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Biomedical subjects

S K Reddy

Publications and source records attributed to S K Reddy.

At least 19 recordsLinked to original sources

The contralateral slip. An avoidable complication and indication for prophylactic pinning in slipped upper femoral epiphysis.

Between July 1994 and June 2004, 60 patients with 76 slipped upper femoral epiphyses were managed within the adult trauma service of three hospitals. Treatment was by a single cannulated screw. Of these cases, 53 were unilateral, in 17 of which uncomplicated prophylactic fixation of the contralateral hip was performed. Of the other 36 cases, nine presented with a subsequent slip despite ongoing out-patient care. The subsequent slip was unpredictable in timing and unrelated to the age at the initial slip. It was more often unstable and in one case avascular necrosis developed. The overall rate of avascular necrosis, although in accordance with the literature, was 60% in acute unstable slips with a slip angle greater than 40 degrees. In our experience, prophylactic fixation was safer than continued observation of the contralateral hip.

Acute Disease↗

Eukaryotic-like adenylyl cyclases in Mycobacterium tuberculosis H37Rv: cloning and characterization.

Screening the Mycobacterium tuberculosis H37Rv genomic library for complementation of catabolic defect for cAMP-dependent expression of maltose operon produced the adenylyl cyclase gene (Mtb cya, (1997)) annotated later as Rv1625c (Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S. V., Eiglmeier, K., Gas, S., Barry, C. E., III, et al. (1998) Nature 393, 537-544). The deduced amino acid (aa) sequence (443 aa) encoded by Mtb cya contains a single hydrophobic domain of six transmembrane helices (152 aa) in the amino-terminal half of the protein. Flanking this domain are an arginine-rich (17%) amino-terminal cytoplasmic tail (46 aa) and a carboxyl-terminal cytoplasmic domain (245 aa) with extensive homology to the catalytic core of eukaryotic adenylyl cyclases. Site-directed mutagenesis of Arg(43) and Arg(44) to alanine/glycine showed a loss of adenylyl cyclase activity, whereas mutagenesis to lysine restored the activity. Hence it is proposed that the formation of the catalytic site in Mtb adenylyl cyclase requires an interaction between Arg(43) and Arg(44) residues in the distal cytoplasmic tail and the carboxyl-terminal cytoplasmic domain. Mtb adenylyl cyclase activity at the physiological concentration of ATP (1 mm) was 475 nmol of cAMP/min/mg of membrane protein in the presence of Mn(2+) but only 10 nmol of cAMP/min/mg of membrane protein in the presence of Mg(2+). The physiological significance of the activation of Mtb adenylyl cyclase by Mn(2+) is discussed in view of the presence of manganese transporter protein in mycobacteria and macrophages wherein mycobacteria reside.

Adenosine Triphosphate↗

Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system.

Ethanol consumption and cigarette smoking are common in societies worldwide and have been identified as injurious to human health. This study was undertaken to examine the interactive effects of chronic ethanol and nicotine consumption on the antioxidant defense system in different tissues of rat. Male Fisher-344 rats were divided into four groups of five animals each and treated for 6.5 weeks as follows: (1) Control rats were administered normal saline orally; (2) ethanol (20% [wt./vol.]) was given orally at a dose of 2 g/kg; (3) nicotine was administered subcutaneously at a dose of 0.1 mg/kg; and (4) a combination of ethanol plus nicotine was administered by the route and at the dose described above. The animals were killed 20 h after the last treatment, and liver, lung, kidney, and testes were isolated and analyzed. Chronic ingestion of ethanol resulted in a significant depletion of glutathione (GSH) content in liver, lung, and testes, whereas chronic administration of nicotine significantly depleted GSH content in liver and testes. The combination of ethanol plus nicotine resulted in a significant depletion of GSH content in liver, lung, and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased superoxide dismutase (SOD) activity in liver and decreased SOD activity in kidney. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly decreased catalase (CAT) activity in liver and increased CAT activity in kidney and testes. Chronic ingestion of ethanol resulted in a significant decrease in glutathione peroxidase (GSH-Px) activity in liver and kidney, whereas a combination of ethanol plus nicotine increased GSH-Px activity in liver and decreased GSH-Px activity in kidney and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased lipid peroxidation, respectively, in liver. It is suggested that prolonged exposure to ethanol and nicotine produce similar, and in some cases additive, oxidative tissue injuries in rat.

