Treatment guidelines for rare, early-onset conditions associated with epileptic seizures: a literature review on Rett syndrome and tuberous sclerosis complex.

BACKGROUND: Rett syndrome (RTT) and tuberous sclerosis complex (TSC) are two rare disorders presenting with a range of different epileptic seizures. Seizure management requires careful therapy selection, thereby necessitating development of high-quality treatment guidelines. This targeted literature review (TLR) aimed to characterise country-specific and international treatment guidelines available for pharmacological management of seizures in RTT and TSC. METHODS: A TLR was performed between 25-Jan and 11-Mar 2021. Manual searches of online rare disease and guideline databases, and websites of national heath technology assessment bodies were conducted for the following countries: Australia, Canada, France, Germany, Israel, Italy, Japan, Spain, Switzerland, UK, and US as defined by pre-specified eligibility criteria. Search terms were developed for each condition and translated into local languages where appropriate. Eligible publications were defined as guidelines/guidance reporting pharmacological management of seizures in patients with RTT and TSC. Guideline development methodology, geographical focus, author information and treatment recommendations were extracted from guidelines. An author map was generated using R version 3.5.1 to visualise extent of collaboration between authors. RESULTS: 24 total guidelines were included, of which three and six contained only recommendations for RTT and TSC, respectively (some provided recommendations for ≥ 1 condition). Guideline development processes were poorly described (50% [12 guidelines] had unclear/absent literature review methodologies); reported methodologies were variable, including systematic literature reviews (SLRs)/TLRs and varying levels of expert consultation. Most (83% [20/24]) were country-specific, with guideline authors predominantly publishing in contained national groups; four guidelines were classified as 'International,' linking author groups in the US, UK, Italy and France. High levels of heterogeneity were observed in the availability of treatment recommendations across indications, with 13 and 67 recommendations found for RTT and TSC, respectively. For RTT, all treatment recommendations were positive and sodium valproate had the highest number of positive recommendations (Khwaja, Sahin (2011) Curr Opin Pediatr 23(6):633-9). All TSC treatments (21 medications) received either exclusively negative (National Organization for Rare Disorders (2019)) or positive (Chu-Shore et al. (2010) Epilepsia 51(7):1236-41) recommendations; vigabatrin received the highest number of positive recommendations (Kaur, Christodoulou (2019)). CONCLUSIONS: This review highlights the need for the development of international high-quality and comprehensive consensus-based guidance for the management of seizures with pharmacological therapy in RTT and TSC. TRIAL REGISTRATION: Not applicable.

Positive intergroup contact modulates fusiform gyrus activity to black and white faces.

In this study, we investigated the effect of intergroup contact on processing of own- and other-race faces using functional Magnetic Resonance Imaging (fMRI). Previous studies have shown a neural own-race effect with greater BOLD response to own race compared to other race faces. In our study, white participants completed a social-categorization task and an individuation task while viewing the faces of both black and white strangers after having answered questions about their previous experiences with black people. We found that positive contact modulated BOLD activity in the right fusiform gyrus (rFG) and left inferior occipital gyrus (lIOC), regions associated with face processing. Within these regions, higher positive contact was associated with higher activity when processing black, compared to white faces during the social categorisation task. We also found that in both regions a greater amount of individuating experience with black people was associated with greater activation for black vs. white faces in the individuation task. Quantity of contact, implicit racial bias and negatively valenced contact showed no effects. Our findings suggest that positive contact and individuating experience directly modulate processing of out-group faces in the visual cortex, and illustrate that contact quality rather than mere familiarity is an important factor in reducing the own race face effect.

[Successful preclinical thoracotomy in a 17-year-old man]. / Erfolgreiche präklinische Thorakotomie bei einem 17-jährigen Mann.

We report the case of a 17-year-old man who sustained multiple stab wounds after a knife attack. After arrival of the emergency medical team the patient suffered a cardiac arrest caused by cardiac tamponade. After emergency thoracotomy and open heart massage the patient developed ROSC and could be discharged 13 days later without neurological deficits. Prehospital thoracotomy is rarely performed in Austria but is the only realistic chance for survival in cases of hematopericardium and tamponade. Better training of emergency physicians in Austria concerning surgical resuscitation could increase survival rates especially after penetrating thoracic trauma.

Wide angle crystal spectrometer for angularly and spectrally resolved X-ray scattering experiments.

