Men's preferences for prostate cancer screening: a discrete choice experiment.

BACKGROUND: Screening for prostate cancer (PC) may save lives, but overdiagnosis and overtreatment are serious drawbacks. We aimed to determine men's preferences for PC screening, and to elicit the trade-offs they make. METHODS: A discrete choice experiment (DCE) was conducted among a population-based random sample of 1000 elderly men (55-75-years-old). Trade-offs were quantified with a panel latent class model between five PC screening aspects: risk reduction of PC-related death, screening interval, risk of unnecessary biopsies, risk of unnecessary treatments, and out-of-pocket costs. RESULTS: The response rate was 46% (459/1000). Men were willing to trade-off 2.0% (CI: 1.6%-2.4%) or 1.8% (CI: 1.3%-2.3%) risk reduction of PC-related death to decrease their risk of unnecessary treatment or biopsy with 10%, respectively. They were willing to pay €188 per year (CI: €141-€258) to reduce their relative risk of PC-related death with 10%. Preference heterogeneity was substantial, with men with higher educational levels having a lower probability to opt for PC screening than men with lower educational levels. CONCLUSION: Men were willing to trade-off some risk reduction of PC-related death to be relieved of the burden of biopsies or unnecessary treatments. Increasing knowledge on overdiagnosis and overtreatment, especially for men with lower educational levels, is warranted to prevent unrealistic expectations from PC screening.

Salivary cortisol increases after bariatric surgery in women.

Cortisol increases have been associated with psychological and physiological stress; however, cortisol dynamics after weight loss (bariatric) surgery have not been defined. Obese participants not using exogenous glucocorticoids were eligible to participate. Female participants (n=24) provided salivary cortisol samples at bedtime, upon awakening the following morning, and 30 min after awakening before, and at 6 or 12 months after bariatric surgery. The Medical Outcomes Study Short Form-12 version 2 questionnaire regarding health-related quality of life was also completed. Preoperatively, mean body mass index was 45.1±8.1 kg/m2. Mean late night (1.8±1.1 nmol/l), awakening (10.7±7.4 nmol/l), and after-awakening (11.5±7.9 nmol/l) salivary cortisol values were within normal ranges. The cortisol awakening response (mean 21.1±79.7%, median 13.7%) was at the low end of normal. Preoperatively, participants had lower mental and physical health-related quality of life scores than US adult norms (p<0.001). Salivary cortisol was not correlated with measures of health-related quality of life. Mean BMI decreased over time (p<0.001) and participants experienced improved physical and mental health-related quality of life (p≤0.011). Postoperative late night salivary cortisol was not different from preoperative values. Awakening and after-awakening cortisol levels were higher than preoperative values (15.3±7.7 nmol/l, p=0.013; 17.5±10.2 nmol/l, p=0.005; respectively), but the cortisol awakening response was not changed (mean 26.7±66.2%; median 7.8%). Morning salivary cortisol increased at long-term follow-up after bariatric surgery. Although self-evaluated mental and physical health improved after surgery, the cortisol awakening response is at the low end of normal, which may indicate continued physiological stress.

Gamma-A-blood group antibodies.

The serological characteristics of gammaA-anti-A and anti-B were studied using, as a source, either colostrum, or fractions relatively rich in gammaA obtained from selected potent antisera. gammaA-anti-A and anti-B were never hemolytic nor did they sensitize red cells to agglutination by anticomplement globulin sera. gammaA-anti-A, like gammaG-anti-A and unlike gammaM-anti-A was unaffected by heating at 56 degrees C for 3 hr. On the other hand in the following three characteristics the behavior of gammaA fell between that of gammaG- or gammaM-anti-A: sensitivity to inactivation by 2-mercaptoethanol, ease of neutralization by A substance and degree of enhancement of agglutination in a medium of serum rather than saline. The agglutination produced by gammaA-anti-A was regularly enhanced by addition of anti-gammaA-globulin serum. In searching for gammaA-blood group antibodies of other specificities the following sera were tested: anti-D (32 examples); anti-c (2 examples); anti-Le(a) or -Le(b) (3 examples); anti-K (3 examples); anti-Fy(a) (3 examples), and anti-Jk(a) (3 examples). Only 3 sera, all containing anti-D, sensitized red cells to agglutination by anti-gammaA. There were no discrepancies between results obtained with four different anti-gammaA-globulin sera. Approximately half the sera were fractionated on DEAE-cellulose, and the fractions rich in gammaA tested for their ability to sensitize red cells to agglutination by anti-gammaA; no additional examples of gammaA-antibodies were detected. One of the three examples of gammaA-anti-D appeared in the serum of a woman during the course of deliberate reimmunization. gammaA-anti-D appeared only after three intravenous injections of red cells although the gammaG-anti-D titer rose considerably after a single injection. 3 yr after a fourth injection of Rh-positive cells gammaA-anti-D, as well as gammaG-anti-D, was still present in the serum.

