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ObjectiveThe aim of this study was to evaluate the response of ear, nose, and throat (ENT) symptoms to different immunosuppressive therapies in patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV).MethodsIn this cohort study, patients with AAV treated between January 2010 and April 2020 at 2 Dutch hospitals were included. Clinical, histological, and laboratory data were collected retrospectively. ENT involvement was defined as follows: (1) ≥ 1 ENT symptom according to the Birmingham Vasculitis Activity Score (version 3; BVAS3), and/or (2) presence of saddle nose deformity. Associations between therapy and ENT activity were assessed using logistic regression analysis.ResultsA total of 320 patients with AAV were included, of whom 209 (65.3%) had ENT involvement at some point throughout the disease course. In these 209 patients, median age at disease onset was 52.0 years (IQR 40.0-62.0) and 45.5% were male. Median BVAS3 was 12.0 (IQR 6.0-18.0) at diagnosis. Despite immunosuppressive therapy, 50% (n = 77) of the patients had ENT symptoms at relapse and 29.1% (n = 59) had ENT activity at their last visit. No statistically significant difference in ENT activity at last visit was observed between patients treated with oral or intravenous cyclophosphamide (CYC, n = 137) compared to rituximab (RTX, n = 55; adjusted odds ratio 0.59, 95% CI 0.33-1.06; P= 0.08). Lower age at disease onset and female sex were independently associated with ENT activity at last follow-up.ConclusionIn this cohort, CYC and RTX therapy had similar therapeutic effects on ENT symptoms in AAV. Persistent ENT activity is a common feature despite immunosuppressive therapy.

Background: Most pre-dialysis patients are medically eligible for home dialysis, and home dialysis has several advantages over incentre dialysis. However, accurately selecting patients for home dialysis appears to be difficult, since uptake of home dialysis remains low. The aim of this study was to investigate which medical or psychosocial elements contribute most to the selection of patients eligible for home dialysis.Methods: All patients from a Dutch teaching hospital, who received treatment modality education and subsequently started dialysis treatment, were included. The pre-dialysis programme consisted of questionnaires for the patient, nephrologist and social worker, followed by an assessment of eligibility for home dialysis by a multidisciplinary team. Clinimetric assessment and logistic regression were used to identify domains and questions associated with home dialysis treatment.Results: A total of 135 patients were included, of whom 40 were treated with home dialysis and 95 with incentre haemodialysis. The key elements associated with long-term home dialysis treatment were part of the domains ‘suitability of the housing’, ‘self-care’, ‘social support’ and ‘patient capacity’, with adjusted odds ratios ranging from 0.13 for negative to 18.3 for positive associations.Conclusion: The assessment of contraindications by a nephrologist followed by the assessment of possibilities by a social worker or dialysis nurse who investigates four key elements, ideally during a home visit, and subsequent detailed education offered by specialized nurses is an optimal way to select patients for home dialysis.

Anatomically modern humans originated in Africa around 200 thousand years ago (ka)1–4. Although some of the oldest skeletal remains suggest an eastern African origin2, southern Africa is home to contemporary populations that represent the earliest branch of human genetic phylogeny5,6. Here we generate, to our knowledge, the largest resource for the poorly represented and deepest-rooting maternal L0 mitochondrial DNA branch (198 new mitogenomes for a total of 1,217 mitogenomes) from contemporary southern Africans and show the geographical isolation of L0d1’2, L0k and L0g KhoeSan descendants south of the Zambezi river in Africa. By establishing mitogenomic timelines, frequencies and dispersals, we show that the L0 lineage emerged within the residual Makgadikgadi–Okavango palaeo-wetland of southern Africa7, approximately 200 ka (95% confidence interval, 240–165 ka). Genetic divergence points to a sustained 70,000-year-long existence of the L0 lineage before an out-of-homeland northeast–southwest dispersal between 130 and 110 ka. Palaeo-climate proxy and model data suggest that increased humidity opened green corridors, first to the northeast then to the southwest. Subsequent drying of the homeland corresponds to a sustained effective population size (L0k), whereas wet–dry cycles and probable adaptation to marine foraging allowed the southwestern migrants to achieve population growth (L0d1’2), as supported by extensive south-coastal archaeological evidence8–10. Taken together, we propose a southern African origin of anatomically modern humans with sustained homeland occupation before the first migrations of people that appear to have been driven by regional climate changes.

