European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Effects of replacing maize silage with lucerne silage and lucerne silage chop length on rumen function and milk fatty acid composition.

The objective of this study was to investigate whether higher lucerne (Medicago sativa; alfalfa) silage inclusion rate and longer lucerne chop length improves rumen function through increased provision of physically effective fiber, when included in a maize and lucerne silage-based total mixed ration. Diets were formulated to contain a 50:50 forage:concentrate ratio [dry matter (DM) basis] and be isonitrogenous and contain equal levels of neutral detergent fiber (320 g/kg). The forage portion of the offered diets was composed of maize and lucerne silage DM in proportions (wt/wt) of either 25:75 (high lucerne; HL) or 75:25 (low lucerne; LL). Second-cut lucerne was harvested and conserved as silage at either a long (L) or a short (S) chop length (geometric mean particle lengths of 9.0 and 14.3 mm, respectively). These variables were combined in a 2 × 2 factorial arrangement to give 4 treatments (HLL, HLS, LLL, LLS), which were fed in a 4 × 4 Latin square design study to 4 rumen-cannulated, multiparous, Holstein dairy cows in mid lactation. Effects on DM intake, chewing behavior, rumen volatile fatty acid concentration, rumen pH, rumen and fecal particle size, milk production, and milk fatty acid profile were measured. Longer chop length increased rumination times per kilogram of DM intake (+2.8 min/kg) relative to the S chop length, with HLL diets resulting in the most rumination chews. Rumen concentrations of total volatile fatty acids, acetate, and n-valerate were higher for the HLS diet than the other 3 diets, whereas rumen propionate concentration was lowest for the HLL diet. Physically effective fiber (particles >4 mm) percentage in the rumen mat was increased when L chop length was fed regardless of lucerne inclusion rate. No effect of treatment was observed for milk yield, although milk protein concentration was increased by L for the LL diet (+1.6 g/kg) and decreased by L for the HLL diet (-1.4 g/kg). Milk fat concentrations of total cis-18:1 (+3.7 g/100 g of fatty acids) and 18:3 n-3 (+0.2 g/100 g of fatty acids) were greater with HL. In conclusion, longer lucerne silage chop length increased time spent ruminating per kilogram of DM intake, but had no effect on rumen pH in the present study. Increasing dietary lucerne inclusion rate had no effects on rumination activity or rumen pH, but decreased the ratio of n-6:n-3 polyunsaturated fatty acid concentrations in milk fat.

Retention of solute and particle markers in the digestive tract of chinchillas (Chinchilla laniger).

The chinchilla (Chinchilla laniger) is a herbivorous hystricomorph South American rodent for which no mean digesta retention times have been reported so far. Six animals (mean body mass ± standard deviation: 513 ± 99 g) on a diet of grass hay and lucerne-based pellets were given a pulse dose of a solute (cobalt-EDTA) and a particle (chromium-mordanted fibre, <2 mm) marker with subsequent frequent faecal collection. Dry matter intake was 45.2 ± 8.0 g/kg(0.75) /day. Mean retention times were 22.2 ± 5.3 h for solutes and 25.4 ± 5.2 h for particles, with the difference being not significant within individuals. This indicates the presence of a 'mucus-trap' colonic separation mechanism, which is in accord with morphological descriptions of the typical colonic furrow in chinchillas. Corresponding to a strategy of colonic digesta separation and caecotroph formation, secondary marker excretion peaks indicated coprophagic events that were spaced approximately 12 h apart. Given that these retention times appear longer than measures reported for rabbits (Oryctolagus cuniculus) or guinea pigs (Cavia procellus), it would be interesting to compare the digestive efficiency of chinchillas on high levels of dietary fibre to other species.

Digestive physiology, metabolism and methane production of captive Linné's two-toed sloths (Choloepus didactylus).

