Infiltration of Prostate Cancer by CD204+ and CD3+ Cells Correlates with ERG Expression and TMPRSS2-ERG Gene Fusion.

BACKGROUND: The aim of the study was to detect CD204 + and CD3 + cells in the infiltrate of benign prostatic hyperplasia, prostatic intraepithelial neoplasia and prostatic cancer in prostate specimens after radical prostatectomy. Another goal was to determine correlation of the intensity of the infiltration with ERG oncoprotein expression as well as with the presence of activat-ing translocation TMPRSS2-ERG. MATERIALS AND METHODS: To confirm the translocation, we used fluorescence in situ hybridization. Imunohistochemistry was used to detect the presence of ERG oncoprotein and for assesment of the number of CD204+ and CD3+ infiltrat-ing cells. We determined the capability to infiltrate malignant structures accord-ing to differences in infiltration of benign and malignant prostate structures. RESULTS: Biometric analysis confirmed that the number of CD204+ macrophages in the malignant structure was significantly higher than in the benign prostatic hyperplasia regardless of the fusion pattern. Increased infiltration by CD3+ cells was only detected in malignant structures of the prostate in a group with normal signal pattern and in a group with TMPRSS2-ERG fusion. Expression of ERG positively correlated with CD204+ and CD3+ cells infiltration of malignant structures only in cases where the TMPRSS2-ERG fusion was found. In the group with a break in the TMPRSS2 gene, a positive correlation was only found between ERG expression and CD204+ macrophages infiltration. In cases with a normal signal pattern, no correlation was found. In the group with TMPRSS2-ERG fusion we observed significantly more cases with a good capability of CD204+ cells to infiltrate malignant structures, unlike the group with a normal signal pattern, where there were more cases with the weak reactivity of CD204 + cells to infiltrate the malignant structures. The same was observed for CD3+ cells. CD204+ macrophages and CD3+ T-lymphocytes in the group with TMPRSS2-ERG gene fusion, infiltrated the malignant prostate structures more intensely, but their effect on malignant transformation may be different. CONCLUSIONS: The association between the presence of the TMPRSS2-ERG fusion and the different capability of inflammatory cells to infiltrate malignant structures has not been reported so far. The results confirm the important role of the activated ERG gene, due to TMPRSS2-ERG fusion, in the development of inflammation of the prostate as well as the effect of inflammatory cells on the course of neoplastic process. This leads to considerations about introduc-ing immunomodulatory modalities into prostate cancer therapeutic protocols. Key words: prostate cancer -  TMPRSS2-ERG gene fusion -  ERG -  immune response -  CD204+ macrophages -  CD3+ T-lymphocytes.

Sympatric divergence and clinal variation in multiple coloration traits of Ficedula flycatchers.

Geographic variation in phenotypes plays a key role in fundamental evolutionary processes such as local adaptation, population differentiation and speciation, but the selective forces behind it are rarely known. We found support for the hypothesis that geographic variation in plumage traits of the pied flycatcher Ficedula hypoleuca is explained by character displacement with the collared flycatcher Ficedula albicollis in the contact zone. The plumage traits of the pied flycatcher differed strongly from the more conspicuous collared flycatcher in a sympatric area but increased in conspicuousness with increasing distance to there. Phenotypic differentiation (PST ) was higher than that in neutral genetic markers (FST ), and the effect of geographic distance remained when statistically controlling for neutral genetic differentiation. This suggests that a cline created by character displacement and gene flow explains phenotypic variation across the distribution of this species. The different plumage traits of the pied flycatcher are strongly to moderately correlated, indicating that they evolve non-independently from each other. The flycatchers provide an example of plumage patterns diverging in two species that differ in several aspects of appearance. The divergence in sympatry and convergence in allopatry in these birds provide a possibility to study the evolutionary mechanisms behind the highly divergent avian plumage patterns.

Endovascular treatment of acute basilar artery occlusion: time to treatment is crucial.