Methylmercury: bacterial degradation in lake sediments.

During the first 50 days of a long-term period of incubation of lake sediments with inorganic mercury (Hg(2+)), low concentrations of methylinercury were observed to build up. Upon continued incubation there was a rapid decrease in amount of methylmercury in the system and a concomitant evolution of volatile inorganic mercury (Hg(0)). Transfer of the mixed culture to growth media containing methylmercury resulted in the degradation of methylmercury and the volatilization of Hg(0). Four bacterial isolates were obtained from the mixed culture which, in pure culture, rapidly degraded methylmercury to methane and Hg(0). The presence of methane in head space gases was confirmed by flameionization gas chromatography, and the presence of Hg(0) in head space gases was confirmed by mass spectrometry.

Parasitization of a hydrothermal vent limpet (Lepetodrilidae, Vetigastropoda) by a highly modified copepod (Chitonophilidae, Cyclopoida).

The limpet Lepetodrilus fucensis McLean is very abundant at hydrothermal vents on the Juan de Fuca and Explorer Ridges in the northeast Pacific Ocean. This limpet is parasitized by an undescribed chitonophilid copepod throughout the limpet's range. The parasite copepodite enters the mantle cavity and attaches to the afferent branchial vein. The initial invasive stage is a vermiform endosome within the vein that develops an extensive rootlet system causing an enlargement of the afferent branchial vein. Subsequently, an ectosomal female body grows outside the vein to sizes up to 2 mm in width. Once a dwarf male attaches, egg clusters form and nauplii are released. In over 3000 limpets examined from 30 populations, prevalence averaged about 5% with localized infections in female limpets over 25%. After the establishment of limpet populations at new vents, copepod prevalence increased over the succeeding months to 3 years. Host effects were marked and included castration of both sexes and deterioration in gill condition which affected both food acquisition and the gill symbiont. There was a significantly greater parasite prevalence in larger females which likely modifies the reproductive and competitive success of local host populations.

Are some QALYs more equal than others?

Including societal preferences in allocation decisions is an important challenge for the health care sector. Here, we present results of a phased discrete choice experiment investigating the impact of various attributes on respondents' preferences for distribution of health and health care. In addition to the renowned equity principles severity of illness (operationalized as initial health) and fair innings (operationalized as age), some characteristics of beneficiaries (culpability and having dependents) and the disease (rarity) were included in the choice experiment. We used a nested logit model to analyse the data. We found that all selected attributes significantly influenced respondents' choices. The phased inclusion showed that additional attributes affected respondents' preferences for previously-included attributes and reduced unobserved variance. Although not all these attributes may be considered relevant for decision making from a normative perspective, including them in choice experiments contributes to our understanding of societal preferences for each single attribute.

Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 6. 2-Indol-3-yl- and 2-azaindol-3-yl-dipyridodiazepinones.

Modification of the non-nucleoside inhibitor of HIV-1 reverse transcriptase nevirapine (Viramune) by incorporation of a 2-indolyl substituent confers activity against several mutant forms of the enzyme.

Receptor-mediated angiotensin II transcytosis by brain microvessel endothelial cells.

Angiotensin II (Ang II) uptake and transport across monolayers of bovine brain microvessel endothelial cells (BMECs) was demonstrated. Ang II transport was linear up to 2 h, saturable with a K(m) of 1.7 nM, and tended to be polarized with the apical-to-basolateral transport being greater. [3H]Ang II transport was found to be inhibited by excess unlabeled Ang II, by the Ang II analog sarathrin, and by the endocytic inhibitor phenylarsine oxide. Ang II-(2-8) and-(3-8) were shown to significantly increase the transport of Ang II. These results demonstrate for the first time the receptor-mediated transcytosis of Ang II across brain microvessel endothelium.

Beliefs about smoking cessation among out-of-school youth.

