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Biomedical subjects

M Mehta

Publications and source records attributed to M Mehta.

At least 19 recordsLinked to original sources

A phase II study of preradiation chemotherapy followed by external beam radiotherapy for the treatment of patients with newly diagnosed glioblastoma multiforme: an Eastern Cooperative Oncology Group study (E2393).

Recent publications support the use of preradiation chemotherapy in the treatment of selected primary brain tumors. In the pediatric population, this treatment strategy often delays radiotherapy and may improve the outcome in patients. This manuscript describes the use of a preradiation chemotherapy approach for adult patients with newly diagnosed glioblastoma multiforme. The main objective of this trial was to determine the feasibility of delivering up to 3 monthly cycles of a 72 h continuous simultaneous intravenous infusion of BCNU (40 mg/m2/day) and cisplatin (40 mg/m2/day). Patients were evaluated for tumor response or progression after each cycle. Following the completion of the chemotherapy treatments or evidence of tumor progression, patients underwent external beam radiotherapy. A dose of 45 Gy was delivered to the pretreatment tumor volume plus surrounding edema and a margin of 3.0 cm. An additional 14.4 Gy was delivered to the preoperative volume plus a 2 cm margin. Fifty patients were enrolled, 47 were eligible and analyzable. Overall, 79% of patients were able to complete at least 2 cycles of treatment, exceeding the predefined measure of feasibility. One patient achieved a complete response, 10 patients a partial response and 18 patients had stable disease at completion of the chemotherapy treatments. Twenty-four patients experienced grade 4 toxicity, mostly hematologic. All patients were able to undergo radiotherapy following chemotherapy. These results indicate that a preradiation strategy is feasible. Although responses to the chemotherapy were seen, a phase III trial is needed to determine whether this approach provides an advantage over standard treatment; such a phase III trial has been undertaken by ECOG.

Adult↗

Does the endovascular repair of aortoiliac aneurysms pose a radiation safety hazard to vascular surgeons?

OBJECTIVES: Endovascular aortoiliac aneurysm (EAIA) repair uses substantial fluoroscopic guidance that requires considerable radiation exposure. Doses were determined for a team of three vascular surgeons performing 47 consecutive EAIA repairs over a 1-year period to determine whether this exposure constitutes a radiation hazard. METHODS: Twenty-nine surgeon-made aortounifemoral devices and 18 bifurcated devices were used. Three surgeons wore dosimeters (1) on the waist, under a lead apron; (2) on the waist, outside a lead apron; (3) on the collar; and (4) on the left ring finger. Dosimeters were also placed around the operating table and room to evaluate the patient, other personnel, and ambient doses. Exposures were compared with standards of the International Commission on Radiological Protection (ICRP). RESULTS: Total fluoroscopy time was 30.9 hours (1852 minutes; mean, 39.4 minutes per case). Yearly total effective body doses for all surgeons (under lead) were below the 20 mSv/y occupational exposure limit of the ICRP. Outside lead doses for two surgeons approximated recommended limits. Lead aprons attenuated 85% to 91% of the dose. Ring doses and calculated eye doses were within the ICRP exposure limits. Patient skin doses averaged 360 mSv per case (range, 120-860 mSv). The ambient (> 3 m from the source) operating room dose was 1.06 mSv/y. CONCLUSIONS: Although the total effective body doses under lead fell within established ICRP occupational exposure limits, they are not negligible. Because radiation exposure is cumulative and endovascular procedures are becoming more common, individuals performing these procedures must carefully monitor their exposure. Our results indicate that a team of surgeons can perform 386 hours of fluoroscopy per year or 587 EAIA repairs per year and remain within occupational exposure limits. Individuals who perform these procedures should actively monitor their effective doses and educate personnel in methods for reducing exposure.

