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Biomedical subjects

V Chandrasekaran

Publications and source records attributed to V Chandrasekaran.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cerebrospinal fluid contains biologically active bone morphogenetic protein-7.

Bone morphogenetic proteins (BMPs) regulate the development and function of many types of neurons. However, little is known of the actual concentrations of BMPs in the various parts of the brain. In this study, we considered the possibility that BMPs might be present in cerebrospinal fluid (CSF). Western blot analysis of normal adult bovine CSF revealed the presence of dimeric and monomeric forms of BMP-7, and the concentration of this molecule was found to be approximately 12 ng/ml in a radioimmunoassay. Since BMP-7 is known to induce dendritic growth in rat sympathetic neurons, this was used as a bioassay to examine the biological activity of the BMP-7 present in CSF. Addition of normal bovine CSF to cultures of sympathetic neurons produced a dose-dependent increase in dendritic growth and the magnitude of this response approximated that obtained with maximally effective concentrations of exogenous BMP-7. Moreover, CSF-induced dendritic growth was inhibited by follistatin, a protein that can sequester BMPs, and by either of two monoclonal antibodies that react with BMP-7. These results show that, unlike most other neurotrophic factors, BMP-7 is a constituent of normal CSF and is present at concentrations sufficient to elicit a near maximal biological response.

Activins↗
PubMed2001

Serial evaluation of serum neopterin in HIV seronegative patients treated for tuberculosis.

OBJECTIVE: To delineate the course of serum neopterin (s-neo) concentrations in patients with pulmonary tuberculosis who are on anti-tuberculosis therapy. DESIGN: S-neo concentrations were measured by high performance liquid chromatography (HPLC) in 39 patients treated for pulmonary tuberculosis at pretreatment, at one month and at end of treatment. It was also measured in 11 relapse cases and their matched controls at the above time points and at the time of relapse. The results were correlated with bacteriological and radiological findings. RESULTS: All patients had elevated levels of s-neo at pretreatment which had declined at 1 month and were near normal at the end of treatment. The decline was more significant in patients with moderate lesions, suggesting that immune activation is maximum in this group of patients. The mean decrease was 37% at one month and 66% at the end of treatment. The corresponding decreases were 11% and 56% in patients with limited lesions and 11% and 45% in those with extensive lesions. It continued to fall after completion of therapy in patients who did not relapse, whereas an increase after completion of therapy was associated with bacteriologically proven relapse. CONCLUSIONS: The measurement of s-neo concentration could be of help in evaluating response to therapy. This study provides a rational basis for the association between s-neo concentration and relapse.

Adult↗
PubMed2000

Pulmonary embolectomy in a child.

We report the case of a 14-year-old boy treated successfully by pulmonary embolectomy for massive pulmonary embolism, 18 days after bilateral hip surgery. He has a family history of pulmonary embolism and an inherited antithrombin deficiency. His diagnosis was confirmed by spiral computed tomography scan. We believe that pulmonary embolectomy has a role in selected cases in children.

Adolescent↗
PubMed2000

Pericardiectomy using an oscillating saw.

We describe the use of a microoscillating saw on the heart to remove calcific pericardium. This microoscillating saw proved indispensable to achieve a safe pericardiectomy in a 55-year-old woman with thick, severe idiopathic calcific constrictive pericarditis.

Calcinosis↗
PubMed2000

Retinoic acid regulates the morphological development of sympathetic neurons.

Interactions between all-trans-retinoic acid (RA) and bone morphogenetic proteins (BMPs) affect the expression of neurotrophin receptors in sympathetic neurons (Kobayashi et al., 1998). In this study, we examined the possibility that similar interactions might regulate the morphological development of these neurons. Under control conditions, embryonic rat sympathetic neurons formed axons but not dendrites; cells exposed to RA had a similar appearance. Profuse dendritic growth was observed upon exposure to BMP-7, and this was reduced by approximately 70% by RA. This inhibitory effect of RA was mediated primarily by retinoic acid receptors (RARs) and it exhibited substantial specificity because it was not associated with changes in either axonal elongation or cell survival. Moreover, mRNAs for enzymes required for synthesis of RA were expressed in the sympathetic neurons and retinoid activity was released from superior cervical ganglia. These observations suggest that retinoids may function as endogenous morphogens and regulate neural cell shape and polarity in developing sympathetic ganglia.

