A trial-based economic evaluation of the CaFaSpA referral strategy for axial spondyloarthritis.

OBJECTIVE: To assess the cost-utility from healthcare and societal perspectives of the digital CaFaSpA referral strategy (CS) for axial spondyloarthritis (axSpA) in primary care patients with chronic low back pain (CLBP). METHOD: A cluster randomized controlled trial was performed in the Netherlands. General practice units were randomized into CS or usual care (UC). Economic evaluation was performed from the healthcare and societal perspectives within a 12-month time horizon. Outcome measures encompassed disability [Roland-Morris Disability Questionnaire (RMDQ)] and health-related quality of life (EQ-5D-3L). Direct medical (iMTA Medical Consumption Questionnaire) and indirect costs (iMTA Productivity Cost Questionnaire), including productivity loss, were evaluated. Incremental cost-utility ratios (ICURs) were calculated. RESULTS: The study included 90 GP clusters with 563 patients (CS: n = 260; UC: n = 303) (mean ± sd age 36.3 ± 7.5 years; 66% female). After 12 months, no minimal important differences in outcomes were observed for RMDQ (-0.21, 95%CI -1.52 to 1.13) or EQ-5D (-0.02, 95%CI -0.08 to 0.05). However, total costs were significantly lower in the CS group owing to lower productivity loss costs. The ICUR for RMDQ was €18,059 per point decrease and €220,457 per quality-adjusted life year increase. CONCLUSIONS: Digital referral did not decrease the overall healthcare status of patients after 1 year of follow-up and appears to be more cost-effective than UC. Therefore, CS can be used as an appropriate primary care referral model for CLBP patients at risk for axSpA. This will accelerate timely provision of care by the right caregiver.

Impact of triage by a rheumatologist on appropriateness of referrals from primary to secondary care: a cluster randomized trial.

OBJECTIVE: The quality of referrals is often criticized, and the effectiveness of improvement efforts remains uncertain. We assessed the impact of a rheumatologist triaging patients in primary care on the appropriateness of referrals to secondary care, healthcare utilization, and patient experience and outcomes. METHOD: A cluster randomized controlled trial was conducted with patients experiencing musculoskeletal complaints. Intervention practices deployed an experienced rheumatologist triaging patients through in-person review. Usual care was performed in control practices, where practitioners referred patients based on their own judgement. The primary outcome was the proportion of inflammatory rheumatic diseases (IRDs) diagnosed by rheumatologists in referred patients. Healthcare utilization (iMTA Medical Consumption Questionnaire), quality of life (EuroQol 5 Dimensions), and experience of care (Consumer Quality Index) were determined after 3 months of follow-up. Data were analysed according to the intention-to-treat principle. RESULTS: In total, 544 participants were included [mean age 51.4 (range 18-87) years; 24% were men]. Of all referred patients, 51% had an IRD in the intervention group versus 21% in the control group (p = 0.035). After 3 months of follow-up, patients from the triage intervention showed lower healthcare utilization (p = 0.006) and higher quality of life (p = 0.011), without a decline in experienced quality of care (p = 0.712), compared to controls. CONCLUSION: Triage by a rheumatologist in primary care provides appropriate care and adequate experience of care, leading to a higher quality of life. Long-term evidence is needed to assess the value on cost-effectiveness before implementing this strategy nationwide.

Clinical, laboratory and epidemiological aspects of HPV infection in a low-income population from South Bahia, Brazil.

The aim of this study was to determine the prevalence and risk factors for human papillomavirus (HPV) infection in the Southern region of the State of Bahia, evaluating the performance of alternative complementary methods for cervical lesion detection. Cervical samples from women who attended healthcare units were collected and diagnosed by visual inspection, cervical cytology and nested polymerase chain reaction (PCR). Moreover, hemi-nested PCR was performed to detect different HPV genotypes. The prevalence of HPV infection was 47·7%, with genotype 16 detected in most cases. Infection was associated with dyspareunia and bleeding (P < 0·001, odds ratio (OR) 5·6, 95% confidence interval (CI) 2·815-11·14) and hormonal contraceptive use (P = 0·007, OR 2·33, 95% CI 1·25-4·34). There was a positive correlation between positive PCR and positive visual inspection, cervical cytology and symptoms reported. Furthermore, visual inspection was twice as specific, and had a greater positive predictive value than cytology. We showed a high prevalence of HPV infection in Southern Bahia, with HPV 16 being the most common type, and visual inspection being most effective at detecting HPV lesions, corroborating the suggestion that it can be applied in routine gynecologic examinations for low-income populations.

