[The revised version of the Y-BOCS: responsivity and other psychometric properties]. / De herziene versie van de Y-BOCS: responsiviteit en andere psychometrische eigenschappen.

BACKGROUND: The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a widely used semi structured clinician-rated interview to assess the presence and severity of obsessive-compulsive disorder (OCD). The scale is revised (Y-BOCS-II) to overcome several psychometric limitations, for example by extending the scoring for better discrimination within higher severity levels. AIM: To examine the responsiveness and other psychometric properties of the Y-BOCS-II in a Dutch clinical sample. METHOD: The Y-BOCS-II was translated into Dutch (Y-BOCS-II) and administered to 110 patients seeking therapy for OCD. This was done twice, before and after treatment. The original Y-BOCS was simultaneously rated. Self-report measures regarding depression, symptom severity and OCD symptoms were assessed. RESULTS: The Y-BOCS-II had a good internal consistency (Cronbach’s α = 0.84), test-retest (ICC = 0.81) and inter-rater reliability (ICC = 0.94). The construct validity proved to be modest to good. The responsiveness over time was in favour of the Y-BOCS-II, compared with the YBOCS-I, particularly in the severely affected OCD patients. CONCLUSION: The Y-BOCS-II severity scale is a reliable and valid instrument for accurately assessing the severity of OCD symptoms and for measuring treatment-induced change. This second version also has clinical and psychometric advantages over the YBOCS-I. When these findings are sufficiently replicated, use of the YBOCS-II as the new common standard seems recommendable.

Culture of 3D bioprinted bone constructs requires an increased fluid dynamic stimulation.

In vitro flow-induced mechanical stimulation of developing bone tissue constructs has been shown to favor mineral deposition in scaffolds seeded with cells directly exposed to the fluid flow. However, the effect of fluid dynamic parameters, such as shear stress (SS), within 3D bioprinted constructs is still unclear. Thus, this study aimed at correlating the SS levels and the mineral deposition in 3D bioprinted constructs, evaluating the possible dampening effect of the hydrogel. Human mesenchymal stem cells (hMSCs) were embedded in 3D bioprinted porous structures made of alginate and gelatin. 3D bioprinted constructs were cultured in an osteogenic medium assessing the influence of different flow rates (0, 0.7 and 7 ml/min) on calcium and collagen deposition through histology, and bone volume (BV) through micro-computed tomography. Uniform distribution of calcium and collagen was observed in all groups. Nevertheless, BV significantly increased in perfused groups as compared to static control, ranging from 0.35±0.28 mm3, 11.90±8.74 mm3 and 25.81±5.02 mm3 at week 3 to 2.28±0.78 mm3, 22.55±2.45 mm3 and 46.05±5.95 mm3 at week 6 in static, 0.7 and 7 ml/min groups, respectively. SS values on construct fibers in the range 10-100 mPa in 7 ml/min samples were twice as high as those in 0.7 ml/min samples showing the same trend of BV. The obtained results suggest that it is necessary to enhance the flow-induced mechanical stimulation of cell-embedding hydrogels to increase the amount of mineral deposited by hMSCs, compared to what is generally reported for the development of in vitro bone constructs. STATEMENT OF SIGNIFICANCE: In this study, we evaluated for the first time how the hydrogel structure dampens the effect of flow-induced mechanical stimulation during the culture of 3D bioprinted bone tissue constructs. By combining computational and experimental techniques we demonstrated that those shear stress thresholds generally considered for culturing cells seeded on scaffold surface, are no longer applicable when cells are embedded in 3D bioprinted constructs. Significantly, more bone volume was formed in constructs exposed to shear stress values generally considered as detrimental than in constructs exposed shear stress values generally considered as beneficial after 3 weeks and 6 weeks of dynamic culture using a perfusion bioreactor.

Sustained conduction of vasomotor responses in rat mesenteric arteries in a two-compartment in vitro set-up.