Although the majority of adolescents in the 13-18 age range are at school, there is a need to target specific groups of young smokers such as unemployed youth. For those young people who are not at school, few directed programs are available in either prevention or cessation and information is needed about the design and delivery of appropriate programs for this population. This report presents the results from a survey of unemployed youth and students at vocational colleges about various aspects of smoking cessation. The majority of out-of-school youth smokers had not tried to quit, but 52% were contemplating action to quit. Only a quarter of the smokers had quit for more than a week. Few young smokers would use a recognised program though more females would change to a lower nicotine brand, quit with the help of a friend or participate in a group quit program. The method of quitting most would recommend to peers is 'use of will power'. Incentives to quit were attractive to only a third of the smokers, and many enhancing and inhibiting factors for participation in programs were identified. In particular, efforts to quit increased their confidence in quitting, supporting the need to assist those who are contemplating action to quit. Programs need to incorporate input from youth and be tailored for them but not necessarily for different groups such as non-secondary school students and unemployed youth.

Dimensions of perceived social support in clinically depressed and nondepressed female caregivers.

The relationship between social support and depression was studied in 165 women caring for frail family members. The Arizona Social Support Interview Schedule (Barrera, Sandler, & Ramsay, 1981), which includes 4 dimensions of availability and use of resources and satisfaction with and need for support, was used to examine 7 categories of supportive activity. Depression was assessed according to Research Diagnostic Criteria (Spitzer, Endicott, & Robins, 1978) with the Schedule of Affective Disorders and Schizophrenia (Endicott & Spitzer, 1978). There were no differences in overall satisfaction with received support in comparisons of depressed and nondepressed caregivers. However, depressed caregivers (n = 87) reported a higher incidence of negative interactions with others. Both groups appeared to have equal access to social support, with nondepressed caregivers (n = 78) reporting significantly greater use of those resources.

Separation-individuation conflict as a model for understanding distressed caregivers: psychodynamic and cognitive case studies.

Caring for a frail relative can be a stressful undertaking. Caregivers are faced with a series of losses, and old interpersonal wounds are often reopened. Project Assist was designed to study the efficacy of time-limited psychodynamic and cognitive/behavioral therapies for experienced and recent caregivers. It offers psychotherapy that can assist caregivers in separating their own emotions, identity, and well-being from those of the care receiver. This process appears necessary for the individuation and mental health of caregivers.

Low-vision rehabilitation with older adults.

Vision loss increases dramatically with age but relatively little attention has been paid to blind and low-vision rehabilitation with older adults in the health care literature. The present article describes the nature and etiology of vision loss in older adults and provides an overview of the techniques and technologies available to help older adults overcome the disabilities associated with loss of vision.

Sliding oblique osteotomy for the treatment of hallux abducto valgus associated with functional hallux limitus.

This is a retrospective study of 27 patients (35 feet) with hallux abducto valgus associated with hallux limitus who underwent a sliding oblique osteotomy for surgical treatment between August 1997 and June 1998. Radiographic analysis and range-of-motion measurements were evaluated with an average follow-up of 65 days (range, 26-100). Preoperative criteria included < 45 degrees of dorsiflexion of the first metatarsophalangeal joint with weightbearing, no evidence of degenerative joint disease at the first metatarsocuneiform joint, and no previous surgical procedures on the first ray. The average preoperative intermetatarsal angle was 9 degrees, hallux abductus angle 17 degrees, and first metatarsal declination angle 15 degrees. The average postoperative intermetatarsal angle was 6.6 degrees, hallux abductus angle 10.3 degrees, and first metatarsal declination angle 21.7 degrees. Eighteen patients (22 feet) had a follow-up of over 6 weeks, and the first metatarsophalangeal joint was evaluated. The average gain in postoperative range of motion with weightbearing was 22.3 degrees.

AT1 receptors mediate angiotensin II uptake and transport by bovine brain microvessel endothelial cells in primary culture.

The endothelial lining of the blood-brain barrier tightly controls the distribution of peptide hormones between the central nervous system and the circulation. By using primary cultures of brain microvessel endothelial cells, an in vitro model of the blood-brain barrier, we report here the uptake and transport of the octapeptide angiotensin II by a specific receptor population. With the angiotensin II antagonists losartan (AT1 specific) and PD 123,319 (AT2 specific), we showed that both the uptake and transport of angiotensin II were mediated by the AT1 receptor. Western blot analysis confirmed the existence of the AT1 receptor in our cell-culture model. Rhodamine 123 studies also suggested that both angiotensin II antagonists, but not angiotensin II, were substrates for the P-glycoprotein efflux system, thus restricting the transport of these compounds. These results suggest an AT1 receptor mediates uptake and transport of angiotensin II at the blood-brain barrier and may contribute to the regulation of cerebrovascular levels of the peptide.

Evidence that IFN-alph/beta induces two antiviral states active against different viruses.