A novel wide angle spectrometer has been implemented with a highly oriented pyrolytic graphite crystal coupled to an image plate. This spectrometer has allowed us to look at the energy resolved spectrum of scattered x rays from a dense plasma over a wide range of angles (approximately 30 degrees ) in a single shot. Using this spectrometer we were able to observe the temporal evolution of the angular scatter cross section from a laser shocked foil. A spectrometer of this type may also be useful in investigations of x-ray line transfer from laser-plasmas experiments.

Characterisation of two serine protease inhibitors expressed in the pituitary gland.

Serine protease inhibitors (serpins) are a family of structurally related proteins that play key roles in the regulation of proteolytic homeostasis. We have isolated a novel intracellular serpin, termed raPIT5a, from the rat pituitary gland. Northern blot analysis indicated raPIT5a mRNA expression in a range of tissues, including the adrenal gland and the brain. In situ hybridisation histochemistry revealed raPIT5a mRNA expression in specific cell populations in the rat pituitary gland, adrenal gland, and pancreas. Based on sequence similarities to other intracellular serpins, we predicted raPIT5a may inhibit the pro-apoptotic serine protease granzyme B. We confirmed this experimentally by identification of a stable inhibitory complex between granzyme B and raPIT5a. To determine whether granzyme B or granzyme B-related enzymes were expressed in the rat pituitary gland, we performed PCR using primers predicted to amplify granzyme B and two other published granzyme sequences. We identified rat natural killer protease-1 (RNKP-1), the rat homologue of granzyme B, and a novel putative serine protease highly similar to granzyme-like protein III (GLP III), which we termed GLP IIIa. These data suggest raPIT5a may regulate apoptosis in the pituitary by inhibition of granzyme B or GLP IIIa, or members of the caspase enzyme family which have similar substrate specificity. We have also identified expression of a second serpin, called neuroserpin, in pituitary tissue and found that it alters the morphology of the AtT20 corticotrope cell line, presumably through changes in cell adhesion. These results identify new roles for serpins in pituitary cell function.

Comparison of 5-aminolaevulinic acid and porphyrin photosensitization for photodynamic therapy of malignant bronchial stenosis: a clinical pilot study.

BACKGROUND AND OBJECTIVES: Photosan, a mixture of porphyrin oligomers as sensitizer for photodynamic therapy (PDT), carry the risk of prolonged photosensitivity of the skin. New sensitizer such as 5-aminolaevulinic acid (ALA) with low rates of skin phototoxicity appear to be promising alternatives. The aim of this study was to evaluate the efficacy of ALA compared to Photosan for PDT in malignant tracheo-bronchial stenosis. Reduction of tumor stenosis, increase in quality of life, and phototoxicity were considered as primary objectives. Improvement in clinical symptoms due to reduction of tumor stenosis, for example hemotysis, dyspnea, and poststenotic pneumonia were considered as secondary objectives. PATIENTS AND METHODS: After diagnostic work-up, photosensitization was done in 16 patients with ALA (60 mg/kg BW, oral, 6-8 hours prior to PDT) and in 24 patients with Photosan (2 mg/kg BW, i.v., 48 hours before PDT). The light dose was calculated as 100 J/cm(2) tumor length. Light at 630 nm was applied using a pumped dye laser. In both groups, additional hyperbaric oxygenation was applied at a level of 2 absolute atmospheric pressure. RESULTS: Stenosis diameter and Karnofsky performance status showed a significant improvement in favor of the Photosan-group, P = 0.00073 and 0.00015, respectively. In both groups no sunburn occurred due to phototoxicity of the sensitizer. CONCLUSION: Despite the limitations of a non-randomized study, photosensitization with Photosan seems to be more effective in PDT of malignant tracheo-bronchial stenosis compared to ALA.

Boerhaave's syndrome: a continuing challenge in thoracic surgery.

BACKGROUND/AIMS: Boerhaave's syndrome accounts for 30-40% of esophageal disruption. The current literature regarding the management of these patients and problems in treatment remains controversial. METHODOLOGY: Between 1988 and 1998, 14 patients with Boerhaave's syndrome were treated in our unit. Five primary repairs and 9 esophagectomies were performed. A retrospective review of these patients' records was carried out. The patients were divided into two groups. Group I: minor esophageal leak, local mediastinitis and hyperdynamic septic shock. All 5 cases were treated by primary repair. Group II: moderate to severe esophageal leak, severe mediastinitis and hypodynamic septic shock. All 9 cases were treated by transthoracic esophagectomy. RESULTS: Group I: No postoperative mortality. The mean ICU stay was 4.6 days. The mean hospitalization time was 14 days. Group II: The postoperative mortality was 22.2%. The mean ICU stay was 28 days. The mean hospitalization time was 45 days. CONCLUSIONS: The choice of which operative approach should be made in patients with Boerhaave's syndrome requires critical assessment of the patient's overall status, the duration of leak and the extent of mediastinal and pleural contamination.

