Improved detection of mycobacteria in CF and tissue samples grown in mycobacteria growth indicator tube incubated at 30°C compared to conventional growth conditions of liquid and solid media.

This study evaluates the growth of mycobacteria in samples from cystic fibrosis (CF) patients and tissue samples using the mycobacteria growth indicator tube (MGIT) incubated at 30°C in comparison to conventional MGIT cultures incubated at 37°C in a BACTEC MGIT 960 device and solid media incubated at 36°C and 30°C. A total of 1,549 samples were analyzed, of which 202 mycobacterial isolates were cultured from 197 positive specimens, including five mixed cultures. The highest detection rate was achieved from MGIT at 30°C, with 84.2% of mycobacterial isolates (170 of 202), which was significantly higher than any other culture condition (P < 0.0001 for any condition). MGIT at 37°C yielded 61.4% (124 of 202) of the recovered isolates, whereas Löwenstein Jensen (LJ) and Stonebrink at 36°C, and LJ and Stonebrink at 30°C retrieved 47.0% (95), 49.5% (100), 50.0% (101), and 53.0% (107) of the isolates, respectively. Of the 53 isolates that were grown exclusively under one culture condition, the highest number of isolates (36) was recovered from MGIT incubated at 30°C. MGIT at 37°C recovered eight of the 53 isolates, whereas LJ incubated at 30°C and Stonebrink incubated at 30°C and 36°C recovered five, three, and one isolate, respectively. No isolates were grown exclusively from LJ incubated at 36°C. In CF patients and tissue samples, MGIT cultivated at 30°C for 8 weeks increases the performance of mycobacterial culture. IMPORTANCE: Our study shows that the addition of mycobacteria growth indicator tube (MGIT) liquid culture incubated at 30°C improves the detection of mycobacteria from CF and tissue samples. MGIT incubated at 30°C recovered significantly more mycobacterial isolates than MGIT incubated at 37°C and significantly more isolates than either Lowenstein Jensen or Stonebrink solid media incubated at either 36°C or 30°C. Of 202 mycobacterial isolates recovered from 1,549 specimens, 170 were recovered from MGIT incubated at 30°C, followed by MGIT incubated at 37°C with 124 isolates and solid media culture conditions that recovered between 95 and 107 mycobacterial isolates. All conventional culture conditions combined without MGIT incubated at 30°C recovered 166 isolates. MGIT incubated at 30°C recovered the highest number of isolates detected exclusively by a single culture condition and recovered mycobacterial isolates of highly relevant mycobacterial species, including Mycobacterium abscessus and Mycobacterium tuberculosis.

Relations between a standardized experimental stressor and cutaneous sensory function in patients with chronic pruritus and healthy controls: an experimental case-control study.

BACKGROUND: While chronic pruritus (CP) is a frequent symptom, many aspects of its underlying pathophysiological mechanisms still need elucidation. Research on sensory cutaneous function and on the influence of stress has been conducted mainly in patients with atopic dermatitis but is lacking for patients with CP. OBJECTIVE: To assess whether a standardized social stressor influences cutaneous sensory function in patients with CP in comparison with healthy controls (HC). METHODS: Case-control study; 33 CP and 30 HC were submitted to the standardized quantitative sensory testing protocol before and after the Trier Social Stress Test and 1 h later. Intraepidermal nerve fibre density (IENFD) was determined. RESULTS: Mechanical pain sensitivity and mechanical detection thresholds were significantly higher in CP than in HC, and mechanical detection thresholds increased more in CP than in HC over the three measurements. In both groups, cold pain threshold increased and heat pain threshold decreased from before to after the stress test and remained constant 1 h later. Only in CP, almost all QST tests induced at least a small amount of pruritus, which was not significantly altered by the stress test. IENFD in pruritic skin was significantly reduced in CP when compared to healthy controls. CONCLUSION: Peripheral thermal sensory function was not altered in CP despite reduced IENFD in lesional skin, but we could demonstrate central sensitization processes specifically in CP and influences of an acute stressor inducing more sensitivity to thermal pain in both groups.

[Psychological aspects of pruritus and therapy options]. / Psychische Aspekte bei Pruritus und Therapieoptionen.

