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S Hughes

Publications and source records attributed to S Hughes.

At least 73 records · Page 4Linked to original sources

Molecular typing of Mycobacterium bovis isolates from Cameroon.

In order to gain a better understanding of the molecular epidemiology of Mycobacterium bovis isolates in Cameroon, 75 isolates of M. bovis collected in three provinces of northern Cameroon were studied by spoligotyping. For 65 of these isolates, typing was also carried out by pulsed-field gel electrophoresis (PFGE) with DraI, and 18 of the isolates were also typed by restriction fragment length polymorphism (RFLP) analysis with probe IS6110-RHS. Molecular typing of the isolates by these techniques revealed a high degree of homogeneity, with 10 spoligotypes for 75 isolates, four PFGE profiles for 65 isolates, and three RFLP types for 18 isolates. Some types were present in the three different provinces, while some were confined to one or two areas. These results suggest that geographical mapping of M. bovis strains could be helpful for the control of bovine tuberculosis at the regional level. An interesting feature of all the spoligotypes was the absence of spacer 30, suggesting a common origin for all of the Cameroon isolates tested; an evolutionary scenario for the isolates is discussed. In addition, a comparison of the three techniques showed that for M. bovis strain differentiation in Cameroon and in surrounding countries, spoligotyping would be a more discriminating and practical tool for molecular typing than the other two techniques used in this study.

Animals↗

Genetic diversity among Mycobacterium bovis isolates: a preliminary study of strains from animal and human sources.

Mycobacterium bovis has the broadest host range of species in the Mycobacterium tuberculosis complex and is responsible for disease in humans and diverse animal species. We report on genotypic differences at multiple loci among 13 isolates derived from a range of human and animal infections. All isolates were classified as M. bovis by phenotypic analysis but could be subdivided into five distinct genotypes based on polymorphisms at the pncA and oxyR loci, the status of the RD5 deletion region, and the spoligotype pattern. These findings suggest the existence of a spectrum of strains with genotypic characteristics between those of M. tuberculosis and M. bovis.

Aged↗

Is Mycoplasma hominis a vaginal pathogen?

OBJECTIVE: To evaluate the role of Mycoplasma hominis as a vaginal pathogen. DESIGN: Prospective study comprising detailed history, clinical examination, sexually transmitted infection (STI) and bacterial vaginosis screen, vaginal swabs for mycoplasmas and other organisms, follow up of bacterial vaginosis patients, and analysis of results using SPSS package. SETTING: Genitourinary medicine clinic, Royal Liverpool University Hospital. PARTICIPANTS: 1200 consecutive unselected new patients who had not received an antimicrobial in the preceding 3 weeks, and seen by the principal author, between June 1987 and May 1995. MAIN OUTCOME MEASURES: Relation of M. hominis isolation rate and colony count to: (a) vaginal symptoms and with the number of polymorphonuclear leucocytes (PMN) per high power field in the Gram stained vaginal smear in patients with a single condition--that is, candidiasis, bacterial vaginosis, genital warts, chlamydial infection, or trichomoniasis, as well as in patients with no genital infection; (b) epidemiological characteristics of bacterial vaginosis. RESULTS: 1568 diagnoses were made (the numbers with single condition are in parenthesis). These included 291 (154) cases of candidiasis, 208 (123) cases of bacterial vaginosis, 240 (93) with genital warts, 140 (42) chlamydial infections, 54 (29) cases of trichomoniasis, and 249 women with no condition requiring treatment. M. hominis was found in the vagina in 341 women, but its isolation rates and colony counts among those with symptoms were not significantly different from those without symptoms in the single condition categories. There was no association between M. hominis and the number of PMN in Gram stained vaginal smears whether M. hominis was present alone or in combination with another single condition. M. hominis had no impact on epidemiological characteristics of bacterial vaginosis. CONCLUSION: This study shows no evidence that M. hominis is a vaginal pathogen in adults.

Adult↗

Increased throughput for fragment analysis on an ABI PRISM 377 automated sequencer using a membrane comb and STRand software.

This manuscript outlines our protocol for using a freely downloadable fragment analysis software package (STRand) together with a 96+4 RapidLoad membrane comb to increase throughput of samples for fragment analysis on ABI sequencers without costly upgrades from the manufacturer. We outline how using these products allows one to score 90 lanes of sample per gel on an ABI PRISM 377XL (64-lane sequencer), saving both time and money in the processing of samples. This protocol is a major modification to those suggested by the manufacturer. This protocol gives more consistent results that are easier to score than standard protocols, and it reduces reagent costs. Interest in fragment analysis (primarily microsatellites and AFLPs) is steadily increasing among both population ecologists and geneticists, and methods that simultaneously increase sample throughput while reducing costs associated with these analyses by over 50% per gel should prove useful to anyone using an ABI, MJ Basestation, or LI-COR automated sequencer for fragment analysis.

