A new side effect of BCG immunotherapy — BCG-induced arthritis in man

Summary Ten of 159 patients showed arthritic symptoms during the course of BCG immunotherapy for advanced cancer. The arthritic symptoms occurring after BCG injections had the following characteristics: (1) The incidence of arthritis was closely correlated with the host immunologic responsiveness to BCG; (2) These symptoms usually occurred 1–5 months after the first BCG injection (7/10); (3) The arthritic symptoms usually started with morning stiffness (9/10), which was followed by acute inflammatory signs in the affected joints. They gradually subsided in response to treatment with nonsteroid antiinflammatory drugs, but were not completely cured while the effectiveness of BCG continued; (4) The symptoms were aggravated by additional BCG injections (8/10). (5) This form of arthritis could be differentiated from rheumatoid arthritis, tuberculous, or purulent arthritis by its clinical course and by roentgenograms of the affected joints. It is thought to be induced by the adjuvant effect of BCG, and is a new side effect of BCG immunotherapy.     

Propranolol in the Control of Schizophrenic Symptoms

All schizophrenic symptoms remitted completely in six out of 14 adults who had not responded to phenothiazine drugs and who were then given propranolol. Another patient improved markedly and four improved moderately. Two had minimal or transient improvement, and one left hospital unchanged after a short, severe, toxic reaction. The six with complete remissions all began to improve within a few days of starting propranolol and the florid symptoms remitted completely after three to 26 days. They were stabilized on a daily dose of 500-3,500 mg of propranolol and at the time of writing had remained well for up to six months. Two patients who stopped propranolol after their symptoms remitted relapsed severely within a few days. Toxic effects (ataxia, visual hallucinations, and confusional states) were related to the rate of increase rather than to the absolute dose of propranolol. After the procedure was modified unwanted effects were usually mild or absent.     

The Psychosomatic Emergency

Many psychiatric problems present themselves under the guise of physical rather than mental symptoms.These occur in several categories: (1) Psychological problems which work in conjunction with definitive organic pathology, such as the fear of death. (2) Symptoms produced by altered physiology or biochemistry resultant from an acute orchronic stress state. (3) A combination of A and B above. (4) Patients with an intense disease, such as hypochondriasis. (5) Psychiatric symptoms, such as depression, anxiety or apathy which develop antecedent or subsequent to a fearfully anticipated illness or procedure.These patients have certain characteristics in common. (1) They manifest a disproportionate concern over symptoms. (2) The symptoms are inconsistent with the usual pattern of organic disease. (3) The onset is concurrent with states of conflict. (4) There is usually a personal and family history of psychic and psychosomatic disorders. (5) Other psychiatric disorders are usually present. (6) Secondary gain is usually evident.These patients can be successfully treated within the hospital setting and within the framework of psychiatric consultation and psychotherapy.     

Association of anal symptoms with anal high grade squamous intraepithelial lesions (HSIL) among men who have sex with men: Baseline data from the study of the prevention of anal cancer (SPANC)

BackgroundThe association between anal high-grade squamous intraepithelial lesion (HSIL) and anal symptoms has not been systematically investigated.MethodsThe Study of Prevention of Anal Cancer is a prospective cohort study of men who have sex with men (MSM) ≥ 35 years old in Sydney, Australia. Self-reported symptoms were collected. Anal cytology and high-resolution anoscopy were undertaken. Using baseline visit data, men negative for squamous intra-epithelial lesion (SIL) were compared with men diagnosed with composite-HSIL (cytology and/or histology). Logistic regression analyses were performed to assess the association of symptoms with HSIL.ResultsAmong 414 MSM included (composite-HSIL (n = 231); negative for SIL (n = 183)), 306 (73.9%) reported symptom(s) within the last 6 months. There was no association between any symptom and composite-HSIL. A significant association between anal lump and a larger burden of HSIL (at least 2 intra-anal octants) (anal lump within last month: p = 0.014; anal lump within last 6 months: p = 0.010) became non-significant after adjusting for HIV-status and recent anal warts (anal lump within last month: p = 0.057; anal lump within last 6 months: p = 0.182).ConclusionsAmong MSM age 35 years and older, most anal symptoms are not a useful marker of anal HSIL.     

