Assessment of male fertility in patients with Hodgkin's lymphoma treated in the German Hodgkin Study Group (GHSG) clinical trials.

BACKGROUND: Infertility is one of the most significant side-effects in long-term survivors of successfully treated Hodgkin's lymphoma (HL). PATIENTS AND METHODS: The fertility status was assessed in male HL patients enrolled into trials of the German Hodgkin Study Group from 1988 to 2003. RESULTS: In pre-treatment analysis (n = 202), 20% of patients had normozoospermia, 11% azoospermia and 69% had other dyspermia. In post-treatment analysis (n = 112), 64% of patients had azoospermia, 30% other dyspermia and 6% normozoospermia (P < 0.001). Azoospermia was observed in 90% of patients treated with chemotherapy alone, 67% of those treated with combined modality and 11% of those treated with radiotherapy alone (P < 0.001). Azoospermia was more frequent after 4x cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, dacarbazine (COPP/ABVD) (91%), 8x bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) baseline (93%) and 8x BEACOPP escalated (87%) compared with 2x COPP/ABVD (56%; P = 0.003). There was a statistically significant difference in post-treatment follicle-stimulating hormone (FSH) levels between patients with azoospermia and those with preserved spermatogenesis (P = 0.001). CONCLUSIONS: Depending on the treatment received, male HL patients are at high risk of infertility after treatment. FSH might be used as surrogate parameter for male fertility in future studies.

14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced-stage Hodgkin's lymphoma: results of a pilot study of the German Hodgkin's Lymphoma Study Group.

PURPOSE: This multicenter pilot study assessed the feasibility and efficacy of a time-intensified bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen given in 14-day intervals (BEACOPP-14) with granulocyte colony-stimulating factor (G-CSF) support in advanced Hodgkin's lymphoma. PATIENTS AND METHODS: From July 1997 until March 2000, 94 patients with Hodgkin's lymphoma stage IIB, III, and IV were scheduled to receive eight cycles of BEACOPP-14. Consolidation radiotherapy was administered to regions with initial bulky disease or residual tumor after chemotherapy. RESULTS: All patients were assessable for toxicity and treatment outcome. Eighty-six patients received the planned eight cycles of BEACOPP-14. Consolidation radiotherapy was given in 66 patients. Chemotherapy could generally be administered on schedule. Dose reductions varied among drugs but were generally low. Acute toxicity was moderate, with World Health Organization grade 3/4 leukopenia in 75%, thrombocytopenia in 23%, anemia in 65%, and infection in 12% of patients. A total of 88 patients (94%) achieved a complete remission. Four patients had progressive disease. At a median observation time of 34 months, five patients have relapsed, one patient developed a secondary non-Hodgkin's lymphoma, and three deaths were documented. The overall survival and freedom from treatment failure rates at 34 months were 97% (95% confidence interval [CI], 93% to 100%) and 90% (95% CI, 84% to 97%), respectively. CONCLUSION: Acceleration of the BEACOPP baseline regimen by shortening cycle duration with G-CSF support is feasible and effective with moderate acute toxicity. On the basis of these results, the German Hodgkin's Lymphoma Study Group will compare the BEACOPP-14 regimen with BEACOPP-21 escalated in a prospective multicenter randomized trial.

Transthoracic echocardiography using second harmonic imaging: diagnostic alternative to transesophageal echocardiography for the detection of atrial right to left shunt in patients with cerebral embolic events.

