[From reconstruction to function : Hands-on training in tympanoplasty using real-time feedback]. / Von der Rekonstruktion zur Funktion : Tympanoplastik-Training mit Real-Time-Feedback.

BACKGROUND: Surgery of the middle ear requires a very high level of fine motor skills. Due to the increased potential for complications in middle ear operations, it is appropriate to acquire these skills beforehand by operating on a model. OBJECTIVE: How satisfactory is the training on suitable models? Are the skills acquired from working on a model transferable to intraoperative situations? Will the type of model and its use for training influence ear surgery in the future? MATERIAL AND METHODS: Available publications and own experiences with the Dresden tympanoplasty model (DTM) are analyzed and discussed. RESULTS: Although middle ear surgery makes very high demands on the surgeon and there is a significant risk for severe complications to the ear as a sense organ, there are currently very few options to train surgeons in advance. The DTM is a validated training model, which is capable of closing this gap. Due to the possibility of using a real-time feedback variation of the model, the understanding for reconstruction quality and intraoperative acoustic stress can be improved. The translation of the real-time feedback idea into actual middle ear surgery can improve reconstruction quality in the future. CONCLUSION: Training on suitable models is indispensable, especially when training as a surgeon to carry out middle ear operations. Adding another sense perception to the internal and external quality assessment of tympanoplasty by inclusion of the real-time feedback option, can optimize learning and operating processes.

[Spectroscopic investigation of the middle ear mucosa]. / Spektroskopische Untersuchung der Mittelohrschleimhaut.

BACKGROUND: The middle ear mucosa (MEM) plays a central role in the middle ear due to its function of providing regular ventilation. To date, assessment of the state of the MEM is only possible subjectively by the surgeon. An objective characterization of the state of the MEM is desirable. OBJECTIVE: The aim of this study was to enable objective characterization of the MEM and test infrared (IR) spectroscopy as a possible diagnostic tool for clinical use. MATERIALS AND METHODS: During middle ear surgery, 48 MEM samples were collected and divided into four groups according to clinical appearance: group I: normal MEM; group II: sclerotic MEM; group III: inflammatory thickened MEM; group IV: granulated MEM. After collection, samples were analyzed by IR spectroscopy to identify characteristic IR spectra. RESULTS: In the supervised analysis of the selected images, the biochemical differences representing the decisive factors for classification into groups I to IV were characterized. The differences in amide bands, carbohydrates, lipids, and proteins permit reliable separation of the clinical categories. CONCLUSION: Spectroscopic investigations enable objective characterization of the MEM. Conclusions regarding biochemical differences make it possible to weigh up treatment options. Routine use of IR spectroscopy in the operating theater requires histopathological comparison and an extended dataset with reference values of the individual groups.

Robotic stereotactic ablative radiotherapy for renal cell carcinoma in patients with impaired renal function.

BACKGROUND: Robotic stereotactic ablative radiotherapy (SABR) is currently under investigation as a noninvasive treatment option for patients with renal cell carcinoma (RCC). For radiation therapy of RCC, tumor motion and the need for high ablative doses while preserving the remaining renal parenchyma is a challenge. We aimed to analyze the safety and efficacy of robotic radiosurgery in RCC in a specific difficult subgroup of patients with impaired renal function. METHODS: We retrospectively identified all patients with RCC, treated with robotic SABR and motion compensation in our institution between 2012 and 2017. Either single fraction SABR of 24 or 25 Gy or 3 fractions of 12 Gy prescribed to the 70% isodose line was applied. Local control, overall survival, radiation side effects were evaluated together with renal function and tumor motion. RESULTS: We analyzed data of 13 lesions treated in 10 patients with clear cell RCC and a mean age of 70.5 ± 13.6 years (range: 48-87). Prior to SABR, 8 patients underwent previous complete and/or partial nephrectomy, 7 patients presented with chronic kidney disease ≥ stage 3. The median of minimum, mean and maximum planning target volume doses were 23.2, 29.5 and 35.0 Gy for single fraction and 24.4, 42.5 and 51.4 Gy for the three fractions regime. Persistent local control by robotic SABR was achieved in 9 out of 10 patients (92.3% of all lesions) within a median follow-up period of 27 month (range: 15-54). One patient underwent nephrectomy due to progressive disease and sufficient renal function of the contralateral kidney. Renal function remained stable with a mean estimated glomerular filtration rate (eGFR) of 51.3 ± 19.7 ml/min at baseline and 51.6 ± 25.8 ml/min at follow-up. The largest respiratory-induced tumor motion was seen in superior-inferior direction, compensated by the CyberKnife with mean targeting errors of maximal 2.2 mm. CONCLUSIONS: Robotic SABR is technically feasible for the treatment of RCC in preexisting kidney disease with good local tumor control at about 2 years follow-up. Robotic SABR with motion tracking offers a valid treatment option for patients, who are at increased risk for progression to end-stage renal disease due to partial nephrectomy or ablative techniques.

