The use of confidence intervals for individual utilities: limits to formal decision analysis for treatment choice.

This paper discusses the use of confidence intervals for utility measurements. Classic test theory is applied to estimate confidence intervals for utilities. The theory is enhanced to calculate confidence areas for combined utilities and confidence bands for the threshold line. As an example it is shown that, if confidence intervals are taken into account, the implied preferred treatment of T3-larynx carcinoma patients is uncertain for a wide range of utilities, considering the mediocre reliability of most methods of utility assessment. This implies that although utility measurement and formal decision analysis can be a useful way to look at the decision problem, ambiguity, which must be resolved by other means, will often remain.

Patient participation in clinical decision-making for treatment of T3 laryngeal cancer: a comparison of state and process utilities.

PURPOSE: To study the use of two different approaches, and feasibility of four commonly used utility assessment methods to assess preferences for treatment of T3-laryngeal cancer by surgery or radiation therapy (RT). METHODS: Utility assessment methods, namely, time trade-off (TTO), standard reference gamble (SRG), rating scale (RS), and direct comparison (DC), were used to assess utilities in two groups of former cancer patients (n = 10 for both), a group of clinicians (n = 9), and a group from the general population (n = 10). For the treatment modalities, ie, surgery and RT, two types of scenarios were developed and used: the state scenario, which describes a stable health state after treatment, and the process scenario, which describes a dynamic process. First, utilities were assessed based on state scenarios. Next, respondents were thoroughly informed and educated with respect to the relevant aspects of both treatment modalities. Subsequently, utilities were again assessed, but now based on the process scenarios. The outcome of each approach was calculated and expressed in a quality-adjusted life-expectancy (QALE) score for each treatment modality, and the treatment with the highest outcome was said to be the preferred treatment modality. RESULTS: In general, a higher QALE score for each treatment modality was found for clinicians and for the general population as compared with the former-cancer-patient groups. When the outcome of both approaches was compared on an individual level dependent on the utility assessment method, 32% to 43% of respondents showed an inconsistent treatment preference. CONCLUSION: The approach to assess utilities and the extent to which respondents are informed about treatment modalities have a major effect on individual treatment preferences.

Effects of fetal bovine serum, FSH and 17beta-estradiol on the culture of bovine preantral follicles.

We describe a 7-d culture in droplets of collagen gel of isolated small bovine preantral follicles in medium with or without 10% fetal bovine serum (FBS). In addition, the effect of human recombinant FSH and 17beta-estradiol on the morphology and growth of the preantral follicles was investigated in medium without FBS. After culture in medium with 10% FBS, the increase in follicle diameter was 13.1 +/- 8.4 microm, the percentage of BrdU-labeled cells was 49.9 +/- 11.3 and the number of cells per area granulosa was 11.1 +/- 1.8. Omission of serum from the culture medium had no effect on the percentage of labeled cells, but the diameter increase was lower and the cells were smaller. Apparently, serum affects the size of the granulosa cells from small preantral follicles rather than the stimulation of cell proliferation. Addition of human recombinant FSH and/or 17beta-estradiol to serum-free medium resulted in a larger diameter increase during culture compared with that of the control. With FSH, this was due to an increase in cell proliferation, while with estradiol this was caused by an increase in granulosa cell size. The effects of simultaneous treatment with FSH and estradiol was simply the combination of their individual effects. In conclusion, small bovine preantral follicles can be cultured for 7 d in the absence of serum and hormones. The follicles increase in diameter and react to FSH with enhanced cell proliferation and to estradiol with an increase in cell size.

Quality of life and maladjustment associated with hair loss in women with alopecia androgenetica.

Quality of life and maladjustment related to hair loss were studied by means of a standardized interview in a group of 58 women with alopecia androgenetica who applied for treatment at the Department of Dermatology. The hair loss was found to have a negative influence on the quality of life on the majority of them. In 88%, hair loss had negative effects on their daily life; in about 75%, the hair problems were manifested in negative self-esteem and about 50% experienced social problems. General psychosocial maladjustment in relation to hair loss was indicated in almost one-third of the women.