IFN-alpha/beta has been suggested to require only one round of mRNA and protein synthesis to induce an antiviral state. We have examined the mechanism of induction of the antiviral states shown against three types of viruses: mengovirus (plus strand, sense RNA), vesicular stomatitis virus (VSV, minus strand RNA), and vaccinia virus (DNA). Mouse L cells were treated with IFN-alpha/beta and cycloheximide and then with actinomycin D on a schedule which allowed only one round of mRNA and protein synthesis. The cells were challenged with virus under single cycle growth conditions to determine the amount of antiviral activity against the particular challenge virus employed. These studies confirmed that most of the antiviral effect directed against VSV is achieved with one round of macromolecular synthesis. However, most of the antiviral effect directed against mengovirus and vaccinia virus seemed to require more than one round. These results suggest that IFN-alpha/beta induces two different antiviral states: one requiring one round of synthesis which is primarily responsible for the inhibition observed for VSV; and another requiring more than one round of synthesis which is primarily responsible for the inhibition observed for mengovirus and vaccinia virus.

Bioactivity and immunological characterization of a cholera toxin-cross-reactive cytolytic enterotoxin from Aeromonas hydrophila.

A cytolytic enterotoxin of molecular weight 52,000 was isolated and purified from culture supernatants of a human diarrheal isolate (SSU) of Aeromonas hydrophila. The toxin reacted with cholera antitoxin when tested in an enzyme-linked immunosorbent assay and by Western blot (immunoblot) analysis. The appearance of cytotoxic and hemolytic activities in culture supernatant occurred simultaneously 8 h after the initial inoculation of the culture. Loss of hemolytic activity and cholera toxin cross-reactivity was correlated with heat and pH inactivation. Homologous antibodies neutralized the cytotoxic and hemolytic activities associated with the toxin, but cholera antitoxin did not neutralize these activities. The toxin also possessed enterotoxic activity as demonstrated by fluid accumulation in rabbit ligated intestinal loops. When purified cytolytic enterotoxin was injected intravenously into mice, death occurred within 2 min, whereas mice injected with whole cells or sonicated cell fragments died after several hours or days. Results from 51Cr release experiments demonstrated that the cytolytic enterotoxin had significant membrane-damaging capability. These results indicated that the cytolytic and enterotoxic activities expressed by the described A. hydrophila toxin may contribute significantly to the pathogenesis of disease associated with A. hydrophila.

Endoscopic plantar fasciotomy: a retrospective analysis of results in 53 patients.

This retrospective study analyzes satisfaction of patients who had undergone an isolated endoscopic plantar fasciotomy (EPF) between January 1994 and January 1997. A subjective survey was completed and returned by 53 patients (a total of 69 feet), and a chart review was performed to determine final outcome. Postoperative follow-up averaged 7.2 months (range, 4-42 months). Postoperative pain levels were scored on a 7-point scale at 1 week, 1 month, and 6 months. Forty-three patients (81.1%) were satisfied with the EPF procedure and 10 patients (18.9%) were unsatisfied.

Evolutionary conservation of intron position in a subfamily of genes encoding carbohydrate-recognition domains.

The structure of the gene encoding a chicken liver receptor, the chicken hepatic lectin, which mediates endocytosis of glycoproteins has been established. The coding sequence is divided into six exons separated by five introns. The first three exons correspond to separate functional domains of the receptor polypeptide (cytoplasmic tail, transmembrane sequence, and extracellular neck region), while the final three exons encode the Ca(2+)-dependent carbohydrate-recognition domain. These results, as well as computer-assisted multiple sequence comparisons, establish this receptor as the evolutionary homolog of the mammalian asialoglycoprotein receptors. It is interesting that the chicken receptor falls into a subfamily of proteins along with the mammalian asialoglycoprotein receptors, since the saccharide-binding specificity of the chicken receptor resembles more closely that of a different set of calcium-dependent animal lectins, which includes the mannose-binding proteins. The portions of the genes encoding the carbohydrate-recognition domains of these proteins lack introns. The results suggest that divergence of intron-containing and intron-lacking carbohydrate-recognition domains preceded shuffling events in which other functional domains were associated with the carbohydrate-recognition domains. This was followed by further divergence, generating a variety of saccharide-binding specificities.

Review of Aeromonas enterotoxins.

This report reviews the work of other investigators regarding Aeromonas toxins and describes work conducted in our laboratory relating to the biochemical characterization of a cytolytic factor with an antigenic moiety that cross-reacts with cholera toxin (referred to as CTC-cytolysin), as well as the purification and partial characterization of a non-CTC enterotoxin. These two toxins were produced by Aeromonas hydrophila, isolate SSU, and are capable of causing fluid accumulation in animal models.