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[New treatment for orbital non-Hodgkin's lymphoma: 2 cases treated with rituximab].

INTRODUCTION: Orbital non-Hodgkin's lymphoma is a rare tumor whose diagnosis is often difficult. Treatment of latent lymphoma have been changing because of progress in immunotherapy. OBSERVATION: We report two patients treated with rituximab (antibody anti-CD20). Two women, 50 and 59 years old, presented low-grade, IE-stage lymphoma. One was conjunctival MALToma, the other was orbitopalpebral, type A, of WFC classification, follicular, with small cells. Immunohistochemistry showed a diffused marking for Ac anti-CD20. Both patients received intravenous rituximab as a first treatment in December 2000, 375 mg/m2, four injections per week. We did not note any major undesirable effects. Both have been in complete remission for 4 years. These patients continue to be followed up. DISCUSSION: Rituximab's efficacy has been proved mainly in follicular LMNH or in recurrent forms. The recurrence may be more frequent in MALT lymphoma. This medical treatment has low hematologic toxicity. CONCLUSION: Rituximab offers an alternative for low-grade lymphoma treatment that is well tolerated by the patient.

Antibodies, Monoclonal↗

[Secondary obstructive megaureter with detrusor-sphincter dyssynergia in children].

29 boys with secondary obstructive megaureter due to detruzor-sphincter dyssinergy were treated in 1989-1998. To normalize detruzor-sphincter relations, transurethral sphincterotomy was made in 25 boys. Later, 16 of them underwent autocatheterization of the urinary bladder and received alpha-adrenoblockers. Reconstructive plastic operations were performed in 34.5% (secondary megaureter of the degree III-IV). The author thinks more valid not to use the term "secondary obstructive megaureter" but to integrate this compound urinary tract lesion (megaureter with dyssinergy associated with diffuse dysplastic changes in the kidneys) into one syndrome. In secondary megaureter, longitudinal ureteral modelling is valid as this facilitates its reimplantation. Urodynamic examinations of the lower urinary tracts showed that sphincterotomy reestablished micturition in many cases, though high miction and intraabdominal pressure in dysadaptation of detruzor evidences for the existence of detruzor-sphincter dyscoordination in latent denervation of the urinary bladder.

Adolescent↗

[Comparison of indirect and direct measurement of transferrin in healthy and sick children (author's transl)].

In 207 children chemical measurement of total iron binding capacity (TIBC) and direct immunological evaluation of transferrin by radial immunodiffusion were compared. In addition, serum ferritin was measured in nearly all cases, to exclude iron deficiency. In 14 newborns, 20 infants and 35 older children TIBC and transferrin values correlated significantly (p < 0.001), as well as in various disorders (infections, hyporegenerative anemia, beta-thalassemia, acute blood loss) and in prelatent, latent and manifest iron deficiency. Standard deviations of both methods were comparable. Anemia and hyposideremia due to infection could be clearly distinguished from iron deficiency of all stages. The diagnosis of prelatent iron deficiency, however, can be definitely established only by measurement of serum ferritin or other more complicated procedures (59Fe2+-whole body retention test, estimation of diffuse iron in bone marrow macrophages). An interesting finding was the negative significant correlation (r = 0.69) between the two iron binding proteins in serum, transferrin and ferritin. In summary, the simple radial immunodiffusion technique for transferrin with its minimal requirement of serum can be recommended for pediatric routine laboratories in the differential diagnosis of anemia and hyposideremia, before unnecessary iron medication is institued.

Adolescent↗

Worker-client exchanges and contraceptive use in rural Bangladesh.

In this article, longitudinal data from rural Bangladesh are used to assess the impact of household visits from family planning workers on contraceptive use. A panel of women was interviewed in a demographic survey and reinterviewed every 90 days for six successive rounds. Regression methods are used to estimate the effect of these encounters on the odds that a woman will use contraceptives. Statistical controls adjust for the potentially confounding effects of underlying demand for contraception. Findings suggest that both male and female worker-initiated exchanges have an effect, although the impact of outreach is more pronounced if the worker is female. Estimated effects are consistent with the hypothesis that the predominant impact of outreach is to crystallize existing latent demand for contraception. Results also suggest, however, that female worker outreach generates new demand by fostering ideational change.

