Biomedical subjects

K Rai

Publications and source records attributed to K Rai.

At least 19 recordsLinked to original sources

PubMed2005

The evolving role of alemtuzumab in management of patients with CLL.

New insights into prognostic markers and the pathophysiology of chronic lymphocytic leukemia (CLL) are beginning to change the concept of CLL treatment. Alemtuzumab has evolved as a potent and effective therapeutic option for patients with CLL. Specifically, alemtuzumab has demonstrated substantial efficacy in fludarabine-refractory patients and has shown impressive responses when administered subcutaneously in first-line therapy. A group of experts gathered to discuss new data related to the use of alemtuzumab in CLL and to assess its place in the rapidly changing approach to treating patients with this disease. The main goals of this program were to update the management guidelines that were previously developed for alemtuzumab-treated patients and to provide community oncologists with guidance on the most effective way to integrate alemtuzumab into a CLL treatment plan.

Alemtuzumab↗

PubMed2004

Experience with Implanon in a northeast London family planning clinic.

AIM: The primary objective of the study was to evaluate the continuation rates of a relatively new long-acting method of contraception, Implanon. The secondary objective was to study discontinuations related to bleeding problems and their management. METHOD: A retrospective review of records of women fitted with Implanon was undertaken during February 2000--January 2003. RESULTS: Results from the secondary objective will be the subject of a separate communication. Of the 147 implants fitted, 132 records could be retrieved; of these, 97% of the women had pre-insertion counselling by the clinician. The most common indications for Implanon usage were choice of a long-acting method, unhappy experience with other contraceptive methods and suboptimal compliance with contraceptive pills and injectables. The median age of fitting was 25 years and 36% of the women were nulliparous. No problems were experienced with fitting or removal of implants. Twenty (15%) women were lost to follow-up. Twenty-two implants were removed by the end of the study period, with 12 (60%) removals attributed to prolonged heavy/light bleeding. There were no known pregnancies during the study. Given that 15% of the women could not be followed up or contacted, the assumed lifetimes of Implanon using the Kaplan-Meier method are 0.90 (95% confidence interval 0.82-0.95) at 12 months, 0.80 (0.67-0.88) at 24 months and 0.75 (0.58-0.85) at 35 months. The confirmed lifetimes are 0.84 (0.71-0.91) at 12 months, 0.63 (0.42-0.78) at 24 months and 0.53 (0.28-0.73) at 35 months. CONCLUSION: Although not free of side-effects, Implanon can be a good choice for women who are properly informed and counselled and seek long-term 'forgettable' contraception.

Adult↗

PubMed2002

Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed.

PURPOSE: We conducted a retrospective analysis to evaluate the safety and efficacy of Campath-1H, an anti-CD52 humanized monoclonal antibody, in previously treated T-prolymphocytic leukemia (T-PLL) patients in a compassionate-use program. PATIENTS AND METHODS: Seventy-six patients with T-PLL (including four chemotherapy-naive patients) received 3, 10, and 30 mg of Campath-1H on sequential days, followed by 30 mg three times weekly, as 2-hour intravenous infusions, for 4 to 12 weeks. RESULTS: Median patient age was 60 years (range, 35 to 84). Spleen liver, lymph node, and skin involvement were present in 64%, 40%, 54%, and 18% of patients, respectively. All tested patients had CD2, CD7, CD4, and/or CD8 positivity, whereas CD5 and CD3 were positive in 98% and 96% of tested patients, respectively. The objective response rate was 51% (95% confidence interval [CI], 40% to 63%), with a 39.5% complete response (CR) rate (95% CI, 28% to 51%). The median duration of CR was 8.7 months (range, 0.13+ to 44.4), and median time to progression was 4.5 months (range, 0.1 to 45.4) compared with 2.3 months (range, 0.2 to 28.1) after first-line chemotherapy. The median overall survival was 7.5 months (14.8 months for CR patients). The most common Campath-1H-related adverse events were acute reactions during or immediately after infusions. Fifteen infectious episodes occurred during treatment in 10 patients (13%), leading to treatment discontinuation in three. Eight patients experienced possibly related, late-onset infections. Severe thrombocytopenia and/or neutropenia occurred in six patients (8%), leading to treatment discontinuation in four. Two treatment-related deaths occurred. CONCLUSION: Campath-1H is an active drug in T-PLL patients for whom first-line therapy has failed. It has a favorable risk/benefit ratio and should be prospectively investigated in chemotherapy-naive patients.

