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Biomedical subjects

S R Patel

Publications and source records attributed to S R Patel.

At least 73 records · Page 4Linked to original sources
PubMed1997

Pyomyositis: clinical features and predisposing conditions.

OBJECTIVE: To describe the manifestations of nontropical pyomyositis and associated comorbid conditions that may predispose to pyomyositis. METHODS: A retrospective review of 13 patients with pyomyositis seen at our center including one illustrative case report. Reports of tropical and nontropical pyomyositis were found by review of Index Medicus, Medline, and references from published cases and clinical review papers. RESULTS: All 13 patients had variable presentations including fever, muscle pain, tenderness, and swelling. Eleven patients had comorbid conditions that may have led to their infection, including one with human immunodeficiency virus and 3 with history of trauma. Staphylococcus aureus was found to be a causative organism in 7 patients, 2 patients had multiple organisms isolated, and 2 had no organisms isolated. Eleven patients had successful treatment with intravenous antibiotics and either computerized tomographic scan guided percutaneous or open operative drainage. CONCLUSION: Onset of pyomyositis is usually insidious, with progression to purulent collections. Comorbid conditions likely predispose patients to pyomyositis and may contribute to delay in diagnosis and treatment. Increased awareness of this disease, especially in an immunosuppressed patient, should lead to earlier diagnosis and treatment with improved outcomes.

AIDS-Related Opportunistic Infections↗
PubMed1996

Phase II study of paclitaxel in patients with previously treated osteosarcoma and its variants.

BACKGROUND: Patients with osteosarcoma and its variants who did not respond to standard chemotherapy including doxorubicin, ifosfamide, cisplatin, and high dose methotrexate were treated with paclitaxel so that its therapeutic activity in these patients could be determined. METHODS: We conducted a Phase II study of paclitaxel in patients with conventional osteosarcoma (10), malignant fibrous histiocytoma of the bone (3) and dedifferentiated chondrosarcoma (2) whose disease had progressed after prior standard chemotherapy including doxorubicin, cisplatin, ifosfamide, and high dose methotrexate. Paclitaxel was administered at a starting dose of 175 mg/m2 as a 24-hour infusion with standard premedication every 21 days or upon hematologic recovery (absolute granulocyte count [AGC] > 1500/microliters, platelets > 100,000/microliters). Neupogen was not used routinely. The study was conducted based on a two-stage design. A total of 17 patients were entered into the protocol. Two were ineligible since they had Ewing's sarcoma. Responses were assessed radiographically and pathologically when feasible, using standard criteria. RESULTS: Fifteen eligible patients were treated in the first stage of the study. Median age of the patients was 31 years (range, 19-61 yrs). There were 8 females and 7 males with a Zubrod performance status of 0 or 1. One patient achieved a mixed response and 14 developed progressive disease. Median AGC nadir was 0.3, on Day 13, lasting 5 days. Median platelet nadir was 134, on Day 8. There were no Grade III or IV nonhematologic toxicities and no deaths related to treatment. CONCLUSIONS: Paclitaxel, at this dose and schedule, is well tolerated but inactive in this patient population.

Adult↗
PubMed1996

Effect of Schiff base formation on the function of the calcitriol receptor.

The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs) of the target genes. We have shown that the interaction of VDRs with VDREs is inhibited by uremic toxins. We hypothesize that uremic toxins form Schiff bases with the lysine residues of the VDR DNA binding domain and inhibit the VDR interaction with the VDRE. In this study, pyridoxal 5'-phosphate was used as a probe to test Schiff base formation as the inhibitory mechanism, since it forms Schiff bases with steroid receptors. Pyridoxal 5'-phosphate inhibited the VDR binding to the VDREs and chemically modified the DNA binding domain of the VDR in vitro. The inhibition was reversed when pyridoxal 5'-phosphate was preincubated with lysine. Further, this chemical agent also blocked the production of chloramphenicol acetyltransferase (CAT) enzyme induced by calcitriol in cells transfected with a constructed VDRE attached to a CAT reporter gene. This finding is consistent with the hypothesis that pyridoxal 5'-phosphate could interact with the VDR and impair its DNA binding within cells. Since induction of 24-hydroxylase synthesis is a receptor mediated process, we studied the effect of pyridoxal 5'-phosphate on the synthesis of renal 24-hydroxylase in rats. When pyridoxal 5'-phosphate was infused to rats, renal 24-hydroxylase activity was suppressed, consequently, degradation of calcitriol was also reduced in these animals. Thus, chemicals capable of Schiff base formation potentially could alter the physiological function of VDR and calcitriol.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1995

A 15-year experience with chemotherapy of patients with paraganglioma.