Relationships among strains of bean common mosaic virus and blackeye cowpea mosaic virus - members of the potyvirus group

In host-range studies, bean common mosaic virus strains (BCMV-NL1, -NL3 and -NY 15) usually induced distinct systemic symptoms in susceptible bean cultivars and latent infection in several Vigna genotypes (except NY15 which gave mosaic symptoms in the latter), while blackeye cowpea mosaic virus (B1CMV-W) caused distinct systemic symptoms in several Vigna genotypes and only weak systemic symptoms in a few bean genotypes only. Biologically, B1CMV-W was closest to BCMV-NY15 and less close to -NL1. When using antisera to the three BCMV strains and five strains of B1CMV (including a strain originally considered cowpea aphid-borne mosaic virus CAMV-Mor) in SDS-immunodiffusion and ELISA, BCMV-NL1 and -NY15 were found to be closely related to each other and to BICMV-Fla, -NR and -W, and less closely to BICMV-Ind and -Mor. Serological relationships of BCMV-NL1 and -NY15 to BCMV- NL3 were more distant, which is in line with the biological distinction of NL3 in causing temperature-independent necrosis in bean cultivars with the necrosis gene I. PAGE analysis of coat proteins revealed that the three strains of BCMV and B1 CMV-W have similar but non-identical molecular masses. Although molecular hybridisation may further elucidate quantitative relationships between potyvir-uses, variation within and among the potyviruses may continue to pose problems in their classification and identification.     

Seed transmission of broad bean stain virus and Echtes Ackerbohnenmosaik-Virus in field beans (Viciafaba)

When grown in a glasshouse during spring or autumn field bean (Vicia faba minor) seedlings infected with seed-borne broad bean stain virus (BBSV) or Echtes Ackerbohnenmosaik-Virus (EAMV) usually showed symptoms on some leaves within 4 wk of emergence. Symptoms caused by each virus were indistinguishable. The viruses were transmitted as often through unblemished seeds as through seeds with necrotic patches or stains on the seed coat, and sometimes as often through large as through small seeds. Soaking seeds for 24 h in solutions of 8-azaguanine or polyacrylic acid did not decrease transmission. Both viruses were detected in nearly mature seeds by inoculation to Phaseolus vulgaris but neither virus was detected in fully ripened seeds by inoculation or serological tests. The percentage of seeds from field plots that produced infected seedlings when sown in a glasshouse was closely related to the percentage of parent plants that showed symptoms of BBSV and/or EAMV at the end of flowering. The relationship seemed similar in different cultivars. On average EAMV was transmitted through more seeds than BBSV, probably because more parent plants were infected with EAMV. Inspection of seed crops for symptoms of BBSV and EAMV at the seedling stage and again at the end of flowering is probably the most practicable way of identifying progeny seed lots with little or no infection.     

Early mobilisation and outcome in acute sprains of the neck.

OBJECTIVE--To assess the long term effect of early mobilisation exercises in patients with acute sprains of the neck after road accidents. DESIGN--Single blind randomised prospective study of patients receiving physiotherapy, advice on mobilisation, or on an initial period of rest followed up after two years by postal questionnaire. SETTING--Accident and emergency department in urban hospital. PATIENTS--247 Consecutive patients (mean age at injury 30.6 years) presenting within 48 hours after injury with no pre-existing disease of the neck or serious skeletal injury. Of these, 167 patients responded to the questionnaire; 77 who responded but had not completed their treatment or review course were included in the analysis as a fourth group (non-attenders). MAIN OUTCOME MEASURE--Presence of symptoms after two years. RESULTS--Of the 167 patients (68%) responding, the percentage of patients still with symptoms was not significantly different in those receiving rest or physiotherapy (46%, 12/26 v 44%, 24/54), but that in those receiving advice on early mobilisation was significantly lower (23%, 11/48, p = 0.02). Of the 104 patients without symptoms, 94 (90%) recovered within six months and 62 (60%) within three months. Patients without symptoms who received advice or physiotherapy wore a collar for a significantly shorter time than those with persistent symptoms (mean duration 1.4 (SD 0.7) months v 2.8 (1.6) months, p = 0.005 and 1.6 (1.1) months v 1.8 (1.3) months, p = 0.006 respectively). CONCLUSIONS--Advice to mobilise in the early phase after neck injury reduces the number of patients with symptoms at two years and is superior to manipulative physiotherapy. Prolonged wearing of a collar is associated with persistence of symptoms.     

