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Rajinder Singh

Publications and source records attributed to Rajinder Singh.

At least 19 recordsLinked to original sources
PubMed2006

Characterisation of Ercc1 deficiency in the liver and in conditional Ercc1-deficient primary hepatocytes in vitro.

The ERCC1/XPF complex is responsible for incision at the 5' side of the lesion during nucleotide excision repair and is also involved in homologous recombination and interstrand cross-link repair. The aim of the current study was to set up a better model for examination of Ercc1 deficiency in the murine liver and to determine the DNA lesions responsible for the premature polyploidy observed. We used the Cre/lox system with an adenovirus carrying Cre recombinase to conditionally induce Ercc1 deficiency in murine hepatocytes in vitro. Increased levels of apoptosis were apparent in our Ercc1-deficient cultures, both spontaneously and after UV irradiation and oxidative DNA damage. Increased apoptosis was also observed in simple Ercc1-deficient livers and the time course of the development of polyploidy was characterised. Livers from simple Ercc1 knockout mice contained mitochondria with disrupted outer membranes. Lipid accumulation was observed in older Ercc1-deficient hepatocyte cultures and in young Ercc1-deficient and wild-type livers. Lipids disappeared from the wild-type livers with age, but persisted in Ercc1-deficient livers, suggesting that a reduced ability to repair oxidative DNA damage and a malfunction of oxidative pathways could be responsible for the Ercc1-deficient liver phenotype. Real-time RT-PCR was used to determine differences in expression of cell cycle regulation and survival genes between Ercc1-deficient and control livers. Higher mRNA levels of Igfbp2, a possible marker for polyploidy, and p21 were detected in Ercc1-deficient livers. The pro-apoptotic factor, Bax, showed increased levels of mRNA expression in young Ercc1-deficient livers. However, no elevation in the levels of reactive oxygen species, or of malondialdehyde DNA adducts, a product of oxidative DNA damage, were found in Ercc1-deficient liver and no elevated levels of genes involved in the oxidative damage response were seen.

Animals↗
PubMed2006

Evaluation of enzyme-linked immunosorbent assay and liquid chromatography-tandem mass spectrometry methodology for the analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine in saliva and urine.

While ELISA is a frequently used means of assessing 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) in biological fluids, differences in baseline urinary 8-oxodG levels, compared to chromatographic techniques, have raised questions regarding the specificity of immunoassays. Recently, ELISA of salivary 8-oxodG has been used to report on periodontal disease. We compared salivary 8-oxodG levels, determined by two commercial ELISA kits, to liquid chromatography-tandem mass spectrometry (LC-MS/MS) with prior purification using solid-phase extraction. While values were obtained with both ELISA kits, salivary 8-oxodG values were below or around the limit of detection of our LC-MS/MS assay. As the limit of detection for the LC-MS/MS procedure is much lower than ELISA, we concluded that the assessment of salivary 8-oxodG by ELISA is not accurate. In contrast to previous studies, ELISA levels of urinary 8-oxodG (1.67 +/- 0.53 pmol/mumol creatinine) were within the range reported previously only for chromatographic assays, although still significantly different than LC-MS/MS (0.41 +/- 0.39 pmol/mumol creatinine; p = 0.002). Furthermore, no correlation with LC-MS/MS was seen. These results question the ability of ELISA approaches, at present, to specifically determine absolute levels of 8-oxodG in saliva and urine. Ongoing investigation in our laboratories aims to identify the basis of the discrepancy between ELISA and LC-MS/MS.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation.