Adult↗

[Intraoperative ultrasonic evaluation of the residual thyroid weight in thyroidectomy in diffuse toxic goiter].

The amount of thyroid tissue to be ablated in unresponsive Basedow disease has mainly, until now, been empirically evaluated. An attempt has been made, using intraoperative ultrasonography, to evaluate the residual tissue. This method allows weight calculation of the thyroid lobe to be ablated through two sonographic measurements of the superior pole axes. This technique provides a precise codification of the intervention and reduces the incidence of recurrence. The results six months after operation prove just two cases of latent hypothyroidism (10%).

Graves Disease↗

A pathologic study of Hodgkin's disease in Korea and its association with Epstein-Barr virus infection.

BACKGROUND: The incidence of Hodgkin's disease (HD) in Korea and other Asian countries is much lower than in western countries and its association with the Epstein-Barr virus has not been well characterized. METHODS: We evaluated the clinical, morphologic, and immunohistochemical features of 87 patients with Hodgkin's disease and also analyzed patients for Epstein-Barr virus (EBV) using in situ hybridization for EBV DNA, RNA, and latent membrane protein (LMP1). RESULTS: There were 68 males and 19 females, with a mean age of 38 years. Mixed cellularity was the most prevalent subtype. Expression of EBV RNA (EBER:EBV-encoded RNA) was detected in 60 of 87 cases (69%): 1 of 1 (100%) with lymphocyte predominance, nodular; 4 of 7 (57%) with lymphocyte predominance, diffuse; 10 of 17 (59%) with nodular sclerosis; 38 of 51 (75%) with mixed cellularity; and 7 of 11 (64%) with lymphocyte depletion. Positivity was higher in advanced clinical stages; 4 of 7 patients (57%) with Stage I; 6 of 12 patients (50%) with Stage II: 7 of 9 patients (75%) with Stage III; and 5 of 5 patients (100%) with Stage IV HD EBV DNA was detected in 9 of 25 cases tested (36%). LMP1 was seen in 39 of 87 cases (45%). EBER and LMP1 positivity were higher in children and older adults than in adults aged between 15-50 years. Immediate early mRNAs (BHLF:Bam H-fragment, lower strand frame) was seen in a single patient. CONCLUSIONS: HD in Korea showed a high incidence of mixed cellularity subtype and a high prevalence of EBV. EBV was detected in all subtypes, including a case of nodular lymphocytic predominance, and in all age groups, and showed correlation with mixed cellularity subtype and higher clinical stage. The expression of EBER and LMP were more frequently seen in children and older adults, suggesting a lowered immune surveillance in those age groups or a different pathophysiology of HD among different age groups.

Adolescent↗

Intranuclear foci containing low abundance herpes simplex virus latency-associated transcripts visualized by non-isotopic in situ hybridization.

During latent infection of neurons with herpes simplex virus type 1 (HSV-1), several RNA transcripts of varying abundance arise from a single locus within the virus repeats. The functions of latency-associated transcripts (LATs) are unknown and the relationship between the various RNA species requires further clarification. Reported here is a novel approach to the study of HSV transcripts during latency, based on the increasing realization that cellular and viral RNAs are synthesized and processed by macromolecular complexes that occupy discrete compartments within the nucleoplasm of a cell. High resolution non-isotopic in situ hybridization was used to study the intranuclear topology of HSV-1 LATs in primary sensory neurons of latently infected mice and humans. Low abundance (minor) LATs were localized to sharply defined intranuclear foci of 1 to 3 microns in diameter. On average, there were 2.6 to 2.8 foci/LAT+ neuronal profile (5 microns), representing 13 to 14 foci/cell. In contrast to the focal deployment of minor LATs, the more abundant latency-associated RNAs were distributed diffusely throughout the nucleoplasms of latency infected neurons, with prominent sparing of nucleolar regions. These data establish a foundation for studying the synthesis, processing and transport of LATs in vivo. It should now be possible to investigate the nature of those cellular products which associate with HSV-1 encoded LATs in vivo and thereby determine whether minor LATs are associated with previously characterized macromolecular complexes, such as those responsible for processing of pre-messenger RNA.

Animals↗

Characterization of the transcriptional repressor RBP in Epstein-Barr virus-transformed B cells.