Learning while multitasking: short and long-term benefits of brain stimulation.

We employed a simulated production task that mimics the real-world skill acquisition required of operators working in control rooms of power plants to assess short and long-term effects of transcranial random noise stimulation (tRNS). tRNS has shown potential for enhancing learning and performance of cognitive skills. Forty subjects (24 female) learned how to execute the simulated production task during the training phase and were required to perform a secondary task during the skill acquisition phase while they received active (12 min) or sham tRNS on DLPFC. After 2 weeks they had to recall the task again without any stimulation. The results demonstrate that tRNS promoted better multitasking as reflected by better performance in a secondary task during and immediately after tRNS. However, 2 weeks later, beneficial effect of tRNS on retention was moderated by general mental ability. Particularly, tRNS benefited those with lower general mental ability. Practitioner summary: By using a simulated production task, we assessed the effects of tRNS on learning and skill retention. The study indicates that neurostimulation can enhance the learning of multiple complex tasks. Moreover, it shows that retention of those tasks can be supported by neurostimulation, especially for those with lower general mental ability.

[Vocational rehabilitation after total laryngectomy]. / Berufliche Rehabilitation nach Laryngektomie.

BACKGROUND: Aim of this study was to find out how many patients after a total laryngectomy (TLE) return to work successfully and what factors support vocational rehabilitation. PATIENTS AND METHODS: Laryngectomees (n=231) aged up to 60 years completed questionnaires and structured interviews before TLE (t1), before rehabilitation (t2), at the end of rehabilitation (t3), 1 year after TLE (t4), 2 years after TLE (t5), and 3 years after TLE (t6). RESULTS: Prior to TLE, 38% of all respondents were employed, 34% were unemployed, 23% received disability-related and 3% age-related pension retirement. One year after TLE, 13% were employed, 15% 2 years and 14% 3 years after TLE. Unemployed were 10% (t4), 5% (t5), and 7% (t6) of the patients. For 59% of all respondents it was very important to have a job. Predictors of successful vocational rehabilitation were employment prior to TLE, age <50 years, being self-employed or clerical employee, good physical functioning, good speech intelligibility, high motivation to go back to work, and support from colleagues. CONCLUSION: Only few laryngectomees return to work. However, even before TLE only a third of the patients was employed, another third was unemployed. Most of the patients receive pension retirement after TLE. As return to work is important for many patients, patient consultations should consider possibilities to support vocational rehabilitation before offering to apply for retirement.

IDAC-ALPHA: AN ALPHA DOSIMETRY SOFTWARE FOR NORMAL ORGANS AND TISSUES.

Radiopharmaceuticals have been used for the treatment of various forms of cancer since the 1940s. In recent years, the advantages of alpha emitting radionuclides have emerged as a favourable treatment option. However, most alpha emitting radionuclides have long decay chains with long-lived daughter radionuclides. This leads to uncertainties in the dosimetry for normal organs and tissues, when established dosimetry models are employed. The aim of this project is to assign each progeny its own biokinetic behaviour. The novel dosimetry model was applied to 223Ra-dichloride, frequently used for the treatment of patients with metastatic bone disease from castration-resistant prostate cancer. In this dosimetry model, individual biokinetics for each daughter radionuclide was included. This resulted in a decrease in absorbed dose to bone surfaces and red marrow and increased absorbed dose to liver and kidney, when compared with dosimetry models assuming that the daughter nuclides follow the biokinetics of the parent radionuclide.