OBJECTIVES: We sought to evaluate whether transthoracic contrast echocardiography using second harmonic imaging (SHI) is a diagnostic alternative to transesophageal contrast echocardiography (TEE) for the detection of atrial right to left shunt. BACKGROUND: Paradoxic embolism is considered to be the major cause of cerebral ischemic events in young patients. Contrast echocardiography using TEE has proven to be superior to transthoracic echocardiography (TTE) for the detection of atrial shunting, SHI is a new imaging modality that enhances the visualization of echocardiographic contrast agents. METHODS: We evaluated 111 patients with an ischemic cerebral embolic event for the presence of atrial right to left shunt using an intravenous (IV) contrast agent in combination with three different echocardiographic imaging modalities: 1) TTE using fundamental imaging (FI); 2) TTE using SHI; and 3) TEE. The severity of atrial shunting and the duration of contrast visibility within the left heart chambers were evaluated for each imaging modality. Image quality was assessed separately for each modality by semiquantitative scoring (0 = poor to 3 = excellent). Presence of atrial right to left shunt was defined as detection of contrast bubbles in the left atrium within the first three cardiac cycles after contrast appearance in the right atrium either spontaneously or after the Valsalva maneuver. RESULTS: A total of 57 patients showed evidence of atrial right to left shunt with either imaging modality. Fifty-one studies were positive with TEE, 52 studies were positive with SHI, and 32 were positive with FI (p<0.001 for FI vs. SHI and TEE). The severity of contrast passage was significantly larger using SHI (61.6+/-80.2 bubbles) compared to FI (53.7+/-69.6 bubbles; p<0.005 vs. SHI) but was not different compared to TEE (43.9+/-54.3 bubbles; p = NS vs. SHI). The duration of contrast visibility was significantly longer for SHI (17.4+/-12.4 s) compared to FI (13.1+/-9.7 s; p<0.001) and TEE (11.9+/-9.6 s; p<0.02). Mean image quality improved significantly from FI (1.5+/-0.8) to SHI (2.0+/-0.8; p<0.001 vs. FI) and TEE (2.5+/-0.7; p<0.001 vs. SHI). CONCLUSIONS: In combination with IV contrast injections, TEE and SHI have a comparable yield for the detection of atrial right to left shunt. Both modalities may miss patients with atrial shunting. In young patients with an unexplained cerebrovascular event and no clinical evidence of cardiac disease, a positive SHI study may obviate the need to perform a TEE study to search for cardiac sources of emboli.

Context-dependency of the relation between left ventricular mass and AGT gene variants.

In the European Project on Genes in Hypertension (EPOGH), we investigated in three populations to what extent in a family-based study, left ventricular mass (LVM) was associated with the C-532T and G-6A polymorphisms in the angiotensinogen (AGT) gene. We randomly recruited 221 nuclear families (384 parents and 440 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for covariables, and subjected to multivariate analyses, using generalized estimating equations and quantitative transmission disequilibrium tests in a population-based and family-based approach, respectively. We found significant differences between the two Slavic centres and Mirano in left ventricular mass index (LVMI) (94.9 vs 80.4 g/m2), sodium excretion (229 vs 186 mmol/day), and the prevalence of the AGT -6A (55.7 vs 40.6%) and -532T (16.8 vs 9.4%) alleles. In population-based as well as in family-based analyses, we observed positive associations of LVMI and mean wall thickness (MWT) with the -532T allele in Slavic, but not in Italian male offspring. Furthermore, in Slavic male offspring, LVMI and MWT were significantly higher in carriers of the -532T/-6A haplotype than in those with the -532C/-6G or -532C/-6A allele combinations. In women, LVMI was neither associated with single AGT gene variants nor with the haplotypes (0.19 < P <0.98). In Slavic offspring carrying the AGT -532C/-6G or -532C/-6A haplotypes, LVMI significantly increased with higher sodium excretion (+3.5 g/m2/100 mmol; P=0.003), whereas such association was not present in -532T/-6A haplotype carriers (P-value for interaction 0.04). We found a positive association between LVMI and the AGT -532T allele due to increased MWT. This relation was observed in Slavic male offspring. It was therefore dependent on gender, age and ecogenetic context, and in addition it appeared to be modulated by the trophic effects of salt intake on LVM.

