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Aims To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. Methods People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. Results In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. Conclusion This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.

The use of animal models of infection is essential to advance our understanding of the complex host-pathogen interactions that take place during Aspergillus fumigatus lung infections. As in the case of humans, mice need to suffer an immune imbalance in order to become susceptible to invasive pulmonary aspergillosis (IPA), the most serious infection caused by A. fumigatus. There are several immunosuppressive regimens that are routinely used to investigate fungal growth and/or immune responses in murine models of invasive pulmonary aspergillosis. However, the precise consequences of the use of each immunosuppressive model for the local immune populations and for fungal growth are not completely understood. Here, to pin down the scenarios involving commonly used IPA models, we employed light sheet fluorescence microscopy (LSFM) to analyze whole lungs at cellular resolution. Our results will be valuable to optimize and refine animal models to maximize their use in future research., Aspergillus fumigatus is an opportunistic fungal pathogen that can cause life-threatening invasive lung infections in immunodeficient patients. The cellular and molecular processes of infection during onset, establishment, and progression of A. fumigatus infections are highly complex and depend on both fungal attributes and the immune status of the host. Therefore, preclinical animal models are of paramount importance to investigate and gain better insight into the infection process. Yet, despite their extensive use, commonly employed murine models of invasive pulmonary aspergillosis are not well understood due to analytical limitations. Here, we present quantitative light sheet fluorescence microscopy (LSFM) to describe fungal growth and the local immune response in whole lungs at cellular resolution within its anatomical context. We analyzed three very common murine models of pulmonary aspergillosis based on immunosuppression with corticosteroids, chemotherapy-induced leukopenia, or myeloablative irradiation. LSFM uncovered distinct architectures of fungal growth and degrees of tissue invasion in each model. Furthermore, LSFM revealed the spatial distribution, interaction, and activation of two key immune cell populations in antifungal defense: alveolar macrophages and polymorphonuclear neutrophils. Interestingly, the patterns of fungal growth correlated with the detected effects of the immunosuppressive regimens on the local immune cell populations. Moreover, LSFM demonstrates that the commonly used intranasal route of spore administration did not result in complete intra-alveolar deposition, as about 80% of fungal growth occurred outside the alveolar space. Hence, characterization by LSFM is more rigorous than by previously used methods employing murine models of invasive pulmonary aspergillosis and pinpoints their strengths and limitations.

Wilms tumor (WT) is the most common kidney cancer in childhood. Mutations in the microprocessor genes DROSHA and DGCR8 have been identified as putative oncogenic drivers, indicating a critical role of aberrant miRNA processing in WT formation. To characterize the in vivo role of DROSHA mutations during kidney development and their oncogenic potential, we analyzed mouse lines with either a targeted deletion of Drosha or an inducible expression of human DROSHA carrying a tumor-specific E1147K mutation that acts in a dominant negative manner. Both types of mutation induce striking changes in miRNA patterns. Six2-cre mediated deletion of Drosha in nephron progenitors led to perinatal lethality with apoptotic loss of progenitor cells and early termination of nephrogenesis. Mosaic deletions via Wt1-cre

Aims\ud To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries.\ud \ud Methods\ud People with diabetes aged 18–65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected.\ud \ud Results\ud A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (PPPPPConclusions\ud Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes.

Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation. In the absence of RhoA, increased Cdc42 activity and MK hyperpolarization triggers GPIb-dependent transmigration of entire MKs into BM sinusoids. These findings position Cdc42 (go-signal) and RhoA (stop-signal) at the centre of a molecular checkpoint downstream of GPIb that controls transendothelial platelet biogenesis. Our results may open new avenues for the treatment of platelet production disorders and help to explain the thrombocytopenia in patients with Bernard–Soulier syndrome, a bleeding disorder caused by defects in GPIb-IX-V., Platelets derive from large precursor cells (megakaryocytes) in the bone marrow. Dütting et al. show that megakaryocyte polarization and platelet biogenesis in the bone-marrow sinusoids are directed by adhesion receptor GPIb signalling and resulting balanced antagonism between RhoA (stop-signal) and Cdc42 (go-signal).