The efficacy of clove oil as an anaesthetic and in euthanasia procedure for small-sized tropical fishes

Abstract Clove oil is used as a fish anesthetic because it is a natural and inexpensive product with low toxicity risks. The goal of the present study was to determine the appropriate concentration of clove oil for small-sized tropical fish to be used in mark-recapture studies or when individuals are to be sacrificed. We applied three different clove oil concentrations (D1=0.05 mL, D2=0.10 mL and D3=0.20 mL per 500 mL of water) on three small-sized fish species. We found a negative relationship between induction time and treatment for two species (Hyphessobrycon sp.1 and Hemigrammus sp.), while concentration was unrelated to recovery time. Fish body length was positively related to induction time in the D2 treatment for Hemigrammus sp., and negatively for Hyphessobrycon sp.1 in the D1 treatment, but was unrelated to recovery time for three species and treatments. Mortality rates varied across treatments, but higher rates were observed with higher clove oil concentrations. We conclude that 0.05 mL of clove oil per 500 mL of water is the most efficient dose for studies where fish will be released back to their natural habitats, while 0.20 mL of clove oil is recommended for studies that require fish euthanization for further laboratory analyses.

Resumo O óleo de cravo é recomendado como anestésico para peixes por ser produto de origem natural, baixo custo e apresentar poucos riscos de intoxicação. O objetivo deste trabalho foi determinar concentrações adequadas de óleo de cravo para anestesiar ou eutanasiar peixes de pequeno porte em ambiente natural. Foram testadas três concentrações do anestésico (D1=0,05 mL, D2=0,10 mL e D3=0,20 mL) em três espécies de peixes de pequeno. Houve uma relação negativa entre o tempo para a sedação dos indivíduos e a concentração para duas espécies (Hyphessobrycon sp.1 e Hemigrammus sp.), porém não foi encontrada relação entre o tempo para recuperação e as concentrações. Os exemplares maiores de Hemigrammus sp. levaram mais tempo para serem sedados no tratamento D2, já o contrário foi observado para Hyphessobrycon sp.1 no tratamento D1, enquanto que não houve efeito do comprimento no tempo de recuperação das três espécies. A mortalidade dos indivíduos variou entre as três concentrações do anestésico e as maiores taxas de mortalidade ocorreram nas maiores concentrações. Desse modo, a concentração de 0,05 mL é eficiente para estudos que envolvem manuseio e a soltura dos peixes, enquanto que a concentração de 0,20 mL é recomendada em estudos onde os peixes precisam ser sacrificados.

The efficacy of clove oil as an anaesthetic and in euthanasia procedure for small-sized tropical fishes / A eficiência do óleo de cravo como anestésico e em procedimentos de eutanaisa em peixes de pequeno porte

Abstract Clove oil is used as a fish anesthetic because it is a natural and inexpensive product with low toxicity risks. The goal of the present study was to determine the appropriate concentration of clove oil for small-sized tropical fish to be used in mark-recapture studies or when individuals are to be sacrificed. We applied three different clove oil concentrations (D1=0.05 mL, D2=0.10 mL and D3=0.20 mL per 500 mL of water) on three small-sized fish species. We found a negative relationship between induction time and treatment for two species (Hyphessobrycon sp.1 and Hemigrammus sp.), while concentration was unrelated to recovery time. Fish body length was positively related to induction time in the D2 treatment for Hemigrammus sp., and negatively for Hyphessobrycon sp.1 in the D1 treatment, but was unrelated to recovery time for three species and treatments. Mortality rates varied across treatments, but higher rates were observed with higher clove oil concentrations. We conclude that 0.05 mL of clove oil per 500 mL of water is the most efficient dose for studies where fish will be released back to their natural habitats, while 0.20 mL of clove oil is recommended for studies that require fish euthanization for further laboratory analyses.