AIM: To evaluate the safety and efficacy of multimodal endovascular treatment (EVT) of acute basilar artery occlusion (BAO), including bridging therapy [intravenous thrombolysis (IVT) with subsequent EVT], to compare particular EVT techniques and identify predictors of clinical outcome. MATERIALS AND METHODS: This retrospective, multi-centre study comprised 72 acute ischaemic stroke patients (51 males; mean age 59.1 ± 13.3 years) with radiologically confirmed BAO. The following data were collected: baseline characteristics, risk factors, pre-event antithrombotic treatment, neurological deficit at time of treatment, localization of occlusion, time to therapy, recanalization rate, post-treatment imaging findings. Thirty- and 90-day outcomes were evaluated using the modified Rankin scale with a good clinical outcome defined as 0-3 points. RESULTS: Successful recanalization was achieved in 94.4% patients. Stepwise binary logistic regression analysis identified the presence of arterial hypertension (OR = 0.073 and OR = 0.067, respectively), National Institutes of Health Stroke Scale (NIHSS) at the time of treatment (OR = 0,829 and OR = 0.864, respectively), and time to treatment (OR = 0.556 and OR = 0.502, respectively) as significant independent predictors of 30- and 90-day clinical outcomes. CONCLUSION: Data from this multicentre study showed that multimodal EVT was an effective recanalization method in acute BAO. Bridging therapy shortens the time to treatment, which was identified as the only modifiable outcome predictor.

Androgenetic alopecia and polymorphism of the androgen receptor gene (SNP rs6152) in patients with benign prostate hyperplasia or prostate cancer.

BACKGROUND: Both androgenetic alopecia (AGA) and carcinoma of the prostate (CaP) or benign prostatic hyperplasia (BPH) are androgen-dependent disorders. OBJECTIVE: To investigate the relationships between male androgenetic alopecia, androgen receptor (AR) gene polymorphism (SNP rs6152) and clinical characteristics of BPH and prostate cancer. METHODS: Overall, 309 male subjects with prostate disease (BPH or CaP) were examined. We evaluated the standard grades of AGA (I-VII) by Hamilton-Norwood classification and 195 patients were also assessed by phototrichogram. Prostate-specific antigen (PSA) and testosterone levels were also measured. Polymorphism rs6152 of the AR was evaluated from blood samples by PCR-RFLP. Data were statistically evaluated. RESULTS: The expected positive correlation between age and AGA grade and the expected negative correlation between hair density and age and between anagen/telogen and AGA were found. A statistically significant difference between patients with A and G alleles in terms of AGA grade was found. The predominant G allele was more frequent in patients with higher grade of alopecia and in patients with significantly higher PSA. There was no correlation between diagnosis (BPH or CaP) and polymorphism. Patients with prostate inflammation had a statistically significant higher grade of AGA, together with higher PSA. CONCLUSIONS: We confirmed that the AR gene polymorphism (SNP rs6152 G>A) is associated with the development of AGA and higher PSA levels in patients with BPH but not cancer. A novel finding of our study is that BPH patients with prostate inflammation had a significantly higher grade of AGA together with significantly higher PSA levels.

Relation of ETS transcription factor family member ERG, androgen receptor and topoisomerase 2ß expression to TMPRSS2-ERG fusion status in prostate cancer.

Fusion of TMPRSS2 with ERG in prostate cells is determined by double-strand DNA breaks induced by androgen signaling and transcription stress. The enzyme topoisomerase 2ß (TOP2B) mediating DNA processing, plays an important role in DNA cleavage. The aim of this study was to analyse expression of AR, TOP2B and ERG in relation to TMPRSS2-ERG gene rearrangement and relevant clinicopathological characteristics in prostate cancer (CaP). Immunohistochemical staining and FISH were used for investigation. ERG expression in prostate cell lesions positively correlated with levels of TMPRSS2-ERG fusion gene (p<0.0001). The most significant co-expression of ERG was found with AR in CaP (p=0.001). Significantly more frequent co-expression of ERG was also revealed with TOP2B (p=0.028). ERG protein expression did not correlate with CaP differentiation status as we found no significant differences in ERG expression for different Gleason categories. We demonstrated a statistically significant positive correlation between the percentage of cells with fusion gene TMPRSS2-ERG in CaP and metastatic potential of tumors (p=0.011). Besides these positive corelations of AR with ERG (p=0.001) and TOP2B with ERG (p=0.028), we also demonstrated a significant co-expression of AR with TOP2B (p=0.007) in CaP. There was a statistically significant increase in the TOP2B H-index in locally advanced CaP in comparison with localized tumors (p=0.046). ERG expression correlates with occurrence of TMPRSS2-ERG fusion and with AR-driven malignant transformation. The results indicate that detection of the TMPRSS2-ERG fusion gene and parallel immunohistochemical examination of AR, TOP2B and ERG has diagnostic significance and may be useful in assessing the biological character of the prostate cancer as well as selecting the best treatment.

