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Biomedical subjects

S Bhuta

Publications and source records attributed to S Bhuta.

At least 19 recordsLinked to original sources
PubMed2001

Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a phase I trial.

The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each. The vaccine was well tolerated, and no definite differences were observed among the three formulations. Serologic analyses demonstrated the generation of IgM antibody titers in most patients, with minimal IgG antibody stimulation. There was significant binding of IgM antibodies to MCF-7 tumor cells in 16 patients, whereas IgG antibody reactivity was observed in a few patients. There was evidence of complement-dependent cytotoxicity in several patients. Affinity column purification supported the specificity of IgM antibodies for globo H. On the basis of these data, globo H will constitute one component of a polyvalent vaccine for evaluation in high-risk breast cancer patients.

Adult↗
PubMed2000

Primary melanocytic schwannoma of cervical sympathetic chain.

BACKGROUND: Primary melanocytic schwannoma arising from the cervical sympathetic chain is a rare pigmented nerve sheath tumor. Two cases are presented from an academic medical center. Patients and Methods Patients were initially seen with an enlarging neck mass associated with sympathetic nervous system dysfunction. Radiography demonstrated a mass located posterior to the carotid sheath. Primary therapy consisted of surgical excision and postoperative radiation therapy. RESULTS: The tumors were found to be melanocytic schwannomas arising from the cervical sympathetic chain. The pathologic characteristics of this neoplasm are reviewed. One patient remained disease free for 12 years after treatment, whereas 1 patient died as a result of local recurrence and distant metastases. CONCLUSIONS: Melanocytic schwannoma of the cervical sympathetic chain is a rare nerve sheath tumor of the head and neck that may be misdiagnosed as malignant melanoma. The clinical behavior of this neoplasm is variable. Preoperative neurologic findings, anatomic location, electron microscopy, and immunohistochemistry findings help to establish the diagnosis, and electron microscopy may have a role in distinguishing between benign and malignant lesions. Complete surgical excision is the treatment of choice.

Adult↗
PubMed2000

The shifting patterns of metastatic melanoma.

Management of cutaneous melanoma becomes more difficult as tumor cells metastasize to sites that are remote from the primary tumor. There is a hierarchy of risk associated with cancer spread by different routes and to different organs. Differences in clinical outcome indicate critical variations in pathobiology at different stages in disease evolution. Prevention of the evolution of melanoma is critical, especially beyond the stage of nodal involvement.

Biopsy, Needle↗
PubMed1999

Metal debris from titanium spinal implants.

STUDY DESIGN: A prospective study of tissue surrounding spinal instrumentation was performed using histologic and chemical analysis. OBJECTIVES: To identify and quantify the amount of metal debris generated by titanium pedicle screw instrumentation and to evaluate the histologic response in the spinal tissues. SUMMARY OF BACKGROUND DATA: Microscopic metal particles from the soft tissue surrounding joint arthroplasties have been shown to activate a macrophage response that leads to bone resorption and increased inflammation. The use of titanium spinal implants for spine surgery projects the possibility of generating wear debris in the spine. METHODS: Nine patients with titanium instrumentation from a prior lumbar decompression and fusion procedure who were undergoing reoperation were entered into this study. Tissue samples were collected from areas near the pedicle screw-rod junction, the scar tissue overlying the dura, and the pedicle screw holes. Metal levels for titanium were determined by electrothermal atomic absorption spectroscopy, and histologic analysis was performed by light and electron microscopy. RESULTS: Tissue concentrations of titanium were highest in patients with a pseudarthrosis (30.36 micrograms/g of dry tissue). Patients with a solid fusion had low concentrations of titanium (0.586 microgram/g of dry tissue). Standard light microscopy identified metal particles in the soft tissues. Transmission electron microscopy demonstrated macrophages with numerous secondary lysosomes containing electron-dense bodies and collagenous stroma with electron-dense rod-like profiles consistent with metal debris. CONCLUSIONS: Wear debris is generated by the use of titanium spinal instrumentation in patients with a pseudarthrosis. These particles activate a macrophage cellular response in the spinal tissues similar to that seen in surrounding joint prostheses. Patients with a solid spinal fusion have negligible levels of particulate matter.

