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Biomedical subjects

M Malek

Publications and source records attributed to M Malek.

At least 37 records · Page 2Linked to original sources
PubMed2002

Induction and maintenance of clinical remission by interferon-beta in patients with steroid-refractory active ulcerative colitis-an open long-term pilot trial.

BACKGROUND: The imbalance of pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of inflammatory bowel disease. Shifting this disturbed ratio by means of TNF-antibodies or interferon has been shown to be helpful in treating Crohn's disease and multiple sclerosis, respectively. AIM: This pilot study investigated whether interferon-beta can induce clinical remission in corticoid-refractory ulcerative colitis. METHODS: Twenty-five patients with steroid-refractory active ulcerative colitis (Clinical activity index according to Rachmilewitz: 13.5 +/- 5.2) were treated in an open pilot trial with 0.5 MIU human natural interferon-beta (hn-IFN-beta) i.v. (n=18) or 1 MIU recombinant interferon-beta-1a (r-IFN-beta-1-a) s.c. (n=7) daily with the goal of induction of remission. Subsequent maintenance treatment was carried out for 52.0 +/- 78.8 weeks (range 4-336 weeks) with the same dose, three times per week. RESULTS: Twenty-two of 25 patients (88%) went into remission during induction treatment (hn-IFN-beta 16/18, r-IFN-beta-1a 6/7). Mean time to response was 3.0 +/- 1.3 weeks. Mean length of remission was 13.0 +/- 19.7 months. Only eight of 22 patients in remission relapsed during maintenance treatment. Five of these went into remission again after increasing the dose. Adverse events consisted of slight to moderate flu-like symptoms and slight to moderate hair loss in five of 15 female patients. CONCLUSION: Although this open pilot study included only a small number of patients, the high response rate suggests that interferon-beta may be a safe and effective treatment for steroid-refractory active ulcerative colitis.

Adjuvants, Immunologic↗
PubMed2002

Correlations among selected pork quality traits.

Establishing relationships among specific quality traits is important if significant progress toward developing improved pork quality is to be realized. As part of a study to examine the individual effects of genes on meat quality traits in pigs, a three-generation resource family was developed. Two Berkshire sires and nine Yorkshire dams were used to produce nine F1 litters. Sixty-five matings were made from the F1 litters to produce four sets of F2 offspring, for a total of 525 F2 animals used in the study. These F2 animals were slaughtered at a commercial facility upon reaching approximately 110 kg. Carcass composition traits, pH measurements, and subjective quality scores were made at 24 h postmortem. Loin samples (n = 525) were collected at 48 h postmortem, and meat quality traits were evaluated. These traits included pH (48 h), Hunter L-values, drip loss, glycolytic potential, ratio of type IIa/IIb myosin heavy chains (IIa/IIb), total lipid, instrumental measures of tenderness using the Star Probe attachment of the Instron, cook loss measurements, and sensory evaluations. Significant phenotypic correlations were found between many carcass, instrumental, and biochemical measurements, and sensory quality traits. Star Probe measurements were significantly correlated with drip loss (0.29), glycolytic potential (0.30), pH (-0.29), total lipid (-0.14), and Hunter L-values (0.28). Drip loss was significantly correlated with glycolytic potential (0.36), pH (-0.28), IIa/IIb (-0.10), and Hunter L-values (0.33). Hunter L-values were also significantly correlated with total lipid (0.33) and IIa/ IIb (-0.11). Sensory tenderness, flavor, and off-flavor scores were significantly correlated with drip loss, pH, and glycolytic potential measurements. Marbling score, total lipid, and drip loss were not significantly correlated with sensory juiciness scores, but cooking loss was. Marbling and total lipid were significantly correlated with firmness scores (0.37 and 0.31, respectively). Taken together, the data in this study suggest that changes in some meat quality traits can affect many other meat quality attributes. The correlations yield information that could aid in directing future studies aimed at understanding the underlying biological mechanisms behind the development of many quality traits.

