What do patients and health care professionals view as important attributes in radiotherapy decisions? Input for a breast cancer patient decision aid.

BACKGROUND AND AIM: There is increased attention for shared decision making (SDM) when deciding on radiotherapy for selected patients with Stage 0-2 breast cancer. This study aimed to explore patients' and health care professionals' experiences, decisional attributes and needs as input for the development of a patient decision aid to facilitate SDM. METHODS: Qualitative semi-structured interviews were held with fifteen breast cancer patients, being confronted with a radiotherapy decision one month to eight years earlier. Another fifteen interviews were held with professionals specialized in breast cancer care. Interviews were transcribed verbatim and independently coded by two researchers, who agreed upon relevant issues. RESULTS: Most patients made their decision by weighing the advantages of radiotherapy, i.e. comparing the decrease in recurrence risk with and without radiotherapy, and disadvantages, i.e. possible side effects. Patients and professionals agreed that recurrence risks should be communicated, but not on how to deal with uncertainty. There was wide variation in which, and how, side effects were explained by professionals. The most common side effects mentioned by both patients and professionals were skin toxicity, fatigue and breast deformity. CONCLUSION: Patients and professionals appeared to agree on what type of attributes should be communicated during SDM on radiotherapy, but how this should be done is up for discussion. To ensure the patient's voice these attributes and needs need to be incorporated in the risk communication and value elicitation part of the patient decision aid. The format in which the attributes are communicated should be critically evaluated.

Patients with lichen sclerosus experience moderate satisfaction with treatment and impairment of quality of life: results of a cross-sectional study.

BACKGROUND: Although they are considered relevant, little is known about satisfaction with treatment and health-related quality of life (HRQoL) among patients with lichen sclerosus (LS). OBJECTIVES: In a cross-sectional study, we aimed to examine (i) satisfaction with treatment, (ii) patient characteristics associated with satisfaction and (iii) HRQoL in Dutch patients with LS. METHODS: Members of the Dutch LS Patient Association (n = 750) were invited to complete a web-based survey. We measured satisfaction with treatment with a study-specific questionnaire, and HRQoL with the Skindex-29. We calculated domain scores for symptoms, emotions and functioning, and categorized scores into little, mildly, moderately or severely impaired HRQoL. We used a multiple linear regression analysis to examine whether patient characteristics were associated with treatment satisfaction. RESULTS: In total 303 patients (40·4%) were included. Patients under current treatment (n = 265, 87·5%) were moderately satisfied with their treatment. Patients rated 'treatment effectiveness' as most important, although 58 (22%) were dissatisfied with the effectiveness of their current treatment. More impairment on the HRQoL emotions domain and a higher degree of disease severity were both associated with lower satisfaction with treatment and explained in total 13·5% of the variance in treatment satisfaction. On all HRQoL domains, one-third of the patients (range 34·7-38·9%) reported severe impairment. CONCLUSIONS: Patients with LS are moderately satisfied with their treatment, and one-third of patients experience severe impairment of HRQoL. To improve dermatological care, we recommend enhancement of doctor-patient communication, information provision and organization, which may be more amenable to change than treatment effectiveness or safety.

Biocatalytic conversion of avermectin into 4''-oxo-avermectin: discovery, characterization, heterologous expression and specificity improvement of the cytochrome P450 enzyme.

4''-Oxo-avermectin is a key intermediate in the manufacture of the insecticide emamectin benzoate from the natural product avermectin. Seventeen Streptomyces strains with the ability to oxidize avermectin to 4''-oxo-avermectin in a regioselective manner have been discovered, and the enzymes responsible for this reaction were found to be CYPs (cytochrome P450 mono-oxygenases). The genes for these enzymes have been cloned, sequenced and compared to reveal a new subfamily of CYPs. The biocatalytic enzymes have been overexpressed in Escherichia coli, Streptomyces lividans and solvent-tolerant Pseudomonas putida strains using different promoters and vectors. FDs (ferredoxins) and FREs (ferredoxin:NADP(+) reductases) were also cloned from Streptomyces coelicolor and biocatalytic Streptomyces strains, and tested in co-expression systems to optimize the electron transport. Subsequent studies showed that increasing the biocatalytic conversion levels to commercial relevance results in the production of several side products in significant amounts. Chimaeric Ema CYPs were created by sequential rounds of GeneReassembly, a proprietary directed evolution method, and selected for improved substrate specificity by high-throughput screening.

