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Abstract Chronic obstructive pulmonary disease (COPD) is characterised by the occurrence of exacerbations triggered by infections. The aim of this study was to determine the composition of the lung microbiome and lung virome in patients with COPD in an African setting and to compare their composition between the stable and exacerbated states. Twenty-four adult COPD patients were recruited from three hospitals. Sputum was collected and bacterial DNA was extracted. Targeted metagenomics was performed to determine the microbiome composition. Viral DNA and RNA were extracted from selected samples followed by cDNA conversion. Shotgun metagenomics sequencing was performed on pooled DNA and RNA. The most abundant phyla across all samples were Firmicutes and Proteobacteria. The following genera were most prevalent: Haemophilus and Streptococcus. There were no considerable differences for alpha and beta diversity measures between the disease states. However, a difference in the abundances between disease states was observed for: (i) Serratia (3% lower abundance in exacerbated state), (ii) Granulicatella (2.2% higher abundance in exacerbated state), (iii) Haemophilus (5.7% higher abundance in exacerbated state) and (iv) Veillonella (2.5% higher abundance in exacerbated state). Virome analysis showed a high abundance of the BeAn 58058 virus, a member of the Poxviridae family, in all six samples (90% to 94%). This study is among the first to report lung microbiome composition in COPD patients from Africa. In this small sample set, no differences in alpha or beta diversity between stable and exacerbated disease state was observed, but an unexpectedly high frequency of BeAn 58058 virus was observed. These observations highlight the need for further research of the lung microbiome of COPD patients in African settings.

Purpose: The internet is increasingly used to seek health information. A dental condition of increasing concern and public interest is molar incisor hypomineralisation (MIH), why we evaluated the information quality of German dentists 'websites on the topic of MIH., Methods: A systematic search was performed by two independent investigators using three search engines. The information content of websites on MIH and technical, functional aspects, overall quality, and risk of bias were assessed using validated instruments (LIDA, DISCERN). Practice-related characteristics (practice type, specialization, setting, number and mean age of dentists) were recorded, and associations of these characteristics with websites' overall quality were explored using multivariable linear regression modelling., Results: 70 sites were included. 52% were multipractices in urban areas (49%). The most common age group was middle-aged individuals (41-50 years). The average number of dentists/practice was 2.5. The majority met more than 50% of the DISCERN and LIDA criteria (90%, 91%). The MIH definition was frequently used (67%), MIH symptoms were described (64%), and 58% mentioned therapies. The prevalence of MIH was mentioned less frequently (48%). MIH example photographs were rarely shown (14%). In multivariable analysis, most practice-related factors were not significant for overall site quality. Only chain practices had slightly higher quality in this regard (2.2; 95% CI of 0.3-4.1)., Conclusions: MIH is mentioned on a large proportion of dentists' websites. Overall technical, functional, and generic quality was high. Risk of bias is limited. While most websites provided a basic definition of MIH and its symptoms, important information for patients was missing., (© 2024. The Author(s).)

Background: Despite a positive patch test reaction to para-phenylenediamine (PPD) and/or toluene-2,5-diamine (PTD), many people attempt to continue dyeing their hair with products containing PPD or its derivatives., Objectives: Investigation of elicitation reactions among PPD/PTD-allergic individuals to hair dye products containing the less sensitizing PPD derivative 2-methoxymethyl (ME)-PPD., Methods: Elicitation reactions were studied in 43 PPD/PTD-allergic individuals by a 45-min pretest with an ME-PPD-containing hair dye on their forearm. Upon a negative result this was followed by exposure to subsequent hair colour treatment(s)., Results: Overall, 38 of 43 PPD/PTD-allergic individuals did not develop an elicitation reaction during the pretest with ME-PPD-containing hair dye products, and were eligible for subsequent hair colour treatments. Of these 38 PPD/PTD-allergic individuals, 29 tolerated subsequent hair dyeing with ME-PPD-containing hair dye products, while seven showed mild and two showed moderate/marked allergic reactions upon the first hair colour treatment., Conclusions: Hair dye products with the less sensitizing ME-PPD were tolerated by 29 of 43 (67%) PPD/PTD-allergic individuals throughout continued hair dyeing with an average of nine treatments per year. Five individuals reacted upon pretesting, while only mild-to-moderate/marked skin reactions occurred upon hair dyeing in nine individuals who were not identified by the pretest. To our knowledge this is the first study among PPD/PTD-allergic individuals indicating that a negative 45-min pretest with a hair dye product helps to avoid severe allergic reactions., (© 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: The factors influencing elicitation responses in individuals allergic to p-phenylenediamine (PPD) in hair dyes are not well understood., Objectives: Investigation of the elicitation response to the new, less-sensitizing PPD alternative 2-methoxymethyl-p-phenylenediamine (ME-PPD) under simulated hair dye use conditions., Methods: The cross-elicitation response to ME-PPD (2% in a hair dye test product for 30 min on forearm then rinsing) was analysed at days 2 and 3 in 30 PPD-allergic individuals with diagnostic patch test grades +, ++ or +++ according to the classification of the International Contact Dermatitis Research Group., Results: Cross-reactivity to the ME-PPD-containing hair dye test product was elicited in nine of 30 subjects (30%), while 70% were negative. Cross-reactivity was elicited in two of four cases with grade +++, three of 10 with grade ++ and four of 16 with grade +. Under identical conditions, PPD was previously found to elicit a response in 21 of 27 PPD-allergic individuals. In 18 of these 21 individuals, either the strength of the cross-elicitation response to ME-PPD was decreased or no response occurred., Conclusions: Under simulated hair dye use conditions, a significantly lower degree of cross-elicitation to ME-PPD (30%) was observed than previously reported for PPD (32 of 38, 84%). Additionally, a decreased cross-elicitation strength was observed across all three patch test grades, likely reflecting the reduced skin-sensitization properties of ME-PPD. Consequently, careful dermatological evaluation is required to assess cross-reactivity to ME-PPD in patients allergic to hair dyes., (© 2014 British Association of Dermatologists.)