Defense of phalangid: liquid repellent administered by leg dabbing.

The phalangid Vonones sayi has a pair of exocrine defensive glands that secrete quinones (2,3-dimethyl-1,4-benzoquinone and 2,3,5-trimethyl-1,4- benzoquinone). When distributed, the animal emits the secretion, dilutes it with aqueous regurgitated fluid, and effects dosaged delivery of the mixture by brushing it on the assailant with the tips of its forelegs. Predators such as ants are effectively repelled.

Polyzonimine: A novel terpenoid insect repellent produced by a milliped.

A nitrogen-containing terpene 6,6-dimethyl-2-azaspiro[4.4]non-1-ene (polyzonimine) was isolated from the defensive secretion of the milliped Polyzonium rosalbum. Polyzonimine, which is repellent to such natural enemies of the milliped as ants, acts as a topical irritant to insects (10-4 M induces scratching in cockroaches). Its structure was confirmed by a five-step synthesis starting from 2,2-dimethyl-7-oxabicyclo[4.1.0]heptane.

[Hiatus hernia : Standards and controversies in diagnostics and treatment]. / Hiatushernie : Standards und Kontroversen in Diagnostik und Therapie.

A hiatus hernia is defined as a transdiaphragmatic protrusion/migration of the intrabdominal contents through the esophageal hiatus of the diaphragm. The classification of hiatus hernias is based on anatomical morphological differentiation (types I-IV). The leading symptoms and psychological stress vary with respect to the symptoms, e. g. reflux and compression symptoms. Gastroscopy and multichannel intraluminal impedance pH measurement are obligatory preoperative functional diagnostics. A distinction is made between frequent type I hernia (antireflux surgery), symptomatic paraesophageal, thoracic and mixed hernia types (II-IV). Surgical indications exist in symptomatic type II-IV hernias. Hiatal mesh augmentation reduces recurrences. The complication potential of synthetic meshes must be taken into account. Biological implants show no advantages.

[Medial Unicompartmental Knee Arthroplasty Using Patient-Specific Instrumentation - Accuracy of Preoperative Planning, Time Saving and Cost Efficiency]. / Unilaterale mediale Schlittenprothesen mit patientenspezifischer Instrumentierung - Planungsgenauigkeit, Zeitersparnis und Kosteneffektivität.

BACKGROUND: In the past few years, patient-specific instrumentation (PSI) in knee endoprosthetics has been energetically marketed. PSI can enhance the accuracy of the size and alignment of the prosthesis components. It should also be possible to reduce hospital costs and operating time. It remains unclear whether these putative advantages are achieved in medial unicompartmental knee arthroplasty (UKA). PATIENTS/MATERIAL AND METHODS: Data from 22 patients (24 knees) were analysed retrospectively. The focus was on the reliability of preoperative surgical planning - particularly with regards to the level of experience of the five surgeons involved, who were split into two groups depending on their level of experience, as defined by EndoCert®. Another focus was on the evaluation of actual surgical time and cost effectiveness using PSI. RESULTS: In order to achieve an optimal outcome, preoperative surgical planning had to be modified intraoperatively to a great extent. The femoral component had to be adjusted intraoperatively in 41.7 % of all cases, the tibial component in 58.3 % and the polyethylene insert in 87.5 %. Surgeons equipped with less experience had to change preoperative planning more often than the more experienced surgeons. Utilising PSI increased the operating time of both the less experienced and the more experienced surgeons. PSI planning and lack of surgical experience were the main predictors of increased surgical time. Instead of lowering costs, utilizing PSI increased surgical costs by nearly 1300 $ per case. This was due to increased operating time, license fees and extraordinary expenditure for MRI scans. CONCLUSION: The advertised advantages of PSI were not supported by the data analysed. On the contrary, this technology leads to additional costs, greater operating time and insufficient accuracy in preoperative planning. As not a single study has yet demonstrated better outcomes in terms of alignment and/or function with PSI than with standard instrumentation, additional data are required before PSI can be recommended for routine use in medial UKA.