Self-assembling nucleic acid delivery vehicles via linear, water-soluble, cyclodextrin-containing polymers.

Non-viral (synthetic) nucleic acid delivery systems have the potential to provide for the practical application of nucleic acid-based therapeutics. We have designed and prepared a tunable, non-viral nucleic acid delivery system that self-assembles with nucleic acids and centers around a new class of polymeric materials; namely, linear, water-soluble cyclodextrin-containing polymers. The relationships between polymer structure and gene delivery are illustrated, and the roles of the cyclodextrin moieties for minimizing toxicity and forming inclusion complexes in the self-assembly processes are highlighted. This vehicle is the first example of a polymer-based gene delivery system formed entirely by self-assembly.

Intravascular ultrasound assessment of the morphologic similarities between stenoses located in different arteries in the same patient.

To study the relation in lesion morphology and composition between multiple vessels, intravascular ultrasound studies were performed on both vessels of 131 patients undergoing subsequent 2-vessel angioplasty. Because multiple stenoses in the same patient appear more dissimilar than similar, we conclude that local factors tend to be more important than patient factors in determining the lesion morphology.

Transesophageal 3-dimensional echocardiography: in vivo determination of left ventricular mass in comparison with magnetic resonance imaging.

The objective of this study was to assess the accuracy and reproducibility of transesophageal 3-dimensional echocardiography (3DE) in comparison with magnetic resonance imaging (MRI) for the in vivo calculation of left ventricular mass (LVM). In addition, mass values obtained by M-mode echocardiography were compared with those calculated by MRI. Three-dimensional reconstruction of the left ventricle was performed from a transesophageal and transgastric transducer position with a multiplane transducer in 20 patients. Left ventricular mass was calculated from both transducer positions by using slices of various thicknesses, ranging from 5 to 20 mm. Reproducibility was determined by 5 repeated measurements of mass in each of 5 randomly selected left ventricles. M-mode echocardiography was performed according to the method described by Devereux. For MRI, multiple short-axis views with 10-mm slice thickness were acquired in inspiration hold. Correlation was high for mass determined by 3DE and MRI (for 10-mm slice thickness: r = 0.99; y = 0.99 x - 0.7 g; standard error of estimate = 8.5 g; P <.001). There was no statistical bias, and the limits of agreement ranged from +/-16.4 g to +/-27.2 g, depending on the slice thickness. Variability was lowest for a slice thickness of 10 mm (SD +/- 8.2 g). The reproducibility of mass determination was excellent (mean width of the 95% CI 12.8 g). Left ventricular mass values calculated from the transgastric and transesophageal transducer position were not different from each other (mean bias 0.6 +/- 9.1 g; P = ns). M-mode-based LVM calculations showed systematic overestimation and large measurement variability (bias 23.7 g; 95% CI +/- 92.8 g). Compared with MRI, transesophageal 3DE is an accurate and reproducible method for the determination of LVM and clearly superior to M-mode echocardiography.

Comparison of transesophageal Doppler methods with angiography for evaluation of the severity of mitral regurgitation.

Doppler evaluation of mitral regurgitation remains difficult; thus, a head-to-head comparison of the diagnostic accuracy of Doppler methods was undertaken. Fifty patients with native mitral regurgitation underwent multiplane transesophageal echocardiography within 5 days of catheterization. Angiographic grade of mitral regurgitation and, in 20 patients with grade II-IV regurgitation, invasively determined regurgitant stroke volume were compared with color Doppler area, regurgitant jet diameter, ratio of systolic to diastolic peak pulmonary venous flow velocities, and (based on the proximal convergence zone) maximal regurgitant flow rate and regurgitant orifice area. Rank correlation coefficients of angiographic grade with Doppler parameters were 0.61 for color jet area, -0.61 for pulmonary venous flow velocity ratio, 0.69 for color jet diameter, 0.79 for maximal regurgitant flow rate, and 0.78 for regurgitant orifice area (all P < .01). Convergence zone-based parameters also correlated best (r=0.73) with invasively determined regurgitant stroke volume. Receiver operating characteristic curve analysis confirmed higher diagnostic accuracy for proximal jet width and proximal convergence zone parameters than for color jet area or pulmonary venous flow velocity ratio. Proximal convergence zone parameters and proximal color jet diameter best distinguished severe from mild forms of mitral regurgitation.

