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Biomedical subjects

M Salman

Publications and source records attributed to M Salman.

At least 19 recordsLinked to original sources

Occult renal impairment is common in patients with peripheral vascular disease and normal serum creatinine.

OBJECTIVE: The incidence of peripheral vascular disease (PVD) and angiography/angioplasty is rising annually. The UK Small Aneurysm Trial and other trials have shown renal function is a predictor of increased mortality and failed infrainguinal bypass despite patent vessels. Renal function is classically assessed by serum creatinine (SCr). However, SCr can be normal despite significant renal impairment. A more sensitive test is creatinine clearance (CrCl) as determined by 24-hour urine collection in combination with SCr. We studied the incidence of renal impairment, as defined by CrCl, in PVD patients with normal SCr. METHODOLOGY: All patients with PVD sufficient to necessitate angiography and normal SCr (< or =120 micromol/l - men; < or =97 micromol/l - women) had their CrCl assessed prior to angiography: using both 24-hour urine collection and the Cockcroft-Gault formula. Various blood tests, a detailed history and examination were performed. A control group of arthritic patients, age and sex-matched with similar SCr, also had their CrCl determined. RESULTS: 65 of 76 patients (86%) with normal SCr had a subnormal CrCl (<100 ml/min) and 49 (65%) had a CrCl below 60 ml/min. In the control group of arthritic patients, the proportion having impaired CrCl was significantly less - 67% below 100 mls/min (p=0.0471) and only 15% below 60 mls/min (p<0.0001). The median and interquartile range CrCl of 52 [38-81] mls/min for PVD patients was significantly worse than for control patients (80 [68-119] mls/min -p<0.0001). The Cockcroft-Gault formula for calculating CrCl did not correlate well with the urinary CrCl for the control group but did for PVD patients (p<0.0001). Factors associated with a significantly reduced CrCl were age of at least 75 years, SCr of at least 85 micromol/l and a history of coronary heart disease (all p<0.05). This had a sensitivity of 88% and specificity of 82% for identifying subnormal CrCl. Statin use was associated with a significantly improved CrCl (p=0.040). CONCLUSION: Most PVD patients with normal serum creatinine have occult, significantly impaired renal function as defined by creatinine clearance. Vascular surgeons should include creatinine clearance in pre-operative assessment of renal function especially in patients over 75 years old, with a history of coronary heart disease or a serum creatinine over 85 micromol/l. The method of determining creatinine clearance could be the Cockcroft-Gault calculation or ideally 24-hour urinary creatinine clearance measurement. This would allow appropriate early referral to a nephrologist for further investigation and management. It is worth noting that statin use seems to be associated with a protective effect on renal function.

Aged↗

RBx 7,796: A novel inhibitor of 5-lipoxygenase.

OBJECTIVE: To evaluate the pharmacological profile of RBx 7,796, a novel 5-lipoxygenase inhibitor. MATERIALS AND METHODS: RBx 7,796 was evaluated for 5- lipoxygenase inhibitory potential using human recombinant enzyme and profiled for selectivity against 12 and 15 lipoxygenase. RBx 7,796 was evaluated in cell based assay for inhibition of A23,187 induced LTB(4) release from isolated neutrophils. Ex vivo activity was evaluated for inhibition of A23,187 induced LTB(4) release in blood from treated rats. In vivo efficacy of RBx 7,796 was profiled in LPS induced neutrophilia model in rats and also in ovalbumin induced bronchoconstriction and airway inflammation models in guinea pigs. RESULTS: RBx 7,796, a novel chemotype, showed competitive inhibition of 5-lipoxygenase enzyme with an IC(50) of 3.5 +/- 1.1 microM. RBx 7,796 offered >100 fold selectivity against other related enzymes - 12 and 15 lipoxygenase. RBx 7,796 inhibited release of LTB(4) from human and rat neutrophils in vitro. Upon administration to rats, RBx 7,796 inhibited A23,187 induced LTB(4) release from rat neutrophils. Upon repeated administration, dosed once daily, RBx 7,796 inhibited LPS induced neutrophil influx in rat airway. RBx 7,796 also inhibited allergen induced bronchoconstriction and eosinophil influx in guinea pig airway in a dose dependent manner. CONCLUSION: The results suggest that RBx 7,796, a novel chemotype, is an orally efficacious inhibitor of 5-lipoxygenase enzyme that is effective against both neutrophilic and eosinophilic airway inflammation and shows potent inhibition with once daily administration.

