Evaluation of costs associated with fertility treatment leading to a live birth after one fresh transfer: A global perspective.

Considerable costs are associated with infertility treatment, but little evidence is available on the main drivers of treatment costs. This cost analysis investigated key costs for treatment with assisted reproductive technology (ART) and the proportion of costs attributed to the acquisition of recombinant human follicle-stimulating hormone (r-hFSH) alfa originator for one fresh embryo transfer (ET) leading to a live birth in Spain, Norway, the UK, Germany, Denmark, South Korea, Australia, and New Zealand. The total costs for one ART cycle with a fresh ET leading to a live birth varied between countries (€4108-€12,314). Costs for pregnancy and live birth were the major contributors in European countries, and the costs of oocyte retrieval, monitoring during ovarian stimulation, pregnancy, and live birth were the top contributors in the Asia-Pacific countries, included in this analysis. Acquisition costs for r-hFSH alfa originator contributed to only 5%-17% of the total costs of one ART cycle with one fresh ET leading to a live birth.

Potential of a rumen bolus containing 1,25-dihydroxyvitamin D3 glycosides for the prevention of hypocalcaemia in primiparous and multiparous dairy cows.

Periparturient hypocalcaemia is a widespread metabolic disorder in dairy cows. Clinical and subclinical cases occur primarily in multiparous (Multi) cows, but subclinical cases have also been reported in primiparous (Primi) cows. A preventive strategy was investigated by administering the physiologically active vitamin D3 metabolite, 1,25-dihydroxyvitamin D3 (1,25-dihydroxycholecalciferol, 1,25(OH)2D3) as a rumen bolus. The bolus contained tablets of 1,25(OH)2D3 glycoside extract from Solanum glaucophyllum (SGE), releasing SGE over several days. The aim was to study the effect of a bolus containing 0 (C) or 500 µg (SGE) of 1,25(OH)2D3 on 1,25(OH)2D3 and mineral status in periparturient cows up to three weeks into lactation and on colostrum, milk and calves' blood mineral contents. The bolus was administered three to four days prior to expected calving to Primi and Multi cows fed a herbage-based diet (dietary cation-anion difference of +522 mEq/kg DM). One C or SGE bolus was applied to 12 Primi and 12 Multi cows. Blood was regularly sampled (and selected a posteriori for antepartum samples) in regard to the actual calving day (d0), immediately prior to bolus application and at day -2, 0.5, 1, 1.5, 2, 4, 8, 11, 15, 18 and 22. Additional samples included urine (at bolus application, d0.5 and d2), colostrum, milk samples (weekly) and calves' blood (d2). Blood serum 1,25(OH)2D3 increased between d0.5 and d2 in Primi-SGE, but remained unchanged in Primi-C, as did parathyroid hormone (PTH) and Ca in all Primi. Urinary Ca of Primi-SGE was increased on d2, indicating regulation of Ca excess. Three Multi-C cows with confirmed clinical hypocalcaemia needed treatment and thus were excluded from the dataset and replaced. Blood serum 1,25(OH)2D3 and PTH increased while Ca dropped by 40% between d0.5 and d2 in Multi-C, whereas 1,25(OH)2D3, Ca and PTH remained unchanged in Multi-SGE. Blood serum carboxyterminal telopeptide of type I collagen was higher in Primi than in Multi and increased with time, except in Primi-C. Mineral contents in colostrum, milk and blood serum of calves were not influenced to a relevant degree. In conclusion, Primi-C did not, in contrast to Multi-C, develop subclinical hypocalcaemia (<2.0 mmol Ca/l). Prevention of hypocalcaemia with one SGE bolus applied three to four days prior to expected calving was successful in maintaining blood Ca within normal range in Multi over the critical first two days and up to the first three weeks of lactation, without any observed detrimental effects on cows or calves.

Gut microbiota and voluntary alcohol consumption.

