Chemotherapy in oesophageal cancer.
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Clinical Trials as Topic↗
Biomedical subjects
P Clark
Publications and source records attributed to P Clark.
Phenotype of the endothelium in the human term placenta.
The placental endothelium contributes to regulating transplacental exchange and maintaining the immunological maternofetal barrier. We characterized the endothelial phenotype in human normal term placentae with a panel of antibodies to endothelial antigens using a standardized immunofluorescence method. Placental endothelium strongly expressed vWF, PAL-E, H-antigen, thrombomodulin, PECAM-1, CD34, CD36, ICAM-1, CD44, thy-1, A10/33-1, VE-cadherin, caveolin-1 and HLA-G, whereas occludin, claudin-1, eNOS, angiotensin converting enzyme (ACE), ICAM-2, endoglin and integrin-alphathetabeta(3)were weakly expressed. PGI(2)synthase, tissue factor, E-selectin and VCAM-1 were not detected. Some antigens were heterogenously expressed along the vascular tree or within individual villi. Expression of ACE, eNOS, vWF, P-selectin, E-selectin, integrin alpha(v)beta(3)and endoglin was stronger in the maternal decidual vessels, while PECAM-1, CD44, thy-1 and caveolin-1 expression was stronger in fetal vessels. Some endothelial markers were present in trophoblasts and stroma. Endothelial proliferation was apparent in mature intermediate and terminal villi. There was limited inflammatory response to TNFalpha in explants, characterized by upregulation of vWF, P-selectin, PECAM-1 and CD44, downregulation of thrombomodulin, but no increase in ICAM-1 expression, nor induction of E-selectin, VCAM-1 or tissue factor. These patterns of heterogeneity, proliferative activity and inflammatory activation may underlie the specific physiological roles of the placental endothelium.
Adult↗
Amniotic fluid concentrations of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 during pregnancy and labor.
OBJECTIVE: This study was undertaken to determine whether obstetric factors affect the concentrations of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in the amniotic fluid. STUDY DESIGN: We prospectively collected amniotic fluid samples from 109 women at various stages of pregnancy and labor and determined matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 concentrations by means of enzyme-linked immunosorbent sandwich assay systems. With multiple regression analysis we evaluated relationships between amniotic fluid matrix metalloproteinase 9 concentration and tissue inhibitor of metalloproteinase 1 concentration and the following factors: gestational age, presence of labor, cervical dilatation, membrane status, presence of clinical chorioamnionitis, and microbial colonization of the amniotic fluid. RESULTS: The detectable presence of amniotic fluid matrix metalloproteinase 9 was independently associated with intra-amniotic infection, labor, cervical dilatation, and spontaneous rupture of membranes. Chorioamnionitis and amniotic fluid matrix metalloproteinase 9 concentrations were correlated with tissue inhibitor of metalloproteinase 1 levels. CONCLUSIONS: Intra-amniotic infection, advanced labor, and rupture of membranes before the onset of labor were independently associated with the presence of matrix metalloproteinase 9 in the amniotic fluid. Both pathologic and physiologic processes appear to produce shifts in the balance between degradation and synthesis of the extracellular matrix.
Amniotic Fluid↗
The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease.
OBJECTIVE: Our purpose was to evaluate the effectiveness of a risk-based intrapartum antibiotic prophylaxis strategy for the prevention of early-onset neonatal group B streptococcal disease. STUDY DESIGN: Cases and controls were selected from infants born to women with one or more risk factors: preterm labor or rupture of membranes, prolonged rupture of membranes (>18 hours), fever during labor, or previous child with group B streptococcal disease. Cases were matched with controls by birth hospital and gestational age. Data abstracted from medical records were analyzed to estimate the effectiveness of intrapartum antibiotic prophylaxis. RESULTS: We analyzed data from 109 cases and 207 controls. Nineteen (17%) case versus 69 (33%) control mothers received an acceptable regimen of intrapartum antibiotic prophylaxis. In adjusted analyses, the effectiveness of intrapartum antibiotic prophylaxis was 86% (95% confidence interval, 66%-94%). When the first dose of antibiotics was given > or =2 hours before delivery, the effectiveness increased to 89% (95% confidence interval, 70%-96%); when it was given within 2 hours of delivery, the effectiveness was 71% (95% confidence interval, -8%-92%). Effectiveness was lowest in mothers with intrapartum fever (72%, 95% confidence interval, -9%-93%). On the basis of a 70% prevalence of maternal risk factors expected among cases in the absence of intrapartum antibiotic prophylaxis, we estimate that the risk-based strategy could reduce early-onset group B streptococcal disease by 60%. CONCLUSIONS: The risk-based approach to intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease. To achieve the maximum preventive effect, the first dose of antibiotics should be administered at least 2 hours before delivery.