[Shoulder arthrodesis using an external fixator in the treatment of chronic inflammatory complications of proximal humeral fractures]. / Artrodéza ramene zevním fixatérem v lécbe chronických zánetlivých komplikací zlomenin proximálního humeru.

INTRODUCTION: Chronic osteomyelitis is a serious chronic condition that frequently results in permanent after-effects. Treatment is complex, lengthy and costly. MATERIAL AND METHODS: Between the beginning of 2003 and the end of 2010, 438 operations of the proximal humerus were performed at our department using either angle-stable osteosynthesis or hemiarthroplasty. In four cases out of this group of patients, deep tissue infection affecting the bone developed. These four patients were treated with arthrodesis of the shoulder joint using an external fixation device. Arthrodesis was also the treatment method in a patient who previously received conservative treatment but developed chronic osteomyelitis. RESULTS: Healing of the infectious focus along with the formation of stable, painless shoulder was achieved in all five patients, with the arthrodesis offering full support for the limbs periphery. CONCLUSION: The above method represents an alternative to reverse arthroplasty of the shoulder joint usually performed after infection is cured. While function of the limb usually worsens after arthrodesis, the risk of recurring inflammation is substantially lower.

Ewing's sarcoma of the urinary bladder - the urologic and pathologic differential diagnosis and current therapeutic options.

BACKGROUND: Bladder cancer is 11th most common cancer worldwide. Histologically, most of the tumors are classified as urothelial carcinomas. Less common variants (squamous cell or adenocarcinomas) usually comprise up to 10% of cases. Other types of tumors are exceptional. The finding of Ewing's sarcoma in the bladder is considered extremely rare. CASE: We present the case of a 54-year-old female patient examined for painless hematuria. During the follow-up examination, a bulky tumor of the bladder was detected, but considering the extent of the bladder tumor, only a diagnostic transurethral resection was possible. According to the primary staging, the disease was already advanced at the time of admission with metastatic spread, anemia and present obstruction of the upper urinary tract. RESULTS: Histologically, Ewing's sarcoma was surprisingly demonstrated in the urinary bladder. Anemia caused by hematuria and advanced disease was corrected by blood transfusions and obstruction of the right kidney by puncture nephrostomy. However, despite a very quick diagnosis, completion of staging and preparation of the patient for further treatment, the patient had died before the planned systemic treatment began. CONCLUSION: The diagnosis of Ewing's sarcoma is identical to that of the other bladder tumors, i.e. transurethral resection. In the case of confirmation of this histological type, it is necessary to complete staging examinations and start multimodal treatment. Early systemic chemotherapy plays a key role and if metastatic spread is excluded, radical cystectomy or radiotherapy are included, too. The aim of our communication is to present a rare case of this disease, discuss the differential diagnosis and point out the principles and possibilities of its treatment.

Predictors of good clinical outcome in acute stroke patients treated with intravenous thrombolysis.

OBJECTIVES: Intravenous thrombolysis (IVT) is considered an effective treatment for acute ischemic stroke (IS). However, not all treated patients may achieve good outcome. The aim was to evaluate whether the initial NIHSS and DWI infarct volume could be the predictors for good outcome after IVT. PATIENTS AND METHODS: The set of 125 patients with consecutive hemispheric IS (78 men; mean age 66.0 ± 12.1 years) treated with IVT within 3 h was analyzed. DWI volume was measured on admission. Good outcome was defined as a score 0-2 in modified Rankin Scale. RESULTS: Multivariate logistic regression analysis showed initial NIHSS as an independent predictor of good outcome (P = 0.001). ROC curves showed baseline NIHSS ≤13.5 points and DWI volume ≤13.7 ml as cut-offs related to good outcome. CONCLUSIONS: The initial NIHSS and DWI volume might be the predictors for good clinical outcome in acute stroke patients treated with IVT. The initial NIHSS score seems to be more accurate.

