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M Roberts

Publications and source records attributed to M Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2001

The molecular mechanisms of severe typhoid fever.

Salmonella typhi continues to cause severe disease in many parts of the world, its most feared complication being perforation of ulcerated Peyer's patches within the small intestine, leading to peritonitis with associated mortality. The pathogenesis of this process is not well understood. In this article, we present a theoretical mechanism as to how bacterial factors and host immunological mediators within infected tissue might contribute to the observed intestinal pathology, and propose that necrosis of the Peyer's patches observed in typhoid is caused by a mechanism similar to the Shwartzman and Koch reactions.

Enterotoxins↗
PubMed2001

Intrapartum management of nonvertex second-born twins: a critical analysis.

OBJECTIVE: Our purpose was to assess the impact of the mode of delivery--vaginal delivery versus cesarean section--on the perinatal outcomes of the second-born breech twins. STUDY DESIGN: This study was a retrospective analysis of second-born breech twins with a gestational age of > or =24 weeks at the onset of labor. The patients are divided into three groups: cesarean section without labor (group I), cesarean section after labor (group II), and vaginal breech delivery (group III). RESULTS: There were 141 patients: 40 in group I, 66 in group II, and 35 in group III. There was no birth injury or neonatal death. Group II had one fetus with grade II intraventricular hemorrhage. There was no significant difference among the groups with regard to gestational age, birth weight, hyaline membrane disease, Apgar scores at 1 and 5 minutes, and cord blood gas indices, except venous pH in infants with birth weights <1500 g. CONCLUSIONS: Vaginal delivery of breech second-born twins, with gestational ages of at least 24 weeks, especially those with birth weights of > or =1500 g, appears to be a safe alternative to cesarean section.

Birth Weight↗
PubMed2001

Mycobacterium tuberculosis chaperonin 60.1 is a more potent cytokine stimulator than chaperonin 60.2 (Hsp 65) and contains a CD14-binding domain.

Much attention has focused on the Mycobacterium tuberculosis molecular chaperone chaperonin (Cpn) 60.2 (Hsp 65) in the pathology of tuberculosis because of its immunogenicity and ability to directly activate human monocytes and vascular endothelial cells. However, M. tuberculosis is one of a small group of bacteria that contain multiple genes encoding Cpn 60 proteins. We have now cloned and expressed both M. tuberculosis proteins and report that the novel chaperonin 60, Cpn 60.1, is a more potent inducer of cytokine synthesis than is Cpn 60.2. This is in spite of 76% amino acid sequence similarity between the two mycobacterial chaperonins. The M. tuberculosis Cpn 60.2 protein activates human peripheral blood mononuclear cells by a CD14-independent mechanism, whereas Cpn 60.1 is partially CD14 dependent and contains a peptide sequence whose actions are blocked by anti-CD14 monoclonal antibodies. The cytokine-inducing activity of both chaperonins is extremely resistant to heat. Cpn 60.1 may be an important virulence factor in tuberculosis, able to activate cells by diverse receptor-driven mechanisms.

Amino Acid Sequence↗
PubMed2001

Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance.

Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.

Animal Husbandry↗
PubMed2001

DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells.

The increased availability of saturated lipids has been correlated with development of insulin resistance, although the basis for this impairment is not defined. This work examined the interaction of saturated and unsaturated fatty acids (FA) with insulin stimulation of glucose uptake and its relation to the FA incorporation into different lipid pools in cultured human muscle. It is shown that basal or insulin-stimulated 2-deoxyglucose uptake was unaltered in cells preincubated with oleate, whereas basal glucose uptake was increased and insulin response was impaired in palmitate- and stearate-loaded cells. Analysis of the incorporation of FA into different lipid pools showed that palmitate, stearate, and oleate were similarly incorporated into phospholipids (PL) and did not modify the FA profile. In contrast, differences were observed in the total incorporation of FA into triacylglycerides (TAG): unsaturated FA were readily diverted toward TAG, whereas saturated FA could accumulate as diacylglycerol (DAG). Treatment with palmitate increased the activity of membrane-associated protein kinase C, whereas oleate had no effect. Mixture of palmitate with oleate diverted the saturated FA toward TAG and abolished its effect on glucose uptake. In conclusion, our data indicate that saturated FA-promoted changes in basal glucose uptake and insulin response were not correlated to a modification of the FA profile in PL or TAG accumulation. In contrast, these changes were related to saturated FA being accumulated as DAG and activating protein kinase C. Therefore, our results suggest that accumulation of DAG may be a molecular link between an increased availability of saturated FA and the induction of insulin resistance.