Study design:In 2014, the adult spinal cord injury (SCI) common data element (CDE) recommendations were made available. This project was a review of the adult SCI CDE for relevance to children and youth with SCI.Objectives:The objective of this study was to review the National Institute of Neurologic Disorders and Stroke (NINDS) adult SCI CDEs for relevance to children and youth with SCI.Setting:International.Methods:The pediatric working group consisted of international members with varied fields of expertise related to pediatric SCI. The group convened biweekly meetings for 6 months in 2015. All of the adult SCI CDEs were reviewed, evaluated and modified/created for four age groups: 0–5 years, 6–12 years, 13–15 years and 16–18 years. Whenever possible, results of published research studies were used to guide recommendations. In the absence of empirical support, grey literature and international content expert consensus were garnered. Existing pediatric NINDS CDEs and new CDEs were developed in areas where adult recommendations were not appropriate. After internal working group review of domain recommendations, these pediatric CDEs were vetted during a public review from November through December 2015.Results:Version 1.0 of the pediatric SCI CDEs was posted in February 2016.Conclusion:The pediatric SCI CDEs are incorporated directly into the NINDS SCI CDE sets and can be found at https://commondataelements.ninds.nih.gov.

Study design:Cross-sectional survey.Objectives:To estimate the prevalence, predictors and impact of self-reported pain and spasticity and examine variables affecting quality of life in individuals with a traumatic spinal cord injury (SCI).Setting:Nationwide, Denmark.Methods:An anonymous questionnaire was sent out to individuals with a traumatic SCI. The questionnaire included questions about demographics and SCI characteristics, pain, spasticity and quality of life.Results:In total, 537 questionnaires were completed. Seventy-three percent reported chronic pain of which 60% used descriptors suggestive of neuropathic pain. The average pain intensity and interference were 5.6 (s.d. 2.3) and 5.0 (s.d. 2.8), respectively, on a 0–10 numeric rating scale (NRS), and 28.1% reported severe pain. Seventy-one percent reported spasticity. Average interference of spasticity was 2.9 (s.d. 2.7). Quality of life scores were 6.5 (s.d. 2.5) for life and life situation, 5.5 (s.d. 2.6) for physical health and 6.7 (s.d. 2.6) for mental health on the NRS (0–10). Female gender was associated with lower mental health scores and tetraplegia with lower physical health scores, and high pain interference and shorter time since injury were associated with lower quality-of-life scores for all three parameters. Pain with descriptors suggestive of neuropathic pain was associated with lower quality-of-life scores than pain without such descriptors.Conclusion:Chronic pain and spasticity are common problems after SCI, and in particular, high pain interference is associated with lower quality of life.

In a multicenter clinical and histological Dutch study, the authors report a 2.8% per patient year recurrence rate of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, which contributes independently to subsequent graft loss. Supplemental digital content is available in the text.

OBJECTIVE: To investigate the operating characteristics of the American College of Rheumatology (ACR) traditional format criteria for Wegener’s granulomatosis (WG), the Sørensen criteria for WG and microscopic polyangiitis (MPA), and the Chapel Hill nomenclature for WG and MPA. Further, to develop and validate improved criteria for distinguishing WG from MPA by an artificial neural network (ANN) and by traditional approaches [classification tree (CT), logistic regression (LR)]. METHODS: All criteria were applied to 240 patients with WG and 78 patients with MPA recruited by a multicenter study. To generate new classification criteria (ANN, CT, LR), 23 clinical measurements were assessed. Validation was performed by applying the same approaches to an independent monocenter cohort of 46 patients with WG and 21 patients with MPA. RESULTS: A total of 70.8% of the patients with WG and 7.7% of the patients with MPA from the multicenter cohort fulfilled the ACR criteria for WG (accuracy 76.1%). The accuracy of the Chapel Hill criteria for WG and MPA was only 35.0% and 55.3% (Sørensen criteria: 67.2% and 92.4%). In contrast, the ANN and CT achieved an accuracy of 94.3%, based on 4 measurements (involvement of nose, sinus, ear, and pulmonary nodules), all associated with WG. LR led to an accuracy of 92.8%. Inclusion of antineutrophil cytoplasmic antibodies did not improve the allocation. Validation of methods resulted in accuracy of 91.0% (ANN and CT) and 88.1% (LR). CONCLUSION: The ACR, Sørensen, and Chapel Hill criteria did not reliably separate WG from MPA. In contrast, an appropriately trained ANN and a CT differentiated between these disorders and performed better than LR.