Recent compelling evidence has lead to renewed interest in the role of antibodies and immune complexes in the pathogenesis of several autoimmune disorders, such as rheumatoid arthritis. These immune complexes, consisting of autoantibodies to self-antigens, can mediate inflammatory responses largely through binding and activating the immunoglobulin Fc receptors (FcRs). Using cell-based structure activity relationships with cultured human mast cells, we have identified the small molecule R406 [N4-(2,2-dimethyl-3-oxo-4H-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine] as a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling (EC(50) for degranulation = 56-64 nM). Here we show that the primary target for R406 is the spleen tyrosine kinase (Syk), which plays a key role in the signaling of activating Fc receptors and the B-cell receptor (BCR). R406 inhibited phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 bound to the ATP binding pocket of Syk and inhibited its kinase activity as an ATP-competitive inhibitor (K(i) = 30 nM). Furthermore, R406 blocked Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and BCR-mediated activation of B lymphocytes. R406 was selective as assessed using a large panel of Syk-independent cell-based assays representing both specific and general signaling pathways. Consistent with Syk inhibition, oral administration of R406 to mice reduced immune complex-mediated inflammation in a reverse-passive Arthus reaction and two antibody-induced arthritis models. Finally, we report a first-inhuman study showing that R406 is orally bioavailable, achieving exposures capable of inhibiting Syk-dependent IgE-mediated basophil activation. Collectively, the results show R406 potential for modulating Syk activity in human disease.

Animals↗
PubMed2006

Identification of the Syk kinase inhibitor R112 by a human mast cell screen.

BACKGROUND: Activation of the IgE receptor, FcvarepsilonRI, in mast cells is the key mechanism initiating and propagating pathophysiological responses in allergic rhinitis. OBJECTIVE: Identify and characterize a small molecule inhibitor of IgE-dependent mast cell activation for the treatment of allergic diseases. METHODS: A cell-based high-throughput screen for small molecules that block IgE signaling was performed in cultured human mast cells. A potent inhibitor, referred to as R112, was selected and characterized by using biochemical and cell-based assays. R112 effects on IgE-dependent degranulation and cytokine production was measured in mast cells and basophils and compared with other mast cell inhibitors. RESULTS: R112 inhibited degranulation induced by anti-IgE cross-linking in mast cells (tryptase release, effective concentration for 50% inhibition [EC(50)] = 353 nmol/L) or basophils (histamine release, EC(50) = 280 nmol/L), and by allergen (dust mite) in basophils (histamine release, EC(50) = 490 nmol/L). R112 also blocked leukotriene C4 production and all proinflammatory cytokines tested. Subsequent molecular characterization indicated that R112 is an ATP-competitive spleen tyrosine kinase (Syk) inhibitor (inhibitory constant [K(i)] = 96 nmol/L). Its onset of action was immediate, and the inhibition was reversible. Incubation of mast cells with R112 showed that cytokine production in mast cells was dependent on sustained activation of the FcvarepsilonRI-Lyn-spleen tyrosine kinase pathway. Unlike other mast cell inhibitors, R112 was able to completely inhibit all three IgE-induced mast cell functions: degranulation, lipid mediator production, and cytokine production. CONCLUSION: R112 potently, completely, and rapidly abrogated all mast cell activation cascades triggered by IgE receptor cross-linking. CLINICAL IMPLICATIONS: R112 and its analogues offer a new modality in the treatment of allergic rhinitis.

Aminophenols↗
PubMed2006

R-253 disrupts microtubule networks in multiple tumor cell lines.

PURPOSE: The design and development of synthetic small molecules to disrupt microtubule dynamics is an attractive therapeutic strategy for anticancer drug discovery research. Loss of clinical efficacy of many useful drugs due to drug resistance in tumor cells seems to be a major hurdle in this endeavor. Thus, a search for new chemical entities that bind tubulin, but neither are a substrate of efflux pump, P-glycoprotein 170/MDR1, nor cause undesired side effects, would potentially increase the therapeutic index in certain cancer treatments. EXPERIMENTAL DESIGN: A high-content cell-based screen of a compound library led to the identification of a new class of compounds belonging to a thienopyrimidine series, which exhibited significant antitumor activities. On structure-activity relationship analysis, R-253 [N-cyclopropyl-2-(6-(3,5-dimethylphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazine carbothioamide] emerged as a potent antiproliferative agent (average EC(50), 20 nmol/L) when examined in a spectrum of tumor cell lines. RESULTS: R-253 is structurally unique and destabilizes microtubules both in vivo and in vitro. Standard fluorescence-activated cell sorting and Western analyses revealed that the effect of R-253 on cell growth was associated with cell cycle arrest in mitosis, increased select G(2)-M checkpoint proteins, and apoptosis. On-target activity of R-253 on microtubules was further substantiated by immunofluorescence studies and selected counter assays. R-253 competed with fluorescent-labeled colchicine for binding to tubulin, indicating that its binding site on tubulin could be similar to that of colchicine. R-253 neither is a substrate of P-glycoprotein 170/MDR1 nor is cytotoxic to nondividing human hepatocytes. CONCLUSION: Both biochemical and cellular mechanistic studies indicate that R-253 could become a promising new tubulin-binding drug candidate for treating various malignancies.

