likelihood that carotid plaque will give rise to cerebral ischemia probably relates to the degree of arterial stenosis and to plaque morphology. The aim of this study was to assess whether features seen at CT angiography might be used to predict carotid plaque stability by comparing CT angiograms with histopathologic examinations of the carotid artery bifurcation. METHODS: Nine patients with symptomatic severe carotid stenosis at intraarterial angiography had CT angiography of the carotid bifurcation before carotid endarterectomy. After endarterectomy, multiple sections of the specimens through the carotid bifurcation were examined histologically. Plaque characteristics recorded included the proportion of necrotic/lipid core, presence of hemorrhage, extent of fibrosis, ulceration, calcification, inflammatory cell infiltrate, and fibrous cap thickness. Corresponding CT angiograms were assessed for plaque size, distribution, and radiodensity as well as presence of calcific density and ulceration. Histologic findings and CT angiograms were compared. RESULTS: Plaque with a large necrotic/lipid core, which was often hemorrhagic, was found in 16 of 23 sections, and in 15 of these this histologic appearance corresponded with patchy or homogeneous low density on CT angiograms. Six of seven predominantly fibrous plaques were of soft-tissue density on CT angiograms. High density consistent with calcification was seen more frequently on CT angiograms than it was detected histologically, but CT angiography depicted plaque ulceration poorly (four ulcers at histology; two false-positive and two false-negative findings at CT angiography). CONCLUSION: CT angiography is a promising method for assessing the lumen and wall of the carotid artery. The apparent correlation between histologic appearance and plaque density on CT angiograms has important implications for the prediction of plaque stability, even though ulceration is shown inconsistently.

Arteriosclerosis↗
PubMed1998

Intralaryngotracheal thyroid--ectopic thyroid or invasive carcinoma?

Intralaryngotracheal thyroid is a rare clinical condition with only about 125 cases described so far in the literature. We present an unusual case of intralaryngotracheal thyroid which had many clinical features of malignancy and yet appeared benign on histology. As in this case, well-differentiated thyroid cancer can present with locally aggressive clinical features and can pose a dilemma in management if treatment decisions are guided solely by histological features.

Adult↗