Resumo O óleo de cravo é recomendado como anestésico para peixes por ser produto de origem natural, baixo custo e apresentar poucos riscos de intoxicação. O objetivo deste trabalho foi determinar concentrações adequadas de óleo de cravo para anestesiar ou eutanasiar peixes de pequeno porte em ambiente natural. Foram testadas três concentrações do anestésico (D1=0,05 mL, D2=0,10 mL e D3=0,20 mL) em três espécies de peixes de pequeno. Houve uma relação negativa entre o tempo para a sedação dos indivíduos e a concentração para duas espécies (Hyphessobrycon sp.1 e Hemigrammus sp.), porém não foi encontrada relação entre o tempo para recuperação e as concentrações. Os exemplares maiores de Hemigrammus sp. levaram mais tempo para serem sedados no tratamento D2, já o contrário foi observado para Hyphessobrycon sp.1 no tratamento D1, enquanto que não houve efeito do comprimento no tempo de recuperação das três espécies. A mortalidade dos indivíduos variou entre as três concentrações do anestésico e as maiores taxas de mortalidade ocorreram nas maiores concentrações. Desse modo, a concentração de 0,05 mL é eficiente para estudos que envolvem manuseio e a soltura dos peixes, enquanto que a concentração de 0,20 mL é recomendada em estudos onde os peixes precisam ser sacrificados.

The efficacy of clove oil as an anaesthetic and in euthanasia procedure for small-sized tropical fishes.

Clove oil is used as a fish anesthetic because it is a natural and inexpensive product with low toxicity risks. The goal of the present study was to determine the appropriate concentration of clove oil for small-sized tropical fish to be used in mark-recapture studies or when individuals are to be sacrificed. We applied three different clove oil concentrations (D1=0.05 mL, D2=0.10 mL and D3=0.20 mL per 500 mL of water) on three small-sized fish species. We found a negative relationship between induction time and treatment for two species (Hyphessobrycon sp.1 and Hemigrammus sp.), while concentration was unrelated to recovery time. Fish body length was positively related to induction time in the D2 treatment for Hemigrammus sp., and negatively for Hyphessobrycon sp.1 in the D1 treatment, but was unrelated to recovery time for three species and treatments. Mortality rates varied across treatments, but higher rates were observed with higher clove oil concentrations. We conclude that 0.05 mL of clove oil per 500 mL of water is the most efficient dose for studies where fish will be released back to their natural habitats, while 0.20 mL of clove oil is recommended for studies that require fish euthanization for further laboratory analyses.

ISO-based assessment of accuracy and precision of glucose meters in dogs.

BACKGROUND: Portable blood glucose meters (PBGMs) allow easy glucose measurements. As animal-specific PBGMs are not available everywhere, those for humans are widely used. OBJECTIVES: To assess the accuracy and precision of 9 PBGMs in canine whole blood (WB) and plasma, based on the ISO 15197:2013. ANIMALS: Fifty-nine client-owned dogs attending the Veterinary Teaching Hospital. METHODS: Analytical evaluation of 100 blood samples was performed for accuracy and 23 for precision (glucose 29-579 mg/dL) following ISO recommendations. A PBGM was considered accurate if 95% of the measurements were within ±15 mg/dL from the reference when glucose was <100 mg/dL and within ±15% when it was ≥100 mg/dL, and if 99% of them were within zones A and B in error grid analysis (EG). A hexokinase-based analyzer was used as reference. Ninety samples were assessed for hematocrit interferences. RESULTS: Accuracy requirements were not fulfilled by any PBGM in WB (74% of measurements within the limits for the most accurate) and by 1 only in plasma. However, the EG analysis in WB was passed by 6 PBGM and by all in plasma. The most accurate were also the most precise, with coefficients of variation <5% in WB and <3% in plasma. Hematocrit correlated with bias against the reference method in 4 PBGM (r = -0.243 - [-0.371]; P < .021). CONCLUSIONS AND CLINICAL IMPORTANCE: This disparity among PBGM suggests that meters approved for humans need to be evaluated before use in other species.

Tissue iron deficiency and adiposity-related inflammation in disadvantaged preschoolers from NE Brazil.