Swakopmund is a popular coastal resort in Namibia, especially during the summer holiday season when daily sea temperatures can fluctuate several degrees in a short period. Hourly measurements of the near-bottom water temperature were collected off the Swakopmund Jetty to investigate the thermal variability in relation to local winds. The thermal regime of this coastal region appears to be controlled by the locally forced Ekman offshore transport. Related changes in offshore transport led those of the surf-zone temperature by about one day. A transfer of kinetic energy from the alongshore wind into the temperature field of the nearshore zone dominated relative short time scales (hourly). The longer periods (7-9 days) are associated with the forcing of poleward-directed continental shelf waves. The origin of the 24-25 day frequencies is not clearly understood. However, it characterises the nearshore wind field as well as the water temperature of the surf zone. These relatively long quasi-cycles could originate from rhythmic changes in the regional wind field as a result of changes in the thermal contrast between sea and land areas.

Antineutrophil cytoplasmic antibody (ANCA) tests are used to diagnose and monitor inflammatory activity in Wegener granulomatosis, microscopic polyangiitis and its renal-limited variant (pauci-immune crescentic glomerulonephritis), and Churg-Strauss syndrome. The International Consensus Statement on testing and reporting of ANCA states that ANCA are demonstrated most readily in these conditions by using a combination of indirect immunofluorescence (IIF) of normal peripheral blood neutrophils and enzyme-linked immunosorbent assays (ELISAs) that detect ANCA specific for proteinase 3 or myeloperoxidase. The group that produced the International Consensus Statement has developed guidelines for the corresponding quality control activities, examples of comments for various IIF patterns and ELISA results, and recommendations for ANCA testing when inflammatory bowel disease and other nonvasculitic ANCA-associated autoimmune diseases are suspected.

Systemic vasculitis refers to a condition of blood vessel inflammation, of which the causes are various. In a substantial number of cases, autoantibodies against neutrophil cytoplasm constituents (ANCAs) are present. The authors then refer to the systemic vasculitis as ANCA-associated systemic vasculitis. Renal disease is an unfavorable component, leading to dialysis dependency in a considerable number of patients. This review aims to summarize in brief what was reported about ANCA-associated vasculitis in the recent past. What the exact pathogenic role of ANCAs in the development of systemic vasculitis is remains uncertain, and it is still not clear how their presence leads to the histopathologic lesions called vasculitis.

Background. We reported previously that in renal disease in relation to antineutrophil cytoplasm auto‐antibodies (ANCA)‐associated vasculitis, renal outcome correlates better with the percentage of normal glomeruli than with separate active lesions. This may imply that glomeruli, once affected by necrotizing and crescentic lesions, are irreversibly damaged. We quantified and evaluated the course of renal lesions in the present study.Methods. We retrospectively analysed 31 patients with renal disease in relation to ANCA‐associated vasculitis, all treated with immunosuppressive drugs. In all patients, a renal biopsy was performed at diagnosis. A follow‐up biopsy was performed in all patients on the indication of a suspected renal relapse, after a mean interval of 31 months.Results. The mean percentage of normal glomeruli in the renal biopsy did not change over time (29% in the initial and 30% in the follow‐up biopsy). The mean percentage of glomeruli with crescents, however, significantly decreased from 57 to 30% (P<0.001). The percentage of glomerulosclerosis significantly increased from 12 to 39% (P<0.001). The data were independent of diagnosis, gender, age, time interval between the biopsies, and treatment.Conclusions. This is the first study to quantify glomerular changes between two time points in patients with renal vasculitis. Our results suggest that, on average, no new glomeruli are recruited into the active disease process. The sum of the percentage of crescentic and sclerotic glomeruli in the initial biopsies is larger than the percentage of sclerotic glomeruli in the follow‐up biopsies. Thus, therapy seems not only to prevent normal glomeruli from being recruited into the active disease process for a certain time, but seems also to allow part of the active lesions to revert into a normal phenotype, although another part of the active lesions will be transformed to a chronic phenotype.

