Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study.

BACKGROUND: The anti-interleukin (IL) 6 receptor antibody tocilizumab inhibits signalling of IL6, a key cytokine in rheumatoid arthritis (RA) pathogenesis. OBJECTIVE: To evaluate through the AMBITION study the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA for whom previous treatment with methotrexate/biological agents had not failed. METHODS: This 24-week, double-blind, double-dummy, parallel-group study, randomised 673 patients to either tocilizumab 8 mg/kg every 4 weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20 mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab 8 mg/kg. The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 24. RESULTS: The intention-to-treat analysis demonstrated that tocilizumab was better than methotrexate treatment with a higher ACR20 response (69.9 vs 52.5%; p<0.001), and 28-joint Disease Activity Score (DAS28) <2.6 rate (33.6 vs 12.1%) at week 24. Mean high-sensitivity C-reactive protein was within the normal range from week 12 with tocilizumab, whereas levels remained elevated with methotrexate. The incidence of serious adverse events with tocilizumab was 3.8% versus 2.8% with methotrexate (p = 0.50), and of serious infections, 1.4% versus 0.7%, respectively. There was a higher incidence of reversible grade 3 neutropenia (3.1% vs 0.4%) and increased total cholesterol > or =240 mg/dl (13.2% vs 0.4%), and a lower incidence of alanine aminotransferase elevations >3x-<5x upper limit of normal (1.0% vs 2.5%), respectively. CONCLUSION: Tocilizumab monotherapy is better than methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favourable benefit-risk, in patients for whom treatment with methotrexate or biological agents has not previously failed.

Familial partial deficiency of the third component of complement (C3) and the hypocomplementemic cutaneous vasculitis syndrome.

Familial hypocomplementemia of the third component of complement (C3) was found in four members of a family. The prospositus had cutaneous vasculitis, hypocomplementemia, arthralgia, proteinuria and thrombocytopenia. The combination of clinical, laboratory and pathologic findings resembled the "hypocomplementemic cutaneous vasculitis syndrome" (HCVS) or the "SLE-like syndrome" but serum C3 concentration was 35 to 57 per cent of normal in the propositus and in three relatives. Results of Clq precipitins, cryoglobulins and serologic tests for systemic lupus erythematosus were negative. Proteinuria (815 mg/day) but no hematuria was present. Analysis of the C3 phenotypes in this family showed that three hypocomplementemic members were apparent homozygous C3 slow but one was heterozygous C3 fast-slow. Metabolic studies with 125-Iodinated C3 in the clinically normal mother showed a 50 per cent reduction in C3 synthesis which was consistent with hypocomplementemia documented by serum protein assay. The occurrence of an immune complex-like disease (with characteristics of the HCVS) in a patient with a familial deficiency of C3 suggests that the preexisting C3 deficiency may predispose such persons to certain diseases.

Existence of Sporothrix schenckii as a pulmonary saprophyte.

A 48-year-old male custodian and part-time gardener was hospitalized for treatment of renal tuberculosis. Sputum cultures failed to reveal mycobacteria, but Sporothrix schenckii was isolated over an eight-month period. In the absence of clinical or roentgenographic evidence of active lung disease, we postulate the saprophytic existence of S schenckii in this patient's tracheobronchial tree. Recognition of this state would obviate the need for the commonly accepted therapy for pulmonary sporotrichosis, amphotericin B.

Streptococcus milleri pyomyoma simulating infective endocarditis.

A 37-year-old woman with clinically occult, abscessed uterine myomas presented with fever, anemia, splenomegaly, and viridans streptococcal bacteremia. An initial diagnosis of endocarditis was made, but fever persisted despite appropriate antibiotics. Pelvic pain evolved and laparotomy revealed an infected myoma. Streptococcus milleri was isolated from both the blood and the uterine abscess. Infected uterine myomata may be clinically silent despite producing sustained bacteremia. The occurrence of suppurating myomas and the significance of S milleri isolates are briefly reviewed.