Aortic Aneurysm↗

Field-induced transitions and spatial chaos in the classical XY spin chain

We study the lowest-lying excitation of a classical ferromagnetic XY spin chain, in the presence of a symmetry breaking magnetic field. Extremizing the energy of this system leads to a two-dimensional nonlinear map, whose allowed phase space shrinks with increasing field in a nontrivial manner. The orbits of the map represent the set of extremum energy spin configurations. For each field, we compute the energy of the members of this set and find the lowest energy among them, excluding the obvious ground state configuration with all spins parallel along the field direction. This state turns out to be the unstable fixed point of the map. We show that up to a certain (primary) critical field, a separatrixlike 2pi soliton configuration is the lowest-energy excitation, with an energy very close to the ground state energy. For any field beyond this critical field, the soliton disappears and lowest excitation is a librational configuration corresponding to the outermost orbit in the phase plot at that field. Further, its energy is found to be much higher than the ground state energy, leading to a sharp jump in the difference in energy between the former and the latter at this field. With further increase in the field, sharp jumps in the excitation energy arise at certain secondary critical fields as well. We show that these appear when the corresponding spin configurations become commensurate. This complex behavior of the energy is interpreted and its effect on the magnetization and static susceptibility of the system is also studied.

Journal Article↗

Complications of total hip arthroplasty: MR imaging-initial experience.

PURPOSE: To investigate the use of standard magnetic resonance (MR) imaging sequences with simple parameter modifications for the detection and characterization of total hip arthroplasty (THA) complications. MATERIALS AND METHODS: An initial phantom study was performed with cobalt-chrome and titanium prostheses to establish the imaging parameters for a subsequent clinical study. In the clinical study, coronal and transverse MR imaging of 14 THA prostheses was performed before and after intravenous contrast material administration in 12 patients who were being considered for revision arthroplasty. The images were reviewed for evidence of juxtaarticular or periprosthetic abnormalities, patterns of contrast enhancement, and quality of periprosthetic tissue depiction. RESULTS: Phantom study results showed improved periprosthetic tissue depiction with use of thin sections, increased frequency-encoding gradient strength, and fast spin-echo sequences. The clinical study results demonstrated periprosthetic abnormalities in 11 cases: mechanical loosening in two cases (including one case with an associated periprosthetic fracture); granulomatosis, eight; and infection, one. In 100% of cases, tissue depiction around the femoral component was judged to be of "diagnostic quality." Tissue depiction around the acetabular component was of diagnostic quality in five (36%) cases. In all seven surgically confirmed cases, a correct diagnosis was made preoperatively with MR imaging. CONCLUSION: By using simple modifications to standard MR imaging sequences, diagnostic-quality MR imaging of THA complications can be performed, particularly around the femoral prosthetic stem.

Acetabulum↗

Early repolarization.

Early repolarization (ER) is an enigma. The purpose of this review is to reemphasize the overall electrocardiographic (ECG) pattern of this normal ST variant which continues to challenge the clinician because of its similarity to the current of injury potential to myocardium or an acute pericarditis. The data were provided from the studies identified through computerized searches of Medline, Toxline, Oxford, Agricola, and Bios Afterdark, Cumulative index, and a review of bibliographies of relevant articles on the related subjects. Early repolarization has elevated, upward, concave ST segments, located commonly in precordial leads, with reciprocal depression in a VR, tall, peaked and slightly asymmetrical T waves with notch, and slur on the R wave. The other accompanying features in the ECG are vertical axis, shorter and depressed P-R interval, abrupt transition, counterclockwise rotation, presence of U waves, and sinus bradycardia. Males dominate and patients are often younger than 50 years of age. The incidence of 1 to 2% is found equally common in all races. Degree and incidence of ST elevation decrease as age advances. Exercise or isoproterenol administration may normalize the ST segment. Early repolarization is a benign condition. If the ECG conforms to a classical pattern of ER on serial ECGs, it would exclude the unnecessary hazards of present day revascularization therapy for myocardial infarction such as primary angioplasty or thrombolytic therapy, or aggressive management of acute pericarditis, and so forth. This review concludes with a discussion of comparative ECG features of ER, pericarditis, and myocardial infarction, and provides an algorithm for diagnostic management of patients suffering from these conditions.

Acute Disease↗

Constrictive pericarditis.