BACKGROUND: Paraganglioma is a rare tumor thought to arise from the neuroectodermally derived paraganglionic cells that are dispersed widely along the autonomic ganglia. They can metastasize to bones, lymph nodes, and lungs and occasionally present with spinal cord compression. Up to 60% of retroperitoneal paragangliomas can be functional, with symptoms and signs of norepinephrine overproduction. METHOD: A 15-year experience with chemotherapy of patients with paraganglioma was reviewed. The patient population was identified through a search of the data-base maintained by the Departments of Melanoma-Sarcoma Medical Oncology and Pathology at the University of Texas M.D. Anderson Cancer Center (Houston, TX). RESULTS: Thirteen of 84 patients with histologically confirmed diagnosis of paraganglioma were treated with chemotherapy. The median age was 42 years (range, 25-67 years); there were eight males and five females. Primary sites included retroperitoneum (seven patients), head and neck (two patients), pelvis, bladder, mediastinum, and paravertebral (one patient each). Twelve patients received chemotherapy for metastatic disease, and 1 had an unresectable mediastinal primary tumor. Eleven patients received cyclophosphamide, doxorubicin, and DTIC/dacarbazine (CyADIC)/cyclophosphamide, vincristine, doxorubicin and DTIC/dacarbazine (CyVADIC), and 2 received doxorubicin and dacarbazine (ADIC) at standard doses for a median of 4 cycles (range, 2-12 cycles). Six of 13 patients achieved an objective partial remission (response rate = 46%, 95% confidence interval = 19-73%); 6 other patients had stable disease, and one developed progressive disease. At the time of last follow-up, eight patients were alive with disease, four died, and one patient was alive with no evidence of disease. The median follow-up from diagnosis was 45 months (range, 12-300 months). CONCLUSION: Cyclophosphamide, doxorubicin, dacarbazine chemotherapy is active in the treatment of patients with paraganglioma.

Adult↗
PubMed1995

Extraskeletal myxoid chondrosarcoma. Long-term experience with chemotherapy.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare low-grade soft tissue sarcoma that has been reported to have an indolent nature history, and relatively good prognosis. The majority of primary tumors are located in the extremities and they tend to be bulky at presentation. Studies with long-term follow-up have revealed the development of distant metastases in virtually all patients, eventually resulting in death. We reviewed our experience with EMC over the last three decades. The patient population was identified through a search of the database maintained by the Departments of Patient Studies, Pathology, and Melanoma-Sarcoma Medical Oncology. Eleven patients with histologically confirmed diagnosis of EMC were identified. The median age was 59 (37-81 years), and there were nine males and two females. Nine patients had an extremity location and the remaining two had a chest wall and abdominal wall primary, respectively. The median size of the primary tumor was 10 cm (range: 4-17 cm) in maximum dimension. Ten of the eleven patients received chemotherapy, mainly with doxorubicin- and dacarbazine-based regimens. One patient is currently on beta-interferon. No objective responses were noted, to a median of 4 (2-6) cycles of chemotherapy. Three patients were treated with ifosfamide as a second-line chemotherapy without any benefit. Three patients have expired, two patients are alive with no evidence of disease, and six patients are alive with disease. The median follow-up is 5 years (range: 1.33-17 years) from diagnosis. Although small numbers preclude adequate assessment, there is no evidence of efficacy of standard soft-tissue sarcoma chemotherapy in patients with EMC.

Adult↗
PubMed1995

Myxoid malignant fibrous histiocytoma: experience with chemotherapy.