Acetates↗
PubMed2000

(18)O/(16)O and (13)C/(12)C in an ahermatypic deep-water coral Lophelia pertusa from the North Atlantic: a case of disequilibrium isotope fractionation.

The numerous stable isotope studies of scleractinian photosynthetic reef-building corals in tropical seas have demonstrated the complexity of the biological and environmental factors that give rise to their isotopic composition. Scleractinian non-photosynthetic corals of the deep cold water environment might be expected to reflect the more stable physical environment in the deep sea. However, in comparison, little is known about their isotope systematics. The present study concentrates on specimens of Lophelia pertusa from the north-eastern Atlantic, the Norwegian Shelf and Fjord. Aliquots taken from the theca represent time series and show variations in delta(13)C and delta(18)O of up to 4.7 and 2.4 per thousand, respectively. The variations seem to be related to morphological features of branching. The tendency of higher values near the tip of the polyps reported previously was detected only in some samples. The delta(18)O of the corals are in all cases more negative than the equilibrium values. There is a strong correlation between delta(13)C and delta(18)O forming linear arrays. The difference between these arrays is more pronounced in delta(13)C. The covariation of delta(13)C and delta(18)O indicates an overruling 'kinetic isotope effect'. This is in line with the behaviour of some trace elements. This isotope effect should be regarded as one manifestation of variations in partition coefficients dictated by a biological control on mineralisation (such as food or reproduction) rather than changes in the relative contribution of metabolic carbon affecting delta(13)C, and changes in temperature affecting delta(18)O.

Animals↗
PubMed2000

Retinal function is improved in a murine model of a lysosomal storage disease following bone marrow transplantation.

Mucopolysaccharidoses are heritable lysosomal storage diseases caused by deficiencies in acid hydrolases involved in the sequential degradation of complex glycosaminoglycans (GAGs). In many mucopolysaccharidoses, GAGs accumulate in the retinal pigment epithelial (RPE) cells of the eye resulting in pronounced lysosomal distension. It is not clear how the progressive accumulation of GAGs affects retinal function. Bone marrow transplantation (BMT) is a relatively effective therapy for many lysosomal storage diseases and can result in a dramatic reduction in lysosomal distention in the RPE. Although effective at reducing lysosomal storage, it is not clear how effective syngeneic BMT is at treating retinal dysfunction. Here we show that there is a progressive decrease in the amplitudes of both the dark-adapted (rod-cone) and light-adapted (cone-dominated) flash electroretinograms (ERG) between 8 and 20 weeks of age in a murine model of mucopolysaccharidosis type VII (MPS VII). By 20 weeks, the average dark-adapted b-wave amplitude was 118 microV in MPS VII mice as compared to 469 microV in normal mice of the same strain. MPS VII mice receiving syngeneic BMT at 4 weeks of age have reduced lysosomal storage in retinal pigment epithelial cells and normal ERG amplitudes at 20 weeks of age. Retinal function is impaired in untreated 8 week old MPS VII mice. Following BMT at 8 weeks, rod-cone- and cone-dominated responses recovered to within the normal range by 20 weeks of age. These data demonstrate the temporal pattern of retinal dysfunction in the MPS VII mouse and indicate that BMT can reduce the lysosomal storage and improve retinal function.

Animals↗
PubMed2000

The use of nicotine replacement therapy during hospitalization.

Recent findings suggest that smokers who are hospitalized experience significant craving for cigarettes. Thus, nicotine replacement therapy (NRT) may be a particularly important tool for use during hospitalization. The goal of this study is to evaluate the utilization of the transdermal nicotine patch and/or nicotine gum by hospitalized smokers. The data represented in this article are from 580 smokers who participated in a study of a motivational intervention for smoking cessation that was delivered during hospitalization. The primary outcome for this analysis was use of NRT during hospitalization. The results revealed that, among the entire sample, only 7.1% of the overall sample used NRT during hospitalization; 6% of the hospitalized smokers used the transdermal nicotine patch, and 1.1% used nicotine gum. Use of NRT was significantly greater among patients who reported that they were doing anything to help themselves quit smoking at the time of admission (OR = 4.1), those who were seriously planning to quit smoking within the next 30 days (OR = 2.36), those who were nicotine dependent (OR = 2.81), and those for whom a physician had ever offered to prescribe NRT (OR = 1.9). The finding that there is a very low rate of NRT use during hospitalization provides important information to hospital-based care providers and smoking cessation intervention planners. Barriers to NRT use among hospitalized patients should be identified, and strategies designed to maximize use when appropriate. The AHCPR Guideline on Smoking Cessation recommends routine use of NRT in health care settings. Further research is needed to determine why NRT use was so low. In addition, these data suggest that efforts to increase NRT use during hospitalization are needed.

