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Biomedical subjects

E Smith

Publications and source records attributed to E Smith.

At least 163 records · Page 9Linked to original sources
PubMed1996

Anal and cervical abnormality in women--prediction by human papillomavirus tests.

A total of 151 women at risk of human immunodeficiency virus infection were investigated, to study the strength of the association between cervix and anus regarding the presence of HPV and cytological abnormality. An equal percentage of women had abnormal cervical (12.2%) and anal (12.1%) Papanicolaou smears. HPV measured by PCR was detected in 93.3% of cervical squamous intraepithelial lesions (SIL) compared to 49.1% of normal cervical cytologies, and in 100% of anal SIL and 67.4% of normal anal cytologies, respectively. After controlling for HPV-PCR status, immunodeficiency, as measured by a low CD4+ count and HIV positivity, increased the detection of cervical and to some extent anal squamous intraepithelial lesions (SIL). We evaluated how precisely an HPV test could predict cervical disease and found that the HPV-PCR test was slightly more sensitive than the HPV-hybrid capture (HC) test (PCR: 93.3% vs. HC: 88.9%), whereas the HC test was significantly more specific (83.6% vs. 50.9%), and with a much higher positive predictive value (43.2% vs. 20.6%). Similar results were obtained for anal SIL. HIV positivity increased sensitivity, lowered specificity and increased the positive predictive value of the tests. A diagnosis of cervical SIL was associated with a more than 3-fold increased risk of a simultaneous abnormal anal smear (p < 0.05). In conclusion, cervical and anal disease were significantly associated and almost exclusively seen in the presence of HPV. Immunodeficiency and HIV positivity increased the risk of disease in HPV-positive subjects. Hybrid capture, which requires a higher viral load than PCR to detect HPV, was clearly superior in predicting cervical and anal disease. Altogether, these findings suggest that a high level of HPV infection may be important for the development of SIL in the population studied.

Adult↗
PubMed1996

Increased bone formation in osteocalcin-deficient mice.

Vertebrates constantly remodel bone. The resorption of preexisting bone by osteoclasts and the formation of new bone by osteoblasts is strictly coordinated to maintain bone mass within defined limits. A few molecular determinants of bone remodelling that affect osteoclast activity have been characterized, but the molecular determinants of osteoblast activity are unknown. To investigate the role of osteocalcin, the most abundant osteoblast-specific non-collagenous protein, we have generated osteocalcin-deficient mice. These mice develop a phenotype marked by higher bone mass and bones of improved functional quality. Histomorphometric studies done before and after ovariectomy showed that the absence of osteocalcin leads to an increase in bone formation without impairing bone resorption. To our knowledge, this study provides the first evidence that osteocalcin is a determinant of bone formation.

Animals↗
PubMed1996

Longitudinal study of the effects of pregnancy and other factors on detection of HPV.

OBJECTIVE: An epidemiologic study of 108 pregnant and 192 non-pregnant women was carried out to determine the effects of pregnancy and other factors on the detection of HPV infection, since both or larger numbers of pregnancies and HPV infection are known to be risk factors for cervical cancer. PATIENTS AND METHODS: Study participants were followed up at 3-months intervals for a period of 15 months (1-6 months after delivery). At each visit, two cervical specimens were taken, one for routine cytology and a second for HPV DNA hybridization using Virapap/Viratype, and a 5-ml blood sample was taken and a self-administered questionnaire was completed. RESULTS: In cervical specimens of the initial examination, HPV DNA was detected among 5.0% of pregnant and 5.2% of nonpregnant women, whereas HPV 16/18 was found in 80% of the HPV-positive specimens. Using multiple cervical specimens taken over time, 13.9% of the pregnant and 15.1% of the nonpregnant women tested positive for HPV DNA at least once. Adjusted for study group, age, and the number of available cervical specimens, ever detection of HPV infection (any type) was associated with more sexual partners and larger numbers of cigarettes smoked daily. An autoregressive generalized linear model was used to analyze the time-dependent multiple observations per study subject. Adjusting for age and trimester of pregnancy, the determinants of detecting high-risk HPV types (16/18 and 31/33/35) in the cervical specimen were an abnormal Pap smear, a positive HPV result in a preceding specimen, more than six sexual partners in the lifetime, and currently smoking more than 20 cigarettes per day with odds ratios of 10.9, 5.6, 3.2, and 2.7, respectively. CONCLUSION: Our data provide no evidence for a higher detection rate of HPV during pregnancy.

