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Biomedical subjects

N Subramanian

Publications and source records attributed to N Subramanian.

At least 19 recordsLinked to original sources
PubMed2003

Use of high-frequency jet ventilation in neonates with hypoxemia refractory to high-frequency oscillatory ventilation.

OBJECTIVE: To describe the response to high-frequency jet ventilation in infants with hypoxemic respiratory failure unresponsive to high-frequency oscillatory ventilation. METHODS: This was a retrospective analysis of chart records on demographics, ventilator settings, blood gas analysis and calculated oxygenation index prior to and during the first 7 days of high-frequency jet ventilation in ten consecutive infants. RESULTS: Before the initiation of high-frequency jet ventilation, the ventilatory mean airway pressure (MAP; cmH2O), fraction of inspired oxygen (FiO2) and oxygenation index on high-frequency oscillatory ventilation were 14.3 +/- 1.3, 0.97 +/- 0.02 and 29 +/- 5, respectively. Three hours after the initiation of high-frequency jet ventilation, the oxygenation index improved to 18 +/- 4 (p < 0.001) and the improvement was sustained during the study period. By 6 h of high-frequency jet ventilation, the FiO2 decreased to 0.62 +/- 0.09 (p < 0.01) and, by 1-3 h of ventilation, the MAP decreased to 10.9 +/- 1.3 (p < 0.01). The improvement in FiO2 persisted for 7 days while, although the MAP remained lower throughout the study, the improvement in MAP failed to reach statistical significance after 72 h. No significant changes in pH, pCO2, or pO2 before or during high-frequency jet ventilation were noted. CONCLUSION: High-frequency jet ventilation improves hypoxemic respiratory failure unresponsive to high-frequency oscillatory ventilation in infants. These findings suggest that not all high-frequency ventilatory devices yield the same clinical results.

Airway Resistance↗
PubMed2002

Rare cause for short stature--Kallmann's syndrome--a case report.

Kallmann's syndrome is a neuroendocrine disorder, characterized by hypogonadotropic hypogonadism with hyposmia. We report a 27 year old male who presented with short stature and pain in the lumbar region. On detailed evaluation he had growth retardation, features of hypothalamic hypogonadism as evidenced by endocrimological tests and anosmia since birth. He had co-existent caries spine T10,T11 causing pain in the lumbar region-MRI brain showed normal olfactory pathway while the response to nasal stimulants was markedly attenuated. We present this case for its very care occurrence in the eastern part of the world and the typical feature being normal MRI brain with functional defect of the olfactory pathway.

Adolescent↗
PubMed2001

Dual neurokinin NK(1)/NK(2) antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides.

Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK(2) affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK(2) receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK(1)/NK(2) antagonist.

Animals↗
PubMed2001

Extended radioligand binding profile of iloperidone: a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist for the management of psychotic disorders.

Iloperidone is a novel psychotropic compound currently undergoing Phase III trials. Its affinity for human dopamine and 5-HT(2A) and 5-HT(2C) receptors has been reported previously. This report presents the affinity of iloperidone for a largely extended number of human neurotransmitter receptors. In a few instances human receptors were not available and receptor studies were performed on tissues from laboratory animals. The present data, supplemented with those of, indicate that iloperidone displays high affinity (K(I) < 10 nM) for norepinephrine alpha(1)-adrenoceptors, dopamine D(3) and serotonin 5-HT(2A) receptors. Intermediate affinity (10-100 nM) was found for norepinephrine alpha(2C)-adrenoceptors, dopamine D(2A) and D(4) receptors and serotonin 5-HT(1A), 5-HT(1B), 5-HT(2C) and 5-HT(6) receptors. The affinity for all other receptors was below 100 nM, including norepinephrine alpha(2A), alpha(2B), beta(1), and beta(2), muscarine M(1)-M(5), histamine H(1), dopamine D(1) and D(5), CCK(A) and CCK(B), 5-HT(7), dopamine and norepinephrine transporters. Thus, iloperidone targets a selective set of dopamine, norepinephrine and serotonin receptor subtypes. The affinity for this particular set of receptors indicates that iloperidone has the potential to be a broad spectrum antipsychotic, with efficacy against positive, negative, depressive and cognitive symptoms of schizophrenia, and a low propensity to induce side effects.