BACKGROUND: Besides biological factors, which cause or influence chronic pruritus, more and more attention has recently also been paid to psychological and psychoneuroimmunological factors which uphold the symptom. OBJECTIVES: This review article gives an overview of the state of research regarding psychological and psychoneuroimmunological factors and the resulting therapeutic options. MATERIALS AND METHODS: The article is based on a literature search in the PubMed database. RESULTS: Under experimental conditions, pruritus can be induced by verbal instructions and modulated by placebo and nocebo effects. Stressful life events can also induce pruritus or its exacerbation. This can also be demonstrated on a cellular level. CONCLUSION: The knowledge that pruritus intensity is modulated by cognitions, behavioral factors, and stress is important for the development and application of psychological interventions. More research should be done regarding psychological interventions in the treatment of chronic itch and they should be applied clinically more often.

Optical probes based on G protein-coupled receptors - added work or added value?

In 2003, the first report was published that presented proof of principle for a novel class of FRET biosensors for use in living cells. This novel sensor class was built on the base of GPCRs, which represent an integral transmembrane receptor family passing the membrane seven times and are thus also called the 7TM receptor family. As an estimated number of 30% of all marketed drugs exert their effects by modulating GPCR function, these initial reports promised the gain of novel insights into receptor function. Such FRET sensors have slowly, but progressively, made their way into the standard toolbox for GPCR research as several groups are now reporting on the generation and use of these sensors. By now, FRET sensors have been reported for 18 different GPCRs, and more are expected to be added. These particular receptor sensors have been used to investigate receptor dynamics in living cells to evaluate ligand binding and ligand efficacy in real time, to study voltage and mechanosensitivity of GPCRs or to study the influence of receptor polymorphisms on receptor function in real-time. In this review we will describe the different design principles of these GPCR-based sensors and will summarize their current biological applications in living cells.

Relations between the characteristics and psychological comorbidities of chronic pruritus differ between men and women: women are more anxious than men.

BACKGROUND: Although sex and gender are becoming more important in diagnostics and therapy, there is still little knowledge about sex-specific differences in chronic pruritus (CP). OBJECTIVES: To compare, taking into consideration the characteristics of pruritus, sex-specific differences in psychological symptoms in patients with CP. METHODS: Sociodemographic data, data on the clinical characteristics of the skin and CP were documented over a 1-year period in all patients attending the Competence Center Chronic Pruritus of the University Hospital Münster for the first time. All patients completed the Hospital Anxiety and Depression Scale. Student's t-tests for independent study groups and linear regression analyses were applied. RESULTS: A total of 619 patients (278 men, 341 women) were included in the analysis. Women were more anxious than men, but were not more depressed. A linear regression analysis indicated that depression and anxiety scores in women were related to the average intensity of pruritus during the previous 4 weeks and to a more generalized pruritus at the beginning of CP; older age in women also correlated with the scores on the depression subscale. Interestingly, the associations were different in men: scores on the depression scale were associated with the diagnosis of CP pruritus with multiple scratch lesions. CONCLUSIONS: There are sex-specific differences in the relationship between the psychological symptoms and clinical characteristics of CP; higher anxiety scores were achieved by women. Whether psychological symptoms can be reversed when CP and scratch lesions improve is an issue that needs further exploration.

[Psychosomatic aspects of prurigo nodularis]. / Psychosomatische Aspekte der Prurigo nodularis.

BACKGROUND/OBJECTIVES: This article gives an overview of the theoretical background and the empirical research concerning psychosomatic aspects of prurigo nodularis (PN). MATERIALS AND METHODS: Literature research in PubMed with the search terms "prurigo nodularis", "nodular prurigo", "psych*"; clinical experience and research of the authors. RESULTS: Although reviews on PN frequently mention psychosomatic aspects, there is little empirical research concerning the subject. Psychosomatic aspects of PN may play a role in (1) the etiology of the chronic pruritus; (2) scratching, which leads to the typical nodules of PN; (3) the consequences of the chronic pruritus, the scratching and the skin lesions; (4) comorbidity. There is evidence for higher psychic comorbidity and higher psychopathology (anxiety, depression) in PN patients than in healthy controls, but PN patients were comparable to patients with other pruritic dermatoses. DISCUSSION: Increased levels of psychopathological problems and comorbidities also have been found in other dermatoses; they are not specific for PN. Because all of the research on this topic is cross-sectional, we cannot be sure whether these aspects are etiological factors or consequences of PN or independent comorbidities. Nevertheless, psychosomatic aspects should be considered in diagnosis and treatment of PN patients.

Body concept of patients with chronic pruritus in relation to scratch lesions and psychic symptoms.