Pseudomonas aeruginosa is well adapted to the hospital setting and can cause a wide array of nosocomial infections that occasionally culminate in recalcitrant outbreaks. In the present study, we describe the first nosocomial outbreak of infection caused by blaVIM-2-positive P. aeruginosa in Germany. In November and December 2007, highly resistant P. aeruginosa isolates were recovered from the urine of 11 patients in the Department of Urology of a University Hospital. Bacterial isolates were typed by multilocus sequence typing and screened for known metallo-β-lactamase (MBL) genes by PCR. Environmental sources of transmission were tested for bacterial contamination using surveillance cultures. Furthermore, a matched case–control study was performed in search of medical procedures significantly associated with case status. Typing of recovered isolates confirmed VIM-2 MBL-producing P. aeruginosa of sequence type 175 in all cases. Surveillance cultures did not lead to the identification of an environmental source of the outbreak strain. Case–control analysis revealed retrograde urography as the only exposure significantly associated with case status. The analyses suggest the transmission of a single clone of VIM-2 MBL-producing P. aeruginosa leading to the infection of 11 patients within 47 days. Events in temporal proximity to retrograde urographies appear to have facilitated infection in the majority of cases. Department-specific infection control measures, including reinforced hygiene procedures during retrograde urography, quickly terminated the outbreak.

Moclobemide is the first of a new generation of reversible inhibitors of monoamine oxidase-A (RIMA) with no clinically relevant potentiation of the hypertensive actions of dietary tyramine. The present study was conducted to compare the efficacy and safety of moclobemide with an established irreversible monoamine oxidase inhibitor, tranylcypromine, in depressed patients. Patients were randomized to receive moclobemide (81 patients) or tranylcypromine (79 patients) at individually titrated doses (100-300 mg/day of moclobemide and 10-30 mg/day of tranylcypromine) under double-blind conditions for at least four weeks, in a multicenter trial. Antidepressant efficacy was assessed using items 1-17 of the Hamilton depression rating scale (HAMD-17), the von Zerssen 'Befindlichkeits' scales, a visual analog scale and the clinicians' global impression. Both treatments resulted in significant amelioration of depression as determined by all rating instruments. HAMD-17 scores were reduced by 63% and 58% with moclobemide and tranylcypromine respectively, although the difference between the groups was not significant. The other rating instruments yielded similar results, apart from the clinician's assessment of efficacy at day 28. In this assessment, efficacy was rated as very good/good in 78% of moclobemide treated patients and in 88% of the tranylcypromine treated patients; however, only patients who had not dropped out of the trial were included in this assessment. The tolerability of both drugs was good, although moclobemide appeared to possess a small advantage in this regard since only one patient in this group was prematurely withdrawn from the trial due to inadequate tolerability/adverse events, compared with nine withdrawals in the tranylcypromine group.(ABSTRACT TRUNCATED AT 250 WORDS)

To compare the effects of remifentanil and fentanyl on intraocular pressure during the maintenance and recovery of anaesthesia in patients undergoing elective non-ophthalmic surgery.Thirty-two patients (ASA I-II) were randomized into two groups to receive either a continuous infusion of remifentanil (0.25-0.5 microg kg(-1) min(-1), n =16, Group R) or an intermittent bolus of fentanyl (2-5 microg kg(-1), n = 16, Group F) during the maintenance of anaesthesia. For the induction of anaesthesia, Group R received remifentanil 1 microg kg(-1) and Group F received fentanyl 2 microg kg(-1); both groups then received propofol 2 mg kg(-1) with vecuronium 0.1 mg kg(-1). Anaesthesia in both groups was maintained with a continuous infusion of propofol 4-8 mg kg(-1) h(-1). Ventilation of the lungs was controlled to a constant end-tidal PCO2 of 4.7-5.4 kPa. Blood pressure, electrocardiography, heart rate and oxygen saturation were monitored throughout anaesthesia. Intraocular pressure was determined before surgery, during the maintenance of anaesthesia, 2 min after emergence and in the recovery room using a Perkins hand-held applanation tonometer by an ophthalmologist blinded to the anaesthetic technique.After induction of anaesthesia, a significant decrease in intraocular pressure in the remifentanil group from 13.6 +/- 2.6 to 7.1 +/- 3.1 mmHg (P0.001) and in the fentanyl group from 13.7 +/- 2.2 to 9.7 +/- 3.4 mmHg (P0.001) was observed and maintained during anaesthesia. Thirty minutes after the end of anaesthesia, intraocular pressure returned to baseline values in both groups (remifentanil: 13.9 +/- 2.8 mmHg, P = 0.28; fentanyl: 13.6 +/- 2.3 mmHg, P = 0.59). The intraocular pressure and haemodynamic variables did not differ significantly between the two groups (intraocular pressure, P = 0.7327; blood pressure, P = 0.1295; heart rate, P = 0.8601).Remifentanil maintains intraocular pressure at an equally reduced level compared with fentanyl.