Alcohol is part of the usual diet of millions of individuals worldwide. However, not all individuals who drink alcohol experience the same effects, nor will everyone develop an alcohol use disorder. Here we propose that the intestinal microbiota (IMB) helps explain the different consumption patterns of alcohol among individuals. 507 humans participated in this study and alcohol consumption and IMB composition were analyzed. On the other hand, in 80 adult male Wistar rats, behavioral tests, alcohol intoxication, fecal transplantation, administration of antibiotics and collection of fecal samples were performed. For identification and relative quantification of bacterial taxa was used the bacterial 16 S ribosomal RNA gene. In humans, we found that heavy episodic drinking is associated with a specific stool type phenotype (type 1, according to Bristol Stool Scale; p < 0.05) and with an increase in the abundance of Actinobacteria (p < 0.05). Next, using rats, we demonstrate that the transfer of IMB from alcohol-intoxicated animals causes an increase in voluntary alcohol consumption in transplant-recipient animals (p < 0.001). The relative quantification data indicate that the genus Porphyromonas could be associated with the effect on voluntary alcohol consumption. We also show that gut microbiota depletion by antibiotics administration causes a reduction in alcohol consumption (p < 0.001) and altered the relative abundance of relevant phyla such as Firmicutes, Bacteroidetes or Cyanobacteria (p < 0.05), among others. Benjamini-Hochberg false discovery rate (FDR) correction was performed for multiple comparisons. These studies reveal some of the consequences of alcohol on the IMB and provide evidence that manipulation of IMB may alter voluntary alcohol consumption.

Pharmacokinetics of 1,25-dihydroxyvitamin D3 glycosides from Solanum glaucophyllum extract given in a rumen bolus on blood mineral profiles in dry pregnant dairy cows.

Providing tablets of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active metabolite of vitamin D3, in a rumen bolus may be used as prevention for periparturient hypocalcemia in dairy cows. This study investigated the pharmacokinetics of 1,25(OH)2D3 glycosides extracted from Solanum glaucophyllum (SGE) on blood serum 1,25(OH)2D3, Ca, P and Mg response in dry pregnant dairy cows. Boluses contained tablets of SGE which differed in their release properties (rapid release, slow release and combination) and galenics (200 µg uncoated, 300 µg and 500 µg uncoated or coated, 2 × 500 µg uncoated). Nineteen blood samples were collected from 29 cows between 96 h before and 336 h after bolus administration. Blood serum 1,25(OH)2D3, Ca and P increased between 12 h and 120 h, 12 h and 264 h and 24 h and 264 h, respectively. Highest values were reached at 30 h, 72 h and 120 h for 1,25(OH)2D3, Ca and P, respectively. Baseline values were then reached at 216 h for 1,25(OH)2D3 and 336 h for Ca and P. Concentration of Mg decreased between 24 h and 216 h, before reaching values comparable to baseline at 264 h. Highest Ca values were obtained with the combined rapid and slow release properties (500 µg) and there was no effect from coating on pharmacokinetics. In conclusion, the antepartum oral SGE bolus administration may be suitable for the prevention of periparturient hypocalcemia.

The influence of dopaminergic polymorphisms on selective stopping.

Although the genetic influence on global stopping has been extensively investigated, little is known about the genetic contribution to other more complex forms of inhibitory control such as selective stopping. The selectivity of inhibitory control can be assessed by using the stimulus-selective stop-signal task. Notably, recent behavioural and neural evidence indicates that individuals can adopt selective but also non-selective stopping strategies to solve it. This study aimed to investigate for the first time the influence of two relevant dopaminergic polymorphisms (in COMT and DRD2 genes) on stimulus-selective stopping in a sample of 529 adults. Results showed that although none of these polymorphisms (neither individually nor in combination) modulate the latency of the stop process in each strategy (the stop-signal reaction time), the choice of strategy was influenced by their interaction. These results suggest that dopaminergic polymorphisms might influence strategy adoption in selective stopping paradigms, which constitutes a novel finding.

Adult-onset hypothyroidism increases ethanol consumption.

