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Biomedical subjects

R Chandra

Publications and source records attributed to R Chandra.

At least 19 recordsLinked to original sources
PubMed2000

Strong field behavior of the NMR signal from magnetically heterogeneous tissues.

A theory for the behavior of the nuclear magnetic resonance (NMR) signal obtained from magnetically heterogeneous tissues is developed for the limit of a strong external magnetic field. If BO is the magnitude of the external magnetic field, it is found that a free-induction signal decays in a time scaling as 1/Bo, a single-spin echo signal decays in a time scaling as 1/Bo(2/3), and a multiple-spin echo signal decays in a time scaling as 1/Bo(2). Moreover, it is shown that the form of the signal decay for a multiple-spin echo sequence may deviate significantly from an exponential. Numerical results for a model consisting of randomly distributed magnetic spheres are used to confirm the theory. In addition, good agreement is demonstrated between the theory and experimental measurements obtained with particle suspensions. The validity and application of the theory to biological tissues are discussed.

Animals↗
PubMed2000

MR imaging of microvasculature.

An imaging technique is proposed in which the contrast is correlated to the morphology of capillaries and other small blood vessels. The technique is based on measurements of the relaxation rates 1/T(2) and 1/T*(2) before and after the injection of a contrast agent. An image is then formed by mapping the quantity Q identical with delta R(2)/(delta R*(2))(2/3), where delta R(2) and delta R*(2) are the changes in the relaxation rates due to the contrast agent. If the contrast agent concentration is sufficiently high, it is shown that Q is given approximately by a simple analytic formula that involves only intrinsic properties of the vascular network and the rate of diffusion. In particular, Q is sensitive to the histologic vessel density. Theoretical predictions for Q are shown to be consistent with experimental data obtained with a rat glioma model and normal cerebral cortex. The imaging technique may be useful in characterizing tumor angiogenesis. Magn Reson Med 44:224-230, 2000.

Animals↗
PubMed2000

The hydropericardium syndrome and inclusion body hepatitis in domestic fowl.

Hydropericardium syndrome, an emerging disease of poultry, has recently been detected in some countries of Asia and America, particularly in broiler birds aged 3-6 weeks. The disease is characterized by its sudden occurrence with high mortality of up to 80% in broilers and low mortality of under 10% in layers, associated with hydropericardium. Its course is of 7-15 days under natural conditions. The causative agent is probably fowl adenovirus serotype 4, belonging to group I aviadenovirus genus of the family adenoviridae, which can be cultivated in primary cell cultures of chicken kidney and embryo liver cells. The transmission of disease occurs laterally by the oral-faecal route. The livers of affected birds show necrotic foci, and basophilic intranuclear inclusion bodies fill the entire enlarged nucleus of some of the hepatocytes. The disease can be diagnosed from its gross lesions, histopathological changes in the liver and by serological tests, such as agar gel diffusion, counter immunoelectrophoresis, indirect haemagglutination and ELISA. It has been brought under control by inactivated liver organ vaccines (0.25 ml/bird) or inactivated cell culture vaccines (10(3.5) LD50/bird) given by the subcutaneous route at 10-15 days of age. The vaccine is effective in the face of an outbreak and significantly reduces the mortality.

Adenoviridae Infections↗
PubMed2000

NMR relaxation in tissues with weak magnetic inhomogeneities.

A theory is presented for describing the effect on the transverse NMR relaxation rate of microscopic spatial inhomogeneities in the static magnetic field. The theory applies when the inhomogeneities are weak in magnitude and the nuclear spins diffuse a significant distance in comparison with a length scale characterizing the inhomogeneities. It is shown that the relaxation rate is determined by a temporal correlation function and depends quadratically on the magnitude of the inhomogeneities. For the case of unrestricted diffusion, a simple algebraic approximation for the temporal correlation function is derived. The theory is illustrated by applying it to a model of randomly distributed magnetized spheres. The theory is also used to fit experimental data for the dependence of the relaxation rate on the interecho time for a Carr-Purcell-Meiboom-Gill pulse sequence. The experimental systems considered are in vitro red blood cell suspensions and samples of human gray matter and rat liver. Magn Reson Med 44:144-156, 2000.

Animals↗
PubMed1999

Deletion analysis of the adenomatous polyposis coli and PTCH gene loci in patients with sporadic and nevoid basal cell carcinoma syndrome-associated medulloblastoma.

