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Biomedical subjects

A Bakker

Publications and source records attributed to A Bakker.

At least 19 recordsLinked to original sources

[Adverse effects after switching to a different generic form of paroxetine: paroxetine mesylate instead of paroxetine HCl hemihydrate].

Two patients, a 29-year-old man and a 32-year-old woman who were being treated with paroxetine HCl hemihydrate for depression and panic disorder with agoraphobia, respectively, unexpectedly developed complaints after switching to paroxetine mesylate. The symptoms were generalised itching with relapse of the depressive disorder in the man, and nausea with diarrhoea in the woman. The symptoms disappeared after the original treatment with paroxetine HCl hemihydrate was resumed. In the first patient, a rechallenge with the mesylate form of paroxetine led to the same complaints which subsided again after using the first product. Those treating such patients, and the patients themselves, should be informed if the delivery form of paroxetine is changed.

Adult↗

[Methods to improve patient compliance in the use of antidepressants].

Compliance during treatment with antidepressants is important, yet about half of the patients stop using antidepressive medication within 3 months. A structured treatment programme, in which the patient actively participates, with extensive education, surveillance of side effects and compliance, simple regimes, improving problem-solving behaviour and eventually engaging and educating family members and friends can improve compliance. This has been demonstrated in published studies. Research has shown that interventions that enhance compliance can lead to a better outcome of the depression.

Antidepressive Agents↗

SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis.

OBJECTIVE: To compare the short-term efficacy of selective serotonin reuptake inhibitors (SSRIs) vs. tricyclic antidepressants (TCAs) in the treatment of panic disorder (PD) a meta-analysis was conducted. METHOD: Included were 43 studies (34 randomized, nine open), pertaining to 53 treatment conditions, 2367 patients at pretest and 1804 at post-test. Outcome was measured with the proportion of patients becoming panic-free, and with pre/post Cohen's d effect sizes, calculated for four clinical variables: panic, agoraphobia, depression, and general anxiety. RESULTS: There were no differences between SSRIs and TCAs on any of the effect sizes, indicating that both groups of antidepressants are equally effective in reducing panic symptoms, agoraphobic avoidance, depressive symptomatology and general anxiety. Also the percentage of patients free of panic attacks at post-test did not differ. The number of drop-outs, however, was significantly lower in the group of patients treated with SSRIs (18%) vs. TCAs (31%). CONCLUSION: SSRIs and TCAs are equal in efficacy in the treatment of panic disorder, but SSRIs are tolerated better.

Antidepressive Agents, Second-Generation↗

Multiple genetic alterations involved in the tumorigenesis of human cholangiocarcinoma: a molecular genetic and clinicopathological study.

PURPOSE: Cholangiocarcinoma (CC) is the second most common malignant tumor in the liver and the molecular genetic alterations involved in the tumorigenesis of CC have not been well studied. PATIENTS AND METHODS: The authors analyzed the loss of heterozygosity (LOH) in four tumor suppressor genes, including the adenomatous polyposis coli (APC) gene, the deleted in colon cancer (DCC) gene, the 8-hydroguanine-specific DNA glycosylase (OGG1) gene, and the p53 gene in 22 surgically resected primary CCs by using microdissection-based PCR amplification and direct DNA sequencing. RESULTS: A total of 19 (86.4%) out of 22 CCs exhibited genetic alterations, of which 11 (57.9%) and eight (42.1%) cases showed one and more than one gene alterations, respectively. The frequency of genetic alterations of the four genes studied ranged in order from high to low as APC (68.8%) > DCC (46.2%) > OGG1 (41.7%) > p53 (37.5%). Based on the pattern of altered genes and their correlation with clinical and pathological parameters, the genetic alterations were classified into three groups: group I: no detectable genetic alterations (n = 3, 13.6%); group II: LOH in APC and/or DCC (n = 9, 40.9%); and group III: LOH in OGG1 and/or p53 occurred separately or combined with LOH in APC and/or DCC (n = 10, 45.5%). The > or = 3-year survival rates between group II and group III are 88.9% and 30%, respectively (P < 0.05). No significant differences were found between genetic alterations and tumor size, tumor type, tumor invasion, TNM staging, and tumor differentiation (P > 0.05). CONCLUSION: Accumulation of multiple genetic alterations are involved in the tumorigenesis of CC, of which genetic alterations of APC and DCC occur at a relatively early stage, and of OGG1 and p53 occur at a relatively late stage during development of CC.

Aged↗

Determinants of change in the intention to use benzodiazepines.