Animals↗
PubMed2001

Cyclosporin A-induced gingival overgrowth is unrelated to allograft function in renal transplant recipients.

BACKGROUND: Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of Cyclosporine-A (CsA). AIM: This study statistically modeled the medical and dental risk factors for the development of GH following CsA administration to determine whether renal function post-transplantation was related to the incidence or extent of GH in 236 consecutive renal transplant patients. METHOD: All patients were at least 6 months post-transplant and medicated with both traditional oral CsA (n=220 individuals) and the new microemulsion form CsA-Me (n=229 individuals). Patients had either received CsA alone (n=45 individuals) or cyclosporine and nifedipine (n=191 individuals). Gingival overgrowth was assessed and computerized data, available for all patients included; pre- and post-transplant medical history and post-transplant renal function, i.e., serum creatinine levels, documented rejection episodes and glomerular filtration rates (GFR). These data together with CsA serum levels and last-recorded dose of CsA, CsA-Me, nifedipine, azathioprine and prednisolone, were analysed by multivariate regression analysis using SPSS. RESULTS: The extent and severity of hyperplasia was significantly correlated with the dosage and serum level of CsA at 3, 6 and 12 months post-transplantation; last recorded dosage, however (p<0.0001), was the most accurate predictor of hyperplasia. Gingivitis (p<0.0001) and plaque (p<0.002), were associated with hyperplasia. Duration of renal replacement therapy, age at transplantation, post-transplant interval serum creatinine levels and documented rejection episodes were unrelated with the extent and severity of GH. Of all the renal variables only the correlation of GFR with last recorded doses of CsA and CsA-Me, approached significance; this was then considered for inclusion in the model. CONCLUSION: In a multiple regression analysis including GFR, however, only last CsA (and CsA-Me) doses and gingivitis score were selected for inclusion in the final model. These data demonstrate that inter-patient variation in the extent and severity of GH and renal function post-transplantation are unrelated and are mediated independently.

Adolescent↗
PubMed2001

Treatment of painful osteoarthritis of the knee with hyaluronic acid. Results of a multicenter Asian study.

Hyaluronic acid is a component of synovial fluid, in osteoarthritis (OA) and shows a change of property of hyaluronic acid especially its viscoelasticity causing degradation of the cartilage. Injection of hyaluronic acid into OA of the knee (Hyalgan 2 ml/wk for 4 doses) in international multicentres gave dramatic responses: decreased pain, increased mobility of the joint after 49 days of injections compared to a placebo (2 ml of normal saline) p<0.01.

Aged↗
PubMed2000

N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide: an orally active neurokinin NK1/NK2 antagonist.

The stereoselective synthesis of N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl+ ++)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (4) and its NK1 and NK2 receptor binding properties are reported. In addition the potent inhibitory effects in vivo on sar9-SP- and beta-Ala-NKA-induced airway bronchoconstriction in guinea pigs are demonstrated.

Administration, Oral↗
PubMed1999

Role of polyphenol oxidase and peroxidase in the generation of black tea theaflavins.

