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Biomedical subjects

M E Jones

Publications and source records attributed to M E Jones.

At least 37 records · Page 2Linked to original sources

Antimicrobial resistance among respiratory pathogens collected in Thailand during 1999-2000.

A multi-center surveillance study was conducted in Thailand during 1999-2000 to determine antimicrobial susceptibilities among the respiratory pathogens Streptococcus pneumoniae (n = 206), Haemophilus influenzae (n = 305), and Moraxella catarrhalis (n = 39). Of the S. pneumoniae isolates collected, 33.5% were penicillin-susceptible, 27.2% intermediate and 39.3% resistant. Expectedly, resistance rates to beta-lactams were higher among penicillin-resistant (ceftriaxone, 14.8%; amoxicillin-clavulanate, 42.0%; cefuroxime, 100%) than penicillin-susceptible (ceftriaxone, 0%; amoxicillin-clavulanate, 0%; cefuroxime, 0%) isolates. Likewise, azithromycin and clarithromycin resistances were 4.3% and 5.8% among penicillin-susceptible isolates, and 77.8% and 95.1% among penicillin-resistant isolates. All S. pneumoniae remained susceptible to vancomycin and 99.5% were susceptible to levofloxacin. Multidrug resistance (resistance to >3 antimicrobial classes) was present in 25.2% of pneumococcal isolates (n = 52), with resistance to azithromycin, penicillin and trimethoprim-sulfamethoxazole the most common phenotype (40/52 isolates; 77.0%). Among the isolates of H. influenzae, the prevalence of beta-lactamase production was 45.2%. All isolates of H. influenzae were susceptible to amoxicillin-clavulanate, azithromycin, ceftriaxone, cefuroxime and levofloxacin while 49.5% were resistant to trimethoprim-sulfamethoxazole. All 39 isolates of M. catarrhalis produced beta-lactamase. Azithromycin (MIC90, < or = 0.03 microg/ml) and levofloxacin (MIC90, 0.03 microg/ml) were the most active agents tested against M. catarrhalis. The results of this study may serve as a baseline for future studies to monitor antimicrobial susceptibilities among respiratory pathogens in Thailand.

Anti-Bacterial Agents↗

Not all muscles meet the same fate when they die.

Two general patterns of cell death are usually described in animals: necrosis and apoptosis. The former is a passive process that displays cellular swelling and lysis, while the latter involves cellular shrinkage and gene-mediated, ATP-dependent processes. Independent of the proximal cause of cell death, cell corpses are almost always removed by phagocytic cells. This is far from universal for all cells however, since phagocytic cells have not been noted during the programmed death of some skeletal muscles in insects. To further explore this, we used a variety of anatomical methods to examine the death of the intersegmental muscles (ISMs) of the moth Manduca sexta. The ISMs are giant cells that die during the 30 h following adult emergence. At no stage examined were hemocytes or other cells associated with the sarcolemma. The failure to detect macrophages was not due to technical limitations since immunohistochemical and functional studies demonstrate their presence in the hemolymph. The absence of phagocytosis to remove ISM corpses suggests that all of the biochemical machinery required for cellular destruction is resident within the ISMs themselves. This is consistent with analysis suggesting that Manduca does not possess sufficient numbers of macrophages to consume the ISMs. Given that insects do not have adaptive immunity, the ability to use a completely cell autonomous process may be a developmental option that cannot be exploited in vertebrates.

Animals↗

Prevalence of antimicrobial resistance among urinary tract pathogens isolated from female outpatients across the US in 1999.