Increased titers of antibodies against streptococcal M12 and M19 proteins in patients with Tourette's syndrome.

It has been suggested that a post-streptococcal autoimmune process may be involved in the pathogenesis of a subgroup of children with tics and obsessive-compulsive symptoms (PANDAS). Elevated antibody titers against streptococcal antigens have also been described in adult patients suffering from Tourette's syndrome (TS). In order to characterise further streptococcal antigens, we focussed on M proteins. M proteins are a major virulence factor of group A streptococci and known to evoke an immunologic cross-reaction with diverse epitopes of human tissue including brain tissue. Therefore, antibodies against M proteins may play a role in the pathophysiology of at least a subgroup of TS patients. Antibodies against M proteins were studied in 25 adult patients suffering from TS and 25 healthy controls after careful medical examination. The antibody titers against the peptides M1, M4, M6, M12 and M19 were estimated by ELISA. Our results show increased titers of antibodies against the streptococcal M12 and M19 proteins in TS patients as compared with controls, while antibody titers against M1, M4 and M6 did not differ between the TS and control groups. Elevated serum titers of antibodies against M12 and M19 proteins support the view that a streptococcus-induced autoimmune process may be involved in TS. The finding of a possible autoimmune origin of TS has implications for both pathophysiology and future therapeutic strategies.

Hair removal in 40 hirsute women with an intense laser-like light source.

Until recently, previously applied methods to remove hair have ultimately proven ineffective or resulted in the formation of scars and small wounds. Different methods for removing hair in a more or less permanent way have been used: electrolysis, thermolysis and the blend method. In this study we describe the removal of hair without side-effects by means of non-laser incoherent emitted light, produced by the ILS flashlamp. In a multicenter study we treated 40 women with a median age of 38.6 years with hirsute hair growth of different hair colours on the upper lip and chin. In general 76.7% of the hair was removed within 6 treatments, with an average fluence of 38.7 J/cm2 and a mean wavelength of 585 nm per patient. A correlation was found between the percentage reduction of hairs and the number of treatments and between hair removal and needle epilation before treatment. Furthermore, a correlation was seen between hair reduction and wavelengths of 570 nm and 550 nm. No association was found between hair removal and clinical data of the patients, nor between hair reduction and technical data of the device. This study presents a new alternative for hair removal.

Correlation of histology, cytogenetics and proliferation fraction (Ki-67 and PCNA) quantitated by image analysis in meningiomas.

Sixty meningiomas were classified histologically according to the WHO criteria and analyzed cytogenetically. The Ki-67 and PCNA proliferation fractions (PRFs) were assessed by immunhistochemistry. The staining results were quantified by TV-image analysis (Miamed, Leica, Germany). Within meningiomas of WHO-grade II/III and those with complete or partial deletion of # 1p, we found a significantly higher mean and maximal Ki-67 PRFs than in those of WHO-grade I and those with all other karyotypes. This was not the case for PCNA PRFs. No differences in PRFs were detectable between histological subtypes. Although these results were obtained after measurement of five high power fields (HPFs) only, the heterogeneity of PRF distribution within the tumors was high. Even after the measurement of 100 HPFs, the 95% confidence intervals were in a range of 18% to 34.3% PRF. This finding seems to be responsible for the moderate interobserver reproducibility of image analytical determination of PRF (r = 0.74). Nevertheless, there was a good correlation between subjective and objective image analytical assessment of PRF (r = 0.83). The significance of the maximum Ki-67 PRF per specimen implies the possibility of selecting those areas which show the highest fraction of positively stained nuclei for measurement, avoiding the problem of intraslide heterogeneity. Thus the time needed for image analytical quantification may be reduced.