To provide good control of intraocular pressure (IOP) during anaesthesia and surgery, we conducted a study comparing the effects on IOP during maintenance and recovery of sevoflurane vs propofol anaesthesia in 33 patients (ASA I-II) undergoing elective non- ophthalmic surgery.Anaesthesia was induced with propofol 2 mg kg(-1), fentanyl 2 micro g kg(-1) and vecuronium 0.1 mg kg(-1). Patients were allocated randomly to receive either propofol 4-8 mg kg(-1) h(-1) (group P; n=16) or 1.5-2.5 vol% sevoflurane (group S; n=17) for maintenance of anaesthesia. Fentanyl 2-4 micro g kg(-1) was added if necessary. The lungs were ventilated with 50% air in oxygen. Blood pressure, heart rate, oxygen saturation and end-tidal carbon dioxide were measured before and throughout anaesthesia and in the recovery room. IOP was determined with applanation tonometry (Perkins) by one ophthalmologist blinded to the anaesthetic technique.There was a significant decrease in IOP after induction and during maintenance of anaesthesia in both groups. No significant differences in IOP between the two groups was found.Sevoflurane maintains the IOP at an equally reduced level compared with propofol.

An experimental study was performed on 20 cadaveric human proximal femurs to investigate both the reproducibility of their mechanical behavior under uniaxial compression and the correlation of mechanical properties with geometric dimensions and bone density. These variables were assessed by radiography, physical measurement, and dual-energy X-ray absorptiometry (DEXA). The specimens were immobilized, loaded to the point of fracture, and analyzed with the help of a materials testing machine. The fractures invariably showed a similar pattern both in location (i.e. at the femoral neck) and in nature (i.e. "axial-shear" type according to the AO classification system). The mechanical properties of the tested proximal femurs correlated negatively with age (r = -0.39) and positively with sex (male femurs were stronger and correlated more closely than female femurs, P = 0.005). They showed a strong positive correlation with head diameter (r = 0.713, P = 0.0004), a moderate positive correlation with both neck axis length (r = 0.63) and neck diameter (r = 0.502), and a slight positive correlation with femoral neck-shaft angle (r = 0.326). All DEXA-based densitometry measures turned out to be powerful predictors of fracture force. The establishment of this solidly reproducible fracture model based on standardized loading conditions should have implications for future research on osteopenia/osteoporosis and preventive stabilization techniques.

We hypothesized that placental cytokeratin (CK) 18 expression and serum levels of tissue polypeptide antigen (TPA), a surrogate marker for CK 18, are increased among women with pregnancy-induced hypertension (PIH).Serum levels of TPA were measured in 46 women with PIH and 46 controls, matched for gestational age and parity, using an immunoradiometric assay. Immunohistochemical detection of CK 18 was assessed in placental specimens of 24 women with PIH and 20 controls. Results were correlated to clinical data.Cytokeratin 18 expression was found in the syncytiotrophoblast of 7 of 20 (35%) and 18 of 24 (75%) placental specimens of controls and women with PIH, respectively (p = 0.008). Median serum levels of TPA in controls and women with PIH were 93.0 U/L (range: 12.5-281.6) and 154.2 U/L (range: 37.3-496.6), respectively (p = 0.001). Serum levels of TPA significantly influenced the odds of presenting with PIH, as well as the odds of developing severe disease (p = 0.003, and p = 0.001, respectively). TPA values were significantly higher among women with severe PIH compared with women with mild PIH and controls, independent of gestational age (p = 0.004). Among women with severe PIH, serum TPA was inversely correlated with fetal birth weight (r = -0.3; p = 0.001)Cytokeratin 18 is overexpressed in the syncytiotrophoblast of women with PIH. Serum levels of TPA are elevated among women with PIH and correlate with disease severity and low fetal birth weight.

Despite the fact that congenital adrenal hyperplasia (CAH) is one of the most common inborn endocrine disorders, some patients are not identified, or may even die, in an acute salt-losing crisis. In a retrospective study covering the last 30 yr, we examined the time elapsing before diagnosis of CAH patients, in 5 Middle European countries, and the mortality rate in diagnosed patients and their siblings during childhood; we also attempted to estimate how many patients are not diagnosed clinically each year. Basic and follow-up clinical data and the family histories of 484 patients with classical forms of CAH diagnosed between 1969 and 1998 were collected and recorded in 5 Middle European countries. The sex-ratio, time elapsing before diagnosis, and mortality among siblings and patients were calculated, and the number of undiagnosed patients was estimated. We found significantly fewer genetic males (43.0%) than females (57.0%) among 484 classic CAH patients, and the percentage of diagnosed boys did not increase with time; 64.7% of them suffered from the salt-wasting (SW) form, and 35.3% from the simple virilizing (SV) form, of the disease. The diagnosis of CAH was established significantly later in males than in females in both forms [SW: 26 vs. 13 days (median), P0.0001; SV: 5.0 vs. 2.8 yr, P = 0.03]. Infant mortality in the general population was significantly lower than in either siblings (1.8% vs. 7.0%; P0.0001) or in SW (2.29% vs. 11.3%; P0.0001). According to our calculations, by our current praxis of clinical ascertainment, 2-2.5 SW and up to 5 SV stay undiagnosed, out of 40 expected CAH patients per year in the countries investigated. Both clinical detection and treatment of CAH patients, at least in males, were insufficient in the five Middle European countries examined during the last 30 yr. Neonatal mass screening and/or greater awareness of the medical community are discussed as ways of improving the efficacy of CAH management. Our experience may be applicable to other countries with similar health care systems.

