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Biomedical subjects

R Iyer

Publications and source records attributed to R Iyer.

At least 19 recordsLinked to original sources
PubMed2006

Radiation injury: imaging findings in the chest, abdomen and pelvis after therapeutic radiation.

Radiation may be used as adjuvant or primary therapy in a variety of tumors in the chest, abdomen and pelvis. Therapeutic radiation affects not only malignant tumors but also surrounding normal tissues. The risk of injury depends on the size, number and frequency of radiation fractions, volume of irradiated tissue, duration of treatment, and method of radiation delivery. Concomitant chemotherapy can act synergistically to produce injury. Other predisposing factors include infection, prior surgery and chronic illness like hypertension, diabetes mellitus and atherosclerosis. Radiation changes vary, based on the target organ and the time from completion of therapy. While most serious complications related to radiotherapy are relatively uncommon, given the number of patients that are treated and the relatively long latency period for development of radiation changes, follow-up imaging studies frequently have findings that should be recognized as radiation related. Familiarity with the spectrum of imaging findings after radiation injury permits differentiation from other etiologies such as recurrent malignancy. The following will discuss imaging findings that may be seen during imaging surveillance in patients with malignancy affecting the chest, abdomen and pelvis.

Abdominal Neoplasms↗
PubMed2004

Controversies in the multimodality management of locally advanced esophageal cancer: evidence-based review of surgery alone and combined-modality therapy.

Most patients with esophageal cancer present with locoregional disease, and the optimal initial management is controversial. The current National Comprehensive Cancer Network (NCCN) practice guidelines support diverse treatment options for locoregional disease, including surgical resection alone, definitive chemoradiation therapy, and preoperative combined-modality (neoadjuvant/trimodality) therapy. Many cancer centers worldwide favor a neoadjuvant approach, although the evidence supporting this practice is inconsistent. A concise review of the literature is presented. The topics discussed do not necessarily reflect each author's opinions or clinical practices.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Automated lung outline reconstruction in ventilation-perfusion scans using principal component analysis techniques.

The present work addresses the development of an automated software-based system utilized in order to create an outline reconstruction of lung images from ventilation-perfusion scans for the purpose of diagnosing pulmonary embolism. The proposed diagnostic software procedure would require a standard set of digitized ventilation-perfusion scans in addition to correlated chest X-rays as key components in the identification of an ideal template match used to approximate and reconstruct the outline of the lungs. These reconstructed lung images would then be used to extract the necessary PIOPED-compliant features which would warrant a pulmonary embolism diagnosis. In order to evaluate this issue, two separate principal component analysis (PCA) algorithms were employed independently, including Eigenlungs, which was adapted from the Eigenfaces method, and an artificial neural network. The results obtained through MATLAB(TM) simulation indicated that lung outline reconstruction through the PCA approach carries significant viability.

Algorithms↗
PubMed2003

False positive Kleihauer tests and unnecessary administration of anti-D immunoglobulin.

This obstetric case shows two false negative Kleihauer tests and two persistently positive Kleihauer tests leading to unnecessary administration of anti-D immunoglobulin. A diagnosis of hereditary persistence foetal haemoglobin (HPFH) was only confirmed by access to flow cytometry making use of both anti-HbF and anti-D labels. The case highlights the importance of a high index of clinical suspicion for HPFH and the importance of access to flow cytometry estimation of minor RhD red cell populations postnatally in RhD-negative mothers.

Adult↗
PubMed2002

Orotracheal fibreoptic intubation for rapid sequence induction of anaesthesia.

We assessed whether flexible fibreoptic-guided orotracheal intubation could be rapidly and successfully achieved during a simulated rapid sequence induction in 30 anaesthetised and paralysed patients. Rapid sequence induction was simulated by applying practised cricoid pressure. Using a flexible fibreoptic laryngoscope with camera and closed circuit television, an anaesthetist experienced with the technique performed orotracheal endoscopy and intubation with a cuffed 7.0-mm Portex tracheal tube through a VBM Bronchoscope Airway. Fibreoptic intubation was successful at the first attempt in 28 patients (93%); two patients required two attempts. Mean (SD) time from removal of the facemask from the patient's face to the appearance of carbon dioxide in the expired breath after intubation was 111 (46) s (median 100 s; range 54-195 s). There were one or more difficulties in 13 patients (43%). These difficulties were largely avoidable and included problems with fibreoptic equipment, the Bronchoscope Airway, copious secretions, cricoid pressure or railroading of the tracheal tube. Flexible fibreoptic-guided orotracheal intubation may have a place in the management of failed intubation during a rapid sequence induction.