[Quality control of outpatient imaging examinations in North Rhine-Westphalia, Part II]. / Qualitätskontrolle der ambulanten bildgebenden Diagnostik in Nordrhein-Westfalen, Teil II.

PURPOSE: In the state of North Rhine-Westphalia (NRW), Germany, a survey was conducted on radiologic examinations ordered by general practitioners (GPs). Part II of this study aims to determine the quality of the process and outcome. The reference standard is the assessment of both radiologists and physicians without board certification in radiology working at a university hospital and in outpatient facilities. MATERIALS AND METHODS: AllGPs in NRW were asked to cooperate. Participating GPs filled out a questionnaire for each patient. The patients recorded the symptoms prompting the imaging examinations. The radiologists or other physicians performing the examinations were asked to provide the images and written reports and to complete a questionnaire. A file was created for each of the 394 patients with image documentation of at least one examination. Each file, which included medical history, physical findings, imaging documentation and written report, was sequentially forwarded to a board-certified radiologist and to a physician without board certification in radiology working in a university hospital and in an outpatient facility. All physicians were requested to complete a structured questionnaire for each file. RESULTS: The referral diagnoses were rated as medically plausible in 81%, the indications for imaging found correct in 76%, the examination techniques considered appropriate in 69%, the clinical question answered in 63%, the interpretation judged medically correct in 50% and all incidental findings documented in 49%. In retrospect, 32 % of the examinations were judged superfluous. The sequence of multiple examinations performed on a particular patient was rated as appropriate in 51%. The interpretation revealed specialty-related differences. The plausibility of the referral diagnoses had a significant impact on the appropriateness of subsequent diagnostic investigations. Marked deficits showed sonography, performance by non-radiologists, self-referrals by GPs, gastroenterologic radiology and the ICD-10 coding (suspicion of cardiovascular disease). CONCLUSION: In the "best-case" scenario, the process quality proved to have moderate deficiencies and the outcome quality severe deficiencies. In consequence, GPs and radiologists should be more communicative by sharing information and exchanging opinions. GP self-referrals should be restricted. Sonography and examinations performed by physicians without board certification in radiology should undergo stricter quality controls. A more intensive interdisciplinary collaboration is needed to determine the optimum implementation of diagnostic imaging of gastroenterologic and cardiovascular diseases.

[Quality control of outpatient imaging examinations in North Rhine-Westphalia, part I]. / Qualitätskontrolle der ambulanten bildgebenden Diagnostik in Nordrhein-Westfalen, Teil I.

PURPOSE: In the state of North-Rhine Westphalia (NRW), Germany, a survey was conducted on radiologic examinations ordered by general practitioners (GPs). Part I of this study aims to collect characteristic epidemiological data and to assess structural quality. MATERIALS AND METHODS: All GPs in NRW were asked to cooperate. Participating GPs filled out a questionnaire for each patient. The patients recorded the symptoms prompting the imaging examinations. The radiologists or other physicians performing the examinations were asked to provide the images and written reports and to complete a questionnaire. Two university radiologists documented the pertinent test data from the submitted images and written records. Independently of each other, five university radiologists anonymously reviewed the image quality of each examination using structured questionnaires. RESULTS: A total of 920 patients gave their informed consent and participated. Questionnaires from 787 patients, 852 GPs and 611 radiologists or other interpreting physicians as well as the complete survey data from 530 examinations were available. Of 1503 examinations, conventional radiography made up 52 %, sonography 17 %, computed tomography (CT) 13 % and magnetic resonance imaging (MRI) 5 %. Most indications involved the musculoskeletal (37 %) and respiratory systems (24 %). Physicians without board certification in radiology interpreted 1 % of the CT examinations, 26 % of the radiographic examinations and 71 % of the sonographic examinations. Of the 174 self-referrals, 1 % involved CT, 33 % conventional radiography and 66 % sonography. Written reports were available for 95 % of all 469 examinations performed by radiologists and 74 % of all 127 examinations conducted by non-radiologists. Only 44 % of the 23 sonographic studies were self-referrals by the patient's GP. On average, the radiographic techniques were acceptable in terms of diagnostic information and radiation hygiene. Conventional radiographs were better exposed when obtained by radiologists than by non-radiologists (p = 0.038). The delineation of anatomical structures was rated as good to acceptable for MRI, CT and conventional radiography, while the image quality was rated as diagnostically insufficient for sonography (p < 0.0001). The image quality of radiographic and sonographic examinations performed by radiologists was superior in comparison to examinations performed by physicians without board certification in radiology (p < 0.0001). CONCLUSION: Examination technique and imaging quality of MRI, CT and conventional radiography performed on outpatients were in an acceptable diagnostic range, whereas the quality of sonography was inadequate.

