Evidence against a major genetic basis for combined breast and colorectal cancer susceptibility.
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Adult↗
Biomedical subjects
L Brooks
Publications and source records attributed to L Brooks.
Non-attendance at secondary prevention clinics: the effect on lipid management.
BACKGROUND: Secondary prevention of coronary artery disease is effective in reducing morbitiy and mortality. Our aim was to assess lipid management following non-attendance to a hospital based secondary prevention clinic. METHODS: Data were collected over 5 years on statin usage and total cholesterol levels for patients with coronary artery disease following attendance at a cardiac nurse led outpatient clinic. Lipid levels were taken from a central laboratory database, for both patients discharged from clinic and non-attenders. RESULTS: From 935 inpatients discharged from hospital, 248 (29%) defaulted from outpatient follow up. Lipid lowering drug usage was similar (72% vs. 74% for non-attenders, p=NS). Attenders at the nurse led outpatient clinic were more likely to achieve a total cholesterol <5 mmol/L at discharge than non-attenders (70% vs. 43%; p < 0.001), with a lower mean total cholesterol (4.75 +/- 0.06 mmol/L vs. 5.33 +/- 0.08 mmol/L; p < 0.001). Non-attenders subsequently had a greater number of cholesterol measurements than those who were discharged from the hospital based clinic (range 0-12, c2 23.8 on 12 df p < 0.005). Lipid profiles in hospital non-attenders remained inferior with fewer achieving a total cholesterol <5 mmol/L (61% vs. 78%; p < 0.001), and having greater mean total cholesterol levels (4.85 +/- 0.06 mmol/L vs. 4.52 +/- 0.05 mmol/L; p < 0.001). CONCLUSIONS: Patients defaulting from hospital follow up have higher total cholesterols with fewer at target level compared to attenders. Though non-attenders receive subsequent lipid measurement, inferior lipid profiles persist compared to patients who completed hospital follow up to be discharged. Further implementation strategies are needed with regard to lipid management in this patient group.
Adult↗
Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known carriers: attributes, cancer worry, and barriers to testing in a multicenter clinical cohort.
BRCA1/2 test decliners/deferrers have received almost no attention in the literature and this is the first study of this population in the United Kingdom. The aim of this multicenter study is to examine the attributes of a group of individuals offered predictive genetic testing for breast/ovarian cancer predisposition who did not wish to proceed with testing at the time of entry into this study. This forms part of a larger study involving 9 U.K. centers investigating the psychosocial impact of predictive genetic testing for BRCA1/2. Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic testing were evaluated by questionnaire following genetic counseling. A total of 34 individuals declined the offer of predictive genetic testing. Compared to the national cohort of test acceptors, test decliners are significantly younger. Female test decliners have lower levels of cancer worry than female test acceptors. Barriers to testing include apprehension about the result, traveling to the genetics clinic, and taking time away from work/family. Women are more likely than men to worry about receiving less screening if found not to be a carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a more vulnerable group in terms of cancer worry. However, barriers to testing need to be discussed in genetic counseling.
Adult↗
Secondary prevention for coronary artery disease.
BACKGROUND: Secondary prevention of coronary artery disease is effective in reducing morbidity and mortality, but deficiencies in implementation and prescription bias have been identified. AIM: To assess progress in secondary prevention measures for coronary heart disease and whether there was a difference between patient subgroups with angina, post myocardial infarction or revascularization. DESIGN: Retrospective analysis. METHODS: Between 1997 and 2001, data were collected on prophylactic prescribing, demographic and lifestyle information, at baseline and 1 year following attendance at a hospital-based, cardiac-nurse-led out-patient clinic. RESULTS: Patients (n = 945) were entered into the database at hospital discharge and 619 (72%) attended at 1 year. Aspirin and statin prescribing increased, though ACE inhibitor use was less. Mean total cholesterol at baseline reduced to 4.92 +/- 0.11 mmol/l (p < 0.001) in 2000, with a further reduction to 4.59 +/- 0.08 mmol/l at the 1-year visit in 2001 (p < 0.001). The proportion of patients with total cholesterol < 5 mmol/l increased to 38% in 2000, reaching 70% in 2001. Smokers at baseline were similar at around 30%, although this had reduced to 10% in 2001 (p < 0.001). No change in weight was seen for patients with BMI >or=30 (p = NS). No significant differences were seen between patient subgroups (p = NS). DISCUSSION: Secondary prevention measures are improving, especially in prophylactic prescribing, lipid management and smoking cessation, although scope for further improvement remains. No difference was seen between the patient subgroups. Lifestyle measures need to be addressed to gain maximum benefit in addressing overall cardiovascular risk.
