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Primary central nervous system lymphomas--an update.

Primary CNS lymphomas (PCNSL), until recently representing about 1% of all brain tumors, show dramatically increased incidence both in high-risk groups (immunocompromised, AIDS) and in the general population. They are extranodal diffuse non-Hodgkin's lymphomas, the morphology and classification of which are identical to those of systemic lymphomas, although PCNSL show different biological behavior and diagnosis according to the New Working Formulation and updated Kiel classification may be difficult. The majority are large B cell variants of high-grade malignancy; low-grade subtypes and T cell lymphomas are rare. Sixty per cent occur in the supratentorial space (hemispheres, periventricular) and 12% in the posterior fossa; 30% are multiple (50%-70% in AIDS). PCNSL show a male preponderance with a peak incidence in the 5th-7th decade (3rd-4th in AIDS). The duration of diffuse or focal clinical symptoms averages 1-2 months. Computed tomography and magnetic resonance imaging scans show single or multiple or diffuse, often typical lesions. Diagnosis is achieved by evaluation of stereotactic biopsy material or cerebrospinal fluid cytology using immunocytological markers. Current therapy in immunocompetent patients, radiation plus corticosteroids and pre- or postradiation polychemotherapy, shows response rates of 85% with a median survival of 17-44 months, a prognosis similar to that for glioblastoma. Meningeal PCNSL is treated with intrathecal methotrexate or cytosine arabinoside. Transliquoral seeding of PCNSL is frequent, distant metastases occurring in 6%-8%. Therapy of AIDS-related PCNSL makes use of radiation and corticosteroids, and rarely of chemotherapy. The pathogenesis of PCNSL is unknown, but Epstein-Barr virus may be a contributory factor.

Brain Neoplasms↗

Homozygosity for the CARD15 frameshift mutation 1007fs is predictive of early onset of Crohn's disease with ileal stenosis, entero-enteral fistulas, and frequent need for surgical intervention with high risk of re-stenosis.

OBJECTIVE: The identification of CARD15 as a susceptibility gene for Crohn's disease (CD) offers new possibilities for patient classification and risk assessment. The purpose of this study was to carry out a CARD15 sequence analysis in a large single-center IBD cohort and to investigate the impact of different genotypes on disease phenotypes. MATERIAL AND METHODS: A total of 445 unrelated patients with IBD (68.1% CD, 28.5% ulcerative colitis (UC), 3.4% indeterminate colitis (IC)) were included in the study. Clinical data were recorded by detailed questionnaire and analysis of the charts. CARD15 variants (R702W, G908R, 1007fs (frameshift)) were identified by DNA sequence analysis. RESULTS: CARD15 variants were found in 142 inflammatory bowel disease (IBD) patients (31.9%) including 120 CD patients (39.6%). In CD, the presence of two CARD15 variants was associated with ileal disease (p=0.008 versus wild-type (wt); OR 4.04; 95% CI 1.36-11.96) and a fibrostenotic phenotype (p=0.002 versus wt; OR 5.47; 95% CI 1.61-18.58). Subgroup analysis of 19 patients (4.3%) homozygous for the CARD15 variant 1007fs (3020ins C) revealed an association with onset of CD at an early age (p=0.014 versus wt), ileal involvement (p=0.001), and intestinal stenoses in all patients (p=0.001) frequently requiring surgery (73.7%; p=0.093). Of these patients 78.6% developed re-stenoses after surgical resection; 52.6% of the homozygotes were diagnosed as having entero-enteral fistulas. CONCLUSIONS: Patients homozygous for the 1007fs mutation had an early disease onset with long-segment ileal stenoses and entero-enteral fistulas. They frequently needed surgical intervention and had a high risk of re-stenosis. Genotyping therefore appears to be an important diagnostic tool in identifying severely affected patients requiring individualized treatment strategies at an early stage of the disease.

Adolescent↗

Chronic lymphocytic leukaemia--the haematologic basis for diagnosis and treatment.