Adult↗
Amniotic fluid matrix metalloproteinase-8 indicates intra-amniotic infection.
OBJECTIVE: This study was undertaken to determine whether matrix metalloproteinase-8, which is produced by neutrophils, is a useful marker for the detection of intra-amniotic infection. STUDY DESIGN: We performed a case-control study using enzyme-linked immunosorbent assays to detect matrix metalloproteinase-8 in 77 amniotic fluid specimens that were obtained by amniocentesis from women with preterm contractions or preterm labor and intact fetal membranes (n = 66) and from women with preterm premature rupture of membranes (n = 11). RESULTS: Thirty women had culture-proven intra-amniotic infection (cases), 21 of whom had intact membranes. After constructing receiver operating characteristic curves to establish the optimal threshold concentration of matrix metalloproteinase-8 for a positive test result, we detected matrix metalloproteinase-8 in 27 of 30 women with intra-amniotic infection; only 10 of 47 control specimens contained matrix metalloproteinase-8 (P <.001; odds ratio, 33.3; 95% CI, 8.4, 132.7). Matrix metalloproteinase-8 was present in 20 of 21 women with intact membranes and intra-amniotic infection and in only 10 of 45 control subjects (P <.001; odds ratio, 70.0; 95% CI, 8.3, 587.6). Among women with intact membranes, the sensitivity of the assay was 0.95 and the specificity was 0.78. CONCLUSION: Our results indicate that matrix metalloproteinase-8 is highly correlated with intra-amniotic infection and that enzyme-linked immunosorbent assay for matrix metalloproteinase-8 may be a clinically useful test for the diagnosis of intra-amniotic infection in women with preterm contractions and preterm labor.
Amnion↗
Multiple spine fractures in an adolescent snowboarder: case report.
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Adolescent↗
Transfusion triggers for blood components.
Whereas there are general guidelines for acceptable transfusion therapy, optimal transfusion therapy has not been determined for most clinical settings. Recent research has focused on controlled studies of red cell transfusion in specific clinical settings. Better determinations of oxygen delivery and consumption are needed to guide clinicians in determining whether transfusion is justified for patients during the perioperative period, those with coronary artery disease, and those in intensive care units. For sickle cell disease, the role of transfusion for acute complications can be life saving; however, the role of chronic transfusion regimens awaits further research into efficacy. Finally, whereas criteria for the prophylactic transfusion of platelets in hematologic diseases are well described, relatively little information is available on the value of platelet transfusion where the absolute count is less than 100,000 but greater than 50,000. The value of fresh frozen plasma components, both standard and sterilized, also requires elucidation.
Blood Component Transfusion↗
Inclusions in the erythrocytes of eastern water dragons (Physignathus lesueurii).
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Animals↗
Cross-linking of the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase to template-primer.