The diagnosis of constrictive pericarditis remains a challenge because its physical findings and hemodynamics mimic restrictive cardiomyopathy. Various diagnostic advances over the years enable us to differentiate between these two conditions. This review begins with a case report of constrictive pericarditis, followed by a brief history and discussions of etiologies. Clinical features, radiologic, electrocardiographic, angiographic findings, and hemodynamics of constrictive pericarditis are reviewed. The echocardiographic findings are detailed and the recent advances in Doppler flow velocity patterns of pulmonary, mitral, tricuspid valves and hepatic veins are reported. Nuclear ventriculograms depict rapid ventricular filling in constrictive pericarditis and differentiate it from restrictive cardiomyopathy. Endomyocardial biopsy helps further in recognizing the various types of restrictive cardiomyopathies. Computed tomography and magnetic resonance imaging delineate abnormal pericardial thickness in constrictive pericarditis. Association of characteristic hemodynamic changes and abnormal pericardial thickness > 3 mm usually confirms the diagnosis of constrictive pericarditis. Effusive and occult varieties of constrictive pericarditis are briefly described. This review concludes with emphasizing the importance of pericardial resection.

Adult↗

Frey's syndrome after carotid endarterectomy.

Frey's syndrome after carotid endarterectomy (CEA) is due to iatrogenic injury to the auriculotemporal nerve and has not been previously reported. One month after uncomplicated CEA, our patient noted an erythematous flush and copious drainage of clear fluid from the superior portion of his neck wound whenever he ate, or smelled or thought of food. These symptoms lasted for 2 months and eventually resolved without intervention. The cause and treatment of Frey's syndrome is also described.

Aged↗

Tomotherapy.

Tomotherapy is delivery of intensity-modulated, rotational radiation therapy using a fan-beam delivery. The NOMOS (Sewickley, PA) Peacock system is an example of sequential (or serial) tomotherapy that uses a fast-moving, actuator-driven multileaf collimator attached to a conventional C-arm gantry to modulate the beam intensity. In helical tomotherapy, the patient is continuously translated through a ring gantry as the fan beam rotates. The beam delivery geometry is similar to that of helical computed tomography (CT) and requires the use of slip rings to transmit power and data. A ring gantry provides a stable and accurate platform to perform tomographic verification using an unmodulated megavoltage beam. Moreover, megavoltage tomograms have adequate tissue contrast and resolution to provide setup verification. Assuming only translational and rotational offset errors, it is also possible to determine the offsets directly from tomographic projections, avoiding the time-consuming image reconstruction operation. The offsets can be used to modify the leaf delivery pattern to match the beam to the patient's anatomy on each day of a course of treatment. If tomographic representations of the patient are generated, this information can also be used to perform dose reconstruction. In this way, the actual dose distribution delivered can be superimposed onto the tomographic representation of the patient obtained at the time of treatment. The results can be compared with the planned isodose on the planning CT. This comparison may be used as an accurate basis for adaptive radiotherapy whereby the optimized delivery is modified before subsequent fractions. The verification afforded tomotherapy allows more precise conformal therapy. It also enables conformal avoidance radiotherapy, the complement to conformal therapy, for cases in which the tumor volume is ill-defined, but the locations of sensitive structures are adequately determined. A clinical tomotherapy unit is under construction at the University of Wisconsin.

Dose Fractionation, Radiation↗

A mannose-binding glycoprotein found in the 4 day post coital rat uterus is involved in pregnancy.

Experiments were conducted to study the functional implication of a mannose-binding glycoprotein found in the day 4 post coital (p.c.) rat uterus, using a mono-specific polyclonal antibody raised against the glycoprotein. Western Blot and immunohistochemical techniques were employed to study the distribution of the glycoprotein, and the results suggest that this glycoprotein is present only in the day 4 p.c. uterus and is specifically localized in the stromal cells. Administration of anti-UA (Uterine Agglutinin) antiserum against the glycoprotein into the day 4 p.c. uterine lumen inhibits carrying of embryo to term. The antiserum is not embryo toxic. After in vivo in utero intra-luminal administration of anti-UA antiserum in day 4 p.c. rat the antiserum has been specifically localized in the uterine stroma by immunohistochemistry. After intravenous injection, the glycoprotein is cleared mainly through the kidney and liver. The possible role of this glycoprotein in the implantation process in rats has been discussed. From the data it is evident that UA may not be directly involved in sugar-sugar interactions with embryo since it is not present in any significant amount in pregnant uterus from day 5 onwards. Since other experiments show that UA does have some role to play in early pregnancy, UA probably acts through some other factor, and preliminary studies suggest that this factor maybe TGF-beta3.