Adult↗
PubMed1996

Environmental chemicals, respiratory hypersensitization and international chemical safety.

Allergic hypersensitization to a variety of chemicals, natural and synthetic, is a worldwide health problem. Respiratory tract hypersensitization is responsible for significant morbidity and, in some cases, mortality. An important step in managing and controlling health risks, such as allergic hypersensitization, is to identify the chemical hazard, define dose-effect and dose-response relationships, evaluate exposure, and characterize risk. In practical terms, the risk and safety assessment processes lead to the designation of control limits for exposure to chemicals in air, food, water, and consumer products. The objective of exposure limits is to protect the whole human population, including the most susceptible individuals and 'at risk' groups. The existence of susceptible individuals is a factor that must be taken into account when quantitative chemical risk assessments are being made, and should be covered in the risk characterization. Within a population, individual susceptibility is influenced by genetic and environmental factors and these have regional and national differences. There may be cases where hypersusceptible individuals and groups, such as asthmatic children, are not fully protected by regulatory exposure limits. The International Programme on Chemical Safety, as the global programme on identifying and assessing chemical risks to human health and the environment in order to assist countries in effective management, is striving to elucidate the toxicological basis for chemically-associated disease and advance the basic science and methodology of chemical risk and safety assessment.

Adult↗
PubMed1996

Patterns and trends in clinically recognized HIV seroconversions among all newly diagnosed HIV-infected homo-/bisexual men in Denmark, 1991-1994.

OBJECTIVE: To analyse patterns and trends in recently acquired HIV infections among newly diagnosed homo-/bisexual men. DESIGN AND METHODS: All newly diagnosed HIV-positive homo-/bisexual men reported to the mandatory national HIV reporting system in Denmark in 1991-1994. RESULTS: A total of 495 homo-/bisexual men were diagnosed with HIV infection for the first time; 45% had previously been tested HIV-negative, among whom 68% were known to have seroconverted 4 years or less prior to the positive diagnosis. Both proportions increased significantly from 1991 to 1994. Among men previously tested negative, the median interval between last negative and first positive HIV test was 902 days (range, 14-4459 days); 21.3% had seroconverted within 1 year and 55.1% within 3 years. Men previously tested negative were significantly younger than men never tested. Sex with a known HIV-positive partner was associated with having had a previous negative test and with being young. Half of the men had HIV-associated symptoms when diagnosed with HIV. Using a logistic regression model the following variables were associated with being a clinically recognized recent seroconverter: young age, no HIV-associated symptoms when diagnosed as HIV-infected, and ever having sex with an HIV-infected man. CONCLUSION: An increasing proportion of homo-/bisexual men diagnosed with HIV in Denmark in the early 1990s had had a negative HIV test 4 years or less before being diagnosed as HIV-positive. These men were younger and had HIV-associated symptoms less often than men not previously tested. The national HIV reporting system provides valuable information for planning primary HIV prevention programmes.

AIDS Serodiagnosis↗
PubMed1996

IL-4 upregulates tenascin synthesis in scleroderma and healthy skin fibroblasts.

Tenascin (TN), a large extracellular matrix glycoprotein, is transiently expressed during embryonic development, but is absent from most normal adult tissues. TN is reexpressed, however, in healing wounds, in the stroma of some tumors, and in fibrotic diseases such as systemic sclerosis (SSc) and rheumatoid arthritis. To clarify the mechanisms regulating TN expression, we studied the effects of selected cytokines (PDGF, bFGF, TGF-beta, IL-1, IL-4, IL-6, IFN-gamma, and TNF-alpha) found in fibrotic tissue on TN expression by dermal fibroblasts. IL-4 strongly induced TN protein levels (up to 10-fold over the basal level), whereas PDGF and bFGF were less potent inducers of TN than IL-4. All other cytokines tested, including TGF-alpha1, did not stimulate TN synthesis. IL-4 also increased TN mRNA expression, and this effect was blocked by actinomycin D. Cycloheximide increased basal TN mRNA expression and induced TN mRNA in IL-4-treated fibroblasts, suggesting that repressor protein(s) may regulate transcription of the TN gene. Although no differences in constitutive TN expression or effects of cytokines on TN expression were observed between SSc and healthy fibroblasts, these data are consistent with the observations that high levels of both IL-4 and TN are present in the affected skin of patients with SSc. These results suggest that the high level of TN found in the affected tissue of patients with SSc results from the high level of IL-4 present.