RBP, a transcriptional repressor, is intricately involved in Epstein-Barr virus (EBV) transformation of human B cells. The EBV nuclear proteins EBNA-2, -3, -4 and -6 all utilize RBP to regulate the transcription of both cellular and viral genes. This study investigates the isoforms of the RBP protein in Burkitt's lymphoma (BL) cells and in EBV-transformed lymphoblastoid cell lines (LCLs). Two-dimensional gel electrophoresis showed the presence of two different cellular isoforms of RBP; the molecular masses and isoelectric points of these two isoforms corresponded to RBP-Jkappa and RBP-2N. Fractionation studies and green fluorescent protein (GFP)-tagged expression studies demonstrated that both RBP isoforms were located predominantly in the cell nucleus. Interestingly, GFP-tagged RBP-Jkappa showed diffuse, uniform nuclear staining, whereas GFP-tagged RBP-2N showed a discrete nuclear pattern, demonstrating differences between the two isoforms. Within the nuclear fraction of EBV-negative BL cells, RBP existed both in a free form and bound to chromatin, whereas in LCLs the intranuclear RBP was predominantly chromatin-bound. Expression of the EBV latent proteins was found to lead to the sequestering of RBP from the cytoplasm into the cell nucleus and to an increase in the chromatin-bound forms of RBP.

B-Lymphocytes↗

Role of lymphocyte adhesion receptors in transient interactions and cell locomotion.

Lymphocytes adhere to other cells and extracellular matrix in the process of immunological recognition and lymphocyte recirculation. This review focuses on regulation of lymphocyte adhesion and the use of adhesion mechanisms by lymphocytes to obtain information about their immediate environment. The CD2 and LFA-1 adhesion receptors appear to have distinct roles in the regulation of adhesion and modulation of T lymphocyte activation. Adhesion mediated by interaction of CD2 with LFA-3 is dramatically altered by surface charge and adhesion receptor density in such a way that this pathway is latent in resting T lymphocytes but becomes active over a period of hours following T-cell activation. CD2 ligation can mediate or enhance T-cell activation, suggesting that signals from CD2/LFA-3 adhesive interactions are integrated with signals from the T-cell antigen receptor during immunological recognition. A model for the role of LFA-3 lateral diffusion in adhesion is presented, based on the lateral diffusion of different LFA-3 forms in glass supported planar membranes. Interaction of LFA-1 with ICAMs is also regulated by cell activation but in a different way than in interaction of CD2 with LFA-3. LFA-1 avidity for ICAMs is transiently increased by T-cell activation over a period of minutes. Cycles of avidity change are also observed for other T lymphocyte integrins which bind to extracellular matrix components. We propose that integrin avidity cycles may have an important role in the interconnected phenomena of locomotion, initial cell-cell adhesion, and cell-cell deadhesion. Recent observations on recirculation of T lymphocyte subpopulations are discussed in the context of general lessons learned from study of the CD2/LFA-3 and LFA-1/ICAM adhesion mechanisms.

Animals↗

Immunohistochemical assessment of human herpesvirus 8 infection in primary central nervous system large B cell lymphomas.

BACKGROUND/AIMS: Primary central nervous system large B cell lymphomas (PCNSLs) are frequently associated with Epstein-Barr virus (EBV) in patients with AIDS and less frequently in those without AIDS. Human herpesvirus 8 (HHV-8) has been detected in these tumours by the polymerase chain reaction (PCR) at low copy number, suggesting its presence in a cell compartment other than the malignant one. The aim of this study was to use immunohistochemistry to assess HHV-8 infection in a series of PCNSLs from patients with and without AIDS. METHODS: The antibody LN53, which reacts with the latent nuclear antigen 1 (LNA1) of HHV-8, was used on tissue sections from 35 patients (17 with and 18 without AIDS) with PCNSL. In addition, DNA was available for PCR (open reading frame 26 (ORF 26), ORF 72, ORF 75) in three patients (two without AIDS, one with AIDS). RESULTS: None of the 35 cases contained either DNA sequences or LNA1 positive cells. CONCLUSIONS: These results confirm the lack of HHV-8 infection in tumour cells of PCNSL. In addition, HHV-8 infected bystander cells do not express LNA1 latent protein in this setting.