To evaluate placental expression and serum cytokeratin-18 in women with preeclampsia.Serum cytokeratin-18 was evaluated in 44 women with preeclampsia and 44 healthy pregnant women using an immunoradiometric assay. Placental expression of cytokeratin-18 was investigated in specimens from 23 women with preeclampsia and 20 healthy pregnant women by immunohistochemistry.Median serum cytokeratin-18 in women with preeclampsia and healthy pregnant women was 106.7 and 76.0 U/L, respectively (P =.02). Among women with preeclampsia, serum cytokeratin-18 was significantly associated with severity of disease (P =.001) and showed a sensitivity (standard error) and specificity (standard error) of 85% (7%) and 65% (12%), respectively. In placental specimens, the cytoplasm of the syncytiotrophoblast stained positive for cytokeratin-18 with strong and widespread staining in 83% and 45% of placental specimens of women with preeclampsia and healthy pregnant women, respectively (P =.01).Elevated serum cytokeratin-18 values are associated with disease severity in women with preeclampsia. Our data provide additional evidence that the placenta might be the source of the elevated serum cytokeratin-18 values in women with preeclampsia.

We have analysed the results of semi-solid bone marrow cultures in 296 patients with de novo acute myeloblastic leukaemia (AML) and correlated them with the leukaemic karyotype. A favourable prognostic karyotype was found in 52 patients (group A, 18.3%), an intermediate karyotype in 163 patients (group B, 57.4%), and unfavourable cytogenetics were observed in 69 patients (group C, 24.3%). Median colony growth according to the three risk groups was 2 (range 0--344) in group A, 14.5 (range 0--5000) in group B and 50.0 (0--3000) in group C (A vs. B, P0.001; A vs. C, P0.001; B vs. C, P0.01). Among the patients treated with chemotherapy (n = 257), median colony growth was 10 (range 0-5000) in those who achieved complete remission (CR) compared with 56.5 (range 0-1000) in patients without remission (NR) (P = 0.002). The median colony growth of all patients [13/10(5) bone marrow mononuclear cells (BMMCs); range 0--5000] significantly discriminated between patients regarding survival (OS 11 vs. 7 months, P = 0.044). However, multiple Cox regression analysis revealed cytogenetic risk groups as the most important predictor for achieving CR, disease-free and overall survival, with colony growth adding no additional prognostic information. In 64 patients, colony growth was also investigated without the addition of exogenous cytokines. Interestingly, none of the patients with a favourable karyotype exhibited autonomous growth, whereas 50% with an intermediate and 73% of patients with an unfavourable karyotype displayed either partial or full autonomous growth in vitro (P = 0.0004). Our data suggest that the growth potential of the leukaemic clone seems to be critically influenced by the molecular changes emerging from chromosomal abnormalities.

Differentiated thyroid cancer (DTC) is a rare tumor entity with excellent prognosis. Thus, assessment of the efficacy of different treatment modalities requires follow-up for such a long period that the validity of the conclusion may be limited because diagnostic and therapeutic standards have changed substantially. Accordingly, the indication for external radiotherapy is still controversial. The aim of the present retrospective study is to evaluate prognostic factors and the influence of treatment on outcome of differentiated thyroid cancer from a large data base. Patients and Methods: Records of 441 patients (317 females, 124 males; mean age 46 years) with 270 follicular and 171 papillary thyroid carcinomas (pT1–4, pNO-3) were reviewed. Treatment was surgery in 440, radioiodine therapy in 338, postoperative external radiotherapy (50–60 Gy) in 223 patients. In 182 cases the three modalities were combined. Results: The 5-year actuarial survival rate of the whole study population was 95%, 10-year survival 92%. 10-year survival was significantly influenced by: tumor stage (pT1: 100%, pT2: 94%, pT3: 94%, pT4: 79%; p = 0.0005), age ( 60 years: 79%; p = 0.0001) and the presence of lymph node metastases in the follicular subtype (pNO: 96%, pNO1–3: 81%; p = 0.02). No significant differences in survival were found according to gender or histological subtype. External radiotherapy yielded a non-significant (p = 0.06) increase in the 10-year survival rate (87% vs 46%; p = 0.06) in patients with pT4 tumors (n = 60). Conclusion: Prognostic factors predominantly confirmed those reported in the literature. Further clinical studies should clarify, if the trend towards better survival in irradiated patients with pT4 tumors can be confirmed in larger patient groups.