Useful predictors of ovarian stimulation response in women undergoing in vitro fertilization.

Eighty-seven patients undergoing in vitro fertilization were studied to evaluate the prognostic value of different tests in predicting ovarian stimulation response. We studied basal follicle-stimulating hormone (FSH) value on cycle day 3, the clomiphene citrate (CC) challenge test and serum estradiol levels on cycle day 3. Patients with elevated basal FSH levels needed more ampoules of gonadotropins for stimulation and had a higher cancellation rate because of poor response. Patients with abnormal CC challenge test results also needed more ampoules of gonadotropins, but the higher cancellation rate in this group did not reach statistical significance. The basal estradiol level did not contribute to further discrimination between groups. We conclude that basal FSH level on cycle day 3 is a useful prognosticator of ovarian stimulation response.

tip genes act in parallel pathways of early Dictyostelium development.

Analysis of Dictyostelium strains carrying null mutations in tipA showed a primary defect in cell sorting and the formation of tips on the developing mound. To study the process affected in tipA- mutants further, other mutants with a similar phenotype were isolated and characterized. These studies showed three new Dictyostelium genes: tipB, tipC, and tipD. All the tip mutants aggregate into larger than average mounds, which split up and form many lips on their surfaces. Furthermore, each mutant exhibits reduced or aberrant cell-sorting behavior, never makes migrating slugs, and has severely reduced fruiting body and spore production. The mRNA of each tip gene is present in vegetative cells and does not vary significantly with development. Prespore and prestalk gene expression is reduced or delayed in the tip mutants indicating cell type differentiation is dependent on the function of these genes. Developing mutant cells in chimeric mixtures with wildtype cells demonstrated that the defects in each tip mutant behave cell autonomously. The overexpression of TipA in a tipB- background and the overexpression of TipB in a tipA- background significantly improved the morphogenesis of these mutants. These were the only situations in which the expression of one tip gene could compensate for the lack of a different tip gene. Except for the tipA-/tipB- strain, double mutations in the tip genes have additive effects, causing a more severe mutant phenotype with defects earlier in development than single mutants. The tipA-/tipB- double mutant does not show additive effects and is very similar to the tipA-single mutant. Analysis of the effects of double mutations and overexpression indicates that members of this class of genes appear to act through parallel pathways of differentiation and tip formation in early Dictyostelium development. Furthermore, TipA and TipB appear to have some overlapping functions or are involved in the same pathway. The multitipped phenotype observed in all the mutants may be a general result of perturbing early developmental events such as cell type differentiation and cell type proportioning.

Problems related to the cervical stump at follow-up in laparoscopic supracervical hysterectomy.

OBJECTIVES: To evaluate our experience with laparoscopic supracervical hysterectomy (LASH) and to assess the short- and medium-term outcome. METHODS: Retrospective analysis of patient and surgery characteristics from chart review and evaluation of patient satisfaction by a questionnaire. RESULTS: Forty-one patients who underwent LASH were studied with a mean length of follow-up of 27 months. Operative complications consisted of one bladder lesion and one bleeding at the trocar site. Postoperative complications were bladder atony (1), paralytic ileus (1), a pulmonary embolism (1) and vaginal hemorrhage from the colpotomy incision (1). Twenty-five percent of the patients continued to menstruate, and 10% had symptoms of discharge. Overall, 98% of the patients were satisfied with their operation. CONCLUSIONS: Although preservation of the cervix with laparoscopic hysterectomy for benign diseases was satisfactory in most of the cases, several women had complications of the remaining cervix. Special attention should be paid to the careful treatment of the cervical stump. Further prospective studies are needed to evaluate the advantages of retaining the cervix at laparoscopic hysterectomy.

