The effectiveness of a treatment protocol for male lower urinary tract symptoms in general practice: a practical randomised controlled trial

BACKGROUND: Randomised controlled trials have shown the efficacy of several treatment modalities for lower urinary tract symptoms (LUTS) in selected populations. The effectiveness in daily practice has hardly been investigated, especially in primary care and is dependent on choices between all possible treatment options and best investigated in a comprehensive study, including all treatment modalities (watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors, and surgery). AIM: Assessment of the effectiveness of a comprehensive treatment protocol for LUTS in primary care. DESIGN OF STUDY: Randomised controlled trial. SETTING: Fourteen general practices in the Netherlands. METHOD: Intervention: treatment protocol based on a formalised expert opinion. Control condition: usual care. Study population: 208 subjects with moderate to severe LUTS (IPSS > or =8, median = 13). OUTCOME MEASURES: symptom severity (IPSS [International Prostate Symptom Score]), bother score (Dan-PSS [Danish Prostate Symptom Score]), and maximum urinary flow (Q(max)); incidence of acute urinary retention and urinary tract infections. RESULTS: In the intervention group markedly more subjects used an alpha-blocker at end of follow-up than in the usual care group (24% versus 6%). No significant differences were found between intervention and control group in IPSS, Q(max) or Dan-PSS. CONCLUSION: alpha-blockers and watchful waiting are the most frequent treatment modalities for LUTS in primary care. Our study showed no evidence that a protocol using well-defined indications for all possible treatment modalities based on a formalised expert opinion procedure has added value. Based on our results, we cannot recommend a broadening of the indication for alpha-blockers, which, however, seems to be the current trend.     

Insertional inactivation of an intrageneric coaggregation-relevant adhesin locus from Streptococcus gordonii DL1 (Challis).

Transposon Tn916 was used to insertionally inactivate a coaggregation-relevant locus of Streptococcus gordonii DL1 (Challis). One mutant (F11) was isolated that lost the ability to coaggregate with the streptococcal partners of DL1 but retained the ability to coaggregate with partners belonging to other genera. A probe specific for the region flanking the Tn916 insertion was used to isolate a locus-specific fragment from a chromosomal lambda library. Southern analysis of the resulting phagemids revealed that a 0.5-kb EcoRI fragment hybridized with the F11 probe. Cloning of the 0.5-kb EcoRI fragment into the E. coli-streptococcal insertion vector p(omega) yielded pCW4, which was used to insertionally inactivate the putative coaggregation-relevant gene in DL1. Insertion mutants showed altered coaggregation with streptococci but retained wild-type coaggregation properties with other genera of bacteria. Comparison of immunoblots of cell surface proteins showed a 100-kDa protein in DL1 which was not detected in the Tn916 and pCW4 insertion mutants. These results indicate that the 0.5-kb EcoRI fragment is part of an adhesin-relevant locus that is involved in the production of a 100-kDa protein at the cell surface.     

Characterization of a recombinant canine coronavirus with a distinct receptor-binding (S1) domain

Canine alphacoronaviruses (CCoV) exist in two serotypes, type I and II, both of which can cause severe gastroenteritis. Here, we characterize a canine alphacoronavirus, designated CCoV-A76, first isolated in 1976. Serological studies show that CCoV-A76 is distinct from other CCoVs, such as the prototype CCoV-1-71. Efficient replication of CCoV-A76 is restricted to canine cell lines, in contrast to the prototypical type II strain CCoV-1-71 that more efficiently replicates in feline cells. CCoV-A76 can use canine aminopeptidase N (cAPN) receptor for infection of cells, but was unable to use feline APN (fAPN). In contrast, CCoV-1-71 can utilize both. Genomic analysis shows that CCoV-A76 possesses a distinct spike, which is the result of a recombination between type I and type II CCoV, that occurred between the N- and C-terminal domains (NTD and C-domain) of the S1 subunit. These data suggest that CCoV-A76 represents a recombinant coronavirus form, with distinct host cell tropism.     