Computational Biology↗

Chronic stimulation of the peroneal nerve in rats upregulates the pro-opiomelanocortin gene in spinal motoneurones.

Continuous unilateral stimulation of the peroneal nerve in rats for 8 h per day for 2 or 7 days caused significant increases in POMC mRNA and beta-endorphin immunoreactivity in both ipsilateral and contralateral motoneurones. Intermittent stimulation, for 10-min periods with 90-min rest periods, for 8 h per day for 2 days also caused upregulation of POMC mRNA. It is suggested that expression of POMC-derived peptides in motoneurones may be important for maintaining muscle contractile function.

Animals↗

Molecular evidence supports an african affinity of the neotropical freshwater gastropod, Biomphalaria glabrata, say 1818, an intermediate host for Schistosoma mansoni.

Freshwater snails of the genus Biomphalaria, Preston 1910, are the most important and widely distributed intermediate hosts of Schistosoma mansoni, the blood fluke responsible for human intestinal schistosomiasis, in Africa and the Neotropics. S. mansoni is thought to have been imported repeatedly into the Americas during the last 500 years with the African slave trade. Surprisingly considering that the New and Old World separated 95-106 million years (Myr) ago, the disease rapidly became established due to the presence of endemic susceptible hosts. Reconstructing the phylogenetic relationships within Biomphalaria may provide insights into the successful intercontinental spread of S. mansoni. Parsimony and distance analyses of mitochondrial and nuclear sequences show African taxa to be monophyletic and Neotropical species paraphyletic, with Biomphalaria glabrata forming a separate clade from other Neotropical Biomphalaria, and ancestral to the African taxa. A west to east trans-Atlantic dispersal of a B. glabrata-like taxon, possibly as recently as the Plio-Pleistocene (1.8-3.6 Myr ago) according to a general mitochondrial clock, would fit these observations. Vicariance or an African origin for B. glabrata followed by multiple introductions to South America over the past 500 years with the African slave trade seem unlikely explanations. Knowledge of the phylogenetic relationships among important intermediate host species may prove useful in furthering control measures which exploit genetic differences in susceptibility to parasites, and in elucidating the evolution of schistosome resistance.

Africa↗

Aortic root characteristics of human pulmonary autografts.

BACKGROUND: After pulmonary autograft replacement of the aortic valve and root, the pulmonary artery (PA) wall is subjected to higher pressures. Concern exists that this may lead to structural and functional changes in the implanted autograft and subsequent aortic root dilatation and neoaortic regurgitation. We therefore assessed root dimensions and neoaortic regurgitation, morphological structure, and mechanical behavior in patients who underwent the Ross operation. METHODS AND RESULTS: Seventy-four patients who were randomized to undergo aortic valve replacement with an aortic homograft or a pulmonary autograft were followed up echocardiographically for up to 4 years and had their aortic root dimensions measured at the level of the annulus, sinuses, and sinotubular junction. In a separate series of 18 patients who underwent pulmonary autograft surgery and 8 normal organ donors, samples from the PA and aorta were analyzed for medial wall thickness, distribution of the staining of collagen and elastin, and elastin fragmentation. Finally, stress-strain curves were obtained from samples of the PA and aorta from 9 patients who underwent pulmonary autograft surgery and from 1 patient in whom a 4-month-old autograft was explanted. No patient in either group had aortic dilatation at any level of >20% or more than mild aortic regurgitation at up to 4 years of follow-up. The aortic media was thicker in both autografts and normal donors (P:<0.01), and there was a trend for the PA media to be thicker in the autograft group. Elastic fiber in all aortas showed little or no variation, whereas in the PA, there was considerable variation in fragmentation. Patients with higher preoperative PA pressures tended to have lower fragmentation scores (chi(2) P:<0.01). The lower stiffness modulus, higher stiffness modulus, and maximum tensile strength of the aorta was 34% to 38% higher than that of the PA (P:<0.01); however, the 4-month-old autograft appeared to show adaptation in mechanical behavior. CONCLUSIONS: In our series of patients, there was no significant progressive dilatation of the aortic root. We demonstrated differences in the anatomic structure and mechanical behavior of the PA in vitro and highlighted histological and mechanical modes of adaptation.

Adolescent↗

High-field franz-keldysh effect and exciton ionization in semiconductor quantum wires

We investigate the Franz-Keldysh effect and exciton ionization in semiconductor quantum wires. Absorption spectra are calculated near the band gap by solution of the low-density semiconductor Bloch equations in real space. The Sommerfeld factor and field-induced tunnel ionization of the exciton significantly affect the continuum portion of the absorption spectrum and remove the well known divergence problem associated with the 1D density of states at all field strengths. For reasonable electric field strengths substantial and tunable absorption oscillations appear above the band gap. Moreover, for very large fields, transparency can be achieved in the continuum for certain spectral positions.