Adult↗
PubMed1996

Partner notification for HIV infection in Denmark: attitudes and preliminary results.

OBJECTIVES: To examine attitudes, experience and preliminary results of partner notification (PN) for HIV infection in Denmark among the doctors who inform one of their patients about being HIV infected. METHOD: The doctors who had reported to the national HIV surveillance unit about a new-identified HIV infected person, during a 9 months period, were searched for one year later. The traced doctors were interviewed. The results of the interview related to 102 out of 195 (52%) reports were compared between the 48 interviewed general practitioners (GPs) and the 33 interviewed hospital doctors (HDs). The proportion of traced reporting doctors were higher among GPs than among HDs. RESULTS: Both GPs and HDs found it difficult to give a positive HIV test result and wanted trained counsellors to work with them in the PN process. Less experience and fewer post-graduate courses about HIV may explain the GPs' lack of confidence to follow-up asymptomatic HIV positive patients. It was neither a routine for all the GPs or for all HDs to ask about patient behaviour nor to discuss safe sex with their index patients, and screening for other sexually transmitted diseases were seldomly performed. The numbers of partners notified, especially by the doctors were low. CONCLUSIONS: HIV reporting doctors in Denmark are motivated for PN. Educational programmes about counselling and care of HIV infected patients should, however, be offered at intervals, especially to GPs. The outcome of PN can only be measured to a certain level as long as exposed partners are neither obliged to be tested nor to be counselled and as long as information about counselling and testing can not be shared between doctors in different settings.

Attitude of Health Personnel↗
PubMed1996

Diminished soluble and total cellular L-selectin in cord blood is associated with its impaired shedding from activated neutrophils.

We have previously shown that surface levels of the adhesive glycoprotein, L-selectin, are diminished on cord blood neutrophils (polymorphonuclear leukocytes, PMN) and associated with impaired adherence to endothelium under flow conditions. To test the hypothesis that diminished surface levels reflect a total cellular deficiency, we measured L-selectin in PMN lysates and plasma from cord and adult blood. L-selectin content was decreased in cord blood PMN lysates compared with those of adults by both Western blot analyses and ELISA (cord blood, 1195 +/- 160 pg/mL; adult, 1870 +/- 260 pg/mL; X +/- SEM; p < 0.05). Soluble L-selectin levels were also decreased in cord blood plasma (324 +/- 24 ng/mL versus 537 +/- 28 ng/mLiter in adult plasma, p < 0.01). To evaluate L-selectin function, we next compared the dose dependent effect of several chemoattractants on shedding of L-selectin from cord blood and adult PMN. Adult PMN showed greater overall shedding of L-selectin as compared with cord blood PMN after stimulation with fMet-Leu-Phe (p < 0.03) and granulocyte-macrophage colony-stimulating factor (p < 0.02). In contrast, shedding of L-selectin was similar between groups after IL-8 tested stimulation. We conclude that cord blood PMN have a decreased cellular content of L-selectin in addition to an impaired ability to shed surface L-selectin in response to specific inflammatory mediators.

Adult↗
PubMed1996

Phorbol ester regulation of the gonadotropin-releasing hormone (GnRH) gene in GnRH-secreting cell lines: a molecular basis for species differences.

Phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) regulation of the GnRH gene was studied in two mouse GnRH neuronal cell lines, Gn11 and NLT. TPA treatment of NLT cells grown in low serum conditions did not alter endogenous mouse GnRH mRNA levels, indicating that the endogenous mouse gene is not regulated by phorbol esters under these conditions. This result is confirmed in transfection studies in which TPA treatment did not change expression of a mouse GnRH-luciferase reporter gene construct. In contrast, TPA treatment stimulated expression of a human GnRH-luciferase reporter construct, correlating with the expression of the protoon-cogenes c-fos and c-jun. TPA stimulation of the human GnRH gene is mediated by a consensus AP-1 site located at -402 to -396 bp, TGACTCA, which specifically binds c-fos and c-jun in Gn11 and NLT cells and recombinant c-jun in gel mobility shift studies. In contrast, the rodent GnRH genes, when aligned for maximum homology, contain a DNA sequence with a 1-bp difference, TGTCTCA from the human gene. In gel mobility shift studies, this DNA sequence does not form a complex with Gn11 or NLT nuclear extract or with recombinant c-jun. This is the first demonstration of species-specific differences in phorbol ester regulation of GnRH gene transcription and could, in part, explain differences in reproductive function among mammals.