Sloths are renowned for their low metabolic rate, low food intake and low defecation frequency. We investigated factors of digestive physiology and energy metabolism in four captive individuals (mean body mass 10.0 ± SD 3.7 kg) of a hitherto mostly unstudied sloth species, Linné's two-toed sloth (Choloepus didactylus), in a 2-week digestion recording and 23-h respiration experiment on animals fed a standard zoo diet of vegetables and starchy components. Dry matter intake, defecation frequency and particle mean retention time (MRT) in the gastrointestinal tract (GIT) were 12 ± 3 g/(kg(0.75)  day), once every 5 days and >140 h in three individuals, but 53 g/(kg(0.75)  day), daily and 82 h in one individual that was apparently compensating for a period of weight loss prior to the experiment. In all animals, solute marker was eliminated at a faster rate than the particle marker, indicating 'digesta washing' in the sloths' GIT. The overall metabolic rate calculated from oxygen consumption matched the metabolisable energy intake in three individuals [173 ± 22 vs. 168 ± 44 kJ/(kg(0.75)  day)] but not in the fourth one [225 vs. 698 kJ/(kg(0.75)  day)], supporting the interpretation that this animal was replenishing body stores. In spite of the low food intake and the low-fibre diet (209 ± 26 g neutral detergent fibre/kg dry matter), methane production was rather high accounting for 9.4 ± 0.8% of gross energy intake (2.7% in the fourth individual), which exceeded literature data for ruminants on forage-only diets. These results corroborate literature reports on low intake, low defecation frequency, low metabolic rate and long MRT in other sloth species. The long MRT is probably responsible for the comparatively high methane production, providing more opportunity for methanogenic archaea than in other non-ruminant mammals to produce significant amounts of methane.

Effect of shoeing conditions on hoof dimensions in Icelandic and Warmblood horses.

In Icelandic horses (ICE), high, long hooves with added weights are often used to improve gait quality in competitions. From a biomechanical point of view, excessively long hooves can be problematic as they increase forces acting on the distal limb. The study aimed to determine if hoof capsule size and angle of ICE at competitions are comparable to those of Warmblood horses (WB) requiring shoeing. Hoof dimensions and balance were quantified in 13 horses of each breed at the beginning of a shoeing period (BSP), allowing a baseline comparison between breeds, as well as for WB at the end of a shoeing period (ESP) and for ICE when shod for competition (COMP). Left front and hind hoof capsules and bony structures of the hooves were measured on lateromedial and dorsopalmar/dorsoplantar radiographs at BSP (ICE, WB), ESP (WB) and COMP (ICE), respectively, using the software Metron-Hoof-Pro. Compared to WBBSP, ICEBSP had larger hoof capsules relative to the size of P3 and, when controlled for withers height, longer dorsal hoof wall lengths. The comparison of ICECOMP to WBESP indicated that the relative increase in hoof length and volume was greater in ICECOMP compared to WBESP. Hoof balance was closer to previously published values in WBs, while hoof angles in ICE (particularly palmar/plantar angle of P3) were generally larger and thus less problematic. In conclusion, hooves of ICECOMP were relatively larger and less balanced than WBESP, but hoof angles in WB were smaller than in ICE.

Hoof conformation in Icelandic competition horses and its interrelationship with hoof pathologies and tölt performance.