BACKGROUND/OBJECTIVES: Earlier we reported an association between iron deficiency and overweight in Brazilian preschoolers. Here, we investigate whether this is the result of adipose-related inflammation. SUBJECTS/METHODS: Fasting serum C-reactive protein, α-1-acid glycoprotein (AGP), hepcidin, interleukin-6 (IL-6) and leptin, together with two iron biomarkers (serum ferritin and transferrin receptor (sTfR)), were measured in 364 disadvantaged preschoolers with a mean BMIZ (standardised Z-score for BMI) of 0.015, aged 3-6 years and attending day care in Salvador, Brazil. The role of genetic haemoglobin (Hb) disorders, intestinal parasites and dietary iron supply (calculated from serving sizes of 20 weekday menus) were also examined. RESULTS: Forty-eight children (13%) were overweight (BMIZ >1). Prevalence of tissue iron deficiency (sTfR >113.3 nmol/l; 30.6 vs 12.5%; P=0.002) and chronic inflammation (AGP >25 µmol/l; 19 vs 10%; P=0.025) were higher in overweight than in normal-weight children. From multiple regression, BMIZ was a positive predictor of log serum sTfR, ferritin and leptin, but not of log hepcidin or IL-6. Instead, major positive predictors of log hepcidin were log IL-6, followed by an elevated AGP and sex (male), whereas for log IL-6 elevated AGP was the only significant predictor. Besides BMIZ, sex (female) was also a major positive predictor of leptin. Heterozygous variant of sickle cell Hb (n=20), but not helminths, was also a positive predictor of log sTfR. Median dietary iron supply (mg/day) was above the WHO Recommended Nutrient Intake assuming moderate bioavailability and appeared adequate. CONCLUSIONS: The role of adiposity-related inflammation in tissue iron deficiency should be considered even when the prevalence of overweight is relatively low.

Using molecular markers for pedigree reconstruction of the greater amberjack (Seriola dumerili) in the absence of parental information.

Ensuring appropriate levels of genetic diversity in captive populations is essential to avoid inbreeding and loss of rare alleles by genetic drift. Pedigree reconstruction and parentage analysis in the absence of parental genotypes can be a challenging task that relies in the assignment of sibship relationships among the offspring. Here, we used eight highly variable microsatellite markers and three different assignment methods to reconstruct the most likely genotypes of a parental group of wild Seriola dumerili fish based on the genotypes of six cohorts of their offspring, to assess their relative contributions to the offspring. We found that a combination of the four most variable microsatellites was enough to identify the number of parents and their contribution to the offspring, suggesting that the variability of the markers can be more critical than the number of markers. Estimated effective population sizes were lower than the number of breeders and variable among years. The results suggest unequal parental contribution that should be accounted for breeding programs in the future.

Family history of type 2 diabetes is increased in patients with type 1 diabetes.

It has been suggested that type 1 (T1D) and type 2 diabetes (T2D) might share some susceptibility risk factors. A higher prevalence of T2D has been reported in families of Caucasian T1D children than in the general population, although data in adults and multiethnic groups is still lacking. Our goal was to compare the prevalence of T2D family history between adults with T1D from a multiethnic population and a non-diabetic control group. We performed a cross-sectional analysis of 145 adults with T1D and 141 healthy adults (control group) that included an interview and a review of the medical charts. Groups were matched for age, sex, ethnicity and body mass index (BMI). We found a higher prevalence of not only T1D but also T2D in first-degree relatives of patients than in controls (p<0.001 and p=0.042, respectively). These differences were not observed for second/third-degree relatives. When subjects were stratified according to their ethnicity, the higher frequency of T2D in FDR of patients than controls became more striking in non-white (p=0.002) and disappeared in white individuals (p=0.85). To conclude, the prevalence of T1D and T2D was higher in first-degree relatives of patients with T1D than of controls. The difference in T2D family history between patients and controls was specially striking among non-whites, which may represent a peculiarity of T1D in this group.

K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients.

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem.

