Biomedical subjects

J S Smith

Publications and source records attributed to J S Smith.

At least 19 recordsLinked to original sources

PubMed2006

Overexpression of c-Myc and Bcl-2 during progression and distant metastasis of hormone-treated breast cancer.

The aim of this study was to identify molecules involved in the proliferation and survival of recurrent estrogen receptor (ER)-positive breast cancer at the site of metastasis. Most studies of biomarkers are done using the initial primary breast tumor whereas pathological studies of breast cancer lesions after distant recurrence are scarce. Here we evaluated the expression of the oncogenes c-Myc and Bcl-2, mediators of estrogen-dependent proliferation and survival, during breast cancer progression and relapse after adjuvant hormonal therapy. Using a preclinical model of tamoxifen-resistant growth, we found overexpression of c-Myc in all (3/3) and of Bcl-2 in most (2/3) tamoxifen resistant-breast cancer variants. To determine whether c-Myc and Bcl-2 are expressed during breast cancer progression in the clinics we identified breast cancer patients who had received adjuvant hormonal therapy for the treatment of their localized disease and had later experienced relapse. From 583 patients who had received adjuvant hormonal therapy a total of 82 experienced recurrence. Nevertheless, only 22 patients had had a biopsy of their metastatic lesion done after relapse. Twenty-one biopsies were useful for this biomarker study. These biopsies were obtained mostly (20) from breast cancer patients who had received tamoxifen as their adjuvant hormonal therapy. One patient had received an aromatase inhibitor instead. Our results showed that almost all (20) metastatic recurrences expressed ER. Expression of c-Myc was observed in 18 out of 19 metastatic lesions scored while expression of Bcl-2 was detected in 17 out of 21 metastatic tumors. A correlation between ER expression and Bcl-2, but not with c-Myc, was found in these recurrent metastatic lesions. In addition, c-Myc expression was correlated with the nuclear grade of the metastatic lesion. Thus, the frequent expression of c-Myc and Bcl-2 in metastatic breast cancer recurrences suggests that combining hormonal therapy with strategies to block c-Myc and Bcl-2 may prevent growth of ER-positive breast cancer at the site of metastasis.

Adult↗

PubMed2006

Human papillomavirus in men: comparison of different genital sites.

OBJECTIVE: To elucidate which anatomical sites need to be sampled to detect human papillomavirus (HPV) infection in the lower male genital tract. METHOD: In an HPV survey of Mexican soldiers (median age 24 years; range 16-50 years), a cell sample from 2 cm deep into the distal urethra (group 1; n = 168 men), or 0.5 cm deep into the meatus urethralis (group 2; n = 414 men) was collected, along with a sample from the external genitalia. The different samples were tested for 27 HPV types using a polymerase chain reaction based strip assay. RESULTS: HPV DNA was detected more frequently in external genitalia samples (46.4%) than in the urethra (20.8%) or meatus samples (12.1%). Lack of samples from the urethra or meatus would have led to 5.1% and 1.5% false HPV negative results, respectively. The most frequently detected high risk HPV types (HPV 59, 52, 51, and 16) were similar in different sites, whereas low risk types were found rarely in urethra samples. CONCLUSIONS: The addition of cell samples from the meatus to those from external genitalia contributed negligibly to the evaluation of the prevalence of HPV in men. HPV detection was slightly improved by the addition of urethra samples, but the gain may not justify the discomfort of the procedure in large epidemiological studies.

Adolescent↗

PubMed2006

Type specific seroprevalence of HSV-1 and HSV-2 in four geographical regions of Poland.

