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Biomedical subjects

S H Advani

Publications and source records attributed to S H Advani.

At least 19 recordsLinked to original sources

Primary non-Hodgkin's lymphoma of the spleen presenting as space occupying lesion: a case report and review of literature.

Primary splenic lymphoma (PSL) is rare with a reported incidence of less than 1%. Diffuse large cell pathology has been reported in 22-23% of the cases and is felt to have poor outcome. This study reports a 50 year old male who presented with fever and weakness. He was found to have a mass lesion in the spleen documented by CT scan. A splenectomy was performed which showed non-Hodgkin's lymphoma. Immunohistological studies showed a positivity for CD20 and CD30.

Antigens, CD20↗

Impaired cell motility in chronic myeloid leukemic granulocytes related to altered cytoskeletal pattern.

The bactericidal activity of polymorphonuclear leucocyte (PMNL) against infection stimulates cytoskeletal changes accompanied with alteration in adhesion and locomotion. Microfilaments, the motile apparatus is known to regulate these changes by polymerization of monomeric G-actin to fibrous F-actin. PMNL from chronic myeloid leukemia (CML) patients have been reported to be defective in locomotion in response to synthetic peptide, n-formyl-methionyl-leucyl-phenylalanine (fMLP) but the mechanism leading to defective locomotion and their spatial reorganization remains unclear. Therefore, in order to study the cause of defective motility of PMNL from CML patients the spatial distribution and reorganization of microfilaments and microtubules in response to fMLP have been examined by transmission electron (TEM) and scanning electron microscopy (SEM). Under SEM, the PMNL-CML surface appeared smoother with reduced ruffling resulting in rounding off cells with lesser polarized morphology. Unstimulated PMNL from normal as well as CML subjects showed shorter and fewer microtubules and evenly distributed microfilaments as compared to fMLP stimulated PMNL. It is proposed that the cause of defective locomotion was due to reduced surface activity as a consequence of altered cytoskeletal configuration. This phenomenon seems to be related to impaired functional appendages and as a whole led to the defective cell motility and hence reduced chemotaxis in PMNL from CML patients.

Cell Death↗

Safe and efficacious use of procedural sedation and analgesia by non-anesthesiologists in a pediatric hematology-oncology unit.

BACKGROUND: Children often require relief of pain and anxiety while undergoing diagnostic and therapeutic procedures. Procedural sedation and analgesia (PSA) is the safe and effective control of pain, anxiety and motion so as to allow a necessary procedure to be performed and to provide an appropriate degree of memory loss or decreased awareness. OBJECTIVE: To prospectively describe procedural sedation and analgesia as performed in the pediatric oncology unit and to report the success of sedation and the incidence of complications. METHODS: IV Midazolam and IV Ketamine were used for PSA in pediatric oncology patients undergoing painful procedures. RESULTS: Between June 2004 and December 2004, 55 diagnostic and therapeutic procedures were performed using PSA in 16 children. There were 9 boys and 7 girls with a median age of 11 years. Twelve patients had hematolymphoid malignancies and 4 patients had solid tumors. The indication for PSA were bone marrow aspiration and or biopsy in 7 patients, therapeutic lumbar puncture in 43 patients, bone marrow aspiration and lumbar puncture in 4 patients and skin biopsy in 1 patient. All 55 procedures were successfully completed. Adverse events occurred in 15 (27%) episodes and included transient drop in oxygen saturation, vomiting, dizziness and disinhibition with crying spells. Average time to arousable state and full recovery was 22 minutes and 31 minutes respectively. None of the patients complained of post procedure pain nor recalled the procedure at the follow up visit. CONCLUSION: Procedural sedation and analgesia using midazolam and ketamine is a safe and efficient method of limiting anxiety and procedure related pain and can be successfully administered by non-anaesthesiologists. The complication rate is low and can be easily managed.

Adolescent↗

Myelomatous pleural effusion.

Serous effusions in multiple myeloma are uncommon but a myelomatous pleural effusion occurring in these patients is extremely rare. Here we report a rare case of a 38 years lady who was diagnosed to have multiple myeloma and subsequently developed pleural effusion. The myelomatous nature of the effusion was first diagnosed on cytology and subsequently confirmed by a pleural biopsy. The pleural effusion showed an initial response to chemotherapy but subsequently recurred.

Adult↗

First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: a multicenter, randomized, phase III study.