Osteoporosis in hemodialysis patients is associated with high morbidity and mortality and, although extensively studied by noninvasive methods, has never been assessed through bone biopsy. The aim of this study was to use histomorphometry to evaluate osteoporosis and identify factors related to its development in hemodialysis patients. We conducted a cross-sectional study involving 98 patients (35 women and 63 men; mean age: 48.4 +/- 13 years) on hemodialysis for 36.9 +/- 24.7 months. Patients were submitted to transiliac bone biopsy with double tetracycline labeling. The bone metabolism factors ionized calcium, phosphorus, bone alkaline phosphatase, deoxypyridinoline, intact parathyroid hormone, and 25(OH) vitamin D were evaluated, as were the bone remodeling cytokines osteoprotegerin (OPG), soluble receptor-activator of NF-kappabeta ligand (sRANKL) and tumor necrosis factor-alpha (TNF)alpha. Osteoporosis was defined as trabecular bone volume (BV/TV) greater than 1 s.d. below normal (men <17.4%; women <14.7%). Forty-five patients (46%) presented osteoporosis, which was correlated with white race. We found BV/TV to correlate with age, OPG/sRANKL ratio, TNFalpha levels, and length of amenorrhea. In multiple regression analysis adjusted for sex and age, length of amenorrhea, white race, and OPG/sRANKL ratio were independent determinants of BV/TV. Histomorphometric analysis demonstrated that osteoporotic patients presented normal eroded surface and low bone formation rate (BFR/BS). Osteoporosis is prevalent in hemodialysis patients. Low BFR/BS could be involved in its development, even when bone resorption is normal. Cytokines may also play a role as may traditional risk factors such as advanced age, hypogonadism, and white race.

Liver injury and viremia in mice infected with dengue-2 virus.

The goal of this study was to test the feasibility of BALB/c mice as an experimental model in the study of dengue disease. BALB/c mice were intraperitoneal infected with DENV-2 obtained from a human patient. Histopathological analysis of infected animals revealed liver injury with viral antigens detection. In initial stages, the most prominent lesions were vacuolization and diffuse steatosis in hepatocytes. Serum levels of ALT and AST increased progressively, reaching the highest values 7 days p.i. and decreasing at the 14th day. Since levels of circulating virus were very low, viremia was analyzed in C6/36 cells. Virus presence was detected by ultrastructural analysis, confirmed by RT-PCR assays. Period of viremia was analyzed by flow cytometry with cells incubated with mouse-infected sera collected in different days, revealing peak virus levels at the 7th day p.i. All such data correlate to the development of the disease described in humans.

Histopathological aspects of Dengue-2 virus infected mice tissues and complementary virus isolation.

The difficulty in studying dengue virus (DENV) infection in humans and in developing a virus vaccine is the absence of a suitable animal model which develops the full spectra of the Dengue haemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Despite the fact that viruses have been found in various animal tissues, we isolated DENV from tissues of adult BALB/c mice, inoculated with DENV serotype 2 (DENV-2) obtained from human serum. Viruses were ultrastructurally identified and immunolocalized by immunofluorescence techniques in C6/36 mosquito cell cultures, inoculated with tissues (liver, lung, kidney and cerebellum) macerate supernatant from mice, 48 h post-infection (p.i.). These organs, collected at the same stage of infection, were examined histologically. The histopathological analysis revealed focal alterations in all tissues examined. Liver contained focal ballooned hepatocytes, but without modifying the average diameter of the majority of hepatocytes. Sinusoidal lumen was significantly diminished at this stage but portal and centrolobular veins became congested. Lungs exhibited hemorrhagic foci in the alveolar space, vascular congestion and focal alveolitis. Cerebellar tissue showed rare foci of neuronal compactation (Purkinje cells) and perivascular oedema. In kidneys it was observed an increase in glomerular volume with augmented endocapillary and mesangial cellularity, with reactivity to anti-IgM in all glomeruli of infected mice. In conclusion, DENV-2 was found in all tissues examined early in the evolution of infection. Presence of viruses in tissues has mainly led to hemodynamic alterations with generalized vascular congestion and increased permeability, and mast cell recruitment in lungs. The latter could participate in the vascular modifications in tissues.

First Report of Dollar Spot Caused by Sclerotinia homoeocarpa on Agrostis stolonifera in Argentina.