Alcohol Oxidoreductases↗
PubMed1999

Leukemia inhibitory factor and ciliary neurotrophic factor cause dendritic retraction in cultured rat sympathetic neurons.

Dendritic retraction occurs in many regions of the developing brain and also after neural injury. However, the molecules that regulate this important regressive process remain largely unknown. Our data indicate that leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) cause sympathetic neurons to retract their dendrites in vitro, ultimately leading to an approximately 80% reduction in the size of the arbor. The dendritic retraction induced by LIF exhibited substantial specificity because it was not accompanied by changes in cell number, in the rate of axonal growth, or in the expression of axonal cytoskeletal elements. An antibody to gp130 blocked the effects of LIF and CNTF, and both cytokines induced phosphorylation and nuclear translocation of stat3. Moreover, addition of soluble interleukin-6 (IL-6) receptor to the medium endowed IL-6 with the ability to cause dendritic regression. These data indicate that ligands activating the gp130 pathway have the ability to profoundly alter neuronal cell shape and polarity by selectively causing the retraction of dendrites.

Animals↗
PubMed1999

Thrombotic thrombocytopenia purpura: a single institution experience.

TTP is a disease with protean manifestations leading to errors in diagnosis. Critical reevaluation of a single observer's experience at LIJMC over a 7-year period is compared to that in published literature. We retrospectively analyzed presentation, clinical course, treatment, and outcome of 15 patients treated for TTP between 1990 and 1997 by one of the authors (V.C.). Minimal diagnostic criteria for TTP were unexplained moderate to severe thrombocytopenia (platelet count <100,000/cmm), microangiopathic hemolytic anemia, with or without low grade fever, and no other attributable etiologies. Neurologic and/or renal dysfunction constituted severe grade. Age range was 5-86 years, with one patient age 5, the youngest yet to date reported with classic TTP. Female to male ratio was 2:1. Overall survival rate was 87%; 40% of patients experienced immediate relapse within the first 4 weeks of presentation; and predisposing causes for immediate relapse appear to be intercurrent infections and severity of presentation. There was a 40% incidence of late relapses of TTP. Two patients with an unusually high number of late recurrences (6 and 16) were HCV-Ab positive and the possible role of persistent HCV infection in recurrent TTP was explored.

Adolescent↗
PubMed1999

Primary aortic valve replacement with allografts over twenty-five years: valve-related and procedure-related determinants of outcome.

OBJECTIVES: Allografts offer many advantages over prosthetic valves, but allograft durability varies considerably. METHODS: From 1969 through 1993, 618 patients aged 15 to 84 years underwent their first aortic valve replacement with an aortic allograft. Concomitant surgery included aortic root tailoring (n = 58), replacement or tailoring of the ascending aorta (n = 56), and coronary artery bypass grafting (n = 87). Allograft implantation was done by means of a "freehand" subcoronary technique (n = 551) or total root replacement (n = 67). The allografts were antibiotic sterilized (n = 479), cryopreserved (n = 12), or viable (unprocessed, harvested from brain-dead multiorgan donors or heart transplant recipients, n = 127). Maximum follow-up was 27.1 years. RESULTS: Thirty-day mortality was 5.0%, and crude survival was 67% and 35% at 10 and 20 years. Ten- and 20-year rates of freedom from complications were as follows: endocarditis, 93% and 89%; primary tissue failure, 62% and 18%; and redo aortic valve replacement, 81% and 35%. Multivariable Cox analyses identified several valve- and procedure-related determinants: rising allograft donor age and antibiotic-sterilized allograft for mortality; donor more than 10 years older than patient for endocarditis; rising donor age minus patient age, rising implantation time (from harvest to aortic valve replacement), and donor age more than 65 years for tissue failure; and rising donor age minus patient age, young patient age, rising implantation time, and subcoronary implantation preceded by aortic root tailoring for redo aortic valve replacement. Estimated 10- and 20-year rates of freedom from tissue failure for a 70-year-old patient with a viable valve from a 30-year-old donor and no other risk factors were 91% and 64%; the figures were 71% and 20% if the donor age was 65 years. The rates of freedom from tissue failure for a 30-year-old patient with a 30-year-old donor were 82% and 39%; the figures were 49% and 3% with a 65-year-old donor. Beneficial influences of a viable valve were largely covered by short harvest time (no delay for allografts from brain dead organ donors or heart transplant recipients) and short implantation time. CONCLUSIONS: Primary allograft aortic valve replacement can give acceptable results for up to 25 years. The late results can be improved by the use of a viable allograft, by matching patient and donor age, and by more liberal use of free root replacement with re-implantation of the coronary arteries rather than tailoring the root to accommodate a subcoronary implantation.