Animals↗

Leishmania and HIV co-infection: dermatological manifestations.

Leishmania species can cause a wide spectrum of cutaneous disease in HIV-positive patients: asymptomatic, localized cutaneous, mucosal, muco-cutaneous, diffuse cutaneous or post-kala-azar leishmaniasis. In such cases, which are usually severely immunocompromised, the leishmanial parasites reach the skin of the human host by dissemination after either a new infection (resulting from the bite of infected sandfly or, probably, the sharing of contaminated syringes by intravenous-drug users) or the re-activation of a latent infection. Recent experience and past observations on the dermatology of leishmaniasis in those with Leishmania/HIV co-infection are reviewed here.

AIDS-Related Opportunistic Infections↗

[Application of O-PLS in fundamental study of non-invasive measurement of human blood glucose concentration with near infrared spectroscopy].

Near-infrared diffuse reflectance spectroscopy is a promising approach to the non-invasive prediction of blood glucose levels. However, because the measured object is human body whose physiological structures are so complicated that it is very difficult to separate the information of glucose from the overlapped spectra using the traditional modeling method. A new regression method called orthogonal projections to latent structures (O-PLS), which integrated the orthogonal signal correction (OSC) preprocessing into the regular PLS modeling, was applied to the optimization and interpretation of the glucose near-infrared spectroscopy model. Applying O-PLS resulted in removal of non-correlated variation in spectra and reduced model complexity with preserved prediction ability, improved interpretative ability of variation in spectra.

Blood Glucose↗

Pathogenesis of pulmonary hypertension in tuberculosis.

The pathogenic factors involved in the increase of pressure in the pulmonary artery in 55 tuberculous patients with manifest, and 50 patients with latent pulmonary hypertension were examinated and analyzed in detail. The authors consider decisive the restriction of pulmonary blood bed together with the decrease of functional parenchyma. In the increase of arterial pressure also the functional vasoconstriction participates. An important role plays here hypoxemia adversely affecting the cardiac function. Hypoxemia, of all pathogenic factors, represents the most serious limitation of pulmonary diffusion, though other agents may not be primarily important for the onset and development of pulmonary hypertension. The originating pulmonary hypertension in tuberculosis does not necessitate compensating mechanisms such as polyglobulia, hypervolemia, or increase of the minute cardiac volume normally present in severe and protracted hypoxemia. The prognosis of patients with the mean pulmonary artery pressure higher than 30 mmHg (3.33 kPa) is very bad, the median survival being about 10 months. Contrarily, a low-grade pulmonary hypertension may not, per se, provide sinister prognostic outlooks. Here rather some other agents capable of influencing the perspectives seen to be of major importance.

Blood Pressure↗

Cellular environment of metabolites and a metabonomic study of tamoxifen in endometrial cells using gradient high resolution magic angle spinning 1H NMR spectroscopy.

High resolution magic angle spinning (HRMAS) 1H NMR spectroscopy was used to metabolically characterise Ishikawa cells, a human cell line derived from endometrial adenocarcinoma. The spectra obtained had well-resolved resonances from the nucleotide derivatives of uridine and adenosine. Using a combination of diffusion- and relaxation-weighted spectroscopy, the cellular environment of key metabolites previously identified as related to cell growth was also investigated. As Ishikawa cells are hormone-responsive, the metabolic action of tamoxifen, a selective estrogen receptor modulator (SERM), was also investigated. Cells were exposed to 5, 1 and 0.1 microM tamoxifen. Using the statistical regression technique of prediction to latent structures by partial least squares, a predictive model was built modelling the metabolic profile of the cells against exposure to tamoxifen. These spectral changes were characterised by increased resonance intensities from ethanolamine (3.26 ppm), glucose (3.34-3.94 ppm), glutamate (2.14, 2.32 ppm), tyrosine (7.24 ppm), uridine (7.85 ppm) and adenosine (8.20 ppm), and a relative decrease in contributions from myo-inositol resonances (3.30, 3.62, 3.55 ppm). The nucleotide changes suggest that tamoxifen affects RNA transcription, while the changes in ethanolamine and myo-inositol concentrations are indicative of cell membrane turnover.