During the summer of 2000, circular, yellow-to-brown, blighted, 2- to 4-cm-diameter patches were observed on creeping bentgrass (Agrostis stolonifera) putting greens (cv. Pennlinks) maintained at a 4- to 5-mm height on a golf course in Pilar (Buenos Aires, Argentina). Symptomatic leaves had transverse chlorotic bands that sometimes extended to the tip with brown lesions inside the bands. A fungus was isolated from symptomatic tissue after surface sterilization with 2% bleach for 1 min and plating on 2% potato dextrose agar (PDA). The mycelium was fluffy and white. The culture turned olive to brown and developed black stromata on the lower side of the plate base after 2 weeks. Pathogenicity tests were performed on 2-month-old healthy plants of A. stolonifera (cv. Crenshaw) grown in sterilized sand. Recently cut, 14-mm-diameter plugs of A. stolonifera were placed in 22- × 17-cm plastic trays filled with a sterilized mixture of 50:50 soil/sand (vol/vol). Plants were maintained at a 7-mm height. Two sources of inoculum were prepared; one was cultured on PDA at 22 to 25°C for 10 days and the other was prepared by incubating in sterilized soil at room temperature for 14 days. Twenty pieces of 1-cm-diameter agar blocks containing mycelium were placed in each plug at the base of the plants. In the infested soil inoculation, 25 g of soil were distributed among the plants on the substrate surface. Control plants were treated with either sterile PDA pieces or noninfested soil. The trays were irrigated with sterilized distilled water, covered with polyethylene bags, and kept in a controlled environment chamber at 25°C with 12 h per day of fluorescent light for 30 days. Leaf chlorosis appeared 7 and 10 days after inoculation for the agar-plug and infested-soil methods, respectively. Leaf necrosis was observed at day 23. Controls remained asymptomatic. The inoculated fungus was reisolated from symptomatic leaf tissue. The pathogen was identified as Sclerotinia homoeocarpa (1,2). To our knowledge, this is the first report of Sclerotinia homoeocarpa causing dollar spot disease on Agrostis stolonifera in Argentina and the first report of a disease on golf courses in our country. References: (1) J. E. M. Mordue. Sclerotinia homoeocarpa. No. 618 in: Descriptions of Pathogenic Fungi and Bacteria. CMI, Kew, Surrey, UK, 1979. (2) R. W. Smiley. Dollar Spot. Pages 14-16 in: Compendium of Turfgrass Diseases. The American Phytopathological Society, St. Paul, MN, 1983.

Use of OM-85 BV in children suffering from recurrent respiratory tract infections and subnormal IgG subclass levels.

BACKGROUND: Recurrent acute respiratory tract infections (RARTIs) in children are related to IgG subclass deficiencies. The aim of the trial was to evaluate the effect of OM-85 BV in the number of RARTIs as well as in the IgG subclass levels. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial. Patients of ages three to six years, having three or more documented ARTIs during the last six months with subnormal IgG subclass levels were included. Patients took either one capsule of OM-85 BV (3.5 mg) or placebo orally every day for ten consecutive days per month during three consecutive months. Patients were followed three further months without drug intake. IgG subclass levels were determined before and after treatment. RESULTS: IgG4 levels diminished after the OM-85 BV treatment (-3 [-8.0, -1.0] median difference [95 % CI] p < 0.05 by Wilcoxon test). No other significant changes in IgG subclasses were observed. After six months the patients in the OM-85 BV group (n = 20) experienced 2.8 1.4 (mean SD) ARTIs, while the patients in the placebo group (n = 20) suffered 5.2 1.5 ARTIs (-2.4 [3.3, -1.5] mean difference [95 % CI] p < 0.001 by Student's t test). Three patients with OM-85 BV had gastrointestinal events related to drug administration, as well as three placebo patients. CONCLUSION: This study demonstrated the clinical benefit of OM-85 BV in patients suffering from RARTIs and subnormal levels of IgG subclasses. This trial opens new perspectives in the research of the mechanism of action of OM-85 BV.

Immunolocalization of PTCH protein in odontogenic cysts and tumors.

The human patched gene (PTCH) functions in both embryologic development and tumor suppression. PTCH mutations have been found in odontogenic keratocysts. However, the expression and localization of the protein product of the gene have not been determined in odontogenic tumors and cysts. We investigated 68 odontogenic lesions by immunohistochemistry, and compared their PTCH expression with that in basal cell carcinomas. All odontogenic lesions, including two keratocysts with truncating mutations, were positive for PTCH. Different types of lesions had different amounts of staining. Lack of staining was noted in the majority of basal cell carcinomas. Taken together, these data suggest that odontogenic keratocysts arise with heterozygous mutations of the PTCH gene.