AIM: Conduction of vasomotor responses may contribute to long-term regulation of resistance artery function and structure. Most previous studies have addressed conduction of vasoactivity only during very brief stimulations. We developed a novel set-up that allows the local pharmacological stimulation of arteries in vitro for extended periods of time and studied the conduction of vasomotor responses in rat mesenteric arteries under those conditions. METHODS: The new in vitro set-up was based on the pressure myograph. The superfusion chamber was divided halfway along the vessel into two compartments, allowing an independent superfusion of the arterial segment in each compartment. Local and remote cumulative concentration-response curves were obtained for a range of vasoactive agents. Additional experiments were performed with the gap junction inhibitor 18ß-glycyrrhetinic acid and in absence of the endothelium. RESULTS: Phenylephrine-induced constriction and acetylcholine-induced dilation were conducted over a measured distance up to 2.84 mm, and this conduction was maintained for 5 minutes. Conduction of acetylcholine-induced dilation was inhibited by 18ß-glycyrrhetinic acid, and conduction of phenylephrine-induced constriction was abolished in absence of the endothelium. Constriction in response to high K+ was not conducted. Absence of remote stimulation dampened the local response to phenylephrine. CONCLUSION: This study demonstrates maintained conduction of vasoactive responses to physiological agonists in rat mesenteric small arteries likely via gap junctions and endothelial cells, providing a possible mechanism for the sustained functional and structural control of arterial networks.

Does activation of midbrain dopamine neurons promote or reduce feeding?

BACKGROUND: Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced DA activity. On the other hand, psychostimulant drugs that increase DA signalling suppress food intake. This poses the questions of how endogenous DA neuronal activity regulates feeding, and whether enhancing DA neuronal activity would either promote or reduce food intake. METHODS: Here, we used designer receptors exclusively activated by designer drugs (DREADD) technology to determine the effects of enhancing DA neuronal activity on feeding behaviour. We chemogenetically activated selective midbrain DA neuronal subpopulations and assessed the effects on feeding microstructure in rats. RESULTS: Treatment with the psychostimulant drug amphetamine or the selective DA reuptake inhibitor GBR 12909 significantly suppressed food intake. Selective chemogenetic activation of DA neurons in the ventral tegmental area (VTA) was found to reduce meal size, but had less impact on total food intake. Targeting distinct VTA neuronal pathways revealed that specific activation of the mesolimbic pathway towards nucleus accumbens (NAc) resulted in smaller and shorter meals. In addition, the meal frequency was increased, rendering total food intake unaffected. The disrupted feeding patterns following activation of VTA DA neurons or VTA to NAc projection neurons were accompanied by locomotor hyperactivity. Activation of VTA neurons projecting towards prefrontal cortex or amygdala, or of DA neurons in the substantia nigra, did not affect feeding behaviour. CONCLUSIONS: Chemogenetic activation of VTA DA neurons or VTA to NAc pathway disrupts feeding patterns. Increased activity of mesolimbic DA neurons appears to both promote and reduce food intake, by facilitating both the initiation and cessation of feeding behaviour.

d-cycloserine addition to exposure sessions in the treatment of patients with obsessive-compulsive disorder.

BACKGROUND: Preliminary studies have shown that the addition of the partial NMDA-agonist d-cycloserine (DCS) might be promising in enhancing the results of exposure therapy in obsessive-compulsive disorder (OCD). We examined the effect of DCS addition to exposure therapy in a somewhat larger sample of OCD patients with special attention to subgroups, because of the heterogeneity of OCD. METHODS: A randomized, double-blind, placebo controlled trial was conducted in 39 patients with OCD. Patients received 6 guided exposure sessions, once a week. One hour before each session 125mg DCS or placebo was administered. RESULTS: Scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) declined more in the DCS group than in the placebo group, but the difference did not reach statistical significance (P=0.076, partial η2=0.13). Response percentages also did not differ between the DCS and the placebo group (37% and 15% respectively). In the 'cleaning/contamination' subgroup a significant effect was found in favour of DCS (P=0.033, partial η2=0.297). CONCLUSIONS: The results of this study did not support the application of DCS to exposure therapy in OCD. Some specific aspects need further investigation: efficacy of DCS in a larger 'cleaning/contamination' (sub-)group, DCS addition only after successful sessions, interaction with antidepressants.