Background: A practice with a follow-up meeting post death (FUMPD) with physician and staff for family members of patients who died in the intensive care unit (ICU) was started as a quality project to improve the support of families in post-ICU bereavement. A quality improvement control was conducted after 4 years., Method: The quality improvement control was made retrospectively as an anonymous non-coded questionnaire. Part A related to the FUMPD. Part B inquired if we could contact the family member again for a research project to evaluate family support post-ICU bereavement. The questionnaires were sent to 84 family members of 56 deceased patients., Results: Part A: 46 out of 84 family members answered and had attended a FUMPD. Ninety-one percent of the family members thought that we should continue to offer FUMPD. Seventy-eight percent were satisfied with their meeting. Eighty percent felt that they understood the cause of death. The majority wanted the meeting to take place within 6 weeks of death. Ninety-one percent rated the physician as important to be present at the meeting. The social worker was rated more important to attend the meeting than the assistant nurse. Ninety-one percent wanted to discuss the cause of death.Part B: 54 out of 84 family members answered. Twenty out of 54 did not want us to contact them again., Conclusion: A routine with a Follow-Up Meeting Post Death with the ICU team for the families of the patients who die in the ICU is appreciated. The presence of the physician is important., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Usage of hair dye products containing p-phenylenediamine (PPD) is a concern for PPD-allergic individuals., Objectives: The present study investigates the role of dose and exposure time on elicitation of allergic contact dermatitis under conditions of permanent hair dyeing., Methods: Elicitation responses after application of a typical hair dye product containing 2% PPD for 30 min followed by rinsing were analysed in 38 PPD-allergic individuals with a documented history of hair dye-related allergy. Skin binding experiments in vitro were performed to distinguish the dose available for elicitation from the dose applied., Results: A positive reaction was elicited in 20 of 20 patients with grades ++ to +++ and 12 of 18 with grade + according to the classification of the International Contact Dermatitis Research Group. Under conditions of diagnostic patch testing (48 h exposure), the dose available for elicitation is more than 10-fold higher compared with the dose available for hair dyeing (30-min exposure, rinsing of product)., Conclusions: This investigation demonstrates that under simulated hair dye use conditions the actual exposure to PPD is more than an order of magnitude lower than under diagnostic patch testing, although sufficient to elicit a clearly noticeable reaction in 84% of PPD patch test-positive individuals., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists.)