OBJECTIVE: To examine the type specific seroprevalence of herpes simplex virus (HSV) types 1 and 2 infections, stratified by age and gender, and associated risk factors for HSV-2 seropositivity in Poland. METHODS: 2257 serum samples of individuals from 15-65 years were randomly selected from serum banks in four different geographical regions of Poland, including the Zachodnio-pomorskie, Warmińsko-mazurskie, Lubelskie, and Mazowieckie districts. Type specific serum antibodies to HSV-1 and HSV-2 were detected using HerpeSelect IgG ELISA tests. RESULTS: Overall prevalences of type specific HSV-1 and HSV-2 serum antibodies were 90.4% and 9.3%, respectively. Age standardised HSV-2 seroprevalence was higher in women (9.7%) than men (8.8%) (p = 0.06), and increased notably with age from 4% in 15-24 year olds to 12% in those aged 50-65 years. HSV-1 seroprevalence was consistently higher than HSV-2 seroprevalence in each specific age group, ranging from 74.5% in 15-24 year olds to 98.8% in 50-65 year olds. HSV-2 seroprevalence varied significantly by geographical region, with the highest prevalence in the Zachodnio-pomorskie district (12%). Significant multivariate risk factors for HSV-2 seropositivity included older age, female gender, and geographical place of residence. CONCLUSION: This large survey found a notably high seroprevalence of HSV-1, even among young female adolescents 15-19 years of age (80%). HSV-2 seropositivity was under 12% in all age groups surveyed in Poland, tending to be among the lowest overall HSV-2 seropositivity rates reported thus far in Europe.

Adolescent↗

PubMed2006

Effects of polyvinyl chloride overwrap film, high-oxygen modified atmosphere packaging, or ultra-low-oxygen modified atmosphere packaging on bone marrow discoloration in beef humerus, rib, thoracic vertebra, and scapula.

Meat retailers have reported bone marrow discoloration to be a problem, especially in modified atmosphere packages (MAP). Therefore, it is important to determine the prevalence and cause(s) of bone marrow discoloration in different beef bones and packaging systems. Thirty-six beef humeri, ribs, scapulas, and thoracic vertebrae from USDA Select and Choice carcasses were obtained from a commercial abattoir, cut into 2.54-cm-thick sections at 4 d postmortem, and packaged into 1 of 3 systems: 1) polyvinyl chloride film (PVC) overwrap; 2) high-oxygen (80% O2, 20% CO2) MAP; and 3) ultra-low-oxygen (70% N2, 30% CO2) MAP. Instrumental reflectance and visual color scores were taken on d 0, 2, and 4, and on d 0 to 4 of display, respectively. Bone marrow was extracted from humeri, ribs, and thoracic vertebrae for analysis but not from scapulas. Ribs, scapulas, and thoracic vertebrae packaged in PVC and high-oxygen MAP developed undesirable gray or black discoloration. In ultra-low-oxygen MAP, mean visual color scores were acceptable throughout the entire display period. Discoloration (darkening) was more extensive for ribs, scapulas, and thoracic vertebrae than for humeri, especially for bones packaged in PVC and high-oxygen MAP. Humeri had lower (P < 0.05) a* values (larger positive a* values indicate a redder color) than the other bones. The a* values for ribs, scapulas, and thoracic vertebrae decreased (P < 0.05) over time. Chroma showed that bone marrow discolored during display, but graying was dramatically less for all bones packaged in ultra-low-oxygen MAP and for humeri in PVC and high-oxygen MAP. Humeri marrow had lower (P < 0.05) 2-thiobarbituric acid reactive substances (TBARS) than did ribs and thoracic vertebrae marrow. Ultra-low-oxygen MAP resulted in the least amount of change in TBARS from d 0 to 4, whereas thoracic vertebrae marrow had greater (P < 0.05) TBARS values at d 4 of display than at d 0 in PVC and high-oxygen MAP. Humeri marrow had dramatically less total Fe and hemoglobin than did that of ribs and thoracic vertebrae for all packaging systems. Myoglobin was undetectable in humeri marrow. The much larger amounts of Fe and hemoglobin in ribs and thoracic vertebrae likely contribute to marrow discoloration. Bone marrow discoloration was distinct in ribs, scapulas, and thoracic vertebrae packaged in PVC or high-oxygen MAP. Bones packaged in ultra-low-oxygen MAP had minimal discoloration.

Animals↗

PubMed2006

Effects of energy level on methionine utilization by growing steers.