Aged↗
PubMed1999

Bioavailability of rifampicin, isoniazid and pyrazinamide in a triple drug formulation: comparison of plasma and urine kinetics.

SETTING: The present study assesses bioavailability indices for rifampicin, isoniazid and pyrazinamide when administered to healthy volunteers separately or in a fixed triple-drug formulation, Rifater 125 SCT. OBJECTIVE: To compare the pharmacokinetics of rifampicin, isoniazid and pyrazinamide based on their blood concentrations up to 12 hours with the proportions of the doses of the drugs and their metabolites excreted in urine up to 12 hours, and to assess the bioavailability indices for the free and fixed triple drug formulations. DESIGN: An open cross-over study was conducted in 18 healthy volunteers with normal hepatic and renal functions to whom the drug combinations were administered in free and fixed dose formulations a week apart, to the same subject. RESULTS: Concentrations of the three drugs/metabolites were assessed in blood and urine. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both the free and the new fixed triple drug formulation. CONCLUSION: Human bioavailability studies provide direct straightforward information, particularly when studying compounds such as rifampicin and other major anti-tuberculosis drugs. The results of the present study indicate that the pharmacokinetic properties of rifampicin, isoniazid and pyrazinamide as assessed after individual and combined administration do not change when combined in a single pharmaceutical preparation. The bioavailability indices calculated based on plasma concentrations and urinary levels for all three drugs compared well.

Adult↗
PubMed1998

Late results of a valve-preserving operation in patients with aneurysms of the ascending aorta and root.

OBJECTIVES: There is still no agreement about the best method of dealing with malfunction of the aortic valve caused by aneurysm or dissection of the aortic root. The experience, rationale, and development of a valve-preserving technique introduced and used since 1979 is described. METHODS: During this period 158 patients (78% of all patients undergoing resection of aneurysm of the ascending aorta) were operated on using this technique. Their ages ranged from 2 to 72 years (mean 46.6 years). Of the patients 107 were male and 51 were female. A total of 68 patients had skeletal manifestations of Marfan's syndrome. The original disease was chronic aneurysm of the ascending aorta or root in 92 (58.2%), chronic dissection in 17 (10.8%), and acute dissection in 49 (31%) patients. One hundred eleven additional procedures were performed in 84 patients. In all there were five early deaths (4.6% +/- 2%) in the 109 patients with chronic aneurysm and one death in the 103 patients operated on electively (0.97% +/- 0.9%). Actuarial survival for patients operated on for chronic aneurysm was 93.3%, 88.0%, 79.0%, and 57.9% at 1, 5, 10, and 15 years and 96.8%, 91.2%, 82.0%, and 60.0% for those operated on electively. Actuarial survival for patients operated on for acute dissection was 72.8%, 63.4%, and 53.3% at 1, 5, and 10 years. The probability of needing reoperation was 3.0% +/- 2%, 11% +/- 0.5%, and 11% +/- 0.5% at 1, 5, and 10 years. There were no instances of infective endocarditis or thromboembolic complications except in two patients operated on early in the series who had cusp extension. No anticoagulants were used. Echocardiography showed reduction in left ventricular end-systolic and end-diastolic dimensions, which was maintained. At the end of follow-up trivial or no aortic regurgitation was demonstrated in 63.6%, mild to moderate in 33.3%, and severe in 3%. CONCLUSIONS: Valve-sparing operations are possible in a large proportion of patients with aneurysms of the ascending aorta and the medium and long-term results are encouraging.

Adolescent↗
PubMed1998

Bioluminescence assay of adenosine triphosphate in drug susceptibility testing of Mycobacterium tuberculosis.