Demographic and sociostructural changes put pressure on care services for the elderly within the German welfare system: There is a need for facilities and new concepts. This also requires more and flexible domestic services, which are poorly developed in the German social system. Because the German range of care provider types is easy to navigate, there is increased demand for consumer information and recommendations. Considering the domains of care services, which have been widely distributed to the powerful non-profit welfare organizations, the status quo vs. new flexible service will challenge consumers confidence and choice, especially since todays elderly are more active and have more expendable income. The recently instituted "long-term care insurance" encourages, for the first time, competition between nonprofit organizations and commercial providers. Nevertheless, a clearly perceptible "polarization of age" draws attention to persisting challenges to social policy. Therefore, the increasing competition among types of care providers urges for a truly independent quality control, as well as an effective "welfare mix".

A hand grenade exploded in a VW-Bus killing the female passenger. The paper describes how examination of damage to the material of the drivers seat, seat cushion and to a blanket was able to provide information which helped to reconstruct the effects of the explosion and to determine the position of the grenade at the moment of detonation.

Mobilisation of patients with paraplegia is frequently associated with acute inflammatory processes of soft tissues and muscles in the neighbourhood of joints, where subsequently heterotopic bone formation develops. Rehabilitation is then seriously compromised. For this clinical situation, no local therapeutic options exist so far except extensive resection. To evaluate if radiotherapy early in the course of the disease prevents heterotopic bone formation or if--in case of already manifest ossification and consecutive resection--recurrence can be avoided.In 20 patients with paralysis, 25 regions were irradiated with (mostly) 10 Gy in single fractions of 2 to 2.5 Gy using 8 MV photons. In 15 patients radiotherapy was performed as a primary treatment in the status of myositis; 7 patients were treated after (subtotal) resection of already manifest ossifications (2 patients were treated twice, primarily and postoperatively).In a minimum follow-up of 12 weeks, none of the 20 irradiated patients showed any progression of the developing or already manifest ossification; thus mobilisation and rehabilitation could be carried out as desired. No side effects occurred.The preliminary results of the present study suggest that radiotherapy is an effective local treatment with minimal side effects for the prevention of heterotopic bone formation in patients with paraplegia. Treatment should be started early in the course of the disease. Further evaluation in a prospective study seems desirable.

Between 1980 and 1991, ionizing radiation was applied for analgesic purposes to 181 patients (97 men, 84 women, mean age 54 [29-81] years) with degenerative-inflammatory skeletal disease. The long-term effects were evaluated by questionnaire. Radiation of 2.5 to 6.0 Gy achieved lasting pain relief in 21 of 30 patients (70%) with arthritis of the shoulder or humeroscapular periarthritis, 15 of 21 (71%) with arthritis of the hip, in 12 of 15 (80%) with heel spurs or Achilles tendon bursitis and 10 of 11 (91%) with epicondylitis. Pain relief lasted for longer than two years in 41 of the 77 patients (53%). There were no side effects at the stated dosage. According to dose measurements the theoretical risk of malignant tumour induction is 20-40/million radiated patients and thus four orders of magnitude below the spontaneous malignant tumour incidence rate. The genetic risk is even lower. Ionizing radiation of degenerative-inflammatory diseases is thus an effective form of treatment with few side effects.

Survival of glioblastoma patients can be double by postoperative radiation but nevertheless rarely exceeds one year. It is therefore desirable to minimize treatment time and hospitalisation. Aim of our study is to investigate the feasibility of a reduction of treatment time by accelerated fractionation. Out of 110 patients treated for glioblastoma from 1975 to 1988 in our institution postoperative radiation was performed in 79 patients using three different fractionation schedules: 60 Gy in six weeks, single fractions 2 Gy (n = 38), 35 Gy in two weeks, single fractions 3.5 Gy (n = 27), 45.5 Gy in 2.5 weeks, single fractions 3.5 Gy (n = 14). No statistically significant differences in both the mean overall and disease free survival were evaluated between the three groups. The larger fraction size was well tolerated and no relevant increase of early or late adverse reactions occurred. As the duration of treatment can be reduced from six to two weeks, this accelerated fractionation schedule seems to be a reasonable alternative to conventional fractionation.

