Thromboprophylaxis for atrial flutter.
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Biomedical subjects
Publications and source records attributed to S Kamath.
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Airway inflammation in children can be assessed by nonbronchoscopic bronchoalveolar lavage (BAL). Little is known about the repeatability of cell counts in the BAL obtained. Children (n=43) attending for elective surgery were studied. Cell counts were obtained following a nonbronchoscopic lavage. Two samples were obtained with either: 1) the catheter wedged in the same position (n=21) or 2) the catheter reinserted and wedged again (n=22). Slides (n=30) from nonbronchoscopic lavage samples were selected at random and two independent observers counted 500 cells on each slide on two occasions. The repeatability of the lavage sampling and cell counting was assessed for different cell types. The inter- and intra-observer repeatability for the differential cell counting demonstrated that there was good repeatability for all cell types except lymphocytes (interobserver: Lin's concordance coefficient 0.42; repeatability coefficient 0.66). Quantification of eosinophil (%) was highly repeatable using either method (Lin's concordance coefficient 1) 0.99, 2) 0.95; repeatability coefficient 1) 0.58, 2) 1.36). Nonbronchoscopic lavage is a repeatable technique for the quantification of eosinophils. Variation in the sampling method can be reduced by taking two separate samples and averaging the differential cell counts. Furthermore, increasing the number of cells counted should ensure accurate quantification of lymphocytes.
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OBJECTIVES: To study the clinical profile of hypertension in the elderly, development of end organ complications and the effect of hypertension with other risk factors in producing these complications. METHODS: One hundred and thirty six elderly patients attending the Hypertension Clinic were included in the study. A detailed history was taken that included presenting illness, family history of hypertension, diabetes, coronary artery disease, dyslipidaemia and history of addictions. Physical examination included systemic examination with measurement of waist to hip ratio and fundoscopy for retinopathy. Renal and liver function tests (RFT, LFT), blood sugar, lipid profile, X-ray chest, electrocardiography (ECG), 2-D echocardiography, abdominal ultrasound and computed tomography (CT) scan head (if indicated) were other important investigations done. RESULTS: Seventy-nine patients were in the age group of 60-65 years, of which 42 (30.9%) were males. Headache was the commonest chief complaint in 77.9% patients; whereas 24 patients were asymptomatic. Obesity, diabetes, alcohol, dyslipidaemia and family history were important determinants of hypertension. Lipid profile was abnormal in 55.9% patients. Isolated systolic hypertension (ISH) was found in 56.6% patients. Grade II hypertensive retinopathy was observed in 29.4% patients with uncontrolled blood pressure. Left ventricular hypertrophy (LVH) was the commonest ECG manifestation seen in 36.8% patients of which 26.5% had uncontrolled blood pressure. LVH could be diagnosed in 46.4% patients by 2-D echo. Patients with uncontrolled blood pressure and ISH had increased incidence of cardiovascular and cerebrovascular complications. Cardiovascular complications were seen in 19.1% patients having dyslipidaemia and hypertension. Cerebrovascular complications were seen in 15.4% patients having hypertension with LVH. Treatment included calcium channel blockers and/or other drugs. CONCLUSIONS: The elderly hypertensive patients tend to have ISH. Family history of hypertension is an important determinant of hypertension. Uncontrolled hypertension, ISH, LVH and other associated risk factors are responsible for cardiovascular and cerebrovascular morbidity.
Interleukin-2 (IL-2) belongs to a class of soluble, regulatory proteins known as cytokines. It is a 133 amino acid glycoprotein secreted by T(H) lymphocytes and other cells following activation by antigens, mitogens and other cytokines. It stimulates the proliferation and cytotoxicity of T lymphocytes. It also enhances the microbicidal and cytotoxic activities of NK cells, B lymphocytes, macrophages and monocytes. IL-2 can now be produced in unlimited quantities by recombinant DNA technology and used therapeutically to modulate the immune system in a number of diseases. A number of different studies have demonstrated its therapeutic value in HIV +ve and AIDS patients. It has been approved by US-FDA for treatment of metastatic renal cell carcinoma (RCC) and metastatic melanoma. Routine detection of soluble IL-2 receptor in blood could be useful as a diagnostic marker in some autoimmune diseases. Agents that antagonize IL-2 find application as immunosuppressants. The main adverse effect of IL-2 is capillary leak syndrome caused by increased capillary permeability and extravasation of fluid. In days to come, IL-2 is likely to play an increasingly important role in management of viral infections, malignancies and a number of other diseases conditions.
Yamanouchi in collaboration with Protein Design Labs (PDL), is developing YM-337, a humanized antibody (C4G1) for the potential treatment of coronary artery disease, including myocardial infarction, arterial thrombosis and ischemic stroke. The antibody is based on a Yamanouchi murine antibody specific for the glycoprotein (GP) IIb/IIIa receptor found on human platelets 11942421. By June 1999, Yamanouchi was carrying out phase II trials on YM-337 in high-risk percutaneous transluminal coronary angioplasty (PTCA) patients in Europe and the US [326891]. These were ongoing in May 2001 [409092], [411763]. Phase II trials for the potential treatment of ischemic stroke were also underway by this time in Europe and the US [411763]. By 1998, Yamanouchi and PDL had an agreement for the development of a SMART C4G1. Yamanouchi holds exclusize worldwide rights to YM-337 and is responsible for all clinical trials and obtaining regulatory approval. As part of the collaboration, PDL has received milestone payments for humanization of the antibody and is entitled to receive royalties on product sales [274540].