Biocompatible Materials↗
PubMed1999

Unintentional parathyroidectomy during thyroidectomy.

OBJECTIVES: In the United States thyroidectomy is a frequently performed surgery by both general and head and neck surgeons. Even the most experienced thyroid surgeon, however, has probably received a pathology report stating that an incidental parathyroid gland or parathyroid tissue was found in the submitted thyroidectomy specimen. The aim of this report is to explore some of the pathologic and clinical characteristics of unintentional parathyroidectomy during thyroidectomy. STUDY DESIGN: A retrospective review was performed of thyroidectomies performed at the University of California, Los Angeles, Center for the Health Sciences between 1989 and June 1998 which had pathology reports showing parathyroid tissue contained within the thyroidectomy specimen. This excluded any tissue submitted separately to be evaluated for parathyroid tissue and parathyroid tissue removed unintentionally during a thyroidectomy for a different procedure such as a laryngectomy or surgery for parathyroid disease. METHODS: The pathology slides were reviewed to determine the incidence of unintentional parathyroid tissue removal, the size of the parathyroid tissue found within the thyroid specimen, the location of the parathyroid tissue (extracapsular, intracapsular, intrathyroidal), and whether this unintentional parathyroidectomy during thyroidectomy caused clinical consequences. RESULTS: Four hundred fourteen applicable thyroidectomies were performed during this time with 45 (11%) discovered cases of unintentional parathyroidectomy during thyroidectomy. Twenty-five (56%) cases were discovered during thyroidectomy for benign disease, and 20 (44%) during thyroidectomy for malignant thyroid disease. All the parathyroid tissue was normal and was found in extracapsular (58%), intracapsular (20%), or intrathyroidal (22%) locations. Of these 45 cases, recurrent laryngeal nerve paralysis was found only in two patients who had the nerve resected intentionally during the thyroidectomy, and none of the patients developed permanent hypocalcemia. CONCLUSIONS: Incidental parathyroid gland tissue was reported in 11% of the thyroidectomies performed in our series, without the clinical consequence of hypocalcemia. The majority (78%) of this parathyroid tissue was found in the extracapsular and intracapsular locations; therefore it is possible that these parathyroid glands may be identified and preserved with more meticulous inspection of the thyroid capsule during and after thyroidectomy to decrease the incidence of unintentional parathyroidectomy during thyroidectomy in the future.

Carcinoma↗
PubMed1997

Controlled periadventitial administration of verapamil inhibits neointimal smooth muscle cell proliferation and ameliorates vasomotor abnormalities in experimental vein bypass grafts.

OBJECTIVE: Inhibition of early myointimal proliferation may improve longterm patency of vein grafts, but the clinical use of many experimental drugs is limited by systemic toxicity. To determine whether this goal can be achieved by low-dose targeted drug administration, we constructed a polymeric system delivering verapamil and evaluated the effects on local and downstream vein graft morphology, neointimal smooth muscle cell proliferation, and vasomotor function. METHODS: Ethylene-vinyl acetate polymeric delivery systems were constructed, containing 2% verapamil by weight. These are flexible, biocompatible, and nonbiodegradable matrices, delivering the drug at a rate of 10 micrograms/day. The autologous external jugular vein was used to create a carotid artery bypass graft in hypercholesterolemic (n = 22) rabbits. Verapamil-containing matrices (n = 12) or plain polymers (control, n = 10) were wrapped around the proximal third of the veins after reperfusion. Graft vasomotor function was evaluated and was also compared with function of an additional group of normocholesterolemic vein grafts (n = 8). RESULTS: Twenty-eight days after grafting, intimal index (intima/media thickness ratio) was 31% lower, neointima/original lumen surface ratio was 26% lower, and residual luminal area was 71% greater (4.00 +/- 1.2 mm2 versus 2.34 +/- 0.9 mm2, all p < 0.01) under verapamil matrices compared with control grafts. Neointimal smooth muscle cell content was reduced from 45.4% to 28.2%, and net neointimal smooth muscle cell thickness was reduced by 47% (30 microns vs 15.8 microns, both p < 0.01). Verapamil-treated segments distal to the matrices also showed significantly lower neointimal smooth muscle cell density and increased lumen size. Sensitivity to serotoin and vasomotor responses to serotonin, norepinephrine, and sodium nitroprusside in distal segments were significantly lower in verapamil-treated grafts than in controls. CONCLUSIONS: Periadventitial controlled administration of verapamil below 1% of the systemic dose effectively inhibits myointimal hyperplasia in vein grafts. Local polymeric drug delivery may be readily applicable to coronary revascularization operations.