It has been reported earlier that when macerated tea leaf is fermented at lower pH, the resultant black tea contains increased levels of theaflavin, an important quality marker in black tea. In an attempt to investigate the biochemistry and chemistry underlying this observation, in vitro oxidation experiments using polyphenol oxidase (PPO) from fresh tea leaves, horseradish peroxidase (POD), and tea catechins, precursors for theaflavins, were carried out. In vitro oxidation experiments using crude tea PPO resulted in higher content of theaflavins at pH 4.5 in comparison with pH 5.5, the normal pH of the macerated tea leaf. When purified PPO was used in the in vitro system, surprisingly a reversal of this trend was observed, with more theaflavins being formed at the higher pH. A combination of pure tea PPO and POD led to an observation similar to that with the crude enzyme preparation, suggesting a possible role for POD in the formation or degradation of theaflavin. POD was observed to oxidize theaflavins in the presence of H(2)O(2), leading to the formation of thearubigin, another black tea pigment. This paper demonstrates that tea PPO, while oxidizing catechins, generates H(2)O(2). The amount of H(2)O(2) produced is greater at pH 5.5, the optimum pH for PPO activity, than at pH 4.5. Hence, an observed increase of theaflavins in black teas fermented at pH 4.5 appears to be due to lower turnover of formed theaflavins into thearubigins.

Biflavonoids↗
PubMed1999

Oral combination chemotherapy in the management of AIDS-related lymphoproliferative malignancies.

An oral combination chemotherapy regimen initially developed for AIDS-related non-Hodgkin's lymphoma includes lomustine (CCNU), etoposide, cyclophosphamide, and procarbazine. This regimen takes advantage of oral administration, the in vitro synergy of these drugs and their first-line efficacy in lymphoma, and the ability of lomustine and procarbazine to cross the blood-brain barrier. This regimen was used to treat 38 patients with AIDS-related non-Hodgkin's lymphoma. The overall objective response rate was 66% (34% complete response rate) with a 5% CNS relapse rate, and a median survival duration of 7.0 months. One-third of the patients survived for 1 year, 11% for 2 years, and half of the patients survived free from progression of their lymphoma. On the basis of these results, this oral regimen was modified and administered to 5 patients with AIDS-related primary CNS lymphoma as part of a sequential combined-modality chemotherapy and radiation regimen. Rapid progression of CNS disease was observed in this group of patients, with a median survival duration of 1.0 month. The identical regimen was administered to 7 patients with AIDS-related Hodgkin's disease: we observed a 71% partial remission rate and a median survival duration of 7.0 months. Myelosuppression remains the most significant clinical toxicity. Our results with this oral regimen appear comparable to those of standard intravenous combination chemotherapy regimens in patients with AIDS-related non-Hodgkin's lymphoma.

Administration, Oral↗
PubMed1998

Selective dorsal rhizotomy as a treatment option for children with spastic cerebral palsy.

Cerebral palsy is the most common motor disorder originating in childhood and spasticity is the most frequent manifestation. The treatment strategies to reduce spasticity and thereby ameliorate the attendant gait abnormalities have included physiotherapy, orthoses, antispastic medications, orthopaedic surgery and neurosurgery. Of these, the neurosurgical procedure known as selective dorsal rhizotomy has gained widespread exposure, and indeed acceptance, over the past two decades, despite there being some controversy as to its efficacy. In this paper we review: cerebral palsy, including classification and treatment; selective dorsal rhizotomy, including historical background, patient selection, operative procedure, clinical outcome and complications; and gait analysis studies, including temporal-distance parameters, joint kinematics, normalisation for growth, and long-term follow-up. Both the short-term (1 year) and long-term (10 years) evidence has demonstrated that selective dorsal rhizotomy not only reduces spasticity but it also provides lasting functional benefits as measured by improved range of motion during gait. Rhizotomy is not a panacea for children with spastic diplegia but it is an important treatment option for the clinician to consider. Copyright 1998 Elsevier Science B.V.

Journal Article↗
PubMed1998

Gait before and 10 years after rhizotomy in children with cerebral palsy spasticity.