Differentiating ischemic from hemorrhagic stroke using plasma biomarkers: the S100B/RAGE pathway

Although neuroimaging is useful in differentiating ischemic (IS) from hemorrhagic (ICH) stroke in the Emergency Department, a wide-available rapid biochemical test would add advantages in the pre-hospital triage and management of stroke patients. Our aim was to examine the predictive value of a panel of blood-borne biomarkers to differentiate IS from ICH. Admission blood samples obtained within 24h from stroke symptoms onset were tested by ELISA for CRP, D-dimer, sRAGE, MMP9, S100B, BNP, NT-3, caspase-3, chimerin-II, secretagogin, cerebellin and NPY. The complete protocol was achieved in 915 patients (776 IS, 139 ICH). Among blood samples obtained <6 h from symptoms onset (n=337), S100B levels were increased in ICH (107.58 vs 58.70 pg/mL; p<0.001) whereas sRAGE levels were decreased (0.77 vs 1.02 ng/mL; p=0.009) as compared to IS. In this subset of patients S100B (OR 3.97 95% CI 1.82-8.68; p=0.001) and sRAGE (OR 0.22 95% CI 0.10-0.52; p<0.001) were independently associated with ICH. A regression tree was created by CART method showing good classification ability (AUC=0.762). Similar results were found for samples obtained within 3 h. In conclusion, a combination of biomarkers including those of the S100B/RAGE pathway seems promising to achieve a rapid biochemical diagnosis of IS versus ICH in the first hours from symptoms onset. This article is part of a Special Issue entitled: Translational Proteomics.     

STEM INFECTION OF COTTON BY XANTHOMONAS MALVACEARUM (E. F. SM.) DOWSON

Varying the position of stem inoculation, the concentration of inoculum and the age of plant affected the reaction of cotton, Gossypium sp., to infection with Xanthomonas malvacearum (E. F. Sm.) Dowson.
The extent of stem discoloration, internal and external, and the probability of disease ocurring in leaves by bacteria moving within the plant increased ( a ) the nearer the point of stem inoculation was to the apex, and ( b ) the higher the concentration of inoculum. The leaf symptoms were not the angular spots typical of primary leaf infection. Instead, bacteria seemed to lodge in, discolour and blacken sections of leaf veins. Then tissue next to the affected veins became water-soaked and leaf sectors dependent upon these veins died and dried. These symptoms usually developed 14 to 55 days after inoculation in the expanding leaves.
The amounts of stem discoloration and the probabilities of leaf symptoms developing were less when hypocotyls of old plants were inoculated than when hypocotyls of young plants were inoculated. The probabilities of leaf symptoms developing were similar, however, when young tissues in young and old plants were inoculated.
American cotton, Gossypium hirsutum , was less affected by stem inoculation than Egyptian cotton, G. barbadense. Of the resistance factors against primary leaf infection only B_6m gave appreciable stem resistance.     

Suppression of humoral immunity in chickens prevents transient paralysis caused by a herpesvirus

Marek's disease virus (MDV)3 is a highly oncogenic herpesvirus that usually causes visceral lymphomas and lymphoid infiltration of the peripheral nerves in chickens. A relatively rare encephalitic condition, first found in farm flocks and referred to as transient paralysis (TP), is also caused by MDV(1). TP symptoms occur 9 to 11 days after MDV inoculation and range from mild ataxia to profound coma. Most birds recover by 24 to 72 hr after onset of symptoms, although severely affected birds may die within the same time period. Previous studies in this laboratory (2) showed that susceptibility to TP is a recessive trait controlled by major histocompatibility complex (MHC) genes (i.e., B complex genes of chickens). Inbred line G-B1 chickens (B13/B13) are resistant to TP, whereas chickens from related inbred lines G-B2 (B6/B6) and G-B3 (B15/B15) are highly susceptible. In this study chickens were immunosuppressed by neonatal cyclophosphamide (CY) treatment or surgical bursectomy (BX) to determine the possible role of antibodies in the pathogenesis of TP.     