Immunohistochemical localization and analysis of kallikrein-related peptidase 7 and 11 expression in paired cancer and benign foci in prostate cancer patients.

Kallikrein-related peptidases 7 and 11 (KLK7/KLK11) share a high degree of structural similarity with PSA (KLK3) and other KLKs. The aim of this study was to evaluate differences in KLK7/ KLK11 expression in paired cancer/benign prostate foci and to determine possible associations with clinicopathological parameters. Seventy archived paraffin-embedded tissue samples obtained from radical prostatectomy were stained for KLK7, KLK11, PSA and PSMA and expression was evaluated semiquantitatively. The results showed statistically significant differences for all studied proteins between BPH and CaP foci. Both KLK7 (P=0.026) and KLK11 (P<0.001) expressions were decreased in prostate cancer cells compared to normal/benign prostate cells. Positive correlations were found for both KLK7 (Rs=0.74, P<0.001) and KLK11 (Rs=0.35, P=0.003) between CaP and BPH. We found a statistically significant upregulation of KLK11 in advanced cases compared to localized ones (P=0.026). For the first time, we report lower expression of KLK11 in CaP compared to BPH and slight upregulation of KLK11 in advanced tumors compared to localized ones. Our observations support the diagnostic potential of KLK7/KLK11 for early prostate cancers but further studies on larger cohorts are needed in order to validate the clinical value of these biomarkers and clarify their biological role in prostate development and tumorigenesis.

Conceptual design of Thomson scattering diagnostics for the COMPASS-U tokamak.

The Thomson scattering (TS) diagnostic, one of the key diagnostics used on the tokamaks around the world, is planned for the COMPASS-U tokamak, which is recently under design and construction in the Institute of Plasma Physics in Prague, Czech Republic. This tokamak is supposed to be a world-unique, high magnetic field device with hot walls, allowing for the study of the plasma exhaust in advanced operational scenarios and testing cutting-edge technologies relevant to future fusion reactors, e.g., use of liquid metals. The core and edge TS systems are planned to be designed and operational, with a limited performance, already in the early stage of the tokamak operation. In this contribution, requirements and the most important constraints defining the TS system design are presented. The impact of both the possible collection lens location and spatial resolution on the plasma pedestal observation is simulated. Design considerations also take into account the high-resolution TS core and edge systems available from the COMPASS tokamak, which will be reused. The collection lenses will be newly built. Extension of the detection system will complete the plasma radius coverage in the future. The divertor TS is considered for later periods.

Thrombolytic treatment of ischaemic stroke occurring during a migrainous attack: a case report.

Authors report a case of young female suffering from the acute ischaemic stroke with right-sided hemiplegia, hemianopsia and hemihypoaesthesia during a migrainous attack without aura. Magnetic resonance imaging detected infarction in the left occipital lobe and occlusion of branches of the posterior cerebral artery (PCA). Combined treatment with systemic thrombolysis and sonothrombolysis was used, leading to the early PCA recanalization, and to a favourable clinical outcome after 1 month. Intravenous thrombolytic treatment administered within the therapeutic window may be useful in cerebral ischaemia associated with migraine when an arterial occlusion is documented.

Occurrence of diabetes mellitus in spontaneous intracerebral hemorrhage.

The role of diabetes mellitus (DM) in the etiopathogenesis of spontaneous intracerebral hemorrhage (SICH) is controversial. The aim was to assess the role of DM in our SICH patients. In a hospital-based cross-section study, the occurrence of DM prior to a hemorrhagic stroke was observed in 80 SICH patients (44 males, aged 36-87 years, mean 67.1 +/- 11.9 years; 36 females, aged 56-86 years, mean 71.1 +/- 8.3 years), and in a control group (CG) of 80 age- and sex-matched patients with low back pain. All patients were treated at the Departments of Neurology and Neurosurgery, University Hospital, Olomouc, Czech Republic. Two-sample t test and Pearson's homogeneity chi(2) test were applied when assessing statistical significance. DM was found in 37.5% of SICH patients versus 22.5% of CG subjects (P < 0.05). DM occurs significantly more frequently in SICH patients in the Olomouc region of the Czech Republic when compared to the general population.