Clinically diagnosis may be incidental when absolute lymphocytosis is uncovered at routine medical examination. More usually there is a recurrent sinopulmonary infection reflecting a varying degree of humoral and cellular immune deficiency. Autoimmune phenomena may result in haemolytic anaemia or thrombocytopenia. Expanding tumour bulk underlies the lymphadenopathy which may be prominent. Diagnosis is confirmed on morphology of the smear where atypical variants need to be distinguished from other indolent lymphoproliferative disorders. Immunophenotyping is indispensable in classification. Prognosis is predicated by cytogenetics and markers of tumour biology that include beta-2 microglobulin and peripheral blood lymphocyte doubling time. Management is dictated by symptoms and signs of progression superimposed upon performance status that includes age. Disease that is asymptomatic and truly indolent, particularly in the elderly, qualifies for a careful watch-and-wait policy. In other circumstances stratification to therapy requires entry into peer-reviewed protocols if optimal outcome is to be achieved. Established regimens, of demonstrably equal efficacy, are pulsed single-agents exemplified by chlorambucil or combinations of cyclophosphamide with vincristine and prednisone. The purine analogues, particularly when administered with an alkylating agent and mitoxantrone, are emerging as superior options. In selected patients any properly accredited program will make provision for escalation in chemotherapy requiring haematopoietic stem cell transplantation on the one hand or use of serotherapy with CD52 antibodies on the other. Less commonly, but in a defined subgroup, immunoglobulins directed against membrane CD20 may be effective. Perspective for the generalist is anchored in recognising that the previous cavalier approach to drug medication, with or without radiotherapy, is unwise whereas integrated management is now the international standard of practice. The previous anachronism of dabbling by occasional therapists is to be deprecated since this will generally deny patients access to proper diagnosis and risk-adjusted multi-disciplinary treatment.

Antineoplastic Agents↗

Clinicopathologic features and incidence of invasive lobular carcinoma in Japanese women.

Intending to clarify the true incidence of invasive lobular carcinoma of the breast in Japanese women as well as the frequency of unilateral multicentricity, 362 cases of clinically defined monocentric breast cancer without pre-operative biopsy (previously fine needle aspiration or needle biopsy were routinely carried out for every case) were examined by whole mammary gland serial sectioning. On the basis of pathology and the World Health Organization classification of breast tumors, each case was assigned to one of two main histologic types: invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). Invasive lobular carcinoma was further separated into classic and variant types by employing previously published criteria. Twenty-one cases of ILC (5.8%) were diagnosed, which is more than in most previous Japanese studies. Unilateral multicentric breast carcinoma was detected in 9.5% of ILC and 16.1% of IDC (the difference was found not significant). Microscopically, ILC tumors were found to be, on average, larger than IDC. Patients with classic type ILC tended to be younger than those with variant type or IDC. Estrogen receptor expression was found more frequently in variant type ILC than in classic type. These results suggest that the incidence of invasive lobular carcinoma of the breast in Japanese women is low and that unilateral multicentricity is not significantly higher in ILC than in IDC.

Adult↗

[Specific strategies in the treatment of young and middle-age patients with spontaneous intracerebral hemorrhage].

The paper is based on the analysis of 235 young and middle-age patients with non-traumatic cerebral hemorrhage. Tactics of treatment is determined for each group depending on bleeding localization in accordance with World Health Organization's classification (1981). Operative treatment is recommended for lateral site of hematomas of 25 cm3 and more signs of media structures dislocation of 5 mm and more. With the development of hypertension-hydrocephal syndrome surgical intervention is directed at its elimination and where possible at hematoma's ablation. The amount of operative interventions is limited in case of medial and mixed variants of hemorrhages especially when bleedings affect mesencephal structures. In conditions of a neurosurgical clinic a pharmacotherapy is used as an independent one, as a preparation for surgical treatment as well as during operation and in postoperative period.

Adult↗

Electrocardiographic tall R waves in the right precordial leads. Comparison of recently proposed ECG and VCG criteria for distinguishing posterolateral myocardial infarction from prominent anterior forces in normal subjects.