The pharmacokinetics of zinc from zinc gluconate: a comparison with zinc oxide in healthy men.

OBJECTIVE: Zinc supplementation is beneficial in some clinical conditions such as age-related macula degeneration (AMD). It has been suggested that zinc absorption is influenced by the form in which zinc is ingested. Therefore, the pharmacokinetics of zinc gluconate (organic) were compared with those of zinc oxide (inorganic). METHODS: 12 healthy male subjects aged between 21 and 31 years (24 years median) orally received daily doses of 20 mg metal zinc as zinc gluconate and 17.4 mg metal zinc as zinc oxide under randomized crossover conditions for 14 days each with at least 14 days as a washout. Zinc plasma concentrations were measured by means of inductively coupled plasma-atomic emission spectroscopy. RESULTS: C(max) was found 18.3% (10.3 - 26.3%) higher following multiple-dose administration of zinc gluconate as compared to zinc oxide (mean; 0.95% confidence interval of the relative differences between both treatment conditions; p < 0.05). AUC(0-24h) was noted 8.1% (1.9 - 14.3%) higher after zinc was given as zinc gluconate when compared to zinc oxide (p < 0.05) whereas t(max) did not differ between both treatment conditions. CONCLUSIONS: Zinc absorption in humans could be improved by zinc complexation with gluconate.

[Thoracic real-time MRI: experience from 2200 examinations in acute and ill-defined thoracic diseases]. / Thorakale Echtzeit-MRT: Erfahrungen aus 2200 Untersuchungen bei akuten und unklaren thorakalen Erkrankungen.

PURPOSE: To retrospectively assess the indication for thoracic real-time MRI, demonstrate typical findings, analyze the diagnostic potential in subgroups with suspected pulmonary embolism (PE) and aortic dissection (AD), and describe the influence of real-time MRI on the role of MRI in acute thoracic diseases. MATERIALS AND METHODS: From July 2001 to February 2005, real-time MRI was applied in 2,256 examinations in 1,714 patients. MRI was the primary diagnostic modality for these thoracic diseases as computed tomography has been available only since 2003. Characteristics of the TrueFISP sequence applied were: TR/TE/flip angle 3.1 ms/1.6 ms/59 degrees , respectively. FOV 340 - 360 mm, matrix size 156 to 192 x 256 pixels, slice thickness 3 to 4 mm, slices overlapped by 50 %. Acquisition time was 0.4 to 0.5 s per image. Three hundred and twenty transverse, coronal and sagittal images were acquired in three minutes. No breath holding, and only minimal patient cooperation, was required. Turbo-spin-echo sequences as well as ECG-gated and contrast-enhanced sequences were added depending on the indication. RESULTS: Most common indications were: acute thoracic nonspecified disease (n = 276, 12.24 %), PE (n = 573, 25.4 %), bleeding (n = 154, 6.8 %), AD (n = 222, 9.8 %), topographic information in complex findings (n = 654, 29.0 %). Real-time MRI was the sole MRI technique applied in 180 examinations (8.0 %), ECG-gated real-time MRI was applied in 87 examinations and breath hold was used in 107 examinations. PE was diagnosed in 181 examinations; reference techniques (MRI, computed tomography, single photon emission computed tomography) confirmed 170 of these and detected 19 more cases (sensitivity 90.0 %, specificity 97.1 %). Real-time MRI detected 141 suspected AD and 53 more nonsuspected AD. Of these, 191 were confirmed by other MRI techniques, surgery or clinical course (98.5 %). Real-time MRI coincidentally detected 56 pulmonary tumors, all were confirmed with computed tomography. Thus, especially vascular diseases could be easily assessed with real-time MRI, while computed tomography had advantages in the evaluation of the lung parenchyma. CONCLUSION: Real-time MRI both enables emergency MRI examinations for thoracic diseases in clinical patients in unstable condition and allows an explorative style of working in patients with nondefined acute thoracic diseases.