BACKGROUND: Medulloblastomas can occur sporadically or may be associated with hereditary tumor syndromes including familial adenomatous polyposis (FAP) and nevoid basal cell carcinoma syndrome (NBCCS). METHODS: The authors performed a retrospective analysis for allelic deletion of the adenomatous polyposis coli (APC) and PTCH gene loci using paraffin embedded medulloblastoma specimens from patients who were admitted to Children's National Medical Center in Washington, DC, between 1982 and 1997. Thirty-five cases from which tumor and normal tissue could be procured were analyzed. Two of the analyzed cases had a positive family and personal history for NBCCS; in both cases the histology of the medulloblastoma revealed a desmoplastic phenotype. Thirty-three cases were not known to be associated with hereditary disease; 2 of those cases revealed desmoplastic and 31 cases revealed nondesmoplastic "classic" medulloblastoma histology. RESULTS: Although medulloblastoma tumorigenesis has been associated strongly with FAP associated with APC germline mutation, none of the 22 informative sporadic cases revealed loss of heterozygosity of the APC gene locus. PTCH gene deletion was detected in the tumors of both patients with NBCCS. In contrast, only 1 of 33 sporadic medulloblastomas revealed PTCH gene deletion. The sporadic case with PTCH gene deletion did not demonstrate the desmoplastic phenotype. CONCLUSIONS: In conjunction with previous studies, the data from the current study confirm that allelic deletion occurs in NBCCS-associated medulloblastomas, consistent with the role of PTCH as a tumor suppressor gene. However, in sporadic medulloblastomas, allelic deletion of PTCH is an infrequent event. Morphologic examination in conjunction with genetic analysis of PTCH gene deletion in medulloblastoma tissue may prove to be a quick and efficient test with which to screen for NBCCS in patients with medulloblastomas. Although medulloblastoma is a component of Turcot syndrome with demonstrated APC mutations, APC gene deletions appear to be absent or very uncommon in patients with sporadic and NBCCS-associated medulloblastomas.

Adenomatous Polyposis Coli↗
PubMed1999

beta-Adrenergic action on wild-type and KPQ mutant human cardiac Na+ channels: shift in gating but no change in Ca2+:Na+ selectivity.

OBJECTIVE: Prior studies of the modulation of the Na+ current by sympathetic stimulation have yielded controversial results. Separation of the Na+ and Ca2+ currents poses a problem in myocyte preparations. The gating of cloned Na+ channels is different in oocytes compared with mammalian expression systems. We have examined the sympathetic modulation of the alpha-subunit of the wild-type human cardiac Na+ channel (hH1) and the long QT-associated mutant, delta KPQ, expressed in human embryonic kidney cells. METHODS: Stable cell lines of hH1 and delta KPQ were established in human embryonic kidney cells. Whole-cell and single-channel currents were measured with the patch-clamp technique. Sympathetic stimulation was effected by exposure to isoproterenol or 8-bromo-cAMP. Na+ channel activation and inactivation were determined using standard voltage clamp protocols. Ca2+:Na+ permeability ratio was determined under bi-ionic conditions. RESULTS: We observed a qualitatively different effect of sympathetic stimulation on the cardiac Na+ current from that reported in frog oocytes: activation and inactivation kinetics were shifted to more negative potentials. This shift was similar for both hH1 and delta KPQ. [delta V0.5 for inactivation: 8.3 +/- 1.7 mV, p < 0.001 (hH1); 6.8 +/- 0.9 mV, p < 0.001 (delta KPQ)]. Increased rate of closed-state inactivation contributed to the shifting of the inactivation-voltage relationship. Open-state inactivation was not affected as mean open times were unchanged. Reversal potential measurement in hH1 suggested a low Ca2+:Na+ permeability ratio of 0.017, uninfluenced by sympathetic stimulation. In delta KPQ, the size of the persistent relative to the peak current was increased with 8-bromo-cAMP from 3.0 +/- 0.7% to 4.3 +/- 0.6% (p = 0.056). CONCLUSIONS: Sympathetic stimulation exerts multiple effects on the gating of hH1. Similar effects are also seen in delta KPQ which may increase arrhythmia susceptibility in long QT syndrome by modifying the Na+ channel contribution to the action potential.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Retinoic acid in association with tin-metalloporphyrins influences heme metabolism in vivo in rats.