Animals↗
PubMed2001

The cost utility analysis of riluzole for the treatment of amyotrophic lateral sclerosis in the UK.

This study reports the results of a long-term economic evaluation of riluzole in the treatment of amyotrophic lateral sclerosis (ALS) versus best supportive care in the United Kingdom. The aim was to assess the cost implications of the life extension offered by riluzole through cost utility analysis based on patient assessed utilities of different health states.A Markov model was used to assess the cost-effectiveness of Rilutek with best supportive care. Transition possibilities and the distribution of patients by health states were taken from a cohort of 954 patients drawn from a large randomised, double blind, placebo-controlled, multicentre trial between 1992 and 1994 in the first 18 months and used to extrapolate the model to assess the long-term prolongation of life. Four distinct health states were used corresponding to mild, moderate, severe and terminal states. Costs associated with Rilutek included the acquisition cost and bi-monthly monitoring for raised ALT levels. Patient assessed utilities were collected by use of the standard gamble technique. 77 patients were entered into the study from two centres (King's, London and Preston) in the UK. Mean utilities for each of the health states was generated and, given that the data were skewed, a sensitivity analysis was undertaken with the median utility values. The implications of life extension offered by riluzole versus best supportive care were assessed both in terms of life extension projected and quality adjusted survival using patient based utilities. Using the Markov model and the transitional probabilities the base case cost per life year gained was estimated at pound sterlings 14,370 and applying Standard Gamble utility scores, the base case cost per QALY was assessed as pound sterlings 20,904. The effect of discounting costs and benefits altered the cost effectiveness analysis to pound sterlings 17,760 per life year gained while a sensitivity analysis around median or mean scores for the utility weight resulted in a range of pound sterlings 19,020 to pound sterlings 25,794 per QALY gained.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0 MeV. The measured solar neutrino flux is 2.32+/-0.03(stat)+0.08-0.07(syst)x10(6) cm(-2) x s(-1), which is 45.1+/-0.5(stat)+1.6-1.4(syst)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry (Phi(n)-Phi(d))/Phi(average) is 0.033+/-0.022(stat)+0.013-0.012(syst). The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L. upper limit of 40x10(3) cm(-2) x s(-1), which is 4.3 times the BP2000 SSM prediction.

Journal Article↗
PubMed2001

Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.

Journal Article↗
PubMed2001

Effects of the digenean parasites Labratrema minimus and Cryptocotyle concavum on the growth parameters of Pomatoschistus microps and P. minutus from Southwest Wales.

During the present study, about 800 specimens of gobies (Pomatoschistus microps and P. minutus) from two sites at Gower Peninsula, Southwest Wales, were studied. Both species were infected with the digenean parasites Labratrema minimus and Cryptocotyle concavum. The effects of these parasites on host-growth parameters such as the condition factor, the gutted condition factor, the hepatosomatic index, and the gonadosomatic index were considered. The results of multiple regression and hierarchical analysis of variance (ANOVA) show that in P. microps, increasing numbers of C. concavum in the peritoneum appear to reduce the hepatosomatic index, whereas rising numbers of L. minimus increase it. In P. minutus, increasing numbers of L. minimus in the liver and muscle decrease the hepatosomatic index and the gonadosomatic index. The opposite effects of L. minimus on the hepatosomatic index of these host species are discussed.

Animals↗
PubMed2001

A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. I. Growth and body composition.