Aged↗
Changes in haemoglobin during interferon alpha-2b plus ribavirin combination therapy for chronic hepatitis C virus infection.
Interferon alpha and ribavirin (RBV) combination therapy is associated with decreases in haemoglobin (Hb) concentrations and anaemia. The aim of this analysis was to better characterize the magnitude and frequency of Hb changes and risk factors. This retrospective analysis evaluated treatment-related changes in Hb in 677 patients who participated in either of two interferon alpha-2b plus RBV studies for chronic hepatitis C virus (HCV) infection. Study 1 included 192 interferon alpha-naïve patients randomized to receive RBV 1000-1200 mg/day plus interferon alpha-2b 3 million IU daily or three times weekly for 48 weeks. Study 2 included 485 interferon alpha-experienced patients randomized to receive RBV 1000-1200 mg daily plus interferon alpha-2b 3 million IU daily or three times weekly for 4 weeks, followed by three times weekly dosing for 44 weeks. More than 50% of all patients experienced a decrease in Hb > or =30 g/L. Women were 4.4 times as likely as men to experience a Hb level of <100 g/L; however, men were at a 40% higher risk to experience a Hb decline of >30 g/L from baseline. Daily use of interferon alpha-2b did not impact the magnitude of Hb decrease. In this pooled analysis, RBV dose reduction resulted in increases in Hb concentration of approximately 10 g/L. Lower baseline creatinine clearance, higher baseline Hb levels and increased age were independently associated with increased risk of Hb decreases of >27.7%. Lower baseline weight was not associated with increased risk of Hb decrease. Substantial Hb decreases occur frequently with interferon alpha/RBV combination therapy. Sex, the magnitude of the Hb decline and renal function are potentially important factors to consider in patients receiving RBV. Further research is needed to determine the impact on virological response and to develop strategies to manage the medical consequences.
Anemia, Hemolytic↗
The effects of homeopathic Argentum nitricum on test anxiety.
OBJECTIVES: (1) To replicate a study of the efficacy of Argentum nitricum 12X in the reduction of test anxiety as demonstrated previously. (2) To investigate the correlation between individuals identified to match the A. nitricum profile and the reduction of test anxiety. To compare traditionally prepared homeopathic A. nitricum 12X with radionically-prepared A. nitricum 12X and placebo. DESIGN: A double blind, placebo-controlled, randomised clinical trial with three arms. SETTING: The study was conducted at Southern Cross University, Lismore, Australia. SUBJECTS: Sixty-two test anxious university students. INTERVENTIONS: Subjects were randomised to one of three groups: traditionally prepared homeopathic A. nitricum 12X, radionically-prepared A. nitricum 12X, or placebo. After screening, each group received treatment twice a day for 4 days after which they were re-tested. OUTCOME MEASURES: Primary: The Revised Test Anxiety Scale. Secondary: The Test Anxiety Scale; 36-item A. nitricum questionnaire. RESULTS: The results of this study did not replicate the Stanton study. No correlation between the reduction of test anxiety and the A. nitricum profile was demonstrated. No significant differences between treatments were demonstrated. CONCLUSION: This study demonstrated that homeopathic A. nitricum 12X does not reduce test anxiety in a general population of university students.