OBJECTIVE: To examine attitudes and beliefs associated with changes in the intention to use benzodiazepines during the six-month period after first benzodiazepine use. DESIGN: Population-based 6-month follow-up with 3 measurement points (baseline, 2 weeks after inclusion, 6 months after inclusion). SETTING: Starting or initial benzodiazepine users were included during a period of 4 months from November 1994 in the only pharmacy of a Dutch community of 13,500 people. MEASURES: Variables proposed by the Model of Planned Behaviour and the Health Belief Model. Drug exposure data from automated pharmacy records. RESULTS: At baseline, the intention to use benzodiazepines was primarily predicted by the perceived norm of the general practitioner regarding benzodiazepine use, and by the participants' own attitudes. After fourteen days, the determinants of change in the intention to use benzodiazepines were the initially perceived norm of the general practitioner and the change in the severity of participants' illnesses. After six months, the change in the severity of the illness and the perceived health benefits of benzodiazepines at the time of inclusion were the main determinants of the change in the intention to use benzodiazepines between the second and third measurement point. The intention to use benzodiazepines showed a decrease during follow-up. The three intention measures were significant predictors of actual benzodiazepine use during the year following baseline assessment. CONCLUSION: The study sheds light on interesting determinants of decrease or increase in the intention to use during the six-month period after first benzodiazepine use.

Adult↗

Frequent allelic imbalance and loss of protein expression of the DNA repair gene hOGG1 in head and neck squamous cell carcinoma.

Reactive oxygen species produced by aerobic cellular metabolism or through exposure to environmental carcinogens can cause oxidative DNA damage by generating DNA base lesions and strand breakage. Prime among these base lesions is the conversion of guanine to 8-oxoguanine. Among 20 or so oxidative DNA base lesions, 8-oxoguanine is the most abundant and is critical in terms of mutagenesis because it is capable of mispairing with adenine, which, if not sufficiently repaired, may lead to G:C to T:A transversion upon DNA replication. The gene encoding human 8-oxoguanine DNA glycosylase 1 (hOGG1), capable of excision repair of 8-oxoguanine, has been recently cloned, characterized, and mapped to the short arm of chromosome 3 (3p25-26), a region showing frequent loss of heterozygosity (LOH) in head and neck squamous cell carcinoma (HNSCC). In the present study, we developed a tissue microdissection approach designed for use with formalin-fixed, paraffin-embedded specimens which is capable of detecting and characterizing the hOGG1 allelic loss using two highly informative, intragenic single nucleotide polymorphisms. Among 45 cases of HNSCC, 18 cases were informative. We analyzed these 18 cases and found that 11 showed evidence of hOGG1 allelic loss. By immunohistochemical staining on a total of 71 HNSCC cases using a commercially available anti-hOGG1 antibody, we showed that hOGG1 gene expression was markedly suppressed in up to 38% of the cases. The frequent allelic imbalance and suppression of the hOGG1 gene thus imply that repair for oxidative DNA damages may be relevant in future studies on head and neck squamous carcinogenesis.

Carcinoma, Squamous Cell↗

Absence of jaagsiekte sheep retrovirus DNA and RNA in bronchioloalveolar and conventional human pulmonary adenocarcinoma by PCR and RT-PCR analysis.

Bronchioloalveolar adenocarcinoma (BAC) morphologically resembles sheep pulmonary adenomatosis (SPA), a contagious ovine pulmonary adenocarcinoma caused by the jaagsiekte sheep retrovirus (JSRV). Previously, positivity for JSRV by immunostaining, reverse-transcription polymerase chain reaction (RT-PCR), and Western blot was reported in most nonmucinous BACs. Our objective in this study was to analyze additional BAC subtypes and conventional adenocarcinomas (CA) to further substantiate this association. Tumor tissue was microdissected from unstained paraffin sections of 26 cases of formalin-fixed, paraffin-embedded BAC (7 mucinous, 17 nonmucinous, 2 sclerosing) and 29 cases of CA. Positive controls consisted of 2 separate paraffin blocks of known SPA. Primer sequences were derived that were capable of hybridizing to all reported strain variants of both the DNA (endogenous) and RNA (exogenous) forms of JSRV. Each sample was tested using both PCR (DNA) and RT-PCR (RNA). All BAC and CA cases were negative for JSRV. Positive controls yielded PCR products that were sequenced and precisely matched the published prototype stain of JSRV. To control for negative effects of tissue fixation, dilutions of positive control tissue were added to BAC and CA samples. Detection of JSRV was evident at 1:50 dilution. Although the possibility of a viral association with BAC cannot be excluded, this study shows that the association with JSRV is probably very weak, if present at all.

Adenocarcinoma, Bronchiolo-Alveolar↗

[Screening for asymptomatic Chlamydia trachomatis infection in pregnancy; cost-effectiveness favorable at a minimum prevalence rate of 3% or more].

