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Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 127 records · Page 7Linked to original sources
PubMed2000

Doppler ultrasound of the maternal uterine arteries: disappearance of abnormal waveforms and relation to birthweight and pregnancy outcome.

BACKGROUND: To assess whether the gestation at which abnormal uterine artery waveforms disappear is related to birthweight and complications of pregnancy. METHODS: A prospective study of outcome of pregnancy after a uterine artery Doppler screening program set in an inner city teaching hospital. One thousand five hundred and twenty-four consecutive women attending the Obstetric Department for a routine anomaly scan at between 19 and 21 weeks gestation had maternal uterine arteries assessed using color wave Doppler. Those women in whom the flow was deemed abnormal were recalled for a further scan at 24-26 weeks gestation. The main outcome measures were birthweight, gestation at delivery and incidence of pre eclampsia. RESULTS: The women in whom the uterine artery blood flow was normal at 20 weeks had babies with significantly higher mean birthweight than those who normalized between 20 and 24-26 weeks gestation ('late normalizers') after adjustment for confounding factors; gestational age, maternal height, parity, ethnic group and smoking (mean difference=173 g, 95% confidence intervals 42 to 303 g). CONCLUSIONS: The timing of trophoblast invasion, as reflected by abnormal uterine artery waveforms, may have an effect on birthweight.

Adult↗
PubMed1999

Urinary kallikrein excretion in normotensive and hypertensive pregnancies: 8 years later.

In a previous longitudinal study of urinary kallikrein (UK) excretion in pregnancy we reported that women with low inactive UK (IUK) to creatinine ratio (IUK:Cr), measured at 16-20 weeks gestation, were at increased risk of developing pregnancy induced hypertension. In this study, 8 years later, we have recalled 14 women who had an IUK:Cr < or = 170 (Gp1) and became hypertensive in late pregnancy and 14 women who had IUK:Cr > 170 and remained normotensive (Gp2). Resting blood pressure (BP) and BP response following application of cutaneous cold to assess vasoconstrictor reactivity were measured. A timed urine sample was also collected for measurements of components of the kallikrein kinin system (KKS): IUK, active UK (AUK), kininogen (UKg), urinary kinins (UKi). Urinary creatinine (UCr) was also measured. The correlation between IUK:Cr during the 1989-1990 study and current measurement was r2 = 0.52, p < 0.0001. Although resting BP was higher in Gp1 than Gp2 this was not significantly different. However, there was a greater change in diastolic BP in Gp1 than in Gp2 in response to the cold pressor test (p < 0.04). Excretion rates of IUK, UKg and UKi were significantly lower in Gp1, p < 0.006, p < 0.003, p < 0.03, respectively. AUK was also reduced in Gp1 but did not reach statistical significance. Women with reduced activity of the renal KKS combined with increased sympathetic drive may be at increased risk of developing hypertension.

Adult↗
PubMed1999

Culture of human renal tubular cells: positive selection of kallikrein-containing cells.

Human renal tubular cells derived from nephrectomy specimens were maintained in culture and grown to confluence. Immunocytochemistry, using a panel of antibodies selected for their ability to bind to different cell types within the nephron, showed the cells to be predominantly of epithelial origin with no significant contamination by fibroblasts or cells of endothelial origin. Ten to thirty percent of the cells expressed the putative distal marker, epithelial membrane antigen (EMA), a finding confirmed by flow cytometry. Cells expressing EMA were positively selected from mixed cultures by magnetic activated cell sorting (MACS). Kallikrein activity, expressed as mU/10(6) cells, in the EMA +ve cells, was increased fourfold to sixfold when compared with that in the EMA -ve cells. Cultures of characterized human renal tubular cells and sub-populations enriched with distal cells should prove useful in studies of synthesis and release of parameters of the kallikrein kinin system (KKS) to physiological stimuli. Furthermore, a better understanding of the toxic effect on the KKS of clinically useful drugs, particularly those used for immunosuppression, may lead to therapeutic interventions to lessen unwanted effects.

Cell Culture Techniques↗
PubMed1999

In and on: investigating the functional geometry of spatial prepositions.

Spatial prepositions such as in and on seem to denote semantically indeterminate spatial relations. This reflects, in part, the physical relationships between the objects in the scenes that they are used to portray. We argue that such physical relationships are best represented in terms of an inherently dynamic functional geometry which incorporates notions of location control. Two experiments are reported. They investigate the degree to which independent judgements of location control predict choice of description across a range of scenes. The results show that judgements of location control predict viewer's choice of description under certain circumstances. In the absence of prototypical geometric relations, control information has a strong influence on choice of description. However, when the scenes portray prototypical geometric relations, control information has less of an effect. The results support a hybrid account of the semantic representation underlying the prepositions with both a geometric and a functional component to it.

