Immunotherapy with partially purified and standardized tree pollen extracts

Patients allergic to pollen from alder, birch and hazel were hyposensitized during a 3-year period with either birch pollen extract alone (n = 24) or a mixture of one or more of alder, birch and hazel pollen extracts (n = 27). The effect of the treatment was evaluated by RAST and tandem crossed-radioimmunoelectrophoresis (tandem-CRIE). The patient' specific IgE response to the major allergens of alder (Aln g I), birch (Bet v I) and hazel (Cor a I and Cor a II), as measured by tandem-CRIE, and the total specific IgE response, measured by RAST, decreased significantly (Pc less than 0.05) during immunotherapy, irrespective of the extract used during the treatment. There was no significant difference (Pc less than 0.05) between the two treatment groups. The results obtained indicate either that birch pollen extract alone is adequate in the treatment of the studied patient group or the patients had been sensitized towards birch pollen alone.     

In vivo administration of anti-CD4 monoclonal antibody prolongs survival in longtailed macaques with experimental allergic encephalomyelitis

The in vivo administration of monoclonal antibody (mAb) to the CD4 antigen associated with helper T cells has been successful in prolonging the survival of nonhuman primates with experimental allergic encephalomyelitis (EAE). EAE was induced in 17 outbred longtailed macaques (Macaca fascicularis) by inoculation of homologous myelin basic protein (BP) in complete Freund's adjuvant (CFA). Treatment was begun at the onset of clinical signs. Eleven animals were treated with anti-CD4 mAb Leu3a (eight) or OKT4a (three). Of the six control animals, two received anti-CD8 mAb (Leu2a), and four were treated with saline. Specific T- and B-cell subsets which have been implicated in the development of EAE were monitored throughout the course of the disease by one- and two-color immunofluorescence (IF). The monkey anti-BP antibody and anti-mouse immunoglobulin (IgG) responses were measured by enzyme-linked immunoassay (ELISA) techniques, as were the levels of free-circulating murine IgG. The nature of the infiltrating lymphocytes in the brain was evaluated histologically post mortem. Our results indicate that anti-CD4 mAb can prolong survival and in some cases completely reverse the clinical appearance of the disease; however, relapses did occur. Treatments with Leu3a or OKT4a anti-CD4 mAbs reversed the ongoing depletion of CD4+ and CD8+ cells caused by the development of EAE and appeared to reduce the size and degree of inflammation in brain lesions. These treatments did not induce immunologic tolerance to mouse IgG since all of the anti-CD4-treated animals produced high titers of anti-mouse IgG antibodies. Treatment with Leu2a (anti-CD8) had no effect on the development of EAE. These results suggest that CD4+ cells are important to the pathogenesis of EAE in macaques and that manipulation of this subset with monoclonal antibodies may provide effective treatment of human demyelinating disease.     

Enzyme-linked immunosorbent assay for detection of immunoglobulin M antibody against the Reiter treponeme flagellum in syphilis

An enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin M (IgM) antibodies against the periplasmatic flagellum of the Reiter treponeme is described. IgM in the test samples was bound to anti-IgM-coated microtest plates, and flagellum-specific IgM antibody was subsequently detected by incubation with a purified flagellum preparation and monospecific anti-flagellum conjugate. Rheumatoid factor, antinuclear antibodies, or flagellum-specific IgG did not interfere. The specificity of the ELISA for IgM antibodies was 99.5% for sera from 200 blood donors and 98.6% for 147 patient sera that gave false-positive reactions in other syphilis serological tests. The sensitivity was 88.5% for sera from 87 patients with first-time primary syphilis, 93.5% for sera from 62 patients with first-time secondary syphilis, 21.4% for sera from 42 patients who were reinfected, and 0% for sera from 13 patients with late syphilis. Of the sera from 153 patients with treated syphilis, 7.2% had IgM antibodies, and sera from patients with primary or secondary syphilis generally had no IgM antibodies 6 months after treatment. The finding of IgM antibodies indicates that patients should receive antisyphilis treatment if they have not been treated recently, but a negative result does not exclude the possibility of active syphilis. The method may prove useful for the diagnosis of congenital syphilis in newborns.     

