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Biomedical subjects

S Reddy

Publications and source records attributed to S Reddy.

At least 19 recordsLinked to original sources
PubMed2006

Retrieval of abdominal organs for transplantation.

BACKGROUND: Organ retrieval and donor management are not yet standardized. Different transplant centres apply various techniques, such as single or dual organ perfusion, dissection in the cold or warm, and single or en bloc organ removal. These different approaches may cause inconvenience, especially when more than one organ retrieval team is involved. METHODS: Cochrane Library, Medline and PubMed were searched for publications on multiorgan donor/donation, retrieval technique and procurement. Levels of evidence and grades of recommendation were evaluated based on current advice from the Oxford Centre for Evidence-Based Medicine. RESULTS: Multiorgan donation itself does not compromise the outcome of individual organ transplants. Dissection of abdominal organs for transplantation is best performed after cold perfusion. Abdominal organs should be removed rapidly, en bloc, and separated during back-table dissection in the cold, particularly if pancreas or intestine is included. Perfusion itself should be carried out after single cannulation of the aorta with an increased pressure. CONCLUSION: Although the literature on organ retrieval is extensive, the level of evidence provided is mainly low. Nevertheless, optimized donor treatment and organ retrieval should increase the number and quality of cadaveric donor organs and improve graft function and survival.

Abdomen↗
PubMed2006

The casualty profile from the Reading train crash, November 2004: proposals for improved major incident reporting and the application of trauma scoring systems.

OBJECTIVE: To report the casualty profile of the major incident at the Royal Berkshire Hospital, Reading, following the Ufton Nervet Train crash, November 2004. To make further proposals regarding major incident reporting and implementation of trauma-scoring systems. METHOD: Retrospective analysis of emergency department and hospital notes. Calculation of index Injury Severity Score (ISS) and Trauma and Injury Severity Score (TRISS) in all patients. RESULTS: Of 61 casualties, the majority (74%) were seen in the minors area of our emergency department with a mixture of blunt impact and penetrating glass injuries. One died and 16 were admitted. 10% had an ISS >16. All surviving patients had a TRISS predicted probability of survival >90%. CONCLUSION: We propose mandatory major incident reporting within 6 months of a major incident to aid development of a national database. As previously proposed, this will aid education and facilitate future major incident planning. We further propose the widespread use of trauma scoring systems to facilitate comparative analysis between major incidents, perhaps extrapolating this to develop a major incident score.

Adult↗
PubMed2005

Decreased expression of DMPK: correlation with CTG repeat expansion and fibre type composition in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a trinucleotide repeat-expansion, cytosine-thymine-guanine (CTG)n, in the 3' untranslated region of a gene encoding the myotonic dystrophy protein kinase (DMPK). To correlate CTG expansion and protein expression, we studied muscle specimens from 16 adult DM1 patients using three anti-DMPK antibodies for immunoblotting. We estimated the amount of the full-length DMPK (85 kDa) in muscle biopsies from normal controls and from DM1 patients carrying different (CTG)n expansions. We found that DMPK concentration was decreased to about 50% in DM patients' muscles; the protein decrease did not seem correlated with the CTG repeat length. However, the fibre type composition in skeletal muscle seemed somehow to affect DMPK decrease, as the lowest level of the enzyme was found in patients with the lowest content of type 1 fibre.

Adult↗
PubMed2005

Analysis of two components of flight using recombinant inbred lines of Drosophila melanogaster.

Complex activities require precise coordination of their components for successful action. The genetic basis underlying coordination of traits may range from relatively static pleiotropic associations to more flexible genetic associations that recombine in phenotypes under continuous selective modification by the environment. Successful flight in insects depends on the precise integration of numerous component physiological processes. Here we examine the genetic basis of two of its components, flight duration and rate. To study flight we created recombinant inbred populations from stocks of this laboratory known for their significantly longer duration flights. A heritable basis for these traits was found and determined to be positively correlated between sexes. Correlations of flight length with rate were negative within sexes, suggesting a trade-off, but were significant in males only. Composite interval mapping using the recombinant inbred (RI2) design was used to locate the QTLs for these traits and test for pleiotropy. Four QTLs affecting duration or wing beat rate were found on chromosomes II and III. Tests for pleiotropy showed some effects on traits of QTLs were common to both sexes while others were sex-specific. No QTL was pleiotropic for both traits, suggesting that correlations between flight duration and rate of wing beat are determined by a combination of linkage and environmental factors.

