Molecular basis of hereditary C1q deficiency--revisited: identification of several novel disease-causing mutations.

C1q is the central pattern-recognition molecule in the classical pathway of the complement system and is known to have a key role in the crossroads between adaptive and innate immunity. Hereditary C1q deficiency is a rare genetic condition strongly associated with systemic lupus erythematosus and increased susceptibility to bacterial infections. However, the clinical symptoms may vary. For long, the molecular basis of C1q deficiency was ascribed to only six different mutations. In the present report, we describe five new patients with C1q deficiency, present the 12 causative mutations described till now and review the clinical spectrum of symptoms found in patients with C1q deficiency. With the results presented here, confirmed C1q deficiency is reported in 64 patients from at least 38 families.

Juvenile idiopathic arthritis and risk of cancer: a nationwide cohort study.

OBJECTIVE: Reports of therapy-related adverse events suggest an elevated rate of malignancy in patients with juvenile idiopathic arthritis (JIA) treated with biologic therapies. However, the scarcity of data on the underlying risk of malignancy in JIA hampers interpretation of these signals. Therefore, the aim of this study was to determine the risk of cancer in patients with JIA as compared with that in the general population. METHODS: Through linkage with a national database, the Swedish Patient Register (comprising inpatient discharges in 1969-2007 and specialist outpatient visits in 2001-2007 in Sweden), a national JIA cohort (n = 9,027) was identified, and each JIA case was matched with 5 general population comparators. Using data from the Swedish Cancer, Census, Death, and Biologics Registers, the occurrence of cancer, vital status, and start of a biologic therapy were identified. The relative risk (RR) of first occurrence of a primary cancer in patients who had not been treated with biologics (biologics-naive patients with JIA) was estimated using Poisson regression, stratified a priori by year of earliest identification of JIA (before 1987 versus 1987 and thereafter). In sensitivity analyses, the data were followed up to 1999, when biologics first became available. RESULTS: In this biologics-naive JIA cohort, 60 malignancies were observed during 131,144 person-years of followup, compared with 266 cancers observed during 661,758 person-years in the general population comparator (0.46 cases/1,000 person-years versus 0.40 cases/1,000 person-years; RR 1.1, 95% confidence interval [95% CI] 0.9-1.5). Patients with JIA identified before 1987 were not at increased risk of cancer, whereas JIA identified in 1987 and thereafter was significantly associated with incident lymphoproliferative malignancies (RR 4.2, 95% CI 1.7-10.7) and cancers overall (RR 2.3, 95% CI 1.2-4.4). Sensitivity analyses did not reveal any ready explanation for this heterogeneity. CONCLUSION: Although absolute risks were low, an elevated risk of malignancy was observed among biologics-naive patients in whom the diagnosis of JIA was made in the past 20 years, which may have implications for the interpretation of cancer signals in patients with JIA treated with newer therapies.

Effect of joint injections in children with juvenile idiopathic arthritis: evaluation by 3D-gait analysis.

AIM: To investigate how gait patterns change after intra-articular corticosteroid injections (ICIs) in the lower extremities. METHODS: Eighteen children, aged 5-16 y, with juvenile idiopathic arthritis (JIA) and lower extremity involvement participated in the study. Sixty-four joints in the lower extremities were treated with ICIs. The Visual Analogue Scale (VAS, 0-100 mm) was used to assess pain. A 3D motion analysis system and two force plates were used to measure gait parameters, kinematics and kinetics. The first gait analysis was performed before treatment with ICIs, and a second one was done 8-17 d after treatment. RESULTS: The participants' average rating of pain decreased from 26 mm on the VAS before ICI to 11 mm (p = 0.001) after treatment. The self-chosen walking velocity was significantly faster (p = 0.02) after treatment. The range of knee and ankle joint angles during gait increased significantly (p = 0.03 and 0.04) after treatment. At loading response, the hip extension moment increased (p = 0.01) as did knee flexion moment, and plantar flexion moment at pre-swing increased significantly (p = 0.02 and 0.002) after treatment. The ankle also generated more power (p = 0.005) after treatment. CONCLUSION: The study shows positive effects of treatment with ICIs in the lower extremities--especially regarding pain, walking velocity and joint moments. The data indicate that ICI treatment influences the gait pattern also in joints that have not been injected.