Electrocardiographic tall R waves in the right precordial leads may be present in patients with posterior myocardial infarction, right ventricular hypertrophy, various conduction disturbances, and some forms of cardiomyopathy and in clinically otherwise normal subjects with prominent anterior electromotive forces. Clinical uncertainty most often arises in distinguishing possible prior posterolateral myocardial infarction (PMI) from the unusual normal variant (PAF). The ECGs and VCGs of 15 subjects with posterolateral infarction were compared with tracings from 12 subjects with no evidence of cardiac disease, all individuals demonstrating tall R waves (R/S greater than 1.0 in V1 and/or V2) in the right precordial leads on surface ECG. By standard ECG, the infarction group was characterized by taller T waves in leads V1 and V2, shorter T waves in V6, greater T2-T6 index, and a more negative two variable function as described by Nestico. By VCG, the infarction group was characterized by a more anteriorly oriented T loop, more leftward maximal frontal plane QRS vector and a lower calculated -45 degrees/ab, as described by Suzuki. An algorithm was proposed that permitted proper classification (PAF vs. PMI) based on ECG criteria in 75% of subjects with 90% accuracy. This compared favorably with performance of the Frank vectorcardiogram, including using more recently proposed criteria. Routine use of the VCG, therefore, in this clinical setting may no longer be justified.

Diagnosis, Differential↗

Evidence of three-dimensional variability in scoliotic curves.

In the current study, 98 patients with idiopathic scoliosis were selected for analysis. The object of this study was to determine whether three-dimensional variability exists within each class of the King classification, and to evaluate the currently used King classification in its ability to categorize different scolioses adequately. Anteroposterior and lateral radiographs were digitized, and three-dimensional models were reconstructed for each spine. Several parameters were recorded for each individual: age, gender, four Cobb angles, (1) anteroposterior, (2) lateral, (3) maximum (Cobb angle at the plane of maximum deformity), and (4) minimum (Cobb angle at the plane of minimum deformity), and the orientation of the planes of maximum and minimum deformity. Most of the curves were kyphotic, but a small percentage in each class were hypokyphotic or lordotic. This was not seen in the analysis in which the individual King classes were compared. It was seen, however, when the authors reanalyzed the data after having pooled the subjects and reclassified them according to presence or absence of kyphosis. The King classification was shown to be inadequate for describing spinal deformities in three dimensions, because different variants of sagittal spine configurations were seen which can look identical on the anteroposterior view. Therefore, the need for a new three-dimensional classification, which takes this variability into account, is established.

Adolescent↗

Unusual intracardiac tumor in a child. Inflammatory pseudotumor or "granulomatous" variant of myxoma?

An intracardiac tumor arising in the right atrium of a young child is reported. Morphologically, the lesion was reminiscent of "plasma cell granulomas," but unprecedented in this location. Based on clinical manifestations, laboratory findings, histologic and ultrastructural characteristics of the mass, the speculation is put forth that this lesion may represent a cardiac myxoma with atypical structural features. An extension of this proposal is a pathogenetic sequence that would try to reconcile the complex clinical course of some myxomas with the described structural observations. Alternative choices for classification of the lesion are also given consideration.

Child, Preschool↗

[Hereditary neuropathies].

BACKGROUND: Hereditary neuropathies constitute a heterogeneous group of diseases that make up a significant proportion of peripheral nerve disease cases. MATERIAL AND METHODS: The paper is based on a review of recent literature, including searches on Medline, and our own clinical and research experience. RESULTS: Charcot-Marie-Tooth disease, itself a heterogeneous disease, is the most common hereditary neuropathy. Several variants of neuropathy are associated with hereditary metabolic disorders. Diagnostic methods include nerve conduction velocity studies and electromyography, quantitative sensory testing, molecular genetic diagnostic testing, and in selected cases processing of nerve biopsies and skin biopsies for determination of epidermal nerve fibre densities. INTERPRETATION: A thorough family history of neuropathic symptoms and signs, and preferably clinical and electrophysiological examination of relatives is essential for the diagnosis of hereditary neuropathy. Molecular genetic analysis is promising for accurate classification of these diseases. Nerve biopsy is only helpful in selected cases.

Charcot-Marie-Tooth Disease↗

Management of locally advanced breast cancer (stage III): a review.