In order to improve the four-beat-rhythm and forelimb action of the tölt in Icelandic horses (ICE), special shoeing techniques are applied particularly in the front hooves by increasing hoof length and height, or by adding weight to the distal limbs. Although regulations limit dorsal hoof wall length (LDHW) in competition ICE, their shoeing often deviates from a biomechanically optimal distal limb conformation. This study aimed to qualitatively and quantitatively describe current shoeing practices of ICE in competition. Moreover, the influence of LDHW on the occurrence of deviations from a standard hoof conformation, as well as on tölt performance was investigated. At four European competition sites, hoof dimensions of 133 randomly selected ICE were measured manually, and limb conformation and hoof balance were described. Dorsopalmar/-plantar and lateromedial radiographs of the left front and hind hooves were taken of each horse. Various parameters related to hoof dimensions and balance were measured on radiographs using the Metron-Hoof-Pro software. Flares of the dorsal hoof wall had the highest prevalence of all investigated hoof deformities. Multiple logistic regression analysis revealed that longer LDHW was associated with the occurrence of toe flares (P = 0.045), a broken hoof pastern axis (P = 0.003), and asymmetry of the quarter wall heights (P = 0.015). However, horses with a longer LDHW achieved higher scores in competition. In spite of its positive effect on tölt performance, a long LDHW is not recommendable as it may be associated with a higher prevalence of certain hoof deformities.

Review: Comparative methane production in mammalian herbivores.

Methane (CH4) production is a ubiquitous, apparently unavoidable side effect of fermentative fibre digestion by symbiotic microbiota in mammalian herbivores. Here, a data compilation is presented of in vivo CH4 measurements in individuals of 37 mammalian herbivore species fed forage-only diets, from the literature and from hitherto unpublished measurements. In contrast to previous claims, absolute CH4 emissions scaled linearly to DM intake, and CH4 yields (per DM or gross energy intake) did not vary significantly with body mass. CH4 physiology hence cannot be construed to represent an intrinsic ruminant or herbivore body size limitation. The dataset does not support traditional dichotomies of CH4 emission intensity between ruminants and nonruminants, or between foregut and hindgut fermenters. Several rodent hindgut fermenters and nonruminant foregut fermenters emit CH4 of a magnitude as high as ruminants of similar size, intake level, digesta retention or gut capacity. By contrast, equids, macropods (kangaroos) and rabbits produce few CH4 and have low CH4 : CO2 ratios for their size, intake level, digesta retention or gut capacity, ruling out these factors as explanation for interspecific variation. These findings lead to the conclusion that still unidentified host-specific factors other than digesta retention characteristics, or the presence of rumination or a foregut, influence CH4 production. Measurements of CH4 yield per digested fibre indicate that the amount of CH4 produced during fibre digestion varies not only across but also within species, possibly pointing towards variation in microbiota functionality. Recent findings on the genetic control of microbiome composition, including methanogens, raise the question about the benefits methanogens provide for many (but apparently not to the same extent for all) species, which possibly prevented the evolution of the hosting of low-methanogenic microbiota across mammals.

A rationale for epidural analgesia in the treatment of multiple rib fractures.

Thoracic epidural analgesia (EA) is described as an alternative to controlled ventilation in patients presenting with multiple rib fractures. Lung mechanics were especially studied in 6 patients selected from a total of 49. The average ICU stay for this group was 4.5 days (2-11) and the mean age 55.7 years. The EA group was compared with 51 patients primarily ventilated who had an average stay in the ICU of 9.8 days and a mean age of 44.7 years. Mean number of rib fractures of the ventilated group at 6.5 was almost equal to the mean of 6.8 in the EA group. There was a difference in the number of associated fractures, 98 in the ventilated group compared to 35 in the EA group. Severe pulmonary and cerebral contusion were the two most important factors in enforcing the need to ventilate. The success of the method is evidenced by the increase in functional residual capacity (FRC), dynamic lung compliance (Cdyn), vital capacity (VC), the decrease of airway resistance (R) and a significantly increase of PaO2 (p less than 0,001) for the EA group with a balanced fluid therapy. All this accounts for the clinical observation of diminishing paradoxical movement of the flail segment.

Epidural analgesia or mechanical ventilation for multiple Rib fractures?