A Multimedia Mobile Phone–Based Youth Smoking Cessation Intervention: Findings From Content Development and Piloting Studies

Background

While most young people who smoke want to quit, few access cessation support services. Mobile phone–based cessation programs are ideal for young people: mobile phones are the most common means of peer communication, and messages can be delivered in an anonymous manner, anywhere, anytime. Following the success of our text messaging smoking cessation program, we developed an innovative multimedia mobile phone smoking cessation intervention.

Objective

The aim of the study was to develop and pilot test a youth-oriented multimedia smoking cessation intervention delivered solely by mobile phone.

Methods

Development included creating content and building the technology platform. Content development was overseen by an expert group who advised on youth development principles, observational learning (from social cognitive theory), effective smoking cessation interventions, and social marketing. Young people participated in three content development phases (consultation via focus groups and an online survey, content pre-testing, and selection of role models). Video and text messages were then developed, incorporating the findings from this research. Information technology systems were established to support the delivery of the multimedia messages by mobile phone. A pilot study using an abbreviated 4-week program of video and text content tested the reliability of the systems and the acceptability of the intervention.

Results

Approximately 180 young people participated in the consultation phase. There was a high priority placed on music for relaxation (75%) and an interest in interacting with others in the program (40% would read messages, 36% would read a blog). Findings from the pre-testing phase (n = 41) included the importance of selecting “real” and “honest” role models with believable stories, and an interest in animations (37%). Of the 15 participants who took part in the pilot study, 13 (87%) were available for follow-up interviews at 4 weeks: 12 participants liked the program or liked it most of the time and found the role model to be believable; 7 liked the role model video messages (5 were unsure); 8 used the extra assistance for cravings; and 9 were happy with two messages per day. Nine participants (60%) stopped smoking during the program. Some technical challenges were encountered during the pilot study.

Conclusions

A multimedia mobile phone smoking cessation program is technically feasible, and the content developed is appropriate for this medium and is acceptable to our target population. These results have informed the design of a 6-month intervention currently being evaluated for its effectiveness in increasing smoking cessation rates in young people.     

Immunolocalization and expression of prohibitin,a mitochondrial associated protein within the rat ovaries

This study was designed to determine the cellular distribution and pattern of expression for the mitochondria‐associated protein, prohibitin, during the transitional stages of follicular differentiation within the rat ovary. Immunohistochemical staining techniques were used on frozen sections to examine the localization of prohibitin to preantral, antral, preovulatory, and atretic follicles. Prohibitin localization was also determined in corpus luteum from adult rats, in addition to those from infant and juvenile ovaries, before and after gonadotropin stimulation. Western and Northern blotting techniques were used for qualitative and quantitative assessment of prohibitin expression levels within the ovary. Prohibitin was localized within granulosa cells of infant and juvenile ovaries in a relatively heterogeneous staining pattern. The oocyte also exhibited robust prohibitin expression at all stages of follicular development. In addition, strong prohibitin expression was evident in the corpus luteum as well as in follicles undergoing atresia. Additional data derived from studies involving a GnRH‐agonist indicate that increases in prohibitin protein expression correlate with the initial events of apoptosis. Collectively, these results support a growth regulatory role for prohibitin within the rat ovary. Therefore, we propose that prohibitin may serve as an important regulator of granulosa cell fate during follicular development. Anat Rec 256:40–48, 1999. © 1999 Wiley‐Liss, Inc.     