Background: Transplant vasculopathy leads to neointimal proliferation of allograft arteries, and alpha4beta1-integrin (very late antigen-4 [VLA-4]) seems to play an important role in the pathogenesis. This study evaluates the effect of a new, synthetic, VLA-4 blocker (S3429) on transplant vasculopathy in a rat cardiac transplant model., Methods: After transplantation (Lewis to Fisher), rats were divided randomly into 6 therapy groups: Group 1, n = 14, saline solution (vehicle); Group 2, n = 14, 3 mg/kg/day cyclosporine; Group 3, n = 21, 10 mg/kg/day S3429 + 3 mg/kg/day cyclosporine; Group 4, n = 21, 5 mg/kg/day S3429 + 3 mg/kg/day cyclosporine; Group 5: n = 21, 10 mg/kg/day S3429; Group 6, n = 21, 5 mg/kg/day S3429. Cyclosporine was given continuously until rats were killed. S3429 was either given for the entire study time or was discontinued after 20 days and animals were killed at Day 80. Twenty-eighty days after grafting, we assessed vasculopathy prevalence and mean vessel occlusion in coronary arteries., Results: Cyclosporine decreased the prevalence of vasculopathy and mean vessel occlusion compared with controls. We observed a further decrease in prevalence and mean vessel occlusion with 80 days of therapy with S3429 and cyclosporine. After discontinuing S3429 therapy at Day 20, prevalence and mean vessel occlusion increased to values seen in cyclosporine-treated animals at Day 80. S3429 alone decreased mean vessel occlusion only within the first 20 days compared with controls but had no effect on the prevalence of vasculopathy., Conclusion: Because of the further decrease with S3429 therapy and the dramatic increase after discontinuation of S3429 therapy, we conclude that blocking VLA-4 receptors may prevent the development of transplant vasculopathy.

Introduction: Complement-mediated tubular injury may play an important role in the progression of renal diseases. C3d is a presumed marker of complement activation. Its precursor C3dg has been detected in the urine of patients with membranous nephropathy. However, little is known of the renal handling of C3d or its excretion in other renal diseases., Methods: We measured the urinary excretion of albumin, IgG, beta2-microglobulin (beta2m), and of complement C3d in patients with tubulo-interstitial nephritis (TIN; n= 8), in patients with membranous nephropathy (n = 35) and in patients with nonmembranous glomerular diseases (23 nonproliferative and 21 proliferative). Fractional excretions (FE) were calculated using creatinine clearance as marker of GFR., Results: C3d was not measurable in the urine of the healthy controls, but was detectable in seven out of eight of the TIN patients (median excretion 0.11 mU min-1, range 0.006-2.4 mU min-1). In these patients the urinary excretion of beta2m was clearly elevated (median 26.6 micro g min-1, range 1.0-103 micro g min-1). The FE of C3d correlated with the FE of beta2microglobulin (r = 0.83, P = 0.01), and their ratio amounted to 0.03 (range 0.003-0.06), a value in agreement with the expected sieving coefficient. Urine C3d was detectable in all but three of the patients with glomerular diseases (median excretion 0.36 mU min-1, range 0.004-7.9 mU min-1); C3d-excretion did not differ between the three subgroups of patients with glomerular diseases. FEC3d correlated with FEIgG (r = 0.88, P < 0.01). The ratio FEC3d/FEbeta2m was 0.78 (range 0.04-9.99). Selected patients with membranous nephropathy were re-analyzed after (partial) remission of proteinuria. Reduction of proteinuria resulted in a decrease of C3d excretion., Conclusion: Urinary excretion of C3d is elevated in patients with TIN, most likely as a mere consequence of decreased tubular reabsorption. In patients with glomerular diseases urinary excretion of C3d is increased and related to proteinuria, independent of the underlying glomerular disease. In these patients there is evidence of increased local formation of C3d.

Pemphigus and bullous pemphigoid (BP) are blistering skin diseases associated with IgG autoantibodies to desmosomal and hemidesmosomal components. When autoantibodies to desmogleins 1 and 3 from patients with pemphigus foliaceus (PF) and pemphigus vulgaris (PV) or rabbit antibodies against the murine hemidesmosomal component BP180 are passively transferred into neonatal mice, they induce blisters in the skin of the mice. To develop an animal model that would duplicate the findings in the skin of the patients more closely, full-thickness human skin from healthy volunteers was grafted onto SCID mice. Injection of the purified IgG fraction from the serum of PF and PV patients led to subcorneal and suprabasal splits in the human grafts and human IgG was deposited intercellularly in the upper and lower layers of the epidermis, respectively. Interestingly, anti-BP180 autoantibodies purified from the serum of BP patients and from a rabbit immunized with recombinant human BP180 strongly bound to the basement membrane zone of the grafts (n=32), fixed murine complement, led to the recruitment of neutrophils to the upper dermis of the graft, but did not induce subepidermal blisters. We report a novel experimental model for PF and PV which should greatly facilitate further studies to dissect the immunopathological mechanisms in these diseases. Specifically, this model can be used to identify pathogenically relevant epitopes on human desmogleins 1 and 3 and to develop novel strategies for the treatment of pemphigus.