Insulin-like growth factor-II delays myocardial infarction in experimental coronary artery occlusion.

OBJECTIVE: We have previously shown that short pulses of myocardial ischemia cause increased mRNA expression of the insulin-like growth factor II (IGF-II) gene. The expression of IGF-II precedes the expression of its binding protein 5 (IGFBP-5). The cardioprotective actions of the IGF-II peptide and of its binding protein 5 as well as the underlying mechanisms were investigated in this study. METHODS AND RESULTS: Human recombinant IGF-II (0.25 microgram/ml) was applied by means of direct intramyocardial infusion (IM) for 60 min prior to a 60 min LAD occlusion and 120 min reperfusion. Myocardial infarction, compared to the region at risk, was significantly decreased by IGF-II treatment, whereas infusion of Krebs-Henseleit buffer did not show any protective effect (IGF-II, 78.75 +/- 1.51%; control, 100%; P < 0.005). A comparable degree of cardioprotection was observed after infusion of an equipotent concentration of recombinant human insulin (0.02 IU/ml; 88.25 +/- 1.45%; P < 0.05). Lavendustin A (100 microM), an inhibitor of protein tyrosine kinases, prevented the observed cardioprotection. The protective effect of IGF-II was lost when IGFBP-5 was simultaneously infused. CONCLUSION: IGF-II, a peptide that binds to the insulin receptor and whose mRNA is rapidly transcribed by cardiac myocytes following ischemic stress, is cardioprotective and mimics ischemic preconditioning. Its observed actions are probably based on its metabolic effects and are mediated by the insulin or the IGF-I receptor. IGFBP-5, whose expression follows IGF-II's expression with a short delay, inhibits the cardioprotection afforded by IGF-II and may thus account for the limited temporal duration of ischemic preconditioning.

Coordinate expression of the insulin-like growth factor system after microembolisation in porcine heart.

OBJECTIVES: Coronary microembolisation in the pig heart induces angiogenesis in a model of sterile inflammation due to focal necrosis. We have recently shown in this model that insulin-like growth factor I (IGF-I) is involved in inflammation-linked angiogenic processes due to its enhanced transcription after 72 h of ischaemia by infiltrating monocytes in areas of microsphere-induced focal necrosis where capillary sprouting could be detected. To obtain further insights into this process we studied by means of Northern blot analysis and in situ hybridisation the gene expression of other members of the IGF family, i.e. the six IGF binding proteins (IGFBPs), the insulin receptor, and the type I IGF receptor. METHODS: Myocardial injury was induced by injection of 25 microns non-radioactive microspheres into the left circumflex artery (LCx) in pigs that were killed after 3-24, 72, or 168 h of microembolisation. Tissue was collected from a non-ischaemic control area and the LCx region of the same heart for further analysis. RESULTS: We found decreased IGFBP-5 (2.7-fold; P < 0.02) mRNA concentrations after 72 h of microembolisation in ischaemic tissue versus control tissue from the same heart, preceded by a 1.9-fold elevated level of IGFBP-3 mRNA at 3-24 h (P < 0.05). IGFBP-6 was increased in ischaemic tissue at all time points studied. In situ hybridisation identified myocytes as the main producers of IGFBP-3 and IGFBP-6 mRNA. The mRNA levels of IGFBP-2, IGFBP-4, the insulin receptor, and the type I IGF receptor were constitutively expressed but did not change after microembolisation. Neither in heart nor in other organs studied transcripts of IGFBP-1 could be detected. Furthermore, we demonstrated that mRNA of the other components of the IGF system was expressed in almost all porcine organs except liver. CONCLUSION: These results indicate a coordinate gene expression of the IGF system in microembolised porcine myocardium, compatible with a role of IGF-I, IGFBP-3, IGFBP-5, and IGFBP-6 in inflammation-linked angiogenesis and/or repair processes.

Insulin-like growth factor I is involved in inflammation linked angiogenic processes after microembolisation in porcine heart.