Gait in children with juvenile chronic arthritis. Timing and force parameters.

OBJECTIVES: To examine gait in children with juvenile chronic arthritis (JCA) with reference to velocity, ground reaction forces and temporal parameters. METHODS: Fifteen children with JCA were assigned into two groups (uni- and bilateral involvement and classified as pauci- or polyarticular arthritis). Fourteen healthy children participated in the control group. Light-beams were used to determine walking velocity and the children with JCA rated their pain on a visual analogue scale. Two force plates registered the ground reaction forces and foot-switches were used to obtain temporal parameters. RESULTS: The mean velocity for the children with JCA was significantly less than for the healthy controls. Velocity normalized to height showed a tendency for the children with JCA to walk slower than controls. Differences between JCA children and healthy controls were observed for peak vertical forces during heel contact and push-off. No temporal differences were observed between the groups. CONCLUSIONS: Such kinetic and temporal information may provide the clinician with a sensitive tool for pre- and post assessment of intra-articular steroid injections and/or physical therapy.

The Swedish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Swedish language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Swedish CHAQ CHQ were already published and therefore were revalidated in this study. A total of 129 subjects were enrolled: 69 patients with JIA (13% systemic onset, 39% polyarticular onset, 25% extended oligoarticular subtype, and 23% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Swedish version of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

Lower extremity isometric joint torque in children with juvenile chronic arthritis.

OBJECTIVE: To determine the intratester reliability of joint torque testing with a hand-held dynamometer (HHD) during contractions of four major lower extremity muscles in children with juvenile chronic arthritis (JCA) and to compare results for children with JCA to results for children without disability. METHODS: Eleven children with JCA and 14 children with normal musculoskeletal function were tested with a HHD using isometric muscle contractions of the right quadriceps, hamstrings, tibialis anterior and triceps surae. RESULTS: Intratester reliability values exceeded the 0.92 level, regardless of the number of trials, for all motions tested. Statistically lower joint torque values were found in a subgroup of children with JCA for contractions of the tibialis anterior (p=0.003) and triceps surae (p=0.05) muscles. CONCLUSIONS: HHD offers a reliable means of testing the joint torque generated with contraction of these lower extremity muscles in children with JCA. Findings in children with JCA compared to children without disability agree with previous reports concerning quadriceps muscle function, but also point to concerns for muscles associated with generating ankle joint torque.

Education in the management of juvenile chronic arthritis. Changes in self-reported competencies among adolescents and parents of young children.

OBJECTIVE: The purpose was to evaluate changes in self-reported competencies following an education program among parents of children with juvenile chronic arthritis (JCA) and among adolescents with JCA. METHODS: The self-reported, 24-item MEPS questionnaire was used for evaluating the program. Fifty-five parents and 11 adolescents completed the questionnaire before, directly after, and four months after the eight-hour program. RESULTS: Parents in the education program improved significantly concerning their self-reported competencies on medical, exercise, pain and social support issues, while the adolescents showed only minor improvement. The parents' positive development in some comparisons was also significant in relation to that of a non-educated group, whose responses remained mainly unchanged over the four months. CONCLUSION: Given the advantages of the education program indicated in the study, parent education should be a self-evident part of the treatment in JCA.

Smaller tidal volumes with room-air are not sufficient to ensure adequate oxygenation during bag-valve-mask ventilation.

