Patient age is a strong independent predictor of 13C-aminopyrine breath test results: a comparative study with histology, duplex-Doppler and a laboratory index in patients with chronic hepatitis C virus infection

1. Noninvasive tests for the staging of chronic hepatitis C virus (HCV) infection would be an attractive alternative to liver biopsy. The 13C-aminopyrine breath test (ABT) has been proposed for the noninvasive assessment of hepatic function and partly correlates with fibrosis. We aimed to investigate causes for the lack of discriminatory power for different degrees of hepatic fibrosis. 2. Eighty-three patients (median age 49 years (28-78 years)) with chronic HCV infection underwent the ABT after an oral load of 75 mg N,N-dimethyl-13C-aminopyrine. Portal vein flow was assessed by duplex-Doppler and a laboratory index (aspartate aminotransferase to platelet ratio index or APRI) was calculated. Parameters were compared with liver histology. 3. The cumulative 13C-recovery differed significantly between patients without relevant fibrosis (fibrosis score 0-2) and cirrhosis (5-6), beginning after 30 min of sampling (P < 0.05). The ABT did not discriminate patients with fibrosis scores 3-4 from the remaining two patient groups. Sensitivity and specificity for the prediction of cirrhosis was 73.4-82.8% and 63.2-68.4%, depending on the sampling time. Compared with the fibrosis score (P = 0.04), patient age was a highly significant independent predictor for the 13C-recovery (P < 0.0001). Aspartate aminotransferase to platelet ratio index and duplex-Doppler predicted cirrhosis with 76.6%vs. 87.5% sensitivity and 63.2%vs. 68.4% specificity. 4. Our data suggest an age-dependent decrease of cytochrome P450 activity which probably accounts for the large overlap of ABT results that preclude clear differentiation. This is also consistent with former pharmacodynamic trials. Age-adapted reference ranges could improve ABT results.     

Korrelation einer „Latenten Hyperthyreose“ mit psychischen und somatischen Veränderungen

Summary The study reported here was undertaken to establish the degree to which a person in a preclinical state of hyperthyroidism, with (by definition) euthyroid T3 and T4 levels but suppressed TRH on testing, already exhibits psychological changes and clinical symptoms. Two groups of 20 patients each, with clear clinical and preclinical hyperthyroidism (as defined by laboratory parameters), were studied, as well as a group of 20 controls. The subjects' psychological state of mind was investigated using self-rating scales, including the state-trait-anxiety inventory (STAI), Befindlich-keits-Skala (Bf-S'), depression scale (D-S'), and a list of adjectives (EWL-K) with 14 different aspects of affective moods. Cognitive achievements were evaluated using the d2 test. Subjects were examined for somatic symptoms in accordance with Crooks' index of hyperthyroidism.The results clearly showed that typical psychological and somatic changes are already present in preclinical hyperthyroidism, these changes being partly identical with those of definite hyperthyroidism. In both patient groups, a significant increase in anxiety, a sense of not feeling well, and emotional irritability were found, as well as a tendency towards depressiveness, and an increased lack of vitality and activity. Attentiveness and concentration in both patient groups were lower than in the control group. Both patient groups showed the same prevalence of symptoms, such as palpipations, preference of cold over heat, excessive sweating, nervousness, fine digital tremor, and increased heart rate.With regard to the results, the diagnosis preclinical hyperthyroidism thus gains importance. Further prospective studies are required to answer the question whether antithyroidal treatment will influence the described psychological and somatic state of patients with preclinical hyperthyroidism.

---

Abkürzungsverzeichnis BF-S Befindlichkeitsskala - D-S Depressivitäts-Skala - EWL-K Eigenschaftswörterliste, Kurzform - PR Prozentrangwert - RW Rohwert - STAI statetrait-anxiety-inventory - T3 Trijodthyronin - T4 Thyroxin - TBG Thyroxinbindendes Globulin - TRH Thyreotropin releasing hormone - TSH Thyreoidea stimulating hormone - TT3 Gesamt-Trijodthyronin - TT4 Gesamt-Thyroxin Herrn Professor Dr. K. Schöffling zum 65. Geburtstag gewidmet     

Enzymatische Galaktosebestimmung ohne Enteiweißung und ohne Zentrifugation in sehr kleinen Blutmengen (10 µl)