Effects of pelvic and lower extremity stabilization on isometric trunk extension and flexion muscle strength*

The purpose of this study was to evaluate the effect of varying the type of pelvic and lower extremity stabilization on isometric trunk extension and flexion muscle strength measurements. Two pelvic stabilization systems, one consisting of fixation of the anterior superior iliac spines and sacrum (pelvic fixation) and the second, a strap across the anterior superior iliac spines and a posterior pad at the sacrum (pelvic strap) were compared. The lower extremities were or were not strapped at the thigh, calf, and feet. Torque values for the pelvic fixation system were not different from the pelvic strap system with lower extremity stabilization. Torque values were less with no lower extremity stabilization with both pelvic stabilization systems for flexion but not for extension muscle contractions. The use of an extensive pelvic stabilization system did not produce greater isometric force output than the use of a simple pelvic strap. The use of lower extremity stabilization did produce greater isometric flexion force output than the use of no lower extremity stabilization. J Ortho Sports Phys Ther 1987;9(3):111-117.     

Phaeohyphomycosis caused by the fungal genera Bipolaris and Exserohilum. A report of 9 cases and review of the literature

We have reported 7 new cases of Bipolaris infection and 2 of Exserohilum infection, which demonstrate the capability of these 2 genera to cause invasive as well as "allergic" disease. As noted previously, it is likely that all of the cases of "Helminthosporium" and Drechslera infections reported in the literature were caused by Bipolaris or Exserohilum. Infections due to these 2 genera are probably more common than previously recognized. They should be included in the differential diagnosis of central nervous system and disseminated fungal disease, sinusitis, keratitis, peritonitis associated with continuous ambulatory peritoneal dialysis, and allergic bronchopulmonary disease. These various entities have distinct histopathologic characteristics. With disseminated disease in the immunocompromised patient, the most frequent findings are acute inflammation with prominent vascular invasion, thrombosis, and infarction. In contrast, granulomatous inflammation and leukocytoclastic vasculitis are seen in meningoencephalitis caused by these fungi. The histologic features of allergic bronchopulmonary disease and sinusitis are similar. A chronic inflammatory infiltrate of lymphocytes, plasma cells and eosinophils within edematous granulation tissue is found in addition to squamous metaplasia and thickening of the basement membrane. Infections caused by Bipolaris/Exserohilum and Aspergillus show many clinical and pathologic similarities despite the lack of taxonomic relationship between these fungi. Both cause disseminated disease in immunocompromised patients that is characterized by tissue necrosis and vascular invasion. Both cause central nervous system disease, osteomyelitis, and sinusitis and are associated with allergic bronchopulmonary disease. Sinusitis, the most common form of disease caused by Bipolaris and Exserohilum, occurs in otherwise healthy patients with nasal polyposis and allergic rhinitis. Although pathologic evidence of bone invasion may not be found, there frequently is radiographic evidence of invasive disease. Most patients who are treated initially with surgical debridement and amphotericin B have apparently been cured. However, longer follow-up will be necessary in these patients. Amphotericin B appears to be the treatment of choice for invasive infections caused by Bipolaris/Exserohilum species. Ketoconazole and other imidazole derivatives may also be effective in certain of the disease entities caused by these black moulds; however, their role has yet to be defined.(ABSTRACT TRUNCATED AT 400 WORDS)     

ZK 91296, a partial agonist at benzodiazepine receptors

ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl--carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.     

Evaluating Differences in Whole Blood,Serum, and Urine Screening Tests for Zika Virus,Puerto Rico,USA, 2016

We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015–2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens.     

The effects of exposure to microgravity and reconditioning of the lumbar multifidus and anterolateral abdominal muscles: implications for people with LBP