In the current study we report the perturbation of key enzymes of the heme metabolic pathway, i.e. delta-amino levulinic acid synthase, heme oxygenase and biliverdin reductase, in vivo by administration of retinoic acid (RA) and retinoic acid in association with tin-metalloporphyrins, viz., tin-protoporphyrin (SnPP) and tin-mesoporphyrin (SnMP) in the liver, spleen, heart and lung of rats. RA at a dosing regimen of 50,000 I.U. stimulated splenic ALA-S activity, whereas co-administration of tin-metalloporphyrins with RA antagonised the RA mediated induction of ALA-S. In the other tissues viz., liver, heart and lung our results showed a diminution of ALA-S activity on RA administration, the level of repression was further attenuated when tin-metalloporphyrins were co-administered with RA. This marked suppression of ALA-S brought forth by concurrent administration of RA and tin-metalloporphyrins is suggestive of the beneficial effect of this formulation in acute attacks of porphyria, similar to heme. Furthermore, our results emphasize that the combined dosing of RA with tin-metalloporphyrins leads to a substantial decline in bilirubin levels due to a profound inhibition of HMOX in the probed tissues. The features of the combined action of RA and tin-metalloporphyrins in vivo lead to a substantial suppression of formation of the potentially toxic metabolite bilirubin, and the enhancement of disposal of the untransformed substrate (heme) of the enzyme that is inhibited. These results define some of the characteristics of a therapeutically useful formulation and represent a new therapeutic approach for the amelioration and management of hyperbilirubinemia.

5-Aminolevulinate Synthetase↗
PubMed1999

Reasons for outpatient referrals from generalists to specialists.

OBJECTIVE: To determine the relative importance of medical and nonmedical factors influencing generalists' decisions to refer, and of the factors that might avert unnecessary referrals. DESIGN: Prospective survey of all referrals from generalists to subspecialists over a 5-month period. SETTING: University hospital outpatient clinics. PARTICIPANTS: Fifty-seven staff physicians in general internal medicine, family medicine, dermatology, orthopedics, gastroenterology, and rheumatology. MEASUREMENTS AND MAIN RESULTS: For each referral, the generalist rated a number of medical and nonmedical reasons for referral, as well as factors that may have helped avert the referral; the specialist seeing the patient then rated the appropriateness, timeliness, and complexity of the referral. Both physicians rated the potential avoidability of the referral by telephone consultation. Generalists were influenced by a combination of both medical and nonmedical reasons for 76% of the referrals, by only medical reasons in 20%, and by only nonmedical reasons in 3%. In 33% of all referrals, generalists felt that training in simple procedures or communication with a generalist or specialist colleague would have allowed them to avoid referral. Specialists felt that the vast majority of referrals were timely (as opposed to premature or delayed) and of average complexity. Although specialists rated most referrals as appropriate, 30% were rated as possibly appropriate or inappropriate. Generalists and specialists failed to agree on the avoidability of 34% of referrals. CONCLUSIONS: Generalists made most referrals for a combination of medical and nonmedical reasons, and many referrals were considered avoidable. Increasing procedural training for generalists and enhancing informal channels of communication between generalists and subspecialists might result in more appropriate referrals at lower cost.

Ambulatory Care↗
PubMed1999

The lateral pectoral flap.

The lateral pectoral flap is a new pedicled flap based on the superficial thoracic artery which arises from the subscapular artery and courses along the lateral border of pectoralis major. The flap consists of skin, subcutaneous tissue and the underlying pectoral epimysium. It has been used successfully to resurface contralateral soft tissue defects over the fingers, thumb and dorsum of the hand in eight cases. The advantages of this flap are that it provides reliable soft tissue cover to the hand, which can be kept in an elevated position resting comfortably on the contralateral pectoral region with the forearm and arm aligned conveniently in the cross-chest position. It does not interfere with clothing and dressing the lower part of the body in contrast to the groin, hypogastric or lower abdominal flaps, and it allows early ambulation. Primary closure of the donor site in the majority of cases is an added benefit.

Adolescent↗
PubMed1999

Adjunctive oral corticosteroids reduce renal scarring: the piglet model of reflux and acute experimental pyelonephritis.