Animals↗

The utility of urgent colonoscopy in the evaluation of acute lower gastrointestinal tract bleeding: a 2-year experience from a single center.

OBJECTIVE: Urgent colonoscopy is often recommended to evaluate acute rectal bleeding. However, it may not identify a source because of blood in the lumen or inadequate preparation. Our aim was to determine the utility of urgent colonoscopy as the initial test for acute rectal bleeding. METHODS: This was a retrospective chart review of all patients discharged in 1997 and 1998 with an International Classification of Diseases, 9th Revision, code for hematochezia or rectal bleeding. RESULTS: We identified 514 charts but excluded 424 because of inaccurate coding. In the 90 with confirmed acute rectal bleeding, colonoscopy was the initial test in 39; age, sex, and race distributions were similar to those who did not have colonoscopy. A definite source of bleeding was seen at colonoscopy in only three patients, a probable source in 26, and no source in 10. Therapeutic intervention in four patients with a definite or probable source was successful in three. The commonest reasons for not performing urgent colonoscopy were bleeding from presumed hemorrhoids or bleeding that was clinically insignificant. Spontaneous resolution of bleeding and length of hospital stay were not affected by urgent colonoscopy. Five patients had surgery for unrelated reasons. In-hospital mortality was 2% and was unrelated to bleeding. CONCLUSION: Urgent colonoscopy as the initial investigation in acute lower GI tract bleeding probably does not alter the outcome in most cases. Identification of a definite bleeding source leading to successful therapeutic intervention is rare. Spontaneous resolution is frequent, length of hospital stay is similar, and clinical outcome is excellent regardless of whether or not urgent colonoscopy is performed.

Acute Disease↗

Breakthrough pain in cancer patients: new therapeutic approaches to an old challenge.

Breakthrough pain is a well recognized but ill-defined phenomenon that occurs commonly in the presence of otherwise stable, persistent pain. It is defined now as a "transient pain episode that occurs, or breaks through from the otherwise stable background pain." Breakthrough pain is usually associated with moderate to severe pain and may form a predictor of poor response to treatment with routine pharmacotherapy. Breakthrough pain is also associated with functional impairment and psychological distress. The assessment and treatment should be multidimensional. Although primary therapies such as chemotherapy, radiation treatment, and surgical options are explored, the mainstay of treatment is pharmacotherapy. Nonpharmacologic methods, such as orthotic devices and joint stabilizations along with behavioral methods, should be explored. Anesthetic and neurosurgical procedures are performed on a limited number of patients based on the prognosis, intractable nature of pain, and favorable risk/benefit ratio. Newer oral transmucosal fentanyl offers a favorable pharmacokinetic and pharmacodynamic profile and ease of administration.

Analgesics↗

Oxygen consumption and respiration following two yoga relaxation techniques.

The present study was conducted to evaluate a statement in ancient yoga texts that suggests that a combination of both "calming" and "stimulating" measures may be especially helpful in reaching a state of mental equilibrium. Two yoga practices, one combining "calming and stimulating" measures (cyclic meditation) and the other, a "calming" technique (shavasan), were compared. The oxygen consumption, breath rate, and breath volume of 40 male volunteers (group mean +/- SD, 27.0 +/- 5.7 years) were assessed before and after sessions of cyclic meditation (CM) and before and after sessions of shavasan (SH). The 2 sessions (CM, SH) were 1 day apart. Cyclic meditation includes the practice of yoga postures interspersed with periods of supine relaxation. During SH the subject lies in a supine position throughout the practice. There was a significant decrease in the amount of oxygen consumed and in breath rate and an increase in breath volume after both types of sessions (2-factor ANOVA, paired t test). However, the magnitude of change on all 3 measures was greater after CM: (1) Oxygen consumption decreased 32.1% after CM compared with 10.1% after SH; (2) breath rate decreased 18.0% after CM and 15.2% after SH; and (3) breath volume increased 28.8% after CM and 15.9% after SH. These results support the idea that a combination of yoga postures interspersed with relaxation reduces arousal more than relaxation alone does.