Interaction effects on number fluctuations in a Bose-Einstein condensate of light.

We investigate the effect of interactions on condensate-number fluctuations in Bose-Einstein condensates. For a contact interaction we variationally obtain the equilibrium probability distribution for the number of particles in the condensate. To facilitate comparison with experiment, we also calculate the zero-time delay autocorrelation function g((2))(0) for different strengths of the interaction. Finally, we focus on the case of a condensate of photons and find good agreement with recent experiments.

Registration of structurally dissimilar images in MRI-based brachytherapy.

A serious challenge in image registration is the accurate alignment of two images in which a certain structure is present in only one of the two. Such topological changes are problematic for conventional non-rigid registration algorithms. We propose to incorporate in a conventional free-form registration framework a geometrical penalty term that minimizes the volume of the missing structure in one image. We demonstrate our method on cervical MR images for brachytherapy. The intrapatient registration problem involves one image in which a therapy applicator is present and one in which it is not. By including the penalty term, a substantial improvement in the surface distance to the gold standard anatomical position and the residual volume of the applicator void are obtained. Registration of neighboring structures, i.e. the rectum and the bladder is generally improved as well, albeit to a lesser degree.

Dual implantation of a radio-telemeter and vascular access port allows repeated hemodynamic and pharmacological measures in conscious lean and obese rats.

Expansion of physiological knowledge increasingly requires examination of processes in the normal, conscious state. The current study describes a novel approach combining surgical implantation of radio-telemeters with vascular access ports (VAPs) to allow repeated hemodynamic and pharmacological measures in conscious rats. Dual implantation was conducted on 16-week-old male lean and obese Zucker rats. Continued viability one month after surgery was observed in 67% of lean and 44% of obese animals, giving an overall 54% completion rate. Over the five-week measurement period, reliable and reproducible basal mean arterial pressure and heart rate measures were observed. VAP patency and receptor-independent vascular reactivity were confirmed by consistent hemodynamic responses to sodium nitroprusside (6.25 µg/kg). Acutely, minimal hemodynamic responses to repeated bolus administration of 0.2 mL saline indicated no significant effect of increased blood volume or administration stress, making repeated acute measures viable. Similarly, repeated administration of the ß-adrenoceptor agonist dobutamine (30 µg/kg) at 10 min intervals resulted in reproducible hemodynamic changes in both lean and obese animals. Therefore, our study demonstrates that this new approach is viable for the acute and chronic assessment of hemodynamic and pharmacological responses in both lean and obese conscious rats. This technique reduces the demand for animal numbers and allows hemodynamic measures with minimal disruption to animals' welfare, while providing reliable and reproducible results over several weeks. In conclusion, dual implantation of a radio-telemeter and VAP introduces a valuable technique for undertaking comprehensive studies involving repeated pharmacological tests in conscious animals to address important physiological questions.

Sequential bilateral cochlear implantation in children: parents' perspective and device use.

OBJECTIVE: The purpose of this study was (1) to measure parental expectations before surgery of a sequentially placed second cochlear implant and compare these results with parental observations postoperatively and (2) to measure device use of the second cochlear implant and compare to unilateral implant use. METHODS: Thirty prelingually deaf children with a unilateral cochlear implant (mean age at first implant 1.8 years) received a second implant at a mean age of 5.3 years. To measure parental expectations and observations, parents completed the Parents' Perspective before surgery of the second implant and after 12 and 24 months. The questionnaire included 1 additional question on sound localization. Device use of both the first and second implants was assessed retrospectively after 6, 12 and 24 months of implant use. Device use of the study group was also compared to a reference group of 30 unilateral implant users matched for age at second implantation. RESULTS: Parental expectations with regard to sound localization were significantly higher than the observed changes within the first year of bilateral implant use. The observed changes in communication, listening to speech without lipreading, and speech and language skills met or surpassed parental expectations. Irrespective of age at second implantation, the second implant was significantly less worn than the first implant. No significant difference was observed between the use of the second implant of the study group and device use of the reference group. Second implant use was significantly correlated with the difference in speech recognition between the 2 implants alone. CONCLUSIONS: Preoperative parental expectations were too high with regard to the observed localization skills within the first year of bilateral implant use. The study showed that several of these sequentially implanted children had more difficulties in wearing the second implant than in wearing the first implant during the rehabilitation period. The present results suggest that this is caused by the dominant first implant performance. Such data are of high importance in order to provide parents with realistic counseling on what they can expect from sequential bilateral cochlear implantation.