In the United States, trimethoprim-sulphamethoxazole (TMP-SMX) is the recommended first-line treatment for uncomplicated urinary tract infections (UTIs) in females, in regions with resistance rates of <10-20%. Unfortunately, current data on regional resistance is often not readily available to physicians and regional variability in resistance remains largely unknown. This report presents antimicrobial susceptibility data for TMP-SMX and three other commonly tested antimicrobials organized by state and region to demonstrate current regional variability in resistance in the US. In the last quarter of 1999, 5739 fresh clinical isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Staphylococcus saprophyticus were collected from 202 laboratories throughout the US. Susceptibility testing was performed against TMP-SMX, cephalothin, nitrofurantoin and ciprofloxacin using broth microdilution. Data were analyzed by patient age and specimen source, and by state and region. In the US as a whole, resistance to TMP-SMX was 16.8% for E. coli, 7.8% for K. pneumoniae, 12.1% for P. mirabilis and 3.0% for S. saprophyticus, but these rates showed considerable regional variation. By state, E. coli resistance ranged from 7.4% in Pennsylvania to 33.3% in Iowa (among states with > or =50 isolates tested). Regionally, resistance for all uropathogens taken together ranged from 8.5% in East South-Central to 22.8% in West South-Central. Ciprofloxacin demonstrated the broadest activity of the antimicrobials tested and was more active than TMP-SMX against all pathogens. Resistance to TMP-SMX among E. coli now approaches or exceeds 20% in some areas. As resistance among uropathogens reaches clinically significant levels in many areas, continued regional surveillance is essential to ensure the provision of effective empiric therapy for urinary tract infections.

Adolescent↗

Aromatase-deficient (ArKO) mice accumulate excess adipose tissue.

Aromatase is the enzyme which catalyses the conversion of C19 steroids into C18 estrogens. We have generated a mouse model wherein the Cyp19 gene, which encodes aromatase, has been disrupted, and hence, the aromatase knockout (ArKO) mouse cannot synthesise endogenous estrogens. We examined the consequences of estrogen deficiency on accumulation of adipose depots in male and female ArKO mice, observing that these animals progressively accrue significantly more intra-abdominal adipose tissue than their wildtype (WT) litter mates, reflected in increased adipocyte volume and number. This increased adiposity was not due to hyperphagia or reduced resting energy expenditure, but was associated with reduced spontaneous physical activity levels, reduced glucose oxidation, and a decrease in lean body mass. Elevated circulating levels of leptin and cholesterol were present in 1-year-old ArKO mice compared to WT controls, as were elevated insulin levels, although blood glucose was unchanged. Associated with these changes, the livers of ArKO animals were characterised by a striking accumulation of lipid droplets. Our findings demonstrate an important role for estrogen in the maintenance of lipid homeostasis in both males and females.

Adipose Tissue↗

The ovarian phenotype of the aromatase knockout (ArKO) mouse.

Targeted disruption of exon 9 of the cyp19 gene gives rise to a non-functional aromatase enzyme incapable of converting androgens to oestrogens. The aromatase knockout (ArKO) mouse is, thus, characterised by a dysfunctional pituitary-gonadal axis, which manifests in non-detectable levels of oestrogen in serum. These mice also exhibit elevated levels of circulating gonadotrophins (luteinising hormone (LH) and follicle stimulating hormone (FSH)) and testosterone. The ArKO mouse is infertile due to folliculogenic disruption and a failure to ovulate. The age-dependent ovarian phenotype revealed a block in follicular development at the antral stage and a complete absence of corpora lutea. By 21-23 weeks of age haemorrhagic cystic follicles were present and by 1 year there were abnormal follicles, an absence of secondary and antral follicles and atretic primary follicles. Interstitial tissue remodelling was extensive and exemplified by an increase in collagen deposition and an influx of macrophages, coincident with the loss of follicles. In mice, maintained on a soy-free and, thus, phytoestrogen-free diet, the ovarian phenotype was accelerated and exacerbated. In conclusion, the ovarian phenotype of the ArKO mouse can be attributed to the altered hormonal environment brought about by the absence of aromatase and the failure of androgens to be converted to oestrogens in the presence of elevated gonadotropins.

Age Factors↗

'Clicking-brain syndrome': a curious cause of insomnia.

This case report describes a curious cause of insomnia. A 93-year-old woman presented to our follow-up clinic with the complaint of insomnia secondary to an audible click emanating from her skull. The site of loud biphasic-sound production corresponded to an area of the scalp where a squamous cell carcinoma had been removed 11 years previously.

Aged↗

The road to ovulation: the role of oestrogens.

