Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series.

BACKGROUND: Mortality associated with surgery for phaeochromocytoma has dramatically decreased over the last decades. Many factors contributed to the dramatic decline of the mortality rate, and the influence of an α-receptor blockade is unclear and has never been tested in a randomized trial. We evaluated intraoperative haemodynamic conditions and the incidence of complications in patients with and without α-receptor blockade undergoing surgery for catecholamine producing tumours. METHODS: Haemodynamic conditions and perioperative complications were assessed in 110 patients with (B) and 166 without (N) α-receptor blockade. Data were analysed as a consecutive case series of 303 cases and subsequently via propensity score matching, and presented as mean and confidence interval (CI). RESULTS: No difference in maximal intraoperative systolic arterial pressures (B = 178 mm Hg (CI 169-187) vs N = 185 mm Hg (CI 177-193; P = 0.2542) and hypertensive episodes above 250 mm Hg were found (P = 0.7474) for the closed case series. No major complications occurred. Propensity score matching (75 pairs) revealed a significant difference of 17 mm Hg in maximal intraoperative systolic bp for these selected pairs (P = 0.024). CONCLUSIONS: Only a slight difference in mean maximal systolic arterial pressure was detected between patients with or without an α-receptor blockade. There was no difference in the incidence of excessive hypertensive episodes between groups and no major complications occurred. The basis for the general recommendation of perioperative α- receptor blockade for phaeochromocytoma surgery demands further study.

Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early-stage Breast Cancer.

Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age < 50 years, tumor size, luminal B (HER2-) subtype and breast-conserving therapy were additional risk factors for local recurrence. Compared to the luminal A subtype, the risk of systemic recurrence was higher for all other subtypes; additional risk factors for systemic recurrence were lymphatic invasion, absence of systemic therapy and mastectomy. Conclusion: Overall, the risk of local and loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.

Additional prognostic value of lymph node ratio over pN staging in different breast cancer subtypes based on the results of 1,656 patients.

PURPOSE: Although the impact of lymph node ratio (LNR: ratio of metastatic to resected LNs) in breast cancer (BC) has been investigated, its prognostic value in molecular subtypes remains unclear. Our aim was to evaluate the impact of LNR compared to pN-stage in BC subtypes. PATIENTS/METHODS: We analyzed the impact of LNR and pN-stage on disease-free (DFS) and overall survival (OS) in 1,656 patients with primary BC who underwent primary axillary surgery (removal of ≥10 LNs) between 1998 and 2011. The cut-off points for LNR were previously published. Using immunohistochemical parameters tumors were grouped in luminalA, luminalB/HER2-, luminalB/HER2+, HER2+ and triple negative (TNBC). RESULTS: For the entire cohort 5/10-year DFS and OS rates were 88/77% and 88/75%, respectively. LNR and pN-stage were independent prognostic parameters for DFS/OS in multivariate analysis in the entire cohort and each molecular subgroup (p < 0.001). However, increasing LNR seemed to discriminated 10-year DFS slightly better than pN-stage in luminalA (intermediate/high LNR 65/44% versus pN2/pN3 71/53%), luminalB/HER2- (intermediate/high LNR 48/24% versus pN2/pN3 41/42%), and TNBC patients (intermediate/high LNR 49/24% versus pN2/pN3 56/33%). CONCLUSIONS: LNR is an important prognostic parameter for DFS/OS and might provide potentially more information than pN-stage in different molecular subtypes.

Clinicopathological differences between breast cancer in patients with primary metastatic disease and those without: a multicentre study.

OBJECTIVE: Approximately 6% of breast cancer (BC) patients present with primary metastatic disease (pmBC) at first diagnosis. The clinicopathological differences between tumours from patients who have metastatic disease and those who do not are unclear. METHODS: This study was an exploratory analysis of patients with pmBC treated in 8 German breast cancer centres between 1998 and 2010. Phenotypes were defined using the following immunohistochemical markers: oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2). The control arm included the group of patients who had neither local recurrence nor distant metastases at a follow-up of at least 30 months after initial diagnosis. RESULTS: A total of 2214 patients were included. Of these, 1642 had non metastatic BC, and 572 had pmBC. Eighty-five patients (15%) with pmBC were diagnosed at stage T1. On multivariate analysis, factors associated with pmBC were as follows: positive lymph node status, grade 3, lobular histology and Luminal B phenotype (Her 2 positive). Of the sample, 197 patients (34%) with pmBC were diagnosed as stage T2, 90 patients (16%) were diagnosed as stage T3, and 200 patients (35%) were diagnosed as stage T4. Only positive lymph node status and grade 3 were reported as risk factors for distant metastases in patients with stage T3 and T4 cancer. CONCLUSION: There are differences in the clinicopathological features among breast cancer patients with primary metastases and those without. Receptor expression and histological type play a minor role in the risk for metastasis in patients with stage T3 and T4 disease when compared to patients with T1 pmBC tumours. On initial diagnosis, lobular histology and Luminal B positivity (Her 2 positive) in T1 pmBC were determined to be risk factors for primary metastatic disease.