We evaluated the effect of energy supplementation on Met use in growing steers. Six ruminally cannulated Holstein steers (228 +/- 8 kg of BW) were used in a 6 x 6 Latin square and fed 2.8 kg of DM/d of a diet based on soybean hulls. Treatments were abomasal infusion of 2 amounts of Met (0 or 3 g/d) and supplementation with 3 amounts of energy (0, 1.3, or 2.6 Mcal of GE/d) in a 2 x 3 factorial arrangement. The 1.3 Mcal/d treatment was supplied through ruminal infusion of 90 g/d of acetate, 90 g/d of propionate, and 30 g/d of butyrate, and abomasal infusion of 30 g/d of glucose and 30 g/d of fat. The 2.6 Mcal/d treatment supplied twice these amounts. All steers received basal infusions of 400 g/d of acetate into the rumen and a mixture (125 g/d) containing all essential AA except Met into the abomasum. No interactions between Met and energy levels were observed. Nitrogen balance was increased (P < 0.05) by Met supplementation from 23.6 to 27.8 g/d, indicating that protein deposition was limited by Met. Nitrogen retention increased linearly (P < 0.05) from 23.6 to 27.7 g/d with increased energy supply. Increased energy supply also linearly reduced (P < 0.05) urinary N excretion from 44.6 to 39.7 g/d and reduced plasma urea concentrations from 2.8 to 2.1 mM. Total tract apparent OM and NDF digestibilities were reduced linearly (P < 0.05) by energy supplementation, from 78.2 and 78.7% to 74.3 and 74.5%, respectively. Whole-body protein synthesis and degradation were not affected significantly by energy supplementation. Energy supplementation linearly increased (P < 0.05) serum IGF-I from 694 to 818 ng/mL and quadratically increased (P < 0.05) serum insulin (0.38, 0.47, and 0.42 ng/mL for 0, 1.3, and 2.6 Mcal/d, respectively). In growing steers, N retention was improved by energy supplementation, even when Met limited protein deposition, suggesting that energy supplementation affects the efficiency of AA use.

Animal Nutritional Physiological Phenomena↗

PubMed2006

Effects of energy source on methionine utilization by growing steers.

We evaluated the effects of different supplemental energy sources on Met use in growing steers. Ruminally cannulated Holstein steers were used in two 6 x 6 Latin squares, and data were pooled for analyses. In Exp. 1, steers (148 kg) were fed 2.3 kg of DM/d of a diet based on soybean hulls. Treatments (2 x 3 factorial) were abomasal infusion of 0 or 3 g of l-Met/d, and supplementation with no energy or with glucose (360 g/d) or fat (150 g/d) continuously infused into the abomasum. In Exp. 2, steers (190 kg) received 2.6 kg of dietary DM/d and were provided (2 x 3 factorial) with 0 or 3 g of l-Met/d, and with no supplemental energy or with acetate (385 g/d) or propionate (270 g/ d) continuously infused into the rumen. In both experiments, the energy sources supplied 1.3 Mcal of GE/d, and all steers received basal infusions of 400 g of acetate/d into the rumen and a mixture (125 g/d) of all essential AA except Met into the abomasum. Nitrogen balance (18.8 vs. 23.5 g/d; P < 0.01) and whole-body protein synthesis (2.1 vs. 2.3 kg/d; P < 0.07) were increased by Met supplementation, indicating that protein deposition was limited by Met. Supplemental energy reduced (P < 0.01) urinary N excretion and increased (P < 0.01) N retention without differences among energy sources. Increases in N retention in response to Met were numerically greater when energy was supplemented. Efficiency of supplemental Met use was 11% when no energy was supplemented but averaged 21% when 1.3 Mcal of GE/d was provided. Whole-body protein synthesis and degradation were not affected by energy supplementation. Serum insulin concentrations were increased by glucose and propionate supplementation. Serum IGF-I concentrations were increased by supplementation with Met or glucogenic sources of energy. In growing steers, N retention was increased by energy supplementation even though protein deposition was limited by Met, suggesting that energy supplementation improves the efficiency of AA use. These responses were independent of the source of energy.

Acetic Acid↗

PubMed2005

Effect of SBE7-beta-cyclodextrin complexation on carbamazepine release from sustained release beads.