Adult↗

PubMed2001

Prevalence of HTLV-I-associated T-cell lymphoma.

In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials.

Black or African American↗

PubMed2001

Reversal of paclitaxel induced neutropenia by Withania somnifera in mice.

The effect of aqueous extract of Withania somnifera (L. Solanaceae) was studied against paclitaxel induced neutropenia in mice. After paclitaxel 1 mg/kg, i.v. administration significant fall in total WBC and absolute neutrophil count was observed on day 3 and day 5. W. Somnifera (200 mg/kg, p.o.) per se produced significant increase in neutrophil counts. W. somnifera (200 mg/kg, p.o.) when administered for 4 days before paclitaxel treatment and continued for 12 days caused significant reversal of neutropenia of paclitaxel. The findings of the study suggest the potential of W. somnifera as an adjuvant during cancer chemotherapy for the prevention of bone marrow depression associated with anticancer drugs.

Animals↗

PubMed2000

Long-term follow-up of remission duration, mortality, and second malignancies in hairy cell leukemia patients treated with pentostatin.

The nucleoside analogue, pentostatin, has demonstrated high complete response rates and long relapse-free survival times in patients with hairy cell leukemia, a disease that historically had been unresponsive to treatment. Long-term data on duration of overall survival and relapse-free survival and incidence of subsequent malignancies with this agent are lacking. Patients completing the treatment phase of a randomized, intergroup study who received pentostatin as an initial treatment or who crossed over after failure of interferon alpha were followed for survival, relapse, and diagnosis of subsequent malignancies. Two hundred forty-one patients treated with pentostatin as initial therapy (n = 154) or who crossed over after failure of interferon alpha (n = 87) were followed for a median duration of 9.3 years. Estimated 5- and 10-year survival rates (95% confidence interval) for all patients combined were 90% (87%-94%) and 81% (75%-86%), respectively. In the 173 patients with a confirmed complete response to pentostatin treatment, 5- and 10-year relapse-free survival rates were 85% (80%-91%) and 67% (58%-76%), respectively. Survival curves for patients initially treated with pentostatin and those crossed over were similar. Only 2 of 40 deaths were attributed to hairy cell leukemia. The mortality rate and incidence of subsequent malignancies were not higher than expected in the general population. Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses. Subsequent malignancies do not appear to be increased with pentostatin treatment.

Adult↗

PubMed2000

Effect of antioxidants on pyrogallol-induced delay in gastric emptying in rats.

The effect of a free radical generator pyrogallol on gastric emptying was studied in rats. Pyrogallol at doses of 25, 50, 100 and 150 mg/kg (i.p.) produced dose-dependent inhibition of gastric emptying. Pretreatment with vitamin C (100 and 500 mg/kg, p.o.), and vitamin E (100 and 500 mg/kg, p.o.) significantly reversed the inhibition in gastric emptying caused by pyrogallol 100 mg/kg. However, the combination of vitamin C and vitamin E (100 mg/kg) produced synergistic effect. Glutathione (100 mg/kg i.v.) 5-min pretreatment also reversed the inhibition of gastric emptying caused by pyrogallol 100 mg/kg. Ondansetron (3 mg/kg, p.o.) significantly reversed the pyrogallol effect. The effect of pyrogallol on malondialdehyde (MDA) levels and 5-HT levels in the stomach tissue was also studied. Pyrogallol at a dose of 100 mg/kg, i.p., significantly increased MDA levels and 5-HT levels in the stomach. Pretreatment with a combination of vitamin C and vitamin E (100 mg/kg, p.o.) and glutathione (100 mg/kg, i.v.) significantly ameliorated the rise in stomach tissue MDA caused by pyrogallol but had no significant effect on the rise in 5-HT levels caused by pyrogallol. The effect of different doses of 5-HT on gastric emptying was also studied. 5-HT had a differential effect on gastric emptying. The low and high doses (0.1, 0.3 and 30 mg/kg, i.p.) significantly inhibited the gastric emptying while doses ranging from 1 to 10 mg/kg, i.p., had no significant effect on the gastric emptying. The pretreatment with antioxidants, combination of vitamin C and vitamin E (100 mg/kg each, p.o.) and glutathione (100 mg/kg, i. v.) had no effect on the 5-HT (0.3 mg/kg, i.p.)-induced delay in gastric emptying. The result indicate the role of free radicals gastric emptying, and antioxidants may be of potential therapeutic value in disease conditions where free radicals are known to be released and the gastrointestinal effects are observed as symptoms or side effects of drug therapy.