Cytogenetic analysis of day-7 bovine embryos by cytophotometric DNA measurements.

A Feulgen staining procedure that stains the DNA of individual fixed nuclei stoichiometrically was used to analyse cytophotometrically the incidence of total ploidy and mixoploidy in 28 day-7 bovine embryos that had been fixed after collection ('non-cultured' embryos). The influence of culture on the incidence of chromosome abnormalities was further studied in another group of 24 embryos ('cultured' embryos) by culturing them for 24 h in Whittingham's medium. Of the total 52 embryos studied, two appeared to be entirely abnormal: one embryo was completely haploid, whereas the other embryo was completely triploid. Individual hyperdiploid nuclei and hypodiploid nuclei were frequently observed in the otherwise diploid embryos. As haploid polar bodies can still be present in morulae and blastocysts (to a maximum of three), only embryos with more than three hypodiploid nuclei were considered as abnormal. Of the 'non-cultured' embryos, 33.3% had one or more hyperdiploid nuclei, whereas 51.9% had more than three hypodiploid nuclei. In this latter group, 35.7% of the embryos also had hyperdiploid nuclei. The results also showed that day-7 bovine embryos that are completely haploid, completely triploid or mixoploid cannot be detected only by examining their morphology. It is concluded that the incidence of, especially, mixoploidy in embryos can be better studied by measuring the DNA content of the individual nuclei of an embryo rather than by analysing chromosomes, as in the latter method only dividing cells can be analysed. The presence of hyperdiploid and hypodiploid nuclei may indicate the frequent occurrence of mitotic segregation failures during mitosis in bovine embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival and proliferation of rat gonocytes in vitro.

Quiescent gonocytes were isolated from fetal testes of rat 18-day post coitum and cultured alone or on monolayers of somatic cells from different origins. The gonocytes specifically adhered to Sertoli cells, isolated from 21 to 23-day-old rat testes; this adherence was necessary for their survival in vitro. Addition of follicle-stimulating hormone and testosterone to these cultures did not increase the viability of the gonocytes. Serum was found to be deleterious to the germ cells. Electron-microscopic examination of Sertoli-cell-gonocyte co-cultures revealed the presence of numerous adhesion plaques between these cells, indicating that Sertoli cells and gonocytes are able to communicate in vitro. Gonocytes, in co-culture with Sertoli cells, were viable for at least 9 days. The gonocytes did not spontaneously resume proliferation. The simple culture system described in the present paper should be useful in studying the nature of the factors that are responsible for sending the quiescent gonocytes into the cell cycle and for stimulating the formation of A spermatogonia, a process characterizing the start of spermatogenesis.

A monoclonal antibody recognizing a differentiation marker on rat gonocytes.

Monoclonal antibodies (MAb) were raised against a testicular membrane fraction from 18-day post coitum (p.c.) rat testes. One antibody, designated 4B6.3E10 (mu, kappa), was obtained which specifically reacted with gonocytes in the fetal testis. No significant cross-reactivity with other tissues from the 18-day p.c. embryo was found. MAb 4B6.3E10 was reactive with rat gonocytes from 17-day p.c. until the day of birth. Germ cells at later stages of testis development did not show any labelling. The epitope recognized by 4B6.3E10 is a carbohydrate as periodate treatment leads to a loss of reactivity of the antibody. By SDS-PAGE and Western blotting of proteins extracted from a testicular membrane fraction from 18-day p.c. testes, MAb 4B6.3E10 was found to recognize at least 3 protein moieties with apparent molecular weights in the ranges of 80-100, 120, 160-180 kDa (either under reducing- or non-reducing conditions). The results suggest that MAb 4B6.3E10 recognizes a specific differentiation marker for fetal rat gonocytes.