Administration, Cutaneous↗
PubMed2000

An estradiol matrix transdermal system for the prevention of postmenopausal bone loss.

OBJECTIVE: The aim of this study was to evaluate the efficacy, safety, and tolerability of 2 years' application of an estradiol matrix transdermal system for the prevention of postmenopausal bone loss. METHODS: In this multicenter, randomized, placebo-controlled, parallel-group study, 261 surgically or naturally postmenopausal women were randomized to apply the estradiol matrix transdermal system (0.025, 0.0375, 0.05, or 0.1 mg/d) or matching placebo twice a week for 2 years. The study was double blind with respect to treatment (active vs placebo) but not to the dose levels of active treatment (because of the differing sizes and shapes of the patches). In addition to receiving the assigned treatment, the 100 nonhysterectomized women received 2.5 mg medroxyprogesterone acetate daily throughout the study. RESULTS: The evaluable group (n = 259) had a mean age of 52 years and a mean duration of menopause of 32 months. Following 2 years of treatment, there were significant differences in favor of estradiol between all doses of the estradiol matrix transdermal system and placebo in terms of the percentage change from baseline in the bone mineral density (BMD) of the L1-L4 anteroposterior lumbar spine (0.1 and 0.05 mg/d, P < 0.001; 0.0375 mg/d, P = 0.024; 0.025 mg/d, P = 0.002). Percentage changes from baseline in the BMD of the femoral neck after 2 years of treatment also consistently demonstrated the efficacy of the estradiol matrix transdermal system compared with placebo (all, P < or = 0.044). The estradiol matrix transdermal system was well tolerated. CONCLUSION: The estradiol matrix transdermal system was effective in preventing postmenopausal bone loss at dosages of 0.025 to 0.1 mg/d, and had a safety profile consistent with the known effects of estrogen/progestin.

Administration, Cutaneous↗
PubMed2000

Carbohydrate biopolymers enhance antibody responses to mucosally delivered vaccine antigens.

We have evaluated the ability of two carbohydrate biopolymers, chitosan and gellan, to enhance antibody responses to subunit influenza virus vaccines delivered to the respiratory tracts of mice. Groups of mice were vaccinated three times intranasally (i.n.) with 10 microg of purified influenza B/Panama virus surface antigens (PSAs), which consist of hemagglutinin (HA) and neuraminidase (NA), either alone or admixed with chitosan or gellan solutions. Separate groups were vaccinated subcutaneously (s.c.) with PSAs adsorbed to Alhydrogel or chitosan or gellan alone i.n. Serum antibody responses were determined by enzyme-linked immunosorbent assay (ELISA) for influenza virus-specific immunoglobulin G (IgG) and by HA inhibition (HAI) and NA inhibition (NAI) assays. The local respiratory immune response was measured by assaying for influenza virus-specific IgA antibody in nasal secretions and by enumerating nasal and pulmonary lymphocytes secreting IgA, IgG, and IgM anti-influenza virus-specific antibodies by enzyme-linked immunospotting (ELISPOT). When administered alone i.n., B/Panama PSA was poorly immunogenic. Parenteral immunization with B/Panama PSA with Alhydrogel elicited high titers of anti-B/Panama antibodies in serum but a very poor respiratory anti-B/Panama IgA response. In contrast, i.n. immunization with PSA plus chitosan stimulated very strong local and systemic anti-B/Panama responses. Gellan also enhanced the local and serum antibody responses to i.n. PSA but not to the same extent as chitosan. The ability of chitosan to augment the immunogenicity of influenza vaccines given i.n. was confirmed using PSA prepared from an influenza A virus (A/Texas H1N1).

Animals↗
PubMed2000

Comparison of abilities of Salmonella enterica serovar typhimurium aroA aroD and aroA htrA mutants to act as live vectors.

We compared the ability of Salmonella enterica serovar Typhimurium SL1344 aroA aroD (BRD509) and aroA htrA (BRD807) mutants to act as live vectors for delivery of fragment C of tetanus toxin (FrgC). FrgC was expressed in these strains from either pTETnir15 or pTEThtrA1. BRD509FrgC(+) strains elicited approximately 2-log-higher serum anti-FrgC antibody titers than BRD807FrgC(+) strains. All mice immunized with BRD807pTEThtrA1, BRD509pTEThtrA1, and BRD509pTETnir15 (but not BRD807pTETnir15) were protected against tetanus.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed2000

Diametric effects of bacterial endotoxin lipopolysaccharide on adrenal and Leydig cell steroidogenic acute regulatory protein.