Adult↗

Effect of yoga training on maze learning.

The performance in a maze learning task was assessed in adults of either sex (n = 31) before and after 30 days of yoga training and in an age and gender matched control group of subjects who did not receive training in yoga. Subjects were blind folded and used the dominant hand to trace the path in a wooden pencil maze. At each assessment, subjects were given 5 trials, without a gap between them. Performance was based on the time taken to complete the maze and the number of blind alleys taken. The time and error scores of Trial 1 were significantly less after yoga (two-factor ANOVA, Tukey test). Repeating trials significantly decreased time scores at Trial 5 versus Trial 1, for both groups on Day 1 and for the control group on Day 30. Hence the yoga group showed improved performance in maze tracing at retest 30 days later, which may be related to this group being faster learners and also the effect of yoga itself. Yoga training did not influence maze learning, based on the performance in 5 repeat trials.

Adult↗

Identification of profilin and src homology 3 domains as binding partners for Drosophila enabled.

Drosophila Enabled (Ena) was first identified as a genetic suppressor of mutations in the Abelson tyrosine kinase and subsequently was shown to be a member of the Ena/vasodilator-stimulated phosphoprotein family of proteins. All members of this family have a conserved domain organization, bind the focal adhesion protein zyxin, and localize to focal adhesions and stress fibers. Members of this family are thought to be involved in the regulation of cytoskeleton dynamics. The Ena protein sequence has multiple poly-(L-proline) residues with similarity to both profilin and src homology 3 binding sites. Here, we show that Ena can bind directly to the Drosophila homolog of profilin, chickadee. Furthermore, Ena and profilin were colocalized in spreading cultured cells. We report that the proline-rich region of Ena is responsible for this interaction as well as for mediating binding to the src homology 3 domain of the Abelson tyrosine kinase. These data support the hypothesis that Ena provides a regulated link between signal transduction and cytoskeleton assembly in the developing Drosophila embryo.

Animals↗

Pain and loss of function in head and neck cancer survivors.

Head and neck cancers are relatively uncommon malignancies and the characteristics of pain and functional impairments in survivors are not well studied. To characterize the incidence, location, severity, types and causes of pain; associated functional impairments, and pain management methods, the medical charts of 40 consecutive outpatients with biopsy-proven head and neck cancers were reviewed. Pain was severe in 52% (N = 21), and was located near sites of tumor origin. Pain was caused by tumor recurrence in 35% (N = 14), treatment sequelae in 30% (N = 12), multiple etiologies in 25% (N = 10), and unrelated causes in 10% (N = 4). Pains were mixed nociceptive and neuropathic pain in 37.5% (N = 15), nociceptive pain in 32.5% (N = 13), myofascial in 13.0% (N = 6), neuropathic in 7.5% (N = 3); and other mixed types in 7.5% (N = 3). Despite the high prevalence of dysphagia (82%), 60% used orally administered opioid-nonopioid analgesics. Physical disfigurement (87.5%; N = 35), dysphagia (62.5%, N = 25), and jaw dysfunction (40.0%; N = 16) were the most frequent physical impairments. Multiple regression analysis showed that the presence of skull base or mandibular bone involvement had significant influence on the severity of pain (P = 0.03, adjusted R2 0.25) We conclude that pain in head and neck cancer can be chronic, severe, and persistent despite completion of oncologic treatment.

Adult↗

Dose response of ethanol ingestion on antioxidant defense system in rat brain subcellular fractions.