Myxoid malignant fibrous histiocytoma (MFH) is an intermediate grade tumor with a definite metastatic potential but a relatively indolent natural history compared to the pleiomorphic variant of MFH. Little is known about its sensitivity to chemotherapy. We reviewed our experience with chemotherapy in myxoid MFH between 1986 and 1992. The patient population was identified through a search of the database maintained by the Departments of Melanoma-Sarcoma Medical Oncology and Pathology: 55 patients with histologically confirmed diagnosis of myxoid MFH were identified. Chemotherapy was administered to 18 of these patients (10 females, 8 males). The median age was 65 (range: 30-76). Ten patients had an extremity primary, seven had a trunk or retroperitoneal primary, and one patient had head and neck as the site of primary tumor. The median size of the primary tumor was 11 cm (range: 5-23 cm) in maximum dimension. Seven patients received chemotherapy in the neoadjuvant setting, eight received it for recurrent or metastatic disease, and three received it postoperatively after complete resection of the tumor. All patients received doxorubicin and dacarbazine with or without cyclophosphamide. Of the 15 patients evaluable for response, 4 achieved an objective response (one CR, 3 PRs, RR = 27%) to a median of 3 cycles (range: 1-7 cycles). At the time of last follow-up, eight patients are alive with no evidence of disease, two patients are alive with disease, and eight patients have expired. The median follow-up is 51 months (range: 26-216 months) from diagnosis. The relatively small sample precludes any definitive conclusions; however, it seems that doxorubicin- and dacarbazine-based chemotherapy has modest activity in myxoid MFH.

Adult↗
PubMed1995

Altered vitamin D metabolism and receptor interaction with the target genes in renal failure: calcitriol receptor interaction with its target gene in renal failure.

The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with the vitamin D response elements of the target genes. Although decreased VDR concentration in renal failure could diminish the biological action of calcitriol, recent study indicates that uremic toxins could modify the VDR DNA-binding domain and inhibit the binding of the VDR to the vitamin D response elements. The latter reaction could also account for end-organ resistance in renal failure. The inhibitory action of uremic toxins has been tested in vivo by a method using gene transcription. It was demonstrated that uremic ultrafiltrate blocks calcitriol-induced chloramphenical acetyltransferase reporter constructs containing a synthetic vitamin D response element in JEG-3 cells. Taken together, the findings indicate that uremia could underlie the calcitriol resistance in renal failure. The modification of the VDR may involve Schiff base formation between lysine residues of the VDR DNA-binding domain and reactive aldehydes accumulated in uremia. This suggestion is on the basis of the finding that the VDR and other steroid receptors form Schiff bases with pyridoxal 5'-phosphate and weaken the binding of these receptors to the DNA cellulose.

Animals↗
PubMed1995

Inhibition of calcitriol receptor binding to vitamin D response elements by uremic toxins.

The genomic action of calcitriol (1,25-dihydroxy-vitamin D3) is mediated through the interaction of the calcitriol receptor (VDR) with vitamin D response elements (VDREs). Although renal failure is associated with resistance to the action of calcitriol, the mechanism of this resistance is not well understood. Therefore, we used the electrophoretic mobility shift assay to compare the ability of VDRs from normal and renal failure rats to bind to the osteocalcin gene VDRE. The results indicate that VDRs from renal failure rats have only half the DNA binding capacity as VDRs from control rats, despite identical calcitriol binding. Furthermore, incubation of normal VDRs with a uremic plasma ultrafiltrate resulted in a loss of > 50% of the binding sites for the osteocalcin VDRE. When VDRs bound to DNA as heterodimers with retinoid X receptors, the inhibitory effect of the uremic ultrafiltrate was due to a specific interaction with the VDR, not retinoid X receptors. In addition, uremic ultrafiltrate blocked calcitriol-induced reporter gene activity in transfected JEG-3 cells. Taken together, the results indicate that an inhibitory effect of a uremic toxin(s) on VDR-VDRE binding could underlie the calcitriol resistance of renal failure.