A protocol for treating thoracic trauma is proposed. Severe pulmonary lesion with increased venous admixture (e.g. contusio, atelectasis, aspiration) is treated by mechanical ventilation. Rib fractures with minor pulmonary lesion and therefore with only moderately abnormal gas exchange but with remarkably reduced vital capacity (even with flail chest) are controlled by thoracic epidural analgesia following vital capacity, tidal volume and respiratory rate. If both a severe pulmonary lesion and serial rib fractures are present, the patient is ventilated for 2-3 days and then extubated to breath spontaneously with epidural analgesia. The indication for a mechanical ventilation or for spontaneous breathing with thoracic epidural analgesia is therefore deducted more from functional variables than from morphological facts. The course of a consecutive series of 283 patients is presented. 155 patients were treated with primary ventilation and 112 patients with primary epidural analgesia, while 16 patients could be managed with general analgesia. The duration of treatment morbidity and mortality show this protocol to be very useful.

Separation of basic solutes by reversed-phase capillary electrochromatography.

The separation of basic solutes at low pH by capillary electrochromatography (CEC) has been investigated. The feasibility of separation of basic solutes by CEC was demonstrated. Influence of operational parameters, solvent composition, pH, temperature on retention and selectivity of the separation of a mixture of basic, neutral and acidic drug standards has been investigated. The observed elution behavior has been modeled to account for both chromatographic retention and differential electrophoretic mobility of the solutes. This model was verified experimentally. It is demonstrated in this work that the elution window of solutes in reversed-phase CEC is expanded to range from -1 to infinity.

Towards the column bed stabilization of columns in capillary electroendosmotic chromatography. Immobilization of microparticulate silica columns to a continuous bed.

This article discusses a novel method generating a continuous bed inside the CEC column. The column bed composed of microparticulate reversed-phase silica is completely immobilized by a hydrothermal treatment using water for the immobilization process. This process eliminates the manufacture of frits of both ends of the column and all problems associated with their preparation. Fundamental studies on operational parameters will be presented such as the dependence of the immobilization on the column temperature, the type of stationary phase and the column back pressure. The immobilized CEC columns show the same high column efficiency as packed columns with frits.

Respiratory assistance on surgical wards with continuous positive airway pressure (Turbo-PEEP-Weaner).

Based on our own experience, we introduce a new continuous positive airway pressure device. The patient can breathe continuously positive airway pressure through a tight face mask, and thus the postoperative reduction in functional residual capacity is counteracted. This is shown by the well-documented clinical course of a 62 year old man who had respiratory insufficiency after proximal selective vagotomy.

Advances in capillary electrochromatography.

This paper presents practical aspects of capillary electrochromatography (CEC). Preparation of capillary columns, including terminating frits and immobilization of the packed bed, is described in detail. Longevity and reproducibility of CEC columns is demonstrated. Instrumental aspects, sample introduction, sensitivity of detection, and gradient elution are discussed in detail. A number of examples that illustrate the versatility of CEC, in particular, for providing an isocratic separation alternative to conventional gradient separation in HPLC, are given.

[Analysis of the external and internal surface of human dura mater with scanning electron microscopy]. / Análisis de la superficie externa e interna de la duramadre humana mediante microscopia electrónica de barrido.

INTRODUCTION: In recent years several studies have raised questions about the anatomy of the human dura mater. Our objective has therefore been to examine its tridimensional structure with the aid of the scanning electron microscope. METHOD: Samples were taken from 4 human cadavers (70, 72, 77 and 78 years old) between 8 and 12 hours after death. After fixing in glutaraldehyde phosphate buffer, dehydration in acetone and elimination of the acetone at the critical point, treatment with carbon and metallization with gold, the external and internal surfaces were examined. RESULTS: The external, or epidural, surface of the dura mater is made up of thin collagen fibers joined in bands running in different directions. The outer surface and lower layers of the dura contain elastic, interwoven fibers surpassing 2 microns in diameter. The inner surface, which is smooth and glossy, is formed of thin ribbons of arachnoids that are fused and tightly attached to the structure of the dura mater. CONCLUSION: The outer surface of the dura mater consists mainly of collagen fibers which alone or in groups run in different directions: longitudinally, horizontally or obliquely, depending on the are studied. These findings contradict the classical descriptions of the dura mater as having parallel, longitudinally placed collagen fibers in the tangential plane.

