Terminal deoxynucleotidyl transferase (TdT) and membrane receptors in human leukemia and lymphoma — First experience with lyophilized cells

Summary Surface marker analyses and TdT assays were performed on cells from 31 patients. A variety of diagnoses were made and categorized as follows: acute leukemia (group I), non-Hodgkin lymphoma (group II) and diverse diagnoses (group III). Levels of TdT in the range from 0 to 7.9 U/mg lyophilized blasts from the peripheral blood were found in AL. This corresponds to 0–95 U/10⁸ cells. Preparations of mononuclear cells from the peripheral blood of healthy donors showed TdT values up to 0.88 U/mg or 10.6 U/10⁸ cells. High TdT activity was observed in a patient with AML, type M1 according to the FAB classification. In a patient with ALL (L1) cytostatic treatment effected the clearance of TdT activity from the peripheral blood cells and at the same time induced a significant increase of E rosette forming cells. Combined studies of the TdT activity and cell surface markers may enable us to define remissions and relapses of AL more precisely than it is possible by conventional cytological methods.Within the group II two patients with moderate TdT activities of 1.2 and 1.28 U/mg, respectively, were observed whose cells were of prolymphocytic or unclassifiable appearance, respectively. The TdT assay may be helpful to identify such cells of unknown origin and in addition may provide the means of discrimination between such cases and ALL patients who mostly show high TdT activities.Another result of our studies was the finding of moderate TdT activity of 1.2 U/mg with cells from the pleural effusion of a patient with Hodgkin's disease. Cells from malignant effusions from a patient with melanoma and a patient with teratoid carcinoma showed no TdT activity. Cells form the peripheral blood and from the bone marrow of a patient with blast crisis of CML showed TdT activity of 1.52 and 2.72 U/mg, respectively. Two other patients with blast crisis were negative. Not TdT activity was found in leukemic plasma cells.Our results show that lyophilized cells can be used for determinations of TdT activity. This greatly facilitates multi-parameter studies including cytological, cell surface marker and biochemical analyses.

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Abbrevations PBL peripheral blood lymphocytes - AL acute leukemia - AML acute myeloid leukemia - AUL acute unclassified leukemia - CML chronic myeloid leukemia - ML malign lymphoma of non-Hodgkin type - FCS fetal calf serum - DMSO dimethylsulfoxyde - PBS Dulbeccos phosphate buffered salt solution - SIg surface membrane bound immunoglobulin - ALL acute lymphoblastic leukemia - IF immunofluorescence - EDTA ethylenediamine tetraacetate - LL lymphoblastic lymphoma Supported by Deutsche Forschungsgemeinschaft, Bad Godesberg, We445 and SFB 102     

Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients

There is a genetic contribution to the idiopathic restless legs syndrome (iRLS). An autosomal dominant mode of inheritance is suspected, but as yet no gene has been identified. To assess the frequency and characteristics of the hereditary restless legs syndrome (RLS) in comparison to those of non-hereditary RLS, we analysed the clinical data of 300 RLS patients. All 300 patients diagnosed as RLS according to the criteria of the International RLS Study Group were examined using a standard questionnaire covering demographic data, family history, clinical symptoms, subjective sleep disturbances and course of the disease. In all patients a complete neurological examination was performed, and in selected cases electrophysiological examinations and polysomnographic studies. Family history was rated as definitely positive when at least one first-degree relative was examined and classified as RLS according to the criteria by one of the authors. If it proved impossible to contact family members to verify reports of a family history, the patients were classified as only having a "possible positive family history." 232 of the 300 patients had iRLS and 68 secondary RLS due to uremia (uRLS). 42.3% of the patients with iRLS and 11.7% of those with uRLS were classified as having "definite positive" hereditary RLS, with a further 12.6% of iRLS patients and 5.8% of uRLS patients as having "possible positive" hereditary RLS. Patients with definite hereditary RLS were significantly younger at the age of onset than those with a negative family history (35.45 vs. 47.17 years, p < 0.05). The clinical characteristics of the disease were similar in both groups, except that women with hereditary RLS experienced a worsening of symptoms during pregnancy (19.1% vs. 2.6%, p < 0.05). Our study shows that patients with hereditary RLS may experience an earlier onset of the disease. Hereditary and non-hereditary RLS present with similiar clinical signs and symptoms.     

MR-guided biopsies with a newly designed cordless coil in an open low-field system: Initial findings

The purpose of this study was to examine the feasibility and safety of MR-guided biopsies with a newly designed cordless coil in an open low-field magnetic resonance (MR) system. Eleven patients were biopsied using a low-field system (0.2 T, Magnetom Concerto, Siemens) by using the new cordless coil (Siemens). The biopsies were performed in different organ systems [liver (n=7), abdomen (n=1), shoulder (n=1), pelvis (n=1) and hip (n=1)]. The procedures were guided using T1-weighted FLASH (fast low-angle shot) sequences. The lesions were biopsied using the coaxial technique through a 15-gauge puncture needle with a 16-gauge biopsy handy. Coil handling, image quality and complications were evaluated. Imaging quality and visualization of the lesions were optimal up to a penetration depth of 9 cm. In all cases the biopsy procedures were successfully performed with MR guidance without any complications. Pathological findings revealed seven cases of malignant tissue and four cases of non-malignant tissue. The use of the cordless coil allows improved patient access during the biopsy and an improved handling of the coil system. MR-guided biopsy using the novel cordless coil system can be performed safely and precisely with easy handling of the coil. This coil concept, however, is restricted to special indications.     

Hybrid [F]-FDG PET/MRI including non-Gaussian diffusion-weighted imaging (DWI): Preliminary results in non-small cell lung cancer (NSCLC)

Purpose

To assess the feasibility of non-Gaussian DWI as part of a FDG-PET/MRI protocol in patients with histologically proven non-small cell lung cancer.