RATIONALE: Only in Europe it can be estimated that more than 20 million of people would be affected by hypothyroidism in some moment of their life. Given that ethanol consumption is so frequent, it would be reasonable to ask what the consequences of ethanol consumption in those individuals affected by hypothyroidism are. OBJECTIVES: To study the interaction between hypothyroidism and ethanol consumption. METHODS: We study ethanol consumption in a rat model of methyl-mercaptoimidazole-induced-adult-onset hypothyroidism and thyroid T4/T3 hormone supplementation. Also, we studied the effects of ethanol on motor activity, memory, and anxiety. RESULTS: We found that hypothyroidism increased the voluntary ethanol consumption and that this was enhanced by thyroid hormone supplementation. Hypothyroidism was associated with motor hyperactivity which was prevented either by T4/T3 supplementation or ethanol. The relationship between hypothyroidism, ethanol, and anxiety was more complex. In an anxiogenic context, hypothyroidism and T4/T3 supplementation would increase immobility, an anxiety-like behavior, while in a less anxiogenic context would decrease rearing, a behavior related to anxiety. Regarding memory, acute ethanol administration did not alter episodic-like memory in hypothyroid rats. Gene expression of enzymes involved in the metabolism of ethanol, i.e., Adh1 and Aldh2, were altered by hypothyroidism and T4/T3 supplementation. CONCLUSIONS: Our results suggest that hypothyroid patients would need personalized attention in terms of ethanol consumption. In addition, they point that it would be useful to embrace the thyroid axis in the study of ethanol addiction, including as a possible therapeutic target for the treatment of alcoholism and its comorbid disorders.

Interactive diffusion-based smoothing and segmentation of volumetric datasets on graphics hardware.

OBJECTIVE: Volume segmentation with concurrent visualization is becoming an increasingly important part of medical diagnostics. This is due to the fact that the immediate visual feedback speeds up evaluation of the segmentation process, hence enhances segmentation quality. Therefore, our aim was to develop a method for volume segmentation and smoothing which achieves interactive performance on standard PCs and is useful in clinical practice (i.e. fast and of high quality). METHODS: Our application is based on seeded region growing and nonlinear isotropic as well as anisotropic diffusion. We use current GPUs (graphics processing units) to speed up the computation of the diffusion process and use hardware-accelerated interactive volume rendering. RESULTS: Using our approach the user can observe the diffusion process in real-time, change parameters interactively and view the result in a high-quality 3D direct volume rendering (DVR). CONCLUSION: The interactive nature of our algorithm and simultaneous visualization improved the usability of our segmentation and smoothing algorithm and proved useful in the clinical workflow. Using our application we were able to speed up the (an)isotropic diffusion process to achieve interactive performance.

Characterization of a novel androgen-sensitive, prostate-specific antigen-producing prostatic carcinoma xenograft: LuCaP 23.

Prostatic carcinoma has proven extremely difficult to establish as cell lines or xenografts. In this article, we describe a new series of prostate cancer xenografts propagated in athymic mice, designated LuCaP 23, developed from prostate metastases harvested at autopsy shortly after death. Tumor from three separate metastatic deposits was developed into three xenograft sublines: two from lymph node metastases (LuCaP 23.1 and 23.8) and one from a liver metastasis (LuCaP 23.12). Fluorescence in situ hybridization analysis confirms the xenografts are human. Histologically, the xenografts are comprised of columnar epithelial cells arranged in a glandular pattern. Tumor doubling times range from 11 to 21 days for the three sublines. The cells secrete large amounts of prostate-specific antigen (PSA) with PSA indices of 1.27, 1.63, and 5.21 ng/ml/mm3 for the mice bearing the LuCaP 23.1, 23.8, and 23.12 sublines, respectively. Following androgen deprivation a temporary decrease in PSA secretion and a decrease in tumor size are noted in most tumors. Eventually, the tumors become androgen independent and resume growth in castrate hosts. The degree of PSA response to castration and time to PSA nadir correlate with time to progression. Thus, unlike most existing models of prostatic carcinoma, this novel xenograft exhibits many phenotypic characteristics of clinical prostatic carcinoma, including androgen sensitivity. These properties make this xenograft an excellent model for future study.

Development of new biotin/streptavidin reagents for pretargeting.

The high affinity of biotin for streptavidin has made this pair of molecules very useful for in vivo applications. To optimize reagents for one potential in vivo application, antibody-based pretargeting of cancer, we have prepared a number of new biotin and streptavidin derivatives. The derivatives developed include new radiolabeled biotin reagents, new protein biotinylation reagents, and new biotin multimers for cross-linking and/or polymerization of streptavidin. We have also modified streptavidin by site-directed mutation and chemical modification to improve its in vivo characteristics, and have developed new reagents for cross-linking antibody fragments with streptavidin. A brief overview of these new reagents is provided.