Animals↗
PubMed2005

Dopaminergic influence on thyrotropin secretion in primary hypothyroidism.

This study was conducted to assess the influence of dopamine on thyrotropin secretion in patients with primary hypothyroidism before and after optimized L-thyroxin replacement therapy. Thyrotropin responses to dopamine infusion (4 microg/kg/min over 3 hours) and IV metoclopramide (10 mg bolus), a dopamine receptor blocker were studied in 25 consecutive patients with primary hypothyroidism before and after achieving stable euthyroid state and compared with 15 normal age-matched controls. Thyrotropin response to both dopamine infusion (decremental) and IV metoclopramide bolus (incremental) was greater in patients with primary hypothyroidism than that in the control subjects. Thyrotropin response was greater in women than in men. The magnitude of decremental thyrotropin response to dopamine infusion and the incremental response to IV metoclopramide bolus significantly correlated with the basal T3 and T4 levels. Thyrotropin response was blunted to dopamine infusion but not to metoclopramide at follow-up after six-month replacement with L-thyroxin, and both the responses were comparable in women and men in patient group. We conclude that modulation of dopaminergic system by dopamine or by dopamine receptor blocker has a greater influence on thyrotropin secretion in patients with primary hypothyroidism than euthyroid normal subjects.

Adult↗
PubMed2005

PET/CT imaging: detection of choroidal melanoma.

AIM: To determine the size of untreated choroidal melanomas resolved by whole body positron emission tomography fused with computed tomography (PET/CT). METHODS: 50 consecutive patients with untreated choroidal melanomas underwent whole body PET/CT. A functionally fused helical CT scan and 18-fluoro-2-deoxyglucose (FDG) PET scans were employed. The tumours were identified (both quantitatively and qualitatively) and compared with clinical measurements derived from ophthalmoscopic, angiographic, and ultrasonographic imaging. Standardised uptake values (SUV) of more than 2.5 were considered positive. RESULTS: Among the 50 patients with choroidal melanoma, PET/CT scan SUVs of more than 2.5 were noted in 14 (28%) tumours. No AJCC T1 class tumours, 33.3% of T2 melanomas, and 75% of T3 melanomas were physiologically identifiable on PET/CT. With respect to COMS group classifications, no small choroidal tumours, 33% of medium, and 75% of large melanomas were physiologically identifiable. The sole ring melanoma was identifiable on PET/CT imaging. The smallest tumour physiologically identifiable by PET/CT had basal dimensions of 3x5.9 and an apical height of 2.9 mm. CONCLUSION: Though PET/CT was found to be capable of physiologically identifying certain medium (T2) and most large sized (T3) choroidal melanomas, physiological imaging was not completely dependent upon tumour size. Functionally fused PET/CT localised the tumours within the eye and assessed their physiological activity.

Adult↗
PubMed2005

Whole body PET/CT for initial staging of choroidal melanoma.

AIM: To investigate the value of whole body positron emission tomography/computed tomography (PET/CT) in screening for metastatic choroidal melanoma in patients initially diagnosed with choroidal melanoma. METHODS: 52 patients with choroidal melanoma underwent whole body PET/CT as part of their metastatic investigation. PET/CT scans were used as a screening tool at the time of their initial diagnosis. A physical examination, liver function tests, and a baseline chest x ray were also obtained. PET/CT images (utilising intravenous18-fluoro-2-deoxyglucose (FDG)) were studied for the presence of metastatic melanoma. The standards for reference were further imaging and/or subsequent biopsies. RESULTS: Two of 52 (3.8%) patients were found to have metastatic melanoma before treatment. The most common sites for metastases were the liver (100%), bone (50%), and lymph nodes (50%). Brain involvement was also present in one patient. One patient (50%) had involvement of multiple sites. Haematological liver enzyme assays were normal in both patients. PET/CT showed false positive results in three patients (5.7%) when further evaluated by histopathology and/or additional imaging. In seven patients (13.4%) PET/CT imaging detected benign lesions in the bone, lung, lymph nodes, colon, and rectum. CONCLUSION: PET/CT imaging can be used as a screening tool for the detection and localisation of metastatic choroidal melanoma. Liver enzyme assays did not identify liver metastases, while PET/CT revealed both hepatic and extrahepatic metastatic melanoma. PET/CT imaging may improve upon the conventional methods of screening for detection of metastatic disease in patients initially diagnosed with choroidal melanoma.