BACKGROUND: There are only a few studies about the body concept of patients with chronic pruritus. We examined the body concept of this group of patients taking into account subgroup-specific differences, limitations of quality of life and the comparison to patients with eating disorders and a healthy control group. METHODS: 284 participants with chronic pruritus filled in the Frankfurt Body Concept Scale, the Hospital Anxiety and Depression Scale and the Dermatology Life Quality Index. Statistical analysis was performed using t tests, variance analysis and Pearson's correlations. RESULTS: Patients with chronic pruritus had a more negative body concept than healthy individuals but a less negative concept than patients with eating disorders. Higher levels of depression and anxiety were related to a more negative body image. CONCLUSION: The body concept of patients with chronic pruritus should be taken into consideration when planning therapy. Whether the body concept changes after successful treatment has to be examined in further studies.

Gender differences in chronic pruritus: women present different morbidity, more scratch lesions and higher burden.

BACKGROUND: Although sex and gender are increasingly perceived as important factors in medicine, there is only very little knowledge on these issues in patients with chronic pruritus (CP). OBJECTIVES: The aim of this retrospective study was to compare multiple parameters of CP in a large representative group of patients and to assess any sex and gender differences. METHODS: Patients (n = 1037, 54·8% women) with CP (> 6 weeks' duration) were analysed concerning gender differences in multiple parameters, including quality of life, CP-underlying diseases, co-morbidities and clinics. We used McNemar tests for dependent variables, and χ(2) tests and t-tests for independent variables, to evaluate gender-specific differences. RESULTS: Men were significantly older (P < 0·001) than women and had significantly more often cardiovascular (P < 0·001) and urogenital (P < 0·0001) co-morbidities, a higher number of co-medications (P = 0·041), and more often dermatological and systemic diseases leading to CP. Women had more neuropathic and psychosomatic diseases underlying the CP. They significantly more often showed a worsening of the CP by emotional (P = 0·002) and psychosomatic factors (P = 0·046). Women reported more often on localized itching occurring in attacks, with stinging, warmth and painful qualities (P < 0·05). Women significantly more often showed chronic scratch lesions and prurigo nodularis (P = 0·001), in contrast to men who significantly more frequently had CP on noninflamed skin (P = 0·004). In addition, women obtained higher visual analogue scale scores (P = 0·031) and reported a higher impact on quality of life (P = 0·033) than men. CONCLUSIONS: There are gender-specific differences not only in the quality, localization and triggering of CP but also in the underlying disease and scratching behaviour. These facts must be taken into account in the medical care of patients with CP and when conducting any kind of clinical research on itch. Further research is needed to achieve a gender-specific and gender-adapted diagnostics and treatment of CP.

[Selected psychosomatic aspects of dermatologic practice]. / Ausgewählte psychosomatische Aspekte in der dermatologischen Praxis.

In recent years, mental disorders and diseases have moved more and more into the focus of public attention and play an increasingly larger role in clinical practice. Dermatologists are familiar with the relationship between psyche and skin, but they not are only confronted with patients whose mental illness afflicts the skin, but also by those with problems of coping with serious and/or stigmatizing skin diseases. Furthermore, there are psychological influences on the course of various dermatologic diseases. The present article provides an overview over the complex interactions between mental and cutaneous disease and presents treatment options.

Human allo-reactive CD4+ T cells as strong mediators of anti-tumor immunity in NOD/scid mice engrafted with human acute lymphoblastic leukemia.

Adoptive immunotherapy with donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) may not only mediate Graft-versus-Leukemia (GvL) reactivity, but also induce Graft-versus-Host Disease (GvHD). As HLA-class II molecules are predominantly expressed on hematopoietic cells, CD4+ T cells may selectively mediate GvL reactivity without GvHD. Here, we assessed the capacity of human CD4+ T cells to act as sole mediators of GvL reactivity in a NOD/scid mouse model for human acute lymphoblastic leukemia and chronic myeloid leukemia in lymphoid blast crisis. Highly purified CD4+ DLI eradicated the leukemic cells. The anti-tumor immunity was mediated by a polyclonal CD4+ T cell response comprising cytokine-producing T-helper and cytolytic T-effector cells directed against the mismatched HLA-class II molecules of the patients. Furthermore, primary leukemic cells acquired an antigen-presenting cell (APC) phenotype in vivo after DLI, as well as in vitro after co-culture with leukemia-specific CD4+ T cells. In conclusion, our results show that CD4+ T cells can be strong mediators of anti-tumor immunity, and provide evidence that cross-talk between CD4+ T cells and leukemic cells is the basis for induction of leukemic cells with an APC phenotype. These data emphasize the clinical relevance of CD4+ T cell based immunotherapy as treatment modality for hematological malignancies after alloSCT.