BACKGROUND: This randomized, phase III study compared the efficacy and safety of first-line gemcitabine versus epirubicin in the treatment of postmenopausal women with metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients aged > or = 60 years (median 68 years) with clinically measurable MBC received either gemcitabine 1200 mg/m(2) or epirubicin 35 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. RESULTS: Of 410 patients entered, 397 (198 gemcitabine and 199 epirubicin) were randomized and qualified for the time to progressive disease (TTP) and survival analyses. Total cycles administered in 185 gemcitabine and 192 epirubicin patients, respectively, were 699 (mean 3.5, range 0-12) and 917 (mean 4.6, range 0-10). Epirubicin demonstrated statistically significant superiority in TTP (6.1 and 3.4 months, P=0.0001), overall survival (19.1 and 11.8 months, P=0.0004), and independently assessed response rate (40.3% and 16.4% in 186 and 183 evaluable patients, P <0.001). For gemcitabine (n=190) and epirubicin (n=192), respectively, common WHO grade 3/4 toxicities were neutropenia (25.3% and 17.9%) and leukopenia (14.3% and 19.3%). Of the 28 on-study deaths (17 gemcitabine, 11 epirubicin), three were considered possibly or probably related to treatment (gemcitabine). CONCLUSIONS: Postmenopausal women > or =60 years of age with MBC tolerate chemotherapy well. In this study, epirubicin was superior to gemcitabine in the treatment of MBC in women age > or =60, confirming that anthracyclines remain important drugs for first-line treatment of MBC.

Aged↗

Activation of HHV-6 in lymphoproliferative disorders: a polymerase chain reaction-based study.

HHV-6 is a latent herpes virus persisting throughout the adult life of the infected host in an integrated form and is often activated in immunocompromised situations. Detection of HHV-6 DNA in the plasma of an individual indicates the presence of active viral replication in the host. Because lymphomas are known to be associated frequently with host immunosupression, we studied activation of HHV-6 in 98 patients diagnosed with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). HHV-6 activation was documented in 34% of cases of non-Hodgkin's lymphoma and 39% of those of Hodgkin's disease; however, no correlation of activation status with pathological types of Hodgkin's disease and between copy numbers in peripheral blood mononuclear cell DNA and the corresponding plasma DNA was noticeable.

Cohort Studies↗

Imatinib in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of gastrointestinal tract. The tumors express the cell surface transmembrane receptor KIT that has a tyrosine kinase activity and is a protein product of KIT protoeoncogene. These tumors occur in the whole of Gastrointestinal tract. Treatment includes surgical resection for localized tumors. For metastatic disease treatment options include systemic chemotherapy, radiation therapy, with a response rate of less than 10%. Presently Imatinib; a tyrosine kinase inhibitor has shown promising result with response rates upto 59-69% in phase II results in metastatic setting; and ongoing phase II & phase III trials in adjuvant setting will help to establish its role as an adjuvant to surgery. We have treated eleven patients of metastatic GIST with Imatinib and we hereby present these cases.

Adult↗

Benign multilocular cystic nephroma.

This article reports a case of cystic nephroma to bring awareness about the benign nature of this condition. The patient presented with a painless abdominal mass. Computed tomography showed a homogeneous, multicystic tumor of the superolateral portion of the left kidney with thin septa without solid parts. Histology confirmed the diagnosis of cystic nephroma.

Female↗

Use of a reduced-intensity conditioning regimen for allogeneic transplantation in patients with chronic myeloid leukemia.

Reduced-intensity conditioning that harnesses the potential of a graft-versus-tumor (GVT) effect has been proposed as an alternative to conventional myeloablative allogeneic stem cell transplantation. The primary aim is engraftment and this can be achieved with minimal immunosuppression. In this report, we describe the use of such regimens for CML in 17 patients who received human leukocyte antigen (HLA)-matched sibling allografts. Conditioning was with fludarabine, antithymocyte globulin (ATG) and busulfan for the first 11 patients, whereas fludarabine, busulfan and TBI were used for the remaining six patients. Engraftment was prompt in most of the cases. Complications and need for supportive therapy in the immediate post-transplant period were reduced drastically. Only two patients (both in the TBI group) died within the first 100 days. Acute graft-versus-host disease (GVHD) grade II-IV was seen in seven patients. Complications occurred later on. Chronic GVHD was observed in 11/17 patients. Lung infection and GVHD were the major killers. In surviving patients, after a median follow-up of 30 months (range 37-21 months), 6/17 (35.3%) are alive. Five are disease free and one patient is still in relapse even after a second donor lymphocyte infusion. Total treatment time and cost were more than with conventional transplants. We conclude that reduced-intensity transplantation still requires further refinement.

Adolescent↗

Hypercalcemia induced by parathyroid hormone-related peptide after treatment of squamous cell carcinoma of oral cavity.

Squamous cell carcinoma of the head and neck is a rare cause of humoral hypercalcemia of malignancy. This paraneoplastic syndrome is usually one of the presenting symptoms of the disease. We report a case of squamous cell carcinoma of the oral cavity that presumably elaborated parathyroid hormone-related peptide (PTH-rP) and caused hypercalcemia only after radiotherapy and chemotherapy.

Carcinoma, Squamous Cell↗

Leukemia in infants.