Patients classified as having locally advanced breast cancer constitute a heterogeneous population of patients with variable prognoses among subgroups. Analysis of reported series has been complicated by the use of a wide variety of staging classifications and the inclusion by some (and not by others) of inflammatory carcinoma in reporting of end results. In spite of difficulties in this literature review, certain conclusions are possible: The 1983 AJCC-UICC staging system would appear to be a reasonable system for assuring comparability of results in future clinical trials. Although the precise frequency of LABC among series cannot be determined with certainty, this presentation probably constitutes less than 20% of series in the Western world. Recognizing that axillary lymph node status is the single most important prognostic variable in primary breast cancer, it has been reported that LABC with large local tumors are associated with neoplastic involvement of axillary lymph nodes in 65-80% of cases, thus connoting a poor prognosis. Patients with T3N0 lesions may constitute a subgroup of patients with relatively indolent (possibly receptor-positive) disease who might have a reasonably good prognosis compared with other variants of LABC, with approximately 75% to 82% of patients surviving five years with surgery alone. Surgery alone for the overall category of LABC is associated with a 20-31% ten-year survival rate, with local control varying from 50-75% in two reported series. Most radiation therapy (XRT) series deal with patients considered inoperable; hence five-year survival statistics in most series range between 10-20%. Selected radiation therapy series may yield results comparable to surgical series. Where reported, XRT has been associated with median survivals in the range of 25 months. Local control with XRT is likely a function of radiation dose, and the use of external beam or iridium implant boosts to the primary tumor mass for increased local control is worthy of continued study. The combination of XRT and mastectomy appears to be superior to either modality alone in terms of local control and survival, although this conclusion is based on analysis of retrospective studies. Combined modality therapy with systemic therapeutic modalities (hormonal and/or chemotherapy) plus the local modalities of surgery and radiation therapy appear promising. Prospective controlled trials using a uniformly accepted staging classification coupled with gathering of useful biological data (such as cytokinetic perturbation data, receptor information, marker studies, etc) should lead to improved treatment approaches in the future.

Antineoplastic Combined Chemotherapy Protocols↗

Serology of Neisseria gonorrhoeae. Demonstration by co-agglutination and immunoelectrophoresis of antigenic differences associated with colour/opacity colonial variants.

Serological classification of Neisseria gonorrhoeae by co-agglutination (COA) into previously described antigen classes W and J was confirmed in the present work. Immunization of rabbits with classified organisms gave antibodies which produced the expected results when used in the preparation of COA reagents. Colour/opacity colonial variants of isogenic strains, characterized by stereomicroscopy as opaque and transparent, respectively, were found to influence immunization, absorption, co-agglutination and precipitation in immunoelectrophoresis (IE). It was shown by COA and IE that organisms of opaque colonies often contained an extra antigenic factor(s) which resisted heating at 100 degrees C but was sensitive to treatment with pronase. They were extracted by heating the organisms in saline or lithium chloride solution. Serological classification with COA in clinical isolates was reproducible with reagents for antigen classes W and J. Colony morphology dependent reactions, mostly due to organisms of opaque colonies, occurred in 7% with reagents for antigen class W and in 20% for antigen class J.

Agglutination Tests↗

The prevalence and clinical profile of angiographic coronary ectasia.

Coronary artery ectasia, a variant of coronary atherosclerosis, is a relatively rare entity. Review of literature did not reveal an exclusive study on isolated ectasia. We decided to analyse the clinical presentation and angiographic prevalence of this subset. A retrospective study of patients who underwent coronary angiogram in our institute over the past six years was carried out and the epidemiological, clinical and angiographic characteristics of patients with isolated ectasia were analysed. Distribution of ectasia was with a modification of the Markis classification. Among 6938 angiograms analysed, 134 (2%) had isolated ectasia. Of the 118 symptomatic patients, 34 (25%) had a history of or presented with infarction, with correlation between the territory of infarction and the ectatic vessel in 32 patients. Of 62 patients with lipid abnormality, Hypertriglyceridemia in 42 (65%) was the most common. The left anterior descending artery was the most common vessel involved. Diffuse ectasia most commonly involved the right coronary artery. One patient had spontaneous coronary dissection. There is a relatively high prevalence of isolated coronary ectasia with predominant involvement of the right coronary vessel when diffuse and the left anterior descending artery when discrete. This entity is not innocuous and warrants a detailed study on the available management options.

Adult↗

Myelodysplastic syndromes: the pediatric point of view.