The associations of neck pain with radiological abnormalities of the cervical spine and personality traits in a general population.

Degenerative changes are considered to be a common cause of neck pain. In addition to this cause, personality traits could contribute to the complaint of neck pain. We investigated the associations of neck pain with personality traits, disc degeneration and osteoarthritis (OA) on radiographs of the cervical spine in a general population of 5,440 men and women between 20 and 65 years of age. Disc degeneration was associated with neck pain in the men but not in the women. OA of the facet joints was not related to neck pain, either in the men or the women, but the personality traits, neuroticism and injuredness, were. Among those with severe disc degeneration or OA of the cervical spine, neuroticism was a strong independent determinant of pain. Our findings show that neuroticism is a more powerful determinant of neck pain than radiological signs of disc degeneration or OA in the general population.

Psychological characteristics of women with androgenetic alopecia: a controlled study.

The psychological characteristics and the hair problems of 58 females with androgenetic alopecia were compared with a group of women with non-apparent dermatological diseases, and with a group of men with androgenetic alopecia. The women with androgenetic alopecia had higher scores for self-sufficiency and social inadequacy compared to women with non-visible dermatological complaints, and they scored higher for inadequacy, rigidity and general psychological maladjustment than the men and had lower scores for injuredness self-evaluation and self-esteem. The women with androgenetic alopecia had more psychosocial problems, which they attributed to the hair loss, than the other groups.

The association of frequent headaches with personality and life events.

The associations between personality traits, life events and frequent headaches were studied in a sample of 5766 adult subjects between 20 and 65 years of age from the general population. Subjects with at least weekly headaches had more life events and higher inadequacy, social inadequacy, rigidity and injuredness than subjects with less frequent headaches. These relationships were not observed in subjects of 50 years of age and older, with the exception of the association with inadequacy. From the traits measured, inadequacy had the highest odds ratios for frequent headaches and showed a modest interaction with the presence of a life event. These findings are in agreement with Sarason's interactional model.

Psychologic characteristics of men with alopecia androgenetica and their modification.

Psychologic characteristics were studied in a sample of 168 men with alopecia androgenetica who participated in a clinical trial on the efficacy of minoxidil gel. In general, no evidence of psychologic malfunctioning was found. Instead, a slightly more adequate psychologic state was indicated. However, specific problems associated with hair loss were reported by a substantial number of men. Responders with cosmetic improvement in the group over 35 years of age improved more regarding general psychologic maladjustment, inadequacy, and self-evaluation than those who did not respond. A reverse trend was, however, found in the group younger than 35 years of age, where the nonresponders improved more. An explanation for these findings is derived from the theory of cognitive dissonance.

Cell-cell interaction between rat Sertoli cells and mouse germ cells in vitro.

An antiserum against rat germ cell membranes was prepared, and after absorption with protein extracts of rat liver and kidney and mouse testis, this antiserum reacted only with rat germ cell membranes and juxtanuclear vesicles in rat Sertoli cells. Germ cell-free rat Sertoli cell monolayers were cultured in vitro. Freshly isolated mouse germ cells adhered to these monolayers within 1 h. After a minimum of 3 days of such a co-culture, immunofluorescence and immunoblotting revealed that the mouse germ cells had obtained rat-antigenic determinants in their membranes. Our results indicate that this appearance of rat-specific antigens on mouse germ cells is specific and inducible.

Humoral immune response of dogs after vaccination against leptospirosis measured by an IgM- and IgG-specific ELISA.

An IgM- and IgG-specific ELISA was used to measure the antibody response stimulated in dogs by vaccination with a leptospiral bacterin containing chemically inactivated Leptospira interrogans serotype icterohaemorrhagiae and serotype canicola leptospires. All dogs produced anti-leptospiral IgM and IgG. The IgM production was of the primary response type after each vaccination (primary vaccination, booster vaccination and annual revaccination). A substantial anti-leptospiral IgG response could be demonstrated only after the first booster vaccination and the annual revaccination. Annual revaccination resulted in a higher and much longer persisting IgG response than did the first booster vaccination. A revision of the vaccination scheme is suggested.