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Nucleoside diphosphate kinase (Ndk) is a ubiquitous enzyme which functions in balancing the nucleotide pool of the cell. We have recently reported that in addition to being intracellular in both mucoid and nonmucoid Pseudomonas aeruginosa, Ndk is also secreted into the extracellular environment by mucoid P. aeruginosa cells. This secreted Ndk has biochemical activity similar to the intracellular Ndk and is 16 kDa in size. To demonstrate that Ndk is indeed secreted and to localize the secretion motif, we constructed an ndk knockout mutant, which lacks both intracellular and extracellular forms of Ndk. In this study, we report the construction of deletion derivatives made from the carboxy-terminal region of Ndk. These deletion derivatives were introduced into the ndk::Cm knockout mutant and were examined for the intracellular and extracellular presence of Ndk. It was observed that the carboxy-terminal 8-amino-acid region is required for the secretion of Ndk into the extracellular region. This region has the sequence DXXX, where X is a predominantly hydrophobic residue. Such sequences represent a conserved motif in proteins secreted by the type I secretory pathway in gram-negative microorganisms. To investigate the significance of this motif in the secretion of Ndk, we constructed a fusion protein of Ndk and the blue fluorescent protein (BFP) as well as a fusion protein of mutated Ndk (whose DTEV motif has been changed to AAAA) and the BFP. The presence of extracellular Ndk was detected only in the ndk::Cm knockout mutant harboring the wild-type BFP-Ndk protein fusion. We could not detect the presence of extracellular Ndk in the ndk::Cm knockout mutant containing the mutated BFP-Ndk protein fusion. In addition, we have also used immunofluorescence microscopy to localize the wild-type and mutated BFP-Ndk proteins in the cell. The significance of these observations is discussed.
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AIM: To study the effect of losartan potassium in the treatment of mild to moderate hypertension and to compare its efficacy and adverse effect profile with enalaparil maleate. MATERIAL AND METHODS: One hundred and forty five patients with mild to moderate essential hypertension were enrolled in this randomized, double blind, controlled, parallel and multicentric study. Seventy two patients received losartan potassium 50 mg and seventy three received enalapril maleate 5 mg. RESULTS: Losartan potassium reduced the DBP to < 90 mm Hg in 59% of the patients at the end of 8 weeks compared to 45% in the enalapril maleate group. DBP was reduced by 10 or > than 10 mm Hg in 89% of the patients with losartan as compared to the baseline whereas it was 80% in the enalapril group. Percentage of side effects seen in losartan and enalapril groups were 12 and 22 respectively. CONCLUSION: Losartan potassium is an efficacious antihypertensive agent in mild to moderate hypertension. It also has fewer side effects when compared to enalapril maleate.
BACKGROUND: We sought to determine whether diagnoses established through the Banff schema for evaluation of renal allograft pathology have implications for clinical management, compared with diagnoses established using descriptive terminology. METHODS: All patients included in this study had mild to severe allograft rejection diagnosed, and, as part of a therapeutic protocol, they received OKT3 as primary anti-rejection therapy. We conducted a retrospective review of their renal allograft biopsy specimens and reclassified them, using the Banff schema, without knowledge of clinical information, laboratory data, or previous biopsy interpretation. Although there is no strict correspondence between descriptive diagnostic terminology and the criteria used in the Banff schema, for the purpose of comparisons, the following approximation was used: mild and mild to moderate rejection=Banff borderline and Banff grade 1, moderate and moderate to severe rejection=Banff grades 2A and 2B, and severe rejection=Banff grade 3. The diagnosis was considered concordant when the diagnosis by descriptive terminology and Banff grading were within the adopted approximation. RESULTS: Of 96 biopsies specimens with mild to severe allograft rejection, 10 were insufficient for diagnosis, and three had changes of chronic allograft rejection. Of the remaining 83 biopsy specimens, 34 (41%) were concordant in interpretation of rejection grades, whereas 49 (59%) were discrepant. The greatest degree of concordance was in grades 2A (66.7%, 18 of 27) and 2B (64.7% 11 of 17), and the lowest was in the borderline category (11.8%, 2 of 17). The greatest degree of discrepancy was in normal and grade 3 (100%, 3 of 3 and 2 of 2, respectively), and the lowest was in grade 2A (33.3%, 9 of 27). Although primary anti-rejection therapy with OKT3 resulted in a high reversal rate of rejection (98%), there were 5 deaths, 12 graft loses, six episodes of serious infections, and three malignancies in this group of patients during a mean follow-up period of approximately 38 months. CONCLUSIONS: Because patients with borderline changes and grades 1 and 2A rejection may be treated differently from patients with higher grades (2B and 3), the use of the Banff schema may allow for better adjustment of immunosuppressive therapy in response to specific grades of acute allograft rejection and may result in decreased complications of immunosuppressive therapy.
We have implemented a Finite Difference Thermodynamic Integration (FDTI) approach to estimate the binding free energy relative to methotrexate (MTX) of three unreported inhibitors of DHFR. The validity of the calculation methodology was first proved by evaluating the relative binding free energy difference for two well-known anticancer agents aminopterin and methotrexate. The usefulness of the method in drug design has been demonstrated by the fact that inhibitor 5, designed by us was found to bind more tightly than MTX, by as much 7.5 kcal/mole and is a worthy candidate for further pharmacological investigations.