Biomedical subjects
Publications and source records attributed to T Ghose.
Drug eluting stents have made a significant impact on restenosis. However, there are concerns regarding delayed "catch-up" of restenosis. In this case report we present two such patients with delayed occurrence of restenosis after drug eluting stent implantation.
The purpose of this study was to assess the 1-year clinical outcome of patients with multi-vessel coronary artery disease (CAD) who underwent coronary stenting, and to compare the results with single-vessel coronary stenting carried out during the same period. We evaluated the in-hospital and 12-month clinical outcomes [death, Q-wave myocardial infarction (MI) and repeat revascularization rates at one year] in 384 consecutive patients treated with coronary stents in 2 (92% of patients) or 3 of the native coronary arteries and compared the outcome to 624 consecutive patients undergoing stenting in a single coronary artery between January 1, 1997 and January 31, 1999. The overall procedural success was obtained in 99% of patients with 2- or 3-vessel stenting and 98% of patients with single-vessel stenting. Procedural complications were similar (2.9% vs 2.6%; p = 0.12). During follow-up, target lesion revascularization was 16% in multi-vessel and 14% in single-vessel stenting (p = 0.38) and repeat revascularization was also similar for both groups (19% vs. 20%; p = 0.73). There was no difference in death (0.8% vs. 1.3%; p = 0.31) and Q-wave MI (0.7% vs. 1.4%; p = 0. 16) in the 2 groups. Overall cardiac event-free survival was similar for both groups (76% vs. 78%; p = 0.54). Multi-vessel stenting in carefully selected patients in our experience had a high procedural success with very low complication rates. The one-year clinical outcomes were acceptable and were similar to the results of single-vessel stenting.
Primary coronary stenting is being increasingly used in patients undergoing primary coronary angioplasty for acute myocardial infarction. In this prospective study we evaluated our experience of direct angioplasty in 68 patients with acute myocardial infarction of whom 57 received intracoronary stents using high-pressure deployment (> or =12 atmospheres) with adjunct aspirin and ticlopidine therapy without coumadin. All patients underwent pre-discharge follow-up angiography. Stent implantation was successful in all patients. Stent thrombosis was not seen in any patient. However, TIMI grade 3 flow was obtained in only 51 patients (89.6%) with evidence of slow flow present in remaining six patients. Follow-up angiograms showed no stent thrombosis but five out of the six patients (83%) with slow-flow phenomenon persisted to have slow flow. These patients had lower left ventricular ejection fraction as compared to patients with TIMI 3 flow at follow-up angiography (27.5 +/- 10.2% vs. 42.1 +/- 15.2%, P < .001) and a high mortality (two out of six) within 30 days. Primary stenting is safe and feasible in the majority of patients with good short-term outcomes, but persistent slow-flow phenomenon with adverse clinical outcome is seen in a small but significant number of patients.
Surgical transmyocardial laser revascularization has been reported to improve clinical outcome in patients with refractory angina who are not candidates for angioplasty or bypass surgery. We investigated the feasibility and safety of a nonsurgical, percutaneous technique for laser channel creation using energy from a holmium:yttrium-aluminium-garnet (YAG) laser. The laser energy was directed through a fiber enclosed in a catheter to the ventricular myocardium creating channels between the blood pool and the myocardium. Thirty-five patients with angina and coronary anatomy not amenable to revascularization with coronary angioplasty or bypass surgery underwent percutaneous transluminal myocardial revascularization. A total of 15 +/- 5 channels were formed per patient. There was no procedure-related mortality. One patient developed cardiac tamponade requiring thoracotomy and another a minor self-limiting pericardial effusion. There was no worsening of regional wall motion function in any patient. All patients were discharged alive after a postprocedure hospital stay of 2.1 +/- 1.4 days. Mean Canadian Cardiovascular Society (CCS) functional class declined from 3.68 +/- 0.4 before procedure to 0.82 +/- 0.7 at 30 days (P < 0.01). At 3 months, mean angina class was 0.94 +/- 0.65 (n = 35; P < 0.01) and at 6 months, mean angina class was 1.08 +/- 0.58 (n = 26; P < 0.01). One patient required repeat revascularization after 5 months for progression of disease in a degenerated saphenous venous graft supplying different region of myocardium. We conclude that transmyocardial revascularization using holmium:YAG laser by percutaneous technique can be carried out safely with encouraging early results and a very low complication rate. The symptomatic relief seen up to 6 months has been excellent. The long-term effects of this technique on mortality and relief of angina, however, remain to be defined. Cathet. Cardiovasc. Intervent. 47:287-291, 1999.