Cross-linking experiments were performed with human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutants with unique cysteine residues at several positions (positions 65, 67, 70, and 74) in the fingers subdomain of the p66 subunit. Two approaches were used--photoaffinity cross-linking and disulfide chemical cross-linking (using an oligonucleotide that contained an N(2)-modified dG with a reactive thiol group). In the former case, cross-linking can occur to any nucleotide in either DNA strand, and in the latter case, a specific cross-link is produced between the template and the enzyme. Neither the introduction of the unique cysteine residues into the fingers nor the modification of these residues with photocross-linking reagents caused a significant decrease in the enzymatic activities of RT. We were able to use this model system to investigate interactions between specific points on the fingers domain of RT and double-stranded DNA (dsDNA). Photoaffinity cross-linking of the template to the modified RTs with Cys residues in positions 65, 67, 70, and 74 of the fingers domain of the p66 subunit was relatively efficient. Azide-modified Cys residues produced 10 to 25% cross-linking, whereas diazirine modified residues produced 5 to 8% cross-linking. Disulfide cross-linking yields were up to 90%. All of the modified RTs preferentially photocross-linked to the 5' extended template strand of the dsDNA template-primer substrate. The preferred sites of interactions were on the extended template, 5 to 7 bases beyond the polymerase active site. HIV-1 RT is quite flexible. There are conformational changes associated with substrate binding. Cross-linking was used to detect intramolecular movements associated with binding of the incoming deoxynucleoside triphosphate (dNTP). Binding an incoming dNTP at the polymerase active site decreases the efficiency of cross-linking, but causes only modest changes in the preferred positions of cross-linking. This suggests that the interactions between the fingers of p66 and the extended template involve the "open" configuration of the enzyme with the fingers away from the active site rather than the closed configuration with the fingers in direct contact with the incoming dNTP. This experimental approach can be used to measure distances between any site on the surface of the protein and an interacting molecule.
Cross-Linking Reagents↗
Performance characteristics of putative tests for subclinical chorioamnionitis.
OBJECTIVE: To evaluate amniotic fluid glucose, matrix metalloproteinase (MMP)-9, interleukin (IL)-6, and IL-12 for diagnosing subclinical chorioamnionitis in women with preterm labor. METHODS: Forty-four women in preterm labor at 22-35 weeks gestation with suspected subclinical chorioamnionitis underwent amniocentesis. Amniotic fluid analysis included Gram stain, culture, and determination of glucose, MMP-9, IL-6, and IL-12 concentrations. Median values of these analytes were compared using the Mann-Whitney U test. Sensitivity, specificity, and positive and negative predictive values were calculated for tests using a positive amniotic fluid culture or delivery within 24 hours as the key outcome variables. RESULTS: Amniotic fluid concentrations of glucose, MMP-9, and IL-6 correlated closely with positive culture or delivery within 24 hours. IL- 12 concentrations did not correlate with either a positive culture or delivery within 24 hours. CONCLUSIONS: Amniotic fluid glucose, MMP-9, and IL-6 reliably predict microbial invasion of the amniotic cavity or imminent delivery. IL- 12 values did not correlate with amniotic fluid culture results or imminent delivery.
Amniocentesis↗
beta-cell genes and diabetes: quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor-1alpha and glucokinase mutations.
Mutations in the beta-cell genes encoding the glycolytic enzyme glucokinase (GCK) and the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the most common causes of maturity-onset diabetes of the young (MODY). Studying patients with mutations in these genes gives insights into the functions of these two critical beta-cell genes in humans. We studied 178 U.K. and French MODY family members, including 45 GCK mutation carriers and 40 HNF-1alpha mutation carriers. Homeostasis model assessment of fasting insulin and glucose showed reduced beta-cell function in both GCK (48% controls, P<0.0001) and HNF-1alpha (42% controls, P<0.0001). Insulin sensitivity was similar to that of control subjects in the GCK subjects (93% controls, P = 0.78) but increased in the HNF-1alpha subjects (134.5% controls, P = 0.005). The GCK patients showed a similar phenotype between and within families with mild lifelong fasting hyperglycemia (fasting plasma glucose [FPG] 5.5-9.2 mmol/l, interquartile [IQ] range 6.6-7.4), which declined slightly with age (0.017 mmol/l per year) and rarely required pharmacological treatment (17% oral hypoglycemic agents, 4% insulin). HNF-1alpha patients showed far greater variation in fasting glucose both between and within families (FPG 4.1-18.5 mmol/l, IQ range 5.45-10.4), with a marked deterioration with age (0.06 mmol/l per year), and 59% of patients required treatment with tablets or insulin. Proinsulin-to-insulin ratios are increased in HNF-1alpha subjects (29.5%) but not in GCK (18.5%) subjects. In an oral glucose tolerance test, the 0- to 120-min glucose increment was small in GCK patients (2.4+/-1.8 mmol/l) but large in HNF-1alpha patients (8.5+/-3.0 mmol/l, P< 0.0001). This comparison shows that the clear clinical differences in these two genetic subgroups of diabetes reflect the quantitative and qualitative differences in beta-cell dysfunction. The defect in GCK is a stable defect of glucose sensing, whereas the HNF-1alpha mutation causes a progressive defect that alters beta-cell insulin secretion directly rather than the sensing of glucose.