Acid-related diseases following retrosternal stomach interposition.

BACKGROUND/AIMS: Esophagectomy and reconstruction with retrosternal stomach interposition implies bilateral truncal vagotomy, which supposedly causes gastric functional impairment. METHODOLOGY: Esophagectomy and reconstruction with retrosternal stomach interposition was performed on 15 men (mean age: 58.4 years) and 3 women (mean age: 43.6 years). The stomach was pedicled on the right gastric and right gastroepiploic artery without performing pyloroplasty. The cervical side-to-end anastomosis was sutured manually. The functional results were assessed 2-4 years postoperatively, by determining 24-hour qualitative intragastric pH-measurement, fluoroscopical gastric emptying studies, fasting gastrin levels, and endoscopy with biopsy studies. RESULTS: Endoscopy and biopsy confirmed esophagitis in 12 patients, gastritis in 15 and a gastric ulcer in 1 case. Fluoroscopic examination documented a normal passage of contrast medium in 17, slight impairment in 1 case treated by balloon dilatation of the pylorus. Qualitative intragastric pH-measurement revealed a total pH < 3 in 22.5-98.05% of measuring events (mean: 74.31%) within 24 hours, in 18 cases. Only 4 patients had pH < 3 in less than 50%. Fasting gastrin levels (normal range: 25-110 mU/L) varied from 48.78 mU/L-168.20 (mean: 85.23 mU/L). Only 3 patients had levels > 110 mU/L (maximum: 168.20 mU/L). CONCLUSIONS: Acid-related diseases may also occur after truncal vagotomy and retrosternal stomach interposition. Routine follow-up endoscopy and biopsy studies should be done to prevent inflammatory complications and maintain the patient's quality of life.

Combined photodynamic therapy and hyperbaric oxygenation in carcinoma of the esophagus and the esophago-gastric junction.

OBJECTIVES: The photochemical reaction of photodynamic therapy (PDT) depends on the presence of molecular oxygen. Due to anoxic regions in tumor tissue and vascular shutdown during PDT the efficiency is limited. Therefore, the use of hyperbaric oxygen which increases the oxygen in tumor tissue, as well as the amount of singlet oxygen, may enhance the efficiency of PDT. PATIENTS AND METHODS: After diagnostic work-up, photosensitization was carried out with a hematoporphyrin-derivate 2 mg/kg BW 48 h prior to PDT. The light dose was calculated as 300 J/cm fiber tip. Thirty-one patients were treated by PDT alone and 44 patients received PDT under hyperbaric oxygen at a level of two absolute atmospheric pressure. RESULTS: Improvement regarding stenosis-diameter could be obtained in both treatment arms with no significant difference (P=0.82). The dysphagia-score and tumor-length also decreased in both groups and showed a significant difference in favour of the PDT/HBO-group (P=0. 0064 and P=0.0002, respectively). The median overall survival for the PDT-group was 7 months and for the PDT/HBO-group 12 months (P=0. 0098). CONCLUSION: According to this prospective non-randomized study, combined PDT/HBO represents a new approach in the treatment of esophageal and cardia cancer which appears to have enhanced the efficiency of PDT.

Computed tomography or ultrasonically guided pigtail catheter drainage in multiloculated pleural empyema: a recommended procedure?

OBJECTIVES: The role of image-guided pigtail catheter drainage in the treatment of pleural empyema is associated with different outcomes, dependent on the stage of the disease. No agreement concerning its use exists. METHODOLOGY: Fourteen patients at a fibropurulent stage of pleural empyema initially treated with computed tomography (CT) or ultrasonically guided pigtail catheter drainage were reviewed. All patients were admitted with clinical symptoms of sepsis. Chest X-ray, CT scan and/or ultrasonography and thoracentesis with biochemical examination revealed multiloculated pleural empyema. Despite the diagnosis of multiloculated empyema, CT or ultrasonically guided pigtail catheter drainage was performed. However, septic symptoms deteriorated and all cases proceeded to thoracotomy with decortication. RESULTS: Image-guided drainage failed in all patients. Septic symptoms disappeared within 24-48 h after decortication. The patients recovered without sequela, were discharged 6-15 days (mean: 9.2 days) postoperatively and were able to return to normal physical activity. CONCLUSIONS: Computed tomography or ultrasonically guided pigtail catheter drainage can not be recommended in the case of a fibropurulent stage of empyema thoracis.