We reported previously that in renal disease in relation to antineutrophil cytoplasm auto-antibodies (ANCA)-associated vasculitis, renal outcome correlates better with the percentage of normal glomeruli than with separate active lesions. This may imply that glomeruli, once affected by necrotizing and crescentic lesions, are irreversibly damaged. We quantified and evaluated the course of renal lesions in the present study.

BACKGROUND: Stress is thought to be abortogenic and psycho-neuro-immunological pathways have been suggested to be involved in triggering miscarriages. From experiments in pregnant mice exposed to stress some insights into the underlying mechanisms have been gained, delineating immunological imbalances as a cause of pregnancy failure. In order to test the validity of the conclusions drawn from murine experiments and the role of stress in human pregnancy loss, the following study was performed. METHODS: We used an established perceived stress questionnaire and measured the stress score of women with a confirmed diagnosis of first trimester spontaneous abortion (n = 94). Decidual tissue was investigated by immunohistochemistry and in-situ hybridization to detect the presence and distribution of immunocompetent decidual cells [CD56+ natural killer (NK) cells, CD8+and CD3+ T cells, tryptase+ mast cells (MCT+) and tumour necrosis factor (TNF)-α+ cells]. The patient cohort was divided into women experiencing low or high levels of stress. RESULTS: In the decidua of women with high stress scores we observed significantly higher numbers of MCT+, CD8+ T cells and TNF-α+ cells per mm2 tissue (P ≤ 0.05). No significant differences between individuals with lower or higher stress scores could be observed with respect to decidual CD56+ NK and CD3+ T cells. CONCLUSIONS: Using a questionnaire to score perceived stress in humans may be a valid approach to assess non-biased stress scores. Stress-triggered abortion in humans, identified by a questionnaire, can be linked to immunological imbalances.

Stress is thought to be abortogenic and psycho-neuro-immunological pathways have been suggested to be involved in triggering miscarriages. From experiments in pregnant mice exposed to stress some insights into the underlying mechanisms have been gained, delineating immunological imbalances as a cause of pregnancy failure. In order to test the validity of the conclusions drawn from murine experiments and the role of stress in human pregnancy loss, the following study was performed.

PROBLEM: Pregnancy can be considered as a model of successfully controlled tissue invasion. Cellular mediated immunity appears to regulate the controlled invasion of fetal trophoblast cells. In endometrium cancer, a dysregulation of invasive malignant cells can be observed. Since immuncompetent cells are known to be involved in recognition and rejection of ‘non‐self’ antigens, we investigated the presence and distribution pattern of CD3, CD8, CD56, and CD68 positive cells in decidua from normal and failing pregancies, compared with malignant and benign endometrium.
 METHOD OF STUDY: Decidual tissue from first trimester normal pregancies (NP; n=15) and abortion (AB; n=12), endometrial samples from premenopausal women (NE; n=8), and endometrioid adenocarcinoma (EA; n=8) were examined by immunohistochemistry using monoclonal antibody against large spectrum cytokeratin, and against the receptors CD3, CD8, CD56 and CD68, respectively.
 RESULTS: In NP, we observed 32.5% CD3, 44.7% CD56, and 22.9% CD68+cells. In AB, we found 36.9% CD3, 45.3% CD56, and 17.8% CD68+cells. The differences in ratio between normal pregnancy and abortion were not statistically significant. In NE, we counted 39.5% CD3, 30.2% CD56 and 30.2% CD68+cells. In EA, we observed 47.9% CD3, 12.4% CD56 and 39.7% CD68+cells. The decrease of CD56 positive cells in endometrioid adenocarcinoma was statistically significant. Interestingly, we found 4.1% of cells positive for CD8 in NP, 4.9% in AB, 22.7% in NE, and 48.2% in EA.
 CONCLUSIONS: The increase of CD8 cells in NE, and particularely in EA, and decrease of CD56 cells, compared with NP or AB, suggests an interaction between CD8 cells and CD56 cells. Studying different pathological situations in the uterus, such as malignancies or ectopic pregnancies, might help us to understand the mechanisms involved in the maintenance of pregnancy.