Myelodysplastic syndromes (MDS) are clonal disorders of the multipotent hematopoietic stem cell characterized by ineffective hematopoiesis and associated with marrow hypercellularity, increased intramedullary cell death and peripheral cytopenias of varying severity. Patients with myelodysplasia have a propensity (20% to 30% of cases) to undergo transformation into acute myeloid leukemia (AML), and a large body of evidence indicates that MDS represent steps in the multiphasic evolution of AML. Progression of the disease is characterized by expansion of the abnormal clone and inhibition of normal hematopoiesis leading to deterioration of the blood cell count and/or development of AML. MDS are relatively unusual in childhood, representing only 3% of pediatric hematological malignancies, although it has been reported that up to 17% of pediatric AML cases may have a previous myelodysplastic phase. The first systematic attempt at morphological classification of MDS was provided by the French-American-British (FAB) group. However, the FAB classification of MDS is only partially applicable in children. Some variants are extremely rare or absent (refractory anemia with ring sideroblasts and chronic myelomonocytic leukemia), and other peculiar pediatric disorders, represented by juvenile chronic myelogenous leukemia (JCML) and the monosomy 7 syndrome, are not included. Moreover, since there is a partial overlap between pediatric MDS and myeloproliferative disorders and the variants occurring in young children have rather specific features, some confusion still surrounds the nosographical definition of childhood MDS, so that none of the proposed classifications are widely accepted and used. Characteristically, some genetic conditions such as Fanconi's anemia, Shwachman's and Down's syndromes predispose to the development of MDS in childhood. The most common variants of childhood MDS are represented by JCML and the monosomy 7 syndrome, both disorders typically occurring in young children. JCML is characterized by a spontaneous growth of granulocyte-macrophage progenitors that show a striking hypersensitivity to granulocyte-macrophage colony-stimulating factor. Clinical presentation resembles that of some myeloproliferative disorders, with massive organomegaly usually not observed in the classically reported variants of MDS. Clinical features of the monosomy 7 syndrome resemble those observed in JCML and a differential diagnosis between these two entities relies upon the higher percentage of fetal hemoglobin, the more pronounced decrease in platelet count and, in some cases, the lack of the peculiar cytogenetic abnormality in the latter. With the number of children being cured of cancer constantly rising, a significant increase in secondary or chemotherapy-related myelodysplasia is being observed, and these disorders represent a formidable challenge for pediatric hematologists due to their poor response to chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗

Radix entomolaris: identification and morphology.

The Royal Dental College, Copenhagen, houses an extensive collection of human teeth, extracted in Denmark. At present, the collection includes 398 permanent mandibular molars with a root complex containing a lingually-located supernumerary root. This macrostructure is called radix entomolaris (RE). By analyzing the large number of available specimens it was possible to establish uniform and precise criteria for the identification of RE on M1 inf, M2 inf, and M3 inf. The analyses included separate as well as non-separate RE. The representation of the RE variants according to tooth types was mapped. Furthermore, the following relevant clinical variables with respect to RE were registered: degree of separation, divergence, apical bend, apical gracility, and fusion. Because of the nature of the material, the investigation was mostly qualitative and non-metric. The results should be of interest to clinical dentists, dental morphologists, and dental anthropologists.

Classification↗

Diffuse large B-cell lymphoma: one or more entities? Present controversies and possible tools for its subclassification.

Diffuse large B-cell lymphoma (DLBCL) is the commonest type of lymphoid tumour world-wide. This category was included both in the REAL and WHO Classification aiming to lump together all malignant lymphomas characterized by the large size of the neoplastic cells, B-cell derivation, aggressive clinical presentation, and the need for highly effective chemotherapy regimens. These tumours are detected as primary or secondary forms both at the nodal and extranodal levels, in immunocompetent hosts as well as in patients with different types of immunosuppression. They display a significant variability in terms of cell morphology and clinical findings, which justifies the identification of variants and subtypes. Among the latter, the primary mediastinal one does actually correspond to a distinct clinicopathological entity. Immunophenotypic, tissue microarray and molecular studies underline the extreme heterogeneity of DLBCLs and suggest a subclassification of the tumour, based on the identification of different pathogenic pathways, which might have much greater relevance than pure morphology for precise prognostic previsions and adoption of ad hoc therapies. The more recent acquisitions on the pathobiology of DLBCLs are reviewed in the light of the authors' experience, aiming to contribute to the existing debate on the topic.

Animals↗

[Intra-arterial regional perfusion in destructive forms of acute pancreatitis].