Adenocarcinoma↗
PubMed2006

Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences.

Silibinin, a flavonolignan from milk thistle, has intestinal cancer chemopreventive efficacy in rodents. It is a strong antioxidant and modulates the insulin-like growth factor (IGF) system by increasing circulating levels of IGF-binding protein 3 (IGFBP-3) and decreasing levels of IGF-I. Here, the hypothesis was tested that administration of oral silibinin generates agent levels in human blood and colorectal and hepatic tissues consistent with pharmacologic activity. Patients with confirmed colorectal adenocarcinoma received silibinin formulated with phosphatidylcholine (silipide) at dosages of 360, 720, or 1,440 mg silibinin daily for 7 days. Blood and biopsy samples of normal and malignant colorectum or liver were obtained before dosing, and blood and colorectal or hepatic tissues were collected at resection surgery after the final silipide dose. Levels of silibinin were quantified by high-pressure liquid chromatography-UV, and plasma metabolites were identified by liquid chromatography-mass spectrometry. Blood levels of IGFBP-3, IGF-I, and the oxidative DNA damage pyrimidopurinone adduct of deoxyguanosine (M1dG) were determined. Repeated administration of silipide was safe and achieved levels of silibinin of 0.3 to 4 micromol/L in the plasma, 0.3 to 2.5 nmol/g tissue in the liver, and 20 to 141 nmol/g tissue in colorectal tissue. Silibinin monoglucuronide, silibinin diglucuronide, silibinin monosulfate, and silibinin glucuronide sulfate were identified in the plasma. Intervention with silipide did not affect circulating levels of IGFBP-3, IGF-I, or M1dG. The high silibinin levels achieved in the human colorectal mucosa after consumption of safe silibinin doses support its further exploration as a potential human colorectal cancer chemopreventive agent.

Administration, Oral↗
PubMed2006

Detection and quantitation of benzo[a]pyrene-derived DNA adducts in mouse liver by liquid chromatography-tandem mass spectrometry: comparison with 32P-postlabeling.

The polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P) is a proven animal carcinogen that is potentially carcinogenic to humans. B[a]P is an ubiquitous environmental pollutant and is also present in tobacco smoke, coal tar, automobile exhaust emissions, and charred food. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using electrospray ionization and selected reaction monitoring (SRM) has been developed for the detection of 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE-N(2)dG) adducts formed in DNA following the metabolic activation of B[a]P to benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (B[a]PDE). The method involves enzymatic digestion of the DNA sample to 2'-deoxynucleosides following the addition of a stable isotope internal standard, [(15)N(5)]B[a]PDE-N(2)dG, and then solid phase extraction to remove unmodified 2'-deoxynucleosides prior to analysis by LC-MS/MS SRM. The limit of detection of the method was 10 fmol (approximately 3 B[a]PDE-N(2)dG adducts per 10(8) 2'-deoxynucleosides) using 100 microg of calf thymus DNA as the matrix. Calf thymus DNA reacted with B[a]PDE in vitro and mouse liver DNA samples at different time points following dosing intraperitoneally with 50, 100, and 200 mg/kg B[a]P was analyzed. Three stereoisomers of the B[a]PDE-N(2)dG adduct were detected following the reaction of calf thymus DNA with B[a]PDE in vitro. The levels of B[a]PDE-N(2)dG DNA adducts in the mice livers were found to increase in a dose-dependent manner with adducts reaching maximal levels at 1-3 days and then gradually decreasing over time but still detectable after 28 days. A very good correlation (r = 0.962, p < 0.001) was observed between the results obtained for the mouse liver DNA samples using LC-MS/MS SRM as compared to those obtained using a (32)P-postlabeling method. However, the levels of adducts observed following (32)P-postlabeling using butanol enrichment were approximately 3.7-fold lower. The LC-MS/MS method allowed the more precise quantitation of DNA adduct levels that were structurally characterized, in addition to a reduction in the time taken to perform the analysis when compared with the (32)P-postlabeling method.