Adolescent↗
Predictive testing for BRCA1/2: attributes, risk perception and management in a multi-centre clinical cohort.
The aim of this multi-centre UK study is to examine the attributes of a cohort offered predictive genetic testing for breast/ovarian cancer predisposition. Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation. This is the first large multi-centre study of this population in the UK. The study evaluates mental health, perceived risk of developing cancer, preferred risk management options, and motivation for genetic testing. Participants were assessed when coming forward for genetic counselling prior to proceeding to genetic testing. Three hundred and twelve individuals, 76% of whom are female, from nine UK centres participated in the study. There are no gender differences in rates of psychiatric morbidity. Younger women (<50 years) are more worried about developing cancer than older women. Few women provide accurate figures for the population risk of breast (37%) or ovarian (6%) cancer but most think that they are at higher risk of developing breast (88%) and ovarian (69%) cancer than the average woman. Cancer related worry is not associated with perceived risk or uptake of risk management options except breast self-examination. The findings indicate that younger women may be particularly vulnerable at the time of the offer of a predictive genetic test.
Adult↗
Effect of hirudin vs heparin on haemostatic activity in patients with acute coronary syndromes; the GUSTO-IIb haemostasis substudy.
AIMS: We compared the effects of hirudin and heparin on thrombin generation and activity among 350 patients with acute coronary syndromes enrolled in the GUSTO-IIb trial. METHODS AND RESULTS: We obtained blood at baseline; at 4, 8, and 24h into infusion; at drug termination; and 6 and 24h after termination. We assayed for thrombin activity (fibrinopeptide A, activated protein C, thrombin-antithrombin complex), thrombin generation (prothrombin fragment 1.2), and platelet activation (platelet factor 4). Median baseline fibrinopeptide A and platelet factor 4 levels were elevated. Thrombin formation tended to increase with hirudin and decrease with heparin; by 8h into infusion, thrombin formation was significantly less for heparin (P<0.01). Most patients showed reduced thrombin activity and platelet activation during infusion of either agent. Hirudin-assigned patients had significantly lower fibrinopeptide A levels during infusion. Six h post-termination, both groups had increased thrombin activity. Thrombin formation was increased in heparin patients (P<0.0001), significantly more than with hirudin (P=0.005). Higher values of haemostasis markers tended to be associated with poorer 30-day outcomes. CONCLUSION: Although hirudin did not prevent generation of new thrombin, it appeared to inhibit thrombin activity more than did heparin and produced slower increases in thrombin formation after discontinuation. The reelevation of thrombotic markers after stopping intravenous antithrombin therapy and the tendency toward increased thrombotic events with post-treatment increases in marker levels suggest an ongoing, clinically significant prothrombotic state. These results raise the possibility of improving on current antithrombotics by preventing thrombin generation and thrombin activity and by sustained suppression of the prothrombotic state.
Acute Disease↗
Profile and prevalence of aspirin resistance in patients with cardiovascular disease.
We determined the prevalence and clinical predictors of aspirin resistance by prospectively studying 325 patients with stable cardiovascular disease who were receiving aspirin (325 mg/day for > or =7 days) but no other antiplatelet agents. We also compared the detection of aspirin resistance with optical platelet aggregation, a widely accepted method, with a newer, more rapid method, the platelet function analyzer (PFA)-100, a whole blood test that measures platelet adhesion and aggregation ex vivo. Blood samples were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate (ADP) and arachidonic acid, and by PFA-100 using collagen and/or epinephrine and collagen and/or ADP cartridges to measure aperture closure time. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and a mean aggregation of > or =20% with 0.5 mg/ml arachidonic acid. Aspirin semiresponders were defined as meeting one, but not both of the above criteria. Aspirin resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time (< or =193 seconds). By optical aggregation, 5.5% of the patients were aspirin resistant and 23.8% were aspirin semiresponders. By PFA-100, 9.5% of patients were aspirin resistant. Of the 18 patients who were aspirin resistant by aggregation, 4 were also aspirin resistant by PFA-100. Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women (34.4% vs 17.3%, p = 0.001) and less likely to be smokers (0% vs 8.3%, p = 0.004) compared with aspirin-sensitive patients. There was a trend toward increased age in patients with aspirin resistance or aspirin semiresponders (65.7 vs 61.3 years, p = 0.06). There were no differences in aspirin sensitivity by race, diabetes, platelet count, renal disease, or liver disease.