Oestrogens have been known for many years to have a direct influence on folliculogenesis. Oestradiol-17beta (E2) and its analogues have both proliferative and differentiative effects on somatic cells of follicles. Nevertheless, definitive proof of an obligatory role for oestrogen in folliculogenesis and elucidation of the mechanisms subserving its different actions in follicular cells remains elusive. Several recent developments permit a re-examination of the roles and actions of E2 in the follicle. They are: (i) the discovery of a second form of the oestrogen receptor, ERbeta; (ii) the advent of genetically modified mice with deletions in the ERalpha (alphaERKO) ERbeta (BERKO) and the double ER deletions (alphabetaERKO); and (iii) a mouse model of oestrogen deficiency (ArKO) by targeted disruption of the cyp 19 gene encoding the aromatase enzyme. Recent information derived from these models is reviewed to re-assess the roles and actions of oestrogens in follicular dynamics and the phenotypic differentiation of ovarian somatic cells in the ovary. The data demonstrate that oestrogen is obligatory for normal folliculogenesis and that the phenotype of the ovarian somatic cells depends on the steroid milieu. The ArKO mouse provides a model to test the roles of the respective ERs in proliferation and differentiation using specific agonists and antagonists, and to study regulation of the differentiation of ovarian and testicular somatic cells.

Animals↗

Need for annual surveillance of antimicrobial resistance in Streptococcus pneumoniae in the United States: 2-year longitudinal analysis.

Although changing patterns in antimicrobial resistance in Streptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniae antimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997-1998 and 1998-1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997-1998 were encountered in 1998-1999. This longitudinal surveillance study of resistance in S. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

Anti-Bacterial Agents↗

Multidrug-resistant urinary tract isolates of Escherichia coli: prevalence and patient demographics in the United States in 2000.

Concurrent resistance to antimicrobials of different structural classes has arisen in a multitude of bacterial species and may complicate the therapeutic management of infections, including those of the urinary tract. To assess the current breadth of multidrug resistance among urinary isolates of Escherichia coli, the most prevalent pathogen contributing to these infections, all pertinent results in The Surveillance Network Database-USA from 1 January to 30 September 2000 were analyzed. Results were available for 38,835 urinary isolates of E. coli that had been tested against ampicillin, cephalothin, ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Of these isolates, 7.1% (2,763 of 38,835) were resistant to three or more agents and considered multidrug resistant. Among the multidrug-resistant isolates, 97.8% were resistant to ampicillin, 92.8% were resistant to trimethoprim-sulfamethoxazole, 86.6% were resistant to cephalothin, 38.8% were resistant to ciprofloxacin, and 7.7% were resistant to nitrofurantoin. The predominant phenotype among multidrug-resistant isolates (57.9%; 1,600 of 2,793) included resistance to ampicillin, cephalothin, and trimethoprim-sulfamethoxazole. This was the most common phenotype regardless of patient age, gender, or inpatient-outpatient status and in eight of the nine U.S. Bureau of the Census regions. Rates of multidrug resistance were demonstrated to be higher among males (10.4%) than females (6.6%), among patients > 65 years of age (8.7%) than patients < or = 17 (6.8%) and 18 to 65 (6.1%) years of age, and among inpatients (7.6%) than outpatients (6.9%). Regionally, the rates ranged from 4.3% in the West North Central region to 9.2% in the West South Central region. Given the current prevalence of multidrug resistance among urinary tract isolates of E. coli in the United States (7.1%), continued local, regional, and national surveillance is warranted.

Adolescent↗

Prevalence of molecular types and mecA gene carriage of coagulase-negative Staphylococci in a neonatal intensive care unit: relation to nosocomial septicemia.

Molecular typing of isolates revealed that neonatal coagulase-negative staphylococcal (CONS) septicemia is most frequently caused by predominant, antibiotic-resistant CONS types, which are widely distributed among both neonates and staff of the neonatal unit, suggesting cross-contamination. Therefore, infection control measures may be valuable in the prevention of this common nosocomial septicemia.

Bacteremia↗

Acculturation status, birth outcomes, and family planning compliance among Hispanic teens.

This study examined acculturation status, selected demographic and pregnancy indices, and the relationship to birth outcomes and family planning patterns among a convenience sample of 63 Hispanic adolescents aged 13 to 19 years and attending community-based prenatal clinics. Findings suggest that Hispanic teenagers who are the first generation in the United States and traditional in their world view are compliant with prenatal and postpartum care and have healthy babies and birth outcomes. Gravidity and gestational age of the infant were significant predictors of birth weight, accounting for 30% of the variability in birth weight. Generation in the United States accounted for 8% of the variance in family planning compliance. Higher gravidity was associated with increased infant birth weight and a decreased likelihood for return for family planning visits during the 1st year postbirth. Teens who were first generation in the United States were more likely to return for family planning visits during the 1st year. School nurses are in a pivotal position to design intervention programs that build on traditional cultural prescriptions for healthy behaviors during and after pregnancy.