The European Resuscitation Council has recommended decreasing tidal volume during basic life support ventilation from 800 to 1200 ml, as recommended by the American Heart Association, to 500 ml in order to minimise stomach inflation. However, if oxygen is not available at the scene of an emergency, and small tidal volumes are given during basic life support ventilation with a paediatric self-inflatable bag and room-air (21% oxygen), insufficient oxygenation and/or inadequate ventilation may result. When apnoea occurred after induction of anaesthesia, 40 patients were randomly allocated to room-air ventilation with either an adult (maximum volume, 1500 ml) or paediatric (maximum volume, 700 ml) self-inflatable bag for 5 min before intubation. When using an adult (n=20) versus paediatric (n=20) self-inflatable bag, mean +/-SEM tidal volumes and tidal volumes per kilogram were significantly (P<0.0001) larger (719+/-22 vs. 455+/-23 ml and 10.5+/-0.4 vs. 6.2+/-0.4 ml kg(-1), respectively). Compared with an adult self-inflatable bag, bag-valve-mask ventilation with room-air using a paediatric self-inflatable bag resulted in significantly (P<0.01) lower paO(2) values (73+/-4 vs. 87+/-4 mmHg), but comparable carbon dioxide elimination (40+/-2 vs. 37+/-1 mmHg; NS). In conclusion, our results indicate that smaller tidal volumes of approximately 6 ml kg(-1) ( approximately 500 ml) given with a paediatric self-inflatable bag and room-air maintain adequate carbon dioxide elimination, but do not result in sufficient oxygenation during bag-valve-mask ventilation. Thus, if small (6 ml kg(-1)) tidal volumes are being used during bag-valve-mask ventilation, additional oxygen is necessary. Accordingly, when additional oxygen during bag-valve-mask ventilation is not available, only large tidal volumes of approximately 11 ml kg(-1) were able to maintain both sufficient oxygenation and carbon dioxide elimination.

Optimisation of tidal volumes given with self-inflatable bags without additional oxygen.

The European Resuscitation Council has recommended smaller tidal volumes of 500 ml during basic life support ventilation in order to minimise gastric inflation. One method of delivering these tidal volumes may be to use paediatric instead of adult self-inflatable bags; however, we have demonstrated in other studies that only 350 ml may be delivered, using this technique. The reduced risk of gastric inflation was offset by oxygenation problems, rendering the strategy of attempting to deliver tidal volumes of 500 ml with a paediatric self-inflatable bag questionable, at least when using room-air. In this report, we assessed the effects of a self-inflatable bag with a size between the maximum size of a paediatric (700 ml) and an adult (1500 ml) self-inflatable bag on respiratory variables and blood gases during bag-valve-mask ventilation. After induction of anaesthesia, 50 patients were block-randomised into two groups of 25 each. They were ventilated with room-air with either an adult (maximum volume, 1500 ml) or a newly developed medium-size (maximum volume, 1100 ml; Dräger, Lübeck, Germany) self-inflatable bag for 5 min before intubation. When compared with the adult self-inflatable bag, the medium-size bag resulted in significantly lower exhaled tidal volumes and tidal volumes per kg bodyweight (624 + 24 versus 738 +/- 20 ml, and 8.5 +/- 0.3 versus 10.7 +/- 0.3 ml kg(-1), respectively; P < 0.001), oxygen saturation (95 +/- 0.4 versus 96 +/- 0.3%; P < 0.05), and partial pressure of oxygen (78 +/- 3 versus 87 +/- 3 mmHg; P < 0.05). Carbon dioxide levels were comparable (37 +/- 1 versus 37 +/- 1 mmHg). Our results indicate that smaller tidal volumes of about 8 ml x kg(-1) (approximately 600 ml), given with a new medium-size self-inflatable bag and room-air, maintained adequate carbon dioxide elimination and oxygenation during bag-valve-mask ventilation. Accordingly, the new medium-size self-inflatable bag may combine both adequate ventilatory support and reduced risk of gastric inflation during bag-valve-mask ventilation.

Perceived ability to manage juvenile chronic arthritis among adolescents and parents: development of a questionnaire to assess medical issues, exercise, pain, and social support.

OBJECTIVE: To develop a questionnaire to assess perceived ability to manage juvenile chronic arthritis (JCA) among adolescents and parents. METHODS: The questionnaire contained 24 (parents' version) and 23 (adolescents' version) questions accompanied by visual analog scales in the areas of knowledge, skill, behavior, attitudes, and self-efficacy. One hundred seven persons participated in the examination of validity and 25 in the examination of test-retest reliability. RESULTS: Factor analyses indicated that the questionnaire, now termed the MEPS (abbreviation for "medical issues, exercise, pain, and social support") questionnaire, contained 4 underlying dimensions: medical issues, exercise, pain, and social support, including 9, 4, 7, and 4 questions, respectively. The content of the questionnaire was judged mainly to be easily understood, relevant, and exhaustive. Intraclass correlation coefficients for the test-retest reliability of the questionnaire answers over a week ranged from 0.68 to 0.96 for single questions. CONCLUSION: The MEPS questionnaire appears to be a valid and reliable tool for assessing the perceived ability to manage JCA. Whether it is sufficiently responsive to interventions remains to be investigated.