[Structural analysis of the thickness of human dura mater with scanning electron microscopy]. / Análisis estructural del espesor de la duramadre humana mediante microscopia electrónica de barrido.

INTRODUCTION: The only references to the thickness of the human dura mater, reporting its size at various levels, are now 50 years old. Our aim was to study its tridimensional structure with the aid of the scanning electron microscope. METHOD: The samples, which were taken 8-12 h after death from 4 human cadavers between 70 and 78 years old, were examined on 2 orthogonal planes (radial longitudinal and transversal). RESULTS: The architectural structure of the external membrane of the meninges was unusual. The dura mater is made up of elastic collagen fibers organized in successive parallel planes on the surface of the medulla. Each plane constitutes a unit which we will call a sub-laminae. The sub-laminae are found in groups of 8 to 12 that form larger units called laminae, which are between 4 and 5 microns thick. The full thickness of the dura mater at the level of the third lumbar vertebrate contains from 78 to 82 laminae which together measure 270 microns. CONCLUSION: The dura mater is made up of a large number of sublaminae that are concentrically parallel to the surface of the medulla. The fibers in general run in all directions and are oriented differently in each sub-lamina. The orientation of fibers that can be seen on the outer or epidural surface corresponds only to the fibers of the outermost lamina, which has a thickness of 78 to 82 microns. A needle that pierces the dura mater passes through some 700 to 800 sublaminae, each with its own particular distribution of fibers.

[Iatrogenic spinal epidermoid tumors. A late complication of spinal puncture]. / Tumores epidermoides espinales iatrogénicos. Una complicación tardía de la punción espinal.

INTRODUCTION. Epidermoid tumors in the spinal canal are rare. Whether congenitally or iatrogenically caused, they form as the result of epidermal cells implanted within the spinal channel. Such implantation can occur during a variety of procedures and events such as bullet wounds, surgery, myelography or punctures for diagnosis, anesthesia or treatment. Although this complication is not discussed in books or journals on anesthesiology, we have found it mentioned in over 100 published cases reporting iatrogenically caused spinal epidermoid tumors. ETIOPATHOGENESIS. Iatrogenic epidermoid tumors of the spine derive from the implantation of epidermal tissue transported inside the spinal canal during lumbar punctures without guidance or with inadequate guidance. There is ample evidence that such tumors are iatrogenic. All cases occur in patients with a history of lumbar puncture. They are rarely associated with congenital anomalies. They are extramedullary. They tend to develop near sites of earlier lumbar puncture, usually near the conus medullaris and the cauda equina. Iatrogenic epidermoid tumors of the spine have been reproduced experimentally in two studies in which autologous skin fragments were implanted in the spinal canal. CLINICAL SIGNS. These tumors are well tolerated by patients for extended periods of time, ranging from 2 to 10 years. At the cauda equinus, tumors can grow slowly for long periods without signs of nerve compression. Symptoms are directly related to tumor size and site. All patients with tumors at the cauda equinus report severe pain radiating toward the roots of compressed nerves. Nuclear magnetic resonance makes it possible to detect the tumor without administration of intrathecal contrast. At present gadolinium-DTPA improves the image so that these tumors can be distinguished from other types. The prognosis for epidermoid tumors of the spine is good, as they are histologically benign. Treatment is always surgical. CONCLUSION. Although the causal relation between epidermoid spinal tumors and lumbar puncture is well documented, anesthesiologists are not sufficiently aware of this possible complication. Between 1977 and 1995, 28 new cases were published. We believe that a deeper understanding of such rare complications will show us how to prevent them while providing appropriate use of epidural and subarachnoid anesthesia.

[Electron microscopy of the lesions produced in the human dura mater by Quincke beveled and Whitacre needles]. / Microscopia electrónica de las lesiones producidas en la duramadre humana por las agujas de bisel Quincke y Whitacre.