Adenocarcinoma↗

Estimation of operating characteristics for dependent diagnostic tests based on latent Markov models.

We describe a method for making inferences about the joint operating characteristics of multiple diagnostic tests applied longitudinally and in the absence of a definitive reference test. Log-linear models are adopted for the classification distributions conditional on the latent state, where inclusion of appropriate interaction terms accommodates conditional dependencies among the tests. A marginal likelihood is constructed by marginalizing over a latent two-state Markov process. Specific latent processes we consider include a first-order Markov model, a second-order Markov model, and a time-nonhomogeneous Markov model, although the method is described in full generality. Adaptations to handle missing data are described. Model diagnostics are considered based on the bootstrap distribution of conditional residuals. The methods are illustrated by application to a study of diffuse bilateral infiltrates among patients in intensive care wards in which the objective was to assess aspects of validity and clinical agreement.

Biometry↗

Leishmania and human immunodeficiency virus coinfection: the first 10 years.

Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack of randomized prospective treatment trials; therefore, coinfected patients are treated by conventional regimens. Prophylactic therapy is suggested to be helpful in preventing relapses.

Animals↗

Scoring of visual field measured through Humphrey perimetry: principal component varimax rotation followed by validated cluster analysis.

PURPOSE: To extract unidimensional, well-separated latent scores that are anatomically and clinically valid from 52 standardized variables collected by Humphrey visual field (VF) perimetry (Carl Zeiss Meditec, Dublin, CA). METHODS: Visual field data of 437 patients were collected and classified by a glaucoma specialist into seven clinical groups: irregularities of VF (IVF), nasal step (NaS), arcuate scotoma (AC), paracentral scotoma (PCS), blind-spot enlargement (BSE), diffuse deficit (DD), and advanced deficit (AD). The number and content of constituent variable scores were identified by principal components analysis followed by Varimax Rotation and simple clustering, taking spatial distribution homogeneity and visual system anatomy into account. Unidimensionality was checked by a stepwise Cronbach alpha curve. Clinical predictability of the derived scores was checked by comparing clinical groups (ANOVA). RESULTS: Patients older than 60 years comprised 53.3% of the sample. The average mean deviation was -9.2 dB and pattern standard deviation was 6.5 dB. Six scores were identified: four peripheral scores (nasal superior, NS; nasal inferior, NI; temporal superior, TS; and temporal inferior, TI) and two paracentral scores (PCSs; superior, PCSS; and inferior, PCSI). Cronbach alpha was always >0.90. The six scores decreased sequentially from IVF to DD to AD. Scores of AC were lower in NS, NI, and TS; PCSS was less in PCS; BSE scores were less in TS and TI; NaS scores were less in NS and NI. CONCLUSIONS: Six well-separated, optimal scores were obtained from the Humphrey perimetry matrix. Internal reliability was good. It was possible to discriminate between clinical subgroups. Further analyses, based on longitudinal data, must be performed to confirm these findings.

Cluster Analysis↗

Malignant mesothelioma: a review of 35 cases with diagnosis and prognosis.

Twenty-five men and 10 women with malignant mesothelioma seen at the Austin Hospital between 1965 and 1978 were reviewed. The patients ranged in age from 34 to 79 yr. Prognosis was poor but was somewhat better for patients with epithelioid tumours than for patients with fibrous mesotheliomas and biphasic tumours. A history of occupational exposure to asbestos was obtained in the majority of patients, the latent period being from 18 to 52 yr. Ten patients had no history of asbestos exposure. The pathological diagnosis was established on tissue obtained at open biopsy in 22 cases and at post mortem in 11. Needle biopsy provided a diagnosis in only 2 cases. Cytology suggested a diagnosis of mesothelioma in 1 case. Gross pathology in general conformed with a diffuse confluent-nodular serosal tumor. A right sided preponderance was found in pleural tumours, and metastases were found rather more frequently than is usually reported. Histological features were distinctive in the majority of cases provided that sufficient material was examined. Recognition of coexisting patterns was often more helpful in making the diagnosis than any one single feature. Histochemical reactions are useful in distinguishing mesothelioma from mucin-secreting adenocarcinoma. In a majority of cases the histology and histochemistry were not characteristic and the diagnosis depended on the clinical features and the absence of another primary source of tumour.

Adult↗