Course of molecular hemostatic markers during and after different surgical procedures.

STUDY OBJECTIVE: To establish the most vulnerable time of thrombi formation with regard to the plasmatic (noncellular) part of the coagulatory and fibrinolytic systems. DESIGN: Nonrandomized observational study. SETTING: A surgical and an orthopedic unit and the central laboratory of a university hospital. PATIENTS: 61 consenting ASA physical status I and II inpatients undergoing four different types of surgery: total hip replacement (THR): 16 patients; hemicolectomy: 15 patients; endoscopic cholecystectomy: 15 patients; subtotal thyroid resection: 15 patients. INTERVENTIONS: The time course of 11 procoagulatory and fibrinolytic parameters was examined during the different types of surgery. Blood samples were drawn on the day before surgery, directly before the induction of general anesthesia, 1 to 2 hours postoperatively, and on the mornings of postoperative days 1, 2, 3, 4, and 5. MEASUREMENTS AND MAIN RESULTS: The coagulation samples were centrifuged within 1 hour of collection at 2,300 g for 15 minutes at 4 degrees C. Hemoglobin, hematocrit, platelets, fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time, antithrombin III, and protein C were determined immediately on laboratory arrival of the samples. The samples were aliquoted at -70 degrees C. They were thawed within 2 weeks and prepared for the following assays: thrombin-antithrombin III complexes (TAT-complexes), D-dimers, and plasminogen activator inhibitor type 1. Maximum activation of coagulation is not reached until 2 hours postoperatively and slowly decreases until normal values are reached around the fifth postoperative day. Parameters displaying the greatest changes are TAT-complexes and D-dimers. The type of surgery with the most pronounced changes was total hip replacement, followed by hemicolectomy, cholecystectomy, and subtotal thyroid resection. CONCLUSION: The total hip replacement and hemicolectomy groups show similar and strong activation of the procoagulatory and fibrinolytic systems. Much less pronounced are the changes during endoscopic cholecystectomy and subtotal thyroid resection. Maximum activation occurs 1 to 2 hours postoperatively.

Analysis of gamma delta V region usage in normal and diseased human intestinal biopsies and peripheral blood by polymerase chain reaction (PCR) and flow cytometry.

The intestinal population of gamma delta T cell receptor (TCR)-bearing cells was characterized with regard to V delta and V gamma subtype expression. For this purpose, we utilized V gene-specific PCR of mRNA prepared from intestinal biopsies. Predominant expression of the V delta 1 subtype was demonstrated in the small intestine of patients with coeliac disease and in the inflamed colon of patients with inflammatory bowel diseases (IBD: ulcerative colitis and Crohn's disease) as well as in colon biopsies taken from macroscopically normal areas of colon. Although intestinal gamma delta T cells preferentially expressed V delta 1, other V delta transcripts could be detected, of which V delta 2 and V delta 5 were commonly expressed. Analysis of biopsies from mesenteric lymph nodes demonstrated a V delta repertoire similar to the mucosa. In peripheral blood on the other hand, high expression of both V delta 2 and V delta 1 was found. The predominant expression of V delta 1 transcripts in the intestinal mucosa of IBD patients correlated well with protein cell surface expression as analysed by flow cytometry using V delta 1- and V delta 2-specific antibodies. Selective expansion of gamma delta T cells could not be demonstrated within the inflamed mucosa as shown by mRNA analysis and flow cytometry. Instead, IBD patients demonstrated a decreased proportion of TCR gamma delta-carrying T cells in the inflamed mucosa compared with macroscopically normal area of colon. On the other hand, a significantly increased percentage of T cells bearing the gamma delta TCR was found in peripheral blood of patients with Crohn's disease compared with healthy individuals, indicating that local mucosal inflammation may influence the circulating gamma delta T cell population.

Amino acid levels in the critically ill preterm infant given mother's milk fortified with protein from human or cow's milk.