Decade-scale regimes of sardine Sardinops sagaxand anchovy Engraulisspp. have been observed in the productive coastal waters of the North-Western, North-Eastern and South-Eastern Pacific and the South-Eastern Atlantic. In each of these systems, the two genera fluctuate out of phase with each other. The subdominant genus may initiate a recovery while the other species is still abundant, so population growth is not necessarily a response to a vacant niche. Rather, it appears to be triggered by formation of one or a few powerful year-classes. At high population levels, quality of sardine and their eggs decreased in Japan, leading to decreased production and survival of eggs, poor year-classes and stock collapse. Excessive fishing of strong year-classes early in the recovery stage may prevent a species from assuming dominance, so influencing the natural succession of species. This may greatly alter the structure and functioning of an ecosystem. For example, a mesopelagic forage fish may replace an epipelagic one, with severe repercussions for predators that can only feed in the upper ocean, e.g. some seabirds. Biological factors also may influence the succession of forage fish. For example, off California, peaks in abundance of predatory species such as bonita Sarda, and chub mackerel Scomber, separate those of the planktivorous sardine and anchovy. In the Pacific Ocean, sardine distribution has change greatly. Compared with its range when scarce, a population at a high level of biomass can extend 1 000–1 800 miles farther along the coast and 400–2 200 miles farther out to sea. In different periods of high biomass, sardine did not always have the same distribution. In the 1930s and 1940s, near simultaneous fluctuations of sardine in the North-Western and North-Eastern Pacific were in phase. In the 1980s and 1990s, sardine in the North-Western and South-Eastern Pacific were fluctuating in phase. However, along the west coast of North America, sardine started their most recent increase later than in other regions of the Pacific Ocean. This increase is continuing, whereas sardine populations in the North-Western and South-Eastern Pacific have decreased both in catch and geographic distribution since the late 1980s. Therefore, the North-Eastern Pacific has moved out of phase with other major Pacific sardine populations. This may be because abundance of sardine in the California Current has not yet reached a level at which density-dependent effects exert a major influence. Sardine and anchovy in the South-Eastern Atlantic have been out of phase with populations in the Pacific Ocean, especially those off Peru and Chile. Over the last 300 years, episodic fisheries for Bohuslän herring Clupea harengusin Sweden coincide with periods of high anchovy abundance off California. Near simultaneous fluctuations of fish stocks in widely separated regions support the view that they are sometimes influenced by climate operating at a global scale. Changes of the gyre-scale circulation seem to be major factors in the decadal climate. In Australia, sardine have a wide range, but the less productive waters support a much lower biomass than is found in the other four systems. Engraulisoccur in some systems from which Sardinopsare absent, for example, Brazil, where they and Sardinellaare segregated vertically in the water column.

The aim of the current study was to identify the subcellular compartment(s) responsible for the hydrolysis of chylomicron remnant-retinyl esters, in J774.1 cells. The cells were incubated with medium containing chylomicron remnant [(3)H]retinyl ester. Subcellular fractionation was used to separate early endosomes from late endosomes and lysosomes. About 26% and 80% of the total [(3)H]retinyl esters taken up by the J774 cells were hydrolyzed after 10 min and 60 min of chase, respectively. In the early endosomes, there was a 4-fold increase of radioactivity (nearly all radioactivity associated with retinyl esters) during the first 10 min of chase. The radioactivity in early endosomes was reduced by 43% from 10 min to 60 min and remained stable from 60 to 180 min of chase. From 10 to 60 min the amount of retinol in early endosomes increased from 44% to 82%, indicating an efficient hydrolysis of retinyl esters. Less than 10% and 5% of the total cell-associated radioactivity was found in the late endosomes and lysosomes during the entire chase period. In the chase medium, 84% of the total amount of retinoid released during 180 min was present already after 10 min. The percentage of retinol in the medium increased from 25% to 82% during incubation from 10 to 180 min.These data suggest that retinyl esters are endocytosed together with the chylomicron remnant particle and hydrolyzed in the early endosomes in this cell model.-Hagen, E., A. M. Myhre, T. E. Tjelle, T. Berg, and K. R. Norum. Retinyl esters are hydrolyzed in early endosomes of J774 macrophages.