The effect of SBE7-beta-cyclodextrin together with hydroxypropylmethyl cellulose (HPMC) or polyvinylpyrrolidone (PVP) on the saturated solubility and delivery of carbamazepine (a poorly soluble drug) from sustained release (SR) beads was investigated. Carbamazepine solubility at room temperature increased from 0.1 to 5.4mg/ml by forming an inclusion complex with SBE7-beta-cyclodextrin (15%w/v). HPMC (0.1%w/v) also increased the aqueous solubility of carbamazepine, acting both alone and synergistically with SBE7-beta-cyclodextrin, to produce solubility values of 0.26 and 8.1mg/ml respectively. PVP (0.1-0.5%w/v) had no effect on carbamazepine solubility, either alone or in combination with SBE7-beta-cyclodextrin. The addition of SBE7-beta-cyclodextrin to SR beads increased the rate of carbamazepine release. In addition, comparable release rates where obtained when lower ratios of SBE7-beta-cyclodextrin together HPMC were incorporated in the SR bead. Therefore this ternary drug cyclodextrin polymer system was considered preferable over the binary drug cyclodextrin system for SR beads, as less cyclodextrin was required. However, both binary and ternary approaches were considered suitable techniques to improve the release rate and potentially the in vivo bioavailability of poorly soluble drugs that had previously exhibited slow or incomplete release from SR beads.

Algorithms↗

PubMed2005

Commentary from the front lines: American physician assistants working in a United Kingdom emergency department.

Physician assistants (PAs) have been an integral part of the emergency medicine team in the USA for the past 30 years. This review outlines the reasons why PAs can play a vital role in UK National Health Service (NHS). The experience of American PAs working in one NHS trust are discussed, highlighting the cultural differences in the environment of the emergency departments in the two countries that will influence the scope of practice of PAs in the UK.

Emergency Medical Technicians↗

PubMed2004

Prevalence of papillomavirus infection in women in Ibadan, Nigeria: a population-based study.

To investigate the prevalence of and the risk factors for cervical infection with human papillomavirus (HPV) in an inner-city area of Ibadan, Nigeria, we interviewed and obtained a sample of cervical cells from 932 sexually active women aged 15 years or older. A total of 32 different HPV types were identified with an HPV prevalence of 26.3% overall and 24.8% among women without cervical lesions; or age-standardised to the world standard population of 28.3 and 27.3%, respectively. High-risk HPV types predominated, most notably HPV 16, 31, 35 and 58. In all, 33.5% of infections involved more than one HPV type. Unlike most populations studied so far, HPV prevalence was high not only among young women, but also in middle and old age. Single women (odds ratio, OR=2.1; 95% confidence interval, CI=1.1-3.9) and illiterate women (OR=1.7; 95%CI=1.1-2.5) showed increased HPV positivity. Associations were also found with anti-Herpes simplex-2 antibodies (OR=1.6; 95% CI: 1.1-2.1) and with the husband's extramarital relationships (OR=1.6: 95% CI: 1.0-2.6). High prevalence of HPV in all age groups may be a distinctive feature of populations where HPV transmission continues into middle age and cervical cancer incidence is very high.

Adolescent↗

PubMed2004

Cryoablation of benign breast tumors: evolution of technique and technology.

We report on improvements in cryoprobe design and techniques of cryoablation as a minimally invasive alternative to open surgery for the treatment of benign breast tumors. In the study, which was conducted in 12 centers, 124 lesions in 102 patients were monitored for a period of 12 months after cryoablation. Two different treatment techniques were used: Double HI FREEZE and Tailored Freeze. In patients treated with the Tailored Freeze technique significantly better results were recorded 12 months after the procedure: the median reduction in tumor volume was 91%, 73% of all tumors treated were nonpalpable, 84% of lesions less than 2.5 cm in maximum diameter were nonpalpable, and none of the 31 mammograms performed yielded abnormal findings. Patient satisfaction was good to excellent in 92% of the patients. The safety profile of this technique was excellent; all complications were minor. Evolution of cryoablation freezing techniques, coupled with improvements in cryoprobe design, has resulted in significant improvements in both safety and effectiveness.

Adult↗

PubMed2004

Unexpected pulmonary uptake of adenovirus vectors in animals with chronic liver disease.