Journal Article↗

Efficacy of nebulized fluticasone propionate compared with oral prednisolone in children with an acute exacerbation of asthma.

The aim of the present study was to investigate the efficacy and safety of nebulized fluticasone propionate (FP Nebules) compared with oral soluble prednisolone in children with an acute exacerbation of asthma. The study used an international, multi-centre, randomized, double-blind, parallel group design. Three hundred and twenty-one patients, aged 4-16 years old, who presented with an acute exacerbation of asthma, were randomly allocated to either nebulized FP (1 mg b.d.) or oral prednisolone (2 mg kg(-1) day(-1) for 4 days then 1 mg kg(-1) day(-1) for 3 days) for 7 days. Patients in the FP group showed a significantly greater increase in diary card morning peak expiratory flow (PEF) over 7 days compared with patients in the prednisolone group (difference = 9.51 min(-1), CI = 2.1, 16.8, P = 0.034). Similar increases for both treatments were shown for evening PEF. Clinic PEF improved with both treatments, but was significantly greater in patients taking FP after 7 days (difference = 11.41 min(-1), CI = 2.8, 20.0, P = 0.029). Both treatments reduced symptom scores to a similar extent. The two treatments were well tolerated, and there was no difference in the incidence of adverse events. The present study demonstrated that nebulized FP is at least as effective as oral prednisolone in the treatment of children presenting with an acute exacerbation of asthma.

Acute Disease↗

Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from malignant (or premalignant) neoplasms?

OBJECTIVE: To determine whether the long-term behavior of cystic mucinous neoplasms of the pancreas could be predicted using a novel, precisely defined classification of benign mucinous cystadenomas, noninvasive proliferative cystic mucinous neoplasms, and invasive mucinous cystadenocarcinomas. The primary interest was to obtain long-term follow-up after complete resection to determine the recurrence rates based on this objective classification. BACKGROUND: Current understanding is that all cystic mucinous neoplasms of the pancreas are potentially malignant and that mucinous cystadenomas, when completely removed, are biologically benign. Cystadenocarcinomas are thought to be less aggressively malignant than ordinary ductal adenocarcinoma, but reported recurrence rates vary widely and are unpredictable. METHODS: All patients who underwent "curative" resection for cystic mucinous neoplasms at Mayo Clinic Rochester from 1940 to 1997 were identified. All available pathology slides, gross specimens, and clinical records were reviewed, eliminating patients with inadequate documentation. Neoplasms were reclassified as mucinous cystadenomas, noninvasive proliferative mucinous cystic neoplasms, or invasive cystadenocarcinomas based on specific histologic criteria. RESULTS: Of 84 patients (70 women, 14 men) with cystic mucinous neoplasms of the pancreas, 54 were classified as cystadenomas, 23 as noninvasive proliferative cystic mucinous neoplasms, and only 7 as cystadenocarcinomas. Recurrent disease developed in none of the 77 patients without invasion, but 5 of the 6 patients surviving resection for cystadenocarcinomas died of recurrent cystadenocarcinoma within 5 years. CONCLUSIONS: When the neoplasm is completely resected and subjected to adequate histopathologic examination based on these objective criteria, absence of tissue invasion predicts a curative operation and detailed follow-up may be unnecessary. In contrast, a histologic diagnosis of invasive cystadenocarcinoma portends a dismal prognosis, similar to that of typical ductal adenocarcinoma of the pancreas.

Adenocarcinoma, Mucinous↗

Novel risk factors for coronary heart disease: emerging connections.

In only 50% of cases of coronary heart disease (CHD) is the cause attributable to the established risk factors of hypertension, cigarette smoking, and elevated total and low-density lipoprotein (LDL) cholesterol levels. This finding has led to research examining other markers for CHD that may have a causal link to the atherothrombotic process. Several of these "emerging" risk factors are reviewed in this article: lipoprotein(a); small dense LDL particle size; hyperhomocysteinemia; and inflammatory, infectious, and hemostatic factors. Evaluation of each of these factors includes a review of the epidemiologic evidence, examination of the pathologic mechanism(s) by which the factor might participate in atherothrombosis, and the clinical utility of screening. Finally, and most relevant for the practicing clinician, the following is addressed: Does evidence exist that selective modification of these risk factors is associated with net clinical benefit?

Arteriosclerosis↗

Calcium and digoxin vs. calcium alone for severe verapamil toxicity.

