Ketanserin accelerates wound epithelialization and neovascularization

We investigated the acute effects of topical ketanserin, a 5-HT₂ (serotonin) receptor blocker, on wound epithelialization and vascularization with the use of the hairless mouse ear model. Varying concentrations of Ketanserin (0%, 0.2%, 2.0%, 20% weight/volume) were administered to standardized full-thickness skin wounds on the dorsum of the hairless mouse ear immediately after surgery and daily thereafter. With the use of video microscopy and computer-assisted planimetry, vascularization and epithelialization were traced every third day until the wounds were fully healed. Arteriole diameters at selected sites near the skin wound were measured before wound creation and after wounding. It was concluded that topically administered ketanserin significantly accelerates both the vascular ( p < 0.001 at 2% and 20% concentrations) and epithelial ( p < 0.001 at 20% concentration) rates of wound healing in full-thickness nonpathologic skin wounds. Vasodilation of terminal arterioles was not a major response to Ketanserin. Faster epithelialization was possibly due to direct effect of ketanserin on epithelial cells.     

Automated screening versus manual screening: a comparison of the ThinPrep imaging system and manual screening in a time study

The ThinPrep Imaging System (TIS) is an automated system that assists cytotechnologists in the primary screening of ThinPrep liquid based cervical samples. Between June 1, 2004, and April 1, 2005, four experienced cytotechnologists participated in the study in which the duration of the screening procedure was timed for each of the 11,354 slides included. In every slide 22 fields of view were reviewed, and the samples that contained potentially abnormal cells were fully screened. The screening time was reduced by 42% (mean) (p < 0.001). By manual rescreening of the negative TIS samples, abnormal cells were found in 10 samples (false negative rate 0.14%). In every case the abnormal cells had been identified by the scanner, but misinterpreted by the cytotechnologist. These findings stressed the importance of carefulness in the interpretation of the marked fields and beyond that helped the cytotechnologists and pathologists to have more confidence in the automated system.     

Biological cost of single and multiple norfloxacin resistance mutations in Escherichia coli implicated in urinary tract infections

Resistance to fluoroquinolones in urinary tract infection (UTIs) caused by Escherichia coli is associated with multiple mutations, typically those that alter DNA gyrase and DNA topoisomerase IV and those that regulate AcrAB-TolC-mediated efflux. We asked whether a fitness cost is associated with the accumulation of these multiple mutations. Mutants of the susceptible E. coli UTI isolate Nu14 were selected through three to five successive steps with norfloxacin. Each selection was performed with the MIC of the selected strain. After each selection the MIC was measured; and the regions of gyrA, gyrB, parC, and parE, previously associated with resistance mutations, and all of marOR and acrR were sequenced. The first selection step yielded mutations in gyrA, gyrB, and marOR. Subsequent selection steps yielded mutations in gyrA, parE, and marOR but not in gyrB, parC, or acrR. Resistance-associated mutations were identified in almost all isolates after selection steps 1 and 2 but in less than 50% of isolates after subsequent selection steps. Selected strains were competed in vitro, in urine, and in a mouse UTI infection model against the starting strain, Nu14. First-step mutations were not associated with significant fitness costs. However, the accumulation of three or more resistance-associated mutations was usually associated with a large reduction in biological fitness, both in vitro and in vivo. Interestingly, in some lineages a partial restoration of fitness was associated with the accumulation of additional mutations in late selection steps. We suggest that the relative biological costs of multiple mutations may influence the evolution of E. coli strains that develop resistance to fluoroquinolones.     

Combination of real-time PCR and sequencing to detect multiple clinically relevant genetic variations in the lactase gene

Background: Lactase persistence is an autosomal dominant trait commonly distributed in Europe as well as some parts of east Africa and the Arabian Peninsula. Using real-time PCR to detect the ?13910C?>?T variant common in the European population is a reliable analysis although other variants in the probe-binding site may cause errors in analysis. The aim of this study was to determine the prevalence of the variants in a Danish cohort examined for lactose intolerance as well as to improve the real-time PCR analysis for detection of the different variants.

Methods: We genotyped 3395 routine samples using real-time PCR for the ?13910C?>?T-variant. All consecutive samples identified as ?13910CC were sequenced using Sanger Sequencing. Using the SDS software we examined various quality value settings to improve on the genetic analysis.

Results: Using real-time PCR resulted in 100% successful genotyping of the ?13910C?>?T variant. By using a quality value of 99% and sequencing the undetermined samples we improved the ability of the assay to identify variants other than ?13910C?>?T. This resulted in a reduction of the diagnostic error rate by a factor of 2.4 while increasing the expenses only 3%.

Conclusions: We conclude that using a quality value of 99% in the SDS software significantly improves the diagnostic efficiency of the real-time PCR assay for detecting variants associated to lactase persistence.     

Emotional Intensity and Emotion Regulation in Response to Autobiographical Memories During Dysphoria

Retrieving personal memories may provoke different emotions and a need for emotion regulation. Emotional responses have been studied scarcely in relation to autobiographical memory retrieval. We examined the emotional response to everyday involuntary (spontaneously arising) and voluntary (strategically retrieved) memories, and how this response may be different during dysphoria. Participants (20 dysphoric and 23 non-depressed) completed a structured diary where the intensity of basic emotions and regulation strategies employed upon retrieval of memories were rated. Brooding, memory suppression, and emotional suppression were higher for all individuals’ involuntary memories than voluntary memories. Negative emotions and regulation strategies were greater for dysphoric individuals for both involuntary and voluntary memories after controlling for the valence of the remembered events. The results provide new insights into the understudied topic of emotional responses to everyday memories and suggest a novel interpretation of the intrusive nature of memories in psychological disorders, such as depression.     

