Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19

Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (+/- standard deviation) S/R ratio for citalopram was 0.67 +/- 0.25 and for desmethylcitalopram, 0.68 +/- 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.     

Leaching of organic acids from irradiated EVA plastic as a function of solution pH and polarity

The leaching of several target organic acids from an irradiated ethylene vinyl acetate material, such as those used as a solution product container, is examined as a function of solution pH and polarity. The targeted compounds included highly soluble weak acids such as acetic and formic acids, and larger, more lipophillic acids such as myristic, palmitic, and stearic acids. The leaching of these compounds was examined over a pH range of 3 to 11 and in various ethanol/water proportions. While pH and solution polarity had only a modest impact on the accumulation of the acetic and formic acids, the accumulation of the fatty acids was greatly affected by both factors. It is suggested that the accumulation of these leachables at high pH is influenced by two processes. The first process, partitioning, the speciation of the acidic leachables (protonated versus dissociated form) contributes to the pH trends observed. In this case, entities that already exist in the plastic partition themselves between the plastic and solution via migration. A second, more important, contributor to the leaching of these acids is a pH-dependent increase in their availability arising from an unspecified reactive process.     

Vulvar pain,sexual behavior and genital infections in a young population: a pilot study

BACKGROUND: To study the prevalence of pain during intercourse in a young population and analyze factors that may be associated with vulvar pain. METHODS: During a 2-month period, 172 women (aged 12-26 years) consulting four different adolescent health centres in Stockholm, Sweden, responded to a questionnaire concerning sexual habits, history of infections, and genital symptoms a priori vulvar pain. Multiple logistic regression model was used to evaluate the independent effects of the variables associated with vulvar pain. RESULTS: One-third of the women reported regular pain during and/or after intercourse. Having regular sexual intercourse before the age of 16 years and using oral contraception for more than 2 years were independent variables increasing the risk of vulvar pain. There was a correlation trend between vulvar pain and lack of sexual desire, recurrent candida infections, and urinary tract infections. However, there was no correlation to sexually transmitted diseases. More than 4 years of regular intercourse and coitus at least 4 times a week were factors that inversely correlated to vulvar pain. CONCLUSIONS: One-third of young women answering a questionnaire at adolescent health centres reported regular pain during and/or after intercourse. Early regular coitus and long-time use of oral contraceptives were factors associated with vulvar pain. Frequently rubbing a vulnerable mucosa may result in irreversible damage and vulvar vestibulitis syndrome.     

Adolescents' perceptions of oral health and influencing factors: a qualitative study

Accounts of self-perceptions of oral health have hitherto been rare, although they are of great interest for strategies in health promotion. The objective of this study was to increase our knowledge of adolescents' perceptions of oral health and influencing factors. Semi-structured interviews of 17 Swedish adolescents were performed. Criteria for strategic sampling were age (15, 18 years), gender (male, female), and dental health (healthy, unhealthy). Data were analyzed according to the constant comparative method. Areas of focus were general oral health, personal oral health, dental care, and life-style issues. Oral health awareness was generally low among the informants. Two categories of oral health were identified: action (the physical things we do to effect the condition of our mouths) and condition (the physical status of the mouth). Conditional aspects were most frequent in evaluations of personal oral health. The informants considered their possibilities to influence oral health limited. Perceptions of influences on oral health were related to personal and professional care, social support and impact, and external factors. 'Concern for oral health' was derived as the core category in perceived influence on oral health. The study indicates that it is important to find factors that enhance adolescents' awareness of their own resources and to seek mechanisms that govern internalization. There is a need to find strategies to convey such knowledge to the intermediaries: dental personnel and parents.     

Natural killer (NK) cell function is a strong prognostic factor in colorectal carcinoma patients treated with the monoclonal antibody 17-1A

Tumor cells might be susceptible to different effector functions of the immune system. This cytotoxic capacity has been utilized to analyze the prognostic significance of peripheral blood mononuclear cells (PBMC) in patients with metastatic colorectal carcinoma (CRC) treated with the monoclonal antibody (MAb)17-1A. Such analysis might form the basis for future patient selection and may lead to improvements in therapeutic strategies. Between 1986 and 1998, 73 patients were treated with regimens containing MAb17-1A. Prior to therapy, the lytic capability of PBMC was assayed against: K562 (4 hr assay), the CRC cell line SW948 (4 hr and 18 hr assays) and antibody-dependent cellular cytotoxicity (ADCC, 18 hr assay). Since the study was performed over 13 years, the assays were checked for time-related bias. Reproducibility over time was satisfactory. Patients exhibited a significantly higher cytotoxic capability in all 4 assays compared to healthy control donors. No correlation to clinical outcome was noted for 18 hr ADCC and 18 hr spontaneous cytotoxicity. Pretreatment natural killer (NK) cell cytotoxicity (K562) was significantly related to overall survival (OS), progression-free survival (PFS), and response rate. OS for patients with high and low NK cell cytotoxicity was 71 vs. 30 weeks, respectively (p = 0.007). NK cell cytotoxicity (K562) was an independent prognostic factor for OS (p = 0.016). Pretreatment NK cell activity is a strong prognostic factor for patients with metastatic CRC receiving MAb17-1A therapy and is a predictor for OS, PFS and response. These results should be considered when designing antibody-based therapeutic protocols.     