Acculturation↗

Weight-bearing, pain and walking velocity during primary transtibial amputee rehabilitation.

OBJECTIVE: To explore the relationships between weight-bearing, pain and walking velocity in the first four weeks of prosthetic training. SUBJECTS: Consecutively referred transtibial amputees (n = 27). DESIGN: Longitudinal study. SETTING: Inpatient rehabilitation centre. INTERVENTIONS: Measurements of static weight-bearing (SWB), perceived pain during the SWB test and self-selected walking velocity (VEL) were taken at entry, and at four weeks into the prosthetic training programme. Path analysis was conducted using a series of linear regression analyses to determine predictors of walking velocity at week 4. RESULTS: Significant improvements from week 1 to week 4 were found in SWB, reported pain and velocity. SWB at week 4, when coupled with age, predicted 66% of the variance in walking velocity at week 4. Pain did not directly predict velocity. However, SWB at entry and perceived pain at week 4 predicted 56% of the variance in SWB at week 4. CONCLUSIONS: These analyses suggested a model in which SWB and age were both significantly related to velocity, and further, that pain played a role in velocity through a relationship mediated by its direct effect on SWB. Unlike age, SWB is a predictor of velocity that might be altered through pain reduction, wound-healing and rehabilitative interventions.

Adult↗

Estrogen and spermatogenesis.

Although it has been known for many years that estrogen administration has deleterious effects on male fertility, data from transgenic mice deficient in estrogen receptors or aromatase point to an essential physiological role for estrogen in male fertility. This review summarizes the current knowledge on the localization of estrogen receptors and aromatase in the testis in an effort to understand the likely sites of estrogen action. The review also discusses the many studies that have used models employing the administration of estrogenic substances to show that male fertility is responsive to estrogen, thus providing a mechanism by which inappropriate exposure to estrogenic substances may cause adverse effects on spermatogenesis and male fertility. The reproductive phenotypes of mice deficient in estrogen receptors alpha and/or beta and aromatase are also compared to evaluate the physiological role of estrogen in male fertility. The review focuses on the effects of estrogen administration or deprivation, primarily in rodents, on the hypothalamo-pituitary-testis axis, testicular function (including Leydig cell, Sertoli cell, and germ cell development and function), and in the development and function of the efferent ductules and epididymis. The requirement for estrogen in normal male sexual behavior is also reviewed, along with the somewhat limited data on the fertility of men who lack either the capacity to produce or respond to estrogen. This review highlights the ability of exogenous estrogen exposure to perturb spermatogenesis and male fertility, as well as the emerging physiological role of estrogens in male fertility, suggesting that, in this local context, estrogenic substances should also be considered "male hormones."

Animals↗

Elevated androgens and prolactin in aromatase-deficient mice cause enlargement, but not malignancy, of the prostate gland.

Although androgens are the main steroids controlling the growth of the mammalian prostate, increasing evidence demonstrates that estrogens also regulate prostate development and growth. This study describes the effects of estrogen deficiency using aromatase knockout mice (ArKO) with targeted disruption of the cyp19 gene. Serum and tissue testosterone and 5alpha-dihydrotestosterone as well as serum PRL levels are significantly (P < 0.05) elevated in mature male ArKO mice. Histological, stereological, and immunohistochemical studies demonstrated enlargement of the ventral, anterior, and dorsolateral lobes of the prostate in young and older ArKO mice. Hyperplasia of the epithelial, interstitial, and luminal compartments was identified and associated with up-regulation of androgen receptors. There was no evidence of malignancy as the animals aged (up to 56 weeks). The changes observed in the prostates of ArKO mice were unaffected by maintaining mice on regular or soy-free diets. It is concluded in ArKO mice that, despite the long-term elevation of androgens and PRL, the absence of estrogen in these animals does not result in induction of malignancy in the prostate gland.

Androgens↗