OBJECT: Selective dorsal rhizotomy is a neurosurgical procedure performed for the relief of spasticity in children with cerebral palsy, but its long-term functional efficacy is still unknown. The authors sought to address this issue by means of an objective, prospective study in which quantitative gait analysis was used. METHODS: Eleven children with spastic diplegia (mean age at initial surgery 7.8 years) were evaluated preoperatively in 1985 and then at 1, 3, and at least 10 years after surgery. For comparison, 12 age-matched healthy individuals were also studied. Retroreflective targets were placed over the hip, knee, and ankle joints, and each individual's gait was videotaped. The video data were subsequently entered into a computer for extraction and analysis of the gait parameters. An analysis of variance yielded a significant time effect (p < 0.05), and post hoc comparisons revealed differences before and after surgery and with respect to the healthy volunteers. The knee and hip ranges of motion (59 degrees and 44 degrees, respectively, for healthy volunteers) were significantly restricted in children with spastic diplegia prior to surgery (41 degrees and 41 degrees, respectively), but were within normal limits after 10 years (52 degrees and 45 degrees, respectively). The knee and hip midrange values (31 degrees and 3 degrees, respectively, for healthy volunteers), indicative of posture, were significantly elevated preoperatively (42 degrees and 15 degrees) and increased sharply at 1 year (56 degrees and 18 degrees), but by 10 years they had decreased to within normal limits (36 degrees and 9 degrees). Step length and velocity improved postoperatively but were not within the normal range after 10 years. Ten years after surgery these patients not only had increased ranges of motion, but also used that movement at approximately a normal midrange point. CONCLUSIONS: Selective dorsal rhizotomy is an effective method for alleviating spasticity. Furthermore, the authors provide evidence to show that lasting functional benefits, as measured by improved gait, can also be obtained.

Adolescent↗
PubMed1997

A monoclonal antibody to avidin dissociates quaternary structure and curtails biotin binding to avidin and streptavidin.

An anti-avidin mAb, viz., H12G4, is shown to release bound biotin in a dose-dependent manner from holoavidin and holostreptavidin and inhibit the binding of ligand to the two apoproteins. The release of biotin by this mAb is accompanied by quenching of ligand-induced enhanced fluorescence of the FITC-avidin conjugate. In terms of mechanism of release of bound biotin, we demonstrate that on binding to the Fab fragment of the mAb, the native tetrameric holoavidin undergoes dissociation progressively with time to monomers with no bound biotin associated with the latter. Based on the immunoreactivity associated with defined overlapping fragments of avidin obtained by chemical cleavage, the epitope recognized by mAb H12G4 has been localized to residues 58-96 of the primary sequence. By pepscan method of epitope mapping, this mAb is shown to identify a minimal core sequence of 87RNGK90 in avidin and a corresponding sequence of 84RNAH87 in streptavidin.

Amino Acid Sequence↗
PubMed1997

Mapping the common antigenic determinants in avidin and streptavidin.

An epitope scan analysis of the whole sequence of avidin and core streptavidin using polyclonal antibodies to these two antigens reveal the presence of multiple common epitopes in both the proteins. These antigenic determinants consist mostly of either identical or similar residues. The antibody recognition sites in both antigens are shown to be localized to homologous regions.

Amino Acid Sequence↗
PubMed1996

Spontaneous, extra-dural haematoma causing spinal cord compression.

We describe a patient with acute compression of the spinal cord by a spontaneous extra-dural haematoma. This rare condition is often misdiagnosed. We believe that an urgent MRI scan is indicated in patients presenting with progressive neurological deficit following spinal trauma. This allows the diagnosis of extra-dural haematoma to be made rapidly and for prompt decompression of the cord.

Aged↗
PubMed1996

Antigenic similarities among biotin-binding proteins.

Using polyclonal antisera to avidin, streptavidin, and biotin binding protein-II (BBP-II), the extents of immunological cross-reactivities shared by this family of biotin-binders were investigated. In Western blot analysis, varying degrees of cross-reactivities among these proteins depending on the antisera used was observed. Using liquid phase radioimmunoassay, evidence for the existence of common antigenic determinants shared by all the biotin-binders was deduced. Antibodies directed against such epitopes inhibited the binding of [3H]biotin to as well as displace the bound ligand from all the three high affinity biotin-binders in a dose dependent manner.

Animals↗