Material and methods

15 consecutive patients with histologically proven NSCLC (mean age 61 ± 11 years) were included in this study and underwent whole-body FDG-PET/MRI following whole-body FDG-PET/CT. As part of the whole-body FDG-PET/MRI protocol, an EPI-sequence with 5 b-values (0, 100, 500, 1000 and 2000 s/mm²) was acquired for DWI of the thorax during free-breathing. Volume of interest (VOI) measurements were performed to determine the maximum and mean standardized uptake value (SUV_max; SUV_mean). A region of interest (ROI) was manually drawn around the tumor on b = 0 images and then transferred to the corresponding parameter maps to assess ADC_mono, D_app and K_app. To assess the goodness of the mathematical fit R² was calculated for monoexponential and non-Gaussian analysis. Spearman's correlation coefficients were calculated to compare SUV values and diffusion coefficients. A Student's t-test was performed to compare the monoexponential and non-Gaussian diffusion fitting (R²).

Results

T staging was equal between FDG-PET/CT and FDG-PET/MRI in 12 of 15 patients. For NSCLC, mean ADC_mono was 2.11 ± 1.24 × 10⁻³ mm²/s, D_app was 2.46 ± 1.29 × 10⁻³ mm²/s and mean K_app was 0.70 ± 0.21. The non-Gaussian diffusion analysis (R² = 0.98) provided a significantly better mathematical fitting to the DWI signal decay than the monoexponetial analysis (R² = 0.96) (p < 0.001). SUV_max and SUV_mean of NSCLC was 13.5 ± 7.6 and 7.9 ± 4.3 for FDG-PET/MRI. ADC_mono as well as D_app exhibited a significant inverse correlation with the SUV_max (ADC_mono: R = −0.67; p < 0.01; D_app: R = −0.69; p < 0.01) as well as with SUV_mean assessed by FDG-PET/MRI (ADC_mono: R = −0.66; p < 0.01; D_app: R = −0.69; p < 0.01). Furthermore, K_app exhibited a significant correlation with SUV_max (R = 0.72; p < 0.05) and SUV_mean as assessed by FDG-PET/MRI (R = 0.71; p < 0.005).

Conclusion

Simultaneous PET and non-Gaussian diffusion acquisitions are feasible. Non-Gaussian diffusion parameters show a good correlation with SUV and might provide additional information beyond monoexponential ADC, especially as non-Gaussian diffusion exhibits better mathematical fitting to the decay of the diffusion signal than monoexponential DWI.     

A Practical Approach to the Diagnosis,Evaluation, and Management of Cutaneous Small-Vessel Vasculitis

Cutaneous small-vessel vasculitis (CSVV) is a disorder characterized by neutrophilic inflammation predominantly limited to the superficial cutaneous postcapillary venules. CSVV may be idiopathic or may have a defined cause such as infection, medication, connective tissue disease, or malignancy. CSVV may also be associated with extracutaneous disease or systemic vasculitis. The most common clinical presentation of CSVV consists of symmetrically distributed palpable purpura of the lower extremities. In general, lesional skin biopsy samples should be examined with light microscopy and direct immunofluorescence for adult patients with suspected CSVV. A complete history, review of systems, physical examination, and selected laboratory studies also should be performed to assess for inciting causes or extracutaneous involvement of CSVV. Treatment varies and depends on the chronicity of CSVV, the severity of cutaneous involvement, and the presence or absence of both an underlying cause and extracutaneous involvement of CSVV. An isolated episode of CSVV associated with a known inciting factor may be managed by removal or treatment of the trigger, along with symptomatic measures. First-line systemic treatments for chronic, idiopathic CSVV include colchicine or dapsone, used singly or in combination. Recurrent, chronic, or severely symptomatic CSVV that does not respond to the aforementioned therapies may require initiation of an immunosuppressive agent such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, or rituximab.     

Pityriasis amiantacea: a distinctive presentation of psoriasis associated with tumour necrosis factor-α inhibitor therapy

Pityriasis amiantacea (PA; also known as tinea amiantacea) is a relatively rare but distinctive scalp condition characterized by thick scales that adhere to each other and to the hair shaft, resulting in agglomeration and matting of hair. Temporary alopecia is a common complication. Although a specific cause remains unclear, PA is associated with several inflammatory diseases such as psoriasis and seborrhoeic dermatitis. We present a case of PA as a complication of underlying psoriasis, which developed during tumour necrosis factor (TNF)-α inhibitor therapy for Crohn disease. This paradoxical cutaneous reaction to anti-TNF-α therapy has been recently described as an emerging and perplexing cause of psoriasis and psoriasiform eruptions.     

Calcinosis cutis in autoimmune connective tissue diseases

Calcinosis cutis is a chronic condition involving insoluble calcified deposits of the skin and subcutaneous tissue. It is commonly associated with autoimmune connective tissue diseases and can be a source of pain and functional disability. The likelihood of developing calcinosis varies among the autoimmune connective tissue diseases, with systemic sclerosis and dermatomyositis being the most commonly associated. Identification of therapy for this challenging disorder has been hampered by a paucity of large controlled trials. Although there is no uniformly effective treatment for calcinosis cutis, several surgical and medical therapies have demonstrated varying degrees of benefit in the treatment of calcinosis, including surgical excision, laser therapy, extracorporeal shock wave lithotripsy, diltiazem, minocycline, colchicine, and topical sodium thiosulfate, along with others. Recommendations for the diagnosis and therapy of calcinosis cutis in patients with autoimmune connective tissue diseases are discussed.