A case of duodenal somatostatinoma is described in a patient with Von Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic insufficiency, probably due to distal obstruction of the pancreatic duct by the tumor. Preoperative evaluation with calcium-pentagastrin and tol-butamide stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor was performed. Pathological findings were compatible with duodenal somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the tumor coeluted with the somatostatin-14 standard on high performance liquid chromatography (HPLC).

Iodixanol (Visipaque) is a new nonionic roentgen contrast medium intended for general use. Visipaque is a pharmaceutical formulation of iodixanol which is isotonic and iso-osmotic with blood. Two synthetic routes from 5-nitro-isophthalic acid to iodixanol are described. The chemical structure is confirmed by spectroscopical data (1H-NMR, 13C-NMR, FAB-MS, electrospray-MS, UV, IR and Raman). Chromatographic characteristics are related to the isomerism of iodixanol.

In general, most analyses of radial lip seal behavior assume a static deformation state in the seal lip. Nevertheless, a dynamic excitation of the seal lip always occurs in practice, due to unroundness of the shaft or motions of the shaft center. In this first part of a two part paper the influence of dynamic excitation on the occurrence of clearances in a dry seal-shaft contact is studied, taking into account viscoelasticity and inertia of the seal material. The ultimate goal is to determine whether viscoelastic seal behavior can result in a continuous fluid film or not. First, attention is paid to the mechanical behavior of synthetic rubber under an oscillating load. The seal elastomer shows a glass transition, resulting in a strong increase in stiffness with frequency. Next, a FEM analysis of the seal-shaft contact under dynamic conditions is presented. The steady-state response of the seal is represented by a transfer function approach. It is shown that clearances develop due to viscous and inertial seal material behavior. In practice, these clearances are filled with fluid. Due to entrainment and squeeze effects a fluid film is generated. This phenomenon is designated visco-elastohydrodynamic (VEHD) lubrication, and is subject of Part 2.

Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with different forms of both primary and secondary vasculitis and glomerulonephritis. These antibodies are directed against different enzymes located in granulocyte granules. In this review ANCA-related antigens and solid phase assays for ANCA detection will be discussed. Furthermore, we will address the clinical relevance of ANCA and will deliberate on their possible pathogenic implications.

Restrictive infection of Bacillus subtilis by suppressor-sensitive (sus) mutants of phi 29 has been used to search for cistrons that function in viral assembly. The products of cistrons 7, 9, 10, and 16 are necessary for head morphogenesis. The neck upper collar protein P10 and the tail protein P9 must be present for DNA packaging to occur. The protein P7 must be present for phage-related particles to form. A prohead-like particle has been isolated during 16-restrictive infection. The particle is composed of the proteins Hd, P10, F, and P7. P16 must function for DNA-filled particles to accumulate. A DNA-containing particle produced in the absence of the cistron 11 product may be an intermediate in the phi 29 assembly pathway. The protein P13 interacts with P9 and P11 to form a stable DNA-filled particle. The products of cistrons 2 and 3 are essential for viral DNA synthesis, and in their absence virus-related particles are not detected.

In general, most analyses of radial lip seal behavior assume a static deformation state in the seal lip. Nevertheless, a dynamic excitation of the seal lip always occurs in practice, due to unroundness of the shaft or motions of the shaft center. In this first part of a two part paper the influence of dynamic excitation on the occurrence of clearances in a dry seal-shaft contact is studied, taking into account viscoelasticity and inertia of the seal material. The ultimate goal is to determine whether viscoelastic seal behavior can result in a continuous fluid film or not. First, attention is paid to the mechanical behavior of synthetic rubber under an oscillating load. The seal elastomer shows a glass transition, resulting in a strong increase in stiffness with frequency. Next, a FEM analysis of the seal-shaft contact under dynamic conditions is presented. The steady-state response of the seal is represented by a transfer function approach. It is shown that clearances develop due to viscous and inertial seal material behavior. In practice, these clearances are filled with fluid. Due to entrainment and squeeze effects a fluid film is generated. This phenomenon is designated visco-elastohydrodynamic (VEHD) lubrication, and is subject of Part 2.