BACKGROUND CONTEXTOne of the primary changes in the neuromuscular system in response to microgravity is skeletal muscle atrophy, which occurs especially in muscles that maintain posture while being upright on Earth. Reduced size of paraspinal and abdominal muscles has been documented after spaceflight. Exercises are undertaken on the International Space Station (ISS) during and following space flight to remediate these effects. Understanding the adaptations which occur in trunk muscles in response to microgravity could inform the development of specific countermeasures, which may have applications for people with conditions on Earth such as low back pain (LBP).PURPOSEThe aim of this study was to examine the changes in muscle size and function of the lumbar multifidus (MF) and anterolateral abdominal muscles (1) in response to exposure to 6 months of microgravity on the ISS and (2) in response to a 15-day reconditioning program on Earth.DESIGNProspective longitudinal series.PATIENT SAMPLEData were collected from five astronauts who undertook seven long-duration missions on the ISS.OUTCOME MEASURESFor the MF muscle, measures included cross-sectional area (CSA) and linear measures to assess voluntary isometric contractions at vertebral levels L2 to L5. For the abdominal muscles, the thickness of the transversus abdominis (TrA), obliquus internus abdominis (IO) and obliquus externus abdominis (EO) muscles at rest and on contraction were measured.METHODSUltrasound imaging of trunk muscles was conducted at four timepoints (preflight, postflight, mid-reconditioning, and post reconditioning). Data were analyzed using multilevel linear models to estimate the change in muscle parameters of interest across three time periods.RESULTSBeta-coefficients (estimates of the expected change in the measure across the specified time period, adjusted for the baseline measurement) indicated that the CSA of the MF muscles decreased significantly at all lumbar vertebral levels (except L2) in response to exposure to microgravity (L3=12.6%; L4=6.1%, L5=10.3%; p<.001), and CSAs at L3-L5 vertebral levels increased in the reconditioning period (p<.001). The thickness of the TrA decreased by 34.1% (p<.017), IO decreased by 15.4% (p=.04), and the combination of anterolateral abdominal muscles decreased by 16.2% (p<.001) between pre- and postflight assessment and increased (TrA<0.008; combined p=.035) during the postreconditioning period. Results showed decreased contraction of the MF muscles at the L2 (from 12.8% to 3.4%; p=.007) and L3 (from 12.2% to 5%; p=.032) vertebral levels following exposure to microgravity which increased (L2, p=.046) after the postreconditioning period. Comparison with preflight measures indicated that there were no residual changes in muscle size and function after the postreconditioning period, apart from CSA of MF at L2, which remained 15.3% larger than preflight values (p<.001).CONCLUSIONSIn-flight exercise countermeasures mitigated, but did not completely prevent, changes in the size and function of the lumbar MF and anterolateral abdominal muscles. Many of the observed changes in size and control of the MF and abdominal muscles that occurred in response to prolonged exposure to microgravity paralleled those seen in people with LBP or exposed to prolonged bed rest on Earth. Daily individualized postflight reconditioning, which included both motor control training and weight-bearing exercises with an emphasis on retraining strength and endurance to re-establish normal postural alignment with respect to gravity, restored the decreased size and control of the MF (at the L3-L5 vertebral levels) and anterolateral abdominal muscles. Drawing parallels between changes which occur to the neuromuscular system in microgravity and which exercises best recover muscle size and function could help health professionals tailor improved interventions for terrestrial populations. Results suggested that the principles underpinning the exercises developed for astronauts following prolonged exposure to microgravity (emphasizing strength and endurance training to re-establish normal postural alignment and distribution of load with respect to gravity) can also be applied for people with chronic LBP, as the MF and anterolateral abdominal muscles were affected in similar ways in both populations. The results may also inform the development of new astronaut countermeasures targeting the MF and abdominal muscles.     

Tuberculosis infection and disease in South African adolescents with perinatally acquired HIV on antiretroviral therapy: a cohort study