Nematicidal Activity of Plant Essential Oils against Bursaphelenchus xylophilus (Nematoda: Aphelenchoididae)

The nematicidal activity and poisoning symptoms of 88 plant essential oils against Bursaphelenchus xylophilus were examined by an immersion bioassay. Results were compared with those of three trunk-injection nematicides: fenitrithion, levamisol hydrochloride, and morantel tartrate. As judged by 24 h LC₅₀ values, cinnamon bark oil (0.12 mg/ml) was the most effective nematicide, followed by coriander herb oil (0.14 mg/ml). Potent nematicidal activity was also observed with lemongrass, oregano, thyme red, and clove bud oils (LC₅₀, 0.57-0.88 mg/ml). Fenitrothion was ineffective (LC₅₀, > 10 mg/ml). In typical poisoning symptoms in B. xylophilus, these essential oils exerted rapid nematicidal action and the nematodes killed usually showed an extended shape, whereas levamisole hydrochloride and morantel tartrate usually exhibited semicircular and coiling shapes, respectively. The essential oils described merit further study as botanical nematicides for the control of pine wilt disease caused by B. xylophilus.     

A Prague isolate of wisteria vein mosaic virus

An isolate of wisteria vein mosaic virus (WVMV) obtained fromWisteria sinensis in Prague resembled in its properties WVMV isolates described in Italy and Holland.Nicotiana megalosiphon is reported as a new host of WVMV. Other known host plants showed reactions similar to those described formerly. The incubation period extended in some hosts up to two or four weeks. Pea plants showed symptoms within five to seven days. Species ofApium, Brassica,Datura and others were not susceptible. TIP of Prague isolate of WVMV was 61 °C, at a dilution 1: 5000 47% of plants were infected, and 48 h > LIV > 28 h. Modal particle length was 743 nm. Massive granular inclusions were seen in pea epidermal cells, usually adhering to nuclei that did not show alterations. No serological relation to turnip mosaic virus could be established.     

Presenting symptoms of leprosy at diagnosis: Clinical evidence from a cross-sectional,population-based study

BackgroundLeprosy is associated with different dermatologic and neurologic manifestations within a wide clinical spectrum, causing a great diagnostic challenge. Therefore, we aimed to examine associations between common presenting symptoms of leprosy and stage at diagnosis.Methodology/Principal findingsIn this cross-sectional study, we analyzed population-level data from the Leprosy Management Information System (LEPMIS) in Yunnan, China, from 2010–2020 and enrolled patients with newly detected leprosy. The data of 2125 newly detected leprosy patients, with 5000 symptoms, were analyzed. Numbness (828/5000, 16.56%), erythema (802/5000, 16.04%), Painless nor pruritic skin lesions (651/5000, 13.02%), eyebrow hair loss (467/5000, 9.34%), and tubercles (442/5000, 8.84%) were common symptoms of leprosy. The symptoms related to skin (1935/2533, 76.39%) and leprosy reaction (279/297, 93.94%) were mainly existed in MB group. While the symptoms related to disability (263/316, 83.49%), clinical feature (38/56, 69.09%), and facial features (19/23, 82.61%) were predominantly presented in delayed diagnostic group. Despite low proportions, formic sensation (99/5000, 1.98%), pain (92/5000, 1.84%), pruritus (56/5000, 1.12%), finger contracture (109/5000, 2.18%), muscle atrophy (71/5000, 1.42%), and motor dysfunction (18/5000, 0.36%) were reported during the diagnosis of leprosy. The proportions of skin, skin and nerve, and nerve symptoms as initial symptoms were 33.25%, 44.95%, and 21.80% and as only symptoms were 28.66%, 57.81%, and 13.91%, respectively. In those with physical disability, nerve symptoms were the most frequent symptoms (57.65% and 65.36% for the initial and only symptoms, respectively) compared with skin and skin and nerve symptoms. In the delayed diagnosis group, nerve symptoms were the most frequent symptoms (15.73% and 17.25%) and were associated with the longest diagnostic intervals (mean±SD: 38.88±46.02 and 40.35±49.36 months for initial and only symptoms, respectively) when compared with skin and skin and nerve symptoms.ConclusionsUnderstanding the nature of presenting symptoms and developing symptom awareness campaigns would improve the level of leprosy awareness in the community. As nerve symptoms were related to a higher proportion of physical disability and longer diagnosis interval, we should increase awareness about nerve symptoms. Individuals with nerve symptoms should be considered the target group. Neurology outpatient visits may provide potential screening opportunities, and holding focused training for specialized neurology medical staff would enhance the capacity of the health system to recognize leprosy early.     