OBJECTIVE: Angiogenesis in the porcine heart can be induced by myocardial ischaemia following vascular occlusions. This process is characterised by increased numbers of monocytes/macrophages, known to be potent producers of various mitogens such as insulin-like growth factors (IGF) and interleukins (IL). The aim of the study was to examine gene expression of these factors by means of northern blot hybridisation, slot blot analysis, and in situ hybridisation in a porcine model of coronary angiogenesis. METHODS: Experimental ischaemia and subsequent focal necroses were induced by selective injection of 25 microns microspheres into the left circumflex artery. The hearts were excised after 3-168 h of microembolisation, and tissue was collected from a non-ischaemic control area and the circumflex region of the same heart for further analysis. RESULTS: IGF-I was constitutively transcribed in normal porcine myocardium mainly by myocytes. Following microembolisation, IGF-I mRNA expression was significantly increased in the experimental region (1.8-fold) after 72 h and to a lesser extent after 168 h. In the ischaemic region, characterised by capillary sprouting, numerous mononuclear cells contained IGF-I mRNA. In contrast, IGF-II mRNA levels, constitutively produced by porcine myocytes, were not altered by microembolisation. IL-1 alpha, IL-1 beta, and IL-4 mRNA expression was undetectable in our animal model, whereas IL-6 was constitutively transcribed in normal and ischaemic heart and remained insensitive to microembolisation and focal necrosis. CONCLUSION: After microembolisation, increased IGF-I mRNA expression occurred by infiltrating monocytes in areas of microsphere induced focal necrosis, where capillary sprouting can be detected, suggesting that IGF-I is involved in inflammation linked angiogenic processes.

Insulin-like growth factor II is an experimental stress inducible gene in a porcine model of brief coronary occlusions.

OBJECTIVE: Previous observations have shown that myocardium activates many adaptive processes after brief ischaemia. The aim of this study was to determine whether insulin-like growth factors (IGF) as well as their receptors and binding proteins (IGFBP), which control the activity of the IGF, may play an important role during these processes. METHODS: Ischaemia was induced in anaesthetised open chest pigs by two 10 min occlusions of the left anterior descending coronary artery, separated by 30 min of reperfusion, and followed by reperfusion up to 210 min. Tissue from the ischaemic area and from a non-ischaemic control region of the same heart was examined by means of northern blot, slot blot, and in situ hybridisation. RESULTS: IGF-I, IGF-II, the type I receptor, the insulin receptor, and IGFBP-2-6 are constitutively expressed in porcine myocardium. In situ hybridisation showed that IGF-I and IGF-II are mainly transcribed by myocytes. Ischaemia/reperfusion led to an early and significant increase in IGF-II mRNA compared to non-sham controls but not in comparison with sham operated animals, which already showed a (not significantly) enhanced IGF-II expression. In each case the IGF-II mRNA levels are equal in the control and the experimental region of the same heart. Whereas IGF-II expression was already increased by experimental stress, IGFBP-5 mRNA was enhanced only by ischaemia/reperfusion. The expression of IGF-I, the receptors, and IGFBP-2, 3, 4, and 6 remained unchanged during the experimental protocol. IGFBP-1 was neither expressed nor induced in our model. CONCLUSIONS: IGF-II acts like a stress-response gene activated by the experimental conditions (surgery, anaesthesia) and remains induced during following episodes of ischaemia/reperfusion. A possible interaction of IGFBP-5 with other components of the IGF system may contribute to the preconditioning response.

Interaction of rat peritoneal macrophages with homologous sialidase-treated thrombocytes in vitro: biochemical and morphological studies. Detection of N-(O-acetyl)glycoloylneuraminic acid.