Adult↗
PubMed1999

The role of the Sphingomonas species UG30 pentachlorophenol-4-monooxygenase in p-nitrophenol degradation.

Pentachlorophenol-4-monooxygenase is an aromatic flavoprotein monooxygenase which hydroxylates pentachlorophenol and a wide range of polyhalogenated phenols at their para position. The PCP-degrading Sphingomonas species UG30 was recently shown to mineralize p-nitrophenol. In this study, the UG30 pcpB gene encoding the pentachlorophenol-4-monooxygenase gene was cloned for use to study its potential role in p-nitrophenol degradation. The UG30 pcpB gene consists of 1614 bp with a predicted translational product of 538 amino acids and a molecular mass of 59,933 Da. The primary sequence of pentachlorophenol-4-monooxygenase contained a highly conserved FAD binding site at its N-terminus associated with a beta alpha beta fold. UG30 has been shown previously to convert p-nitrophenol to 4-nitrocatechol. We observed that pentachlorophenol-4-monooxygenase catalyzed the hydroxylation of 4-nitrocatechol to 1,2,4-benzenetriol. About 31.2% of the nitro substituent of 4-nitrocatechol (initial concentration of 200 microM) was cleaved to yield nitrite over 2 h, indicating that the enzyme may be involved in the second step of p-nitrophenol degradation. The enzyme also hydroxylated p-nitrophenol at the para position, but only to a very slight extent. Our results confirm that pentachlorophenol-4-monooxygenase is not the primary enzyme in the initial step of p-nitrophenol metabolism by UG30.

Biodegradation, Environmental↗
PubMed1999

TC21 and Ras share indistinguishable transforming and differentiating activities.

Constitutively activated mutants of the Ras-related protein TC21/R-Ras2 cause tumorigenic transformation of NIH3T3 cells. However, unlike Ras, TC21 fails to bind to and activate the Raf-1 serine-threonine kinase. Thus, whereas Ras transformation is critically dependent on Raf-1 TC21 activity is promoted by activation of Raf-independent signaling pathways. In the present study, we have further compared the functions of Ras and TC21. First we determined the basis for the inability of TC21 to activate Raf-1. Whereas Ras can interact with the two distinct Ras-binding sequences in NH2-terminus of Raf-1, designated RBS1 and Raf-Cys, TC21 could only bind Raf-Cys. Thus, the inability of TC21 to bind to RBS1 may prevent it from promoting the translocation of Raf-1 to the plasma membrane. Second, we found that TC21 is an activator of the JNK and p38, but not ERK, mitogen-activated protein kinase cascades and that TC21 transforming activity was dependent on Rac function. Thus, like Ras, TC21 may activate a Rac/JNK pathway. Third, we determined if TC21 could cause the same biological consequences as Ras in three distinct cell types. Like Ras, activated TC21 caused transformation of RIE-1 rat intestinal epithelial cells and terminal differentiation of PC12 pheochromocytoma cells. Finally, activated TC21 blocked serum starvation-induced differentiation of C2 myoblasts, whereas dominant negative TC21 greatly accelerated this differentiation process. Therefore, TC21 and Ras share indistinguishable biological activities in all cell types that we have evaluated. These results support the importance of Raf-independent pathways in mediating the actions of Ras and TC21.

3T3 Cells↗
PubMed1999

For COPD a combination of ipratropium bromide and albuterol sulfate is more effective than albuterol base.

BACKGROUND: A combination metered-dose inhaler aerosol containing ipratropium bromide and albuterol sulfate has been reported to be more effective than either of its components in patients with chronic obstructive pulmonary disease. The dose of albuterol sulfate is equal in moles per liter to the dose of albuterol base used in the commercially available metered-dose inhalers. OBJECTIVE: To compare the safety and efficacy of the combination of ipratropium bromide and albuterol sulfate with a commonly prescribed albuterol metered-dose inhaler containing albuterol base alone. METHODS: Investigators at different sites performed a double-blind, 29-day trial involving 357 patients with chronic obstructive pulmonary disease. Efficacy measurements were taken at 15, 30, and 60 minutes after treatment with study medication and then hourly up to 6 hours on days 1 and 29 of the trial. The primary end point was improvement in forced expiratory volume in 1 second. Clinical status was followed up and safety monitoring was also performed. RESULTS: The combination produced a significantly greater peak and mean improvement in forced expiratory volume in 1 second over albuterol base alone on both test days. Similar changes were seen with forced vital capacity. Evaluations of clinical status were better for patients receiving combination therapy, and some improvements were statistically significant. The overall incidence of adverse effects was similar in the 2 treatment groups. CONCLUSION: We conclude that a combination of ipratropium bromide and albuterol sulfate is more effective at improving pulmonary function than albuterol base alone, with no potentiation of adverse effects.