Animals↗

The role of veterinary epidemiology and veterinary services in complying with the World Trade Organization SPS agreement.

The agreement on the application of sanitary and phytosanitary measures (SPS agreement) was one of the major products of the GATT's Uruguay round of multilateral trade negotiations, signed in Marrakesh on 15 April 1994. This agreement and others are part of the treaty that established the World Trade Organization (WTO). The WTO superseded the GATT as the umbrella organization for international trade (WTO, 1998a). The SPS agreement's main intent is to provide guidelines and provisions to member countries to facilitate trade while taking measures to protect human, animal or plant life or health. The agreement dictates that all sanitary measures must be scientifically based and not more restrictive than required to avoid the risk identified. The agreement recommends the use of international standards from the World Organization for Animal Health (OIE), Codex Alimentarius (CAC) and the International Plant Protection Convention (IPPC) as the basis for import requirements. If a country chooses to apply more restrictive measures than those in the international standards, it has to justify its position through a risk analysis, thus avoiding the use of sanitary and phytosanitary measures as unjustified barriers to trade. More than ever, veterinary services worldwide are faced with having to fulfill a crucial role in protecting their country's animal health status, provide sound surveillance information on the occurrence of diseases within their territories, and conduct scientifically valid risk analyses to establish justified import requirements. During the past two decades, most countries have experienced resource reduction in their veterinary services. The effect of these policies has been severe, in many cases leading to an inability of veterinary services to conduct their disease prevention and control duties. There is a clear inconsistency between the demands placed on veterinary services and the current level of funding and support they are receiving, particularly in the developing world. This paper analyzes the implications in complying with the SPS agreement and explores the role of veterinary epidemiology in developing viable alternatives that can enhance the veterinary services' ability to perform under the current economic reality. The key provisions of the SPS agreement are regionalization, risk analysis, harmonization, equivalence and transparency. The paper focuses on the contribution of epidemiology in each of these areas in the effective implementation of the SPS agreement.

Animal Diseases↗

Will the new cytogenetics replace the old cytogenetics?

With the advent of array-based comparative genomic hybridization technology, the analog cytogenetic analysis that has been used for the past 100 years could be replaced by the quantitative, microarray-based molecular analysis. Major advantages of the new array-based cytogenetic technologies are the high resolution and the high throughput. This technology is the first to offer an autonomous whole-chromosome analysis in one hybridization reaction for the detection of submicroscopic gains/losses. However, as with any new technology, it needs to be validated with regard to its performance in various applications (e.g. clinical genetic testing and cancer applications), comparative cost, and the data interpretation.

Chromosome Aberrations↗

The construction and evaluation of a questionnaire to identify quantitative criteria for evaluating national Veterinary Services.

This article presents the first part of a large-scale study aimed at developing a method for collecting standard information, based on quantitative criteria, about the national Veterinary Services of Member Countries of the OIE (World organisation for animal health). This information can then be used to assess such Veterinary Services in terms of quality and performance, or for accreditation. The study identified objective and relevant criteria for characterising Veterinary Services and an extensive questionnaire was developed, covering all aspects of the structures and functions of national Veterinary Services, which was sent to a broad range of OIE Member Countries. Each question and its answers were then evaluated and validated. In this way, 49 questions suitable for obtaining quantitative criteria to describe Veterinary Services were identified. In the next step of the study, this complex set of data will be further analysed.

Animals↗

Applied animal behavior and obedience training course: a model for veterinary curricula.