Adult↗
TCL1 is activated by chromosomal rearrangement or by hypomethylation.
TCL1 is an oncogene activated by recurrent reciprocal translocations at chromosome segment 14q32.1 in the most common of the mature T-cell malignancies, T-cell prolymphocytic leukemia. It acts to transport Akt1 to the nucleus and enhance Akt1's serine-threonine kinase activity. TCL1 is also expressed in the B-cell malignancy, Burkitt's lymphoma (BL). However, 14q32.1 breakpoints have not been detected in BL, and we therefore investigated in more detail how expression was activated. No evidence for rearrangement near TCL1 was found in BL. Instead, a NotI site adjacent to the TATA box in the TCL1 promoter was found to be unmethylated. By contrast, tumor cell lines not expressing TCL1 were fully methylated at this NotI site, while normal somatic cells were hemimethylated. We also found that TCL1 was expressed in B-cell chronic lymphocytic leukemia (CLL) and the related disorder splenic lymphoma with villous lymphocytes (unlike in normal mature B-cells), and that the NotI site was unmethylated on both alleles. This correlation of repression and methylation was tested in vitro. When cells with both alleles methylated at the NotI site were demethylated, TCL1 expression was induced. These data provide evidence that in mature B-cell malignancies there is an alternative mechanism of TCL1 activation that apparently involves loss of methylation of one promoter allele. We discuss the significance of this for CLL tumorigenesis and for genomewide hypomethylation in CLL.
Base Sequence↗
An evaluation of the mutagenicity, metabolism, and DNA adduct formation of 5-nitrobenzo[b]naphtho[2,1-d]thiophene.
Thioarenes, sulfur-containing polycyclic aromatic compounds, are environmental contaminants suspected of posing human health risks. In this study, 5-nitrobenzo[b]naphtho[2,1-d]thiophene (5-nitro-BNT), a nitrated-thioarene, was examined for its mutagenicity, metabolism and subsequent formation of DNA adducts. 5-Nitro-BNT was weakly mutagenic in Salmonella typhimurium strains TA98 and TA100 without Aroclor-1254-induced rat liver S9 (S9), and its activity was increased in the presence of S9. Anaerobic metabolism of 5-nitro-BNT by S9 or xanthine oxidase (XO) produced one major metabolite, identified as 5-amino-BNT by NMR, MS, and UV spectroscopy and by comparison with an authentic standard. Aerobic S9 metabolism of 5-nitro-BNT produced a major metabolite, identified as trans-9,10-dihydroxy-9,10-dihydro-5-nitro-BNT (5-nitro-BNT-9,10-diol). Also present was a minor amount of 5-amino-BNT and trans-9,10-dihydroxy-9,10-dihydro-5-amino-BNT (5-amino-BNT-9,10-diol). DNA adduct analyses were performed using the (32)P-postlabeling assay and reversed-phase HPLC. Three major XO-derived calf thymus DNA adducts were detected. On the basis of their chromatographic mobilities, two adducts were identified as reaction products of 5-nitro-BNT with 2'-deoxyguanosine and one adduct with 2'-deoxyadenosine. Incorporation of allopurinol (a specific XO inhibitor) in the incubation mixture resulted in loss of all three adducts, confirming enzymatic mediation by XO. Aerobic S9 activation of 5-nitro-BNT with calf thymus DNA produced three adducts. On the basis of their chromatographic mobilities, two were identified as reaction products of 5-nitro-BNT with 2'-deoxyguanosine and one with 2'-deoxyadenosine. Incorporation of 1-aminobenzotriazole (a P450 inhibitor) in the incubation mixture resulted in a loss of these adducts, confirming enzymatic mediation by P450. Aerobic S9-catalyzed metabolism of 5-nitro-BNT-9,10-diol produced the same DNA adducts as observed with 5-nitro-BNT. Aerobic S9-catalyzed metabolism of 5-amino-BNT-9,10-diol produced the same deoxyadenosine-derived DNA adducts as observed with 5-nitro-BNT and 5-nitro-BNT-9,10-diol. These results provide additional information that both ring oxidation and nitroreduction are involved in the metabolism, DNA adduct formation and mutagenicity of 5-nitro-BNT.