When adenovirus vectors are injected intravenously, most of the virions are quickly taken up by the reticuloendothelial system, primarily by the liver macrophages known as Kupffer cells. However, little is known about the behavior of adenovirus vectors when there is pre-existing liver disease. To study this, we examined the biodistribution of intravenously injected vector in a rat model of cirrhosis induced by bile duct ligation. Using quantitative PCR and fluorescently tagged adenovirus vectors, we observed a significant reduction in vector uptake by the cirrhotic liver and increased accumulation in the lungs. Immunocytochemistry and electron microscopy demonstrated that this was due to changes in the reticuloendothelial system, with the vector being taken up by large numbers of pulmonary intravascular macrophages in the lungs of cirrhotic rats. Interestingly, expression of vector-encoded luciferase was significantly reduced in the livers of cirrhotic rats, but was not increased in the lungs. These data demonstrate that the biodistribution of adenovirus vectors in rats is altered by cirrhosis, which suggests the possibility that these vectors might behave unexpectedly in patients with pre-existing liver conditions, particularly since pulmonary reticuloendothelial changes are known to occur in human disease.

Adenoviridae↗

PubMed2004

Evaluation of a TaqMan PCR assay to detect rabies virus RNA: influence of sequence variation and application to quantification of viral loads.

Published assays that use TaqMan PCR are consistently sensitive, rapid, and readily transferable. Here we describe a TaqMan PCR-based method for the detection of rabies virus (RV) RNA in tissue samples. We show that the method has an acceptable linear range, is both sensitive and specific, and, importantly, correlates with the concentration of infectious virus. In addition, the levels of RV-specific amplification are adjustable according to the levels of an endogenous control (beta-actin mRNA), allowing the calculation of comparable quantities. We tested the capacity of this assay to cope with target sequence variations. The number of sequence mismatches between gene-specific oligonucleotides and the target sequence significantly affects amplification (P < 0.001), and point mutations at the center of the probe can result in false-negative results through the prevention of probe binding and subsequent fluorescence. This study demonstrates that the genetic heterogeneity of RVs may prove a serious obstacle in the development of a diagnostic assay based on TaqMan PCR; however, the quantification of RV levels may prove to be a valuable application of this assay.

Animals↗

PubMed2003

Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis.

Particular types of human papillomavirus (HPV) infection may preferentially progress from high-grade squamous intraepithelial lesions (HSIL) to squamous cell carcinoma of the cervix (SCC). We performed a meta-analysis of published data to compare HPV type distribution in HSIL and SCC. HPV16, 18 and 45 were each more prevalent in SCC than HSIL, whereas the reverse was true for other oncogenic types including HPV31, 33, 52 and 58. These data suggest that HSILs infected with HPV16, 18 and 45 preferentially progress to SCC. This may have implications for follow-up protocols of future HPV-based cervical cancer screening programmes and for HPV vaccine trials.

Carcinoma, Squamous Cell↗

PubMed2003

Human papillomavirus infection and use of oral contraceptives.

Human papillomavirus (HPV) infection is thought to be a necessary but not sufficient cause of most cases of cervical cancer. Since oral contraceptive use for long durations is associated with an increased risk of cervical cancer, it is important to know whether HPV infection is more common in oral contraceptive users. We present a systematic review of 19 epidemiological studies of the risk of genital HPV infection and oral contraceptive use. There was no evidence for a strong positive or negative association between HPV positivity and ever use or long duration use of oral contraceptives. The limited data available, the presence of heterogeneity between studies and the possibility of bias and confounding mean, however, that these results must be interpreted cautiously. Further studies are needed to confirm these findings and to investigate possible relations between oral contraceptive use and the persistence and detectability of cervical HPV infection.

Contraceptives, Oral↗

PubMed2003

Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis.

This study investigated regional variations in the contribution made by different human papilloma (HPV) types to invasive cervical cancer (ICC). A total of 85 studies using polymerase chain reaction to estimate HPV prevalence in ICC were identified. Data on HPV prevalence were extracted separately for squamous cell carcinoma (SCC) and for adeno- and adenosquamous-carcinoma (ADC). A total of 10 058 cases (8550 SCC, 1508 ADC) were included in pooled analyses. The most common HPV types in ICC were, in order of decreasing prevalence, HPV16, 18, 45, 31, 33, 58, 52, 35, 59, 56, 6, 51, 68, 39, 82, 73, 66 and 70. In SCC, HPV16 was the predominant type (46-63%) followed by HPV18 (10-14%), 45 (2-8%), 31 (2-7%) and 33 (3-5%) in all regions except Asia, where HPV types 58 (6%) and 52 (4%) were more frequently identified. In ADC, HPV prevalence was significantly lower (76.4%) than in SCC (87.3%), and HPV18 was the predominant type in every region (37-41%), followed by 16 (26-36%) and 45 (5-7%). The overall detection of HPV DNA was similar in different regions (83-89%). A majority of ICC was associated with HPV16 or 18 in all regions, but approximately a quarter of all ICC cases were associated with one of 16 other HPV types, their distribution varying by region.