Adolescent↗
PubMed2002

Exposure to low-level chemicals and ionizing radiation: reactive oxygen species and cellular pathways.

Reactive oxygen species (ROS), which contribute to the energy landscapes in and around cells, play numerous roles in maintaining normal cell homeostasis as components of signaling pathways. Excessively high levels of ROS, on the other hand, can lead to pronounced DNA damage and a variety of cellular responses, including cell cycle arrests, senescence, apoptosis and possibly cancer. Far less is known, however, about how supra-basal levels of ROS that can be generated in response to low doses of ionizing radiation or chemicals in the environment may bring about untoward or perhaps even beneficial cellular responses. Even so, some evidence suggests that adaptive responses that have been associated with ROS-generating stimuli can have protective effects by fundamentally altering subsequent cellular dose-response profiles to otherwise detrimental stresses. Yet, even these seemingly favorable 'adaptive' effects may have longer-term untoward consequences. Other effects that have been associated with supra-basal levels of ROS, such as enhanced states of cell proliferation, potentially could have a protective function. But again, such increases in cell growth, which may be accompanied by greater than normal ROS-mediated damage to DNA, as well may ultimately favour the expansion of cells with heritable mutations. Unfortunately, the state of the art of our current understanding of how elevated but still low-level increases in ROS that may be induced by environmental stimuli presently precluded incorporation of supra-basal ROS-associated mechanisms in predictive risk assessment models, both at the population level and at the level of individualized risk assessment.

Apoptosis↗
PubMed2001

To move or not to move: measurements of prostate motion by urethrography using MRI.

PURPOSE: Urethrography is commonly used to aid in definition of the prostate apex during CT simulation for prostate cancer. If the position of the prostate were altered by the urethrogram itself, then systematic error could be introduced into the patient's treatment. Sagittal MRI scans were acquired immediately before and after a localization urethrogram to determine the extent of displacement. METHODS AND MATERIALS: Thirteen patients underwent sagittal T2-weighted fast spin echo MRI scans. Patients were scanned supine in an alpha cradle cast in the treatment position. The prostate was contoured by 3 different observers to determine the apex location on the central sagittal MRI section and the center of mass relative to an immobile bony landmark. Statistical multivariate analysis was performed to establish if there was a net displacement of the prostate (systematic error), and to determine the margin required to cover the random prostate position within a 95% confidence interval. RESULTS: There was no significant systematic motion of either the prostate nor its apex in either the anterior-posterior or superior-inferior directions. The average motion of the prostate center of mass was 0.04 +/- 0.40 cm (1 SD) and 0.01 +/- 0.33 cm in the anterior-posterior and superior-inferior direction, respectively. The corresponding figures for location of the apex were 0.05 +/- 0.30 cm and 0.01 +/- 0.33 cm, respectively. The statistical analysis revealed that a margin of 2 mm is sufficient to cover any random motion of the prostate that could occur as a result of the urethrogram 95% of the time. CONCLUSION: Urethrography during CT simulation for prostate cancer does not cause significant prostate displacement or systematic error in planning and delivering external-beam radiation.

Adenocarcinoma↗
PubMed2001

Impact of genotypic variation of Borrelia burgdorferi sensu stricto on kinetics of dissemination and severity of disease in C3H/HeJ mice.

Various genotypes of Borrelia burgdorferi sensu stricto have been previously identified among a large collection of isolates cultured from patients with Lyme disease in the United States. Furthermore, association of specific genotypes with hematogenous dissemination early in the disease course has been observed. The present study assessed kinetics of spirochete dissemination and disease severity in C3H/HeJ mice infected with two different genotypes of B. burgdorferi. Spirochete load in plasma and ear and other tissue samples of infected mice was measured by quantitative PCR, and these data were compared to those obtained by culture and histopathologic analysis. In mice infected with isolate BL206 (a type 1 strain), the peak number of spirochetes was observed in plasma between day 4 and 7, in heart and ear tissue on day 14, and in joints on day 28 postinoculation. There was a correlation between the peak number of spirochetes in plasma on day 4 or 7 and that in ear biopsy and joint specimens on day 14. By contrast, spirochete burdens in plasma of mice infected with isolate B356 (a type 3 strain) were 16- and 5-fold lower than those of BL206-infected mice on days 7 and 14 of infection, respectively. Similarly, approximately 6- and 13-fold fewer spirochetes were detected in the heart tissues of B356-infected mice compared to BL206-infected mice. Histopathologically, severe arthritis and aortitis were noted only in mice infected with isolate BL206. Spirochete dissemination and disease severity vary significantly in mice infected with distinct genotypes of B. burgdorferi, suggesting that genotypic differences in the infecting spirochetes play a key role in the pathogenesis and development of clinical disease.