Animals↗
Long-term follow-up of patients diagnosed with alcohol dependence or alcohol abuse who were evaluated for liver transplantation.
The selection of patients with cirrhosis and the diagnosis of alcohol dependence or abuse who have a long-term high probability of abstinence after orthotopic liver transplantation (OLT) may enhance patient survival and outcomes. The aim of this study is to identify factors that would predict which patients would consume alcohol after OLT. Sixty-one patients with a history of alcohol dependence or abuse underwent OLT from June 1989 to June 1994 and were followed up monthly for a median of 6.9 years after OLT (range, 2.5 to 9.3 years). Survival analysis techniques (Cox proportional hazard model) were used to identify patients at high risk for recidivism. Recidivism occurred in 12 of 61 patients (20%) after OLT during follow-up. Noncompliance, with a relative hazard of 20.9 (95% confidence interval [CI], 5.6 to 78.3; P <.001), and personality disorder, with a relative hazard of 6.0 (95% CI, 1.9 to 18.7; P =.002), independently predicted recidivism among patients who underwent OLT. These data indicate that specific behaviors and psychiatric diagnoses can be used to select patients at high risk for drinking alcohol before and after OLT.
Adult↗
High level expression of deltaN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?
Undifferentiated nasopharyngeal carcinoma (NPC) is an epithelial malignancy that is consistently associated with Epstein-Barr virus (EBV) but which very rarely has p53 gene mutations in primary tumours. Since the tumour suppressor p53 is mutated in most human cancers or the wild type protein is inactivated in a significant number of the remainder, here we have investigated cellular factors that could compromise p53 function in primary NPC. Twenty-five primary tumours were judged to carry only wild type p53 by SSCP analysis of all exons and sequence determination of exons 4-9. Only one tumour was found to express significant levels of hMdm2 and in 24/25 there were no detectable mutations or deletions in exons 1beta and 2 of the p14(ARF) gene. However, immunohistochemistry consistently revealed that all the tumour cells express substantial amounts of the p53-related protein p63. Semi-quantitative RT-PCR analysis of mRNA from tumour biopsies showed that the dominant species expressed was invariably the truncated deltaN-isotype. Since this can block p53-mediated transactivation, it is potentially a dominant-negative isoform. In normal nasopharyngeal epithelium the distribution of p63 was restricted to the proliferating basal and suprabasal layers. We suggest that deltaN-p63 is a good candidate as a suppressor of wild type p53 function in these tumours and also that it may prove to be a valuable diagnostic marker for undifferentiated NPC.
Carrier Proteins↗
Tactile Contact by Deaf and Hearing Mothers During Face-to-Face Interactions With Their Infants.