OBJECTIVE: To estimate the cost-effectiveness of antenatal screening for Chlamydia trachomatis. DESIGN: Pharmaco-economic model analysis. METHOD: The risks of C. trachomatis infection during pregnancy and of complications of the infection as well as the cost of screening for complications (pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, infertility and neonatal pneumonia) and of treatment were estimated. Assumed were a ligase chain reaction on urine and treatment of identified infected cases with erythromycin or amoxicillin (second choice). Cost-effectiveness was calculated and presented in net direct and indirect costs per major complication averted. RESULTS: For C. trachomatis prevalences in pregnancy above 4% benefits exceed the costs. For prevalences between 2.82% and 4.00% net costs are positive, but a major complication averted costs less than f 1000.-. Considering sensitivity analysis as well, screening for C. trachomatis at prevalences above 3% costs less than f 1000.-per major complication averted and might even save costs. No recent Dutch data on C. trachomatis prevalence in pregnancy are published however. CONCLUSION: Given the current information, antenatal C. trachomatis screening can be recommended from a pharmaco-economic perspective if C. trachomatis prevalence in pregnancy is 3% or more.

Adolescent↗

Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects.

We have genetically engineered CD4(+) and CD8(+) T cells with human immunodeficiency virus (HIV) specificity by inserting a gene, CD4zeta, containing the extracellular domain of human CD4 (which binds HIV env) linked to the zeta (zeta) chain of the T-cell receptor (which mediates T-cell activation). Twenty-four HIV-positive subjects received a single infusion of 2 to 3 x 10(10) autologous CD4zeta-modified CD4(+) and CD8(+) T cells administered with (n = 11) or without (n = 13) interleukin-2 (IL-2). Subjects had CD4 counts greater than 50/microL and viral loads of at least 1000 copies/mL at entry. T cells were costimulated ex vivo through CD3 and CD28 and expanded for approximately 2 weeks. CD4zeta was detected in 1% to 3% of blood mononuclear cells at 8 weeks and 0.1% at 1 year after infusion, and survival was not enhanced by IL-2. Trafficking of gene-modified T cells to bulk rectal tissue and/or isolated lamina propria lymphocytes was documented in a subset of 5 of 5 patients at 14 days and 2 of 3 at 1 year. A greater than 0.5 log mean decrease in rectal tissue-associated HIV RNA was observed for at least 14 days, suggesting compartmental antiviral activity of CD4zeta T cells. CD4(+) counts increased by 73/microL at 8 weeks in the group receiving IL-2. There was no significant mean change in plasma HIV RNA or blood proviral DNA in either treatment arm. This sustained, high-level persistence of gene-modified T cells demonstrates the feasibility of ex vivo T-cell gene therapy in HIV-infected adults and suggests the importance of providing HIV-specific T-helper function.

Acquired Immunodeficiency Syndrome↗

Influence of question structure on the recall of self-reported drug use.

Epidemiological studies often rely on self-reported information as a source of drug exposure. Several studies have evaluated the accuracy of self-reported information on drug use. The influence of question structure on the accuracy of recall, however, has not been studied extensively in these studies. In this study we examined the recall accuracy of questionnaire information on drug use in a ongoing public health survey with special attention to the influence of question structure on sensitivity of recall. A sample of 372 hypertensive subjects for whom questionnaire information and pharmacy records were available was examined. Self-reported information on drug use was obtained through questions about medications used for a specific condition and one final open-ended question. This information was compared with the pharmacy medication history. About 71% of all drugs that were currently in use according to the pharmacy records were recalled through the self-administered questionnaire, and 94% of all drugs mentioned in the questionnaire could be traced in the pharmacy records. Recall sensitivity was higher for questions about medications used for a specific indication (88%) than for the open-ended question (41%). The type of drug that was used might have caused part of this difference in recall. We conclude that questionnaire structure might be of influence on the accuracy of recall of self-reported drug use, and more attention should be paid to the structure of questions on drug use.

Adult↗

Conditional identification of phosphate-starvation-response mutants in Arabidopsis thaliana.