Genome scans can be employed to identify chromosomal regions and eventually genes (quantitative trait loci or QTL) that control quantitative traits of economic importance. A three-generation resource family was developed by using two Berkshire grand sires and nine Yorkshire grand dams to detect QTL for growth and body composition traits in pigs. A total of 525 F2 progeny were produced from 65 matings. All F2 animals were phenotyped for birth weight, 16-day weight, growth rate, carcass weight, carcass length, back fat thickness, and loin eye area. Animals were genotyped for 125 microsatellite markers covering the genome. Least squares regression interval mapping was used for QTL detection. All carcass traits were adjusted for live weight at slaughter. A total of 16 significant QTL, as determined by a permutation test, were detected at the 5% chromosome-wise level for growth traits on Chromosomes (Chrs) 1, 2, 3, 4, 6, 7, 8, 9, 11, 13, 14, and X, of which two were significant at the 5% genome-wise level and two at the 1% genome-wise level (on Chrs 1, 2, and 4). For composition traits, 20 QTL were significant at the 5% chromosome-wise level (on Chrs 1, 4, 5, 6, 7, 12, 13, 14, 18), of which one was significant at the 5% genome-wise level and three were significant at the 1% genome-wise level (on Chrs 1, 5, and 7). For several QTL the favorable allele originated from the breed with the lower trait mean.

Animals↗
PubMed2001

A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. II. Meat and muscle composition.

Molecular genetic markers can be used to identify chromosomal regions that contain quantitative trait loci (QTL) that control meat quality and muscle composition traits in farm animals. To study this in pigs, a resource family was generated from a cross between two Berkshire grand sires and nine Yorkshire grand dams. A total of 525 F2 progeny from 65 matings of F1 parents were produced. Phenotypic data on 28 meat quality traits (drip loss, water holding capacity, firmness, color, marbling, percentage cholesterol, ultimate pH, fiber type, and several sensory panel and cooking traits) were collected on the F2 animals. Animals were genotyped for 125 microsatellite markers covering the entire genome. Least squares regression interval mapping was used for QTL detection. Significance thresholds were determined by permutation tests. A total of 60 QTL were detected at the 5% chromosome level for meat quality traits, on Chrs 1, 2, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 17, 18, and X, of which 9 and 1 QTL were significant at the 5% and 1% genome-wise levels (on Chrs 1, 5, 12, 15, and 17), respectively.

Adipose Tissue↗
PubMed2001

Evidence for new alleles in the protein kinase adenosine monophosphate-activated gamma(3)-subunit gene associated with low glycogen content in pig skeletal muscle and improved meat quality.

Several quantitative trait loci (QTL) affecting muscle glycogen content and related traits were mapped to pig chromosome 15 using a three-generation intercross between Berkshire x Yorkshire pigs. On the basis of the QTL location the PRKAG3 (protein kinase, AMP-activated, gamma(3)-subunit) gene was considered to be a good candidate for the observed effects. Differences in the PRKAG3 gene sequences of the founder animals of the intercross were analyzed. The RN(-) mutation previously reported was not present in the cross but three missense substitutions and a polymorphic short interspersed element (SINE) were identified. To confirm the hypothesis that at least one of these mutations was associated with differences in meat quality, >1800 animals from several unrelated commercial lines were genotyped for the candidate substitutions and an association study was performed. The results demonstrate the presence of new economically important alleles of the PRKAG3 gene affecting the glycogen content in the muscle and the resulting meat quality. Haplotype analysis was shown to resolve the effects of PRKAG3 more clearly than analysis of individual polymorphisms. Because of their prevalence in the more common commercial breeds, the potential implications for the pig industry and consumers are considerably greater than the original discovery of the RN(-) mutation. Furthermore, these results illustrate that additional alleles of genes involved in major mutations may play a significant role in quantitative trait variation.

Alleles↗
PubMed2001

Palliation by intratumoral infiltration with natural interferon-beta.