Adult↗
The Glasgow Outcome, APCR and Lipid (GOAL) Pregnancy Study: significance of pregnancy associated activated protein C resistance.
Activated protein C (APC) resistance secondary to Factor V Leiden (FVL) is associated with pregnancy failure and pre-eclampsia (PET). In non-pregnant subjects, the degree of resistance to APC relates to venous thrombosis risk. In pregnancy, resistance to APC occurs in the absence of FVL. We investigated, in an unselected prospective longitudinal study of 1,671 pregnant, non-FVL subjects, the relationship of the APC sensitivity ratio (APC:SR) with demographic variables and pregnancy outcome. Lower APC:SR values at 7-16 weeks gestation were observed in subjects who subsequently developed PET (median APC:SR 2.55, IQR 2.29-2.70 vs 2.69, IQR 2.48-2.93, Mann-Whitney U-test p = 0.003) in the current pregnancy. An APC:SR < the median (2.69) at 7-16 weeks was associated with a 2.95-fold increased risk (CI95 1.2-7.4) of PET in the current pregnancy. No relationship between the APC:SR, at any gestation, and fetal loss was observed. An inverse correlation between the APC:SR and birth weight was noted. Higher APC:SRs were observed in blood group O subjects and smokers. An inverse relationship of the APC:SR with age, diastolic blood pressure and total serum cholesterol was observed.
Abortion, Spontaneous↗
Trauma to the thoracic and lumbar spine in the adolescent.
During adolescence the spine undergoes rapid growth and changes in anatomy and biomechanical properties. Fractures of the adolescent spine are relatively uncommon but may give rise to serious problems. This review describes thoracolumbar fractures in adolescents with respect to epidemiology, anatomy, mechanisms of injury, clinical and radiologic assessment, and nonoperative and operative treatment. The treatment of these injuries follows many of the same principles as spinal fractures in adults but nonoperative treatment is used more frequently because there is less spinal instability and better tolerance of bed rest and spinal immobilization in this young population.
Adolescent↗
Diagnostic confusion caused by dapsone-induced methaemoglobinaemia.
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Anti-Inflammatory Agents, Non-Steroidal↗
Re-emerging syphilis in the UK: a behavioural analysis of infected individuals.
In-depth interviews with 27 individuals infected with syphilis in a recent UK outbreak (out of a total of 58 diagnosed between May 1999 and August 2000 in three city hospitals) were carried out to examine behaviour and attitudes. Most (23/27) participants were homosexual men, seven of whom were HIV positive. Between them, the 23 gay men had 1,494 different contacts in the twelve months prior to their awareness of having syphilis, but only 10% of these contacts could be named. While oral sex (usually unprotected) was the most prevalent behaviour (median = 30 partners per year), only 39% perceived unprotected oral sex as a syphilis risk (c.f. 70% for anal sex). Many gay men (61%) used gamma hydroxybutyrate (GHB) during sex as an aphrodisiac. This syphilis-infected subset of the population had high levels of unprotected and anonymous sex, which brings into question the usefulness of contact tracing to control syphilis outbreaks. The majority of partners were casual oral sex partners. More awareness is urgently needed around syphilis symptoms and risks, and risks of using drugs to reduce sexual inhibitions.
HIV Infections↗
An audit of the investigation and use of anti-D immunoglobulin prophylaxis in Tayside.