Animals↗
PubMed2006

Somaclonal variation in micropropagated oil palm. Characterization of two novel genes with enhanced expression in epigenetically abnormal cell lines and in response to auxin.

In vitro micropropagation based on somatic embryogenesis provides an efficient means to multiply selected genotypes of oil palm (Elaeis guineensis Jacq.). Despite its considerable potential, somatic embryogenesis can yield plants bearing a homeotic flowering abnormality known as mantled. Because the mantled abnormality is epigenetic, it cannot be detected with conventional structural molecular markers. Thus, to develop a means of discriminating among callus cultures carrying or lacking the mantled abnormality, we used a gene expression approach. We describe two novel oil palm genes, EgM39A and EgIAA1, both of which display increased transcript accumulation in epigenetically abnormal calli. EgIAA1 codes for an oil palm relative of the Arabidopsis thaliana (L.) Heynh. AXR3/IAA17 protein involved in early auxin response and EgM39A codes for a protein of unknown function sharing sequence similarities with asparagine synthetases. In addition to their enhanced expression in somaclonal variant callus lines, both genes displayed increased transcript accumulation in response to auxin treatment. Normal seed-derived zygotic embryos germinated in the presence of auxin accumulated increased amounts of EgIAA1 transcripts after a few hours of treatment, suggesting a role in auxin response similar to that demonstrated for IAA genes in other species. The EgM39A gene also displayed enhanced transcript accumulation in auxin-treated zygotic embryos. Although only a small increase was seen after 24 h, greater changes were observed after 15 days. Both genes show potential as early markers of clonal conformity and may help to elucidate the nature of the epigenetic changes causing the mantled abnormality.

Amino Acid Sequence↗
PubMed2006

Comparison of major bile duct injuries following laparoscopic cholecystectomy and open cholecystectomy.

BACKGROUND: The mechanism and extent of major bile duct injuries following laparoscopic cholecystectomy differ from those of open cholecystectomy. METHODS: To identify differences in the demographic profile, timing of injury detection, management strategies and outcome, we undertook a retrospective review and analysis of our experience with 55 major bile duct injuries following both laparoscopic and open cholecystectomies over a period of 9 years. RESULTS: Thirty-one major bile duct injuries resulted from laparoscopic cholecystectomy (56%) and 24 of them were sustained after open cholecystectomy (44%). The median time of presentation was 7 days after laparoscopic cholecystectomy and 14 days following open cholecystectomy (P < 0.001). Twenty-eight (51%) patients had injuries recognized intraoperatively in both groups, of whom 18 patients underwent an attempt at primary repair before referral. All patients required subsequent surgical intervention. There were no differences in the clinical presentations between the two groups. However, serum alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase levels were significantly higher following open cholecystectomy (P < 0.05). There was no significant difference in the level of injury between the two groups. All patients underwent surgical repair in the form of a Roux-en-Y hepaticojejunostomy (including two revision hepaticojejunostomies in each group). Surgical outcome did not differ between the groups; however, better results were seen with Bismuth grades 1 and 2 strictures compared with Bismuth grades 3 and 4 strictures for both groups (P < 0.002). CONCLUSION: Major bile duct injuries following laparoscopic cholecystectomy present earlier and with lower levels of serum alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. There does not appear to be a significant difference between the Bismuth-Strasberg grading of the strictures and the type of surgery carried out.

Adult↗
PubMed2006

Open partial nephrectomy: outcomes from two UK centres.