Prenatal ultrasound observations in subsequent pregnancies with Perlman syndrome.

Perlman syndrome is a rare disease with a poor prognosis. Until now, the specific antenatal diagnostic criteria of this syndrome have not been documented. We report on two pregnancies with Perlman syndrome, in the same woman, in which karyotyping and ultrasound examination were performed. In the first pregnancy, the final diagnosis was made only postnatally, whereas, in the second affected pregnancy, nuchal translucency was seen at 11 weeks. From 23 weeks onwards the classical signs of renal and abdominal enlargement were observed. The impact of non-specific early ultrasound markers on decision-making in pregnancies with family risks, where specific tests are not yet available, must be evaluated.

Restrictive dermopathy and associated prenatal ultrasound findings: case report.

Restrictive dermopathy is a lethal autosomal recessive skin disease. Prenatal diagnosis has not yet been reported. We present a case of restrictive demography and describe the associated prenatal sonographic findings. A continuously open mouth was the most striking feature and this sonographic finding may be a marker of a skin disease.

Sorting of the initial cell types in Dictyostelium is dependent on the tipA gene.

About 8 hr after the initiation of development in Dictyostelium discoideum, a few randomly scattered cells express prestalk specific genes and subsequently sort out to the top of the aggregate where they form a tip. The tip elongates and forms the anterior of the migrating slug before differentiating into a stalk which supports the ball of spores in a mature fruiting body. Using REMI mutagenesis we isolated a mutant strain, AK244, in which the initial aggregate subdivides to give a highly papillated surface. This mutant fails to form slugs and appears to have a defect in sorting of prestalk cells. The disrupted gene, tipA, encodes a novel 83-kDa protein and is preferentially expressed in PST-O cells after the cell types have sorted out. Mutant strains that lack TipA express the prestalk-specific gene ecmA at reduced levels and form very few spores. These defects cannot be overcome by developing the mutant cells in the presence of wild-type cells. Thus, TipA acts in a cell-autonomous manner at an early stage in development. Using strains carrying reporter constructs, we found that mutant cells expressing a prestalk marker remain dispersed in the aggregates. Prespore cells appear to sort such that the base is free of cells expressing cell-type-specific markers. Even after 20 hr of development, when wild-type cells are undergoing terminal differentiation, prestalk cells in tipA mutants form very small clumps, most of which fail to sort to the periphery or the tops of aggregates. The tipA gene appears to play an essential role in the sorting of the initial cell types.

Uncomplicated pregnancy and puerperium after puerperal cerebral venous thrombosis.

In this report we describe an uncomplicated pregnancy and puerperium in a 34 year old patient who had a previous puerperal superior sagittal sinus thrombosis. Heparin was given 3 weeks antepartum and oral anticoagulants 3 months postpartum.

Urine production rate is related to behavioural states in the near term human fetus.

OBJECTIVE: To investigate the relation between hourly fetal urine production rate (HFUPR) and behavioural states 1F and 2F (corresponding to quiet and active sleep, respectively) in normal near term fetuses. DESIGN: An observational study. SETTING: A clinic for antenatal care at a university hospital. SUBJECTS: Nineteen healthy pregnant women examined at 37 to 40 weeks of gestation. MAIN OUTCOME MEASURES: Fetal behavioural states (1F and 2F) were assessed by means of fetal heart rate patterns (FHR A and FHR B). Using real time ultrasonography, HFUPR (ml/h) was estimated during behavioural states 1F and 2F. RESULTS: During behavioural state 1F, HFUPR was significantly higher than during state 2F (P < 0.01). HFUPR falls by 47% from 50.8 +/- 24.4 ml/h in state 1F to 25.7 +/- 15.0 ml/h in state 2F. CONCLUSIONS: During active sleep (state 2F) hourly fetal urine production rate is considerably reduced as compared to quiet sleep (state 1F).