Animals↗
PubMed1997

Clear cell carcinoid tumor of stomach. A variant mimicking gastric xanthelasma.

We report a rare case of gastric carcinoid composed entirely of clear cells with foamy cytoplasm. The patient was a 75-year-old Hispanic woman with atrophic fundic (oxyntic) gland gastritis leading to hypochlorhydria, secondary hypergastrinemia, endocrine cell hyperplasia, and multiple gastric carcinoids. Grossly, the lesion was yellow and distinct from other carcinoids in the gastric mucosa, mimicking gastric xanthelasma. Histologically, the tumor consisted of uniform clusters of polygonal cells with foamy cytoplasm. The formation of cell packets and abundant vascular stroma provided clues to its neuroendocrine nature. This was confirmed by immunoreactivity for chromogranin A and the demonstration of dense core granules ultrastructurally.

Aged↗
PubMed1995

Extracellular and standard University of Wisconsin solutions provide equivalent preservation of myocardial function.

The deleterious effect of hyperkalemic cardioplegic solutions on coronary endothelium has been documented and has also been demonstrated with University of Wisconsin solution. We evaluated a new extracellular University of Wisconsin formulation for efficacy in heart preservation. Six neonatal piglet hearts were arrested with and stored in the standard intracellular University of Wisconsin solution (group 1: K+ 125 mEq/L, Na+ 29 mEq/L). Six piglet hearts were preserved for 24 hours with an extracellular University of Wisconsin solution that differed only in the concentrations of potassium and sodium (group 2: K+ 25 mEq/L, Na+ 129 mEq/L). Hearts underwent modified reperfusion with leukocyte-depleted aspartate-glutamate enriched blood cardioplegic solution followed by conversion to a left-sided working mode on a Langendorff circuit with perfusion from a support pig. Stroke work index was calculated at left ventricular end-diastolic pressures of 3, 6, 9, and 12 mm Hg. Sixty minutes after reperfusion, there was no significant difference in stroke work index between group 1 (16.4 +/- 1.9 x 1000 erg/gm) and group 2 (15.3 +/- 2.7 x 1000 erg/gm). There was also no significant difference in high-energy phosphate stores or myocardial water content between the two groups. Extracellular University of Wisconsin solution provides myocardial preservation equivalent to standard University of Wisconsin solution while preventing exposure of coronary endothelium to high levels of potassium, which justifies its use in clinical heart transplantation.

Adenosine↗
PubMed1993

Perfluorochemical reperfusion yields improved myocardial recovery after global ischemia.

Reperfusion injury remains a limiting factor in extending ischemic storage time for human heart transplantation. In this study, initial myocardial reperfusion with an oxygenated perfluorochemical (Fluosol) was investigated as a means of limiting such injury. Neonatal piglet hearts were arrested with crystalloid cardioplegia, excised, and stored for 12 hours in saline solution at 0 degrees C. Initial reperfusion (10 minutes) was either with whole blood (n = 6), unmodified perfluorochemical (n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (n = 6), and was followed by an additional 40 minutes of whole blood perfusion. Functional evaluation was then completed, and left ventricular biopsy specimens were taken. A control group (n = 7) was evaluated without an intervening period of ischemia. At a left ventricular end-diastolic pressure of 9 mm Hg, hearts stored in whole blood cardioplegia developed a left-ventricular stroke work index of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under the same conditions, perfluorochemical-reperfused hearts achieved a stroke work index of 14.6 +/- 1.3 x 10(3) erg/g, significantly greater than that of the whole blood group (p < 0.001). Stroke work index for hearts reperfused with aspartate/glutamate-enriched perfluorochemical cardioplegia was 19.8 +/- 1.6 x 10(3) erg/g, significantly increased over that of the nonenriched perfluorochemical group (p < 0.01) and not different from values obtained in controls (19.2 +/- 0.8 x 10(3) erg/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Synchronous occurrence of malignant rhabdoid tumor two decades after Wilms' tumor irradiation.