This study investigated the response of the antioxidant defense system in brain subcellular fractions after oral graded doses of ethanol to rat. Four groups of male Fischer-344 rats were orally administered saline, ethanol 2 g, 4 g, and 6 g/kg, respectively, and sacrificed 1 hour post treatment. Brain cytosol, synaptosomes, microsomes and mitochondria were separated by density gradient differential centrifugation and assayed for antioxidant system. A significant and dose-dependent-decrease in superoxide dismutase (SOD) activity was observed in all brain subcellular fractions. Catalase (CAT) activity was significantly decreased in brain mitochondria (67% and 80% of control) at higher doses of ethanol; whereas, CAT activity was significantly increased in cytosol, synaptosomes and microsomes. Glutathione peroxidase (GSH-Px) activity was significantly increased in all brain subcellular fractions except in cytosol at higher dose of ethanol. Malondialdehyde (MDA) content was significantly increased in all brain subcellular fractions showing dose response of ethanol-induced oxidative stress. The increase in MDA levels in the brain synaptosomes and microsomes were higher at 6 g dose of ethanol (155% and 163% of control) when compared to mitochondria and cytosol. Glutathione (GSH) levels were significantly increased in brain cytosol and microsomes at higher dose of ethanol (164% and 159% of control); whereas, the GSH concentration was significantly decreased in brain synaptosomes and mitochondria. The antioxidant enzyme (AOE) activity ratios (GSH-Px/SOD and GSH-Px + CAT/SOD) were dose dependently increased in all brain subcellular fractions, particularly in synaptosomes. The GSH/GSSG ratio was dose dependently increased in brain microsomes. The perturbations in the antioxidant defense system and enhanced lipid peroxidation following graded doses of ethanol ingestion indicate a dose-dependent-oxidative 2133stress response in brain subcellular compartments of rats.

Animals↗

Mutations in Drosophila enabled and rescue by human vasodilator-stimulated phosphoprotein (VASP) indicate important functional roles for Ena/VASP homology domain 1 (EVH1) and EVH2 domains.

Drosophila Enabled (Ena) was initially identified as a dominant genetic suppressor of mutations in the Abelson tyrosine kinase and, more recently, as a member of the Ena/human vasodilator-stimulated phosphoprotein (VASP) family of proteins. We have used genetic, biochemical, and cell biological approaches to demonstrate the functional relationship between Ena and human VASP. In addition, we have defined the roles of Ena domains identified as essential for its activity in vivo. We have demonstrated that VASP rescues the embryonic lethality associated with loss of Ena function in Drosophila and have shown that Ena, like VASP, is associated with actin filaments and focal adhesions when expressed in cultured cells. To define sequences that are central to Ena function, we have characterized the molecular lesions present in two lethal ena mutant alleles that affected the Ena/VASP homology domain 1 (EVH1) and EVH2. A missense mutation that resulted in an amino acid substitution in the EVH1 domain eliminated in vitro binding of Ena to the cytoskeletal protein zyxin, a previously reported binding partner of VASP. A nonsense mutation that resulted in a C-terminally truncated Ena protein lacking the EVH2 domain failed to form multimeric complexes and exhibited reduced binding to zyxin and the Abelson Src homology 3 domain. Our analysis demonstrates that Ena and VASP are functionally homologous and defines the conserved EVH1 and EVH2 domains as central to the physiological activity of Ena.

Amino Acid Sequence↗

Neural blockade for abdominopelvic pain of oncologic origin.

Neural blockade, like other accepted treatments for persistent pain, is not a panacea. Careful assessment is required to elicit the need for complementary interventions, including pharmacological management and psychobehavioral and rehabilitative approaches, combined with attention to the palliation of other symptoms. Celiac and superior hypogastric plexus blocks are well-accepted, effective, and minimally hazardous means for providing palliation of visceral abdominopelvic pain. Although they require radiological imaging, they are relatively undemanding of the experienced anesthesiologist pain specialist and do not deplete patients' limited resources and energy. Because of their uniquely favorable risk:benefit ratio, these procedures should be considered early in the course of treating patients with abdominopelvic pain that is expected to persist.

Abdominal Pain↗

Nitric oxide inducing factor as a measure of antigen and mitogen-specific T cell responses in chickens.