Effect of photodynamic therapy in a multimodal approach for advanced carcinoma of the gastro-esophageal junction.

UNLABELLED: Background and Objective We wanted to determine the role of additional photodynamic therapy in a multimodal approach for the treatment of patients with advanced cancer of the gastro-esophageal junction. Study Design/Materials and Methods We reviewed 53 patients, after endoluminal palliation, with advanced cancer of the gastro-esophageal junction. Combined dilatation and retrograde tumor disobliteration with Nd-YAG laser before photodynamic therapy (PDT), brachyradiotherapy, or both, became necessary in 12 patients. Brachyradiotherapy was carried out in all patients. PDT before brachyradiotherapy was performed in 25 patients. The endoluminal treatment was completed by external beam irradiation in 30 patients (15 cases with PDT and 15 without PDT) with an at least fair performance status. RESULTS: Photodynamic therapy showed a significant difference regarding the mean opening of the tumor stenosis (mean, 6.4 mm; P = 0.0002), the mean decrease in tumor length (3.1 cm; P = 0.00001) and the increase in median survival (13. 8 months; P = 0.001). The combined multimodal approach by using PDT, brachyradiotherapy and external beam irradiation showed a median survival of 16.8 months. However, additional external beam irradiation showed no significant difference (P = 0.11). The rate of severe complications was 5.7%. The mortality rate was 1.9%. CONCLUSION: Photodynamic therapy has been shown to be an effective treatment for palliation of advanced cancer at the gastro-esophageal junction. The use of PDT combined with irradiation was associated with an acceptable survival rate, low rates of complications and reasonable quality of life.

Review of severe osteoradionecrosis treated by surgery alone or surgery with postoperative hyperbaric oxygenation.

We reviewed 41 patients with osteoradionecrosis of the mandible. Each patient was treated by radical resection followed by external beam irradiation. The diagnosis of infected osteoradionecrosis was confirmed clinically, radiologically, and histologically. After operation had failed, 20/41 were given hyperbaric oxygen (HBO) as in 'salvage' treatment. Daily sessions of HBO 2.5 ATA for 60 minutes (mean: 29 sessions) were given. The other 21 patients were treated by operation and antibiotics alone. HBO group (n = 20): The overall success rate for HBO after operation had failed was 13/20. Repeated debridement as first-line treatment followed by postoperative HBO was successful in 12/19. In seven of 19 patients, partial mandibulectomy and microvascular transplantation were required as second-line treatment, and this was successful in five. Primary partial mandibulectomy and microvascular transplantation followed by HBO was successful in 1 patient. Non-HBO group (n = 21): Repeated debridement was successful in 10/11 patients. Partial mandibulectomy was required as second-line treatment in the remaining one. In the other 10, partial mandibulectomy and microvascular transplantation were successful as first-line treatment in four. In the remaining six, further surgical intervention became necessary and were successful for 5-17 months (mean: 13). With a success rate of 13/20, we do not recommend HBO for the treatment of osteoradionecrosis.

Hyperbaric oxygen and photodynamic therapy in the treatment of advanced carcinoma of the cardia and the esophagus.

BACKGROUND AND OBJECTIVE: The photochemical reaction of photodynamic therapy (PDT) depends on the presence of molecular oxygen. Because of anoxic regions in tumor tissue and vascular shutdown during PDT, the efficiency is limited. Therefore, the use of hyperbaric oxygen, which increases the oxygen in tumor tissue, as well as the amount of singlet oxygen, may enhance the efficiency of PDT. STUDY DESIGN/MATERIALS AND METHODS: After diagnostic work-up, photosensitization was carried out with a hematoporphyrin-derivate 2 mg/kg body weight 48 hours before PDT. The light dose was calculated as 300 J/cm of fiber tip. Twenty-three patients were treated by PDT alone and 29 patients received PDT under hyperbaric oxygen at a level of two absolute atmospheric pressures. RESULTS: Improvement regarding dysphagia and stenosis-diameter could be obtained in both treatment arms with no significant difference (P = 0.43 and P = 0. 065, respectively). The tumor length also decreased in both groups and showed a significant difference in favour of the PDT/HBO group (P = 0.002). The mean overall survival was 11.3 months. The mean survival time for the PDT group was 8.7 months and for the PDT/HBO group 13.8 months (P = 0.021). CONCLUSION: According to this pilot study, combined PDT/HBO represents a new approach in the treatment of esophageal and cardia cancer, which appears to have enhanced the efficiency of PDT.