Animals↗
PubMed1995

Chemotherapy in osteosarcoma. Basis for application and antagonism to implementation; early controversies surrounding its implementation.

Chemotherapy in osteosarcoma has had a major impact in attaining metastasis-free survival, and the cure rates with the use of modern regimens range from 65% to 75%. Preoperative chemotherapy has facilitated surgical resection of the primary tumor, rendering increased numbers of candidates for limb salvage. The effects on the primary tumor may be used as a predictive factor in determining outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Myxoid liposarcoma. Experience with chemotherapy.

BACKGROUND: Myxoid liposarcoma (ML) is the most common type of liposarcoma. It has been classified as an intermediate grade tumor with a definite metastatic potential but a relatively indolent natural history. Little is known about its sensitivity to chemotherapy. METHOD: The authors reviewed their experience with chemotherapy in ML from 1986 to 1992. The patient population was identified through a search of the database maintained by the Department of Melanoma-Sarcoma Medical Oncology of the M.D. Anderson Cancer Center. RESULTS: Forty-four patients each with a histologically confirmed diagnosis of ML were identified. Twenty-one were treated with chemotherapy. The median age was 45 years (31-69 years); there were 14 men and 7 women. The ML in 19 patients was in the lower extremity, one in the head and neck, and one pelvic. The median size of the primary tumor was 15 cm (range, 7-48 cm) in maximum dimension. Of the 18 patients who received doxorubicin- and dacarbazine-based chemotherapy as a frontline regimen [median of 3 (2-9) cycles] and were evaluable for response, 8 (1 completed response, 7 partial responses) achieved an objective response (44%, 95% confidence interval 21-67%). Two of the remaining three patients who were also treated with a similar regimen were not evaluable for response (one received chemotherapy postoperatively, and the other received concomitant radiation and doxorubicin), and the third patient received ifosfamide as frontline chemotherapy because of a significant cardiac history. Seven patients received chemotherapy in the neoadjuvant setting, 13 for recurrent or metastatic disease, and 1 postoperatively after complete tumor resection. At the last follow-up, 10 patients were alive with no evidence of disease, 3 were alive with disease, and 8 had died. The median follow-up was 51 months (range, 6-199 months) from diagnosis. CONCLUSION: The authors conclude that doxorubicin- and dacarbazine-based chemotherapy is effective in the treatment of ML.

Adult↗
PubMed1994

An endogenous glycosylphosphatidylinositol-specific phospholipase D releases basic fibroblast growth factor-heparan sulfate proteoglycan complexes from human bone marrow cultures.

Basic fibroblast growth factor (bFGF) is a hematopoietic cytokine that stimulates stromal and stem cell growth. It binds to a glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan on human bone marrow (BM) stromal cells. The bFGF-proteoglycan complex is biologically active and is released by addition of exogenous phosphatidylinositol-specific phospholipase C. In this study, we show the presence of an endogenous GPI-specific phospholipase D (GPI-PLD) that releases the bFGF-binding heparan sulfate proteoglycan and the variant surface glycoprotein (a model GPI-anchored protein) from BM cultures. An involvement of proteases in this process is unlikely, because released proteoglycan contained the GPI anchor component, ethanol-amine, and protease inhibitors did not diminish the release. The mechanism of release is likely to involve a GPI-PLD and not a GPI-specific phospholipase C, because the release of variant surface glycoprotein did not reveal an epitope called the cross-reacting determinant that is exposed by phospholipase C-catalyzed GPI anchor cleavage. In addition, phosphatidic acid (which is specifically a product of GPI-PLD-catalyzed anchor cleavage) was generated during the spontaneous release of the GPI-anchored variant surface glycoprotein. We also detected GPI-PLD-specific enzyme activity and mRNA in BM cells. Therefore, we conclude that an endogenous GPI-PLD releases bFGF-heparan sulfate proteoglycan complexes from human BM cultures. This mechanism of GPI anchor cleavage could be relevant for mobilizing biologically active bFGF in BM. An endogenous GPI-PLD could also release other GPI-anchored proteins important for hematopoiesis and other physiologic processes.

Adult↗