Recurrent and founder mutations in the Netherlands

Background/Methods. Marfan syndrome (MFS) is a heritable connective tissue disorder usually caused by a mutation in the fibrillin 1 (FBN1) gene. Typical characteristics of MFS that have been described include dolichostenomelia, ectopia lentis and aortic root dilatation. However, there is great clinical variability in the expression of the syndrome’s manifestations, both between and within families. Here we discuss the clinical variability of MFS by describing a large fourgeneration Dutch family with MFS. Results. Nineteen individuals of one family with a single missense FBN1 mutation (c.7916A>G) were identified. The same mutation was found in one unrelated person. Clinical variability was extensive and not all mutation carriers fulfilled the diagnostic criteria for MFS. Some patients only expressed mild skeletal abnormalities, whereas aortic root dilation was present in eight patients, an acute type A aortic dissection was recorded in two other patients, and a mitral valve prolapse was present in eight patients. In some patients cardiac features were not present on initial screening, but did however develop over time. Conclusion. MFS is a clinically highly variable syndrome, which means a meticulous evaluation of suspected cases is crucial. Mutation carriers should be re-evaluated regularly as cardiovascular symptoms may develop over time. (Neth Heart J 2010;18:85–9.)     

Methods of investigating populations of the take-all fungus (Ophiobolus graminis) in soil

Attempts to isolate Ophiobolus graminis directly from infested soils failed, so host-infection techniques were used to study soil-borne populations of the fungus. Extracting organic debris from soils and grading it by wet sieving through standard meshes concentrated the fungus. Fractions were tested for infectivity either as layers in pots of sand or by packing into short lengths of polyvinyl chloride tubing, through which wheat seedlings were grown. Coarse debris (retained by 420 μ aperture sieves) was most infectious and usually caused lesions within 3 weeks; whole soil and especially fine debris (< 420 μ) caused fewer and less severe infections, which often became apparent only after 3 weeks. Slight infectivity of the sediment fractions was attributed to imperfect separation of debris. Soil sampled in crop or stubble rows caused more infections than soil from between rows. Usually seedling infection was made manifest by root lesions and runner hyphae, but these symptoms were not always plain or conclusive. Many seedling roots that rotted when kept moist and in the light produced perithecia within 6 weeks. Although perithecia formed on some roots where neither lesions nor hyphae were found, they did not form on all diseased roots. More needs to be known about the factors influencing perithecial formation before it can be used as a reliable confirmatory test.     

Focus: Vaccines: Erythema Multiforme Following Hepatitis A and Pneumococcal Vaccinations

Erythema multiforme (EM) is a rare cell-mediated immune response characterized by target or iris patches or plaques that present symmetrically on the extremities. This condition may be associated with pruritus but is usually self-limited and spontaneously resolves within 5 weeks of onset; prodromal symptoms are rare. Several known cases have been linked to vaccination, but many vaccines used in pediatric care have been reported as causative agents of EM. This case study offers an association of EM following administration of the hepatitis A and pneumococcal vaccines.     