In a patient with Graves' disease who underwent thyroidectomy with subsequent radioiodine therapy thyroid receptor antibody could be detected by radioligand assay. No thyroid tissue could be detected by 131I-scintiscanning. Thyroglobulin was repeatedly negative. Biologic activity of this patients serum could be demonstrated in the nude mice bio assay. 131I-incorporation and secretion of human thyroglobulin could be stimulated by injecting thymusdysplastic nude mice with transplants of thyroid tissue from a patient with Graves' disease with the athyroid patients serum. These results demonstrate evidence for extrathyroidal production and biological actiivty of TRAb in vivo.

Size, shape, location and etiology must all be considered in the differential diagnosis of stroke. A logical sequence of steps will be helpful in the evaluation of individual patients.

22 children got lung scans 3 weeks respectively 12 months after the correction of a tetralogy of Fallot. In 18 cases previous operations were done: 12 times a Blalock-Taussig shunt and 6 times a Brock procedure. For the scan 20-70 mu diameter albumin macrospheres were used, which were labeled with Technetium 99m. The following pathologicla lung changes were seen: 1. Loss of perfusion, typical after Blalock-Taussig shunt procedure; these findings were always on the left side, the site of the anastomosis. 2. Anomalous flow distrubution (=more spheres in the upper than in the lower lobe) in the left lung; these changes were also caused by the Blalock-Taussing shunts, but disappeared within the one year follow-up after the correction. 3. Intrapulmonary rigt-left shunts (according to the dilatation of the alveolar capillaries). These decreased within one year from 9.9+/-1.3 to 4.6+/-0.9%.

Urinary iodine excretion of 1945 schoolchildren aged 13 to 15-years from 24 cities throughout the Federal Republic of Germany (FRG) was measured. For comparison, urinary excretion of 5678 adults from 20 cities was calculated from the 24-hour radio-iodine uptake (RIU) by the method of Oddie. On the average the schoolchildren excreted 25.1 mug iodine per g creatinine: by WHO criteria this can be classified as a grade II iodine deficiency. There was a significant decline of urinary iodine excretion from North to South of the FRG. Urinary iodine excretion of children with thyroid enlargement (21.9 mug/g) was significantly less than that of normal children (26.1 mug/g creatinine; P less th that 0.0005). Urinary iodine excretion of adults averaged 25 to 35 mug/g creatinine, values calculated from RIU agreeing well with those determined chemically. Alimentary iodine intake was found to vary between 30 and 70 mug/d throughout the FRG, which is less than 30% of WHO recommended figures for optimal goitre prevention (150-200 mug iodine per day). Alimentary iodine deficiency has been demonstrated throughout the FRG, increasing from North to South in parallel with an increase in goitre rate. Goitre prevention through compulsory iodinization of salt is recommended.

The duration of thyroid hormone deprivation necessary on the one hand to achieve a sufficiently high endogenous TSH level for the identification of 131I-storing metastases or local relapses, and on the other hand to keep the consequences of thyroid hormone deprivation as low as possible, was determined in 111 athyrotic patients with thyroid carcinoma by means of the basal TSH level or a TRH stimulation test. From the first follow-up examination, a T3 deprivation of 8 days is to be recommended. Low basal TSH levels and marked stimulation in the TRH test should be sufficient cause to prolong the T3 deprivation to 10 days with further examinations. After a longterm suppression of athyrotic patients with thyroid hormone, a decrease in the TSH rise was observed in the course of 2 years, after appropriate interruption of the substitution.

Using quantitative sequential camera scintigraphy and simultaneous separated clearance determinations with 131-I-Hippuran and 169-Yb-EDTA renal function was measured applying a new surgical method which permits in-situ kidney perfusion and cooling in animals and patients. While mongrel dogs of 15 kg average weight (control group of N = 5) showed after 1 hour of normothermic ischaemia a postoperative delay of intrarenal transport of 131-I-Hippuran with reduction of 131-I-Hippuran and 169Yb-EDTA clearances, renal function returned to normal on the first postoperative day after 1-hour (N = 5) and 2-hour (N = 5) hypothermic ischaemia. In patients (N = 9) with hypothermic in-situ perfusion of between 40 and 92 min duration a transient postoperative delay of intrarenal 131-I-Hippuran transport and a reduction of the 131I-Hippuran clearance was observed which returned to almost normal 1 1/2 to 3 months after surgery. The results and the significance of the method discussed and are compared with clinical findings and with radiological and laboratory renal function studies.