Integrating diet therapy and dietary counseling: an alternative education technique.

The purpose of this study was to examine the effects of a change in education methods on learning among students enrolled in a coordinated undergraduate program (CUP). An experimental process applying the principles of diet therapy and counseling in a situation involving volunteer clients was initiated, and the effects were measured. A pretest-post-test design was used for this investigation. Two psychometric instruments, the Myers-Briggs Type Indicator and the Affective Sensitivity Scale, were used to measure changes in attitudes, values, and aptitude. The curriculum of the treatment group (19 juniors in the CUP) was reorganized so that diet therapy and dietary counseling would be taught during the same semester. The laboratory sessions were combined the last 6 weeks of the semester to provide an opportunity for students to counsel clients recruited from the university campus. The comparison group (11 seniors in the CUP) had enrolled in diet therapy the first semester of the junior year and dietetic counseling the second semester; those students were tested during their senior year. The research indicated that the students in the treatment group learned effectively. They significantly increased their awareness, listening, and understanding during the treatment period. The post-test of the treatment group indicated that they had increased perception and more acute affective sensitivity in comparison with the control group.

Efficacy of eprinomectin against mange mites in cattle.

OBJECTIVE: To determine whether eprinomectin was effective against mange caused by Chorioptes bovis and Sarcoptes bovis in cattle. ANIMALS: 80 cows naturally infested with C bovis and 30 cattle experimentally infested with S bovis. PROCEDURE: 6 trials were performed to determine efficacy against C bovis, and 2 trials were performed to determine efficacy against S bovis. In each trial, a group of untreated animals or of animals treated with vehicle alone was compared with a group of animals treated with a 0.5% formulation of eprinomectin applied topically (500 micrograms/kg). Number of mites in skin scrapings was determined prior to treatment and at weekly intervals for 8 weeks after treatment. Severity of skin lesions was evaluated when skin scrapings were obtained. In 5 trials, animals were weighed before and 56 days after treatment. RESULTS: Mite counts for treated cattle were significantly less than counts for control cattle from day 14 onwards in trials to determine efficacy against C bovis and from day 7 onwards in trials to determine efficacy against S bovis. Mites were not detected in scrapings collected from treated cattle on day 56. Mean weight gain of treated cattle was not significantly different from mean weight gain of control cattle in trials evaluating efficacy against C bovis but was significantly greater in trials evaluating efficacy against S bovis. CONCLUSION AND CLINICAL RELEVANCE: Eprinomectin was highly effective against C bovis and S bovis. Because eprinomectin can be administered to lactating cows, it may be useful for controlling mange in cattle.

The treatment of bovine sarcoptic mange (Sarcoptes scabiei var. bovis) using eprinomectin extended-release injection.

The efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated in cattle harbouring induced infestations of Sarcoptes scabiei var. bovis (sarcoptic mange) in three studies conducted in Germany (two studies) and Austria (one study). A total of 44 cattle were included in the studies, 12 in one study and 16 in each of the other two studies. Approximately eight weeks following initial induced infestation, cattle in each study were formed into replicates of two animals each on the basis of pre-treatment bodyweights. Within replicates the animals were randomly allocated to one of two treatments: ERI vehicle (control) or Eprinomectin 5% (w/v) ERI (1.0 mg eprinomectin/kg). Treatments were administered at 1 mL/50 kg bodyweight by subcutaneous injection in front of the shoulder once on day 0. The number of live mites in skin scrapings was determined prior to treatment and at weekly intervals for eight weeks after treatment. Severity of skin lesions was evaluated and scored when skin scrapings were taken. In all studies, animals were weighed before infestation and again prior to and at 56 days after treatment. Mite counts for treated cattle were significantly (p<0.05) lower than counts for controls from Day 7 onwards. Cattle treated with Eprinomectin ERI were Sarcoptes mite-free from seven, 21 or 28 days post-treatment to the end of the study in the three studies, and lesions regressed accordingly. Mean weight gain over the post-treatment period was significantly higher for treated cattle than for controls in two studies. All animals accepted the treatment well.