Animals↗
PubMed2001

Filarial antigens impair the function of human dendritic cells during differentiation.

The antigen-specific T-cell unresponsiveness seen in lymphatic filariasis is mediated, in part, by diminished antigen-presenting cell function and is most specific for microfilariae (MF), the parasite stage found in large numbers in the peripheral circulation. We investigated the effect of MF antigen (MFAg) on dendritic cells (DC) in both their differentiation process from monocyte precursors and also after they have developed into DC. When MFAg was added to cultures of monocytes during their differentiation process to immature DC, the production of interleukin 12 (IL-12) p40, p70 protein, and IL-10 was significantly (P < 0.03) inhibited in response to Staphylococcus aureus Cowan (SAC) and SAC-gamma interferon (IFN-gamma) (60% to 80% inhibition). IL-10 was also inhibited (P = 0.04) in response to CD40 ligand-IFN-gamma. Moreover, MFAg inhibited the mRNA expression of IL-12 p40 and IL-10 as assessed by RNA protection assays. This effect was antigen specific, as another parasite antigen (soluble Toxoplasma gondii antigen) did not inhibit the production of these cytokines. This effect was also not a result of diminished cell viability nor of an alteration in surface expression of most costimulatory surface molecules, including major histocompatibility complex class I and class II. In contrast to exposure throughout the differentiation process, MFAg added to immature DC had no effect on DC cytokine expression. Although MF-differentiated DC were capable of inducing an allogeneic mixed lymphocyte reaction, they did so to a significantly lesser degree than DC without antigen exposure. These data collectively suggest that once DC are differentiated from their precursor cells, they become resistant to changes by MFAg.

Animals↗
PubMed2001

Genetics and regulation of chitobiose utilization in Borrelia burgdorferi.

Borrelia burgdorferi spends a significant proportion of its life cycle within an ixodid tick, which has a cuticle containing chitin, a polymer of N-acetylglucosamine (GlcNAc). The B. burgdorferi celA, celB, and celC genes encode products homologous to transporters for cellobiose and chitobiose (the dimer subunit of chitin) in other bacteria, which could be useful for bacterial nutrient acquisition during growth within ticks. We found that chitobiose efficiently substituted for GlcNAc during bacterial growth in culture medium. We inactivated the celB gene, which encodes the putative membrane-spanning component of the transporter, and compared growth of the mutant in various media to that of its isogenic parent. The mutant was no longer able to utilize chitobiose, while neither the mutant nor the wild type can utilize cellobiose. We propose renaming the three genes chbA, chbB, and chbC, since they probably encode a chitobiose transporter. We also found that the chbC gene was regulated in response to growth temperature and during growth in medium lacking GlcNAc.

Acetylglucosamine↗
PubMed2001

Characterization of Borrelia burgdorferi isolated from erythema migrans lesions: interrelationship of three molecular typing methods.

Genetic diversity among Borrelia burgdorferi isolates recovered from the skin of Lyme disease patients was assessed by ribosomal DNA (rDNA) spacer restriction fragment length polymorphism analysis, genomic restriction site polymorphism analysis, and plasmid content analysis. There was a significant association between the three rDNA spacer types, the six pulsed-field gel types, and plasmid content (P < 0.001). The association between distinct chromosomal and plasmid markers implies a clonal origin for each genotype.

Adult↗
PubMed2000

Molecular basis for the polyamine-ompF porin interactions: inhibitor and mutant studies.

By testing the sensitivity of Escherichia coli OmpF porin to various natural and synthetic polyamines of different lengths, charge and other molecular characteristics, we were able to identify the molecular properties required for compounds to act as inhibitors of OmpF in the nanomolar range. Inhibitors require at least two amine groups to be effective. For diamines, the optimum length of the hydrocarbon spacer was found to be of eight to ten methylene groups. Triamine molecules based on a 12-carbon motif were found to be more effective that spermidine, an eight-carbon trivalent derivative. But differences in inhibition efficiencies were also found for trivalent compounds depending on the relative position of the internal secondary amine group with respect to the terminal groups. Finally, quaternary ammonium derivatives had no effect, suggesting that the nature of the terminal amine is important for the interaction. From these observations, we deduce that inhibition efficiency in the nanomolar range requires a 12-carbon chain triamine with terminal primary amine groups and replacement of the eighth methylene by a secondary amine. The need for this type of molecular architecture suggests that inhibition is governed by interactions between specific amine groups and protein residues, and that this is not simply due to the accumulation of charges into the pore. Together with previous observations from site-directed mutagenesis studies and inspection of the crystal structure of OmpF, these results allowed us to propose three residues (D113, D121 and Y294) as putative sites of interaction between the channel and spermine. Alanine substitution at each of these three residues resulted in a loss of inhibition by spermine, while mutations of only D113 and D121 affected inhibition by spermidine. Based on these observations, we suggest a model for the molecular determinants involved in the porin-polyamine interaction.