Selective angiography of the kidneys was performed in 119 patients with urogenital tuberculosis. The diagnosis was confirmed by bacteriological and/or histological examinations. Diagnostic value. Under optimal technical conditions changes of the small renal arteries even in the parenchymal stage I of renal tuberculosis can be seen. These cannot be diagnosed with other methods. In stage II and III the degree of destruction and the localisation of the specific process can be demonstrated more efficiently by angiography than by urogram. In stage III/3 (kidney without function) the differential diagnosis between tuberculosis and the late form of polycystic renal disease is possible. Therefore the selective renal angiography ought to be performed more frequently for intensive diagnosis and also to reach a definite diagnosis before surgical procedures. Special surgical planning is more precise and knowledge of vascular anatomy reduces the operative risk.

488 PATIENTS WITH Graves' disease were treated by 131Iodine between 1960 and 1974. 427 (87,5%) of these patients were reexamined several times (clinically, 131I-uptake, PB127I, T4 (CPB-A), T3-uptake, and since 1973 TRH-test). The 131I was given as an individually calculated single dose treatment, using 7 000 -- 10 000 rd before 1965 and 6 000 rd thereafter. Two thirds of the patients became euthyroid after a single 131I-dose. In 20% the treatment had to be repeated. These patients show evidently a different biological behaviour of their disease, since multiple treatments revealed a higher rate of failure (33--35%). There is no principal difference between the out-come after 131I-therapy and surgery concerning the rate of failure, respectively relapse (3--4%) and hypothyroidism. Early incidence of hypothyrodism is dose--dependent, as could be shown in patients treated with higher doses before 1965. The reduction of the irradiation dose to 6 000 rd was followed by a drop of hypothyroidism from 18% to 7%. The reasons of late incidence of hypothyroidism are discussed. The incidence of hypothroidism was calculated by three different methods (over-all incidence, incidence within the observed interval after therapy, life-table method). All three methods revealed different results. This has to be taken into account comparing results after radioiodine as well as after surgery. Radioiodine therapy for hyperthyroidism offers a true alternative to surgery.

131-J-Hippuran dynamic camera studies were performed in 50 patients suffering from tuberculosis of the kidney. Sequential scintigraphy indicated marked defects of the parenchyma in 50%, contracted kidneys in 14% and a loss of kidney function in 22%. 58% of the tested cases showed a disturbed drainage of urine. The decrease of function of the involved kidney could be evaluated quantitatively by simultaneous measurement of the J-Hippuran-Clearance. In uro-tuberculosis the advantages of the dynamic camera studies consist in the determination of the function status of the involved and the contralateral kidney. Indications of dynamic camera studies of the kidney in urotuberculosis are: 1. prior to surgery: exact determination of the function of both kidneys, 2. following surgery and during medicamental therapy: control of the postoperative course and control of the functional status during chemotherapy.

Between 1960 and 1972, 305 patients with malignomas of the thyroid gland were surgically treated, irradiated (megavoltage therapy and/or iodine-131), and treated with thyroid hormone according to principles formerly stated. Differentiated adenocarcinomas (34.4% of all the patients) were observed more frequently in women and younger patients, whereas dedifferentiated carcinomas (33.8%) are found relatively more often in men and in an advanced age. Only in 12% of the cases the tumor was discovered in an early stage; thus, an early diagnosis is much too rare so far. In almost two thirds of the patients a spread of metastases occurred. Of these, 11% grew manifest later than five years following the therapy. Distant metastases from differentiated adenocarcinomas accumulated I-131 in sixty per cent, those from undifferentiated carcinomas still in twenty per cent. Treatment results are influenced decisively by histology, tumor spread, age and sex, women less than forty years old with differentiated adenocarcinomas and a circumscribed extension of the tumor having the best prognosis. More prognostic importance is due to the extension of the primary tumor than to the presence of metastases to regionary lymph nodes. Patients with metastases accumulating I-131 have a better chance of survival than those whose metastases do not accumulate. By means of standardized therapeutic rules, utilizing modern therapeutic techniques and based on interdepartmental cooperation, it was possible to improve the results partly by the two- or threefold as compared to a previously treated group of patients.