[Capillaria (Nematoda, Trichuridae) of wild swine (Sus scrofa) in Austria]. / Die Capillarien (Nematoda, Trichuridae) des Wildschweines (Sus scrofa) in Osterreich.

Capillaria (Nematoda, Trichuridae) of wild boar in Austria. In a research on Capillaria species with wild boar in Austria 2 species could be found, C. spec. in the stomach and C. garfiai in the tongue. The morphological characteristics of both species were described and represented C. spec. could only be detected in one of 105 stomachs and intestines. C. garfiai, however, could be proved in 77 (= 69%) of 112 examined tongues. C. garfiai which parasitizes in the tongue epithelium causes pathological changes only to a slight degree, so that it is of almost no pathogenic significance. The frequency of infestation with eggs of Capillaria (with a high probability of C. garfiai) was 14.4% of 319 examined samples of faeces. The validity of C. spec. is discussed. Both species were detected at wild boar in Austria for the first time.

[The observation of coccidia in swine]. / Studie zur Kenntnis der Schweinekokzidien.

The coccidia species of domestic pig and wild boar were compared and defined morphologically and the sporogony of both was examined. No difference could be detected between the coccidia species of domestic pig and wild boar. Six Eimeria and one Isospora species were found: Eimeria debliecki, E. polita, E. porci, E. scabra, E. spinosa, E. suis and Isospora suis. E porci could be found in Austria for the first time. E. cerdonis Vetterling, 1965 is a synonym of E. polita Pellérdy, 1949.

[The development of the body weight of calves with sarcoptic mange before and after treatment with Ivomec pour-on]. / Untersuchungen zur Entwicklung der Körpermasse von Kälbern mit Sarcoptesräude vor und nach der Behandlung mit Ivomec Pour-on.

In 2 stages of a trial the bodyweight of 16 calves (6 Fleckvieh female, 6 Braunvieh female, 4 Braunvieh male), experimentally infected with Sarcoptes bovis, was controlled between birth and until 25 weeks after treatment with Ivomec pour-on (5 mg ivermectin/10 kg b.w.). On the day of treatment and before the turnout to the pasture the living Sarcoptes mites and mange lesions were determined. The two stages were characterized by different degrees of mange, which also became noticeable in the daily increase of bodyweight on an average of 200 g and 570 g respectively compared with the untreated calves. After treatment of the animals of the control group the daily increase in bodyweight within a few weeks was identical with the increase of the bodyweight of the earlier treated calves, whereby 16/19 weeks after the turnout to the pasture (female calves) and the possibility to take in grass ad libitum and 16 weeks after beginning of fattening (male calves) respectively the group of earlier treated calves still showed a higher mean bodyweight of about 27 kg and 24 kg.

[The distribution and biology of Capillaria garfiai from Sus scrofa]. / Zur Verbreitung und Biologie von Capillaria garfiai aus Sus scrofa.

The infestation extent of wild boars (Sus scrofa) with Capillaria garfiai Gallégo & Mas-Coma, 1975 in East-Austria and the localisation of the nematodes in the tongue (n = 159) were examined. The infestation extent (prevalence) was between 66.6 and 90.9 percent. Concerning the location of the parasites in the tongue there was a striking difference between C. garfiai males and females. So, the number of C. garfiai females continuously decreased from the first to the fourth quarter of the tongue, whereas C. garfiai males could be found increasingly in the epithelium of the third quarter. Further, we investigated the biology of C. garfiai and could show, that the development is only involving intermediate hosts, which could be identified as earthworms (Lumbricus terrestris, Allolobophora caliginosa, A. rosea). The morphological characteristics of C. garfiai specimens of wild boars and domestic pigs were compared, but no noticeable differences could be detected.