Acute-Phase Proteins↗

Management of coexisting coronary artery and asymptomatic carotid artery disease: report of a series of patients treated with coronary bypass alone.

BACKGROUND: A retrospective chart review of 94 patients with asymptomatic high-grade carotid stenosis undergoing coronary bypass (and valve replacement in some cases) was performed to determine whether significant carotid lesions can be safely ignored in patients undergoing cardiac surgical procedures. These operations were performed during a 2-year period. PATIENTS AND METHODS: There were 55 men and 39 women, with an age range of 37-89 years. Seventy-one patients had unilateral high-grade carotid stenosis, 17 patients had bilateral high-grade lesions, and six patients had unilateral high-grade stenosis and contralateral occlusion. Associated medical problems were recorded and short-term follow-up was obtained. RESULTS: There was one perioperative stroke and no deaths in this group of patients. CONCLUSIONS: Although these data indicate that high-grade carotid stenoses may be safely ignored during cardiac surgical procedures, a multicentre prospective randomized trial is needed to determine the appropriate treatment of the patient with coexisting carotid and coronary artery disease.

Aged↗

Phase I trial of intravenous thymidine and carboplatin in patients with advanced cancer.

PURPOSE: To evaluate the biologic interactions and toxicities of carboplatin combined with a 24-hour infusion of thymidine 75 mg/m(2) in a phase I trial. PATIENTS AND METHODS: Thirty-two patients with cancer refractory to conventional therapy were treated. The first set of patients (n = 7) received thymidine alone 4 weeks before subsequent planned courses of thymidine combined with carboplatin followed (4 weeks) by carboplatin alone. Carboplatin was administered over 20 minutes at hour 20 of the 24-hour thymidine infusion. The carboplatin dose was escalated in patient groups: 200 mg/m(2) (n = 3); 300 mg/m(2) (n = 7); 350 mg/m(2) (n = 4); 400 mg/m(2) (n = 3); 480 mg/m(2) (n = 10); and 576 mg/m(2) (n = 5). At the maximum-tolerated dose (480 mg/m(2)), five patients received combined therapy first and carboplatin alone second, and five patients received carboplatin first and combined therapy second. Maintenance therapy for stable or responding patients was combined therapy. RESULTS: Evaluation demonstrated a trend toward thymidine protection of carboplatin-induced treatment-limiting thrombocytopenia. Neutropenia with carboplatin alone or in combination was negligible. Thymidine alone had no myelosuppressive effects and produced reversible grade 1 or 2 nausea and vomiting (57%), headache (25%), and grade 1 neurotoxicity (22%). Thymidine did not enhance expected carboplatin toxicities. There was no therapy-related infection or bleeding. Analysis of platinum in plasma ultrafiltrate and urine showed no effect by thymidine. Similarly, thymidine pharmacokinetics was not affected by carboplatin. As predicted, nicotinamide adenine dinucleotide levels in peripheral lymphocytes were increased during exposure to carboplatin and/or thymidine but were decreased by carboplatin alone. In three patients with high-grade glioma, responses included one complete remission (21 months) and one partial remission (14 months) at the 480-mg/m(2)-dose level, and disease stabilization (7 months) at the 400-mg/m(2-dose) level. A minor response was observed in a patient with metastatic colon cancer (5 months) at the 480-mg/m(2)-dose level. CONCLUSION: The combination of carboplatin and thymidine as described is well tolerated. The data presented have resulted in a phase II study by the North American Brain Tumor Consortium.

Adult↗

Evaluation of CSF-adenosine deaminase activity in tubercular meningitis.

Sixty patients of inflammatory brain disease were diagnosed and classified according to clinico-investigational criteria by Ahuja et al into tuberculous meningitis group (36 patients) and non-tuberculous meningitis group (24 patients). Tuberculous meningitis (TBM) patients were classified as probable (9 patients) and possible (27 patients) TBM. Non-TBM group comprised of pyogenic meningitis (8.3%), viral encephalitis (23.3%), cerebral malaria (5%) and enteric encephalopathy (3.3%). Cerebrospinal fluid-adenosine deaminase (CSF-ADA) activities were measured in both TBM and non-TBM groups. Mean CSF-ADA levels in TBM patients was 9.61 +/- 4.10 IU/L and was significantly elevated as compared to viral encephalitis and enteric encephalopathy cases; but difference was insignificant in comparison to pyogenic meningitis (7.92 +/- 0.95 IU/L) and cerebral malaria. Using 8 IU/L as cut off value for diagnosis of TBM a sensitivity of 44% and specificity of 75% was observed.