Sialidase treatment of rat thrombocytes led to an increased binding of these cells to homologous peritoneal macrophages, but had no significant effect on the rate of phagocytosis during the experimental time. As revealed by electron microscopy, the partially desialylated thrombocytes adhere to macrophages predominantly via a small part of the membrane in a way that the discoidal cells adopt a vertical position with regard to the macrophage surface. One adherent macrophage was able to bind up to 55 sialidase-treated thrombocytes. Maximum binding was already reached after release of 13% of sialic acids. This interaction could be inhibited by free D-galactose and compounds with terminal D-galactose residues. Bound thrombocytes were released from the macrophages by treatment with lactose or EDTA. These experiments suggest that the interaction is mediated by a galactose-specific receptor on the macrophage surface and that galactose on thrombocytes is not recognized if it is masked by terminal sialic acid residues. The total sialic acid amount of the thrombocytes studied was about 70 micrograms sialic acid/10(10) cells being composed of 78% N-glycoloylneuraminic acid, 17% N-acetylneuraminic acid and 5% of the novel sialic acid N-(O-acetyl)glycoloylneuraminic acid, which was identified by mass spectrometry. Sixty-two percent of these sialic acids were susceptible to enzymic hydrolysis with Vibrio cholerae sialidase.

Noninvasive quantification of brain edema and the space-occupying effect in rat stroke models using magnetic resonance imaging.

BACKGROUND AND PURPOSE: Brain edema is a life-threatening consequence of stroke and leads to an extension of the affected tissue. The space-occupying effect due to brain edema can be quantified in rat stroke models with the use of MRI. The present study was performed to test 2 hypotheses: (1) Can quantification of the space-occupying effect due to brain edema serve as a noninvasive measure for brain water content? (2) Does morphometric assessment of brain swelling allow determination of true infarct size on MRI after correction for the space-occupying effect of edema? METHODS: Thirty rats were subjected to permanent suture middle cerebral artery occlusion. MRI was performed after 6 or 24 hours, and hemispheric swelling was assessed morphometrically. Interobserver and intraobserver agreements were determined for MRI measurements. In study I, the space-occupying effect due to brain edema was correlated with the absolute brain water content by the wet/dry method. In study II, lesion volumes corrected and uncorrected for edema were calculated on MRI and on TTC staining and compared. RESULTS: Interobserver and intraobserver agreements for MRI measurements were excellent (r>or=0.97). Brain water content and hemispheric swelling correlated well after 6 and 24 hours (r>or=0.95). Corrected lesion volumes correlated with r=0.78 between TTC staining and MRI. Without edema correction, lesion volumes were overestimated by 20.3% after 6 hours and by 29.6% after 24 hours of ischemia. CONCLUSIONS: Morphometric assessment of hemispheric swelling on MRI can determine the increase in absolute brain water content noninvasively and can also provide ischemic lesion volumes corrected for brain edema.

Tricyclic aryl-substituted anticoccidial azauracils.

Syntheses of tricyclic aryl-substituted 6-azauracils are described. These compounds showed anticoccidial activity when tested against Eimeria tenella and E. necatrix. Compound activity was correlated with the chemical shift of the azauracil ring proton. No correlation existed between activity and compound lipophilicity. One of the compounds, 2-(11-oxo-6,11-dihydrodibenzo[b,e]thiepin-3yl)-as-triazine-3,5(2H,4H)-dione (23), was tested extensively against E. tenella and E. brunetti both in vivo and in vitro. Compound 23 controlled mortality due to E. tenella at 62 ppm, and it afforded protection as measured by weight gain at 31 ppm. Compound 23 afforded little protection against E. brunetti. In vitro experiments with 23 showed that it exerted a coccidiostatic effect.

Synthesis and antihypertensive activity of a series of spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2,5'-oxazolidin-2'-one]s.

The 2R*,11bS* and 2S*,11bS* diastereoisomers of the spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2, 5'-oxazolidin-2'-one] system were prepared by stereoselective methods. Evaluation of these compounds for antihypertensive activity by oral administration to the spontaneously hypertensive rat showed the 2S*,11bS* series was the more potent. Within that series it was found that small alkyl substituents at positions 3 and 4' enhanced antihypertensive activity and that methoxyl substitution at positions 9 and 10 was optimal. (2S,3S,11bS)-Spiro-[2-ethyl-9,10-dimethoxy-1,3,4,6,7, 11b-hexahydro-2H-benzo[a]quinolizine-2,5'-oxazolidin-2'-one] [(-)-9e] was one of the most efficacious compounds of this series, while its antipode, (+)-9e, was inactive. Selected compounds in this series were shown to be alpha-adrenoceptor antagonists.