Family study of systemic lupus erythematosus: analysis of the clinical history, skin immunofluorescence, and serologic parameters.

The clinical history, deposition of IgG, IgM, IgA, C3, C4 and properdin at the dermal-epidermal junction (DEJ) of clinically normal skin, serum ANA, DNA-binding, C3, C4, Factor B, and properdin were compared in 27 systemic lupus erythematosus (SLE) probands, 21 first-degree household contact relatives (FDHCR), 19 first-degree nonhousehold contact relatives (FDNHCR), 15 spouses, 26 controls, and 16 chronic discoid lungs lupus erythematosus patients. Female consanguineous relatives of SLE patients had a higher incidence of rheumatic symptoms than male relatives (P less than 0.01). Female FDHCR and male spouses had a higher incidence of protein deposition at the DEJ than sex-matched controls (P = 0.026 and 0.0028). The incidence of protein deposition at the DEJ in FDNHCR did not differ from sex-matched controls. ANA titers of the consanguineous relatives were significantly higher than those of the spouses or sex-matched controls irrespective of household contact with their proband. The observation of protein deposition at the DEJ in normal appearing skin of FDHCR and spouses suggests the importance of environmental factors, whereas the elevations of ANA titers in consanguineous relatives suggests the importance of genetic factors in the pathogenesis of SLE.

On the substantial variation in serological responses in pigs to Sarcoptes scabiei var. suis using different commercially available indirect enzyme-linked immunosorbent assays.

Two trials were carried out to compare the use of different enzyme-linked immunosorbent assays (ELISAs) for the detection of antibodies against Sarcoptes scabiei var. suis. In the first trial, we employed four tests and 70 selected sera from a closed pig farm with sarcoptic mange. The sera were taken from the breeding area as well as from the finishing unit and compared with skin scrapings. The SARCOPTES-ELISA 2001 yielded the most positive results (88.58%), followed by the ELISA of the National Veterinary Institute, Uppsala (70%), the Acar-Test P-ELISA (52.86%), skin scrapings (48.57%), and the CHEKIT Sarcoptest (30%). In the second trial, eight litters from infected sows were examined from weeks 1-12 of life using the CHEKIT Sarcoptest and the SARCOPTES-ELISA 2001. The presence of maternal antibodies was highest on day 7 in both ELISAs and could be detected until weeks 5-9 of life. Antibodies increased as a result of an active immune response between days 56 and 63 in the SARCOPTES-ELISA 2001 and between days 70 and 77 of life in the CHEKIT Sarcoptest. Significant differences between the first and second litters were observed.

Histology of the skin and determination of blood and serum parameters during the recovery phase of sarcoptic manage in cattle after avermectin (Ivomec) treatment.

Calves experimentally infested with Sarcoptes bovis were treated 14 weeks post infectionem with an avermectin pour-on preparation (Ivomec). On day 0 before and 14, 28 and 56 days after treatment mite count, scabies lesion score, histological sections of the skin, blood- (number of erythrocytes, PCV, Haemoglobin, MCV, MCH, MCHC, number of leukocytes, differential blood picture) and serum parameter (GOT/AST, GGT, GLDH, glucose, calcium, magnesium, phosphate, sodium, potassium and chloride) and Sarcoptes specific immunoglobulin G and immunoglobulin M were determined. 14 days after treatment no mites could be found in skin scrapings and the mange lesions were in recovery stage. 28 days after treatment the skin mostly was macroscopically unchanged. On all examination days in skin biopsies hyperkeratosis, mostly accompanied by epidermal hyperplasia and perivascular infiltration with eosinophil granulocytes and mononuclear cells was observed. The dominance of eosinophil granulocytes in the tissue decreased after treatment, while mononuclear cells increased and dominated in most cases on day 28 over eosinophil granulocytes. The differential blood count in most cases showed elevated lymphocytes on all examination days, increase of neutrophil granulocytes and decrease of eosinophil granulocytes between day 0 and 14. Monocytes on day 28 showed a marked decrease, thereafter on day 56 a marked elevation. Slightly increased serum enzyme activities were seen with GLDH and GOT on day 0 before treatment and with GLDH on day 56 after treatment. The specific antibody titer against Sarcoptes antigen showed decreasing immunoglobulin G titre and increasing immunoglobulin M titre during the investigation.