Female↗

PubMed2003

The effect of plants on the degradation and toxicity of petroleum contaminants in soil: a field assessment.

A field project located at the US Naval Base at Port Hueneme, California was designed to evaluate changes in contaminant concentrations and toxicity during phytoremediation. Vegetated plots were established in petroleum (diesel and heavy oil) contaminated soil and were evaluated over a two-year period. Plant species were chosen based on initial germination studies and included native California grasses. The toxicity of the impacted soil in vegetated and unvegetated plots was evaluated using Microtox, earthworm, and seed germination assays. The reduction of toxicity was affected more by contaminant aging than the establishment of plants. However, total petroleum hydrocarbon concentrations were lower by the end of the study in the vegetated plots when compared to the unvegetated soil. Although phytoremediation is an effective approach for cleaning-up of petroleum contaminated soil, a long-term management plan is required for significant reductions in contaminant concentrations.

Bacteria↗

PubMed2003

A population based study of herpes simplex virus 2 seroprevalence in rural Costa Rica.

OBJECTIVES: To determine seroprevalence and determinants of herpes simplex virus 2 (HSV-2) seropositivity, in a random sample of a population based cohort of 10 049 women of Guanacaste, Costa Rica, using a highly sensitive and specific serological assay. METHODS: Seroprevalence was determined by a type specific HSV-2 ELISA assay in an age stratified random sample of 1100 women. Univariate and multivariate logistic regression was used to calculate odds ratios and 95% confidence intervals for risk factors of seropositivity. RESULTS: Overall age adjusted HSV-2 seroprevalence was 38.5% (95% CI, 37.5 to 39.5), and it was strongly associated with increasing age (p(Trend<0.0001)), both among monogamous women and women with multiple sexual partners. A greater number of lifetime sexual partners increased the risk of seropositivity, with a 28.2% (95% CI, 24.4 to 32.2) seroprevalence among monogamous women and 75% (95% CI, 65.6 to 83.0) seroprevalence for those with four or more partners (OR = 7.6 95% CI, 4.7 to 12.4 p(Trend<0.0001)). Barrier contraceptive use was negatively associated with HSV-2 seropositivity (OR 0.54, 95% CI, 0.31 to 0.94). Women with antibodies against HPV 16, 18, or 31 were 1.6 times more likely to be HSV-2 seropositive (OR 1.6, 95% CI, 1.2 to 2.1). CONCLUSIONS: HSV-2 infection is highly endemic in Guanacaste, even among lifetime monogamous women, suggesting a role of male behaviour in the transmission of the infection. Until vaccination against HSV-2 is available, education to prevent high risk sexual behaviour and the use of condoms appear as preventive measures against HSV-2.

Adolescent↗

PubMed2002

Prevalence and determinants of human papillomavirus genital infection in men.

Four-hundred-forty-five husbands of women with invasive cervical carcinoma, 165 of women with in situ cervical cancer, and 717 of control women (age range 19-82 years) were interviewed and a sample of exfoliated cells from the penis obtained in seven case-control studies conducted by the International Agency for Research on Cancer. The characteristics of human papillomavirus-positive and human papillomavirus-negative husbands were compared using odds ratios and 95% confidence intervals. Thirteen per cent of the husbands of control women, 18% of the husbands of women with invasive cervical carcinoma, and 21% of the husbands of in situ cervical carcinoma women were positive for penile human papillomavirus DNA. Human papillomavirus 16 was detected in 45 husbands, human papillomavirus 18, 31 or 33 in 19, and human papillomavirus 6/11 in 6, but the majority of human papillomavirus infection (158) was with other or unspecified human papillomavirus types. The same human papillomavirus type was seldom identified in both husband and wife. The strongest variation in penile human papillomavirus infection was by country, with percentages among the husbands of control women ranging between 3% in Spain and 39% in Brazil. Having had over 50 lifetime sexual partners, compared with only one, was associated with an odds ratio of 2.3.

Adult↗