Biomedical subjects
M Bhargava
Publications and source records attributed to M Bhargava.
Effect of serum and platelet-derived growth factor on chondrocytes grown in collagen gels.
In this in vitro study, cell proliferation, viability, and morphology; proteoglycan (PG) synthesis; and gel contraction were assessed over a 15-day period (on days 3, 6, 9, 12, and 15) for mature bovine chondrocytes cultured in collagen gels. The environment within the gel was varied by changing the concentration of fetal bovine serum (1% and 10%) and platelet-derived growth factor-BB (PDGF; 0, 10, 50, 100 ng/ml) within the gel and incubation media. Our results showed that the amount of serum or PDGF added to the gels had no effect on cell viability, with >95% of cells remaining alive throughout the experiment. There was a significant increase in cell number over time in all groups, with a higher rate of cell proliferation in gels containing 10% serum and higher concentrations of PDGF. In addition, the amount of serum significantly affected gel contraction with or without PDGF. Gels containing 10% serum contracted on day 10-12, while none of the gels containing 1% serum contracted over the course of the experiment. The PG content within each gel increased with incubation time only for the gels containing 1% serum, and 10 or 100 ng/ml of PDGF. However, on a per cell basis, there was no change in the PG content with time when only serum was used and a significant decrease in the rate of PG production with the addition of PDGF (9.1-27.8 pgPG/cell/day). Cell morphology was also affected by PDGF, with the cells becoming more spindle shaped. Cell alignment within the gels appeared to be most affected by gel contraction. Collagen gels can act as cell carriers for the purpose of tissue engineering. These gels provide a three-dimensional environment in which chondrocytes can proliferate and produce matrix. We have shown how this environment can be controlled to affect gel contraction, rates of cell growth and PG production, and cellular morphology while maintaining cell viability. This information will be useful in determining the conditions in which chondrocytes can be grown within collagen gels and combined with cytokines to create an ideal tissue construct.
Severe aplastic anemia evolving into T cell acute lymphoblastic leukemia.
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Fracture of the patella following total knee arthroplasty.
The charts of 21 patients (22 knees) with significant radiographic changes of the patella after total knee arthroplasty were reviewed. The average patient age was 73 years, and average follow-up after arthroplasty was 7.3 years. Lateral release, fat pad excision, quadriceps tendon release, and previous surgery were implicated in the etiology of fracture of the patella. Five cases had type 1 pattern (sclerosis, fragmentation, and no fracture), 5 cases had type 2 pattern (undisplaced fracture and fragmentation), and 12 cases had type 3 pattern (displaced fracture and fragmentation). Type 1 and 2 patterns required no surgical treatment and were rated good to excellent according to the Hospital for Special Surgery Disability Score Sheet. Patients with a type 3 pattern who did not undergo surgery were rated poor to fair, while patients with a type 3 pattern who underwent surgical treatment (patellectomy, removal of the patellar component, or excision arthroplasty for infection) were rated good. Patellectomy is the treatment of choice for patients with displaced fractures of the patella. A classification system for the pattern of patellar changes is proposed.
Leukemoid reaction simulating acute promyelocytic leukemia.
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Haemostatic abnormalities in dengue haemorrhagic fever in the New Delhi outbreak, India.
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Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India.
In order to investigate the phenomenon of multidrug resistance as a possible mechanism for poor response to treatment in patients with acute lymphoblastic leukemia (ALL) from India, a series of 32 cases of de novo untreated ALLs were analyzed by a cDNA-PCR approach to estimate the relative mRNA levels of the MDR-associated genes encoding MDR1, MRP, GSTpi, and GSTmu. The expression of beta2 microglobulin served as an internal standard. Quantifiable transcripts were observed in 20 patients for MRP, in 5 for MDR1, in 24 for GSTpi, and in 19 for GSTmu. The values ranged from undetectable to 132% of the control A549 cell line for MRP, undetectable to 49% of the HL60/DNR control cell line for MDR1, undetectable to 268% of A549 control cell line for GSTpi, and undetectable to 247% of A549 control cell line for GSTmu mRNA. Increased MRP levels were associated with increased GSTpi and GSTmu levels (p<0.01 for both), and increased levels of MDR1 were associated with increased GSTpi levels (p<0.05). The present observations showed no correlation between the MDR1 and MRP values with treatment outcome, in terms of either achieving a complete remission or predilection to early relapse. In view of some recent studies that envisage MRP as an energy-dependent pump involved in the efflux of GSH conjugates, the simultaneous up-regulation of transcription of all these genes might well be part of an integrated detoxification response that has been switched on after exposure to an environmental stress.