Cross-reactivity of ten anti-prostate-specific antigen monoclonal antibodies with human glandular kallikrein.

OBJECTIVES: Prostate-specific antigen (PSA) is commonly used as a marker for prostate disease. Prostate epithelium expresses both PSA and human glandular kallikrein (hK2) proteins, which share 80% sequence homology. The immunologic cross-reactivity of these two proteins could potentially interfere with determination of PSA levels in diagnoses of prostate cancer. We set out to determine the extent of this cross-reactivity for a panel of 10 anti-PSA monoclonal antibodies (mAbs). METHODS: Enzyme-linked immunosorbent assay (ELISA), sandwich assays, and western transfer techniques were used to assess the PSA/hK2 cross-reactivity of the anti-PSA mAbs. RESULTS: We did not detect the hK2 protein with any of the 10 anti-PSA mAbs under western transfer conditions. In ELISA experiments, 8 of 10 mAbs exhibited hK2 cross-reactivity under certain conditions. However, no combination of mAbs tested in sandwich assays exhibited a signal in hK2 cross-reactivity experiments greater than 0.1% of the PSA signal. CONCLUSIONS: We have evaluated 10 anti-PSA mAbs and determined that despite the 80% homology between PSA and hK2 proteins, cross-reactivity with hK2 by these antibodies would not significantly affect the determination of PSA levels by means of sandwich assays.

Influence on hormone levels, lipid metabolism and reversibility of endocrinological changes after leuprorelin acetate depot therapy.

The effect of leuprorelin acetate depot on the endocrine system and on lipid metabolism was evaluated in a multicentre, noncomparative study. During the first month of treatment, suppression of serum oestradiol levels to below 20 pg/ml was achieved and luteinising hormone and follicle-stimulating hormone levels were reduced to less than 50% of pretreatment values. A negative influence on lipid metabolism was not recorded. The high-density lipoprotein/low-density lipoprotein ratio did not change during therapy. Resumption of menstruation occurred within a mean period of 3 months after the last leuprorelin acetate depot injection.

Plasmatic haemostasis in gonadotrophin-releasing hormone analogue therapy: effects of leuprorelin acetate depot on coagulatory and fibrinolytic activities.

The plasmatic parameters of coagulatory and fibrinolytic activity were studied in 15 patients with biopsy-proven endometriosis treated with leuprorelin acetate for 6 months. Bleeding time remained constant, indicating the absence of increased bleeding tendencies. The activity of the main inhibitor of the fibrinolytic response, plasminogen activator inhibitor, was reduced by 25%, suggesting an improvement in fibrinolytic reactivity. Plasma levels of fibrin degradation fragments were reduced by 35%, suggesting a marked reduction in the rate of fibrin generation and degradation. A simultaneous reduction in thrombin-antithrombin III complexes and prothrombin fragment 1 + 2 (-10%) indicated that this effect was induced by reduced procoagulant activity, ie, thrombin generation. These data indicate that in gonadotrophin-releasing hormone (Gn-RH) analogue therapy the basal rate of coagulatory processes is reduced. The frequency and extent of fibrin-generating and degrading processes are reduced, suggesting a beneficial effect of Gn-RH analogues on the risk of thromboembolic disease.

Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study.

During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. Treatment results were judged as good and satisfactory in 82% and 11% of cases, respectively. On the basis of this study, it can be concluded that leuprorelin acetate treatment is safe, well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints.

Experience with leuprorelin acetate depot in the treatment of fibroids: a German multicentre study.