Extrapolation to humans from rodent ozone exposure is limited by the anatomic differences between the species. Ferrets have similar pulmonary structures to humans, with well developed respiratory bronchioles and submucosal glands. We exposed adult ferrets, monkeys, and rats to 1 ppm ozone (O(3)) or filtered air for 8 h followed by 1 h in filtered air. Bronchoalveolar lavage (BAL) analysis, histopathology, and confocal microscopy were used to evaluate ozone-induced epithelial injury and inflammation. BAL showed significantly increased numbers of neutrophils in ozone-exposed as compared with filtered air ferrets, monkeys, and rats. However, there were 3- to 4-fold more neutrophils in monkeys and ferrets per milliliter of BAL than in rats. Ozone-exposed lungs showed a severe, acute infiltration of neutrophils in regions with necrotic epithelial cells, especially in the centriacinar region that was more severe in ferrets and monkeys than rats. We conclude that acute ozone exposure in ferrets induce severe epithelial necrosis and inflammation, results in similar epithelial injury compared with monkeys, and represents a better model of humans than rodents.

In the mouse, activity phase-shifts of the endogenous clock in the suprachiasmatic nucleus (SCN) are associated with phosphorylation of the transcription factor Ca2+/cAMP responsive element binding protein (CREB). CREB phosphorylation is induced by the retino-hypothalamic transmitter pituitary adenylate cyclase-activating polypeptide (PACAP). As detected by immunohistochemistry in SCN slices from wild-type mice, melatonin completely blocked PACAP-stimulated CREB phosphorylation at low concentrations (1 nM). In Mel1a melatonin receptor-deficient mice, the PACAP-induced CREB phosphorylation was inhibited only at melatonin concentrations of 100 nM. This inhibition was, however, blunted by blocking the Mel1b melatonin receptor. Thus, melatonin modulates PACAP-mediated retinal stimuli for clock entrainment primarily via the Mel1a melatonin receptor through molecular interaction within the cAMP-signalling pathway.

The renewed interest in food allergy and its investigation has been hampered by the lack of an appropriate animal model with similar comparative aspects of form and function relative to humans. Therefore we have been characterizing an inbred colony of high immunoglobulin E-producing dogs that were immunized subcutaneously with food antigen extracts in alum and that developed clinical manifestations of food allergy after oral challenges with food antigen. These dogs had appreciably high IgE antibody titer to specific food antigens, as measured by an enzyme-labeled immunodot assay. Skin test results for the food antigens were consistently positive, as evidenced by a wheal-and-flare reaction. Gastroscopic food sensitivity was tested through an endoscope by injecting allergenic food extracts into the gastric mucosa after intravenous injection of Evans blue dye. Mucosal changes included swelling and erythema, some petechiae and blue patching, and in some instances generalized gastric erythema and hyperperistalsis. Examination of immediate-reaction biopsy specimens revealed edema and few inflammatory cells. Examination of late-reaction biopsy specimens revealed increased eosinophil and mononuclear cell infiltrations typical of late-phase allergic inflammatory responses. Direct mucosal challenge with food extracts confirmed the clinical and immunologic evidence of food allergy in these immunized dogs and suggests the usefulness of the atopic dog as a model for food allergy. This model might also be useful in detecting hidden food allergies in unexplained inflammatory gastrointestinal tract diseases.

Pharmacokinetic parameters of methadone were studied in adult dairy goats. Five goats were each given methadone hydrochloride as a single 0.2 mg/kg of body weight dosage by intramuscular (IM) administration. Plasma methadone concentrations were determined for 96 h after dosing. Plasma methadone concentrations after IM administration were best described by an open one-compartment model. Overall elimination half-life (t1/2) was 1.38 h. Peak plasma concentrations were reached 0.25 h after dosing, and the actual plasma concentration averaged 37.8 ng/ml (SD = 12.76) at that time. The data obtained from this study suggest that plasma concentrations, similar to those that are analgesic in humans, can be achieved after IM administration of methadone at a dose rate of 0.2 mg/kg of body weight. In addition, these plasma concentrations can be maintained for up to 3 h after a single injection and, therefore, may provide satisfactory analgesia for such period.

We present a Penning discharge as a possible radiometric transfer standard source in the vacuum UV, primarily in the spectral region below 20 nm. Following the concept of Finley et al., we have designed a Penning source using NdFeB permanent magnets. Emphasis was put on simple operation, quick electrode exchangeability, and easy source readjustment. The radiant intensities of the emission lines from different ionization stages of both buffer gas atoms and atoms sputtered from the cathodes have been studied in various discharge conditions. For selected Al and buffer gas emission lines we determined the absolute radiant intensities by a comparison with the calculable spectral radiant power of the Berlin Electron Storage Ring. A comparison with data from our hollow-cathode transfer standard source is given.