The results of using regional infusion therapy in 17 patients with destructive pancreatitis are analyzed which appeared to be more effective, than the systemic infusion of drugs in stopping the symptoms of endotoxicosis leveling the functional insufficiency of the liver and kidneys, disturbances in hemodynamics and hemostasis. The best results have been obtained when using a modified method of regional therapy (celiac-aortal dislocational regional infusion) in the complex treatment of destructive pancreatitis. This method has a number of advantages as compared with intra-aortic variant of regional therapy. Hospital lethality in the process of using the methods of regional therapy in the complex treatment of destructive pancreatitis was 17.5%. In the control group of patients treated without regional infusion lethality was within the limits of 28%. A modified classification of endotoxicosis according to the degree of the disease is proposed. In order to estimate the severity of the syndrome of intoxication and effectiveness of the given therapy principally new integrative parameters of clinical and laboratory research are used.

Acute Disease↗

[Screening for anti-glycolipid antibody profiles from patients with immune-mediated peripheral neuropathies by Dotzen Ganglio Profile Antibodies].

The presence of anti-glycolipid specific antibodies have been found to be associated with acute and chronic immune-mediated peripheral neuropathies. Recently a number of anti-glycolipid antibody assays have became commercially available. In this study we established specific anti-glycolipid antibody profiles in a series of sera by the Dotzen Ganglio Profile antibodies. This kit screens for the simultaneous detection of ten anti-glycolipid antibodies against GM3, GM2, GM1, GD3, GD1a, GD1b, GT1a, GT1b, GQ1b gangliosides and sulfatides of the IgM and IgG classes. Sera from 89 patients with acute and chronic neuropathies were selected in a well-characterized cohort of banked sera with anti-glycolipid antibody profiles identified by in-house immunodot assay. Serum from 52 clinical variants of Guillain-Barré syndrome with IgG autoantibody profiles and 37 chronic acquired peripheral neuropathy with IgM autoantibody profiles were tested. The assay correctly identified with good agreement 50 of 52 IgG antibody profiles and 32 of 37 IgM antibody profiles. The assay compared well with in-house immunodot assay. It is easy to screen 10 crossreacting glycolipid antibodies to establish specific antibody profiles to define different subgroups of immune-mediated peripheral neuropathies for classification and immune management.

Autoantibodies↗

[Role of molecular screening for common fusion genes in the diagnosis and classification of leukemia].

OBJECTIVE: To assess the value of common fusion genes analysis in the diagnosis and classification of leukemia by multiplex RT-PCR. METHODS: The multiplex RT-PCR, including 8 parallel PCR reactions, could screen 86 mRNA breakpoints or splice variants at the same time, which was important for the diagnosis and prognosis of leukemia. Bone marrow samples from 161 cases of leukemia and 8 cases of myelodysplastic syndrome (MDS) were involved in the study. The distribution of common fusion genes in leukemia was analyzed by the method mentioned above in combination with clinical and morphological features. RESULTS: Ten fusion genes were detected in 115 cases of leukemia, including AML1/ETO, PML/RAR alpha, PLZF/RAR alpha, dupMLL, MLL/AF6, MLL/AF10, CBFbeta/MYH11, BCR/ABL, Hox11, and EVI1 BCR/ABL was positive in all the 52 cases of chronic myeloid leukemia; PML/RAR alpha was found in 21 of 25 acute promyelocytic leukemia (APL), and PLZF/RAR alpha was detected in one case of APL. Sixteen cases of 17 AML1/ETO-positive acute leukemia (AL) belonged to FAB-M2 subtype, and one case was mixed leukemia. Three of 4 AL cases carrying CBFbeta/MYH11 were M4 subtype, and one was M5 subtype. MLL aberrations were found in 16 AL, in which all MLL/AF6 translocation existed in M5 subtype with classic monoblastic characters. Furthermore, BCR/ABL was detected in 5 acute lymphoblastic leukemia (ALL) cases. Fusion genes were also found in 2 MDS cases, of which AML1/ETO positive-MDS-RAEB progressed to AML rapidly. CONCLUSION: Screening of common fusion genes by multiplex RT-PCR is an important tool which could provide useful and reliable molecular genetic information for the diagnosis and treatment of leukemia.

Adolescent↗