Adult↗
PubMed2005

A methodology for the evaluation of disinfection technologies.

There are several concerns associated with the use of chlorine for potable water disinfection. These are the resistance of certain pathogens, the formation of toxic disinfection by-products and the adverse effects on aesthetic water quality. Owing to these concerns the water industry is continually reviewing alternative disinfection technologies. A methodology has been devised that will aid the water industry in evaluating the potential of these technologies. The methodology uses seven criteria to evaluate the technologies, these are: inactivation efficiency, disinfection byproduct (DBP) formation, toxicity, aesthetic water quality, cost, scalability and residual maintenance. Each criterion is assessed by associated questions in order of importance in accordance with a protocol. The criteria are evaluated using UK water quality regulations as standards. Ultraviolet (UV) disinfection was used as an example to demonstrate the methodology. UV was shown to meet all the criteria apart from the provision of a residual disinfectant. Several other disinfection technologies were evaluated using the methodology. Direct electrochemical disinfection and mixed oxidant generators were identified as having the most potential for replacing chlorination.

Disinfection↗
PubMed2005

Duloxetine pharmacokinetics in cirrhotics compared with healthy subjects.

OBJECTIVE: To compare the pharmacokinetics of single-dose duloxetine in cirrhotic and healthy subjects. METHODS: An open-label inpatient study compared duloxetine pharmacokinetics in six subjects with moderate liver cirrhosis (Child-Pugh class B) to those in six healthy subjects. Subjects received a single 20 mg capsule of duloxetine following overnight fasting. Blood samples were collected up to 120 h post dose for determination of plasma concentrations of duloxetine and its major metabolites using a validated LC/MS/MS method. Plasma concentration-time data for duloxetine and its major metabolites were analyzed by noncompartmental methods. Specific pharmacokinetic parameters were assessed statistically using a mixed-effects model. RESULTS: Duloxetine apparent clearance was significantly lower (24 vs 160 l/h, p < 0.05) and AUC values were substantially higher (775 vs 268 ng x (h/ml) in cirrhotic compared to healthy subjects. The half-life of duloxetine was about three times longer (47.8 vs 13.5 h) in cirrhotic than in healthy subjects (p < 0.05). In contrast, there was no significant difference in Cmax or apparent volume of distribution between the two groups. The metabolites exhibited lower levels and longer half-lives in cirrhotic subjects compared to healthy subjects. The lower clearance and slower elimination of duloxetine in cirrhotic individuals is likely attributable to impaired duloxetine metabolism. CONCLUSIONS: The rate of duloxetine elimination is reduced for cirrhotic subjects, making dosage adjustments appropriate. Based on simulations, the duloxetine dose for at least an initial treatment period may need to be reduced and/or less frequently administered for patients with moderate cirrhosis.

Administration, Oral↗
PubMed2004

Fast-tracking revisited: routine cardiac surgical patients need minimal intensive care.