Twenty preterm infants undergoing neonatal intensive care were randomly allocated to one of two feeding regimens: human milk enriched with either human milk protein (HMP) or adapted cow's milk protein (CMP). The birthweights (1076 +/- 301 g; 1031 +/- 309 g) and the gestational ages (28.4 +/- 1.6 weeks; 27.7 +/- 2.1 weeks) were comparable. The amount of protein added to the milk was set at 0.7 g/100 ml in order to provide a total supply of 3.0-3.5 g/kg/24 h. All infants received additional amounts of carbohydrate, calcium, phosphorous, and sodium chloride. Capillary whole blood amino acids were measured with high pressure liquid chromatography (HPLC). The amino acid levels did not differ significantly when the feeding groups were compared week by week, but the glycine/valine ratio was higher (p less than 0.05) in the HMP group after three weeks of fortification. Longitudinal changes after protein enrichment could be demonstrated in both groups. Alanine and threonine increased after one week (p less than 0.01) in both groups. Glycine in the HMP group peaked after two weeks (p less than 0.02), and valine in the CMP group increased (p less than 0.02) after one week on the feeding regimen. However, the amino acids never reached levels above those seen after a meal in normal term newborns. Other variables related to protein intake, such as protein and urea in serum, did not vary between the groups. Growth, expressed as gains in weight, length, and head circumference was poor but comparable. The quality of the protein, whether a human milk protein isolate or a cow's milk whey protein product, used for the fortification of human milk up to a protein load of 3.0-3.5 g/kg/24 h, did not cause any alterations of significance in the amino acid profiles of peripheral blood.

Amino acid profiles by HPLC after filter paper sampling: 'appropriate technology' for monitoring of nutritional status.

This paper describes a rapid analysis of free amino acid levels in capillary blood samples using a modified HPLC system. Capillary whole blood (25 microliters) is dried on a filter paper, extracted and the equivalent of 0.25 microliter of the initial blood sample is used for each amino acid analysis. Nineteen free amino acid levels are determined with a reproducibility of better than +/- 10% for the entire procedure of sampling, preparation and analysis, with the exception of ornithine (+/- 19%) and lysine (+/- 12%). Cystine and proline cannot easily be determined by this method. Alanine, tyrosine, methionine, valine, phenylalanine, isoleucine and leucine concentrations on the filter paper are unaltered after 1, 2 and 21 wk. Storage at room temperature should not be for longer than 2 wk, but storage at +4 degrees C, -18 degrees C and -70 degrees C is acceptable for 21 wk. This new micromethod seems to be a practical and reliable tool. Because of its simplicity and, above all, the need for a minimal amount of capillary blood, it is a valid means for the routine monitoring of amino acid profiles in sick preterm infants on different protein regimens. The sampling and storage methods are also examples of 'appropriate technology' for field studies of nutritional adequacy in population samples derived from infants. This is because centrifugation is not necessary and the fact that the relevant amino acids on the dried filter paper samples display high stability.

Ochratoxin A in swine blood used for evaluation of cereal handling procedures.

In a survey during the years 1985, 1986 and 1987 the quality of Swedish feeding grain was followed by the analysis of ochratoxin A in blood collected from swine at slaughter. The swine herds sampled were selected on feed handling procedures used. From information about the feed used, risk parameters for ochratoxin A contamination were identified. The results showed annual variation in the content of ochratoxin A in the grain and that ochratoxin A increased during storage of grain, particularly in the harvest of 1985. Drying of the grain with forced ambient air was found to be inferior to the use of heated forced air. It was also noticed that more than 9% of the grain was contaminated with ochratoxin A regardless of handling. The pronounced difference between the samples studied was seen mainly as a function of geographical origin, with the island of Gotland having a much higher frequency of positive samples than the rest of Sweden. No correlation between ochratoxin A in swine feed and post mortem signs of infectious diseases in the swine herds was found.

Toxicokinetics of ochratoxin A in several species and its plasma-binding properties.