PURPOSE: We investigate the efficacy of antibiotics combined with corticosteroid in diminishing post-pyelonephritic renal scarring compared to standard antibiotic therapy. MATERIALS AND METHODS: Bilateral vesicoureteral reflux was surgically created in 36 piglets (72 kidneys). A week later each bladder was inoculated by percutaneous injection with a standardized broth culture of Escherichia coli and molten paraffin. 99mTechnetium dimercapto-succinic acid (DMSA) scintigraphy was performed 3 days after introduction of urinary infection to detect the presence of acute pyelonephritis. Acute pyelonephritic lesions seen on DMSA scans were graded according to the percentage of renal zone involvement as grade 1--less than 33%, grade 2--33 to 66% and grade 3--greater than 66% involved. When pyelonephritis was present, piglets were randomized to receive either standard antibiotics or antibiotics and 2 mg./kg. prednisolone daily. 99mTechnetium-DMSA scintigraphy was repeated 2 months after completion of therapy, and the kidneys were harvested for gross and histopathological examination. Each kidney was divided into upper, middle and lower zones for correlation of pathological and imaging findings. Severity of renal scarring was then assessed using histopathological confirmation of gross anatomical findings as grade 1--less than 1, grade 2-1 to 2 and grade 3-greater than 2 cm. RESULTS: Acute pyelonephritis was induced in 136 of 216 renal zones. The sites of renal scarring corresponded anatomically to sites of acute pyelonephritis in all but 5 cases. Overall, the prevalence of post-pyelonephritic scarring was 56.6% (77 of 136) of renal zones. The severity of scarring in both groups correlated with the severity of the initial pyelonephritic lesion. Of the 31 zones that formed grade 3 renal scars the distribution of grades 1, 2 and 3 acute pyelonephritis on the initial DMSA scan was 3, 26 and 71%, respectively. Grade 3 acute pyelonephritis was more likely to result in severe (grade 3) renal scars in the control compared to the steroid treated group (59 versus 31%). Overall, acute pyelonephritis completely resolved in 40% of controls and 51% of steroid treated animals. However, only 9% of control animals with grade 3 acute pyelonephritis demonstrated complete resolution, as opposed to 28% of those receiving steroids. CONCLUSIONS: The risk of renal scarring is greatest after severe acute pyelonephritis involving greater than 66% of a renal zone. Adjunctive oral prednisolone appears to be effective in diminishing renal scarring in severely affected kidneys. In kidneys with mild and moderate acute pyelonephritis antibiotics alone appear to be equally effective in preventing scarring.

Acute Disease↗
PubMed1999

Purification and characterization of Klebsiella pneumoniae cytotoxins.

Isolation, purification and characterization of 3 new cytotoxins of a K. pneumoniae strain isolated from ready to eat pork sausage are reported. Purification process involved extraction of cytotoxins with polymyxin B sulphate, salt precipitation, gel filtration and anion exchange chromatography. Klebsiella cytotoxin (KCT) I, a glycoprotein of about 65 kDa was verocytotoxic, enterotoxic and dermonerotic. KCT II was erythemogenic, verocytotoxic and enterotoxic protein of co 55 kDa, while KCT III was about double in MW (110 kDa) hadverocytotoxicity but neither enterotoxicity nor dermatotoxicity. KCT I and II caused granulation, conglomeration, shrinkage, detachment and lysis of MDBK and Vero cells, while KCT III induced enlargement, vacuolation, granulation, multinucleolation and syncytia formation in exposed cells. All the three cytotoxins induced specific neutralizing antibodies and cytotoxins were detectable in nanogram quantities with enzyme-linked immunosorbant assay using homologous antibodies. None of the anticytotoxin cross-reacted with either heterologous Klebsiella cytotoxins or with verocytotoxic preparations of Shigella dysenteriae.

Animals↗
PubMed1999

Detection, prevalence, purification and characterization of lecithinase of Klebsiella pneumoniae.