Administration, Inhalation↗
PubMed1999

Preeclamptic decidual microvascular endothelial cells express lower levels of matrix metalloproteinase-1 than normals.

In preeclampsia, invasion of intrauterine decidual blood vessels by placental cytotrophoblasts is significantly reduced. This study examined the secretion of matrix metalloproteinases (MMP) by cultured human decidual endothelial cells from normal (NDEC) and preeclamptic (PEDEC) pregnancies. MMPs secreted into the culture medium were measured using zymography, Western blotting, and ELISA. Results were confirmed by Northern analysis. Phorbol myristate acetate, known to induce protease activity in other endothelial cell populations, stimulated MMP1, MMP9, and TIMP1 secretion in both NDEC and PEDEC. Neither tumor necrosis factor-alpha nor transforming growth factor-beta, both thought to have significant roles in the control of placentation, affected MMP secretion. MMP9 and TIMP1 levels were similar between the two cell types; however, MMP1 secretion was markedly different between the cell types. NDEC expressed higher levels of MMP1 under both basal (160 +/- 32 ng/10(6) cells) and stimulated (275 +/- 50) conditions compared to PEDEC (32 +/- 24 and 70 +/- 53, respectively). The lower MMP1 expression of decidual endothelial cells from preeclamptic women may inhibit endovascular invasion by cytotrophoblasts. These findings may, at least partly, explain the relative failure of trophoblasts to invade maternal decidual blood vessels in preeclamptic pregnancy.

Capillaries↗
PubMed1999

Value of ovarian stromal blood flow velocity measurement after pituitary suppression in the prediction of ovarian responsiveness and outcome of in vitro fertilization treatment.

OBJECTIVE: To evaluate whether ovarian stromal blood flow velocity after pituitary suppression is predictive of ovarian response and the outcome of IVF treatment in patients with normal basal serum FSH levels and to compare the predictive value of this test with age, early follicular phase serum FSH level, E2 level, and FSH:LH ratio. DESIGN: Prospective observational study of women undergoing IVF treatment. SETTING: A tertiary referral center for assisted reproduction. PATIENT(S): Eighty-eight women who received the long buserelin acetate treatment protocol. INTERVENTION(S): Transvaginal color and pulsed Doppler measurement of the ovarian stromal peak systolic velocity (PSV) after pituitary suppression and measurement of the basal serum FSH level, E2 level, and FSH:LH ratio. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved and pregnancy rate. RESULT(S): Ovarian stromal PSV was the most important single independent predictor of ovarian response in patients with a normal basal serum FSH level, when compared with age, basal FSH level, E2 level, or FSH:LH ratio. Patients in group 2 (PSV > or = 10 cm/s) had a significantly higher median number of mature oocytes retrieved (11 versus 5.5) and a higher clinical pregnancy rate (35.3% versus 11.3%) than patients in group 1 (PSV <10 cm/s), even after controlling for age. CONCLUSION(S): Ovarian stromal blood flow velocity, after pituitary suppression is confirmed, is predictive of ovarian responsiveness and the outcome of IVF treatment.

Adult↗
PubMed1999

Serum vascular endothelial growth factor concentrations in in vitro fertilization cycles predict the risk of ovarian hyperstimulation syndrome.