Association between larger thymic size and higher thymic output in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy

To examine the impact of thymic size on immune recovery in patients with human immunodeficiency virus (HIV) infection, the thymus was visualized, using computed tomographic scans, in 25 HIV-infected patients who had received highly active antiretroviral therapy (HAART) for 6-18 months and had levels of viremia <500 copies/mL. For comparison, 10 control subjects were included in the study. Total and naive CD4+ cell counts were determined by flow cytometry. To determine thymic output, the number of CD4+ cells containing T cell receptor excision circles (TRECs) was measured. Qualitative immune recovery was evaluated by determination of CD4+ T cell receptor repertoire in 19 of the HIV-infected patients. Larger thymic size was associated with higher CD4+ cell counts (r=0.498; P=.011) and higher CD4+ TREC frequency (r=0.652; P<.001). Furthermore, patients with abundant thymic tissue seemed to have broader immunologic repertoires, compared with patients with minimal thymic tissue (P=.054). These findings suggest that thymopoiesis is ongoing in the adult thymus and contributes to immune reconstitution in HIV-infected patients receiving HAART.     

Characterization of serotonin(4) receptors in adrenocortical aldosterone-producing adenomas: in vivo and in vitro studies

We have previously shown that serotonin (5-HT) stimulates aldosterone secretion from the human adrenal gland through activation of 5-HT(4) receptors. The aim of the present study was to investigate in vivo and in vitro the presence of 5-HT(4) receptors in aldosterone-producing adenomas (aldosteronomas). Eight patients with aldosteronoma received a single oral dose of placebo or cisapride (10 mg). Cisapride administration significantly increased plasma aldosterone within 120 min without any significant change in renin, cortisol, or potassium levels. In two patients, a marked decrease in the plasma aldosterone response to cisapride was observed after surgical removal of the tumor. The effects of 5-HT and selective 5-HT(4) ligands on aldosterone production from aldosteronoma tissues were studied in vitro using a perifusion system technique. 5-HT and the 5-HT(4) receptor agonist cisapride (10(-7) M, 20 min) both stimulated aldosterone secretion from aldosteronoma slices. The 5-HT- and cisapride-evoked aldosterone responses were inhibited by concomitant administration of the specific 5-HT(4) receptor antagonist GR 113808 (10(-7) M, 150 min). PCR amplification revealed the expression of 5-HT(4) receptor mRNA in 13 of 14 aldosteronomas studied. Taken together, these data show that most aldosteronomas, like normal glomerulosa cells, express a functional 5-HT(4) receptor. Our results also suggest that 5-HT, which can be locally released by intratumoral mast cells, may play a role in the pathophysiology of these tumors.     

Birthweight,Childhood Body Mass Index,Height and Growth,and Risk of Polycystic Ovary Syndrome

IntroductionAdult obesity is linked with polycystic ovary syndrome (PCOS), but the importance of body size at ages before PCOS is diagnosed is unknown.ObjectiveTo investigate associations between a woman''s own birthweight, childhood body mass index (BMI), height and growth patterns in relation to her risk of PCOS.MethodsWe included 65,665 girls from the Copenhagen School Health Records Register, born in the period 1960–1996, with information on birthweight and measured weight and height at the ages of 7–13 years. Overweight was defined using International Obesity Task Force (IOTF) criteria. From the Danish National Patient Register, 606 women aged 15–50 years were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression analysis.ResultsBirthweight was not associated with PCOS. At the age of 7–13 years, girls with overweight had a higher risk of developing PCOS than girls without overweight; HR 2.83 (95% CI 2.34–3.42) at age 7 years and 2.99 (95% CI 2.38–3.76) at age 13 years. Furthermore, girls with overweight at both 7 and 13 years had a higher risk of developing PCOS than girls without overweight or overweight at only one age. Height was positively associated with PCOS risk at all ages. Girls who were persistently tall or changed from tall to average height had a higher risk of developing PCOS than girls with average height growth.ConclusionOverweight and tall stature in childhood are positively associated with PCOS risk, but birthweight is not.     

Individualizing recall intervals in child dental care

Abstract Individualizing and extending recall intervals for children have been recommended in Norway to target resources efficiently. Recall intervals were changed for children aged 3–18 years in Drammen from 1991. Clinical time spent by dentists and dental hygienists, dental health status and length of recall intervals were registered from 1990 to 1993. For the child population, the mean recall interval changed from 12.5 to 13.7 months and the annual time spent per child was reduced by 14% from 1990–91 to 1992–93. Adjusted for the decline in number of new decayed teeth, the reduction in time spent was 11%. Children with intervals of 17 to 20 months had fewer new decayed teeth and their care required less personnel time than other children. For children with new decayed teeth, time spent for dental care was not associated with recall interval, while for children without new decayed teeth, longer recall intervals were associated with shorter time for dental care. The variation in number of decayed teeth and time spent for dental care was substantial at all intervals. Individualizing and extending recall intervals to some extent targeted resources at children with more dental disease. However, in the short run, inequality in dental health persisted. Limited extension of recall intervals did not interrupt the long-term trend toward better dental health in the children and substantial resources were saved in the dental services.