Sexual Function, Sexual Activity and Quality of Life in Women with Ovarian and Endometrial Cancer.

Background: Gynecological cancer (GC) is assumed to have an impact on sexual function and activity, but pertinent evidence is currently limited. Patients and Methods: Sexual function and activity were investigated in patients with gynecological cancer (GC) and in a control group (C), using the "Sexual Activity Questionnaire" (SAQ), the "Female Sexual Function Index" (FSFI), and parts of the EORTC QLQ-C30. Results: 727 women (335 GC and 392 C) were given a questionnaire and 22.8 % of them responded. Response rates were equivalent for both groups (23.6 % [GC] and 22.2 % [C]). 51.5 % (C) and 59.5 % (GC) were not sexually active, mainly owing to lack of a partner (37 %) or lack of interest (21 %) (C group), and lack of interest (40 %, p < 0.05), physical problems (31.9 %, p < 0.05), and physical problems suffered by their partner (21 %, p < 0.05) (GC group). There were significant differences between both groups in the SAQ discomfort score (p < 0.05), but no significant differences in quality of life or other scores for sexuality. Conclusion: The quality of sexuality tends to be impaired in GC patients, but this does not appear to influence quality of life. A shift in priorities caused by the considerable anxiety about surviving the cancer might explain our findings.

Chemotherapy for 70-Year-Old Women with Breast Cancer in Germany: A Survey by the German Breast Group.

Aim: Around half of all women in Germany with breast cancer are older than 65 and approximately one third of them is older than 70 years of age. In theory, the preferred therapeutic management of women with breast cancer aged 65 and above corresponds to that formulated for younger patients and complies with the S3 Guidelines and the therapy recommendations formulated by AGO. To study the current therapies used to treat women with breast cancer aged 70 and above in Germany, a survey of the clinics of the German Breast Group (GBG) was done. Method: An online survey was carried out with requests sent to 599 physicians registered as principal investigators in the database of the GBG. The 12-item questionnaire was used to investigate the systematic therapeutic management of 70-year-old patients in different settings. The indication for chemotherapy was taken as a given. Results: In a neoadjuvant setting, 62 % of physicians opted for anthracycline and taxane-based therapy as did 56.6 % of physicians in an adjuvant setting. One third of physicians preferred a taxane-based therapy with the anti-angiogenesis inhibitor bevacizumab as first-line therapy for primary metastatic cancer and after anthracycline-based therapy. Capecitabine (around 30 %) and navelbine (around 20 %) were proposed as second-line neoadjuvant and adjuvant therapies after prior anthracycline- and taxane-based therapy. Conclusion: The chemotherapy regimen prescribed for women with breast cancer aged 70 and above in Germany appears to be relatively standardised and corresponds to the recommendations given in the S3 Guidelines and by the AGO Breast Committee.

Re-operation outcome in patients referred to a gynecologic oncology center with presumed ovarian cancer FIGO I-IIIA after sub-standard initial surgery.