TU-E-213CD-01: Image Guided Adaptive Brachytherapy for Cervical Cancer.

Image-guidance plays an important role in modern radiation therapy, predominantly in external beam planning and delivery. In contrast, brachytherapy is still largely based on systems originally developed in the early 20th century. In recent years, with the advent of high/pulsed dose rate (HDR/PDR) afterloading technology, advanced treatment planning systems and CT and MRI compatible applicators, image-guided adaptive brachytherapy treatments are now achievable. With image guidance, the target can be delineated more precisely, resulting in delivering more controlled doses of radiation to the target while sparing surrounding healthy tissue. GEC-ESTRO guidelines are crucial for implementing robust and standardized image guided adaptive brachytherapy (IGABT). They rely on MRI-guided planning for cervical cancer. MRI can be performed for each brachytherapy (BT) fraction to adaptively plan and deliver the desired radiation dose with less toxicity to surrounding tissues. MR imaging has its advantages, but also challenges and limitations (image artifacts and distortion related to magnetic nonlinearity, MR sequence selection, accuracy of 3D applicator reconstruction) that need addressed. Moreover, MRI technology is not readily available in most Radiation Oncology departments, making its implementation hard. In such settings, CT or US-based planning can be used despite lacking the desired soft tissue resolution to accurately depict the target. Hybrid approaches have been proposed, where a first BT fraction is planed based on MRI, and subsequent fractions are performed with CT-guidance. Moreover, new intracavitary/interstitial applicators are becoming available and data from centers using existent applicators is maturing. Regardless of the type of adaptive image guided and applicators used, there are still ongoing debates regarding the prescription, the relevance of point A dose, treatment planning in general, and the use of inverse planning in particular, role of model-based dose calculation algorithms, adaptive strategies, intrafraction variability, in-vivo dosimetry, dose summation with external beam treatments, to mention just some of the challenges raised by implementing this treatment technique. This symposium is proposing to address all of these issues and update the community at large on the status of image guided adaptive brachytherapy for cervical cancer. LEARNING OBJECTIVES: 1. To discuss the physics perspective of role of IGABT in management of cervical cancer. 2. To compare IGABT approaches: MRI, CT, US, and Hybrid 3. To present the advantages, challenges, and limitations of MRI for IGABT. 4. To discuss hot topics in IGABT including planning strategies, role of model-based dose calculation algorithms, new applicators, dose specification.

[Diagnosis of epilepsy complicated by panic disorder and a non-specific reaction to a SSRI]. / Diagnose epilepsie bemoeilijkt door paniekstoornis met aspecifieke reactie op SSRI.

Differentiating panic disorder form epilepsy can be a difficult task. In this case study the task was made more complicated because the patient was being treated with the selective serotonin reuptake inhibitor (SSRI) citalopram which evoked a partial response, thereby delaying the diagnosis of epilepsy. Research results demonstrate that ssris can have not only an antidepressive and calming effect, they can also have an anticonvulsant effect. However, there are also signs that, as this case illustrates, in the long term the anticonvulsant effect can actually convert to proconvulsant effect.

Should a hearing aid in the contralateral ear be recommended for children with a unilateral cochlear implant?