The aim of this study was to investigate the new synthetic HMG-CoA reductase inhibitor, fluvastatin, for efficacy, safety and tolerability in comparison to cholestyramine. One hundred fifty one primary hypercholesterolaemic patients participated in this double-blind, parallel-group, randomized study. During the first 12 weeks of the study, fluvastatin (20 mg and 40 mg daily) was compared with cholestyramine (16 g per day). In the subsequent, 6-week part of the study, the comparative efficacy, safety and tolerability of 20 mg fluvastatin, combined with cholestyramine (4 g, 8 g, or 16 g) were assessed.

Implantations of pituitary isografts into intact female mice cause marked irregularity and lengthening in estrous cycles. This phenomenon can be produced by a single implantation of two pituitaries. The effect is still apparent 10 to 12 months later. It can be produced although in reduced degree by implantations into animals a year old. The basic mechanism is considered to be a more sustained production of prolactin by the graft. The effects of such transplants are maintained for several months.

Zusammenfassung Nach einem einleitenden Hinweis auf frühere Untersuchungen an sensibilisierten Meerschweinchen, bei denen der Hypothalamus ausgeschaltet wurde, werden zuerst die normalen morphologischen Verhältnisse in dieser Region kurz gestreift. Es wird auf strukturelle Veränderungen an den Nuclei und Zellen bestimmter Kerngebiet des Hypothalamus eingegangen.

Schwere krankhafte Veränderungen wurden mit der Bielschowsky-Methode an den operativ entfernten Grenzstrangganglien von 32 Patienten mit Endangitis obliterans des Gehirns und der Extremitäten, Hyperhydrosis und Akrocyanose der Extremitäten, Raynaudscher Gangrän, Kausalgie, Endarteriitis, renaler und essentieller Hypertonie und Epilepsie festgestellt.

Summary Observations on silver-impregnated sections through the brains of human beings, dogs and guinea pigs show an abundant innervation of the pial arteries. On the basis of the lightmicroscopical findings, two systems of nerve fibres can be distinguished:1.A plexus of fine, nonmyelinated nerve fibres originating from thicker fibre bundles of the adventitia. The fine fibres arborize on the muscle cells of the media of larger and smaller arteries.2.Bundles of myelinated and nonmyelinated fibres, to be found in the periadventitia of larger blood vessels. It is not clear whether there is a connection between these two systems.

Zusammenfassung Die morphologische Eigentümlichkeit nervöser Substanz tritt in der “Zona granulosa” auffälliger in Erscheinung als sonst im Organismus. Die Struktur erweckt den Eindruck einer besonderen sekretorischen Tätigkeit dieses Ortes. Sie steht in engster Verbindung mit den sich hier aufsplitternden Nervenfasern des Tractus tubero-hypophyseus, der vielleicht für die Freisetzung von releasing factors verantwortlich zu machen ist.

Electronmicroscopically observed, the sensory bodies of glabrous skin that contain vegetative fibres can be subdivided as follows: unmyelinated nerve-bodies without capsule; encapsulated, unmyelinated nerve-bodies; unmyelinatted and myelinated nerve-bodies.

With the aid of the electron microscope it had been possible to confirm the existence of intraepithelial nerves in the epidermis of monkeys and dogs. Such nerves were present both in normal epidermis and that which had been subjected to X-ray radiation.

Sprague-Dawley rats with 7,12-dimethylbenzanthracene (DMBA) induced mammary tumors were treated with the cyclic imide CG 603 (1-(morpholinomethyl)-4-phthalimido-piperidindione-2,6), with the androgen drostanolone-propionate (2a-methyldihydrotestosterone propionate) and with both these drugs together.

Beim Diabetes mellitus zeichnen sich Nervenzellgruppen des Tuber cinereum durch konstante strukturelle Veränderungen aus.

Zusammenfassung Durch das thorakoskopische Operationsverfahren vonKux undWittmoser konnten thorakale Grenzstrangganglien von Patienten mit Bronchialasthma, Ulcus ventriculi et duodeni, Hyperhidrosis und Morbus Raynaud zur licht- bzw. elektronenoptischen Untersuchung gewonnen werden.

Implantations of pituitary isografts into intact female mice cause marked irregularity and lengthening in estrous cycles. This phenomenon can be produced by a single implantation of two pituitaries. The effect is still apparent 10 to 12 months later. It can be produced although in reduced degree by implantations into animals a year old. The basic mechanism is considered to be a more sustained production of prolactin by the graft. The effects of such transplants are maintained for several months.