BACKGROUND: Surgery is the mainstay of treatment for early ovarian cancer both as therapeutic and comprehensive staging. Only the latter allows appropriate tailoring of systemic treatment. However, the compliance with guidelines for comprehensive staging has been reported to be only moderate and, therefore, re-staging procedures are commonly indicated to avoid undertreatment. The purpose of our study was to evaluate re-operation in a tertiary gynecologic oncology unit after primary operation for presumably ovarian cancer FIGO I-IIIA in general gynecology departments. MATERIAL AND METHODS: Forty consecutive patients after primary surgery in the outside institutions for presumed early ovarian cancer with assumed tumor spread limited to the pelvis (FIGO I-IIIA) admitted to our department between 1999 and 2007 were included. In 35 cases re-staging surgery in our unit was indicated. The intra- and post-operative results were compared with initial diagnosis and sites of undetected disease were evaluated. Reasons for re-staging and referral pattern were studied. RESULTS: 40 patients were enrolled of whom 53% came by self-referral. Only 18% were referred by the primary surgeon and the remaining patients were referred by their home gynecologist. Only 5 patients (13%) were classified as having had a comprehensive staging by surgical records and pathology reports and 35 patients underwent comprehensive re-staging laparotomy after which 20 patients (50%) experienced an upstaging including 13 patients with final diagnosis of FIGO stage IIIC. Most frequent sites of primarily undetected tumor were peritoneum (pelvic 34%, diaphragm 13%, paracolic 8%), lymph nodes (para aortic 32%, pelvic 11%), intestines 24%, and residual omental tissue 18%. The indication for post-operative chemotherapy was modified in 53% of patients. CONCLUSION: Comprehensive staging of presumed early ovarian cancer has been described as major problem especially outside gynecologic oncology units. Re-staging results in our department confirmed this deficiency by showing a considerable proportion of upstaging associated with alterations of recommendations for systemic treatment. However, series like this may even underestimate the problem, because incomplete staging is unfortunately accompanied by non-systematic referral practices not reflecting staging quality.

Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival.

BACKGROUND: Survival of patients suffering from cerebral metastases (CM) is limited. Identification of patients with a high risk for CM is warranted to adjust follow-up care and to evaluate preventive strategies. PATIENTS AND METHODS: Exploratory analysis of disease-specific parameter in patients with metastatic breast cancer (MBC) treated between 1998 and 2008 using cumulative incidences and Fine and Grays' multivariable regression analyses. RESULTS: After a median follow-up of 4.0 years, 66 patients (10.5%) developed CM. The estimated probability for CM was 5%, 12% and 15% at 1, 5 and 10 years; in contrast, the probability of death without CM was 21%, 61% and 76%, respectively. A small tumor size, ER status, ductal histology, lung and lymph node metastases, human epidermal growth factor receptor 2 positive (HER2+) tumors, younger age and M0 were associated with CM in univariate analyses, the latter three being risk factors in the multivariable model. Survival was shortened in patient developing CM (24.0 months) compared with patients with no CM (33.6 months) in the course of MBC. CONCLUSION: Young patients, primary with non-metastatic disease and HER2+ tumors, have a high risk to develop CM in MBC. Survival of patients developing CM in the course of MBC is impaired compared with patients without CM.

Revitalization of clinical skills training at the University of the Western Cape.

Most educational institutions that offer health related qualifications make use of clinical skills laboratories. These spaces are generally used for the demonstration and assessment of clinical skills. The purpose of this paper is to share our experiences related to the revitalization of skills training by introducing the skills lab method at the School of Nursing (SoN), University of the Western Cape (UWC). To accommodate the contextual changes as a result of the restructuring of the higher education landscape in 2003, the clinical skills training programme at UWC had to be reviewed. With a dramatic increase in the student numbers and a reduction in hospital beds, the skills lab method provided students with an opportunity to develop clinical skills prior to their placement in real service settings. The design phase centred on adopting a skills training methodology that articulates with the case-based approach used by the SoN. Kolb's, experiential learning cycle provided the theoretical underpinning for the methodology. The planning phase was spent on the development of resources. Eight staff members were trained by our international higher education collaborators who also facilitated the training of clinical supervisors and simulated patients. The physical space had to be redesigned to accommodate audio visual and information technology to support the phases of the skills lab method. The implementation of the skills lab method was phased in from the first-year level. An interactive seminar held after the first year of implementation provided feedback from all the role players and was mostly positive. The results of introducing the skills lab method include: a move by students towards self-directed clinical skills development, clinical supervisors adopting the role of facilitators of learning and experiential clinical learning being based on, amongst others, the students' engagement with simulated patients. Finally, the recommendations relate to tailor-making clinical skills training by using various aspects of teaching and learning principles, i.e. case-based teaching, experiential learning and the skills lab method.

Prognostic impact of additional extended surgical procedures in advanced-stage primary ovarian cancer.