Donor/Acceptor Metallocenes: A New Structure Principle in Catalyst Design.

Suitable as highly effective polymerization catalysts is the new class of donor/acceptor metallocenes in which the rotation of the two pi ligands is restricted through the formation of a dative D(+)-->A(-) bond (see picture). Specifically optimized substitution patterns yield excellent properties for the synthesis of high-melting, highly crystalline thermoplastic materials, amorphous thermoplastic materials with high glass transition temperatures as well as polyolefin elastomers with low glass T(g).

Incidental appendix carcinoid. Value of somatostatin receptor imaging.

PURPOSE: Somatostatin receptor scintigraphy is used to diagnose carcinoid of the gastrointestinal tract. Its sensitivity ranges from approximately 75%-100%. Therefore, it was hypothesized that it can be used in the postsurgical follow-up to detect residual carcinoid, recurrence, and metastatic disease. RESULTS: This article is concerned with the findings of somatostatin receptor imaging performed on a 12-year-old girl 8 weeks after appendectomy. Histologic examination showed an incidental appendix carcinoid. Somatostatin receptor scintigraphy performed for detection of lymph node metastatic spread of the carcinoid showed focal tracer accumulation at the former operative site; subsequently, a right hemicolectomy was performed. However, histologic examination of the surgical tissue showed no evidence for carcinoid. CONCLUSION: It is concluded that there are some potential pitfalls for somatostatin receptor imaging at least soon after surgery. Therefore, it should not be used to aid in reoperation.

Preserved left ventricular systolic and diastolic function in normoalbuminuric insulin-dependent diabetic patients with glomerular hyperfiltration.

This study was conducted to test the hypothesis that normotensive, normoalbuminuric IDDM patients with glomerular hyperfiltration may present functional or structural cardiac abnormalities. Eleven normoalbuminuric and normotensive IDDM patients with normal glomerular filtration rate and 11 patients with hyperfiltration were compared with a group of 17 age and sex matched controls. Glomerular filtration rate was measured by the 51Cr-EDTA technique and hyperfiltration was defined as a glomerular filtration rate higher than 134 ml/min/1.73 m2. Phonocardiogram, M-mode and pulsed Doppler two-dimensional echocardiograms were performed to evaluate resting left ventricular dimensions, systolic and diastolic function. Left ventricular dimensions, fractional shortening, mean velocity of fiber shortening, early and late diastolic peak filling velocity, deceleration time, mitral flow velocity integral, and isovolumic relaxation time were similar (ANOVA P > 0.05) in normal controls, diabetic patients with normal glomerular filtration rate, and diabetic patients with hyperfiltration. In conclusion, the results of our controlled observations indicate that normoalbuminuric and normotensive IDDM patients who have normal glomerular filtration rate or hyperfiltration have no Doppler-echocardiographic evidence of functional and structural abnormalities.

Alteraçöes hidroeletrolíticas, ácido-básicas e da funçäo renal em pacientes portadores da síndrome da imunodeficência adquirida / Hydroelectrolyte changes, acid-base and renal function in patients carrier acquired immunodeficiency syndrome

OBJETIVO. Avaliar a influência no curso clínico e a prevalência de distúrbios hidroeletrolíticos, ácido-básicos e da funçäo renal em pacientes portadores da síndrome da imunodeficiência adquirida (SIDA). Casuística e Métodos. A partir de um protocolo preestabelecido, revisaram-se os prontuários da primeira internaçäo de todos os pacientes admitidos durante o primeiro semestre de 1989. RESULTADOS. Noventa e nove pacientes foram estudados. A prevalência de hiponatremia, no momento da baixa, foi de 45% e durante a internaçäo, de 80,7% dos pacientes avaliados. Hipopotassemia esteve presente em 23,1% dos pacientes e acidose metabólica e insuficiência renal em 20,1 e 28,4%, respectivamente. O risco relativo para mortalidade em pacientes com hipopotassemia foi 4,4. Acidose metabólica e insuficiência renal aguda apresentaram riscos relativos de 12,9 e 21,4. Estes fatores, hipopotassemia (p < 0,01), acidose metabólica (p < 0,001) e insuficiência renal aguda (p < 0,001), estiveram significativamente associados à mortalidade. DISCUSSÄO E CONCLUSOES. Conclui-se que existe uma elevada prevalência das alteraçöes avaliadas nos pacientes com SIDA e que o desenvolvimento de hipopotassemia, acidose metabólica e insuficiência renal aguda está significativamente associado à mortalidade nestes pacientes

[Hydroelectrolyte, acid-base, and renal function changes in patients with acquired immunodeficiency syndrome]. / Alterações hidroelectrolíticas, ácido-básicas e da função renal em pacientes portadores da síndrome da imunodeficiência adquirida.