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In animal models of coronary restenosis, intravascular red light therapy (IRLT) using a diode laser source has been shown to reduce neointimal hyperplasia following balloon-induced injury and coronary stenting. We studied the safety and efficacy of catheter-based IRLT for preventing restenosis after coronary stenting in 22 patients with angina pectoris. IRLT was performed using a diode laser (650 nm) at an energy level of 10 megawatts delivered through a rapid exchange balloon system containing the fiberoptics. The procedure was successful in all patients, with no procedural or in-hospital complications. Two patients with recurrence of symptoms had angiography at 3 and 4.1 months respectively. Angiographic follow-up was also done after 6 months in the 20 remaining asymptomatic patients. The mean minimal lumen diameter (MLD) for the whole group at 6 months follow-up was 2.57 +/- 0.62 mm. The calculated late lumen loss was 0.49 +/- 1.12 mm with a late loss index of 0.21 +/- 0.54. Four patients (2 symptomatic and 2 asymptomatic) in the series developed angiographic restenosis. Clinical events at follow-up of 10.9 +/- 3.5 months were repeat angioplasty in 2 patients for symptomatic restenosis with a 91% event free survival. These preliminary results demonstrate that IRLT after coronary artery stenting is safe and feasible; it is associated with low rates of angiographic indices of restenosis.
55 individuals, 44 of whom served as patients and 11 as controls were included in this study. Patient group was further divided into overt and subclinical hypothyroid group each having 22 patients. Patients were examined in a prospective manner and results compared with control group with an aim to evaluate the effect of hypothyroidism subclinical and overt on cardiac status by echocardiography. Variables of heart structure and function were assessed by cross sectional and Doppler echocardiography. IVS dimensions were significantly raised in moderate subclinical and in severe overt hypothyroidism (mean 0.911 +/- 0.038 and 0.973 +/- 0.217 cm). LVPW thickness was significantly increased only in overt hypothyroidism (mean 1.378 +/- 0.246). However RVW and LVID showed no definite pattern of change. Pericardial effusion and Diastolic dysfunction was seen in significant cases only in overt hypothyroidism. To conclude, hypothyroidism both subclinical and overt is associated with cardiovascular alteration both structural and functional. IVS and LVPW thickness are markedly affected, as well as there is impairment of left ventricular function more in diastole.
The anthracyclin antineoplastic agent doxorubicin (Adriamycin) was linked by four different methods of linkage to DalB02, an IgG1 kappa murine monoclonal antibody (mAb) against surface-associated antigens on human chronic lymphocytic leukaemia (CLL) B cells. All the four conjugates fully retained the immunoreactivity of the parent DalB02. When the inhibitory effect of these conjugates was evaluated in vitro against the target D10-1 cells (a clone derived from an Epstein-Barr-virus-transformed human CLL B cell line that binds DalB02) it was observed that one conjugate was more potent than the free drug but the others were not. When 131I-labelled unmodified DalB02 and the 131I-labelled DalB02-containing conjugate that was found to be potent were injected i.v. into nude mice bearing a subcutaneous D10-1 xenograft, the percentages of the injected dose (%ID) of both 131I-DalB02 and the 131I-DalB02-containing conjugate that localized in the tumour were much higher than the %ID of the respective preparations that localized in normal tissues of D10-1-xenografted mice. The systemic toxicity of the conjugate was less than that of the free drug. At an equitoxic dose level, this conjugate was a more effective inhibitor of established D10-1 xenografts than the free drug.
A heteroconjugate (HC) antibody, constructed with the monoclonal antibody (MoAB) Dal K29 to human renal cell carcinoma (RCC) and an anti-CD3 MoAb, could induce a very high level of lysis of human RCC cells when incubated with human peripheral blood lymphocytes (PBL) in vitro (Kerr et al., 1990, J. Immunol., 144, 4060-4067). We now report that this HC antibody selectively localizes in RCC xenografts in nude mice and could inhibit RCC in an ascites tumor xenograft model when administered intraperitoneally together with PBL.