BACKGROUND: Treatment of advanced-stage ovarian carcinoma includes radical cytoreductive surgery, which aims at removing all visible tumor tissue followed by platinum and paclitaxel chemotherapy. Complete tumor resection may require extended surgical procedures. This paper reports on the prognostic impact of extensive surgery and surgical morbidity in patients with advanced-stage ovarian carcinoma. METHODS: Patients with ovarian carcinoma [Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIIB-IV] undergoing primary surgery in our tertiary gynecologic oncology unit between 1997 and 2007 were eligible for this study. The impact of established prognostic factors and the interaction with extent of surgical procedures on survival were assessed. RESULTS: A total of 267 patients aged between 29 and 88 years (median 64 years) were eligible for this study. Overall survival time was improved in patients who underwent complete tumor resection [hazard ratio (HR) 3.61 (1.91-6.61), P < 0.001]. No significant survival difference was observed between completely operated patients in whom extended or standard surgical procedures were applied [HR 1.37 (0.70-2.69), P = 0.358], and severe surgical complications were found to be equally distributed between the two patient groups. CONCLUSIONS: Our results may encourage the application of extended surgical procedures in patients who would otherwise be rendered incompletely debulked after primary cytoreduction. We could demonstrate an impact of complete tumor resection on patient prognosis and this was not traded off for extensive additional surgical morbidity.

Pattern and clinical predictors of lymph node metastases in epithelial ovarian cancer.

Para-aortic lymphadenectomy is part of staging in early epithelial ovarian cancer (EOC) and could be part of therapy in advanced EOC. However, only a minority of patients receive therapy according to guidelines or have attendance to a specialized unit. We analyzed pattern of lymphatic spread of EOC and evaluated if clinical factors and intraoperative findings reliably could predict lymph node involvement, in order to evaluate if patients could be identified in whom lymphadenectomy could be omitted and who should not be referred to a center with capacity of performing extensive gynecological operations. Retrospective analysis was carried out of all patients with EOC who had systematic pelvic and para-aortic lymphadenectomy during primary cytoreductive surgery. One hundred ninety-five patients underwent systematic pelvic and para-aortic lymphadenectomy. Histologic lymph node metastases were found in 53%. The highest frequency was found in the upper left para-aortic region (32% of all patients) and between vena cava inferior and abdominal aorta (36%). Neither intraoperative clinical diagnosis nor frozen section of pelvic nodes could reliably predict para-aortic lymph node metastasis. The pathologic diagnosis of the pelvic nodes, if used as diagnostic tool for para-aortic lymph nodes, showed a sensitivity of only 50% in ovarian cancer confined to the pelvis and 73% in more advanced disease. We could not detect any intraoperative tool that could reliably predict pathologic status of para-aortic lymph nodes. Systematic pelvic and para-aortic lymphadenectomy remains part of staging in EOC. Patients with EOC should be offered the opportunity to receive state-of-the-art treatment including surgery.

Cisplatinum rechallenge in relapsed ovarian cancer patients with platinum reinduction therapy and carboplatin hypersensitivity.

Hypersensitivity reactions have been reported as limiting side effect in patients re-exposed to carboplatin for relapsed gynecologic malignancy. This study analyzed the incidence, clinical features, management, and outcome of carboplatin-associated hypersensitivity reactions. We performed a retrospective study and analyzed medical records of all gynecological cancer patients treated with carboplatin in our institution from 2000 to 2003. No hypersensitivity reactions were observed in 171 patients during the first carboplatin-containing chemotherapy. All six carboplatin-associated hypersensitivity reactions occurred in 69 patients who were re-exposed to carboplatin (9%). The median number of carboplatin cycles prior to hypersensitivity reaction was nine (range, 8-13). Cisplatin rechallenge was performed in five patients, and no hypersensitivity occurred. An increase in neurotoxicity (National Cancer Institute Common Toxicity Criteria grade 2) was documented in two patients who had residual neurotoxicity grade 1 due to prior taxane treatment. Cisplatinum rechallenge is a feasible strategy to overcome carboplatin hypersensitivity. However, close monitoring of neurotoxicity is necessary, particularly in patients with residual neurotoxicity due to prior platinum- and taxane-containing chemotherapy.

Treatment utilisation and trauma characteristics of child and adolescent inpatients with posttraumatic stress disorder.