OBJECTIVE: To define the current achievable outcomes from open partial nephrectomy (OPN) in the UK at a time when other treatments for small kidney tumours are increasingly being advocated. Current knowledge of the effectiveness of OPN is limited by the fact that published data are almost exclusively derived from a very few centres of established world renown. PATIENTS AND METHODS: We retrospectively reviewed 100 consecutive planned OPNs in 90 patients at two UK centres; 93 operations were for suspected cancer. The median (range) tumour size was 3.8 (1.2-9) cm. In all, 42 OPNs were imperative for patients with a single kidney (14), synchronous bilateral tumours (20), or renal impairment alone (eight). In 42 patients with a tumour of < or = 4 cm and a normal contralateral kidney the decision to do OPN was considered elective. There were 10 additional operations in seven patients with Von Hippel-Lindau (VHL) disease. In all, 21 OPNs were in the context of a single kidney. RESULTS: In all, 95 OPNs were successfully completed; one operation was abandoned and there were four nephrectomies, including two for bleeding, one for a positive margin on frozen-section analysis, and one for multifocal tumours. The median warm/cold ischaemia time was 20/33 min. The intraoperative/early complication rate was 36%, including a major complication rate of 11% and re-operation rate for primary bleeding of 3%. Of 36 complications, 30 (83%) were in 23 patients with either an imperative indication or VHL. Complications were more common in the imperative/VHL group (59%) than in the elective/other group (12%). Renal function was preserved in 80 of 100 (80%) OPNs overall. Creatinine levels returned to baseline in 11 of 21 (50%) patients with renal impairment before OPN and in 12 of 20 (60%) with a single kidney, whilst five of 21 (24%) with a single kidney needed dialysis after OPN. The median (range) stay after surgery was 6 (3-50) nights. A malignant diagnosis was confirmed in 76 of 93 (82%) specimens on final histopathology. There were 11 of 100 (11%) positive margins, one managed by immediate conversion to nephrectomy and the remaining 10 managed expectantly. After a median (range) follow-up of 24 (1-69) months there were no deaths from kidney cancer, but three patients had local recurrences and two others had developed metastatic recurrence. CONCLUSION: OPN is complex surgery, especially in the imperative setting, but very good results are achievable outside established centres of world renown. It provides good cancer control in the short term with low renal morbidity. These results may act as a reference point in the UK by which to compare results of new treatments for kidney cancer.

Adolescent↗
PubMed2006

The overactive bladder: review of current pharmacotherapy in adults. Part 1: pathophysiology and anticholinergic therapy.

Overactive bladder is a syndrome characterised by urinary urgency, with or without urge incontinence, and usually with frequency and nocturia. It affects millions of people of all ages worldwide and causes significant morbidity, especially in terms of health-related quality of life. It poses a huge economic burden on health resources. Managing such patients involves a thorough history, physical examination and the use of pertinent investigations before the initiation of treatment. Therapy consists of lifestyle changes, bladder training, anticholinergics, second-line agents such as resiniferatoxin instillation or botulinum toxin injections into the bladder in refractory cases and, finally, in intractable cases, surgery. In the first part of this review of pharmacotherapy for the treatment of this condition, the focus is on the pathophysiological factors potentially involved in overactive bladder and covers the wide range of currently available first-line anticholinergic agents. Treatment algorithms are suggested on the basis of current literature.

Administration, Cutaneous↗
PubMed2006

The overactive bladder: review of current pharmacotherapy in adults. Part 2: treatment options in cases refractory to anticholinergics.

In the first part of this review the potential pathophysiological factors involved in the overactive bladder were outlined, and the wide range of first-line anticholinergic pharmacotherapies available for such patients were reviewed. The second part will focus on the intravesical instillation of resiniferatoxin and injections of botulinum toxin into the bladder to treat overactive bladder and detrusor overactivity. Resiniferatoxin has been shown to increase bladder capacity and improve incontinence in patients with neurogenic and non-neurogenic detrusor overactivity. Botulinum toxin has successfully been used to treat neurogenic and idiopathic detrusor overactivity, with improvements observed in bladder capacity, decreases in detrusor pressures on filling and voiding, and increased volumes at first contraction. Further validation is required for both treatments, in the form of large randomised controlled trials, before their use can be considered routine, with particular focus on dosing required.

Administration, Intravesical↗
PubMed2005

Liquid chromatography-electrospray ionization-mass spectrometry: the future of DNA adduct detection.