The effect of external beam irradiation after endoscopic palliation of esophageal carcinoma.

The aim of this study was to verify the value of additional external beam irradiation (EBR) after endoscopic palliation, regarding quality of life and survival rate. From January 1988 to December 1995, 99 patients with esophageal carcinoma (squamous cell carcinoma 61; adenocarcinoma 38) were reviewed, there were 84 males (mean age: 67 years) and 16 females (mean age: 65 years). Seventeen patients were in stage IIb, 45 stage III and 37 patients in stage IV. HDR-brachyradiotherapy (mean: 14.7 Gy) was carried out in all patients. Additional EBR (mean: 47.8 Gy) after endoluminal palliation was done in 51 cases. At 6-months follow-up swallowing of a semi-solid diet at least was possible in all patients and dysphagia was found with significant difference in favour to EBR only in stage IV (p=0.011). The Karnovsky performance status showed a difference in favour of EBR for stage III and IV (p=0.040 and p=0. 049, respectively). The median overall survival for EBR compared to no EBR was 10 and 7 months, with a 12 months survival rate of 60% and 16% (p=0.0012). However, considering different stages and EBR versus no EBR a significant difference in survival could only be found for stage IIb (p=0.031), a trend in favour of EBR could be found for stage III (p=0.0985) and stage IV (p=0.0543). Tumor regrowth 6-12 months after treatment occurred in 31 cases and was successfully treated with Nd-YAG laser in 25 and stenting in 6 cases. Postirradiation fibrotic stenosis occurred in 12 cases. Improved survival rates after additional EBR can only be expected in stage IIb. However, in case of advanced esophageal carcinoma and fair performance status, EBR after endoluminal palliation help to maintain quality of life.

Four-year experience with pleural abrasion using a rotating brush during video-assisted thoracoscopy.

BACKGROUND: Due to the high recurrence rate in primary spontaneous pneumothorax (PSP), surgical therapy is currently a well-accepted method of treating this condition. There is no general agreement about the best time for surgical intervention (i.e., after the first or second episode) or the optimal surgical approach,--i.e., tube thoracocenteses, thoracotomy, or video-assisted thoracoscopy (VATS) with or without pleurectomy or pleurodesis. The aim of this study was to verify the efficacy of VATS and mechanical brush pleurodesis using a rotating electrical brush system. METHODS: We treated 47 patients with PSP between June 1993 and June 1997. Follow-up ranged from 20 to 56 months. There were 38 male and nine female patients with a mean age of 26 years. Emergency thoracocenteses due to tension pneumothorax became necessary in three patients. All patients were treated by VATS and mechanical brush pleurodesis. Wedge resection was done if bullae or blebs were present (68.1%). RESULTS: Operating time was 20-60 min (mean, 35). There were no intraoperative complications and no conversions to conventional surgery. In the first few postoperative days, postoperative pain was controlled with nonsteroidal antirheumatic drugs and additional morphines. Drainage time was 3-7 days (mean, 4). Hospitalization time was 4-8 days (mean, 5). The recurrence rate was 2.1% (one patient). No postoperative bleeding or wound infection occurred in any of our patients. CONCLUSIONS: VATS combined with mechanical brush pleurodesis using the electrical brush system is a highly effective and safe treatment for patients with recurrent primary spontaneous pneumothorax.

Does hyperbaric oxygen enhance the effect of photodynamic therapy in patients with advanced esophageal carcinoma? A clinical pilot study.