After i.v. or i.p. inoculation of 5 x 10(6) D10-1 cells, a subclone of an Epstein-Barr virus transformed human B-cell chronic lymphocytic leukemia (CLL) line, 100% of nude mice developed solid or ascites tumors and died within 17-60 days of tumor inoculation. There was significant tumor inhibition, including tumor cure, when these tumor-inoculated mice were treated with either unmodified or 131I (300 microCi)-linked Dal B02 (50 micrograms/mouse), a monoclonal antibody directed against surface-associated antigens on human CLL B-cells and several histological types of B-lymphoma cells. There was no significant difference between the antitumor activity of unmodified Dal B02 and 131I-linked Dal B02 when the treatment was given 3 days after i.p. or i.v. inoculation of 5 x 10(6) D10-1 cells. However, when the mice were treated 3 days after i.p. inoculation of 15 x 10(6) D10-1 cells, or 7 days after the i.v. inoculation of 5 x 10(6) D10-1 cells, 131I-linked Dal B02 was a more potent tumor inhibitor than was unmodified Dal B02 (P < 0.05 and P < 0.01, respectively). Two injections of 131I (500 microCi) linked to 100 micrograms of a Dal B02 F(ab')2 fragment preparation also prolonged the survival of i.p. or i.v. tumor-inoculated mice (P < 0.05 and P = 0.05, respectively). In nude mice with established s.c. xenografts of D10-1 cells, two injections of 131I (300 microCi) linked to 50 micrograms of Dal B02 led to complete tumor cure in 3 of 4, mice, but two injections of 50 micrograms of unmodified Dal B02 had no effect on the s.c. xenografts. Two injections of 131I (500 microCI) linked to 100 micrograms of Dal B02 F(ab')2 fragment caused significant tumor inhibition but no tumor cure. 131I (300 microCi) linked to 50 micrograms of a nonspecific IgG1 only led to minor tumor inhibition. A mixture of unmodified Dal B02 and 131I-linked nonspecific IgG1 was not a more potent tumor inhibitor than the 131I-linked nonspecific IgG1 preparation by itself. These results suggest that Dal B02 may be an effective carrier for the radioimmunotherapy of human B-cell CLL and other appropriate B-cell lymphomas, especially in the progressive phase of B-cell CLL, which is usually not amenable to currently available therapeutic modalities.
To establish xenograft models of human B-cell chronic lymphocytic leukemia (CLL), we inoculated 5 x 10(6) D10-1 cells, a subline of Epstein-Barr virus (EBV)-transformed human B-cell CLL with a marker chromosomal anomaly, into SCID or irradiated nude mice by the intravenous (i.v.) or intraperitoneal (i.p.) route. All i.p. tumor-inoculated mice developed rapidly progressive, lethal ascites tumor, and 100% of i.v. tumor-inoculated mice developed disseminated CLL. All mice died of tumor within 8 weeks of tumor inoculation. Tumor-inoculated SCID mice died earlier with wider tumor dissemination than the tumor-inoculated nude mice. All the tumor-inoculated mice had histologically confirmed metastases in lymph nodes, and most of them also had metastases in one or more internal organs. Cytogenetic analysis confirmed the origin of these tumors from the xenografted D10-1 cells. The D10-1 cells harvested from the xenografts did not differ from the parent D10-1 cells as regards (i) reactivity with 2 monoclonal antibodies (MAbs) directed against CLL-associated cell-surface antigens; (ii) rate of proliferation in vitro; and (iii) sensitivity to the 2 chemotherapeutic agents, methotrexate and adriamycin. Administration of 50 micrograms/mouse of Dal B02, an IgG1 (kappa) MAb directed against surface-associated antigens of human B-cell CLL, significantly prolonged the survival of D10-1-inoculated nude and SCID mice. The MAb was more effective in D10-1-inoculated nude mice than in SCID mice. In all the D10-1 xenograft models, the effectiveness of Dal B02 decreased with higher tumor load but increased with the amount of MAb injected. Dal B02 F(ab)'2 fragment failed to demonstrate any anti-tumor activity in D10-1-inoculated nude mice. In vitro assays revealed that Dal B02 had no direct inhibitory effect on D10-1 cells, but could be cytotoxic towards D10-1 cells in the presence of splenic cells or peritoneal macrophages from nude and SCID mice, or together with rabbit complement.