[Prognostic improvement by R1 and R2 lymphadenectomy in stomach carcinoma]. / Zur Frage der Prognoseverbesserung durch R1- und R2-Lymphadenektomie beim Magencarcinom.

In 1986 systematic R2 lymphadenectomy was introduced into the surgery for gastric carcinoma in our institution. In an historic analysis 381 patients of the years 1980-1992 were investigated. The effect of R2 lymphadenectomy was studied after R0 resection and exclusion of inhospital mortality. 81 matched pairs of patients with and without lymphadenectomy (LA) were restaged according to the latest classification of the UICC (1987) and compared in an univariate and multivariate analysis. A significant improvement of the estimated 5-year survival-rate was only seen in UICC-stages II (p = 0.05), IIIA (p = 0.01) and patients without lymph node metastases (pN0, p = 0.01). The multivariate analysis did not show an independent effect of LA on prognosis but of the oncological parameters pT and pN (p = 0.0001). We conclude that LA improves the prognosis of gastric carcinoma in certain early stages but the effect is not as impressive as expected.

[Expanded, radical perineal prostatectomy]. / Die erweiterte, radikale perineale Prostatektomie.

One hundred and twenty-five consecutive patients with prostate cancer underwent an extended, radical perineal prostatectomy according to the technique described by VE Weldon. This technique was modified by an initial complete mobilization of the posterior aspect of the prostate and seminal vesicles from the rectum and pelvic wall, incision of the endopelvic fascia, and partial resection of the dorsal vein complex after suture ligature. The perioperative morbidity was low. An operative revision was necessary in four (3.2%) patients because of arterial bleeding from a drainage channel (n = 1), wound infection (n = 2), and rectocutaneous fistula (n = 1). The in-dwelling catheter was removed on day 4-8 in 104 (83%) patients. Positive surgical margins were diagnosed in 22 (17.6%) patients only. These patients had pT3 (n = 17) and pT4 (n = 5) tumors with a Gleason score > or = 7 (n = 17) mostly; extensive, multifocal capsular penetration (n = 18); seminal vesicle invasion (n = 11); and lymph node metastases (n = 4). The unifocal positive margins were localized at the apex (n = 3), dorsolateral (n = 6) aspect, and bladder neck (n = 4). In nine patients, multifocal positive surgical margins were noted. The risk for a positive surgical margin depends on the serum PSA level, Gleason score, and tumor volume. In case potency preservation is not considered, the extended, radical perineal prostatectomy with the above mentioned modifications should be considered to guarantee a low rate of surgical margins.

Prenatal Clinical Assessment of sFlt-1 (Soluble fms-like Tyrosine Kinase-1)/PlGF (Placental Growth Factor) Ratio as a Diagnostic Tool for Preeclampsia, Pregnancy-induced Hypertension, and Proteinuria.