Sequential carcinoembryonic antigen levels in the therapy of metastatic breast cancer: a predictor and monitor of response and relapse.

Serial measurements of plasma carcinoembryonic antigen (CEA) levels were analyzed in 42 patients with advanced breast cancer undergoing systemic chemotherapy. Pretreatment CEA levels exceeded 5 ng/ml in 22 patients, and 19 of 22 serial assays uniformly heralded tumor regression as well as subsequent tumor relapse. A significant quantitative alteration in CEA levels was established as a minimum change of 20% within 8 weeks of therapy. In 13 of 15 patients responding to chemotherapy and in all patients with CEA levels higher than 35 ng/ml, this criterion was not abrogated, and there were no discordant observations. Rising CEA levels were correlated with subsequent progression of disease in all patients with elevated baseline levels at a minimum of 8 weeks before the progression was clinically evident. In advanced breast cancer the effectiveness of therapy and the development of tumor resistance may be monitored by serial plasma CEA levels, and specific quantitative criteria should be applied.

The relationship between admission symptoms and hospital assaults.

Assessments at hospital admission of patients' potential for violence often rely on limited information, such as the patient's mental status, because detailed clinical and historical information may not be readily available. This study examined the relationship between symptoms at admission as measured by the Brief Psychiatric Rating Scale and later violence of 127 psychiatric inpatients. Patients who showed higher levels of thinking disturbance, hostile-suspiciousness, and agitation-excitement at the time of admission were at greater risk of becoming assaultive during the hospitalization. The findings suggest the usefulness of specific symptom profiles for identifying acute psychiatric patients at risk for violence.

Infrapatellar pigmented villonodular synovitis: arthrographic detection.

An ovoid density was demonstrated by arthrography in the infrapatellar fat pad region of seven patients. In three patients, the density appeared demarcated from the fat pad, and arthrotomy in two of them disclosed a localized pigmented villonodular synovitis. In four patients the density appeared contiguous with the fat pad, and in two of these patients no infrapatellar abnormality was observed at arthrotomy. This arthrographic distinction may provide more specific criteria for the preoperative diagnosis of localized, infrapatellar pigmented villonodular synovitis and thereby prevent overdiagnosis.

Systemic lupus erythematosus in the younger patient: survival studies.

One hundred eighty-two patients fulfilling the American Rheumatism Association criteria for the classification of systemic lupus erythematosus (SLE) were followed prospectively. Sixty-seven had the onset of SLE before age 21, 32 before age 16, and 35 between age 16 and 20. All patients received similar therapy. Only 4 patients received cytotoxic agents. Malar blush, cellular casts, and profuse proteinuria were significantly more common in the 0-15 compared to the adult group (age 21 or older). Five-year survival was 100% for children with membranous or focal lupus nephritis and 85% for diffuse proliferative lupus nephritis.

Oral mucosal ulceration in systemic lupus erythematosus.

In 182 patients with systemic lupus erythematosus (SLE), oral mucosal ulceration occurred in 47 patients (26%), was usually painless (82%), and most often involved the hard palate (89%). Oral ulceration was associated with an increase in overall clinical activity, although this was not accompanied by significant changes in the levels or titers of C3, anti-DNA antibodies, and anti-nuclear antibodies. Necrotizing vasculitis was not observed. Microscopic changes were similar to the skin lesions of SLE and immunoglobulin and complement were found in both the basement membrane and blood vessel walls.