[Hemiarthroplasty for management of proximal humeral fractures]. / Hemiartroplastika v lécbe zlomenin proximálního humeru.

PURPOSE OF THE STUDY: With the advent of angle-stable implant systems in surgical treatment of proximal humeral fractures, the number of indications to shoulder hemiarthroplasty decreased dramatically, because these modern implants provide certain fixation of osteoporotic bone fragments in elderly patients. MATERIAL AND METHODS: The authors report on their experience with shoulder replacement surgery in 29 patients, of which 26 underwent urgent surgery. The indications for acute hemiarthroplasty included humeral head fractures in which destruction of the articular surface exceeded 40 %, and fractures with evident or suspected insufficient vitality of the humeral head in elderly patients. Other indications included intra-operative osteosynthesis with the necessity of subsequent intra-operative conversion. Two patients with late implant failure and one with bone malunion, after conservative treatment of a fracture, were indicated for second stage hemiarthroplasty. The authors draw attention to the most frequent errors associated with this surgery and describe guidelines used in post-operative care. A total of 20 patients were evaluated by the Constant Score at an average follow-up of 12.5 months (range, 6-39 months). RESULTS: Shortly after the operation, loosening of parts of the modular prosthetic system occurred in two patients. Aseptic loosening of the stem was observed in two patients, and early deep wound infection was found in two patients. The implant was removed in two cases, once for its loosening, and once for persisting infection. None of the patients died due to causes related to shoulder hemiarthroplasty. The functional outcomes corresponded to the choice of patients, because the indications for hemiarthroplasty involved the most serious fractures in elderly patients. Post-operative subjective evaluation usually showed only intermittent and mild pain; only four patients complained of severe pain. Arm elevation in the youngest age group, i.e., up to 59 years, was 100 degrees on the average, with a range of 70 to 140 degrees. In the patients 60 to 69 years old, the average elevation was 95 degrees, with a range of 90 to 110 degrees; in the oldest group, i.e., 70 years and older, the average elevation was 75 degrees and the range was 30 to 130 degrees. Excellent outcomes with elevation over 120 degrees were achieved in four patients only. The average Constant Scores in the three age groups were 68, 54 and 42 points, respectively. DISCUSSION: When deciding the indications for hemiarthroplasty, many factors must be considered. Beside the type of fracture and patient's age, a possible impairment of blood supply, which is associated with avascular bone necrosis, must also be taken into account. Criteria for correlation between vascularisation impairment and X-ray findings, with the analysis of advantages and disadvantages of hemiarthroplasty, are described in this article. In the end, an indication scheme for the treatment of proximal humeral fractures is suggested. CONCLUSIONS: Good results achieved in shoulder hemiarthroplasty are related to both the development of modular prosthetic systems for shoulder replacement and a faultless surgery procedure itself. Careful and long-term post-operative care also plays an important role. Functional outcomes after acute hemiarthroplasty are clearly better than those after a second-stage operation performed when conservative treatment or previous osteosynthesis have failed.

Computerized Angiographic Occlusion Rating for Ruptured Clipped Aneurysms is Superior to Subjective Occlusion Rating.