Amino Acid Substitution↗
PubMed2000

Factors underlying the cell growth-related bystander responses to alpha particles.

Increases in cell proliferation are widely viewed as being of importance in carcinogenesis. We report that exposure of normal human lung fibroblasts to a low dose of alpha particles like those emitted by radon/radon progeny stimulates their proliferation in vitro, and this response also occurs when unirradiated cells are treated with supernatants from alpha-irradiated cells. We attribute the promitogenic response to superoxide dismutase- and catalase-inhibitable a particle-induced increases in the concentrations of transforming growth factor beta1 (TGF-beta1) in cell supernatants. TGF-beta1 at concentrations commensurate with those in the supernatants capably induces increases in intracellular reactive oxygen species (ROS) in unirradiated cells. Furthermore, the addition of supernatants from alpha-irradiated cells to unirradiated cells decreases cellular levels of TP53 and CDKN1A and increases CDC2 and proliferating cell nuclear antigen in the latter. Like the increased intracellular ROS bystander effect, this "decreased TP53/CDKN1A response" can be mimicked in otherwise untreated cells by the addition of low concentrations of TGF-beta1. Our results indicate that alpha particle-associated increases in cell growth correlate with intracellular increases in ROS along with decreases in TP53 and CDKN1A, and that these cellular responses are mechanistically coupled. As well, the proliferating cell nuclear antigen and CDC2 increases that occur along with the decreased TP53/CDKN1A bystander effect also would expectedly favor enhanced cell growth. Such processes may account for cell hyperplastic responses in the conducting airways of the lower respiratory track that occur after inhalation exposure to radon/ radon progeny, as well as, perhaps, other ROS-associated environmental stresses.

Alpha Particles↗
PubMed2000

Maximum urine concentrating ability in children with Hb SC disease: effects of hydroxyurea.

Studies in adults with Hb SC disease suggested that hydroxyurea reduced hemolysis and increased red cell hydration. Because increased hydration should diminish the polymerization tendency of Hb S we hypothesized that hydroxyurea might repair the urine concentration defect of HbSC disease. Eight Hb SC disease patients, aged 10 to 17 years, were given hydroxyurea daily. Maximal urine concentrating ability following overnight fasting and after subcutaneous arginine vasopressin (dDAVP), blood counts, and cell volumes were observed for 12-15 months. All patients had impaired urine concentrating ability prior to hydroxyurea treatment and failed to increase their ability to concentrate urine following treatment (maximum urine concentration after an overnight fast and dDAVP, 520-530 mOsm). Mean corpuscular volume (MCV) and reticulocyte MCV increased after administration of hydroxyurea, and the reticulocyte count and ratio of red cell hemoglobin to reticulocyte hemoglobin fell but there was little change in PCV. Hb F increased substantially in 2 patients but showed little change in the remaining patients. There was no evidence that hydroxyurea was associated with increased urine concentrating ability in children with Hb SC disease. These results may reflect irreversible renal medullary damage prior to beginning treatment or insufficient intensity or duration of treatment.

Adolescent↗
PubMed2000

Conservation and heterogeneity of vlsE among human and tick isolates of Borrelia burgdorferi.

The vls (variable major protein [VMP]-like sequence) locus of Borrelia burgdorferi encodes an antigenic variation system that closely resembles the VMP system of relapsing fever borreliae. To determine whether vls sequences are present consistently in low-passage, infectious isolates of B. burgdorferi, 22 blood and erythema migrans biopsy isolates from Lyme disease patients in Westchester County, New York, were examined by Southern blot and PCR analysis. Each of the strains contained a single plasmid varying in size from 21 to 38 kb that hybridized strongly with a vlsE probe based on the B. burgdorferi B31 sequence. In contrast, PCR products were obtained with only 10 of the 22 strains when primers corresponding to the 5' and 3' regions of the B31 vlsE sequence outside the variable cassette region were used. Only 2 of 16 B. burgdorferi-infected tick specimens yielded detectable PCR product. Eight of 10 strains that yielded a PCR product under these conditions were type 1 (a genotype with a high rate of dissemination), according to PCR-restriction fragment length polymorphism analysis of intergenic rDNA sequences, whereas the isolates that did not yield vlsE PCR products were either type 2 or type 3. Comparison of the sequences of cloned PCR products from the patient isolates indicated a high degree of identity to the B31 sequence, with most of the differences restricted to the hypervariable regions known to undergo sequence variation. Taken together, these results both reinforce previous evidence that vls sequences are present consistently in low-passage Lyme disease spirochetes and indicate that both highly conserved and heterogeneous subgroups exist with regard to vlsE sequences.