Detection of BCR-ABL transcripts in acute lymphoblastic leukemia in Indian patients.
Thirty-three patients with acute lymphoblastic leukemia (ALL) from India were studied for the presence of BCR-ABL chimeric transcripts, by a seminested cDNA-PCR. We report the presence of BCR-ABL chimeric transcripts in 4/17 (24%) children (under 15 years) and 3/16 (19%) adults (15-50 years). This is in sharp contrast to the published literature from the West where the presence of BCR-ABL has been reported in only 2-5% children and 35% adults. Whether the presence of BCR-ABL fusion mRNA, which is generally an attribute of ALL in adults and of poorer prognosis, may contribute to chemo-incurability in young Indian patients, remains to be seen, as a larger number of patients are studied for treatment outcome and survival on uniform therapy protocols.
Improvement of pulse oximetry signal by EMLA cream.
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The obstruction of an endotracheal tube by the plastic coating sheared from a stylet: a revisit.
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A prospective study on the incidence of hepatitis B & C infections amongst patients with lymphoproliferative disorders.
Fifty one patients with acute lymphoblastic leukaemia (ALL) and non-Hodgkins lymphoma (NHL) undergoing chemotherapy were studied prospectively to determine the incidence, aetiology and natural course of hepatitis. Of 51 patients (31 NHL and 20 ALL), 22 developed hepatitis. Hepatitis B (IgM anti HBc positive) was the cause in 11 patients (50%), hepatitis C in 4 patients, and septicaemia and cytotoxic drugs in 3 patients each. Malignant infiltration of the liver was the cause in the remaining 1 patient. Hepatitis was predominantly (75%) anicteric. Mean duration of hepatitis was 21 days. Of 51 patients, 21 acquired hepatitis B and/or C virus infection. They had received 6.4 (+/- 3.4) units of packed red cells and 5.3 (+/- 11) units of platelet concentrate as compared to 3.4 (+/- 4.8) units of red cells and 5.3 (+/- 12.1) units of platelet concentrate received by those who did not acquire virus infection (P < 0.05 for packed red cells). Only transient stoppage of chemotherapy was necessary following development of hepatitis and most of the patients who developed hepatitis could complete their chemotherapy schedule. None of the patients who developed viral B or C infection cleared the infection. We conclude that there was a high incidence of hepatitis B and C infection amongst patients with lymphoproliferative disorders with an increased carrier rate. Transfusion was a major risk factor for such infections.
Late relapse in a case of childhood acute lymphoblastic leukemia.
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Indo-French symposium on apoptosis and multidrug resistance.
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Whole blood harvested after granulocyte-colony stimulating factor (Neupogen) mobilization, and reinfused unprocessed after high-dose melphalan treatment, accelerates hematopoietic recovery in patients with multiple myeloma.