Over the past 40 years considerable emphasis has been placed on the development of accurate and sensitive methods for the detection and quantitation of DNA adducts. The formation of DNA adducts resulting from the covalent interaction of genotoxic carcinogens with DNA, derived from exogenous and endogenous sources, either directly or following metabolic activation, can if not repaired lead to mutations in critical genes such as those involved in the regulation of cellular growth and subsequent development of cancer. The major analytical challenge has been to detect levels of DNA adducts at the level of 0.1-1 adducts per 10(8) unmodified DNA bases using only low microgram amounts of DNA, and with high specificity and accuracy, in humans exposed to genotoxic carcinogens derived from occupational, environmental, dietary and life-style sources. In this review we will highlight the merits as well as discuss the progress made by liquid chromatography coupled to electrospray ionization mass spectrometry as a method for DNA adduct detection.

Carcinogens↗
PubMed2005

Detection of DNA damage derived from a direct acting ethylating agent present in cigarette smoke by use of liquid chromatography-tandem mass spectrometry.

Cigarette smoke contains a complex mixture of chemicals, including some that are genotoxic. A number of epidemiological and clinical studies have reported the association of increased DNA adduct levels with the development of lung cancer in smokers. The majority of chemicals present in cigarette smoke require cytochrome P450-mediated metabolic activation to form the ultimate reactive species that covalently binds with DNA. We have investigated the presence of a direct-acting ethylating agent present in cigarette smoke by studying the formation of N-7 ethylguanine (N-7EtG) following exposure of DNA to cigarette smoke in vitro. A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with multiple reaction monitoring (MRM) was developed for the detection of N-7EtG in DNA. DNA samples were subjected to thermal hydrolysis to selectively release the N-7EtG, which was then quantified by LC-MS/MS MRM using a stable isotope internal standard [15N5]N-7EtG. The limit of detection of the method for N-7EtG was 2.0 fmol injected on column with 100 microg of calf thymus DNA as the matrix (0.6 N-7EtG adducts per 10(8) nucleotides). A linear dose-response was observed for the formation of N-7EtG in calf thymus DNA treated with diethyl sulfate at concentrations ranging from 1 to 1000 microM. Calf thymus DNA treated with smoke generated from 1, 5, and 10 commercially available cigarettes resulted in the formation of 1.3, 3.6, and 8.4 N-7EtG adducts per 10(8) nucleotides, respectively. There was a positive correlation between the formation of N-7EtG and the number of cigarettes (r = 0.9938). These results confirm the presence of an as yet unidentified direct acting ethylating agent in cigarette smoke, which is present at levels that can produce DNA damage that could ultimately have adverse implications for human health, particularly in the case of the development of lung cancer.

Alkylating Agents↗
PubMed2004

Pseudoaneurysm of the superior pancreaticoduodenal artery, a rare cause of hemosuccus pancreaticus: report of a case.

Chronic pancreatitis with a pseudoaneurysm is an established cause of hemosuccus pancreaticus. We herein describe a patient with chronic alcoholic pancreatitis associated with hemosuccus pancreaticus due to a pseudoaneurysm of the anterior superior pancreaticoduodenal artery rupturing in a pseudocyst of pancreas in the head region. Angiographic embolization was unsuccessful and therefore a laparotomy, ligation, and excision of the pseudoaneurysm with external drainage of pseudocyst were performed. Hemosuccus pancreaticus is a rare cause of upper gastrointestinal bleeding. Contrast-enhanced computed tomography and angiography is diagnostic in the majority of the cases. Surgery is the treatment of choice. Selective angiographic embolization may be helpful in tiding over the emergency until surgery can be performed.

Adult↗
PubMed2004

Comorbidity assessment in localized prostate cancer: a review of currently available techniques.

Pathological nomograms have allowed urologists to make accurate predictions about the behaviour of localized prostate cancers. However, predicting overall outcome and survival is not solely dependent on tumour characteristics; comorbidity is also a vital determinant of outcome The majority of prostate cancers are diagnosed in men over 65 years of age and many will have significant competing comorbid disease that will need to be accounted when considering eligibility for radical treatment. Most urologists currently make an educated guess about the risk posed by comorbid disease. Such an approach has the potential to allow personal bias to influence what should be an objective measure. This review describes the available methods for objectively assessing comorbid risk and assesses their potential utility to men with localized prostate cancer being considered for radical treatment.

Cardiovascular Diseases↗