Animals↗
PubMed1996

Lamotrigine-induced rash in children.

Of 68 children treated with lamotrigine, a new antiepileptic medication, five developed a rash. One child developed Stevens-Johnson syndrome on lamotrigine monotherapy. Of the five patients with the rash, three were admitted to the hospital (two to the intensive care unit). All recovered completely, but one child had a recurrence of the rash within 30 minutes of reexposure to lamotrigine after 6 months.

Adult↗
PubMed1996

Discontinuation of anticonvulsant therapy in children free of seizures for 1 year: a prospective study.

We studied 97 children who were weaned from antiepileptic drug therapy 1 year after their last seizure. Medication was withdrawn over 4 to 8 weeks, and patients were followed for 12 to 57 months (32.4 +/- 13.1; mean +/- SD) or until seizure recurrence. The overall probability of remaining seizure free was 78% at 3 months, 71% at 6 months, 66% at 12 months, and 61% at 24 months (95% CI, 51, 71), similar to studies that have required longer treatment periods. Factors retained in multivariate analysis were female sex, age at seizure onset over 120 months of age, seizure type, and clinical evidence of neurologic abnormalities. Using these risk factors, a simple method of predicting the 24-month recurrence risk was possible.

Anticonvulsants↗
PubMed1996

Gender, gender role, and drawing skill.

Separate bodies of research suggest that performance in spatial reasoning covaries with gender and with gender role. Typically studies employ a spatial task whose variance is then used to account for differences in scores between gender groups or variance in a measure of gender role. A methodological issue in such research is that the tasks used to represent spatial reasoning may be differentially available or differentially appealing as a function of gender. Also, authors tend to analyze data in terms of either gender or gender role but rarely both. A collection of personality assessments administered to 204 college students each contained a completed Minnesota Multiphasic Personality Inventory (MMPI-2) and a drawing of a human figure. Within MMPI-2 are three measures of gender role. Drawing talent is unquestionably spatial and has the advantage of being equally available and encouraged among the two genders. Male gender predicted drawing skill. Within both genders, self-perceived masculinity in gender role also predicted higher scores on the drawing skill. Outcomes are seen as compatible with Geschwind and Galaburda's 1987 formulation regarding the behavioral manifestations of fetal androgenization.

Adult↗
PubMed1996

Promoter and transcription of type X collagen gene in broiler chickens with tibial dyschondroplasia.

Type X collagen is produced exclusively in hypertrophic chondrocytes of the growth plate of the proximal tibiotarsus and is believed to play an important role during normal development from chondrogenesis to osteogenesis. Chondrocytes of chickens with tibial dyschondroplasia (TD) fail to attain full hypertrophy and the amount of type X collagen, being a marker of hypertrophy, is likely to be reduced. It is not clear whether transcriptional regulation is functional for expression of the type X collagen gene in TD birds. Nucleotide sequence of the type X collagen gene promoter was determined by sequencing PCR-based DNA clones. Nucleotide identity of this fragment between the normal and TD carriers was 97.6%. Both normal and TD birds were similar in a putative transcription start site, the site of TATAA box, and neither had a CCAAT box. However, there were two gaps in TD carriers, four gaps in normals, and five nucleotide substitution sites. By rapid amplification of cDNA ends by PCR (RACE-PCR), transcription of the gene was assessed using total RNA and mRNA from both normal chondrocytes and TD lesions at 3 and 4 wk of age. The RACE-PCR product for type X collagen mRNA was detectable in both normal and TD birds at two stages. No difference was found between them. This result does not support the hypothesis that transcriptional regulation of type X collagen gene is important in TD development of chickens. Variations in the promoter region did not affect transcription of type X collagen gene in TD carrier chickens.

Animals↗