OBJECTIVES: To predict bimodal benefit before cochlear implantation, we compared the performances of participants with bimodal fitting and with a cochlear implant alone on speech perception tests. METHODS: Twenty-two children with a cochlear implant in one ear and a hearing aid in the other (bimodal fitting) were included. Several aided and unaided average hearing thresholds and the aided word recognition score of the hearing aid ear were related to the bimodal benefit on a phoneme recognition test in quiet and in noise. Results with bimodal fitting were compared to results with the cochlear implant alone on a phoneme recognition test in quiet and in noise. RESULTS: No relationship was found between any of the hearing thresholds or the aided phoneme recognition score of the hearing aid ear and the bimodal benefit on the phoneme recognition tests. At the group level, the bimodal scores on the phoneme recognition tests in quiet and in noise were significantly better than the scores with the cochlear implant alone. CONCLUSIONS: Preoperatively available audiometric parameters are not reliable predictors of bimodal benefit in candidates for cochlear implantation. Children with unilateral implants benefit from bimodal fitting on speech tests. This improvement in performance warrants the recommendation of bimodal fitting even when bimodal benefit cannot be predicted.

Radiologist experience and CT examination quality determine metastasis detection in patients with esophageal or gastric cardia cancer.

We aimed to separate the influence of radiologist experience from that of CT quality in the evaluation of CT examinations of patients with esophageal or gastric cardia cancer. Two radiologists from referral centers ('expert radiologists') and six radiologists from regional non-referral centers ('non-expert radiologists') performed 240 evaluations of 72 CT examinations of patients diagnosed with esophageal or gastric cardia cancer between 1994 and 2003. We used conditional logistic regression analysis to calculate odds ratios (OR) for the likelihood of a correct diagnosis. Expert radiologists made a correct diagnosis of the presence or absence of distant metastases according to the gold standard almost three times more frequently (OR 2.9; 95% CI 1.4-6.3) than non-expert radiologists. For the subgroup of CT examinations showing distant metastases, a statistically significant correlation (OR 3.5; 95% CI 1.4-9.1) was found between CT quality as judged by the radiologists and a correct diagnosis. Both radiologist experience and quality of the CT examination play a role in the detection of distant metastases in esophageal or gastric cardia cancer patients. Therefore, we suggest that staging procedures for esophageal and gastric cardia cancer should preferably be performed in centers with technically advanced equipment and experienced radiologists.

On verification of hyperthermia treatment planning for cervical carcinoma patients.

PURPOSE: The aim of this study was to verify hyperthermia treatment planning calculations by means of measurements performed during hyperthermia treatments. The calculated specific absorption rate (SAR(calc)) was compared with clinically measured SAR values, during 11 treatments in seven cervical carcinoma patients. METHODS: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide system. Temperatures were measured using multisensor thermocouple probes. One invasive thermometry catheter in the cervical tumour and two non-invasive catheters in the vagina were used. For optimal tissue contact and fixation of the catheters, a gynaecological tampon was inserted, moisturized with distilled water (4 treatments), or saline (6 treatments) for better thermal contact. During one treatment no tampon was used. At the start of treatment the temperature rise (DeltaT(meas)) after a short power pulse was measured, which is proportional to SAR(meas). The SAR(calc) along the catheter tracks was extracted from the calculated SAR distribution and compared with the DeltaT(meas)-profiles. RESULTS: The correlation between DeltaT(meas) and SAR(calc) was on average R = 0.56 +/- 0.28, but appeared highly dependent on the wetness of the tampon (preferably with saline) and the tissue contact of the catheters. Correlations were strong (R approximately 0.85-0.93) when thermal contact was good, but much weaker (R approximately 0.14-0.48) for cases with poor thermal contact. CONCLUSION: Good correlations between measurements and calculations were found when tissue contact of the catheters was good. The main difficulties for accurate verification were of clinical nature, arising from improper use of the gynaecological tampon. Poor thermal contact between thermocouples and tissue caused measurement artefacts that were difficult to correlate with calculations.

[...with psychotic features? An investigation into the delusional nature of convictions in patients with non-psychotic disorders]. / ...met psychotische kenmerken? Een onderzoek naar het waanachtige karakter van overtuigingen buiten het psychosencluster.