Animals↗

PubMed2000

Novel therapies for chronic lymphocytic leukemia in the 21st century.

Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia diagnosed in the Western Hemisphere. Introduction of the purine analogs has improved outcome for patients with CLL as measured by improvements in disease-free survival and has made it possible to attain a complete remission in a minority of patients with this disease. The therapeutic success with the purine analogs in CLL has led to preclinical and early clinical investigation of a variety of other therapeutic agents. This, combined with advances in the understanding the genetic and immunobiology of CLL, leaves hope that CLL may become a curable disease in this century.

Antibodies, Monoclonal↗

PubMed1999

Cytotoxicity of 2-chlorodeoxadenosine (cladribine, 2-cdA) in combination with other chemotherapy drugs against two lymphoma cell lines.

Cladribine is a purine analog with impressive activity in patients with low-grade lymphoproliferative disorders. We studied the combination of cladribine with other antineoplastic drugs against two human-derived B-cell lymphoma cell lines in vitro. Cladribine was combined with cisplatin, daunorubicin, chlorambucil, paclitaxel or etoposide. Under the experimental conditions studied, only the combination of cladribine and cisplatin showed significantly increased cytotoxicity compared to the effect of either drug alone.

Antineoplastic Agents↗

PubMed1998

Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.

To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged VH genes expressed by 83 B-CLL cells (64 IgM+ and 19 non-IgM+). Our results confirm and extend the observations of a bias in the use of certain VH, D, and JH genes among B-CLL cells. In addition, they indicate that the VH genes of approximately 50% of the IgM+ B-CLL cells and approximately 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the VH family expressed by the B-CLL cell (VH3 expressers displaying more mutation than VH1 and VH4 expressers). In addition, the extent of mutation can be sizeable with approximately 32% of the IgM+ cases and approximately 68% of the non-IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated VH genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and JH gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the VH genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.

Amino Acid Sequence↗

PubMed1998

Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses.

B-cell chronic lymphocytic leukemia (B-CLL) represents a neoplastic disorder caused primarily by defective programmed cell death (PCD), as opposed to increased cell proliferation. Defects in the PCD pathway also contribute to chemoresistance. The expression of several apoptosis-regulating proteins, including the Bcl-2 family proteins Bcl-2, Bcl-XL, Mcl-1, Bax, Bak, and BAD; the Bcl-2-binding protein BAG-1; and the cell death protease Caspase-3 (CPP32), was evaluated by immunoblotting using 58 peripheral blood B-CLL specimens from previously untreated patients. Expression of Bcl-2, Mcl-1, BAG-1, Bax, Bak, and Caspase-3 was commonly found in circulating B-CLL cells, whereas the Bcl-XL and BAD proteins were not present. Higher levels of the anti-apoptotic protein Mcl-1 were strongly correlated with failure to achieve complete remission (CR) after single-agent therapy (fludarabine or chlorambucil) (P = .001), but the presence of only seven CRs among the 42 patients for whom follow-up data were available necessitates cautious interpretation of these observations. Higher levels of the anti-apoptotic protein BAG-1 were also marginally associated with failure to achieve CR (P = .04). Apoptosis-regulating proteins were not associated with patient age, sex, Rai stage, platelet count, hemoglobin (Hb) concentration, or lymph node involvement, although higher levels of Bcl-2 and a high Bcl-2:Bax ratio were correlated with high numbers (>10(5)/microL) of white blood cells (WBC) (P = .01; .007) and higher levels of Bak were weakly associated with loss of allelic heterozygosity at 13q14 (P = .04). On the basis of measurements of apoptosis induction by fludarabine using cultured B-CLL specimens, in vitro chemosensitivity data failed to correlate with in vivo clinical response rates (n = 42) and expression of the various apoptosis-regulating proteins. Although larger prospective studies are required before firm conclusions can be reached, these studies show the expression in B-CLLs of multiple apoptosis-regulating proteins and suggest that the relative levels of some of these, such as Mcl-1, may provide information about in vivo responses to chemotherapy. In vitro chemosensitivity data, however, do not appear to be particularly useful in predicting responses in B-CLL.