OBJECTIVE: Few empirical studies have addressed the impact of trauma exposure and posttraumatic stress disorder (PTSD) on treatment utilisation and outcome in South African youth. This study was undertaken to document demographic, clinical, and treatment characteristics of child and adolescent inpatients with PTSD. DESIGN: A retrospective chart study of all patients presenting to a child and adolescent inpatient unit was conducted between 1994-1996. For children and adolescents diagnosed with PTSD; demographic, diagnostic and treatment variables, including trauma type, family history, and delays in treatment seeking, were documented. SETTING: Child and Adolescent Psychiatric Inpatient Unit, Tygerberg Hospital, Cape Town. SUBJECTS: Children and adolescents (2 to 18 years) presenting to an inpatient unit (n = 737). RESULTS: 10.3% (n = 76) met diagnostic criteria for PTSD. Gender differences were clearly evident: PTSD was six times more prevalent in girls (65 with PTSD were female and 11 were male); girls were most likely to have experienced rape or sexual abuse while boys were most likely to have witnessed a killing. Psychotherapy was the most common intervention for PTSD, followed by treatment with a tricyclic antidepressant. 97.4% of children and adolescents who were treated were improved at treatment endpoint. Delays in seeking treatment and problems with the primary support group were highly prevalent. CONCLUSION: PTSD is a common disorder that is responsive to treatment with psychotherapy and/or tricyclic antidepressants in child and adolescent inpatients. These findings underscore the importance of early identification and treatment of childhood PTSD in mental health settings, in particular tertiary service institutions.

Treatment utilisation and trauma characteristics of child and adolescent inpatients with posttraumatic stress disorder.

OBJECTIVE: Few empirical studies have addressed the impact of trauma exposure and posttraumatic stress disorder (PTSD) on treatment utilisation and outcome in South African youth. This study was undertaken to document demographic, clinical, and treatment characteristics of child and adolescent inpatients with PTSD. DESIGN: A retrospective chart study of all patients presenting to a child and adolescent inpatient unit was conducted between 1994-1996. For children and adolescents diagnosed with PTSD; demographic, diagnostic and treatment variables, including trauma type, family history, and delays in treatment seeking, were documented. SETTING: Child and Adolescent Psychiatric Inpatient Unit, Tygerberg Hospital, Cape Town. SUBJECTS: Children and adolescents (2 to 18 years) presenting to an inpatient unit (n = 737). RESULTS: 10.3% (n = 76) met diagnostic criteria for PTSD. Gender differences were clearly evident: PTSD was six times more prevalent in girls (65 with PTSD were female and 11 were male); girls were most likely to have experienced rape or sexual abuse while boys were most likely to have witnessed a killing. Psychotherapy was the most common intervention for PTSD, followed by treatment with a tricyclic antidepressant. 97.4% of children and adolescents who were treated demonstrated significant improvement. Delays in seeking treatment and problems with the primary support group were highly prevalent. CONCLUSION: PTSD is a common disorder that is responsive to treatment with psychotherapy and/or tricyclic antidepressants in child and adolescent inpatients. These findings underscore the importance of early identification and treatment of childhood PTSD in mental health settings, in particular tertiary service institutions.

Patients presenting with fresh trauma after interpersonal violence. Part I. Alcohol and substance abuse.

BACKGROUND: Patients presenting with fresh trauma frequently have evidence of substance abuse. Nevertheless, few South African studies have measured the levels of both alcohol and other substances in patients presenting with fresh trauma after interpersonal violence. METHODS: A representative sample of patients presenting with fresh trauma to the Trauma Unit of Tygerberg Hospital was selected for study. Subjects were questioned about the nature of the trauma and breath alcohol concentrations were determined. Blood and urine samples for analysis of alcohol and other substances were obtained from approximately half the subjects. RESULTS: Alcohol was found to be present in a majority of patients who presented after interpersonal violence, while other substances were present less commonly. There was a high correlation between clinical history of alcohol use, breath analysis of alcohol and blood alcohol measurement. CONCLUSIONS: Alcohol use plays a significant role in trauma due to interpersonal violence. It is essential to screen victims of interpersonal violence for a history of alcohol and other substances. Breath analysis for alcohol is a useful adjunct to clinical screening.

Patients presenting with fresh trauma after interpersonal violence. Part II. Assault history.

BACKGROUND: Patients presenting with fresh trauma are frequently victims of interpersonal violence. Nevertheless, few South African studies have documented the history surrounding such assaults and their management. METHODS: Patients presenting with fresh trauma to the Trauma Unit of Tygerberg Hospital were selected in order to provide a representative sample. Where patients were victims of interpersonal violence, a history of the current and previous assault(s) was taken. RESULTS: Victims of interpersonal violence often reported that they had been involved in such violence on previous occasions. Nevertheless, these patients had rarely received management from psychosocial services. Patients with a previous history of having been assaulted had a number of distinct characteristics, including female gender and increased substance use. CONCLUSIONS: Trauma has justifiably been described as a recurrent disease. There is an urgent need for effective psychosocial services for victims of interpersonal violence; ideally, this would prevent future multiple hospital admissions.