We describe here an assay to measure responses of T cells to in vitro stimulation with antigens and a T cell mitogen (ConA). Spleen cells from chickens immunized with live viruses and an inactivated antigen produced macrophage activating factors (MAF) in response to in vitro stimulation with homologous antigens. The production of MAF, quantitated by the induction of NO in a retrovirus transformed macrophage cell line, HD11 (Beug et al., 1979, Cell 18, 375) was antigen-specific and correlated well with T cell proliferation. Further studies showed that production of MAF was abrogated by cyclosporin A, anti-CD4 and anti-CD8 monoclonal antibodies. These data suggested that production of MAF required T cell activation and can be used as measure of antigen and mitogen-specific T cell responses in chickens.

Animals↗

Protective efficacy of a recombinant herpesvirus of turkeys as an in ovo vaccine against Newcastle and Marek's diseases in specific-pathogen-free chickens.

We investigated the potential of a herpesvirus of turkey (HVT)-based recombinant virus (rHVT) as an in ovo vaccine to protect specific-pathogen-free chickens against Newcastle disease (ND) and Marek's disease (MD). The rHVT, designed to express fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins of the lentogenic Hitchner B1 strain of ND virus (NDV), as well as glycoproteins A and B of the GA strain of serotype 1 MD virus (MDV) was efficacious in protecting chickens against ND and MD. No adverse effects on hatchability or the survival of chickens were observed following in ovo vaccination with rHVT. A single administration at embryonation day 18 (ED18) or at hatch protected chickens against challenge-exposures with virulent MDV strain RB-1B and velogenic NDV strain GB-Texas (NDV-GB-TX). Vaccinated chickens developed antibodies against both viruses as detected by serological tests, namely, hemagglutination inhibition, virus neutralization and western immunoblotting for NDV, and immunofluorescence and radioimmunoprecipitation assays for MDV. PCR analysis showed that in ovo vaccination with rHVT resulted in a persistent infection leading to systemic immunity against ND for up to 8 weeks of age, the longest period of time tested in this study. However, virus isolation tests indicated that rHVT-vaccinated chickens were only partially protected from the replication of NDV-GB-TX in the trachea. The results of the study indicate that rHVT is safe for both ED18 and posthatch vaccination for ND and MD, and because the vaccine persists, it may induce longer lasting immunity than conventional live NDV vaccines.

Animals↗

Antigen-specific lymphoproliferative responses to tetanus toxoid: a means for the evaluation of Marek's disease virus-induced immunosuppression in chickens.

Antigen-specific lymphoproliferative responses were examined in chickens following immunization with tetanus toxoid (Ttx). The immune competence of chickens was assessed by mitogen assay utilizing phytohemagglutinin (PHA)-stimulation and Ttx-specific antigen proliferation assay (Ttx-APA). Immune spleen cells but not peripheral blood leucocytes demonstrated specific proliferation following stimulation in vitro in a Ttx-APA. In this study, we examined firstly the effects of Marek's disease (MD)-associated immunosuppression on specific immune responses. The humoral and cell-mediated immune responses were monitored by enzyme-linked immunosorbent assay (ELISA) and Ttx-APA, respectively. Secondly, we examined if vaccination against MD using a conventional herpesvirus of turkeys (HVT) vaccine and two recombinant HVT (rHVT) vaccines would affect the development of Ttx-specific immune responses. The rHVT vaccines used in this study included two constructs: one expressing both Newcastle disease virus (NDV) and MD virus (MDV) genes (HVT/NDV/MDV), and another expressing only MDV genes (HVT/MDV). The mitogenic responses of spleen cells of the vaccinated chickens were inconsistent allowing no definitive conclusions about vaccinal immunosuppression. The results of the Ttx-APA indicated that Ttx-specific lymphoproliferative responses provide a meaningful measure of immunosuppression. The MDV-induced immunosuppression resulted in the inhibition of Ttx-specific lymphoproliferation in vitro. Both HVT and rHVT vaccines were not immunosuppressive as indicated by the development of normal Ttx-specific lymphoproliferative responses in chickens. These results indicate that vaccination against MD results not only in the prevention of tumor formation but also protection from possible virus-induced immunosuppression.

Animals↗