Blunted cardiovascular reactivity to acute psychological stress predicts low behavioral but not self‐reported perseverance: A replication study

Emerging evidence suggests that individuals with poor behavioral perseverance show low or blunted physiological responses to acute psychological stress. For example, a recent preliminary laboratory study demonstrated that blunted responders give up sooner and take fewer attempts when endeavoring to complete an impossible puzzle, but do not self‐report poor perseverance. This present research is a replication of the previous study with an increased sample size, longer recovery periods between tasks and addition of social evaluation to the cold pressor. Participants (147) completed a self‐report perseverance questionnaire (Short Grit Scale) and behavioral perseverance tasks (impossible Euler puzzle and socially evaluated cold‐pressor (SECPT)). The number of attempts and time spent trying to complete the unsolvable puzzle, and duration of hand submergent during the SECPT, were recorded as behavioral perseverance measures. Difference in blood pressure (BP) and pulse rate (PR) from baseline to a 10‐min paced auditory serial addition task (PASAT) were computed as reactivity. As previously, reactivity did not relate to self‐reported perseverance and blunted BP reactivity to the PASAT was associated with less time persevering at the unsolvable puzzle. Additionally, blunted BP and PR reactivity to the PASAT related to poorer perseverance during the SECPT. These findings, replicating the previous study, increase confidence that blunted reactivity is a physiological marker of poor behavioral perseverance. Moreover, given that self‐reported perseverance does not relate to reactivity, this suggests that blunted responders are not conscious of this detriment in perseverance, but likely need additional support when persistence is critical (e.g., during behavior change).     

Significance of immune cell function monitoring in renal transplantation after Thymoglobulin induction therapy

Monitoring of immune status in transplant recipients is essential for predicting the risk of rejection or infection. In this study, we assessed the significance of immune cell function in 76 renal allograft recipients after Thymoglobulin induction and initiation of maintenance immunosuppression. Using the Immuknow (Cylex Inc) assay, the amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin (PHA) was measured in patients whole blood. In parallel, the frequency and phenotype of CD4+ T cells were determined by flow cytometry. The Immuknow assay yielded paradoxically high ATP values during the first 3 months post-transplantation, despite very low CD4+ T cell counts. High ATP values were caused by peripheral blood myeloid cells, did not predict rejection, and occurred primarily in transplant recipients who received darbepoietin (p = 0.017). CD4+ T cells displayed predominantly an activated/memory phenotype and comprised a subpopulation of CD25+FOXP3+ cells. Over the first 5 months post-transplantation, mean ATP activity gradually decreased, whereas CD4+ T cell counts slowly increased. Low ATP values were predictive of infection (p = 0.002). Thus Immuknow results need to be interpreted with caution in patients receiving Thymoglobulin induction therapy. Although low ATP levels identify patients at increased risk for infection, high ATP values fail to correlate with rejection and do not justify increased immunosuppression.     

Prenatal detection of unbalanced chromosomal rearrangements by array CGH

Background

Karyotype analysis has been the standard method for prenatal cytogenetic diagnosis since the 1970s. Although highly reliable, the major limitation remains the requirement for cell culture, resulting in a delay of as much as 14 days to obtaining test results. Fluorescent in situ hybridisation (FISH) and quantitative fluorescent PCR (QF‐PCR) rapidly detect common chromosomal abnormalities but do not provide a genome wide screen for unexpected imbalances. Array comparative genomic hybridisation (CGH) has the potential to combine the speed of DNA analysis with a large capacity to scan for genomic abnormalities. We have developed a genomic microarray of approximately 600 large insert clones designed to detect aneuploidy, known microdeletion syndromes, and large unbalanced chromosomal rearrangements.

Methods

This array was tested alongside an array with an approximate resolution of 1 Mb in a blind study of 30 cultured prenatal and postnatal samples with microscopically confirmed unbalanced rearrangements.

Results

At 1 Mb resolution, 22/30 rearrangements were identified, whereas 29/30 aberrations were detected using the custom designed array, owing to the inclusion of specifically chosen clones to give increased resolution at genomic loci clinically implicated in known microdeletion syndromes. Both arrays failed to identify a triploid karyotype. Thirty normal control samples produced no false positive results.

Conclusions

Analysis of 30 uncultured prenatal samples showed that array CGH is capable of detecting aneuploidy in DNA isolated from as little as 1 ml of uncultured amniotic fluid; 29/30 samples were correctly diagnosed, the exception being another case of triploidy. These studies demonstrate the potential for array CGH to replace conventional cytogenetics in the great majority of prenatal diagnosis cases.