The toxicokinetic profile of ochratoxin A was studied after the oral or intravenous administration of 50 ng/g b.w. to fish, quail, mouse, rat and monkey. The elimination half-life varied from 0.68 h after oral administration to fish, up to 840 h after intravenous administration to monkey. The distribution volume ranged from 57 ml/kg in fish to 1500 ml/kg in quail. The plasma clearance was most rapid in quail and fish, 72 and 58 ml/kg.h, respectively, while it was only 0.17 ml/kg.h in monkey. The bioavailability was as low as 1.6% in fish but as high as 97% in mouse. The binding abilities of ochratoxin A to plasma proteins were also studied. From these data we calculated the free fraction of toxin in plasma, which we found to be less than 0.2% in all species investigated (including man) except fish. A similar but smaller investigation on the toxicokinetics and binding properties of ochratoxin B was also performed. Ochratoxin B was more readily eliminated and had a lower affinity for plasma proteins, which partly may explain its lower toxicity.

Carbon-14-ochratoxin A distribution in the Japanese quail (Coturnix coturnix japonica) monitored by whole body autoradiography.

Tissue distribution of the nephrotoxic mycotoxin ochratoxin A was characterized in laying Japanese quail by whole body autoradiography and scintillation counting using 14C-labelled toxin. Periodically for 8 days after one intravenous injection of 14 microCi/bird, corresponding to 70 ng/g body weight, birds were killed, frozen, and sagittal sections of the whole body were placed on X-ray film. In general, the ochratoxin disappeared from the avian body rapidly. Specific retention of radioactivity was seen as a ring-like distribution in yolks and growing follicles. After sectioning, organs and intestinal contents were removed from carcasses in a frozen condition, homogenized, extracted, chromatographed, and the radioactivity in fractions was measured by scintillation spectroscopy. High concentrations of ochratoxin A were found in gastric intestinal contents, probably originating from toxin excreted in the bile.

Thymocytotoxic antibodies in synovial fluid.

Synovial fluid (SF), obtained from patients with juvenile rheumatoid arthritis (JRA), osteochondritis, traumatic synovitis and septic arthritis were tested for the presence of thymocytotoxic activity. Such activity, directed against guinea pig thymocytes, was earlier demonstrated in human serum and shown to be mediated by IgM antibodies and a heat labile factor, most likely complement. The cytotoxic activity was demonstrated in all SFs tested, and was abolished by either one of the following procedures: depletion of IgM by use of anti-IgM-antibody coated protein A-Sepharose, or heating to 56 degrees C for 30 min. Activity was regained when samples inactivated by these two procedures were recombined. The cytotoxic SFs produced similar distortion of cell volume distribution of the target thymocytes as previously has been shown with human serum. The findings indicate that the two cytotoxic activities are identical. In most cases the IgM levels and the cytotoxic activity were lower in SF than in normal serum. Although the material does not permit correlation of cytotoxic activity with specific joint conditions, a high SF cytotoxicity was noted in two out of four patients with JRA. The demonstration of IgM-associated thymocytotoxic activity is of interest both in connection with earlier observations of various specific antibodies in SF and in connection with speculations regarding local immune regulatory activity in the joint.

Tremorgenic mycotoxins from Aspergillus fumigatus as a possible occupational health problem in sawmills.

Wood-trimmers' disease, generally called extrinsic allergic alveolitis, which affects workers in sawmills, is thought to be caused by fungal diaspores. The importance of Aspergillus fumigatus on the surface of wood dried in kilns is accentuated by its ability to produce tremorgenic mycotoxins. Eight strains of A. fumigatus from five different sawmills were isolated and cultivated on liquid media, and one of the strains was also cultivated on wood blocks. Extracts were prepared, and the tremorgenic reactions were induced by oral administration of extracts to rats. Extracts of the strain grown in liquid medium and on wood blocks induced very strong tremorgenic reactions when administered orally to rats. Four other strains induced mild tremorgenic reactions. High-performance liquid chromatography analysis revealed two tremorgenic mycotoxins, verruculogen and fumitremorgen C, in the five toxic strains. One nontoxic strain produced detectable levels of verruculogen. These results, coupled with the known resemblance of the acutely toxic phase of wood-trimmers' disease to the symptoms produced by these tremorgens, imply that wood-trimmers' disease and similar occupational diseases are, at least in part, mycotoxicoses.