Between October 1988 and October 1990 in a noncomparative multicentre study, 114 patients were treated for uterine fibroids with the gonadotrophin-releasing hormone (Gn-RH) agonist, leuprorelin acetate depot. The mean age of the women was 33 years and 55.3% of them had a history of infertility. After confirmation of the diagnosis by ultrasound and/or operation, treatment began between day 1 and 3 of the cycle with leuprorelin acetate depot 3.75 mg subcutaneously. Therapy was carried out for a total of 6 months with one injection every 4 weeks. Treatment was paralleled by measurements of endocrine and metabolic parameters, estimation of myoma and uterine size by ultrasound and self-reporting of the patients of drug-related complaints. Four of the 114 women did not complete the whole treatment, two of them because of general side effects, one because of carcinophobia and unsatisfactory regression of the myoma and the last one for unspecified reasons. During treatment, a mean reduction of the uterine volume of about 67% was observed, in conjunction with shrinkage of the myoma in 92.1% of cases (mean decrease of 56% of the fibroids) with a large interindividual difference. Maximal diminution of uterine and fibroid size had been nearly completely reached within the first 12 weeks of therapy. After 4 weeks of the Gn-RH agonist depot most of the patients had achieved postmenopausal status, which continued throughout the remaining 20 weeks of treatment. In accordance with this finding, the majority of general side effects was due to the hypo-oestrogenic endocrine status. Liver and lipid metabolism was almost unaffected, although increasing calcium and alkaline phosphatase serum levels as well as an increased urinary calcium/creatinine ratio demonstrated an increased metabolic turnover of the bone. Haemoglobin concentrations, however, increased in those cases with fibroid-related anaemia. Thus the slow-release form of leuprorelin acetate is an adjunct to myomectomy especially in those women in whom family planning is not yet completed.

Water-soluble poly-(L-glutamic acid)-Gly-camptothecin conjugates enhance camptothecin stability and efficacy in vivo.

The therapeutic efficacy of 20(s)-camptothecin (CPT) is limited in humans by the instability of the active lactone form due to preferential binding of the carboxylate to serum albumin and by difficulty in formulation. Formation of an ester bond with an amino acid via the hydroxyl group at carbon 20 of CPT stabilizes the lactone. Linking CPT to a high molecular weight (MW) anionic polymer enhances solubility and improves distribution to the tumor through enhanced permeability and retention (EPR effect). Poly-(L-glutamic acid) (PG) is an anionic homo-polymer that can theoretically bind one molecule of a drug via the gamma carboxylic acid of each monomeric subunit. It has been used to make a water-soluble PG-paclitaxel conjugate currently in Phase II clinical trials that contains 37% paclitaxel by weight and is administered in a 10 min infusion without pre-medication. We evaluated the anti-tumor activity of PG conjugates of CPT after a single intraperitoneal injection using subcutaneous murine B-16 melanoma tumor growth as an indicator. Interposition of a glycine (gly) linker allowed CPT loading up to 50% w/w on the polymer. Increasing the PG MW from 33 to 49 kDa enhanced the efficacy without altering the maximum tolerated dose (MTD). In athymic mice bearing ectopic human colon or lung tumors, efficacy was enhanced compared to free camptothecin. Thus, as with paclitaxel, conjugation of CPT to PG enhanced pharmaceutical properties and preclinical efficacy.

Reliability of biographical data, their relations to personality variables and their influence on life-events.

BACKGROUND: First, this study aims to investigate the reliability of biographical and personality data, i.e. analysing the impact of depressive mood on these variables. Second, the influence of early life experience and personality on the reporting of life events was examined. METHODS: Self-reporting questionnaires were administered for a sample of 250 depressive subjects at the beginning, and to assess the influence of depressive mood on the reporting of biographic data at the end of inpatient treatment we used a random sample of 50 subjects out of the 250 patients. RESULTS: Biographical data, unlike personality data, are not significantly influenced by depressive mood and depressive cognition. The number of life-events, and their mean subjective stress, neuroticisms and aim-relatedness are on a direct path strongly influenced by biographical data. That means that the more negatively primary socialisation was reported, the more life-events were communicated, with corresponding increases in the reporting of their subjective stress, and more neuroticism and less aim-relatedness, and vice versa. Neuroticism strongly influences in a positive way, and aim-relatedness negatively influences in a medium way, the number of life-events and their subjective stress. That means the higher neuroticism and the lower aim-relatedness were reported, the more life-events and higher stress were communicated, and vice versa. CONCLUSION: Linear causal processes from mood-independent factors (e.g. biographical factors, vulnerability) may be the beginning of cyclic causal processes, i.e. vicious circles between life-events and mood-dependent factors (e.g. personality variables). LIMITATIONS: According to the design of the investigation there is no differentiation possible between personality and depression. CLINICAL RELEVANCE: To avoid vicious circles between life-events and mood-dependent factors, preventive psychotherapeutic intervention seems to be necessary to avoid the genesis of harmful life-events.