OBJECTIVE: Following cardiac surgery, patients are transferred from the operating theatre to intensive care. This clinical environment has one nurse per patient and facilities for mechanical ventilation. Patients are kept in this setting until the following day. This practice has been challenged with early extubation of patients. At our institution we have established a fast-track policy including the following features: (1) patient selection; (2) operating list scheduling with fast-track patients first; (3) anaesthetic tailored to early extubation; (4) methodical procedure with warm cardiopulmonary bypass; (5) removal of the arterial line; (6) transfer from intensive care to a separate high dependency unit ('step-down') on the day of operation, where the ratio of nurse to patient is one to three and there are no ventilatory facilities and no invasive monitoring; or (7) to keep these patients on ICU but decrease the nurse to patient ratio. METHOD: The case notes of 572 patients who predominantly had myocardial revascularisation, undergoing this process from July 1996 to July 2000 at our institution were reviewed. RESULTS: Mean EUROSCORE for the study group was 1.42. The 30-day mortality rate for the study group was 0.34%, mean intensive care time was 5 h 52 min, mean time to extubation was 3 h 10 min, mean readmission rate to intensive care was 0.34% and mean hospital stay from day of operation (inclusive) was 5.65 days. This process increased our throughput by 14.6% (compared to standard practices). COMMENT: This study demonstrates that transfer of appropriate patients to a high dependency area from intensive care following cardiac surgery is safe. It allows intensive care beds to be used by more than one patient each day and allows significant cost savings by reducing the nursing ratio per patient.

Adult↗
PubMed2004

Immunohistochemical demonstration of leptin in pancreatic islets of non-obese diabetic and CD-1 mice: co-localization in glucagon cells and its attenuation at the onset of diabetes.

Leptin is a 16 kD polypeptide hormone produced predominantly by white adipose tissue and exerts profound effects on food intake and energy balance. More recent studies have shown extra sites of leptin production in human and rodent tissues and have ascribed additional roles for the hormone, e.g., in immune and reproductive functions. A role for the hormone has also been implicated in insulin-dependent diabetes mellitus in the non-obese diabetic (NOD) mouse. However, whether leptin originates from islet cells of the mouse is not known. Here dual-label immunohistochemistry was employed to examine leptin expression in islet cells, and its distribution and cellular sources in pancreatic sections of female NOD/Ak and CD-1 mice of various ages. For comparison, leptin immunolabelling was examined in adult pancreatic sections from male NOD/Ak CD-1, Balb/c and FVB/N mice and female severe combined immunodeficient CB. 17 mice. Pancreatic tissues from adult female guinea pig, sheep and cattle and neonatal pigs were also studied. Our results show that in the day 1 NOD and CD-1 mice, leptin immunolabelling was observed in selective glucagon cells within the developing islets while at days 15 and 22, it became more intense and co-incident. This pattern of staining was maintained at days 40, 90, 150 and 250. In the female NOD mouse, leptin was absent in intra-islet immune cells. Its expression was variable in islets from male NOD and CD-1 mice. In spontaneously diabetic female NOD mice and following acceleration of diabetes with cyclophosphamide, despite the persistence of strong immunolabelling for glucagon in the re-distributed alpha cells, leptin expression was either absent, diminished or present in only a proportion of alpha cells. The reduction in leptin labelling was often associated with diabetic islets which had insulitis in association with only a small number of residual beta cells. Leptin expression was absent in guinea pig, ovine, bovine and neonatal porcine islet cells, despite the expression of intensely labelled glucagon cells. The present results demonstrate leptin co-localization in glucagon cells of the mouse islet. Its expression diminishes in the presence of inadequate insulin. Leptin produced within the mouse islet may have bi-directional influences on leptin and insulin regulation and may play local functions in islet development and metabolism.

Animals↗
PubMed2004

Synthetic peptide derived from alpha-fetoprotein inhibits growth of human breast cancer: investigation of the pharmacophore and synthesis optimization.