Samples and data were collected from twenty-eight female black rhinoceroses (Diceros bicornis) during translocation efforts carried out by the Department of National Parks and Wildlife Management in Zimbabwe. Biological data were collected, cytological examination of vaginal smears was performed, and serum concentrations of follicle stimulating hormone, luteinizing hormone, progesterone, oestriol, and 17-beta-oestradiol were determined by radio-immuno-assay. Prolactin levels were determined for 3 pregnant animals, 1 of which was sampled before and after parturition. Vaginal cytology was not found to be helpful for indicating the oestrous cycle stage for the black rhinoceros, but progesterone and 17-beta-oestradiol levels were found to be useful indicators of pregnancy and possibly of oestrous cycle stage as well.

The aim of the present investigation was to study the effects of high thoracic epidural anesthesia (TEA), including the cardiac sympathetic segments, on ischemic ST-segment changes and left ventricular global and regional wall motion abnormalities. Ten patients with a two- or three-vessel coronary artery disease, all treated with the beta-adrenergic blocker metoprolol because of severe stable angina pectoris, performed two identical exercise stress tests, the first without TEA (control exercise) and the second with TEA (TEA exercise). Before each stress test, intravenous metoprolol was given to achieve maximal or near maximal beta-adrenoceptor blockade. Systolic and diastolic arterial pressures (radial artery cannula), heart rate, and rate-pressure product, as well as global and regional ejection fractions, using equilibrium radionuclide angiography in the left anterior oblique projection, were measured at rest and during maximal exercise. ST-segment analysis (V3 or V5) was performed, and the regional wall motion score was calculated at control exercise and TEA exercise. Intravenous metoprolol or intravenous metoprolol plus TEA at rest did not cause any significant changes of any of the variables. During TEA exercise, systolic arterial pressure, diastolic arterial pressure, and rate-pressure product, but not heart rate, were significantly lower compared to control exercise. The global and anterolateral ejection fractions were significantly higher (52.8% versus 46.5% and 53.2% versus 46.0%, respectively, P less than 0.05), and the regional wall motion score was significantly lower (8.8 versus 11.8, P less than 0.01) during TEA exercise than during control exercise. ST-segment depression was significantly lower during TEA exercise (-1.03 versus -1.84 mV, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

A high current hollow cathode source has been developed as a radiometric source standard for the extreme VUV. The source is operated at a constant current of 2 A with an aluminum cathode and helium or argon as buffer gas at pressures of ~1 hPa. The radiance of spectral lines in the wavelength range from 13 to 60 nm has been determined by comparison to the calculable spectral radiant power of the electron storage ring BESSY. An uncertainty of the order of 13% has been achieved for most of the investigated lines. The spectral emission is stable to better than 5% for an operating time of 30 h. An exchange of the cathode restores the original radiance.

Twenty-three (9 male, 14 female) wild horses (Equus caballus) in the Great Basin Desert were immobilized by ground techniques with succinylcholine chloride during 1,950 person-hr. Induction (means = 2.09 +/- 0.59 min) and recovery (means = 12.4 +/- 5.0 min) were rapid and most animals were returned in less than 10 min to original bands. Dosages ranged from 0.66-0.77 mg/kg body weight and neither abortions nor band changes in group membership resulted. However, a few concerted efforts up to 24 hr were needed to return some animals to original bands and three non-drug related mortalities occurred. The responses of bands to darted members and the overall influence of the operation on reproduction, movements, and social structure are presented.

A multi-centre study with epomediol discoids (200 mg three times daily for 30 days) versus placebo was carried out in 519 patients either with symptoms attributable to hepatopathy and/or alterations in the hepatic function. Epomediol was given to 257 patients chosen at random and the remaining 262 were given placebo. In cases of hepatopathy in which there was no severe damage to the hepatic parenchyma the symptoms of the disease were reduced and the laboratory parameters were improved on treatment with epomediol, whereas the activity of the drug was low in patients with chronic hepatopathy. This confirms that the clinical use of epomediol is most useful in cases of hepatopathy in which the change in hepatic function is still reversible.

The shift of interference fringes near an absorption line is measured. In an advanced evaluation procedure values of Nfl from isolated lines as well as from line groups can be determined over a large dynamic range. Criteria are presented for estimating the sensitivity of the method and for calculating and adjusting the optimum fringe system. In comparison to the conventional hook technique the overall accuracy is improved, a rms error can be given for every single measurement, and an overestimation of small hook distances by an observer is excluded. However, this is at the expense of more measurements and computation. Comparison is made with other dispersion methods. variations are demonstrated.