Animal behavior problems often have detrimental effects on the relationships between pets and their owners and are one of the most frequently given reasons for canine relinquishment. The stressful environment of animal shelters can exacerbate behavior problems; yet most shelters do not have the staff necessary to address this issue adequately. Veterinary students may provide an untapped resource for solving this dilemma. As a service component of the curriculum, Veterinary schools can join with local humane societies to expose students to behavioral issues and concurrently build relationships within the community and perhaps even offer shelter animals a better chance of successful adoption. The following paper describes a "hands-on" undergraduate animal behavior and obedience training psychology course, created as a model to address these needs.

Animal Welfare↗

International trade, animal health and veterinary epidemiology: challenges and opportunities.

The link between international trade, animal health and epidemiology has been recognized for a long time and has taken an additional importance in the aftermath of the Uruguay Round of Multilateral Trade Negotiations of the General Agreement on Tariffs and Trade (GATT) and of the inception of the World Trade Organization. The Agreement on the Application of Sanitary and Phytosanitary Measures of the World Trade Organization demands that sanitary and phytosanitary measures be scientifically based, placing epidemiology at the center of decisions related animal health and trade. This paper analyses the interactions between international trade of animals (and animal products) and epidemiology with discussion on the inputs of epidemiology in surveillance, risk analysis and regionalization.

Animal Diseases↗

Longitudinal studies in the epidemiology of vesicular stomatitis on Costa Rican dairy farms.

Twenty-three Costa Rican dairy herds from an vesicular stomatitis (VS) endemic area were under an active surveillance between April 1997 and March 1999. Ninety-two confirmed cases of VS New Jersey were found. Factors associated with clinical cases of VS virus New Jersey were: Parity (animals of parity 4 or 5 were 5.3 times more likely to present a clinical case than animals of parity 3 and lower; on the other hand, animals of parity 6 and higher showed an odds 4.6 times greater than animals of parity 3 and lower.) Ecological life zone (animals in premountain moist forest were 7.4 times more likely to present clinical cases than animals in lower mountain rain forest). Factors associated with seropositivity at the time of birth were farm and breed (Jersey calves had an odds 14.7 times greater than Holstein calves). Seroconversion, defined as the first twofold increase in the titers of the blood, was associated with farm and showed four peaks during the study period, September (wet season) 1997, February (dry season) 1998, September 1998, and February 1999. Finally, time to event analysis showed difference between farms and age, older animals showed the first seroconversion earlier than younger animals.

Age Distribution↗

Survey of small rodents and hematophagous flies in three sentinel farms in a Costa Rican vesicular stomatitis endemic region.

A survey of rodents and hematophagous flies was conducted on three farms located in an area endemic for vesicular stomatitis to determine the species composition of each zoological group occurring in these areas. Eleven species of small rodents were collected and identified. Individuals from forty-nine species of hematophagous flies of the families Ceratopogonidae, Culicidae, and Phlebotominae were captured and identified. The species compositions in each group were compared between farms. Rodents were tested for antibodies to vesicular stomatitis, New Jersey and Indiana serotypes. Seven species had antibody titers greater than 1:10. Attempts to isolate the virus produced negative results for all the species tested.

Aedes↗

Synthesis of mycolic acids of mycobacteria: an assessment of the cell-free system in light of the whole genome.

Mycolic acids are 70-90 carbon, alpha-alkyl, beta-hydroxy fatty acids constituting a major component of the cell envelope of Mycobacterium tuberculosis. The fact that the mycolic acid biosynthetic pathway is both essential in mycobacteria and the target for many first-line anti-TB drugs necessitates a detailed understanding of its biochemistry. A whole cell-free, but cell particulate- and membrane-containing enzyme preparation for mycolic acid biosynthesis was developed a few years ago and studied extensively. This system was shown to catalyze the synthesis of mature mycolic acids from [14C]acetate, but allows only minimal deposition into the cell wall proper. In the meantime the sequence of the entire genome of M. tuberculosis has been elucidated and its analysis using numerous protein sequence-based algorithms predicted cytoplasmic localization and a soluble, not a particulate, nature for the enzymes involved in the mycolic acid synthetic pathway. Accordingly, we re-assessed the 'cell-free' system for mycolic acid synthesis and concluded that it is probably due to the presence of unbroken cells, since viable cells were recovered from the cell wall preparation. The amount of whole cells depended upon the efficiency of the cell disruption method and conditions, and the amount of mycolic acid synthesized by the putative cell-free system correlated with the content of whole cells. Thus, accumulated results from the use of this 'cell-free' cell wall-based system should be re-evaluated in the light of these new data.