BACKGROUND: A variety of metabolic and renal disturbances have been described in patients with Acquired Immunodeficiency Syndrome (AIDS) but their influence on the clinical outcome has not been reported. The present study was undertaken in order to evaluate the prevalence of fluid and electrolyte, acid-base, and renal function disturbances in AIDS patients. The influence of these abnormalities on the clinical outcome was studied as well. MATERIAL AND METHODS: Following to a previously established protocol, the charts of all patients hospitalized during the first semester of 1989 were reviewed. RESULTS: The prevalence of hyponatremia was 45% and 80.7% at admission and during hospitalization respectively of 99 patients. Hypokalemia was present in 23.1% of the patients. Metabolic acidosis and renal failure were 20.1% and 28.4% prevalent. The relative risk for mortality in patients with hypokalemia was 4.4. Metabolic acidosis and acute renal failure had relative risks of 12.9 and 21.4. CONCLUSIONS: There is an elevated prevalence of fluid and electrolyte, acid-base and renal function disturbances in these patients. The presence of hypokalemia, metabolic acidosis, and renal failure are significantly associated with mortality in AIDS.

HTLV-I-related retroviral markers in Hungarian patients with mycosis fungoides.

Cell and serum samples from 7 Hungarian patients with mycosis fungoides were examined for the presence of HTLV-I-related DNA sequences and antibodies recognizing HTLV-I antigens. DNA sequences distantly related to the proviral DNA of HTLV-I were shown by Southern blot hybridization in 3 patients. Serum samples from these patients contained antibodies reactive with the internal core polypeptides of HTLV-I and HTLV-II, but not with the env gene encoded type-specific HTLV antigens. Restriction enzyme analysis with EcoRI, PstI, BamHI and SacI revealed structural similarity of the provirus(es) integrated in the DNA of mycosis fungoides cells to HTLV-I but not to HTLV-II. Data suggest that these proviruses and HTLV-I are similar to each other along gag and pol regions.

Delayed neurotoxic effects of tri-o-tolyl phosphate in the European ferret.

The development of organophosphorus-induced delayed neurotoxicity (OPIDN) was studied in the European ferret (Mustela putorius furo). A single oral or dermal dose of 250, 500, or 1000 mg tri-o-tolyl phosphate (TOTP)/kg body weight was administered to adult male ferrets. Corn oil served as the vehicle in the oral test and 95% ethanol was the vehicle in the dermal test. At 48 h posttreatment, half the animals in each group were killed by cervical dislocation for assessment of whole-brain neuropathy target esterase (NTE) activity. The remaining 5 animals per group were observed and examined neurologically on a daily basis for a subsequent 54 d. All ferrets dosed dermally with 1000 mg TOTP/kg body weight developed clinical signs characteristic of OPIDN ranging from ataxia to partial paresis. Ferrets administered 250 and 500 mg TOTP/kg body weight via the dermal route displayed variable degrees of hind limb weakness and ataxia. Of the animals dosed orally, only those in the 1000 mg TOTP/kg body weight group showed clinical signs indicative of OPIDN. These signs did not progress beyond mild ataxia. Small amounts of axonal degeneration were noted in the dorsolateral part of the lateral funiculus and in the fasciculus gracilis of spinal cords in ferrets receiving dermal doses of 1000 mg TOTP/kg body weight. Whole-brain neuropathy target esterase activity was also maximally inhibited (46%) in animals receiving 1000 mg TOTP/kg dermally. These results suggest that the ferret is a species that is susceptible to OPIDN.

Arteriograms of the palatine arteries in normal and cleft palate dogs.

Arteriography was used to study the arterial distribution of the hard and soft palate in dogs with and without cleft palate. Selective catheterization of the maxillary arteries produced arteriograms of the palatine arteries. Surgical exposure of the left common carotid artery or the right femoral artery was used for entry into the arterial system. The control dogs demonstrated a normal number of foramina (one on each side) with cross communication of the terminal arteries. The presence of additional foramina on the left side of the cleft as compared with the right side indicates the possibility of greater vascularity unilaterally. These findings may be of clinical significance.