OBJECTIVE: To explore the value of serum vascular endothelial growth factor (VEGF) concentrations during IVF cycles in predicting the risk of ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective study. SETTING: London Women's Clinic. PATIENT(S): One hundred seven women undergoing IVF. Mild OHSS developed in 10 women, moderate OHSS in 7, and severe OHSS in 3. INTERVENTION(S): Serum VEGF concentrations were measured before treatment, after pituitary desensitization, and on the days of hCG administration, oocyte collection, and ET. MAIN OUTCOME MEASURE(S): Serum VEGF concentrations. RESULT(S): Serum VEGF concentrations were higher in women in whom OHSS developed. The increase in the VEGF concentration that occurred between the day of hCG administration and the day of oocyte collection (the "VEGF rise") was an important marker of OHSS. The VEGF rise was higher in women in whom OHSS developed. A higher VEGF rise predicted all cases of OHSS and moderate/severe cases of OHSS with a sensitivity of 100% and a specificity of 60%. A likelihood ratio test showed that adding the VEGF rise or the VEGF concentration on the day of oocyte collection to a regression model as a continuous variable to the number of follicles, the E2 concentration, and the presence of polycystic ovaries significantly contributed to predicting the risk of OHSS. CONCLUSION(S): The results support the role of VEGF as an important nonsteroidal index of ovarian response. The VEGF rise may have an advantage over the E2 concentration, the number of follicles, and the number of oocytes, which individually predict only 15%-25% of cases of OHSS.

Adult↗
PubMed1999

Glyceryl trinitrate and ritodrine in tocolysis: an international multicenter randomized study. GTN Preterm Labour Investigation Group.

OBJECTIVE: To compare the efficacy of transdermal glyceryl trinitrate and intravenous (IV) ritodrine as tocolytics. METHODS: Two hundred forty-five women with preterm labor and intact membranes between 24 and 36 weeks' gestation were randomized to transdermal glyceryl trinitrate or intravenous ritodrine. Treatment was continued until contractions stopped or a maximum of 7 days. Glyceryl trinitrate was administered as a 10- or 20-mg transdermal patch. Intravenous ritodrine was administered according to nationally available guidelines. The primary outcome was prolongation of gestation expressed as a percentage of the time from entry to 37 weeks. Secondary outcomes were proportion of women who delivered the same day, next day, or within 7 and 14 days of entry, and by 32, 34, and 37 weeks. Analysis was by intention to treat. RESULTS: Twelve women (5%) were lost to follow-up. Glyceryl trinitrate and ritodrine prolonged gestation by 74% of time to 37 weeks (difference glyceryl trinitrate-ritodrine 0%; 95% confidence interval (CI) -10%, +10%). There was no significant difference in the proportion of women receiving glyceryl trinitrate or ritodrine who delivered within the specified days from study entry or weeks of gestation; however, 42 women who received glyceryl trinitrate and 58 women who received ritodrine delivered by 37 weeks (difference -11%; 95% CI -24%, +2%). No serious maternal side effects were reported for ritodrine or glyceryl trinitrate. CONCLUSION: We found no overall difference between glyceryl trinitrate and ritodrine in the acute tocolysis of preterm labor but a suggested advantage of glyceryl trinitrate over ritodrine in reducing preterm delivery rate. The maternal side effect profile and treatment discontinuation rates were fewer for glyceryl trinitrate, suggesting it was a safer alternative to ritodrine.

Adolescent↗
PubMed1999

Maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate and intravenous ritodrine.

OBJECTIVE: To determine the maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate compared with ritodrine for acute tocolysis. METHODS: Sixty women in preterm labor were enrolled in this study that was part of a multicenter study of glyceryl trinitrate. Once randomized, the women received transdermal glyceryl trinitrate or intravenous ritodrine for acute tocolysis. Measurements of maternal pulse, blood pressure (BP), and fetal heart rate (FHR) were recorded for up to 24 hours and compared over the treatment course. RESULTS: Changes from baseline in mean maternal heart rate, FHR, and maternal BP (mean arterial pressure [MAP]) were compared between the glyceryl trinitrate and ritodrine groups over the entire treatment course. The mean change from baseline in maternal heart rate was 21.1 beats per minute less (95% confidence interval [CI] 15.7, 26.5, P < .001), and the mean maternal heart rate was 21.8 beats per minute lower (95% CI 16.9, 26.7, P < .001) in the glyceryl trinitrate group. The mean change in FHR was 9.2 beats per minute less (95% CI 3.8, 14.6, P = .001) and the mean FHR significantly lower (6.9 beats per minute, 95% CI 1.9, 11.9, P = .008) during glyceryl trinitrate treatment. Ritodrine had a significantly hypotensive effect on MAP (95% CI -4.3, 0.0, P = .03). Mean arterial pressure was not significantly different over the treatment course. CONCLUSION: At doses required for acute tocolysis, transdermal glyceryl trinitrate had minimal effects on maternal pulse, BP, and FHR, and significantly fewer adverse cardiovascular effects than intravenous ritodrine. Thus, transdermal glyceryl trinitrate might be a safer treatment for women in preterm labor.