Zusammenfassung Es wird eine enzymatische Bestimmungsmethode für Galaktose mitgeteilt, für die nur 10 µl Vollblut benötigt werden. Die Methode arbeitet ohne Enteiweißung und ohne Zentrifugation. Die Vorteile des beschriebenen Verfahrens sind hohe Spezifität, Empfindlichkeit und geringer Arbeitsaufwand. Von besonderem Interesse dürfte dieses Verfahren für Untersuchungen in der Hepatologie sein.Die gleichzeitige Bestimmung von Galaktose und Glucose in 10 µl Blut ist für die Pädiatrie von Interesse.

---

Summary The present report deals with a method for the enzymatic determination of galactose requiring only 10 µl of whole blood and dispensing with deproteinization and centrifugation. This process offers the following advantages:High specificity, sensitivity and time-saving procedure.This procedure should be of a special interest in hepatological research.The simultaneous determination of galactose and glucose using a 10 µl sample of blood is of interest to pediatrics.

     

Ana o 1, a cashew (Anacardium occidental) allergen of the vicilin seed storage protein family

BACKGROUND: The allergens responsible for cashew food allergy have not been well characterized. OBJECTIVES: We initiated a study to clone cDNAs encoding cashew food allergens. METHODS: A cashew cDNA library was screened with human serum for IgE-reactive clones and rabbit IgG anti-cashew extract antisera. Reactive clones were sequenced and expressed, and linear epitopes were identified by means of solid-phase overlapping peptide analysis. Immunoblot inhibition was used to identify the native peptide in cashew extract. RESULTS: Four closely related clones reactive with both human and rabbit antisera were sequenced. Sequence analysis showed that these encode members of the vicilin/sucrose-binding protein family of plant seed storage proteins. Screening of the recombinant protein with sera from 20 patients with cashew allergy and 8 cashew-tolerant patients with allergies to other tree nuts showed that 50% and 25% of sera from patients with cashew allergy and cashew-tolerant subjects, respectively, bound the recombinant protein. The corresponding native allergen protein, designated Ana o 1, was located at approximately 50 kd. Epitope mapping revealed 11 linear IgE-binding epitopes, of which 3 appear to be immunodominant. None of the epitopes were shared in common with those of the peanut vicilin allergen Ara h 1. CONCLUSION: Ana o 1, a vicilin-like protein, is a major food allergen in cashews. Cashew and peanut vicilins do not share linear epitopes.     

Allergen immunotherapy with heat-killed Listeria monocytogenes alleviates peanut and food-induced anaphylaxis in dogs

BACKGROUND: Heat-killed Listeria monocytogenes (HKL) potently stimulates interferon (IFN)-gamma production in CD4 T-lymphocytes, and when used as adjuvant for immunotherapy, reduces immunoglobulin (Ig)E production and reverses established allergen-induced airway hyperreactivity (AHR) in a murine model of asthma. We asked if such treatment could decrease established peanut-induced anaphylaxis or cow's milk-induced food allergy in highly food-allergic dogs. METHODS: We therefore studied four 4-year-old atopic colony dogs extremely allergic to peanut (Group I), as well as five 7-year-old dogs very allergic to wheat, milk and other foods (Group II). All dogs experienced marked allergic symptoms, including vomiting and diarrhea on oral challenge with the relevant foods. The dogs were then vaccinated once subcutaneously with peanut or milk and wheat with HKL emulsified in incomplete Freund's adjuvant. RESULTS: Following vaccination of the allergic dogs with HKL and allergen, oral challenges with peanut (Group I) or milk (Group II) elicited only minor or no symptoms. In addition, skin test end-point titrations showed marked reductions for >10 weeks after treatment, and levels of Ara h 1-specific IgE in serum of peanut sensitive dogs, as demonstrated by immunoblotting, were greatly reduced by treatment with HKL plus peanut allergen. CONCLUSIONS: Thus, HKL plus allergen treatment markedly improved established food allergic responses in dogs, suggesting that such an immunotherapy strategy in humans might greatly improve individuals with food allergy and anaphylaxis.     