BACKGROUND: Curative approaches to tumor therapy have achieved greater importance through new developments such as cytostatic agents and their combination with other therapy concepts, but for the majority of tumor patients only palliative therapy is possible. Size or location of tumor manifestations can result in severe discomfort for patients, in some cases even in a reduction of functionality. PATIENTS AND METHODS: For the purpose of this study, a total of 55 patients with a variety of advanced malignant diseases nonresponding or progressive under radio- and/or chemotherapy were treated by intratumoral injection of natural human fibroblast interferon (nIFN-beta). nIFN-beta was administered intralesionally 3 times per week for at least 4 weeks at doses of 2-8 MIU, depending on tumor size. Local tumor response was observed over a median follow-up period of 18 weeks. RESULTS: In 37 patients (67%) a complete or partial remission of the local tumor manifestation was achieved. Survival times of these patients were improved compared with those of patients without local tumor remission. 16 patients without significant change of tumor volume benefited from the palliative (extensive analgesic) effect of the nIFN-beta therapy. During treatment, none of the patients showed a progression of the locally treated tumor, even when the basic malignant disease progressed. The side effects of the nIFN-beta therapy were tolerable, and no patient discontinued therapy. CONCLUSION: From these observations, intralesional nIFN-beta therapy of malignant tumors appears to be a useful palliative addition to radio- and/or chemotherapy with the aim of local control of tumor growth.

Dose-Response Relationship, Drug↗
PubMed2000

A cost analysis of neonatal care in the UK: results from a multicentre study. ECSURF Study Group.

BACKGROUND: A number of papers have recently been published examining the magnitude of scale economies in neonatal care and the level of activity at which these become attainable. Although these agree there is scope for economies in the production of neonatal care, they debate the extent to which such economies are attainable and how they might best be detected. A major multicentre study of neonatal units in the United Kingdom has produced costing and activity data allowing these issues to be explored afresh. METHODS: A postal questionnaire was used to determine neonatal cost and activity levels in 57 UK neonatal units. Costs for the financial year 1990-1991 related to clinical staffing, support (such as pathology) and overheads (such as heat, light, power and administrative overheads). Activity related to the total number of care days provided and the number of these that were intensive in nature. All data were scrutinized to ensure consistent definitions. A multivariate regression analysis was used to investigate the relationship between costs and activity. RESULTS: A double-log function relating variations in total costs to total days, case-mix and an interaction term provided the best fit to the data. The analysis suggests that significant economies of scale are possible within the observed range of provision of intensive care. CONCLUSIONS: Significant economies of scale may be attainable. Nevertheless, these results should be carefully interpreted. In particular, the costs of neonatal care should not be examined in isolation but in relation to outcomes. In certain instances, units of inefficient scale but acceptable outcome may be defensible on grounds of ease of access.

Health Care Costs↗
PubMed1999

New insights into porcine-human synteny conservation.

Eleven genes were mapped to the porcine genome with the aim of improving the human-porcine comparative gene map. Five of these genes were from regions of the human genome painted by porcine chromosomal probes; of these, two mapped to chromosomes not expected from the painting results. Among the six genes from human regions not painted by porcine chromosomal probes, three genes did not map where expected by the principle of parsimony. Several of the gene assignments indicate the existence of small regions of conserved synteny not detected by heterologous chromosome painting, especially in telomeric regions. We have also detected new rearrangements in gene order within the regions of correspondence between human Chromosome (HSA) 15 and porcine Chromosome (SSC) 1 as well as between HSA4 and SSC8.

Animals↗
PubMed1999

Cost considerations in the evaluation of new therapies for gram-positive bacteria.

The rapid emergence of antibiotic resistance in hospitals and the community, particularly amongst Gram-positive cocci, has not been paralleled by adequate understanding of the true clinical and economic impact of infection with resistant pathogens. Furthermore, the development of novel compounds to combat this threat has been slow until recently when a number of new agents, some with a unique structure and mode of action (e.g. linezolid), are now being developed for clinical use. This paper aims to outline (1) the costs associated with infection by a resistant organism (2) the pharmacoeconomic arguments when considering a new drug and (3) the key decisions when evaluating a new drug such as linezolid, for inclusion in a formulary or policy with particular reference to the treatment of serious Gram-positive infections.

Cross Infection↗
PubMed1999

Cost-effectiveness of prophylactic nasal mupirocin in patients undergoing peritoneal dialysis based on a randomized, placebo-controlled trial.