Sequence-based identification of T-DNA insertion mutations in Arabidopsis: actin mutants act2-1 and act4-1.

A method is presented to facilitate the isolation of mutations in plant genes, which requires knowledge of the target gene or protein sequence, and is independent of mutant phenotype. The polymerase chain reaction was used to amplify the junctions between a T-DNA insert and the gene of interest from pools of mutant plant lines. The approach was used to identify mutations in Arabidopsis thaliana actin genes. The Arabidopsis genome encodes 10 actins in six ancient subclasses each with distinct expression patterns. Primers in the T-DNA border and highly degenerate actin primers, designed from conserved amino acid motifs, were used to prime the amplification. The PCR products were transferred to filters and probed for actin at low stringency. Thus, mutations in all 10 actin genes were screened for simultaneously. Mutations in the vegetative constitutive actin gene, ACT2, and the pollen-specific actin gene, ACT4, were identified in a population of 5300 lines containing approximately 1.5 T-DNA insertions per line. The screen was sensitive enough that actin insertion alleles were easily distinguished among pools of 100 plant lines. PCR techniques were used which accelerated the purification of mutant lines, and segregation, physical mapping, and sequencing of the act2-1 and act4-1 mutations. This strategy should be generally useful in screening mutant libraries made with a variety of plant insertion elements for mutations in any known sequence.

Gadolinium ions inhibit exocytotic vasopressin release from the rat neurohypophysis.

Single rat neurointermediate lobes (n.i.l.s) were fixed by their stalks to a platinum wire clip electrode and incubated in oxygenated Krebs-HEPES medium. Vasopressin release int the medium was determined by radioimmunoassay. Vasopressin secretion was increased by different stimuli and the effects of gadolinium (Gd3+) were tested. Electrical stimulation (15 Hz, three times 1 min with 1 min intervals) increased vasopressin release in a calcium-dependent manner. Gd3+ (10 microM to 3 mM) inhibited the evoked release of vasopressin in a concentration-dependent fashion; at 3 mM the inhibition was 98%. The inhibitory effect of Gd3+ up to 300 microM was antagonized by increasing the calcium concentration in the medium up to 6 mM. The effects of 1 and 3 mM-Gd3+ were unaffected by increasing the calcium concentration. Exposure of n.i.l.s to depolarizing concentrations of potassium (high K+, 60 mM, 30 min) increased the vasopressin release more than 33-fold. The elevated vasopressin release remained constant during six consecutive 5 min periods. In the initial 5 min period 300 microM-Gd3+ reduced the evoked vasopressin release by 80% but during the last 5 min period only by 30%. At 3 mM-Gd3+ vasopressin release was completely blocked during the whole time of incubation with high K+. Vasopressin release induced by exposure of n.i.l.s to cold (4 degrees C, 20 min) was completely inhibited by 3 mM-Gd3+, but reduced by only 25% in the presence of 300 microM-Gd3+. Vasopressin release induced by incubation of n.i.l.s with the ionophore X-537A (lasalocid) (10 microM, 30 min) was reduced by 90% in the presence of 300 microM-Gd3+ and completely prevented by 3 mM-Gd3+. 300 microM-Gd3+, added to the incubation medium, had no significant effect on the vasopressin release from crude synaptosomal preparations evoked by high K+. However, when 300 microM-Gd3+ was already present during the tissue homogenization, the evoked vasopressin release from the synaptosomes was completely blocked. It is concluded that Gd3+ inhibits exocytotic vasopressin release at two different sites. First, Gd3+ may block voltage-regulated calcium channels. Secondly, Gd3+ may inhibit the exocytotic release mechanism by an intracellular site of action. It is speculated that contractile proteins may be the intracellular target for Gd3+.

[Quantitative whole-body skeletal scintigraphy with a gamma camera and pinhole collimator]. / Die quantifizierende Ganzkörper-Skelettszintigraphie mit Gamma-Camera und Pinhole-Kollimator.

Quantitative evaluation of whole-body bone scans is valuable for the description of metabolic activity in systemic bone disease and provides parameters of whole-body activity retention up to 24 h after injection of the radiopharmacon, of bone to soft tissue relation and of the activity in the epiphysis and diaphysis. A combination of whole-body imaging by a gamma-camera with pinhole collimator and a series of single pictures evaluated by the ROI technique is able to record these parameters with sufficient precision. This is demonstrated by measuring phantoms, and patients with and without bone disease. In 34 patients with systemic bone disease the quantitative parameters are altered partially, the changes however are insufficient for their differential diagnosis.