UNLABELLED: Calcium chloride (CaCl(2)) is ineffective in severe calcium channel antagonist overdoses. Digoxin increases intracellular calcium by inhibiting the sodium-potassium adenosine triphosphatase enzymes. OBJECTIVE: To examine the effect of calcium and digoxin on the treatment of verapamil toxicity. METHODS: Sixteen dogs were instrumented to monitor hemodynamics. Verapamil toxicity (50% decrease in mean arterial pressure) was induced with verapamil (VER) at 6 mg/kg/hr and maintained for 30 minutes by titrating the VER rate. Following toxicity, the dogs received either digoxin (0.018 mg/kg) (DIG) (n = 8) or saline (No-DIG) (n = 8). Both groups received VER at three sequential rates (1 mg/kg/hr from 0 to 90 min, 6 mg/kg/hr from 90 to 130 min, and 18 mg/kg/hr from 130 to 170 min). Calcium boluses were given (500 mg at 0 and 15 min; 1 g at 140, 150, and 160 min). Data were analyzed using a repeated-measures analysis of covariance comparing DIG vs No-DIG across the infusion rates and time. Animal weight, does of VER administered during the toxicity phase, and baseline values were included as covariates. Mortality rates were compared at 230 minutes following a total dose of 500 mg of VER. RESULTS: The DIG group had a higher systolic blood pressure (SBP) than the No-DIG group during the 1-mg/kg/hr (early p = 0.028, late p = 0.01), 6-mg/kg/hr (p = 0.051), and 18-mg/kg/hr (p = 0.038) VER infusion rates. There were no deaths in the DIG group and four deaths in the No-DIG group (Fisher = 0.08). Neither ventricular tachycardia nor ventricular fibrillation developed in either group. Other hemodynamic parameters did not show significant changes. CONCLUSIONS: In a model of severe verapamil toxicity, digoxin plus calcium raised SBP and did not result in ventricular arrhythmias when compared with calcium alone.

Animals↗

Subclinical chlamydial infection of the female mouse genital tract generates a potent protective immune response: implications for development of live attenuated chlamydial vaccine strains.

Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4(+) T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection. Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log(10)) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs.

Animals↗

Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis.

PURPOSE: To characterize the topography of and the cellular processes that underlie vascularization of the human retina. METHODS: The vasculature of human eyes obtained from fetuses ranging in age from 14 to 38 weeks of gestation (WG) was examined in Nissl-stained, whole-mount preparations and by anti-CD34 immunohistochemistry. RESULTS: The first event in retinal vascularization, apparent before 15 WG, was the migration of large numbers of spindle-shaped mesenchymal precursor cells from the optic disc. These cells proliferated and differentiated to produce cords of endothelial cells. By 15 WG, some cords were already patent and formed an immature vascular tree in the inner retinal layers that was centered on the optic disc. These processes are consistent with vessel formation by vasculogenesis. Angiogenesis then increased the vascular density of this immature plexus and extended it peripherally and temporally. Maturation of the plexus was characterized by substantial remodeling, which involved the withdrawal of endothelial cells into neighboring vascular segments. The outer plexus was formed as a result of the extension of capillary-sized buds from the existing inner vessels, a process that began around the incipient fovea between 25 and 26 WG. CONCLUSIONS: These observations suggest that the formation of primordial vessels in the central retina is mediated by vasculogenesis, whereas angiogenesis is responsible for increasing vascular density and peripheral vascularization in the inner retina. In contrast, the outer plexus and the radial peripapillary capillaries are formed by angiogenesis only. These mechanisms of retinal vascularization appear similar to those of vascularization of the central nervous system during development.

Antigens, CD34↗

Rejecting family practice: why medical students switch to other specialties.

BACKGROUND AND OBJECTIVES: Medical schools have been encouraged to increase the number of primary care graduates. This study determined the proportion of medical students who change specialty preference during the clinical years and explored how ultimate choice is affected by perceptions of medical specialties acquired during this period. METHODS: A survey was mailed to 397 graduating medical students at the University of California, San Francisco (UCSF) after the National Resident Matching Program Match and before graduation in 1996, 1997, and 1998. RESULTS: The response rate was 81% (320/397). Of 41 respondents who reported that family practice had been their first specialty choice prior to beginning clinical rotations, only 15 (37%) eventually matched in family practice. Comparable numbers for internal medicine and pediatrics were 50% and 69%. Students rejecting family practice were more likely than their colleagues rejecting other specialties to cite insufficient prestige, low intellectual content, and concern about mastering too broad a content area as reasons. CONCLUSIONS: At UCSF, family practice retains fewer interested students than other primary care specialties. To reverse this trend, schools such as UCSF need to raise the prestige of family practice and counter concerns about its intellectual content being impossible to master.

Adult↗