Cell Fractionation↗

Phosphatidylinositol synthesis in mycobacteria.

The metabolism and synthesis of an important mycobacterial lipid component, phosphatidylinositol (PI), and its metabolites, was studied in Mycobacterium smegmatis and M. smegmatis subcellular fractions. Little is known about the synthesis of PI in prokaryotic cells. Only a cell wall fraction (P60) in M. smegmatis was shown to possess PI synthase activity. Product was identified as PI by migration on TLC, treatment with phospholipase C and ion exchange chromatography. PI was the only major product (92.3%) when both cells and P60 fraction were labeled with [3H]inositol. Also, a neutral lipid inositol-containing product (4.1% of the total label) was identified in the P60 preparations. Strangely, PI synthase substrates, CDP-dipalmitoyl-DAG and CDP-NBD-DAG, added to the assay did not stimulate [3H]PI and NBD-PI yield by M. smegmatis. At the same time, addition of both substrates to rat liver and Saccharomyces cerevisiae PI synthase assays resulted in an increase in the product yield. Upon addition of CHAPS to the mycobacterial PI synthase assay, both substrates were utilized in a dose-dependent manner for the synthesis of NBD-PI and [3H]PI. These results demonstrate a strict substrate specificity of mycobacterial PI synthase toward endogenous substrates. K(m) of the enzyme toward inositol was shown to be 25 microM; Mg2+ stimulated the enzyme to a greater degree than Mn2+. Structural analogs of myo-inositol, epi-inositol and scyllo-inositol and Zn2+ were shown to be more potent inhibitors of mycobacterial PI synthase than of mammalian analogs. Lack of sequence homology with mammalian PI synthases, different kinetic characteristics, existence of selective inhibitors and an important physiological role in mycobacteria, suggest that PI synthase may be a good potential target for antituberculosis therapy.

Animals↗

Why does tonsillar herniation not occur in idiopathic intracranial hypertension?

Idiopathic intracranial hypertension (IHH or pseudotumor cerebri) is an uncommon but important cause of headache, characterized by raised intracranial pressure (ICP) in the absence of infection and intracranial pathology on neuroimaging. Lumbar puncture (LP) is usually contra-indicated in situations where the ICP is suspected to be high. However, tonsillar herniation is hardly ever reported after an LP in patients suspected of having IHH. The author postulates that increasing brain stiffness reported in IHH may be the reason for this observation. On the other hand, tonsillar herniation may occur as a late complication following lumbo-peritoneal shunt insertion (occasionally used in the management of patients with IHH). This may be due to the decrease in brain stiffness, i.e. an increase in brain compliance as the condition improves following shunt insertion. Recent advances in magnetic resonance imaging techniques are likely to help us further in understanding the pathogenesis of this curious condition.

Hernia↗

Dot immunobinding assay for detection of bovine herpesvirus 4 antibodies in rabbits.

A dot immunobinding assay (DIA) was used for the detection of antibody against bovine herpesvirus 4 (BHV-4) in experimentally infected specific-pathogen-free male and female rabbits. A semipurified virus preparation was used as the antigen, and protein A/G-horseradish-peroxidase conjugate and diaminobenzidine tetrahydrochloride were used as the detection system. Results of the DIA procedure on serum samples of experimentally infected male and female rabbits were compared with those of a complement-dependent virus neutralization (VN) test. None of the tested sera (0/60 samples) from either male or female rabbits were positive by the complement-dependent VN test. Results of the DIA procedure for the same tested sera were positive in 35 of 60 samples (58%) from BHV-4 infected rabbits, indicating higher sensitivity of DIA procedure as compared with the complement-dependent VN test.

Animals↗