BACKGROUND AND STUDY AIMS: Experimental studies have shown that the cytotoxicity of porphyrins and related substances is mediated mainly by singlet oxygen and that hypoxic cells are less affected by porphyrins and light. In a clinical pilot study we assessed the use of photodynamic therapy (PDT) under hyperbaric oxygen (HBO), compared with PDT under normobaric conditions, in patients with advanced esophageal carcinoma. PATIENTS AND METHODS: After diagnostic work-up and staging, photosensitization in all patients was carried out using hematoporphyrine derivate (HpD) (2 mg/kg bodyweight 48 hours prior to PDT). We then applied light at 630 nm (KTP-Nd: YAG laser with DYE box) at dose of 300 J/cm, delivered by a fiber with a radial light-diffusing cylinder (length 1 cm), inserted through the biopsy channel of the endoscope. Of the patients, 14 (12 with stage III cancers, and two with stage IV cancers) were treated by PDT alone, and 17 patients (15 with stage III cancers, and two with stage IV cancers) received PDT under HBO at a level of 2 absolute atmospheric pressures (ATA). Transcutaneous PO2 levels of 500-750 mm Hg under HBO, compared with transcutaneous PO2 levels of 60-75 mm Hg under normobaric conditions, were measured. RESULTS: Improvements regarding dysphagia and stenosis diameter were obtained in both treatment arms with no significant differences (P = 0.36 and 0.14, respectively). The tumor length also decreased in both groups and showed a significant difference in favour of the PDT/ HBO group (P = 0.002). Kaplan-Meier statistics showed median overall survival for the PDT group and the PDT/HBO group as 7.0 and 12 months respectively. The 12-month survival rate was 28.6% for the PDT group and 41.2% for the PDT/HBO group. Logrank test showed a difference in survival in favor of the PDT/HBO group (P = 0.059). No major treatment-related complication occurred, and the 30-day mortality rate was 0%. CONCLUSIONS: Combined PDT/HBO represents a new approach in the treatment of esophageal cancer which, in this pilot study, appears to have enhanced the efficiency of PDT.

Local and systemic treatment in small cell carcinoma of the esophagus.

Primary small cell carcinoma of the esophagus is a rare and aggressive disease. We report on our experience with two patients having a small cell cancer of the esophagus, being treated with photodynamic therapy combined with irradiation and induction-chemotherapy as well as a review of literature. Both patients were admitted with severe dysphagia, weight loss and a Karnovsky performance status of 90. Diagnostic work-up revealed tumor-stenosis in the proximal third in one and in the distal third in the other case. Clinical staging showed T4N2M0 and T3N2M0, pure small cell carcinoma. Due to dysphagia and lymph node enlargement, local and systemic therapy were considered as first-line treatment. Restaging after three cycles of induction-chemotherapy revealed partial response in both cases. Esophagectomy as a second-line treatment was considered. However, in the preoperative period, one patient developed motorical aphasia. The CT-scan of the brain showed multiple brain metastases. External beam irradiation and further chemotherapy was initiated. The patient died 12 months after admission. The other patient revealed anatomical inoperability at the staging laparoscopy. External beam irradiation and a second session of PDT was performed. The patient is still alive, 12 months after his first admission. The biological behavior of this aggressive disease and metastases in about 50% of patients at admission, as well as significant dysphagia makes combined systemic and local treatment necessary. Nevertheless, after reviewing the literature, esophagectomy and adjuvant chemotherapy may have an advantage pertaining to survival time when anatomical and functional operability is given.

A new intracellular serine protease inhibitor expressed in the rat pituitary gland complexes with granzyme B.

We have cloned a novel serpin (raPIT5a) from a rat pituitary cDNA library which is structurally related to members of the ovalbumin subfamily of serine protease inhibitors. This new cDNA encodes a 374-amino acid protein, designated raPIT5a. raPIT5a was expressed in specific cells in the intermediate and anterior lobes of the pituitary. Recombinant raPIT5a was not secreted suggesting raPIT5a functions to inhibit intracellular proteases. Recombinant raPIT5a formed an SDS-stable complex with human granzyme B, a serine protease which induces apoptosis by activating members of the caspase enzyme family. These data suggest raPIT5a may have a role in regulating granzyme B or related enzymes and apoptosis in the pituitary gland.

Design of a 2 T multipole wiggler insertion device for the SRS.

Two new identical insertion devices have been designed for the Daresbury SRS. They are 2 T permanent-magnet multipole wigglers that will provide high flux in the X-ray region. This paper describes the magnetic and mechanical design of the arrays of steel pole pieces and permanent-magnet blocks. Also given is the engineering design of the support structure that will cope with the very large forces present while maintaining high levels of precision in gap setting and parallelism. The engineering design has been fully assessed using finite-element techniques to predict the deflections of critical parts of the structure. These two devices are due to be installed into the SRS by the end of 1998.