Adenosine Deaminase↗

MR imaging of symptomatic osteochondromas with pathological correlation.

OBJECTIVE: To demonstrate the value of MR imaging in the diagnosis and differentiation of the various symptomatic complications of osteochondromas, providing pathological correlation with emphasis on the usefulness of MR imaging as a single imaging modality in these patients. DESIGN: We retrospectively reviewed all MR examinations of clinically symptomatic osteochondromas (30 patients) performed at our institution between March 1990 and October 1997. PATIENTS: Thirty patients had clinically symptomatic osteochondromas during the study period. Twenty patients were male and 10 were female. There were five cases of multiple osteochondromatosis. Pathological correlation was available in 24 patients. RESULTS AND CONCLUSION: Symptomatic complications included fracture (7%), osseous deformity limiting range of motion (23%), vascular injury (7%), neurological compromise (10%), bursa formation (27%) and malignant transformation (27%). MR imaging was able to diagnose or suggest the etiology for the clinical symptomatology in all cases, demonstrating that it is an ideal imaging modality in the diagnostic evaluation of symptomatic complications of osteochondromas and often avoids the need for further imaging.

Adolescent↗

A cost-effectiveness and cost-utility analysis of radiosurgery vs. resection for single-brain metastases.

PURPOSE: The median survival of well-selected patients with single-brain metastases treated with whole-brain irradiation and resection or radiosurgery is comparable, although a randomized trial of these two modalities has not been performed. In this era of cost containment, it is imperative that health-care professionals make fiscally prudent decisions. The present environment necessitates a critical appraisal of apparently equi-efficacious therapeutic modalities, and it is within this context that we present a comparison of the actual costs of resection and radiosurgery for brain metastases. METHODS AND MATERIALS: Survival and quality of life outcome data for radiation alone or with surgery were obtained from two randomized trials, and radiosurgical results were obtained from a multiinstitutional analysis that specifically evaluated patients meeting surgical criteria. Only linear accelerator radiosurgery data were considered. Cost analysis was performed from a societal view point, and the following parameters were evaluated: actual cost, cost ratios, cost effectiveness, incremental cost effectiveness, cost utility, incremental cost utility, and national cost burden. The computerized billing records for all patients undergoing resection or radiosurgery for single-brain metastases from January 1989 to July 1994 were reviewed. A total of 46 resections and 135 radiosurgery procedures were performed. During the same time period, 454 patients underwent whole-brain radiation alone. An analysis of the entire bill was performed for each procedure, and each itemized cost was assigned a proportionate figure. The relative cost ratios of resection and radiosurgery were compared using the Wilcoxon rank sum test. Cost effectiveness of each modality, defined as the cost per year of median survival, was evaluated. Incremental cost effectiveness, defined as the additional cost per year of incremental gain in median survival, compared to the next least expensive modality, was also determined. To calculate the societal or national impact of these practices, the proportion of patients potentially eligible for aggressive management was estimated and the financial impact was determined using various utilization ratios for radiosurgery and surgery. RESULTS: Both resection and radiosurgery yielded superior survival and functional independence, compared to whole brain radiotherapy alone, with minor differences in outcome between the two modalities; resection resulted in a 1.8-fold increase in cost, compared to radiosurgery. The latter modality yielded superior cost outcomes on all measures, even when a sensitivity analysis of up to 50% was performed. A reversal estimate indicated that in order for surgery to yield equal cost effectiveness, its cost would have to decrease by 48% or median survival would have to improve by 108%. The average cost per week of survival was $310 for radiotherapy, $524 for resection plus radiation, and $270 for radiosurgery plus radiation. CONCLUSIONS: For selected patients, aggressive strategies such as resection or radiosurgery are warranted, as they result in improved median survival and functional independence. Radiosurgery appears to be the more cost-effective procedure.

Brain Neoplasms↗