BACKGROUND: In certain disorders the boundaries between thoughts, obsessions, overvalued ideas and delusions are not always clearly delineated. AIM: To find out whether delusions can be distinguished from the convictions that often accompany anorexia nervosa, obsessive compulsive disorder (OCD), body dysmorphic disorder (BDD) and hypochondriasis, all of which apparently may involve impaired reality testing. METHOD: The literature was reviewed with the help of PubMed, using as key words 'delusions' in combination with 'hypochodriasis', 'anorexia nervosa', 'body image', 'obsessive compulsive disorder' or 'body dysmorphic disorder'. We also searched the Tijdschrift voor Psychiatrie and references of the literature we used. RESULTS: A number of disorders can probably be classified on a spectrum ranging from non-psychotic to psychotic. For instance, OCD, hypochondriasis, BDD and to a lesser degree anorexia nervosa can all be particularized as 'with good insight', 'with poor insight' or 'with psychotic features'. CONCLUSION: Current practice in DSM-IV is to classify OCD, BDD or hypochondriasis and a delusional disorder as separate entities; this way of classifying seems to be an artefact. Our findings indicate that a dimensional system of classifying psychotic systems is preferable to a categorised system.

Ovum pick up and in vitro production in the bovine after use in several generations: a 2005 status.

The first In Vitro Produced (IVP) calf was born in 1981 and the non-surgical Ovum Pick Up (OPU) technique for the bovine was adapted from the human in 1987. Since then, considerable research has been aimed at improving both technologies in the bovine. Both OPU and IVP can now be seen as mature technologies. It can be estimated that more than 200,000 IVP calves have been born world wide to date, and when the two technologies are combined they are capable of producing over 50 calves per donor cow per year, albeit with a large variation between donors. Not many new breakthroughs are expected for OPU. For IVP however, automation and miniaturization as well as a greater understanding of the embryo through the application of gene based technologies such as micro-arrays, may provide an in vitro environment that is more in vivo-like than traditional micro drop/well systems. This improved environment should result in higher embryo developmental rates as well as improved quality and welfare of subsequent offspring. The application of OPU/IVP has progressed from treating infertile high genetic multiple ovulation and embryo transfer (MOET) cows in commercial situations to enhancing breeding scheme designs. With the bovine genome being rapidly sequenced and bovine genes for traits of economic interest becoming available in the coming years, OPU/IVP will prove invaluable in rapidly multiplying rare genes or Quantitative Trait Loci (QTL) of high value. In due course, it is anticipated that Marker Assisted Selection or Gene Assisted Selection (MAS/GAS) schemes will be more widely implemented. In addition, OPU, and particularly IVP, provide the basis for more advanced technologies such as cloning and transgenics. This paper is dedicated to celebrate and recognize the significant contributions made by Theo Kruip (1939-2003) to the wide area of bovine OPU and IVP.

Plasma concentrations of bovine pregnancy-associated glycoprotein (bPAG) do not differ during the first 119 days between ongoing pregnancies derived by transfer of in vivo and in vitro produced embryos.

Calves derived from IVP embryos may suffer from the large offspring syndrome that has been related to effects of in vitro culture on the intrinsic quality of the embryo. Limited information is available on the role of the placenta in such cases. In this study, bovine pregnancy-associated glycoprotein (bPAG) was used as a marker to test whether placental function is influenced by the route of embryo production. Therefore, from day 7 until day 119 of ongoing gestations, resulting from transfer of MOET (n = 53), IVP-co-culture (n = 21) and IVP-SOF (n = 38) embryos, bPAG levels were compared in peripheral plasma of recipients. Plasma progesterone levels were compared as well. From day 25 of gestation onwards, bPAG could be detected in all recipients and the levels were significantly influenced by the day of gestation. Although IVP calves were significantly heavier than the in vivo produced calves, this difference was not reflected in the bPAG profiles of the embryo production groups. Yet, the mean bPAG level of the three last sampling moments (days 105-119) tended to be positively related to the birth weight of the calves, irrespective of the embryo production technique. Progesterone concentrations were not influenced by route of embryo production, but were significantly affected by parity of the recipient and day of gestation.

Experimental comparison of ketamine with a combination of ketamine, butorphanol and medetomidine for general anaesthesia of the Eurasian badger (Meles meles L.).