Tactile contact with an infant plays an important role (though one largely overlooked by researchers until recently) in the development of synchronous interactive dialogues between caregiver and child. Dyads in which one or both partners are deaf present a unique opportunity to examine the use of touch as a means of optimizing or enhancing communication when the number of available sensory channels is restricted. Touch in these dyads may play an important role in eliciting visual attention, in alerting the infant that signed communication is forthcoming, in assisting the infant to achieve emotional regulation, or in simply maintaining contact even when the deaf child has looked away from the partner. The data presented here represent one attempt to investigate the role of touch in relation to deaf infants and deaf parents, for whom it may play a particularly salient role. Both deaf and hearing mothers were observed in videotaped face-to-face interactions with their infants (also either deaf or hearing); maternal behavior was coded for each event during which mothers initiated tactile contact with the infant and was classified according to intensity, location on the infant's body, and type of touch (e.g., active vs. passive). Results of this study indicate that deaf mothers may be especially responsive to the tactile needs of their deaf infants, as shown by qualitative differences in their behavioral interactions with 6- and 9-month-olds. However, hearing mothers with deaf infants also appear to be incorporating more active forms of touch in their interactions, although they tend to rely on longer durations of tactile contact than do the deaf mothers.
Journal Article↗
Novel p53 mutants selected in BRCA-associated tumours which dissociate transformation suppression from other wild-type p53 functions.
Inheritance of germ-line mutant alleles of BRCA1 and BRCA2 confers a markedly increased risk of breast cancer and we have previously reported a higher incidence of p53 mutations in these tumours than in grade matched sporadic tumours. We have now characterized these p53 mutants. The results of these studies identify a novel class of p53 mutants previously undescribed in human cancer yet with multiple occurrences in BRCA-associated tumours which retain a profile of p53-dependent activities in terms of transactivation, growth suppression and apoptosis induction which is close or equal to wild-type. However, these mutants fail to suppress transformation and exhibit gain of function transforming activity in rat embryo fibroblasts. These mutants therefore fall into a novel category of p53 mutants which dissociate transformation suppression from other wild-type functions. The rarity of these mutants in human cancer and their multiple occurrence in BRCA-associated breast tumours suggests that these novel p53 mutants are selected during malignant progression in the unique genetic background of BRCA1- and BRCA2-associated tumours.
Animals↗
Characterization of anti-hepatitis C virus-positive sera not genotyped by restriction fragment length polymorphism or serology.
BACKGROUND: The hepatitis C virus genome is extremely heterogeneous and has been classified into six major genotypes. Genotyping of hepatitis C has been achieved through both direct molecular approach and indirect detection of host genotype-specific antibodies by serological methods. The purpose of this study was to characterize anti-hepatitis C positive sera samples that were not genotyped either by restriction fragment length polymorphism or by serology. METHODS: Two hundred and two patients from northern California with established chronic hepatitis C virus infection were studied by restriction fragment length polymorphism analysis of the 5'-untranslated region amplicon. A serological genotyping assay, based on synthetic peptides derived from non-structural region 4 of the hepatitis C virus genome, was used to determine serological genotype. RESULTS: Of the 202 patients studied, 187 (93%) were polymerase chain reaction-positive. One hundred and eighty-six patients were able to be genotyped by restriction fragment length polymorphism, compared with 144/202 (71%) of patients genotyped by serology (P < 0.0001). Only two of 202 samples showed discordant genotyping results. The distribution of hepatitis C virus genotypes in northern California was found to be type 1a, 41%; 1b, 35%; 2a, 3%; 2b, 10%; 3a, 11%; and 4, < 1%. There was no association between hepatitis C genotypes and age, gender distribution, ethnic origin, presumptive mode of transmission, serum alanine aminotransferase levels and the proportion of patients with cirrhosis. Of the 15 patients who were not genotypable by the molecular assay, four patients were genotyped by serology, with hepatitis C virus genotypes 1, 2 and 3 represented. Of the 58 samples that were not genotyped by serology, 47 were genotyped based on the molecular assay, and the distribution of hepatitis C virus genotypes was similar to that of the overall study population. CONCLUSIONS: These data showed that: (i) molecular genotyping assay based on 5'-untranslated region is more sensitive than serologic genotyping based on the non-structural-4 region but the results were highly concordant; (ii) hepatitis C virus genotypes 1-4 are present in northern California, with genotype 1 being the most prevalent; and (iii) the failure to determine hepatitis C virus genotype based on molecular or serological genotyping assay does not appear to be related to specific hepatitis C genotypes.