Administration, Cutaneous↗
PubMed1999

HIV-risk behaviors in adolescent substance abusers.

Thirty adolescents aged 12-18 years from each group (substance use disorders, psychiatric disorders, and controls) were assessed to explore HIV-risk behaviors and knowledge about HIV/AIDS. Semi-structured instruments for psychiatric and substance use disorders were also administered. There were no significant differences between groups in knowledge of HIV/AIDS. However, chi-square analysis of risk behaviors revealed significant differences between the substance use disorders group and the controls. The knowledge-behavior gap was greater for the substance users than all other groups, in that while they knew an equal amount about HIV/AIDS, they actually engaged in more risky sexual behaviors than the other two groups. It may be that the impulsivity associated with substance use disorders accounts for this difference. It is recommended that HIV/AIDS prevention education and impulse control strategies are included in the treatment of adolescents with substance use disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Plasma levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases -1 and -2 (TIMP-1 and TIMP-2) as noninvasive markers of liver disease in chronic hepatitis C: comparison using ROC analysis.

As chronic liver disease progresses, an imbalance occurs between synthesis and breakdown of extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are involved in degrading ECM while tissue inhibitors of metalloproteinases (TIMPs) prevent their fibrolytic action. We determined if plasma levels of MMP-2, TIMP-1 and TIMP-2 are related to liver histology in patients with chronic hepatitis C. Plasma MMP-2, TIMP-1 and TIMP-2 levels were measured in 43 patients with chronic hepatitis C. Plasma levels of MMP-2, TIMP-1 and TIMP-2 and serum ALT were correlated with liver biopsy score and specificity and sensitivity of the assays in detecting advanced liver disease were calculated from ROC analysis. Plasma TIMP-1 was significantly correlated with histological activity index (r = 0.45), portal inflammation (r = 0.48), periportal necrosis (r = 0.34) and focal necrosis (r = 0.38). Plasma TIMP-2 was significantly correlated with fibrosis (r = 0.43) and confluent necrosis (r = 0.41). Using ROC analysis both TIMP-1 and TIMP-2 had significant diagnostic ability in detecting advanced liver disease (Area under the curve 0.73 for both, p 0.015 and 0.036 respectively). A normal plasma TIMP-1 excluded advanced liver disease. Neither plasma MMP-2 or serum ALT were related to fibrosis or to histological activity index. With increased severity of liver disease in chronic hepatitis C there is increased plasma levels of TIMPs -1 and -2. Plasma TIMP-1 and TIMP-2 are sensitive and to a lesser extent specific in detecting advanced liver disease in chronic hepatitis C and could be used in preference to serum ALT.

Adult↗
PubMed1999

The impact of genetic counselling about breast cancer risk on women's risk perceptions and levels of distress.

Women referred to a familial breast cancer clinic completed questionnaires before and after counselling and at annual follow-up to assess their risk estimate and psychological characteristics. The aims were to determine whether those who attended the clinic overestimated their risk or were highly anxious and whether counselling influenced risk estimates and levels of distress. Women (n = 450) at this clinic were more likely to underestimate (39%) than overestimate (14%) their risk. Mean trait anxiety scores were higher than general population data (t = 4.9, n = 1059, P<0.001) but not significantly different from published data from other screening samples. Overestimators (z = 5.69, P<0.0001) and underestimators (z = -8.01, P<0.0001) reported significantly different risk estimates (i.e. increased accuracy) after counselling, but significant inaccuracies persisted. Over- (n = 12) and underestimators (n = 60) were still inaccurate in their risk estimates by a factor of 2 after counselling. Thirty per cent of the sample scored above the cut-off (5/6) for case identification on a screening measure for psychological distress, the General Health Questionnaire (GHQ). GHQ scores were significantly lower after counselling (t = 3.6, d.f. = 384, P = 0.0004) with no evidence of increasing risk estimate causing increased distress. The risk of distress after counselling was greater for younger women and those who were more distressed at first presentation. The counselling offered was effective in increasing the accuracy of risk perceptions without causing distress to those who initially underestimated their risk. It is worrying that inaccuracies persisted, particularly as the demand for service has since reduced the consultation time offered in this clinic. Further work is needed to evaluate alternative models of service delivery using more sophisticated methods of assessing understanding of risk.

Adult↗
PubMed1999

Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment.

The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer.

Age of Onset↗