Amino Acid Sequence↗
PubMed2000

Radiofrequency ablation: a cure for tachyarrhythmias.

Radiofrequency (RF) ablation is a new modality of pennanently curing patients with various tachycardias using radiofrequency energy, a technique evolved in the past decade. RF ablation was performed on 913 patients with different tachyarrhythmias from April, 1994 to July, 1999. There were 491 men and 422 females aged 42 +/- 34 years (range 1 to 76 years). Supraventricular tachycardia (SVT) was present in 462 patients, accessory pathway mediated atrioventricular re-entrant tachycardia (AVRT) in 355 patients (377 accessory pathways) and idiopathic ventricular tachycardia (VT) in 96 patients. Amongst the patients with SVT, 402 had atrioventricular nodal re-entrant tachycardia (AVNRT), 22 had atrial flutter, 20 had ectopic atrial tachycardia and 18 had atrial fibrillation. RF successfully abolished the tachycardia in 400/402 patients (99.5%) with AVNRT, 330/377 (87.5%) accessory pathways in patients with AVRT, 14/22 patients (63.6%) of atrial flutter, 18/20 patients (90%) of atrial tachycardia and 79/96 patients (82.3%) with idiopathicVT. Successful AV nodal ablation with pacemaker implantation was done in 10/18 patients with chronic atrial fibrillation with fast ventricular rate and tachycardia induced cardiomyopathy. AV nodal modulation for atrial fibrillation was tried in the remaining 8 patients and was successful in 4 (4/8). The overall success rate for all arrhythmias was 93.6%, and there was no mortality. At a follow-up of 6.8 +/- 5.4 months, there was a recurrence in 34/420 patients (8%), in whom successful re-ablation was performed. One patient with AVNRT and another with a parahisian pathway developed complete heart block and were given pacemakers. One patient developed inferior wall infarction on the next day post RF. There were 4 patients who had pericardial tamponade necessitating pericardiocentesis and 2 patients developed deep vein thrombosis, which was treated conservatively. Thus RF ablation is an effective, safe and curative therapy for various arrhythmias.

Adolescent↗
PubMed1999

Hypoxic regions exist in human prostate carcinoma.

OBJECTIVES: The purpose of this study was to characterize, by use of the Eppendorf microelectrode, the extent of hypoxia (range/heterogeneity) in human prostate carcinomas. METHODS: Custom-made Eppendorf pO2 microelectrodes were used to obtain PO2 measurements from the pathologically involved side of the prostate, as well as from a region of normal muscle for comparison. Each set of measurements comprised approximately 100 separate readings of pO2, for a total of 2145 individual measurements. Twelve patients were studied, 7 of whom underwent brachytherapy, 3 a radical prostatectomy, and 2 a cystoprostatectomy. The pO2 measurements were obtained in the operating room, using sterile technique, under spinal anesthesia for the brachytherapy group patients and under general anesthesia for the surgery group patients. The Eppendorf histograms were recorded and described by the median pO2, mean pO2, and percentage of measurements less than 5 mm Hg and less than 10 mm Hg. RESULTS: Because of differences in patient characteristics and the anesthesia employed, control measurements were obtained from nearby normal muscle as an internal control in all but 2 patients. This internal comparison showed that the oxygen measurements from the pathologically involved portion of the prostate were significantly lower than those from normal muscle. Similarly, higher pO2 readings were obtained from the pathologically normal prostates (in the patients with bladder cancer) than from the prostates of patients with prostate carcinoma. Increasing levels of hypoxia were observed with increasing clinical stage. Significant predictors of oxygenation include the type of tissue (pathologically involved prostate versus normal muscle or normal prostate), clinical stage, and type of anesthesia. CONCLUSIONS: This report, to our knowledge, represents the first study to obtain in vivo electrode measurements of oxygen levels in patients with prostate cancer and suggests that hypoxic regions exist in human prostate carcinoma. More patients will be accrued to this prospective study to correlate the oxygenation status of prostate carcinoma with known prognostic factors and treatment outcome.

Adult↗