Asynthetic peptide that inhibits the growth of estrogen receptor positive (ER+) human breast cancers, growing as xenografts in mice, has been reported. The cyclic 9-mer peptide, cyclo[EMTOVNOGQ], is derived from alpha-fetoprotein (AFP), a safe, naturally occurring human protein produced during pregnancy, which itself has anti-estrogenic and anti-breast cancer activity. To determine the pharmacophore of the peptide, a series of analogs was prepared using solid-phase peptide synthesis. Analogs were screened in a 1-day bioassay, which assessed their ability to inhibit the estrogen-stimulated growth of uterus in immature mice. Deletion of glutamic acid, Glu1, abolished activity of the peptide, but glutamine (Gln) or asparagine (Asn) could be substituted for Glu1 without loss of activity. Methionine (Met2) was replaced with lysine (Lys) or tyrosine (Tyr) with retention of activity. Substitution of Lys for Met2 in the cyclic molecule resulted in a compound with activity comparable with the Met2-containing cyclic molecule, but with a greater than twofold increase in purity and corresponding increase in yield. This Lys analog demonstrated anti-breast cancer activity equivalent to that of the original Met-containing peptide. Therefore, Met2 is not essential for biologic activity and substitution of Lys is synthetically advantageous. Threonine (Thr3) is a nonessential site, and can be substituted with serine (Ser), valine (Val), or alanine (Ala) without significant loss of activity. Hydroxyproline (Hyp), substituted in place of the naturally occurring prolines (Pro4, Pro7), allowed retention of activity and increased stability of the peptide during storage. Replacement of the first Pro (Pro4) with Ser maintains the activity of the peptide, but substitution of Ser for the second Pro (Pro7) abolishes the activity of the peptide. This suggests that the imino acid at residue 7 is important for conformation of the peptide, and the backbone atoms are part of the pharmacophore, but Pro4 is not essential. Valine (Val5) can be substituted only with branched-chain amino acids (isoleucine, leucine or Thr); replacement by d-valine or Ala resulted in loss of biologic activity. Thus, for this site, the bulky branched side chain is essential. Asparagine (Asn6) is essential for activity. Substitution with Gln or aspartic acid (Asp), resulted in reduction of biologic activity. Removal of glycine (Gly8) resulted in a loss of activity but nonconservative substitutions can be made at this site without a loss of activity indicating that it is not part of the pharmacophore. Cyclization of the peptide is facilitated by addition of Gln9, but this residue does not occur in AFP nor is it necessary for activity. Gln9 can be replaced with Asn, resulting in a molecule with similar activity. These data indicate that the pharmacophore of the peptide includes side chains of Val5 and Asn6 and backbone atoms contributed by Thr3, Val5, Asn6, Hyp7 and Gly8. Met2 and Gln9 can be modified or replaced. Glu1 can be replaced with charged amino acids, and is not likely to be part of the binding site of the peptide. The results of this study provide information that will be helpful in the rational modification of cyclo[EMTOVNOGQ] to yield peptide analogs and peptidomimetics with advantages in synthesis, pharmacologic properties, and biologic activity.

Amino Acid Sequence↗
PubMed2004

Methadone: applied pharmacology and use as adjunctive treatment in chronic pain.

This article reviews the unique pharmacological properties of methadone and outlines its appropriate clinical application, with focus upon its use in the treatment of chronic pain. Although methadone is most widely known for its use in the treatment of opioid dependence, methadone also provides effective analgesia. Patients who experience inadequate pain relief or intolerable side effects with other opioids or who suffer from neuropathic pain may benefit from a transition to methadone as their analgesic agent. Adverse effects, particularly respiratory depression and death, make a fundamental knowledge of methadone's pharmacological properties essential to the provider considering methadone as analgesic therapy for a patient with chronic pain.

Analgesics, Opioid↗
PubMed2003

In situ microcosms to study the impact of heavy metals resuspended by dredging on periphyton in a tropical estuary.

Ponggol estuary, located on the northeastern coast of Singapore, is heavily impacted by reclamation, dredging, construction and shipping. Tin, lead, nickel, cadmium, copper and zinc in the particulate and dissolved fraction and in sediments were monitored biweekly in the estuary from July 1999 to June 2000. The concentrations of tin, lead, nickel, cadmium, copper and zinc were observed to range from ND-92 ppm, ND-303 ppm, ND-2818 ppm, ND-74 ppm, ND-1117 ppm and ND-137000 ppm, respectively, in the dissolved, particulate and sediments fractions. Intensive dredging activity occurred during the monitoring period, and this may have led to the resuspension and increased bioavailability of particulate metals. Periphytic algae were established on glass slides and exposed to previously measured environmental levels of heavy metals using in situ estuarine microcosms. The toxicity of heavy metals in various fractions to periphytic algae was assessed from the changes in their chlorophyll a content. Cadmium had the least significant effect followed by lead, zinc, nickel, tin and copper at all concentrations tested. A reduction in periphyton biomass (with respect to controls) of 95-100% was observed for treatments with metals in particulate form. In addition, exposure to contaminated sediments for 3 days significantly decreased chlorophyll a by 90-99% compared to controls. High concentrations of zinc (9893-17240 mg l(-1)), copper (5-11 mg l(-1)) and cadmium (1-1.8 mg l(-1)) recorded in the aqueous phase of treatment microcosms, and attributed to release from the contaminated sediments, could account for the toxicity to periphyton.