Meningococcal meningitis is still the commonest neuroinfection in the community in tropics: overview of 62 cases

Within last 17 years we went through all charts of bacterial meningitis within our nationwide survey and among 372 cases we found 62 cases of MM, in 12 cases with meningococcal disease (with shock, petechial effusions or disseminated intravascular coagulation or digital gangrenes). MM was usually observed in young adults without any of investigated risk factors like neoplasia, ENT (ear, nose, throat) focuses, elderly age, sepsis, diabetes, alcoholism, trauma, neonatal VLBW etc. Trauma, diabetes mellitus, alcohol abuse and chronic sinusitis/otitis were significantly less frequently found as a risk factor for MM. Mortality was very low, only 4.8% and was lower than overall mortality in CBM (12.4%, NS). Also the proportion of neurologic sequellae (9.7%) and initial treatment failure (8.1%) were comparable or even lower. This positive outcome results are probably because all N. meningitis strains were susceptible to penicillin, chloramphenicol, cefotaxim, cotrimoxazol or ciprofloxacin. Other reason for low mortality was that most cases received oral antibiotic immediately, even before admission (50 of 62). 95.2% of cases survived, 90.3% without any transient neurological residual symptoms.     

Is the Vertical Transmission of Neotyphodium lolii in Perennial Ryegrass the Only Possible Way to the Spread of Endophytes?

Endophytic fungi live their whole life within host tissues usually without any visible symptoms. Their vertical transmission (seed-plant-seed) has been well described and documented. However, horizontal transmission (plant-plant) needs more clarification. The aim of this study was to assess the extent to which endophytes move vertically in ecotypes of perennial ryegrass and whether there is evidence for the horizontal transmission of endophytes. Ecotypes from grasslands in Poland were collected in the form of living plants and used for vertical transmission analysis. Plants, the seed collected from these plants and plants grown from this collected seed were tested for endophytic infection. Provided that all produced seeds were viable and able to germinate and produce seedlings, the vertical transmission of Neotyphodium endophytes in perennial ryegrass ecotypes was nearly complete. For the horizontal transmission experiment, endophyte-hosting plants (E+) and endophyte-free plants (E-) of four cultivars were planted in the field in close proximity on small plots that were frequently mown. These studies revealed that after 7 months of growth next to E+ plants, the characteristic Neotyphodium spp. mycelia were found in E- plants, which was especially true for plants growing in close proximity to the infected plants. The occurrence of horizontal transmission of endophytes has not been previously demonstrated.     

Effects of Air Pollution and the Introduction of the London Low Emission Zone on the Prevalence of Respiratory and Allergic Symptoms in Schoolchildren in East London: A Sequential Cross-Sectional Study

The adverse effects of traffic-related air pollution on children’s respiratory health have been widely reported, but few studies have evaluated the impact of traffic-control policies designed to reduce urban air pollution. We assessed associations between traffic-related air pollutants and respiratory/allergic symptoms amongst 8–9 year-old schoolchildren living within the London Low Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained using a parent-completed questionnaire and linked to modelled annual air pollutant concentrations based on the residential address of each child, using a multivariable mixed effects logistic regression analysis. Exposure to traffic-related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI 1.00–1.02), NO₂ (1.03, 1.00–1.06), PM₁₀ (1.16, 1.04–1.28) and PM_2.5 (1.38, 1.08–1.78), all per μg/m³ of pollutant, but not with other respiratory/allergic symptoms. The LEZ did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied. These data confirm the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis. Importantly, the London LEZ has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions.     

Reverse hybridization vs. DNA sequencing in the molecular diagnosis of Familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive inflammatory disorder predominantly affecting people living in or originating from areas around the Mediterranean Sea. It is caused by a number of mutations within the MEFV gene, which differently affect the severity of the disease phenotype. Because patients usually present with rather nonspecific clinical symptoms, MEFV genotyping can confirm and refine FMF diagnosis and improve treatment of affected individuals. We have performed a method comparison study on 100 Lebanese FMF patients to evaluate the potential of a rapid reverse-hybridization teststrip-based assay (FMF StripAssay) to serve as a first-line screening test for our population. When results obtained by reverse-hybridization and DNA sequencing of exons 2, 3, 5, and 10 were compared, the FMF StripAssay identified 144/149 mutations, and correctly typed all 12 different MEFV mutations covered. We conclude that reverse-hybridization provides a very rapid, accurate and easy-to-perform screening method, and, in combination with more comprehensive diagnostic methods, represents an efficient strategy for FMF genotyping.