Background: Aim of the study was a critical assessment of the clinical validity of the prenatal determination of sFlt-1/PlGF for preeclampsia (PE), pregnancy-induced hypertension (PIH), and proteinuria. Our analysis was based on a specificity of 95 % and a sensitivity of 82 % for the prediction of preeclampsia, as described by Elecsys (Roche). Methods: In this retrospective study the ratio of the prenatal antiangiogenic factor sFlt-1 (soluble fms-like tyrosine kinase-1) to the proangiogenic factor PIGF (placental growth factor) was analyzed using the electrochemiluminescence immunoassay of Elecsys (Roche Diagnostics, Mannheim, Germany) in 173 pregnant women. Sixty-three women with PE, 34 women with PIH and 6 women with proteinuria were compared to 72 controls. On average, the sFlt-1/PlGF ratio was determined 8 (controls), 2.4 (PE), 3.2 (PIH) and 4.1 (proteinuria) weeks before delivery. The PE and PIH cases were further subdivided into early (< 34 weeks of gestation) and late (≥ 34 weeks of gestation) onset groups. Statistical data analysis was done using the usual descriptive statistics and logistic regression analysis. ROC curves were calculated, and the sensitivity, specificity, and negative and positive predictive value (NPV, PPV) were estimated for a threshold of 85. Results: Although the specificity of the sFlt-1/PlGF ratio was high for PE, the sensitivity was low (only 59.4 %), thus giving unsatisfying results for PE. The sensitivity only increased to 62.5 % for the early-onset PE group. Intriguingly, a high ratio was detected for the combination of IUGR (intrauterine growth restriction) and PE in the early-onset PE group (8 cases). In the control group, 4 cases exceeded the cut-off value of 85 but showed no clinical signs of PE and the birth was unremarkable. In summary, we found that the sFlt-1/PIGF ratio could not be used as a predictive test for preeclampsia but rather as an indicator for the development and estimation of the severity of PE. Thus, the test is less suitable for the reliable exclusion of PE in routine clinical practice. Recommendation: The determination of the sFlT-1/PlGF ratio is only one element for PE diagnosis in addition to the measurement of blood pressure, proteinuria, ultrasound and Doppler.

[Vasoproliferative retinal tumors]. / Vasoproliferative retinale Tumore.

BACKGROUND: Vasoproliferative Tumors of the retina (VPTR) are benign tumors of unknown origin, occurring mostly in otherwise systemically healthy patients. These highly vascularised tumors are characterised by a pink to yellow colour on funduscopy and are usually situated in the inferior part of the retina. They are associated with intraretinal hemorrhages, intra- or subretinal exudates and hyperpigmentation of the retinal pigment epithelium. MATERIALS AND METHODS: We performed a retrospective case review of seven cases which have been diagnosed with VPTR between 2004 and 2006 in the Department of Ophthalmology, University Hospital Zurich. RESULTS: The median follow up was 8 months (range: 1-24 months). We found a presumed underlying cause for the VPTR in 6 out of 7 patients. 3 patients showed a long standing retinal detachment; in the other 3 there was an untreated chronic uveitis. In one case the tumour was surgically excised and histology was performed. CONCLUSIONS: VPTR of the ocular fundus are a distinct entity in the differential diagnosis of intraocular tumors. These benign lesions represent reactive gliovascular proliferations, with varying degrees of both gliosis and of vascular proliferation. VPTR can be idiopathic, or they develop after inflammatory, vascular, traumatic, dystrophic or degenerative ocular diseases, in particular, uveitis. The major differential diagnosis includes other vascular lesions or tumors of the ocular fundus like capillary retinal hemangiomas, Coat' Disease or malignancies. The natural course of VPTR appears to be variable. The therapy is based on tumor size, localisation and complications.

Is cervical dilatation during parturition at term associated with apoptosis?