Analysis of Variance↗
PubMed2003

Rat cytochrome P450C24 (CYP24) does not metabolize 1,25-dihydroxyvitamin D2 to calcitroic acid.

1alpha-Hydroxy-23 carboxy-24,25,26,27-tetranorvitamin D(3) (calcitroic acid) is known to be the major water-soluble metabolite produced during the deactivation of 1,25-(OH)(2)D(3). This deactivation process is carried out exclusively by the multicatalytic enzyme CYP24 and involves a series of oxidation reactions at C(24) and C(23) leading to side-chain cleavage and, ultimately, formation of the calcitroic acid. Like 1,25-(OH)(2)D(3), 1alpha,25-1,25-(OH)(2)D(2) is also known to undergo side-chain oxidation and side-chain cleavage to form calcitroic acid (Zimmerman et al. [2001]. 1,25-(OH)(2)D(2) differs from 1,25-(OH)(2)D(3) by the presence of a double bond at C(22) and a methyl group at C(24). To date, there have been no studies detailing the participation of CYP24 in the production of calcitroic acid from 1,25-(OH)(2)D(2). We, therefore, studied the metabolism of 1,25-(OH)(2)D(3) and 1,25-(OH)(2)D(2) using a purified rat CYP24 system. Lipid and aqueous-soluble metabolites were prepared for characterization. Aqueous-soluble metabolites were subjected to reverse-phase high-pressure liquid chromatography (HPLC) analysis. As expected, 1,23(OH)(2)-24,25,26,27-tetranor D and calcitroic acid were the major lipid and aqueous-soluble metabolites, respectively, when 1,25-(OH)(2)D(3) was used as substrate. However, when 1,25-(OH)(2)D(2) was used as substrate, 1,24(R),25-(OH)(3)D(2) was the major lipid-soluble metabolite with no evidence for the production of either 1,23(OH)(2)-24,25,26,27-tetranor D or calcitroic acid. Apparently, the CYP24 was able to 24-hydroxylate 1,25-(OH)(2)D(2), but was unable to effect further changes, which would result in side-chain cleavage. These data suggest that the presence of either the double bond at C(22) or the C(24) methyl group impedes the metabolism of 1,25-(OH)(2)D(2) to calcitroic acid by CYP24 and that enzymes other than CYP24 are required to effect this process.

Animals↗
PubMed2002

Acrolein-induced cytotoxicity in cultured human bronchial epithelial cells. Modulation by alpha-tocopherol and ascorbic acid.

Acrolein is a highly reactive unsaturated hazardous air pollutant of human health concern, particularly as a component of cigarette smoke. In this study, the mechanisms of acrolein-induced cytotoxicity in human bronchial epithelial cells (HBE1) and the modulating effects of antioxidants were examined. Our results show that acrolein induces a cell death pathway in human bronchial epithelial cells, which retain key features of apoptosis, as indicated by phosphatidylserine (PS) externalization and DNA fragmentation. Acrolein-induced apoptosis was associated with depletion of cellular GSH and intracellular generation of oxidants. Supplementation of cells with either alpha-tocopherol or ascorbic acid was found to strongly inhibit acrolein-induced apoptosis and to prevent the increase in the generation of intracellular oxidants, although GSH depletion was unaffected. Moreover, recovery of cellular GSH levels after acrolein exposure was enhanced following either alpha-tocopherol or ascorbic acid supplementation. The intracellular generation of oxidants following acrolein exposure seems to be an important event triggering the apoptotic response in this model system.

Acrolein↗
PubMed2001

Global burden of cardiovascular diseases: Part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies.

This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiological transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.

Africa↗