Evaluation of Viability of Excised Rat Intestinal Segments in the Ussing Chamber: Investigation of Morphology,Electrical Parameters,and Permeability Characteristics

Purpose. To clarify relations between alterations in electrical and permeability data with time and to elaborate accompanying structural changes of intestinal segments in Ussing chamber experiments. Methods. Excised intestinal segments from the rat were studied in a modified Ussing chamber. Experiments were run up to 180 minutes during which the electrical parameters, PD, SCC, and R, were measured and the permeability coefficients (P_app) of mannitol and propranolol were determined. Each segment was observed under the light microscope for morphological evaluation. Results. PD and SCC values showed a decrease for most segments while the R values remained steady throughout the experiment. The P_app for propranolol increased aborally to the small intestine. For mannitol, the reversed was observed. In some cases, there was a time-dependent change in permeability for these marker molecules. The main morphological changes observed were a decreased nucleo-apical distance, decreased villi amplification factor, initial edema, cell sloughing, and epithelial restitution. Conclusions. The time-dependent changes in permeability coefficients of mannitol and propranolol are suggested to be related to changes in electrical parameters and morphological alterations. Presented data illustrates the importance of information regarding time-dependent structural changes for correct interpretation of permeability data.     

Growth in very preterm children: a longitudinal study

The knowledge about the long-term growth of very preterm children in relation to gestational age at birth is incomplete. Therefore, a retrospective study of longitudinal growth from birth to 7 y of age in 52 of 56 surviving children who were born at a gestational age of <29 wk between 1988 and 1991 to mothers resident in the city of G?teborg, Sweden, was performed. A majority of the children had an initial decrease in weight during the first months of life, followed by an increase, with a maximum weight gain occurring at 36-40 wk postmenstrual age. After a period of decreased weight and length velocity, a second increase in weight velocity was demonstrated from 6 mo to 2 y of corrected age. A corresponding increase in length velocity was found from 2 to 12 mo of corrected age. A later catch-up growth period was found at 4-5 y of age. At 7 y of age, all but two had reached the normal height range of the population. This long-term catch-up in height was established later in those who were born at an earlier gestational age. We conclude that all preterm infants had an initial period of poor growth, which rendered them growth retarded during the first years of life. It took approximately 4-7 y to overcome what the very preterm child lost in growth during the first months of life. However, as a group, they did reach normal height, weight, and weight for height before puberty.     

Chronic Granulomatous Disease-Like Presentation of a Child with Autosomal Recessive PKCδ Deficiency

Journal of Clinical Immunology - Autosomal recessive (AR) PKCδ deficiency is a rare inborn error of immunity (IEI) characterized by autoimmunity and susceptibility to bacterial, fungal, and...     

The use of oral sedatives in dental care

Oral administration of tranquillizing and anxiety-suppressing drugs has long been the commonest method of achieving light sedation. The benzodiazepines are the drugs of first choice. Benzodiazepines given orally may be indicated to avoid 'treatment stress', alleviate mild anxiety before dental treatment, and facilitate sleep on the night before the treatment. Furthermore, they could be used for the dental treatment of medically poor risk patients, particularly those with cardiovascular disease. The drug can be given either in a fractionated dose or a single dose. The recommended doses for diazepam vary from 0.1–0.8 mg/kg body weight, depending on age, with higher doses in children and lower doses in elderly patients. Few side effects are reported.     

Primary care physicians’ concerned voices on sickness certification after a period of reorganization. Focus group interviews in Sweden

Objective: This study explored the views of primary health care (PHC) physicians on sickness certification after reforms in 2005 prompted by the Swedish government to increase the quality and decrease the inequalities, and costs of sickness certification.Design: Qualitative design with focus group interviews. Data were analysed using qualitative content analysis.Setting: Urban and rural PHC centres in Region Västra Götaland, Sweden.Subjects: GPs, interns, GP trainees and locums working in PHC centres 2015. Six focus group interviews with 28 physicians were performed.Main outcome measures: Experiences and reflections about the sickness certification system.Results: The latent content was formulated in a theme: ‘The physicians perceived the sickness certification process as emotive and a challenge to master with differing demands and expectations from authorities, management and patients’. Sickness certification could be easy in clear-cut situations or difficult when other factors besides the pure medical were ruling the decisions. The physicians’ coping strategies for the task included both active measures (cooperation with health care staff and social insurance officers) and passive adaptation (giving in or not caring too much) to the circumstances. Proposals for the future were to transfer lengthy sickness certifications and rehabilitation to specialized teams and increase cooperation with rehabilitation coordinators and social insurance officers.Conclusions: Political decisions on laws and regulations for sickness certification impacted the primary health care making the physicians’ work difficult and burdensome. Their views and suggestions should be carefully considered in future organization of primary care. KEY POINTS In 2005 Swedish government introduced reforms to decrease the inequalities and costs of sickness certification and facilitate the physicians’ work.

• Focus group interviews with Swedish primary care physicians revealed that sickness certification was challenging due to differing demands from authorities, management and patients.
• Coping strategies for the sick-listing task included both active measures and passive adaptation to the circumstances.
• A proposal for future better working conditions for physicians was to transfer lengthy sickness certifications and rehabilitation to specialized teams.