Plants have evolved elaborate metabolic and developmental adaptations to low phosphorus availability. Biochemical responses to phosphate limitation include increased production and secretion of phosphate-acquisition proteins such as nucleases, acid phosphatases, and high-affinity phosphate transporters. However, the signal transduction pathways that sense phosphate availability and integrate the phosphate-starvation response in plants are unknown. We have devised a screen for conditional mutants in Arabidopsis thaliana (L.) Heynh. to dissect signaling of phosphate limitation. Our genetic screen is based on the facultative ability of wild-type Arabidopsis plants to metabolize exogenous DNA when inorganic phosphate is limiting. After screening 50,000 M2 seedlings, we isolated 22 confirmed mutant lines that showed severely impaired growth on medium containing DNA as the only source of phosphorus, but which recovered on medium containing soluble inorganic phosphate. Characterization of nine such mutant lines demonstrated an inability to utilize either DNA or RNA. One mutant line, psr1 (phosphate starvation response), had significantly reduced activities of phosphate-starvation-inducible isoforms of ribonuclease and acid phosphatase under phosphate-limiting conditions. The data suggest that a subset of the selected mutations impairs the expression of more than one phosphate-starvation-inducible enzyme required for utilization of exogenous nucleic acids, and may thus affect regulatory components of a Pi starvation response pathway in higher plants.

Arabidopsis↗

Estimating the prevalence of hypertension corrected for the effect of within-person variability in blood pressure.

The objective of our study was to assess the applicability of using estimates of within-person variance (WPV) from reproducibility studies for a correction of blood pressure values in another study to improve the accuracy of the prevalence estimation of hypertension. Data were collected from two cross-sectional population-based studies on cardiovascular disease risk factors conducted from 1987 to 1995 among 55,026 subjects aged 20-59 years. Correction factors were calculated from a reproducibility study among 924 subjects who were examined in 1989 and 1990. All other studies with repeated measurements of blood pressure were searched in MEDLINE from 1966 onward. Six studies satisfied the inclusion criteria. The prevalence of hypertension, uncorrected and corrected with factors from other studies, were compared with the prevalence of hypertension corrected with the factor from our study. The uncorrected prevalence of hypertension was 17.3% [95%CI:17.0-17.7]. The prevalence of hypertension after correction for WPV with the factor from our study was 13.5% [95%CI:13.2-13.8]. Correction for WPV with factors from the appropriate studies (depending on factors such as number of measurements taken per visit, and time interval between visits) resulted in prevalences ranging from 13.9% to 14.7%. The bias that occurs when no correction for WPV is performed is much larger (29% overestimation) than the bias that occurs when correction factors are derived from other studies (3.1-8.4% overestimation). When repeated measurements of blood pressure are not available in a population study for a sample of that same study, it is advisable to use data from another study to correct for WPV.

Adult↗

Influence of correction for within-person variability in blood pressure on the prevalence, awareness, treatment, and control of hypertension.

We assessed the influence of correction for within-person variability (WPV) on the prevalence, awareness, treatment, and control of hypertension. Data were collected from two cross-sectional population-based studies on cardiovascular disease risk factors from 1987 to 1995 among 56,026 subjects aged 20 to 59 years. Correction factors were calculated from an internal reproducibility study among 924 subjects who were examined in 1989 and 1990. The prevalence of hypertension without a correction of blood pressure values for WPV was substantially overestimated (38%), whereas the prevalence of awareness and treatment of hypertension were substantially underestimated (-13% and -28%). The prevalence of control of hypertension did not change much after this correction. It may be advisable to perform a correction for within-person variability to obtain valid prevalence estimates in surveys that only take one or two measurements of blood pressure.

Adult↗

Sex differences in the medication choice for hypertension in general practice. A study with written case simulations.

The objective of this study was to explore explanations for the preference of physicians to prescribe beta-blockers to hypertensive men and diuretics to hypertensive women. A qualitative study among 12 family physicians was conducted with a combination of written case simulations, semi-structured interviews and statements on attitudes of physicians towards antihypertensive drug choice. Among the male hypertensive cases the most frequently prescribed drugs were beta-blockers, whereas among the female hypertensive cases diuretics were more often prescribed. Physician characteristics associated with a preferred prescribing of beta-blockers to hypertensive men and diuretics to hypertensive women were: older age (no residency in family medicine), the believe that beta-blockers are more effective in men with regard to lowering blood pressure and that diuretics are more effective in women, a non-evidence based attitude and a sex-related attitude towards the choice of beta-blockers and diuretics in general, and in particular towards the prescribing of beta-blockers to hypertensive men because men have a higher absolute risk of coronary heart disease than women. An additional explanation for these findings may be the higher prevalence of ankle oedema among women. Patient characteristics associated with more prescribing of beta-blockers to hypertensive men and diuretics to hypertensive women were: current employment and a "high-risk" profile in terms of blood pressure level and additional cardiovascular risk factors. Although, most considerations underlying a preferred prescribing of beta-blockers to hypertensive men and diuretics to hypertensive women were not evidence-based, the actual choice of antihypertensive drug (diuretic or beta-blocker) was evidence-based. These considerations may also play a role in the sex difference in the choice of calcium antagonists and angiotensin converting enzyme inhibitors and require further investigation.

Adrenergic beta-Antagonists↗