BACKGROUND: High-dose melphalan (HDM) is now a standard treatment for multiple myeloma (MM). Stem cell transplants are fast evolving as an alternative to bone marrow transplants because they are less traumatic and easier to perform. A study was undertaken to test if whole blood harvested after mobilizing peripheral blood stem cells with granulocyte-colony stimulating factor (G-CSF) reinfused as such (without stem cells being processed or concentrated through a cell separator) for rescue after HDM (dose 140-180 mg/m2) in MM accelerates hematopoietic recovery. METHODS: Eight consecutive patients with MM were given HDM after receiving 4-5 courses of infusional vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy. Approximately 6 weeks after the last course of chemotherapy, at the start of the procedure, G-CSF (Neupogen) was given at a dose of 10 microgram/kg subcutaneously daily for 4 days to mobilize stem cells. All of the patients had brisk leukocytosis (18.4-64.6 x 10(9)/L). On day 0 (fifth day after G-CSF), 1 L of blood was removed by phlebotomy and kept at room temperature for 24 hours. This was followed by a rapid intravenous (i.v.) bolus of melphalan at a dose of 140 mg/m2 in the first three patients, 155 mg/m2 in the 4th, 170 mg/m2 in the 5th, and 180 mg/m2 in the 6th, 7th, and 8th patients, applies to all patients along with hydration and diuresis. Twenty-four hours later, I L of blood previously removed was transfused back to the patient without any processing through the cell separator. The numbers of mononuclear cells reinfused was between 0.76 and 3.2 x 10(8)/kg (mean: 1.82 x 10(8)/kg). The number of CD 34+ cells infused in 4 patients ranged from 1.9 to 2.8 x 10(6)/kg (mean: 2.35 x 10(6)/kg). G-CSF was restarted on day 2 at a dose of 5 microgram/kg and given daily until the granulocyte count was 0.5 x 10(9)/L or more for 3 consecutive days. Antibiotics were given whenever a patient developed pyrexia. Platelets were transfused if below 20 x 10(9)/L or for incidences of overt bleeding. RESULTS: Granulocyte counts touched 0 between Days 6 and 10, lasting for an average of 3.4 days. Duration of granulocyte count below 0.5 x 10(9)/L was 6.5 days (range: 5-9), and these rose to 1.0 or more x 10(9)/L by Day 13.7 (range: 13-16). The number of platelet transfusions given per patient was 2.5 (range: 0-4). Intravenous antibiotics were used for 9 days (range: 4-12), and patients were discharged on Day 19 (range: 16-22). Follow-up ranged from 45 to 380 days. CONCLUSIONS: Hematopoietic recovery was rapid in all patients, including those who received doses of melphalan higher than 140 mg/m2. This resulted in less need for platelet transfusions or antibiotics, and hospitalization was short. Our results are historically similar to conventional peripheral blood stem cell transplants but much better than autologous bone marrow transplants, indicating that whole blood after G-CSF provided sufficient progenitor cels for early engraftment. The procedure is less labor intensive insofar as it does not require separation and concentration of stem cells. It has the potential of becoming an alternative to autologous marrow and peripheral blood stem cell transplantation in patients with MM.
Cytogenetic and molecular genetic studies on Indian patients with chronic lymphocytic leukemia.
This is the first cytogenetic and molecular genetic study to find any specific genetic abnormalities in Indian patients with chronic lymphocytic leukemia (CLL). Cytogenetic studies on 18 patients indicated that their karyotypes were relatively simple and trisomy 12 was seen on karyotype evolution in one patient. Fluorescence in situ hybridization (FISH) revealed abnormal clones of trisomy 12 in nine cases and RB gene deletion in 14 of the 29 cases analyzed. Three patients had both clones. Immunoglobulin genes were rearranged in all the cases and TCR beta in none of the 18 cases Southern blotted. BCL-1 was rearranged in one case. No rearrangement of BCL-2 gene was seen in any case. Genetic changes in Indian CLL were more similar to Western CLL than to Japanese CLL, even though India is supposed to be a low incidence area. Therefore, factors (such as HLA and other genetic markers) other than these routine parameters must be studied to explain the low incidence of CLL in India.
Effects of balloon mitral valvuloplasty on left ventricular muscle function.