The evaluation of life event data.

Data from three life event studies are compared. The interviews covered events that occurred within a period of 2 years before interview. The same inventory was used in each of the studies. Samples were drawn from depressives, myocardial infarction patients and an industrial worker population. The patient groups were interviewed twice within 4 weeks. Fewer than 50% of the total number of events reported in the retests were recorded twice. For events reported in both interviews the correlations of subjective appraisals were only moderate. There is considerable fall-off for reports of events occurring more than 6 months before interview. It was expected that the severest events would have the lowest, and the least severe ones the highest frequencies. Instead, inappropriate labels of the rating scales led to clusterings of severity ratings at their extreme points. Numbers of events and severity ratings were positively correlated with measures of depression.

A randomized controlled double-blind study of the effects on hemostasis of two progestogen-only pills containing 75 microgram desogestrel or 30 microgram levonorgestrel.

The effects of two progestogen-only pills containing either 75 microgram desogestrel (DSG) or 30 microgram levonorgestrel (LNG) on hemostasis were investigated in a double-blind, randomized, controlled study of seven treatment cycles in 78 healthy women. DSG reduced factor VII activity (p < 0.05) and prothrombin fragment 1+2 (p < 0.05) and increased protein S (p < 0.001). LNG reduced factor VII activity (p < 0.01) and plasminogen activity (p < 0.01) and increased tissue-plasminogen activator (t-PA) (p < 0.05). At the end of the post-treatment cycle with DSG, protein S (p < 0.01) and t-PA (p < 0.05) were increased and plasminogen activity was decreased (p < 0.05), whereas with LNG, t-PA was increased (p < 0.001) and prothrombin fragment 1+2 (p < 0.05) and plasminogen activity (p < 0.001) were decreased. Between-group comparisons revealed higher values for DSG regarding the anticoagulatory parameter protein S at cycle 7 (p < 0.01) and post-treatment assessments (p < 0.05), and the fibrinolytic parameter plasmin-antiplasmin complex was higher with DSG at cycle 7 (p < 0.05) and at post-treatment (p < 0.05). Both preparations had comparable and potentially favorable effects of hemostasis, and may offer suitable hormonal contraception to women with a personal or family history of venous thromboembolic diseases.

Experimental models and methods in antibody targeting of renal cell carcinoma.

Metastatic renal cell carcinoma (RCC) is incurable and there are few treatment options that assure even a short prolongation in survival. It is the most common malignancy of the adult kidney and accounts for approximately 12,000 deaths per year (1). Due to a lack of diagnostic markers for early detection and the infrequency of notable symptoms early in the disease process, about one third of patients present with known metastatic disease. However, the staging of RCC is an inaccurate science and in 40% of those patients where a nephrectomy is the treatment choice for presumed organ-confined disease, metastases become evident within about 1 yr (2). For reasons that are poorly understood, metastatic RCC has remained relatively resistant to chemotherapy, biological response modifiers and cellular immunotherapy-although, glimpses of encouragement have appeared in numerous studies. These are discussed in great depth throughout the accompanying chapters.

Coping with refractory epilepsy.

We investigated the coping behaviour and its correlation with demographic and illness-related data, depression, locus of control and psychosocial adaptation in 40 patients with intractable epilepsy with primarily or secondarily generalized tonic-clonic seizures. Three standardized self-reporting questionnaires were applied, which are the Freiburg Questionnaire of Coping with Illness (FKV), the von Zerssen Depression Scale (D-S), and the IPC-questionnaire measuring generalized locus of control beliefs; the Social Interview Schedule (SIS), a semi-structured interview, was used to measure the psychosocial adaptation. Active, problem-focused and compliance strategies were predominantly used and regarded as most helpful. Hence, the epileptic patients use similar coping patterns reported in patients with other non life-threatening chronic diseases. The level of depression was moderate and in the range of other chronic somatic diseases. The use of coping patterns, which are regarded as maladaptive, was correlated with distinct depression, a small degree of internal locus of control beliefs and poor psychosocial adaption. These results indicate the possibility to improve psychosocial adjustment by supporting effective strategies.