Between 1977 and 1984 a total of 301 patients with autonomous thyroid adenoma were irradiated with an individually calculated one-time dose of 400 Gy units of 131I. Repeated follow-up tests were made in 217 patients (up to 7.2 years, mean of two years). Pre- and post-treatment diagnosis in all patients consisted of determining T3 and T4, one TRH test, one 131I two-phase test to determine treatment, including quantified scintigraphy (under suppression, if necessary), as well as post-treatment scintigraphy and (post-treatment) 99mTc scintigraphy. The treatment was successful in 98% of patients; there was no difference between compensated and decompensated forms. Euthyroid state was achieved in 87% of patients, with typical findings of compensated T3 oversecretion, as is known to occur with endemic goiter in regions of iodine deficiency. The ability of the thyroid for autoregulatory adaptation to such iodine deficiency is thus preserved. Preclinical hypothyroidism occurred in 11% of patients: it could have been avoided in about half of them. Persistent or recurring autonomous adenoma was observed in 2% of patients as a result of under-dosage. One should thus aim at a dose of 400 Gy, to obtain optimal elimination. Radiation-induced carcinogenesis was not observed: radioiodine treatment and operation are thus of equal value in the causal treatment of autonomous adenoma. Radioiodine treatment is indicated in patients aged over 40 years with additional diseases and increased risk of anaesthesia and operation. It is preferred treatment if there are multiple autonomous adenomas.

Between 1963 and 1971, radioiodine (133I) treatment of a toxic thyroid adenoma was performed in 229 patients, in 70% the dosage being 30000 rd. In 188 patients the results were checked an average of 2 1/2 years later. Subjective improvement or freedom from symptoms was achieved in 76% (in 85% within 3-6 months), body weight increased, serum cholesterol level rose significantly, while pulse rate, pulse amplitude, PB127I and index of free thyroid hormones significantly fell. The 131I two-phase test was inconclusive. 72% of toxic adenomas were inactivated and 88% of patients with still active adenomas were improved or free from symptoms. Clinical improvement apparently preceded the scanning results. Corresponding to the index of free thyroid hormones, 94% were euthyroid, 0.6% hyperthroid, and 2.8% suspected of being hypothryoid. In combination with other findings, especially isotope scanning, 1.7% of patients were suspected of having T3 hyperthyroidism after treatment. A recurrence was observed in 2.1%. The success rate increased with rising radiation dose up to 30000 rd.

In accordance with the recommendations of Pinkel, 147 children with acute lymphoblastic leukemia were treated by a combined cytostatic and radiation therapy during a joint study between May 1971 and Jan. 1, 1974. After a primary cytostatical treatment which brought about a remission of 94% of the patients within four to six weeks, the cranial irradiation was performed, depending on age, with a focal dose of 1500 up to 2400 rd in the course of three or four weeks. Simultaneously, the patients were given methotrexate intrathecally which was followed, later on, by a long-term therapy with cytostatics. By means of this combined treatment, a three-year survival was obtained in 50% (8 of 16) and a complete remission in 44% (7 of 16). The prognosis is the same for boys as for girls. A less favorable prognosis concerns the patients with an initial leukocytosisf more than 50 000 leukocytes/mm3 of blood, an age of more than ten years, and leukemic cells already demonstrable in the cerebrospinal fluid.

The results of 150 placental scans are reported, using 99mTc erythrocytes, 113mIn gelatine and 113mIn tranferrin. Accuracy was checked at surgery and compared with ultra sound findings. In 62% of patients, the indications for placental scintigraphy was suspicion of placenta praevia because of bleeding in late pregnancy. In 38% placental localisation was performed for amniocentesis for Rh incompatibility. Localisation of the placenta was accomplished in 98.6% by scanning and in 95% by ultra sound. Accuracy of scanning was 94% and ultra sound 70%. Placental scanning is at present the most accurate method for a placental localisation and should therefore be used when an accurate diagnosis cannot be achieved by other techniques.

Patients (n = 490) suffering from a major depressive episode according to DSM-III criteria were randomly allocated to groups receiving either moclobemide, imipramine, or placebo treatment. Subjects were treated as out-patients for 6 weeks. On overall assessment of efficacy and on results of the Hamilton Rating Scale for Depression, both moclobemide and imipramine were superior to placebo, but the differences between moclobemide and imipramine were not significant. Premature termination due to insufficient efficacy was more frequent with placebo than with moclobemide or with imipramine, these differences being significant. The overall assessment of tolerance clearly favoured placebo and moclobemide over imipramine. This was also reflected in the frequency of premature terminations due to poor tolerance, as well as in the frequency of adverse events, which were highest in the imipramine group. The only cardiovascular finding was an increase of the mean heart rate with imipramine, maximum at the end of week 1, while placebo and moclobemide displayed no relevant changes. There were no other important drug-related changes.