IntroductionThere are limited data on Tuberculosis (TB) in adolescents with perinatally acquired HIV (APHIV). We examined the incidence and determinants of TB infection and disease in the Cape Town Adolescent Antiretroviral Cohort (CTAAC).MethodsYouth between nine and fourteen years on antiretroviral therapy (ART) for more than six months in public sector care, and age‐matched HIV‐negative adolescents, were enrolled between July 2013 through March 2015 and followed six‐monthly. Data were censored on 31 October 2018. Symptom screening, chest radiograph, viral load, CD4 count, QuantiFERON (QFT) and sputum for Xpert MTB/RIF, microscopy, culture and sensitivity were performed annually. TB infection was defined by a QFT of >0.35 IU/mL. TB diagnosis was defined as confirmed (culture or Xpert MTB/RIF positive) or unconfirmed (clinical diagnosis and started on TB treatment). Analyses examined the incidence and determinants of TB infection and disease.ResultsOverall 496 HIV+ and 103 HIV‐negative participants (median age at enrolment 12 years (interquartile range, IQR 10.6 to 13.3) were followed for a median of 3.1 years (IQR 3.0 to 3.4); 50% (298/599) were male. APHIV initiated ART at median age 4.4 years (IQR 2.1 to 7.6). At enrolment, 376/496 (76%) had HIV viral load <40 copies/mL, median CD4 count was 713 cells/mm³ and 179/559 (32%) were QFT+, with no difference by HIV status (APHIV 154/468, 33%; HIV negative 25/91, 27%; p = 0.31). The cumulative QFT+ prevalence was similar (APHIV 225/492, 46%; 95%CI 41% to 50%; HIV negative 44/98, 45%; 95% CI 35% to 55%; p = 0.88). APHIV had a higher incidence of all TB disease than HIV‐negative adolescents (2.2/100PY, 95% CI 1.6 to 3.1 vs. 0.3/100PY, 95% CI 0.04 to 2.2; IRR 7.36, 95% CI 1.01 to 53.55). The rate of bacteriologically confirmed TB in APHIV was 1.3/100 PY compared to 0.3/100PY for HIV‐negative adolescents, suggesting a fourfold increased risk of developing TB disease in APHIV despite access to ART. In addition, a positive QFT at enrolment was not predictive of TB in this population.ConclusionsHigh incidence rates of TB disease occur in APHIV despite similar QFT conversion rates to HIV‐negative adolescents. Strategies to prevent TB in this vulnerable group must be strengthened.     

Clinical outcome after surgery on schwannomas in the extremities

BACKGROUND Schwannoma is a benign, encapsulated and slowly growing tumor originating from Schwann cells and is rarely seen in the peripheral nerve system. Typical symptoms are soreness, radiating pain and sensory loss combined with a soft tissue mass.AIM To evaluate pre-and postoperative symptoms in patients operated for schwannomas in the extremities and investigate the rate of malignant transformation.METHODS In this single center retrospective study design, all patients who had surgery for a benign schwannoma in the extremities from May 1997 to January 2018 were included. The location of the tumor in the extremities was divided into five groups; forearm, arm, shoulder, thigh and leg including foot. The locations of the tumor in the nerves were also categorized as either; proximal, distal, minor or major nerve. During the pre-and postoperative clinical evaluation, symptoms were classified as paresthesia, local pain, radiating pain, swelling, impairment of mobility/strength and asymptomatic tumors that were found incidentally(with magnetic resonance imaging). The patients were evaluated after surgery using the following categories: Asymptomatic or symptomatic patients(radiating and/or local pain) and those with complications. The follow up period was from the time of surgery until last examination of the particular physician. Multivariate logistic regression analysis was performed to identify independent prognostic factors for postoperative significant symptoms at follow-up.RESULTS We identified 858 cases from the institutional pathology register. We excluded cases with duplicate diagnoses(n = 407), pathology not including schwannomas(n = 157), lesions involving the torso, spine and neck(n = 150) leaving 144 patients for further analysis. In this group 99 patients underwent surgery and there were five complications recorded: 2 infections(treated with antibiotics) and 3 nerve palsies(2 involving the radial nerve and one involving the median nerve) that recovered spontaneously. At the end of follow-up, 1.4 mo(range 0.5-76) postoperatively, we recorded a post-operative decrease in clinical symptoms: Local pain 76%(6/25), radiating pain 97%(2/45), swelling 20%(8/10). Symptoms of paresthesia increased by 2.8%(37/36) and there was no change in motor weakness before and after surgery 1%(1/1). Multivariate analysis showed that tumors located within minor nerves had a significantly higher prevalence of postoperative symptoms compared with tumors in major nerves(odds ratio: 2.63; confidence intervals: 1.22-6.42, P = 0.029). One patient with schwannoma diagnosed by needle biopsy was diagnosed to have malignant transformation diagnosed in the surgically removed tumor. No local recurrences were reported.CONCLUSION Surgery of schwannomas can be conducted with low risk of postoperative complications, acceptable decrease in clinical symptoms and risk of malignant transformation is low.