BACKGROUND AND PURPOSE: The computerized occlusion rating to estimate angiographic occlusion of embolized aneurysms is superior to the subjective occlusion rating. In this study, we compared the 2 methods in the analysis of aneurysms clipped after subarachnoid hemorrhage. MATERIALS AND METHODS: The pre- and postoperative angiographic images (DSA) of 95 selected patients were analyzed and stratified in 4 grades (grade 0 for 100%, grade I for <99%-90%, grade II for <89%-70%, grade III for <70% occlusion) by using the subjective (angiographic) occlusion rating and the computerized (angiographic) occlusion rating. For the subjective occlusion rating, the occlusion rate was estimated; for the computerized occlusion rating, the "occluded" and "nonoccluded" aneurysm areas were automatically calculated in square millimeters after outlining the ideal occlusion line. RESULTS: With the subjective occlusion rating, 75 (78.9%), 12 (12.6%), 7 (7.4%), and 1 (1.1%) and with the computerized occlusion rating 45 (47.4%), 24 (25.3%), 20 (21.0%), and 6 (6.3%) patients had aneurysms stratified to grades 0, I, II and III, respectively. The interobserver variation was significant with the subjective occlusion rating but not with the computerized occlusion rating. The subjective occlusion rating overestimated aneurysm occlusion in 30 (31.6%) patients. Mean values were the following: subjective occlusion rating of 97.5 ± 6.3% and computerized occlusion rating of 93.5 ± 9.7%; P = < .001. No patient rebled, and 4 patients underwent retreatment during 36 ± 38.9 months; the predictive value (log-rank, Kaplan-Meier) of the subjective and computerized occlusion ratings with respect to retreatment was highly significant for both methods (subjective occlusion rating: χ(2), 29.65; P < .001; computerized occlusion rating: χ(2), 35.57, P < .001). CONCLUSIONS: The 2 methods showed remarkable differences in the estimation of the angiographic occlusion rates of clipped aneurysms. The clearly lower interobserver variation of the computerized versus subjective occlusion rating may indicate a superiority of the computerized occlusion rating.

Spontaneous action potential activity in isolated dorsal root ganglion neurons from rats with a painful neuropathy.

One of the physiological changes accompanying neuropathic pain from nerve injury is the spontaneous firing of primary afferent fibers. At least some of this activity is thought to arise from the dorsal root ganglion. We have investigated whether this activity is resident in the cell bodies of dorsal root ganglion neurons and if it is retained in vitro. Dorsal root ganglion neurons from rats with a chronic constriction injury (CCI) from 4 loose ligatures of chromic gut sutures around the sciatic nerve were used. Isolated neurons were studied using the whole cell patch technique in current clamp mode within 6 hours of preparation. Neurons from rats with CCI showed a significantly increased incidence of spontaneous action potential activity (18/88 vs. 1/36 neurons). Firing activity consisted of both random spikes and long trains of regular, rapid spikes, with random activity being the exclusive mode in most cells. Spontaneous resting potential fluctuations (up to 10 m V peak-to-peak) occurred in both control and CCI neurons, and triggered the spontaneous, random action potentials in neurons from CCI rats. Spontaneously firing neurons exhibited more negative action potential threshold (-34.8 mV) when compared to quiescent neurons from ganglia either after CCI (-18.7 mV) or controls (-20.5 mV). These findings show that spontaneous action potential activity after CCI is a property residing in the cell bodies of dorsal root ganglion neurons and is amenable to more detailed analysis using such an in vitro system, allowing better understanding of the cellular changes underlying neuropathic pain from nerve injury.

Alteration of Na+ currents in dorsal root ganglion neurons from rats with a painful neuropathy.

Increased excitability of primary sensory neurons may be important for the generation of neuropathic pain from nerve injury. The currents underlying the action potentials of these neurons are largely carried by Na+, and changes in Na+ currents have been postulated to contribute to this increased excitability. Using patch clamp in whole-cell mode, we recorded Na+ currents from DRG neurons freshly isolated from rats with a chronic constriction injury (CCI), an animal model of neuropathic pain. We found significant changes in Na+ currents after CCI when cell size and Na+ channel properties were used to segregate DRG neurons. Most changes were concentrated in small neurons (< or = 25 microm diameter) and in the slow TTX-resistant current that is predominant in these cells. CCI produced two principal changes in these cells: it shifted the voltage-dependence of activation of the TTX-resistant current to more negative potentials and it reduced the average density of this current. The decrease in density appears to be primarily due to the decrease in the number of small neurons expressing this current. The net result is a change in both activation and steady-state inactivation properties of the total Na+ current to more negative potentials without a significant change in the density of total Na+ current. The change in activation properties of the TTX-resistant Na+ current are similar to those produced by some hyperalgesic autacoids, and may contribute to the increase in primary afferent excitability and hyperalgesia that occurs after this lesion.