AIMS: Cellular turnover may be involved in remodeling of the cervix during parturition. Therefore, the number and localization of apoptotic and proliferating cells during cervical dilatation at term were determined. METHODS: Biopsy specimens from the lower uterine segment of 36 women undergoing cesarean section with a cervical dilatation of < 2 cm (n = 10), 2- < 4 cm (n = 9), 4-6 cm (n = 8), and > 6 cm (n = 9) were examined for nuclear fragmentation by the TUNEL assay, and for cell survival by the apoptosis-blocking bcl-2. Proliferation was marked by Ki-67, epithelial cells by cytokeratin and leukocytes by CD 45. For quantification of apoptotic and proliferating cells, eight random fields of each specimen stained for TUNEL or Ki-67 were blindly counted by two investigators. For statistical evaluation, 90% confidence intervals based on a Poisson distribution were used; groups with non-overlapping intervals were considered significantly different. RESULTS: Apoptotic cells were found exclusively within the stromal compartment, while bcl-2 was expressed in epithelial cells and leukocytes. Proliferating cells were of stromal and epithelial origin. The number of apoptotic as well as proliferating cells ranged from 0 to 2 cells per high-power field (median number 0) in all groups. The confidence intervals were overlapping for all groups, showing no statistical difference between them. CONCLUSION: Apoptosis does not seem to play a decisive role in the process of cervical dilatation during parturition at term.

Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG).

BACKGROUND: Since there are no randomized studies, the treatment of choice for patients with early stage lymphocyte-predominant Hodgkin's lymphoma (LPHL) remains unclear. We thus reviewed all LPHL cases registered in the database of the German Hodgkin Study Group (GHSG) and compared the different treatment approaches, such as extended field (EF), involved field (IF) radiation and combined modality (CM) treatment for LPHL stage IA patients. PATIENTS AND METHODS: One hundred and thirty-one patients with LPHL in clinical stage IA without risk factors were analyzed. Forty-five patients were treated with EF radiotherapy, 45 patients with IF radiation and 41 patients received CM treatment. The median follow-up was 78 months in the EF group, 40 months after CM and 17 months after IF, respectively. RESULTS: A total of 129 patients achieved complete remission (CR and CRu): 98% after EF radiotherapy, 100% after IF radiation and 95% after CM. With a median follow-up of 43 months there were 5% relapses and only three patients died. Toxicity of treatment was generally mild with most events observed after CM. CONCLUSION: In terms of remission induction IF radiotherapy for stage IA LPHL patients is as effective as EF or CM treatment. However, longer follow-up is needed before final conclusion as the optimal therapy.

[Beta receptor blockers in dilated cardiomyopathy (clinical aspects)]. / Betarezeptorenblocker bei dilatativer Kardiomyopathie (Klinik).

Results of 16 international published studies (with a total of 397 patients in NYHA-classes II-III) concerning chronic therapy with beta-adrenoceptor blockade in idiopathic dilated cardiomyopathy were analyzed. 8 studies were placebo controlled. Under beta-blockade cardiac output increased significantly by about 15% and ejection fraction by approximately 30%, apparently due to an improvement in contractility and relaxation of LV myocardium. Therapy was tolerated without complications in 93% of patients when the loading dose was 5 to 15 mg metoprolol/d (or equivalent) and a long-term dose of 100-200 mg/d metropolol (or equivalent) was reached within 4 weeks. Patients with severe heart failure (NYHA IV) had a higher risk of complications. A positive effect of beta-blockade in IDC was achieved in most cases but not earlier than after 2-3 months after initiating therapy. Despite these positive results beta-blockade in patients with IDC may not yet be recommended generally. Sufficient results of controlled trials are still lacking. Important questions with regard to the prognosis under beta-blockade, to the effects of cardioselectivity and intrinsic activity, and to the efficacy of this kind of therapy in the presence of ACE inhibitors have not been answered. Thus, major trials with controlled design are needed.