Adult↗

PubMed1996

Examples of in vivo isotype class switching in IgM+ chronic lymphocytic leukemia B cells.

Chronic lymphocytic leukemia (CLL) usually involves the expansion of a clone of CD5+ B cells synthesizing IgM antibodies. These B cells appear to be blocked at the antigen receptor-expressing stage of B cell differentiation and are thought not to undergo an isotype class switch to IgG or IgA production. In vivo and in vitro studies suggest, however, that in some instances terminal differentiation and isotype switching can occur. To test the hypothesis that in vivo isotype class switching occurs in IgM+ B-type CLL cells, we analyzed the PBMC of 19 CLL patients for the presence of transcripts encoding the rearranged CLL V(H)DJ(H) associated with either gamma or alpha H chains. The molecular data indicate that approximately 50% of B-CLL patients have amplifications of IgM+ B cells that undergo an isotype class switch. Switching to IgA appears to occur more often than to IgG; also, switching can involve different IgG subclasses in individual patients. In many instances, these CLL-related gamma and alpha transcripts are much more plentiful than those of normal B cells that produce the same isotype. These switched transcripts do not reveal evidence for the accumulation of significant numbers of new V(H) gene mutations. The cellular data indicate that B cells with lesser amounts of surface membrane IgD and higher IgM/IgD ratios are more likely to undergo this switching process. Furthermore, B cells expressing IgG and IgA of the same idiotype or V(H) family and the same CDR3 length as those of the CLL IgM+ clone can be identified in the blood of patients studied using multiparameter immunofluorescence analyses. Collectively, these data suggest that not all members of a B-CLL clone are frozen at the surface membrane Ig-expressing stage of B cell maturation, and that some members can switch to the production of non-IgM isotypes. The occurrence of switching without the accumulation of V gene mutations indicates that the processes of differentiation and diversification are not linked.

Adult↗

PubMed1996

Mutator phenotype in a subset of chronic lymphocytic leukemia.

The replication error phenotype (RER+), characterized by widespread microsatellite instability, is an important feature of tumors from patients with hereditary nonpolyposis colorectal carcinoma (HNPCC). This widespread instability affects repeat tracts of all lengths and is usually attributed to mutations of critical mismatch repair genes. Recently, several reports described occasional microsatellite alterations in tumors not associated with HNPCC. However, a true mutator phenotype (RER+) is very rare outside of HNPCC-associated malignancies. We examined 29 cases of chronic lymphocytic leukemia (CLL), the most common leukemia in the Western world for evidence of microsatellite instability. We identified a mutator phenotype in (2/29) 7% of the cases studied. These data suggest that the mismatch repair pathway may be altered in at least a subset of patients with CLL.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

PubMed1996

Differentiating agents do not induce a true hairy cell phenotype in B-CLL cells in vitro.

B-Chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia (HCL) are both differentiated B-cell lymphoproliferative disorders. Prior studies have suggested that phorbol esters and the macrocyclic lactone Bryostatin-1, which are both protein kinase-C activators, can induce the differentiation of B-CLL cells into HCL cells in vitro, as evidenced by morphology, phenotype and TRAP activity. The differentiating effect of all-trans retinoic acid on B-CLL cells has been less extensively studied. We studied the effects of incubating adherence purified B-CLL cells with phorbol myristic acetate (PMA), all-trans retinoic acid (ATRA), and Bryostatin-1. None of these agents induced a true HCL phenotype (CD5-, CD11c/CD25 coexpression) under the conditions studied.

Acid Phosphatase↗

PubMed1996

Clinical and morphological features of cases of trisomy 13 in acute non-lymphocytic leukemia.

Trisomy 13 has been infrequently reported as a primary non-random karyotypic change in myeloid leukemias. To elucidate its clinical significance we examined the clinical and hematological data in nine ANLL patients in whom we found this change, in a series of 175 cytogenetically abnormal ANLL patients. Morphologically, six of the patients were FAB-M1, two were FAB-M4 and one was FAB-M5. Bone marrow aspirates contained more than 90% blasts in eight of the patients. By immunophenotype, TdT was present in four of the patients, CD34 was present in four of five patients tested and CD5 was present in one of five patients tested. Blast cells in all patients expressed two or more myeloid surface antigens. These data suggest the proliferation of an immature myeloid cell in these patients. Complete remission was achieved in seven patients; however, remissions were short-lived. Eight patients expired between 1 and 13 months from diagnosis (median survival 5 months). Combining our findings with data in the published literature on trisomy 13 in ANLL, a larger data set consisting of 29 patients was established to determine better the clinical significance of this cytogenetic entity in ANLL. We found that this cytogenetic change has been reported in all subsets of FAB classification excepting M6 and M7. Median age at presentation was 60 years and no association with gender was noted. Median WBC was 29.5 x 10(9)/l, the majority of patients were thrombocytopenic (median platelet count 86 x 10(9)/l) and median survival was 5.2 months. This study associates trisomy 13 with malignant transformation of myeloid progenitor cells. These patients respond well to induction therapy, but relapse occurs quickly and the survival duration is poor.