We describe the first case of synchronous malignant rhabdoid tumor arising in the pelvis and the lung two decades after both sites were irradiated for Wilms' tumor. Although the malignant rhabdoid tumor phenotype is controversial as a specific clinicopathological entity, this case exhibited classic clinicopathological features of malignant rhabdoid tumor, including tissue features of a trabecular to alveolar growth pattern; cellular features of characteristic eosinophilic cytoplasmic inclusions exhibiting intermediate filament clusters, large nuclei with prominent central nucleoli, and a dual mesenchymal and epithelial immunocytochemistry profile; and clinical features of a rapidly deteriorating course leading to death 2 months after diagnosis. The occurrence of synchronous malignant rhabdoid tumors in sites irradiated for Wilms' tumor raise interesting questions concerning the relationship of radiation-induced malignancies to putative tumor suppressor gene defects, the distinction of synchronous secondaries from primary recurrences and metastases, and finally the quintessential relationship of malignant rhabdoid tumor to Wilms' tumor.

Adult↗
PubMed1993

Electron microscopy in the evaluation of melanocytic tumors.

Melanoma is the "syphilis of malignant tumors", said one of my favorite mentors (Dr Jerome Wollman, Wadsworth VA Hospital, Los Angeles, California). What syphilis is to clinicians, melanoma is to surgical pathologists. By light microscopy, melanoma, especially in its metastatic form, can exhibit any imaginable pattern, can be amelanotic, and the immunostaining can be negative or equivocal. The present review deals with the features of both classic and aberrant forms of melanosomes. In addition to melanosome morphology, spectrum of ultrastructural features of usual and unusual histological variants of melanoma are described and illustrated. Finally, the role of immunoelectron microscopy is discussed briefly.

Humans↗
PubMed1992

The fibroma-like variant of epithelioid sarcoma. A fibrohistiocytic/myoid cell lesion often confused with benign and malignant spindle cell tumors.

Five cases of a previously undescribed variant of epithelioid sarcoma are presented. This variant differs from the usual lesion in its absence of the typical necrobiotic nodular epithelioid pattern. It is instead composed of deceptively bland fibrohistiocytic and myoid cells arranged in a fibroma-like or dermatofibroma-like pattern with an affinity for osseous involvement. The clinical presentation, ultrastructural features, and presence of vimentin and low molecular weight keratin within the tumor cells justifies their designation as an epithelioid sarcoma variant.

Adolescent↗
PubMed1992

Leukocyte-depleted reperfusion of transplanted human hearts prevents ultrastructural evidence of reperfusion injury.

The present study examines whether leukocyte depletion can prevent postreperfusion ultrastructural injury in transplanted human hearts. Thirty-two patients undergoing orthotopic cardiac transplantation were randomized to receive either enriched, warm, whole blood (Group I; n = 16) or enriched, warm, leukocyte-depleted blood (Group II; n = 16) reperfusion. Donor hearts were arrested with 1 liter of 4 degrees C crystalloid cardioplegia and topically cooled. RV endomyocardial biopsies taken at end-ischemia and following reperfusion were assessed in a blinded fashion and graded according to injury (1 = minimal to 4 = severe). The mean ischemic time (Group I = 142 min, Group II = 153 min) was similar in the two groups. End-ischemic biopsies showed mild-moderate interstitial edema and mild capillary endothelial swelling in both groups with similar injury scores (Group 1 = 1.3 +/- 0.09 (means +/- SEM), Group 2 = 1.25 +/- 0.08). Postreperfusion biopsies in Group I showed nuclear chromatin clumping, moderate mitochondrial swelling, marked capillary endothelial swelling, and marked interstitial edema with a grade of 2.6 +/- 0.14 (P less than 0.001, paired t test). In contrast, postreperfusion biopsies in Group II showed minimal changes with a grade of 1.33 +/- 0.09, P less than 0.0001 in comparison to Group I Leukocyte-depleted reperfusion of human transplanted hearts prevents ultrastructural injury. This may allow safe extension of the ischemic period and result in improved graft function.