California↗
Spectrum of p53 gene mutations suggests a possible role for ultraviolet radiation in the pathogenesis of advanced cutaneous lymphomas.
There is evidence that the incidence of primary cutaneous lymphoma, like other forms of non-Hodgkin's lymphoma, is increasing, yet little is known of the pathogenetic events involved in this group of disorders. In this study we examine the frequency and spectrum of P53 gene mutations in a large series of primary cutaneous lymphomas, with particular emphasis on tumor stage mycosis fungoides, as it is in these cases that p53 overexpression has previously been reported. Sixty-six samples from 55 patients with primary cutaneous B cell and T cell lymphomas were analyzed for mutations in exons 5-9 of the P53 gene using polymerase chain reaction/single strand conformational polymorphism, and subsequent cloning and sequencing of genomic DNA. Fourteen separate P53 mutations were identified in blood, skin, and lymph node samples in 13 patients (24%). Twelve of 14 mutations occurred at dipyrimidine sites, eight resulting in C-->T transitions and one in a CC-->TT tandem base transition, a mutation spectrum strikingly similar to that reported in nonmelanoma skin cancer and characteristic of DNA damage caused by ultraviolet B radiation. In the subset of patients with mycosis fungoides, P53 mutations were identified in six of 17 patients with tumor-stage but in none of 12 patients with plaque-stage disease (Fisher's exact test p = 0.027). These data suggest a role for ultraviolet radiation in the pathogenesis of primary cutaneous lymphomas and a possible ultraviolet B-related step in the progression of mycosis fungoides from plaque to tumor-stage disease.
Female↗
The effect of antiplatelet drugs, heparin, and preanalytical variables on platelet function detected by the platelet function analyzer (PFA-100).
The platelet function analyzer (PFA)-100 is a newly developed instrument that provides a rapid, in vitro, quantitative measurement of platelet adhesion and aggregation in whole blood flowing through a small aperture under high shear conditions. Thirty patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and ten normal individuals were included in this study. In vitro and in vivo studies were conducted to discern the effect of combinations of antiplatelet drugs (aspirin, ticlopidine, abciximab) and heparin on the performance of the device as well as the effects of preanalytical variables, such as method of sample collection and ex vivo anticoagulants. Studies were also conducted examining the effect of aperture size (standard 150 microns vs. smaller 120 microns) on the ability of the device to detect the effect of antiplatelet drugs. There was no difference in mean PFA-100 closure time with citrate versus PPACK anticoagulants or with venipuncture vs. sheath sampling. Closure times did not vary with heparin administration. Closure times were slightly longer for patients taking aspirin plus ticlopidine compared to aspirin alone (p = NS). In contrast adenosine disphosphate (ADP) induced platelet aggregation was significantly less in patients that took aspirin plus ticlopidine vs. aspirin alone (p = .0005). In vitro, there was a dose-dependent increase in closure time for both aperture sizes with increasing abciximab concentration. Although both cartridges showed infinite closure times at an abciximab concentration of 2.25 micrograms/mL, there was a slight benefit to using the 120 microns aperture cartridges at abciximab concentrations of 1.75 to 2.0 micrograms/mL. In ten patients who were followed during abciximab therapy to assess the effect of aperture size, the PFA-100 was able to detect in vivo platelet inhibition by abciximab, but detection of recovery from abciximab-induced platelet dysfunction was slightly better for the PFA-100 with the 120 microns aperture compared to the standard 150 microns aperture collagen/ADP cartridge.
Abciximab↗