The refinement of anaesthetic regimes is central to improving the welfare of captured wildlife. The Eurasian badger (Meles meles) has been the subject of an intensive long-term ecological and epidemiological study at Woodchester Park, Gloucestershire, England. During routine trapping operations (June 21st, 2000-January 23rd, 2001) an experimental trial was conducted on 89 badgers to compare the physiological effects of anaesthesia using ketamine hydrochloride alone, and in conjunction with medetomidine hydrochloride and butorphanol tartrate. The mixture induced a significantly longer period of anaesthesia, and either substantially reduced or eliminated the adverse effects associated with ketamine anaesthesia (e.g., excessive salivation, bouts of sneezing, rough recoveries, and muscle rigidity). In a sub-sample of badgers given the mixture, anaesthesia was reversed using atipamezole hydrochloride. Under ketamine anaesthesia, heart rates were initially significantly higher and respiration rates were consistently higher, than in badgers given the mixture. In all badgers heart rates declined and respiration rates increased during anaesthesia, but the rate of change was greatest in animals given only ketamine. Overall, the mixture provided a more balanced anaesthesia characterised by muscle relaxation and complete unconsciousness.

Fetometry and fetal heart rates between Day 35 and 108 in bovine pregnancies resulting from transfer of either MOET, IVP-co-culture or IVP-SOF embryos.

The Large Offspring Syndrome has frequently been reported for in vitro produced calves. The objective of this study was to determine whether any differences in body dimensions (biparietal diameter of the cranium (BPD), cross-section of the abdomen at the insertion of the umbilical cord (CAU)) and heart rate (FHR) can be detected during the first 108 days of gestation between bovine foetuses derived from different methods of embryo production. Three groups of pregnancies with calvings at term resulted from non-surgical transfers of three types of embryos: recipients carrying an embryo obtained by standard MOET procedures (n = 25); recipients carrying an embryo produced in vitro from OPU-derived oocytes, using co-culture-medium (n = 14) or SOF-medium (n = 22). Transrectal ultrasonographic examinations were performed weekly. Ultrasound images were recorded and during off-line analysis FHR, BPD and CAU were determined. For each foetus a curve was fitted and the estimates on fixed time intervals were used as dependent variables in an analysis of variance to detect differences between the three pregnancy groups. Neither gestation length nor birth weight differed significantly between the three pregnancy groups, nor could any differences with respect to BPD, CAU or FHR be detected between Days 35 and 108 of gestation. It is concluded that no differences exist between the early development of bovine foetuses, derived from MOET, IVP-co-culture or IVP-SOF embryos, and resulting in calves with normal birth weights.

Radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate cancer: preliminary results.

OBJECTIVE: To report an interim clinical evaluation of combined external beam irradiation (EBRT) and interstitial or regional hyperthermia in the treatment of locally advanced prostate cancer. PATIENTS AND METHODS: From 1997 to 2001, 26 patients with T3-4/NX/0M0 prostate carcinoma were treated with a combination of conformal EBRT and hyperthermia. Fourteen patients received five weekly regional hyperthermia treatments within an optimization (phase II) study, using the coaxial transverse electrical magnetic system. Twelve patients received one interstitial hyperthermia treatment within a feasibility study (phase I), using the multi-electrode current source system. Irradiation was delivered using a conformal three-field technique, administering 70 Gy in 2-Gy fractions in 7 weeks. RESULTS: The mean initial prostate-specific antigen level was 26 ng/mL. Three patients had a T4 and 23 a T3 tumour; the tumours were classified as well (four), moderately (16) and poorly (six) differentiated. The mean follow-up was 36 months. In the combined treatments there was no toxicity of more than grade 2. In regional hyperthermia the mean index temperature (T90 and T50, i.e. exceeded by 90% and 50% of the measurements) was 40.2 degrees C and 40.8 degrees C, and for interstitial hyperthermia 39.4 degrees C and 41.8 degrees C, respectively. All patients survived; seven patients had a biochemical relapse (27%), three in the regional and four in the interstitial group. The actuarial probability of freedom from biochemical relapse was 70% at 36 months for all patients together, 79% for regional and 57% for interstitial. No factors were found that could be used to predict relapse. CONCLUSIONS: The clinical outcome in these patients with advanced localized prostate cancer seems to compare favourably with most series using irradiation alone, and the treatment caused no severe complications.