Twenty three clinical isolates M. tuberculosis and the reference strain, M. tuberculosis H37Rv were tested for their susceptibility to trifluoperazine (TFP) by the standard broth dilution method and the bioluminescence assay. The results showed that in 15 of the 23 isolates, the minimal inhibitory concentration (MIC) was identical in both the methods and in the remaining 8 isolates the difference in the MIC values between the methods, was less than two fold and was not significant. The findings suggest that the measurement of adenosine triphosphate (ATP) by bioluminescence assay can be employed as an alternative method for the rapid screening of clinical isolates for their susceptibility to anti-mycobacterial agents.

Adenosine Triphosphate↗
PubMed1996

Disappearance of antibodies to Cromer blood group system antigens during mid pregnancy.

The Cromer blood group system consists of 7 high incidence and 3 low incidence antigens that are carried on the complement regulatory glycoprotein called decay-accelerating factor (DAF; CD55). Despite laboratory results that would predict clinical significance, antibodies with specificities in the Cromer blood group system have not been reported to cause hemolytic disease of the newborn. It is possible that strong expression of DAF on the apical surface of antigen-positive fetally derived placental trophoblasts may absorb maternal antibodies that are directed to antigens in the Cromer blood group system. We studied two cases where strongly reactive anti-Cra and anti-Dra became undetectable during second and third trimesters of pregnancies.

Blood Group Antigens↗
PubMed1995

Association of recurrent candidal vaginitis with inheritance of Lewis blood group antigens.

A subset of women with candidal vulvovaginitis have no known risk factors for recurrent episodes. Although there are reports of an association of blood group antigens with various infections, no such association has been described with candidal vulvovaginitis. The ABO, P1, and Lewis group phenotypes of 35 women with recurrent vulvovaginitis but without other chronic infections were determined. These were compared with those of a control group of 40 women without a history of candidal vulvovaginitis. The distribution of ABO blood types and P blood group phenotype did not differ from those in controls. However, vulvovaginitis patients were more likely than controls to be classified as Lea-b- (chi 2 = 6.4, 1 df, P = .011). Women without known predisposing factors may have a genetic predisposition to recurrent vulvovaginitis, as evidenced by a higher frequency of Lea-b- phenotype profiles compared with controls.

ABO Blood-Group System↗
PubMed1993

Bacteriological investigations for short-course chemotherapy under the tuberculosis programme in two districts of India.

To examine the bacteriological profile and the prevalence of drug resistance among patients attending the health facilities where the District Tuberculosis Programme (DTP) was in operation with short-course chemotherapy (SCC) regimens, sputum specimens were collected on admission and the end of treatment in North Arcot district and Pondicherry region. In North Arcot district, rifampicin, isoniazid and pyrazinamide were given twice weekly for the first 2 months followed by rifampicin and isoniazid twice a week for the next 4 months under fully supervised administration. In Pondicherry, rifampicin, isoniazid and pyrazinamide were given daily for the first 2 months followed by rifampicin and isoniazid twice weekly for the next 4 months. Of the patients who had received 80% or more of the drugs, 80% from North Arcot and 92% from Pondicherry were rendered culture-negative for Mycobacterium tuberculosis at the end of treatment. Even among patients with initially resistant bacilli, a high proportion had a favourable response. Before start of treatment, of the 2779 patients from North Arcot, 25% had resistance to one or more drugs including 2% with resistance to rifampicin. In Pondicherry, 13% of the patients had initial resistance to one or more drugs. Initial resistance to rifampicin was observed in 0.9%. None of the initially drug-sensitive patients had acquired resistance to rifampicin at the end of treatment.

Adolescent↗
PubMed1992

Widespread occurrence of multiple drug-resistant Salmonella typhi in India.

Sixteen multiple drug resistant strains of Salmonella typhi belonging to Vi-phage types E1 (14) and O (2) and isolated in Southeast India in 1991 were characterized. All strains were resistant to chloramphenicol and the majority to trimethoprim and ampicillin. In all strains these resistances were encoded by plasmids of the H1 incompatibility group with molecular weights ranging from 110 to 120 megadaltons. Physicians in European countries should be aware that treatment may fail if patients with typhoid fever who have recently returned from the Indian sub-continent are given first-line treatment with chloramphenicol, trimethoprim or ampicillin. With the possible exception of young children, ciprofloxacin is currently the best choice for treatment of such patients.

Ampicillin Resistance↗