Biopsy↗
PubMed1992

Perfluorochemical reperfusion limits myocardial reperfusion injury after prolonged hypothermic global ischemia.

The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial reperfusion injury following global hypothermic ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n = 7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x 10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+ hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)). In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than 0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased over that of PFC (p less than 0.001), and not significantly different from that for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Successful long-term preservation of the neonatal heart with a modified intracellular solution.

UNLABELLED: Current methods of myocardial preservation for transplantation are suboptimal. A newly developed intracellular cardioplegic and storage solution (modified University of Wisconsin solution, group 1) was compared in a randomized, blinded fashion with our present clinical protocol, Stanford cardioplegic solution and saline storage (group 2) in an isolated neonatal pig model. After arrest and storage for 12 hours at 4 degrees C, biopsy specimens were taken from six group 1 hearts and five group 2 hearts for examination under an electron microscope and assessment of high-energy phosphate levels and water content. The remainder (group 1, n = 7; group 2, n = 6) were reperfused with blood for 50 minutes, after which function curves were obtained at left ventricular end-diastolic pressures of 3 to 12 mm Hg and biopsy tissue was taken. Eight control hearts (group 3) were cannulated in situ and perfused on the circuit without arrest or intervening ischemia. Stroke and minute work index curves were approximately threefold and fivefold higher for group 1 (modified University of Wisconsin solution) than for group 2 (Stanford), respectively (p less than 0.01). The hearts preserved with University of Wisconsin solution did not differ in function from unpreserved control hearts (group 3). High-energy phosphate levels were better maintained in group 1 than group 2 (p less than 0.05), and water content was lower (p less than 0.01). Semiquantitative grading of electron micrographs paralleled the functional and biochemical results. CONCLUSION: Modified University of Wisconsin intracellular solution provides markedly better heart preservation than conventionally used cardioplegic and storage solutions.

Adenosine↗
PubMed1991

Complete functional recovery after 24-hour heart preservation with University of Wisconsin solution and modified reperfusion.

Successful long-term myocardial preservation is dependent on optimizing conditions during arrest, storage, and reperfusion. Neonatal piglet hearts were arrested and stored in University of Wisconsin solution (UW) at 4 degrees C for 24 hours and reperfused on a blood-perfused, adult animal-supported isolated circuit. Results were compared with nonischemic continuously perfused control hearts (group 1, n = 5). The initial 10 minutes of reperfusion in groups 2-4 was modified by aspartate/glutamate-enriched leukocyte-depleted blood cardioplegia (group 2, n = 7), leukocyte depletion alone (group 3, n = 9), and aspartate/glutamate-enriched blood cardioplegia alone (group 4, n = 6). After 10 minutes, perfusion was continued with unmodified whole blood. In group 5 (n = 9), unmodified whole blood was used for initial reperfusion as well as subsequent perfusion. The stroke work index was determined 60 minutes after reperfusion. Biopsies for high-energy phosphates, myocardial water content, and electron microscopy were obtained after functional assessment. The stroke work index at left ventricular end-diastolic pressure of 9 mm Hg did not differ between groups 1 and 2 (19.0 +/- 1.4 x 10(3) and 19.0 +/- 1.5 x 10(3) [mean +/- SEM] erg/g, respectively). These were both different from group 5 (13.3 +/- 0.8 x 10(3) erg/g, p less than 0.05). Group 3 showed improved function (15.7 +/- 0.7 x 10(3) erg/g), but this did not reach statistical significance when compared with group 5. No difference was found between groups 4 and 5. Myocardial water content, high-energy phosphate levels, and ultrastructure were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