Glucocorticoids: their role on gonadal function and LH secretion.

The aim of the study was to investigate gonadal function and LH reserve in patients on chronic therapy with supraphysiological doses of GC. We clinically evaluated 17 male subjects (aged 23-56 years-old) on chronic GC therapy. In four subjects (aged 23-39 years-old) randomly selected, three basal blood samples were drawn and pooled for measurement of SHBG, total, free and bioavailable testosterone. Following baseline samples, a GnRH stimulation test was performed. Starting with a priming of 5 micrograms, a bolus of 50 micrograms of GnRH was injected intravenously and samples obtained every 30 minutes for assessment of LH. Four healthy men (aged 24-28 years-old) were used as controls. Patients on steroids referred decreased libido (58%) and impotence (52%) and lower back pain (41%). Total, free and bioavailable serum testosterone were significantly lower than controls (p < 0.01, p < 0.05 and p < 0.05, respectively) while SHBG levels persisted unchanged. Baseline LH and its rise after GnRH was normal. This study shows that chronic GC administration involves gonadal function reducing sexual steroids without changes in baseline and stimulated LH secretion. In addition, the priming with physiological doses of GnRH optimizes the pituitary response to higher GnRH doses.

Suicide as social logic.

Although suicide is not viewed as a mental disorder per se, it is viewed by many if not most clinicians, researchers, and lay people as a real or natural symptom of depression. It is at least most typically seen as the unfortunate, severe, yet logical end result of a chain of negative self-appraisals, negative events, and hopelessness. Extending an approach articulated by the early French sociologist Gabriel Tarde, in this paper I argue that suicide is merely an idea, albeit a very bad one, having more in common with societal beliefs and norms regarding such things as divorce, abortion, sex, politics, consumer behavior, and fashion. I make a sharp contrast between perturbation and lethality, concepts central to Edwin S. Shneidman's theory of suicide. Evidence supportive of suicide as an idea is discussed based on what we are learning from the study of history and culture, and about contagion/cluster phenomena, media/communication, and choice of method. It is suggested that certain individuals are more vulnerable to incorporate the idea and act of suicide into their concepts of self, based on the same principles by which ideas are spread throughout society. Just as suicide impacts on society, so does society impact on suicide.

Survivors of suicide do grieve differently: empirical support for a common sense proposition.

Previous empirical investigations have produced mixed results on the question of whether mode of death differentially affects grief. To further investigate the influence of suicide on grief, 350 previously bereaved university students completed a questionnaire package consisting of several standardized measures. Participants were separated into four groups based on the mode of death experienced as either survivors of suicide (n = 34), accident (n = 57), unanticipated natural (n = 102), or anticipated natural (n = 157) deaths. Hierarchical multiple regression analyses indicated that suicide survivors, compared against the other groups, experienced more frequent feelings of rejection, responsibility, "unique" reactions, and more total grief reactions. Trends indicating increased levels of shame and perceived stigmatization were also evident. Aggregate factors of death "naturalness" and "expectedness" showed less influence than mode of death in influencing grief. Overall, results support previous clinical and research findings and intuitive logic in demonstrating that the grief experienced by suicide survivors includes elements that are less frequently seen in the case of nonsuicidal deaths.

Problem solving, stress, and coping in adolescent suicide attempts.

Twenty adolescents who had made suicide attempts were compared with 20 nonpsychiatric control subjects on measures of problem solving, stress, and coping. The suicidal group did not show evidence of "rigid" thinking or of deficits in the ability to generate solutions to standardized interpersonal problems. However, they did report recent histories of more severe life stress and had inaccurate appraisal of the extent to which stressful events could be controlled. Although suicidal patients were able to generate as many adaptive strategies as control subjects for coping with their own most severe recent real-life stressor, they actually used fewer. They were also more likely to identify maladaptive behaviors as ways of coping. These findings support a transactional model of adolescent suicidal behavior, whereby inaccuracies in the appraisal aspects of problem solving (but not in the solution-generation aspects) in the face of high life stress lead to a reduction in the use of adaptive efforts to cope.