OBJECTIVES: To audit the implementation of national guidelines on the investigation and management of RhD disease in Tayside. SETTING: Tayside region. DESIGN: An eight month retrospective audit. RESULTS: Two hundred and eighty eight completed pregnancies in RhD negative women were observed from a total of 1879 deliveries. Of these, 120 RhD negative and 169 RhD positive babies were delivered from women who had not previously been sensitised. At delivery, anti-D was used appropriately in all cases. Of those assessed to require anti-D (n = 168), 91% received it within 24 hours of delivery. In 59 RhD negative subjects, 75 potential sensitising events occurred antenatally. In 45 of these, the event occurred after 20 weeks gestation and 44 received appropriate anti-D. In 11 (23.7%) of these, no foetomaternal haemorrhage assessment was carried out. CONCLUSION: Despite a significant increase in awareness of antenatal prophylaxis since a previous audit in the region, there is still a significant failure to request FMH assessments following potential antenatal sensitising episodes and after delivery. During the audit period, an EDTA plasma gell-based antibody detection system was commissioned in the region. This has allowed the introduction of internal laboratory referral for FMH assessment. This has allowed accurate knowledge on the possible occurrence of FMH at delivery, but has not had a significant impact on antenatal events.
Female↗
Antibiotic susceptibility profiles for group B streptococci isolated from neonates, 1995-1998.
Antibiotic susceptibility profiles were analyzed for 119 invasive and 227 colonizing strains of group B streptococci isolated from neonates at 6 US academic centers. All strains were susceptible to penicillin, vancomycin, chloramphenicol, and cefotaxime. The rate of resistance to erythromycin was 20.2% and to clindamycin was 6.9%. Resistance to erythromycin increased in 1997. Type V strains were more resistant to erythromycin than were type Ia (P=.003) and type Ib (P=.004) strains and were more resistant to clindamycin than were type Ia (P<.001), type Ib (P=.01), and type III (P=.001) strains. Resistance rates varied with geographic region: in California, there were high rates of resistance to erythromycin and clindamycin (32% and 12%, respectively), and low rates in Florida (8.5% and 2.1%, respectively). Penicillin continues to be the drug of choice for treatment of group B streptococcus infection. For women who are penicillin intolerant, however, the selection of an alternative antibiotic should be guided by contemporary resistance patterns observed in that region.
Anti-Bacterial Agents↗
Estuarine and habitat-related differences in growth rates of young-of-the-year winter flounder (Pseudopleuronectes americanus) and tautog (Tautoga onitis) in three northeastern US estuaries.
Instantaneous growth rates of young-of-the-year winter flounder Pseudopleuronectes americanus (Walbaum) (12.0-60.4 mm standard length, SL) and tautog Tautoga onitis (Linnaeus) (21.4-73.8 mm total length, TL) from three estuarine systems in New Jersey (Great Bay-Little Egg Harbor and Navesink River) and Connecticut (Hammonasset River) were used in an attempt to assess the relative quality of selected nominal habitats. A series of short-term field caging experiments were conducted during 1994 and 1995 in: macroalgae (primarily, Ulva lactuca), eelgrass (Zostera marina), unvegetated areas adjacent to macroalgae and eelgrass and tidal creeks in Spartina dominated marsh. Growth rates varied with habitat, estuary and year. Comparisons across nominal habitats within and among estuaries did not show any one habitat with consistently higher growth, and growth was relatively independent of whether a habitat was vegetated or adjacent to vegetation. The growth rates of winter flounder and tautog from the Hammonasset River were not different among habitats in either year of the study. In the Great Bay-Little Egg Harbor, both winter flounder and tautog had higher growth rates in macroalgae with growth in eelgrass varying significantly between years. Conversely, in the Navesink River both species had higher growth rates in eelgrass. Environmental changes associated with temperature and dissolved oxygen appeared to influence growth rates. Winter flounder growth rate and survival was depressed in tidal marsh creeks in the three estuaries and in vegetated macroalgae habitats in the Navesink River where dissolved oxygen levels were often very low (<2 mgl(-1)) for extended periods. In summary, the growth rates of the young-of-the-year of these two species varied temporally and were dependent on the interaction of both the specific estuary and habitat in which the experiments took place. Further, habitat quality, as defined by relative growth rate, was difficult to evaluate because it can be variable and nominal habitat designations are often not sufficient to define the boundaries of a species habitat requirements.
Journal Article↗