Serodiagnosis of canine leptospirosis by solid-phase enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Leptospira interrogans serotype canicola in dogs was developed and evaluated. Comparison of the ELISA with the microscopic agglutination test (MAT) showed that, during the first two weeks after an experimental infection with serotype canicola, the ELISA detected antibody at higher dilutions than the MAT. After the second week post-infection both tests detected antibody at almost equal titres (r = 0.89). The outer envelope (OE) antigen of serotypes icterohaemorrhagiae, copenhageni and canicola was fairly serotype-specific, whereas the pellet (P) antigen showed more cross-reactivity. Both OE and P antigen of Leptospira biflexa strain Patoc I could be used as cross-reacting antigen in the ELISA. Compared to the MAT, the ELISA has some technical advantages. It is suggested that the ELISA would be useful as a screening test.

Determination of specific anti-leptospiral immunoglobulins M and G in sera of experimentally infected dogs by solid-phase enzyme-linked immunosorbent assay.

The development and evaluation of an enzyme-linked immunosorbent assay (ELISA) to detect specific anti-leptospiral IgM and IgG in sera of dogs experimentally infected with Leptospira interrogans serotype canicola are reported. In all dogs specific anti-leptospiral IgM was detected from the second half of the first week after infection, the maximum being attained during the second week. Subsequently the IgM titre gradually decreased. Specific anti-leptospiral IgG was detected later and increased gradually to reach almost the same level as the IgM titre after two to three months. During the initial stage of the infection, when the microscopic agglutination titre was still negative or very low, a high IgM titre was accompanied by a negative or very low IgG titre in every case. After the initial stage a substantial IgG titre was also detectable. It is suggested that the test is suitable for serodiagnostic purposes, particularly for the diagnosis of a current infection in an individual.

The effect of oral immunization on the population of lymphocytes migrating to the mammary gland of the sow.

Sows were immunized orally with live Escherichia coli according to various immunization schedules. Six pregnant gilts were used; 4 immunized at various intervals during the last month of gestation, 1 control immunized after parturition following suppression of lactation by weaning and 1 non-immunized control. The effect of oral vaccination on cell populations from lymphoid organs was studied. The in vitro proliferative responses of the cell populations to K88 antigen, anti-Ig sera and mitogens were used to demonstrate the distribution of sensitized lymphocytes over different lymphoid organs. The capacity of these cells to produce antigen-specific Ig was determined by in ovo translation of their mRNA. Oral administration of antigen resulted in the appearance of K88-positive cells in lymphoid organs. In lactating sows, sensitized cells preferentially occurred in the mammary lymph nodes, whereas after suppression of lactation such a distribution was not seen. A possible route of migration of sensitized lymphocytes is discussed in relation to the local immune response. The antibody isotype produced by sensitized lymphocytes seemed to depend on the immunization schedule. The most effective schedule was one starting early in gestation and comprising frequent administration of antigen. This caused an optimal distribution of sensitized lymphocytes capable of IgA production.

Induction and effector phases of the immune response: physiological and pathophysiological features.

A review is given on the current state of knowledge about the induction and effector phases of the immune response. Physiological and pathophysiological features of the regulation of the immune response are discussed comparatively for both man and animals.

The histocompatibility complex GLA in the goat.

The current status of research on the major histocompatibility complex of the goat (GLA) is discussed, as well as its similarities to other species, although some of the results are preliminary.

Skin grafting and graft rejection in goats.

As part of a study to define the major histocompatibility complex of the goat and to show certain aspects of its biological function, a skin-grafting technique is described which might also be applicable for similar studies in other ruminant species.