INTRODUCTION: Comparisons of Quincke needles and non traumatic "pencil point" needles in recent years have reported lower rates of post dural puncture headache using the later type. Our new understanding of the morphology of the human dura mater motivated us to study dural lesions caused by the Whitacre 25 G and Quincke 26 G needles, using scanning electron microscopy with the aim of determining whether there is an anatomic basis for the different outcomes. METHOD: The dura mater from three fresh cadavers of individuals aged 65, 70 and 72 years were punctured 40 times at an angle of 90 degrees each time. The Whitacre 25 G needle was used for 20 punctures and the Quincke 26 G needle was used for the other 20. Half the punctures were performed with the bevel in the parallel alignment and the other half with the bevel perpendicular to the spinal column. Fifteen min after causing the punctures, specimens were fixed in solutions of glutaraldehyde phosphate buffer and dehydrated in acetone. After critical point removal of the acetone, after the specimens were treated with carbon and metallized with gold. The lesions were examined externally and internally and expressed as the ratio of area of lesion to diameter of the needle that had caused them. RESULTS: Whitacre needle: each lesion consisted in the superimposition of multiple damaged layers that started to close individually. After 15 min the outermost layers were 90% closed and the innermost ones had closed entirely. Layers in the arachnoid surface of the dura mater had closed from 86 to 88%, while deeper layers in the thick part had closed 97 to 98%. Quincke needle: lesions were V-shaped or half-moon shaped, much like the opening formed by a can opener, on both the external and internal surfaces. Alignment of the bevel of the needle parallel to the spinal column did not lead to a different shape of puncture. After 15 min the lesions had closed 94 to 95% on the epidural surface and 95 to 96% on the arachnoid side, a difference attributable to the retraction of the arachnoid layers over the spinal column. CONCLUSION: Non traumatic beveled dural needles, termed "pencil point needles", only partially separate dural fibers, and lesions caused by these needles develop in a more complex way. The Quincke 26G needle produced a puncture that is morphologically different from that caused by the Whitacre 25G needle, although lesions produced by both types close more than 94% after 15 min. We believe the size of the lesion caused by these needles does not explain the difference in post dural puncture headache due to loss of spinal fluid.

Quantification aspects of constant pressure (ultra) high pressure liquid chromatography using mass-sensitive detectors with a nebulizing interface.

The present contribution investigates the quantitation aspects of mass-sensitive detectors with nebulizing interface (ESI-MSD, ELSD, CAD) in the constant pressure gradient elution mode. In this operation mode, the pressure is controlled and maintained at a set value and the liquid flow rate will vary according to the inverse mobile phase viscosity. As the pressure is continuously kept at the allowable maximum during the entire gradient run, the average liquid flow rate is higher compared to that in the conventional constant flow rate operation mode, thus shortening the analysis time. The following three mass-sensitive detectors were investigated: mass spectrometry detector (MS), evaporative light scattering detector (ELSD) and charged aerosol detector (CAD) and a wide variety of samples (phenones, polyaromatic hydrocarbons, wine, cocoa butter) has been considered. It was found that the nebulizing efficiency of the LC-interfaces of the three detectors under consideration changes with the increasing liquid flow rate. For the MS, the increasing flow rate leads to a lower peak area whereas for the ELSD the peak area increases compared to the constant flow rate mode. The peak area obtained with a CAD is rather insensitive to the liquid flow rate. The reproducibility of the peak area remains similar in both modes, although variation in system permeability compromises the 'long-term' reproducibility. This problem can however be overcome by running a flow rate program with an optimized flow rate and composition profile obtained from the constant pressure mode. In this case, the quantification remains reproducibile, despite any occuring variations of the system permeability. Furthermore, the same fragmentation pattern (MS) has been found in the constant pressure mode compared to the customary constant flow rate mode.