InSNP: a tool for automated detection and visualization of SNPs and InDels

Availability of high quality SNP data is a rate-limiting factor in understanding the impact of genetic variability on gene function and phenotype. Although global projects like HAPMAP generate large numbers of SNPs in an even spacing throughout the human genome, many variation studies have a more focused approach: in the follow-up of positional association findings, candidate gene studies, and functional genomics experiments, knowledge of all variations in a limited amount of sequence (e.g., a gene) is needed. This leads to a large number of resequencing experiments, for which there is a surprising lack of analysis software. We have thus developed specialized software (InSNP) for targeted mutation detection and compared its performance to Polyphred and Mutation Surveyor using 28 amplicons. Out of a total of 579 (InSNP), 644 (Polyphred), and 526 (Mutation Surveyor) SNP predictions, 39 SNPs were confirmed by human expert inspection, with five SNPs missed by Polyphred and one missed by InSNP using the default settings. For InDel detection, out of 70 (InSNP), 28 (Polyphred), and 693 (Mutation Surveyor) InDel predictions, two InDels were confirmed by human expert inspection, with one InDel missed by Polyphred. InSNP provides a user-friendly interface with better functionality for mutation detection than general-purpose sequence handling software. It provides similar SNP detection sensitivity and specificity as the public domain and commercial alternatives in the investigated dataset. We hope that InSNP lowers the barriers to the use of automated mutation detection software and aids in the improvement of the efficiency of such experiments. The Windows installer (setup) program and sample datasets are available at www.mucosa.de/insnp/.     

Facial soft tissue response to maxillo-mandibular advancement in obstructive sleep apnea syndrome patients

Background

Facial profile soft tissue changes after orthognathic surgery are crucial for surgery success. This retrospective study evaluated soft tissue changes after maxillo-mandibular Advancement and counter clockwise rotation surgery in obstructive sleep apnea syndrome patients.

Methods

Thirty-seven obstructive sleep apnea syndrome patients (30 male, 7 female, mean age 35.8 years) whose underwent maxillo-mandibular-advancement and counter clockwise rotation surgery were studied after two intervals of time, presurgical, postsurgical and follow up (1–6 months and 1–5 years) using Dolphing Imaging Software. The soft tissue changes that were evaluated included Glabela, nasal projection, Subnasale, superior incisor, superior lip, inferior incisor, inferior lip, soft tissue B’ point and soft tissue Pogonion. Points were measured from true vertical line on the horizontal plane according to Arnett soft tissue profile analysis. Wilcoxon test was applied for testing differences between T0 (pre surgical), T1 (1–6 months postsurgical) and T2 (1–5 years postsurgical).

Results

Cephalometric points changed to more aesthetic parameters. The largest advancements took place in the mandible, due to patients’ anatomic characteristics and treatment planning, whose were measured at cephalometric points B′ (9,05 mm) and Pog’ (11,92 mm) at T0–T2. In all patients aesthetics goals were accomplished.

Conclusion

This study showed that maxillo-mandibular advancement and counter clockwise rotation surgery is an effective treatment for OSAS, with good aesthetic results.

     

Antibodies to Collagen: Comparative Epitope Mapping in Women with Silicon Breast Implants, Systemic Lupus Erythematosus and Rheumatoid Arthritis

Women with silicone breast implants have a significantly increased frequency of antibodies to collagen types I and II. To characterize the specificity of these antibodies; 70 women without a specific autoimmune disease, according to the criteria of the American College of Rheumatology, but who had silicone breast implants were studied for the presence of serum antibodies to native and denatured human types I and II collagen by ELISA. Positive sera were further studied by immunoblotting using peptides derived by cyanogen bromide digestion of the collagens. Samples of 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid arthritis (RA), and 133 healthy controls were studied concurrently. There was a high frequency of autoantibodies to collagen in each of the study groups when compared to the healthy controls. However, and of particular interest, the epitope specificity of the autoantibodies differed markedly. Sera from women with silicone implants reacted strongly in an individual-specific manner with multiple peptides of type I collagen, whereas sera from women with SLE and RA reacted only weakly with a restricted range of peptides of type I collagen. Sera from women with RA reacted strongly with multiple peptides of type II, whereas sera from women with silicon implants or SLE reacted only weakly. The reactivity of women silicon implants suggests that silicone or its biodegradation products can act as adjuvants in situ to enhance the immunogenicity of type I collagen, or protein-silicone conjugates.