Echocardiographically determined ventricular load and performance were compared in 40 consecutive patients with severe mitral stenosis before and 24 h after successful and uncomplicated balloon mitral valvuloplasty in order to clarify the role of loading conditions in causation of reduced left ventricular ejection fraction. After valvuloplasty, mitral valve area increased 2-fold. A modest increase in ejection fraction (53 +/- 11% to 57 +/- 8%, P = 0.021) occurred with an insignificant increase in end-diastolic volume (44 +/- 10 to 48 +/- 16 ml/m2, P = 0.063) and no change in wall stress (61 +/- 19 to 59 +/- 19 kdynes/cm3, P = 0.85) (10(5) dynes = 1 N). There was no correlation between changes in fractional shortening and wall stress (r = 0.07) and between changes in end-diastolic volume and fractional shortening (r = 0.12). Contractile performance estimated by a performance-afterload relation was unchanged after the valvuloplasty. Factors other than a change in loading conditions might be responsible for a modest improvement in ejection performance following mitral valvuloplasty.
Scatter factor modulates the metastatic phenotype of the EMT6 mouse mammary tumor.
EMT6 is a transplantable mouse mammary tumor cell line that has been utilized widely as a model system to study the effects of various treatments on local tumor growth and pulmonary metastasis. In this study, we examined the cellular mechanisms by which scatter factor (SF), a fibroblast-derived cytokine that stimulates epithelial cell motility, may contribute to tumor-cell dissemination, using the EMT6 model system. In vitro, SF stimulated EMT6 cell motility, invasiveness and cell-surface expression of urokinase (an enzyme required for cell migration through tissue). SF differentially stimulated EMT6 cell adhesion to and migration onto surfaces coated with collagen I and laminin. EMT6 cells treated in vitro with SF and injected i.v. into isogeneic BALB/c-Rw mice showed a small but significant increase (1.7-fold) in lung colony formation as compared with control cells. For EMT6 cells in vitro, SF had no effect on DNA synthesis, cell proliferation, cell size distribution, or in vitro colony-forming ability. Thus, the increase in lung colonization may be due to enhanced ability of SF-treated cells to adhere to subendothelial basement membrane or to invade through tissue. Studies of the tissue distribution of SF in BALB/c-Rw mice demonstrated high levels of active factor in the lung. Thus, the presence of endogenous pulmonary SF may have reduced the degree to which SF treatment stimulated EMT6 lung colonization. Significant SF activity was also found in extracts of EMT6 tumors. Cultured EMT6 cells did not produce SF, but did produce high titers of a soluble low-molecular-weight protein activity that is capable of stimulating SF production in human fibroblasts 3- to 5-fold. EMT6 tumor extracts contained high titers of a similar SF-inducing activity. These observations suggest that SF may contribute to the invasive and metastatic phenotype of EMT6 cells via a paracrine mechanism in which tumor cells induce the production of SF in stromal fibroblasts.
Role of serum ferritin in assessment of disease activity in acute & chronic leukemia.
Serum ferritin (SF) was estimated using double antibody sandwich ELISA in 83 patients of acute and chronic leukemia at various stages of the disease. In 35 patients of acute lymphoblastic leukemia (ALL) in remission, the SF levels fell significantly from 550.63 ng/ml at presentation to 319.56 ng/ml but remained significantly higher than the control values of 46.14 ng/ml. In 28 patients of acute myeloid leukemia (AML), the SF values at 775.0 ng/ml were much higher than those in ALL patients and showed no decline with remission. This pattern was also seen in patients of chronic myeloid leukemia in blast crisis (CML-BC) with SF levels of 804.03 ng/ml at presentation and 717.43 ng/ml at partial remission. The values of SF were lowest in patients of CML in chronic phase ranging from 271.5 ng/ml to 332.12 ng/ml and showed no relationship with variation in total leucocyte count. No correlation was found between SF values and various clinical and laboratory parameters such as age, sex, fever, organomegaly, haemoglobin and total leucocyte count. Thus, while there appeared to be a correlation between remission and SF values in ALL, no such correlation existed between the activity of the disease and SF in other types of leukemia.