We investigated the pharmacokinetics, biodistribution and tumor localization of intravenously injected Dal B01 and Dal B02, two monoclonal antibodies (MoAbs) directed against tumor associated antigens on human chronic lymphocytic leukemia (CLL) B cells, and their F(ab)'2 fragments in nude mice bearing xenografts of the human B cell CLL line D10-1. More of the percentages of the injected dose (% ID) of these two MoAbs and their F(ab)'2 fragments specifically localized in the tumor xenografts than in normal tissues. Compared to intact MoAbs, their F(ab)'2 fragments had lower % ID in tumors and were cleared from circulation faster. Well-defined tumor images were obtained at 24 and 48 h after administration of [131I]Dal B02 F(ab)'2 fragment and at 96-192 h after administration of [131I]Dal B02. A comparison between intravenous and intraperitoneal routes of administration of [131I]Dal B02 did not reveal any difference in the localization of % ID in tumor or normal tissues.
Dal B02, a murine monoclonal antibody against human chronic lymphocytic leukemia (CLL) was radioiodinated using chloramine T (Chl.T), Bolton-Hunter (B-H) or N-succinimidyl-p-iodobenzoate (PIB). The preparations had comparable radiochemical purity (> 97%) and immunoreactive fraction (65-80%) but the Chl.T-based product was most susceptible to deiodination and loss of immunoreactivity. After i.v. injection into CLL-xenografted nude mice, the preparations had identical patterns of clearance from the blood but the PIB-based product led to more radioactivity in liver and spleen and less in the thyroid compared to the other preparations. The Chl.T-based product showed loss of immunoreactivity in circulation and less tumor-localized radioactivity 168 h after administration. The differences between the B-H-based and PIB-based products were less impressive than between PIB-based and Chl.T-based products.
Alpha 1-antitrypsin (alpha 1AT) has been detected in several human tumors and is thought to be a marker of neoplastic change and progression. As the biology of azoxymethane (AOM) induced intestinal tumors in F344 rats has many characteristics of human intestinal tumors, we have investigated alpha 1AT expression in AOM induced rat intestinal tumors. Nine of 12 colonic carcinomas and 6/8 small intestinal carcinomas had alpha 1AT positive tumor cells. Only 1/11 colonic adenomas and 0/3 small intestinal adenomas contained alpha 1AT. Thus alpha 1AT is a marker of malignancy in this model. Inhibition of carcinogenesis by piroxicam and difluoromethyl ornithine inhibited alpha 1AT expression.
Two patients with comminuted, displaced fractures of the distal radius associated with ipsilateral, undisplaced scaphoid fractures were treated by internal fixation of the scaphoid fracture with a Herbert screw in association with external fixation of the distal radial fracture. One of the patients had a limited open reduction of the distal radius combined with bone grafting. Both patients had satisfactory results. Internal fixation of the scaphoid is indicated if distraction is applied to the carpus to treat an associated fracture of the distal radius, even if the scaphoid fracture is undisplaced.
We investigated the localization of intravenously injected DAL K45 and DAL K29, two monoclonal antibodies (MABs) against human renal cell carcinoma (RCC), and their F(ab)2 fragments in nude mice bearing intrarenal transplants of the RCC line Caki-1. More of the MABs or their F(ab)2s specifically localized in the tumor than in any normal tissue with the exception of blood. Compared to parent MABs, F(ab)2s were cleared faster from all tissues. In serum, the MABs and F(ab)2s showed a single radioactive peak retaining partial immunoreactivity. DAL K45-F(ab)2 showed the highest tumor:normal tissue localization ratios and the most distinct gamma-camera image at 24 h.
In this study we described the isolation of a subclonal EBV-transformed human CLL B-cell line with retarded growth rate and metastatic potential from its clonal parent (D10-1), which was karyotyped: 46.XY.dup(1)(q11----q32). The subclone, designated D10-1C, was isolated by limiting dilution of D10-1 following selection in 8-azaguanine-supplemented medium. Chromosome analysis of D10-1C revealed a constitution of 47,XY, + 11.dup(1)(q11----q32). This is the first demonstration that partial trisomy 1q-associated growth advantage in human cancer cells can be retarded by the presence of an additional dose of chromosome 11. Human chromosome 11 had been shown to be responsible for the suppression of tumor development. Whether the same suppressor genes are involved in D10-1C remains to be elucidated. The procedure described here for the enrichment and isolation of a growth-retarded mutant from D10-1 may be applicable in other malignant cell systems.