Adult↗

PubMed1995

Leukemic meningitis in B-cell prolymphocytic leukemia. A clinical, pathologic, and ultrastructural case study and a review of the literature.

BACKGROUND: Leukemic meningitis is rare in B-chronic lymphocytic leukemia (CLL) and B-prolymphocytic leukemia (PLL); a MEDLINE search for reports published 1960 and after disclosed only nine prior reports. A patient with stable Rai Stage II CLL/PL developed mental status changes. Lumbar puncture revealed a lymphocytic pleocytosis with prolymphocytes containing intracytoplasmic inclusions. METHODS: The patient's cerebrospinal fluid lymphocyte population was analyzed by immunophenotyping and electron microscopy. RESULTS: The studies revealed a clonal population of B prolymphocytes, with typical immunophenotypic and ultrastructural characteristics. The patient was treated with intrathecal chemotherapy with eventual resolution of the cerebrospinal fluid pleocytosis and return to his normal neurologic status. Prior studies also have revealed the efficacy of intrathecal chemotherapy. CONCLUSION: Leukemic meningitis in CLL or PLL is responsive to treatment with intrathecal chemotherapy.

Aged↗

PubMed1995

Rapid HCV RNA detection by PCR followed by a new non-radioactive liquid hybridisation assay and comparison with RIBA.

A one-stage polymerase chain reaction (PCR) followed by an automated liquid hybridisation assay was used to examine anti-HCV-positive patients. The presence of HCV-RNA in 251 randomly selected enzyme immunoassay (EIA) positive clinical specimens was compared to their RIBA pattern. An association of a RIBA pattern with presence or absence of HCV-RNA was not detected. One hundred of these samples were also evaluated after dividing them into normal and elevated serum alanin aminotransferase (ALT) levels. PCR results were obtained on the basis of amplification products from two different gene regions (5'-NC region and NS 3). To prove the specificity of the PCR products, a commercially available digoxigenin-based liquid hybridisation assay was evaluated. The sensitivity was comparable to the results obtained after nested PCR. Based on the results of the study, the two-stage PCR can be changed in favour of the easier one-step PCR which offers the advantage of fewer contamination problems.

Alanine Transaminase↗

PubMed1995

Salivary gland hypofunction in elderly patients attending a xerostomia clinic.

OBJECTIVES: To investigate the aetiological factors and the prevalence of salivary gland hypofunction (SGH) in patients complaining of xerostomia. DESIGN: Prospective, clinical study. SETTING: Xerostomia clinic in the Department of Oral Medicine at Liverpool University Dental Hospital. SUBJECTS: 100 consecutive patients, aged 60 years or older, referred for investigation of xerostomia. INTERVENTIONS: Patients were asked specific questions concerning their complaint of oral dryness and associated orofacial symptoms. A detailed medical history was recorded and patients underwent a systematic examination of the head, neck and oral structures. All patients underwent haematological, biochemical, immunological investigations, urinalysis and sialometry. Further investigations and referrals to other specialists were undertaken when appropriate. MAIN OUTCOME MEASURES: The causes of xerostomia were established on the basis of clinical and laboratory findings and SGH was defined as an unstimulated whole salivary flow rate of < 0.2ml/min, RESULTS: The causes of xerostomia were identified as: Sjögren's Syndrome (40), iatrogenic (22), psychogenic (14), idiopathic (19), diabetes (1), candidosis (3) and alcohol (1). Sixty five percent of the patients studied had SGH. CONCLUSIONS: This study has shown that 65% of patients whose presenting complaint was xerostomia had objective evidence of SGH. Several aetiological factors were identified, the most common of which was Sjögren's Syndrome. The possibility of associated systemic diseases should be considered when establishing the aetiology of SGH.

Aged↗