Immune activation results in the activation of adrenal steroidogenesis and inhibition of gonadal steroidogenesis. Previous studies indicated that these effects were caused primarily by activation and suppression of the secretion of ACTH and LH, respectively. However, other evidence indicated a direct effect of the immune system on the gonads. In this study, serum testosterone, quantitated by RIA after lipopolysaccharide injection, showed a significant decrease within 2 h. Parallel measurement of serum LH showed no change. There were no differences in LH receptor or cAMP produced in Leydig cells between vehicle- and lipopolysaccharide-injected mice. The 30-kDa form of the steroidogenic acute regulatory (StAR) protein was quantitated, by Western blot, in Leydig cells and was found to decrease in a time-dependent manner. No change in StAR protein messenger RNA (mRNA) was detected by Northern analysis during this time, nor were any changes found in the levels of mRNA for the steroidogenic enzymes P450scc, 3beta-hydroxysteroid dehydrogenase delta4-delta5-isomerase, or P450c17. In the adrenal, StAR protein was increased, as was StAR protein mRNA. No changes were observed in the levels of mRNA for P450scc, 3beta-hydroxysteroid dehydrogenase delta4-delta5-isomerase, or P450c21. Thus, although the mechanisms of regulation differ, changes in the levels of StAR protein are a sensitive indicator of the steroidogenic capacity of these two tissues.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Thrombolytic therapy for stroke: a review with particular reference to elderly patients.

Clinical trials in the 1990s of intravenous thrombolysis for ischaemic stroke have involved over 3000 patients. Alteplase given within 3 hours of onset significantly reduces the combined end-point of death and disability. Although alteplase appears safe when given up to 6 hours after onset, individual trials have failed to confirm efficacy beyond 3 hours. Meta-analysis indicates that intravenous alteplase given up to 6 hours after stroke onset significantly reduces death or dependence 3 months after stroke. Two trials of intra-arterial pro-urokinase confirm benefits of treatment up to 6 hours in highly selected patients with angiographically confirmed proximal middle cerebral occlusion. Streptokinase increased the risk of early death significantly in 3 trials, with no overall reduction in eventual death and disability. Patients over 80 years have been excluded from most trials of alteplase, and experience in this age group is minimal. Increased incidence and poorer functional outcome in the elderly mean that thrombolysis may have greater absolute benefit in this group than in the young, but there is also a higher prevalence of absolute or relative potential contraindications to treatment (ranging from increased use of anticoagulant drugs to higher prevalence of atrial fibrillation). Further trials are necessary to address age restrictions and other important issues in the use of alteplase. Thrombolysis is likely to remain feasible for a minority of stroke patients of all ages, and there is a need for other acute treatment options.

Aged↗
PubMed2000

A one-centre prospective audit of peri- and postoperative blood loss and transfusion practice in patients undergoing hip or knee replacement surgery.

We prospectively audited peri-operative blood loss and blood transfusion practice in 42 elderly patients (mean age, 71.8 years, 68% female) undergoing hip or knee surgery in an orthopaedic unit. Only in 57% of all operations was blood loss recorded. Compliance with the Maximum Surgical Blood Ordering Schedule (MSBOS) was variable, and Cross-matching to Transfusion (C/T) ratios were low. In 86% of operations, blood had been issued pre-operatively (average three units, range = 1-61 units). Of these patients, 75% subsequently received a transfusion. In 26% of all the operations, the transfusion, although confirmed by the blood transfusion laboratory records, had not been recorded in the medical or nursing notes. The average pre-operative Hb in the transfusion group was 123 g/l (range, 80-144 g/l) and 112 g/l postoperatively and after a transfusion (range, 75-133 g/l). This compared to the non-transfusion group's value of 124 g/l (range, 86-186 g/l) and 113 g/l (range, 77-147 g/l) postoperatively. The high blood issuing and transfusion rates raise the concern that transfusions are being given in response to habit or blood availability, and not medical indications. This would imply that some patients are exposed to unnecessary risks. Furthermore, inadequate documentation of the transfusion process opens the medical profession to criticism and medical, legal and ethical complications regarding patient care. Positive improvements suggested by regular medical audit may help address these problems.

Aged↗