The study objective was to measure the benefits of elimination of nasal carriage of Staphylococcus aureus by calcium mupirocin ointment in patients undergoing continuous ambulatory peritoneal dialysis. The design was a prospective, placebo-controlled, randomized clinical trial. The subjects were 267 patients recruited from nine renal units in Belgium, France and the UK. The main outcome measures were the rate of catheter exit site infection (ESI), rates of other infections and healthcare costs from the perspective of a hospital budget-holder. The rate of ESI caused by S. aureus was significantly reduced from one in 28.1 patient months to one in 99.3 patient months (P = 0.006) and there were also non-significant trends towards lower rates of ESI caused by any organism and peritonitis caused by S. aureus. In comparison with the placebo group, patients in the mupirocin group with ESI had lower antibiotic (P = 0.02) and hospitalization costs (P = 0.065). However, overall costs of antibiotic treatment, for all infections combined, were not significantly different (P = 0.2) and total antibiotic costs (including mupirocin) were significantly higher in the mupirocin group (P = 0.001). Mupirocin prophylaxis would have been cost-neutral if the rate of ESI increased to >75% in the placebo group, or if all healthcare costs increased by 40%, or if the cost of screening was reduced from Pound Sterling 15 to Pound Sterling 3 per patient, or if the cost of mupirocin treatment was reduced from Pound Sterling 93 to Pound Sterling 40 per patient year. In conclusion, savings in healthcare costs are unlikely to be sufficiently great to offset the cost of mupirocin and screening for nasal carriage of S. aureus. The decision about whether or not to implement mupirocin should depend on a local analysis of the value of preventing ESIs caused by S. aureus.

Administration, Intranasal↗
PubMed1999

Decision analysis of histamine H2-receptor antagonist maintenance therapy versus Helicobacter pylori eradication therapy: a randomised controlled trial in patients with continuing pain after duodenal ulcer.

BACKGROUND: Much has been published on the efficacy and cost effectiveness of Helicobacter pylori eradication treatment as an alternative to histamine H2-receptor antagonist maintenance treatment in peptic ulcer disease. However, most studies have analysed and emphasised H. pylori eradication rates rather than management/control of symptoms and the associated cost savings. Although H. pylori eradication therapy is very successful in clearing the infection, dyspeptic symptoms may persist and management of these can be expensive. OBJECTIVE: The aim of this study was to assess the cost implications in controlling symptoms using either H2-receptor antagonist maintenance therapy or H. pylori eradication therapy in patients with duodenal ulcer disease. DESIGN: This was a non-blind, prospective, randomised, parallel-group study comparing maintenance H2-receptor antagonist treatment using ranitidine with H. pylori eradication therapy, with a 1-year follow-up. SETTING: This was a study of outpatients from general practices in Dundee, Scotland, or the Ninewells Hospital, Dundee, gastroenterology clinic. PATIENTS AND PARTICIPANTS: 119 patients with confirmed duodenal ulcer, free from active ulceration at study entry but positive for H. pylori infection, who were receiving maintenance H2-receptor antagonist therapy. INTERVENTIONS: Patients were randomised to receive either continuing maintenance therapy with ranitidine (initially 150 mg daily; 58 patients) or H. pylori eradication therapy using an omeprazole/amoxicillin/metronidazole regimen (or omeprazole/clarithromycin if allergic to penicillin). MAIN OUTCOME MEASURES AND RESULTS: Overall, H. pylori eradication rates were 100% per protocol and 95.1% intention-to-treat. At completion of 1 year of follow-up, 12 of the 61 (19.7%) patients successfully eradicated of H. pylori were still dependent on acid suppression for symptom relief. H. pylori eradication treatment was the least-cost strategy in managing/controlling symptoms at 1 year (168 Pounds vs 210 Pounds per patient; 1996 values). However, over time, post-eradication treatment costs were greater than H2-receptor antagonist therapy costs. Any potential savings were directly related to the proportion of patients needing further treatment post-eradication, the cost of endoscopy and the urea breath test. CONCLUSIONS: If dyspepsia persists long term, H. pylori eradication treatment may not be the least-cost option for patients with duodenal ulcer.

Decision Support Systems, Clinical↗