Lecithinase activity in Klebsiella is a rare trait as out of 208 strains of Klebsiella belonging to 3 species, viz. K. pneumoniae (168), K. planticola (29) and K. oxytoca (11), only 4 strains of K. pneumoniae produced lecithinase positive colonies on egg-yolk-agar. Although cell lysates of 16 K. pneumoniae yielded positive results for lecithinase assay on egg-yolk-agar, 19 strains were detected positive for lecithinase with ELISA using anti-lecithinase serum. Release of up to 52.12% cell-bound lecithinase could be achieved with polymyxin-B treatment at 100 micrograms/ml concentration. Purified lecithinase was determined to be a high molecular weight (70 kDa), crystalizable, anionic (pI, 3.5) protein. It possessed cytolytic, haemolytic and dermonecrotic activities but did not induce fluid accumulation in rabbit ileal loop or infant mouse guts. It was inactivated by boiling, trypsin and chymotrypsin treatment and alkaline pH. Serologically, it was related to lecithinase of Aeromonas caviae and phospholipase-C of Salmonella.

Animals↗
PubMed1998

Nasal sill augmentation in adult incomplete cleft lip nose deformity using superiorly based turn over orbicularis oris muscle flap: an anatomic approach.

Adult incomplete cleft lip nose deformity is not uncommon in India. Poverty, ignorance, and parental neglect account for its late presentation. Besides the classical features of cleft lip nose deformity, the constant findings observed in this patient population have been a widened and depressed nasal sill. This is attributable to the sparse, hypoplastic, and abnormally orientated orbicularis oris muscle in the region of the sill. Failure to restore the nasal sill symmetry by suitably augmenting the sill frequently leads to unsatisfactory and asymmetric results. However, in the literature, satisfactory restoration of the nasal sill has not been given the importance it deserves while performing cleft lip rhinoplasty. We present a method of augmenting the depressed nasal sill in cases of adult incomplete nose deformity using a superiorly based orbicularis oris muscle flap, which is harvested from the soft tissues between the apex of the cleft and the nostril sill. Following de-epithelialization of the overlying skin, the exposed muscle is raised as a superiorly based flap after dissecting it from the underlying mucosa. It is folded, turned over, and tucked into the nasal sill base and anchored to the anterior nasal spine to give the desired augmentation. Satisfactory results have been obtained in 18 cases of nasal deformity associated with incomplete cleft lip. In our opinion, this technique offers a simple and effective method of augmenting the depressed sill by utilizing locally available tissues and without the need for procuring autologous tissue from distant sites.

Adolescent↗
PubMed1998

Multiple effects of KPQ deletion mutation on gating of human cardiac Na+ channels expressed in mammalian cells.

Several aspects of the effect of the KPQ deletion mutation on Na+ channel gating remain unresolved. We have analyzed the kinetics of the early and late currents by recording whole cell and single-channel currents in a human embryonic kidney (HEK) cell line (HEK293) expressing wild-type and KPQ deletion mutation in cardiac Na+ channels. The rate of inactivation increased three- to fivefold between -40 and -80 mV in the mutant channel. The rate of recovery from inactivation was increased twofold. Two modes of gating accounted for the late current: 1) isolated brief openings with open times that were weakly voltage dependent and the same as the initial transient and 2) bursts of opening with highly voltage-dependent prolonged open times. Latency to first opening was accelerated, suggesting an acceleration of the rate of activation. The delta KPQ mutation has multiple effects on activation and inactivation. The aggregate effects may account for the increased susceptibility to arrhythmias.

Animals↗
PubMed1998

Transplacental transfer of measles antibody in Delhi.

OBJECTIVE: To find out the patterns of and the factors, if any, affecting the transplacental transfer of measles antibody. DESIGN: Comparison of measles antibody titres in mothers with titres in cord blood samples. METHODS: Maternal and cord blood samples from 174 full-term pregnant women of middle socio-economic status were tested for hemagglutination inhibition (HI) antibody against measles in Delhi during October 1993 to January 1995. None of the mothers had been immunized against measles. RESULTS: Antibody were undetectable in both maternal and cord samples in only 4 (2.3%) pairs. Mean maternal titre was found to be 2.94 Log2. Transplacental concentration and dilution were respectively observed in 34% and 26% of the samples. Cord titres were more often higher than the maternal values only if the maternal values were low. Overall, cord/maternal ratio of mean titre (Log2) was found to be 1.06. Although the age of the mother and parity had had no significant bearing on the transplacental transfer of measles antibody, cord titres were significantly more often higher than the maternal values as the birth weight increased (Chi-square for linear trend = 5.4; p = 0.02). CONCLUSIONS: The study failed to show appreciable concentration of measles antibodies across the placenta.

Adolescent↗