OBJECTIVE: Acute Leukemia is rare in infants. It is characterized by non-specific symptomatology requiring a high index of suspicion on the part of a pediatrician for referral and diagnosis. It has peculiar biological features, unresponsiveness to treatment and poor prognosis. METHODS: Eighteen infants with acute leukemia were seen during 1994 to 2001 and were analyzed on the basis of clinical and laboratory data. There were 13 cases of Acute Lymphoblastic Leukemia (ALL), 4 cases of Acute Myeloid Leukemia (AML) and one case remained unclassifiable, as the surface markers could not be done. Morphologically 9/13 cases of ALL were of FAB L1 type and remaining of L2 subtype, and 2/4 cases of AML were of FAB M1 type and remaining of M2 subtype. RESULT: Clinical data was available completely only in 11 cases. Hyperleucocytosis was present in 4 cases, organomegaly in 8 cases and lympadenopathy in 5 cases. One patient presented with a chloroma in the retrorbital region although there was no parenchymal involvement of the brain. Immunophenotyping could be done in 13 cases, where 7 cases were diagnosed as CALLA positive-ALL (HLADR+, CD19+, CD10+), 2 cases as Early Pre-B ALL (HLADR+, CD19+, CD10 negative), one as T ALL (cCD3+, CD2+, CD7+) and 3 cases as AML (CD13+, CD33+, HLADR+). None of our patients received treatment.

Female↗

Expression of P53 and bcl-2 proteins in T-cell lymphoblastic lymphoma: prognostic implications.

In patients (pts) with non-Hodgkin's lymphoma (NHL) under 25 years, treatment with MCP-842 protocol, a short duration intense protocol, yields worse survival in pts with lymphoblastic lymphoma (LL) compared to other high grade lymphomas. In order to identify both favourable and unfavourable subgroups in pts with T-cell LL (T-LL) with respect to relapse free survival following treatment with MCP-842 protocol, we analysed the expression of p53 and bcl-2 proteins in 22 pts with T-LL treated at the Tata Memorial Hospital, Mumbai by immunohistochemistry. p53 protein overexpression was noted in 59% cases and bcl-2 overexpression was noted in 29.4% cases. p53 expression correlated with a higher rate of relapse (p = 0.03; RR 7.9). The 5-year relapse free survival (RFS) was better in p53 negative patients compared to positive patients (70 vs 38%) (log-rank sigma = 0.04). In conclusion, in this study, overexpression of p53 protein was common in patients with T-LL. T-LL pts negative for p53 are likely to benefit from the short intense protocol--MCL-842. Bcl-2 protein overexpression was not a prognostic factor in these patients.

Adolescent↗

Proliferating cell nuclear antigen and epidermal growth factor receptor (EGFr) status in renal cell carcinoma patients with polysomy of chromosome 7.

We investigated 40 cases of renal cell carcinoma (RCC) to study the polysomy 7 status in papillary and clear-cell types (nonpapillary RCC) and relationship with clinical, pathological, and biological features such as grade, stage, tumor proliferation rate (PCNA expression) and epidermal growth factor receptor (EGFr) expression and thereby to understand the prognostic significance of polysomy 7 and EGFr expression. In a prospective study, chromosome 7 copy number was analyzed in tumor cells by using fluorescence in situ hybridization (FISH) with an alpha-satellite DNA probe for chromosome 7. Both proliferating cell nuclear antigen (PCNA) and EGFr expression were examined in paraffin sections by immunostaining. The relationship between clinicopathological and clinicobiological parameters was evaluated by appropriate statistical methods. Polysomy 7 was present in 100% of papillary and 56.2% of clear-cell types RCC. In clear-cell RCC, in comparison with polysomy 7-dominant (D) category (20-50% polysomy-7 cells), polysomy 7-major (M) category (>50% polysomy 7 cells) was associated with higher tumor grade (P = 0.05). Polysomy 7 was also correlated with stage of the disease (P = 0.006). The PCNA index ranged between 12.8-89.6% and was comparatively high in high-grade tumors (P = 0.001). The PCNA index was also correlated with polysomy 7 (P = 0.002), and the association was stronger in tumors with polysomy M versus polysomy D category (P = 0.02). The EGFr expression did not correlate with either grade, stage, PCNA, or polysomy 7. The correlation of polysomy 7 with less favorable prognostic factors such as higher tumor grade, stage, and higher proliferative index in the present study indicates that polysomy 7 might be used as a prognostic predictor in clear-cell RCC. Evaluation of clinical end points will confirm the prognostic potential of the genetic marker polysomy 7 in our study.

Adenocarcinoma, Clear Cell↗

CD40 Ligand--an anti-apoptotic molecule in Hodgkin's disease.

The expression of CD40L was investigated in HD involved lymph nodes by flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR). Also an investigation of the role of CD40L in upregulation of the anti-apoptotic gene BclxL in a Hodgkin's disease (HD) derived cell line was undertaken. HD patients (n = 18) had significantly higher numbers of activated CD4+ and CD8+ T cells in the tumor microenvironment as compared to controls (n = 8). HD patients also demonstrated higher numbers of CD4+, CD8+ and CD19+ lymphocytes co-expressing CD40L as compared to controls. The CD40L signal was consistently and significantly upregulated in HD patients (n = 5) as compared to controls (n = 3) at the mRNA level. RT-PCR and FCM analysis revealed that soluble CD40L upregulated BclxL levels in the Fas-sensitive HD cell line HDLM2. We conclude that CD40L can act as an important anti-apoptotic molecule by upregulating BclxL expression in Reed-Sternberg cells of HD and may be partly responsible for their survival 'in-vivo'.

Apoptosis↗