[Splenic lymphoma, diagnosis and treatment]. / Lymphomes spléniques : diagnostic et prise en charge.

Some common clinical situations, such as splenomegaly or lymphocytosis, or less common, such as autoimmune hemolytic anemia, cold agglutinin disease, or cryoglobulinemia can lead to the diagnosis of splenic lymphoma. Splenic lymphoma is rare, mainly of non-hodgkinian origin, encompassing very different hematological entities in their clinical and biological presentation from an aggressive form such as hepato-splenic lymphoma to indolent B-cell lymphoma not requiring treatment such as marginal zone lymphoma, the most frequent form of splenic lymphoma. These entities can be challenging to diagnose and differentiate. This review presents different clinical and biological manifestations suspicious of splenic lymphoma and proposes a diagnosis work-up. We extended the strict definition of splenic lymphoma (lymphoma exclusively involving the spleen) to lymphoma thant can be revealed by a splenomegaly and we discuss the differential diagnosis of splenomegaly.

Acute superior mesenteric vein thrombosis in the setting of cytomegalovirus mononucleosis: a case report and review of the literature.

Cytomegalovirus is a viral genus of the overarching family Herpesviridae, and is of particular importance because of its relevance to human disease. This association is predominantly due to human cytomegalovirus, a well-studied pathogen. In addition to the mononucleosis syndrome that can occur during acute cytomegalovirus viraemia, this virion has been recurrently implicated as a provoking factor for thromboembolic disease in the published scientific literature. As physicians increasingly forgo extensive laboratory investigation in the setting of clinical hypercoagulability, it has also become evident that in some circumstances whether or not a particular investigation alters clinical management is not necessarily the only important question. Viraemia as a provoking factor for thrombosis stands as such an example. The aim of this Grand Round is to further explore the role of cytomegalovirus as it pertains to thromboembolic disease, especially in the present era of viral-associated thromboembolism.

Lymphocyte proliferative responses in dairy cows supplemented with an immunomodulatory feed additive and administered polyvalent vaccination / [Proliferação de linfócitos em vacas leiteiras suplementadas com um aditivo alimentar imunomodulador e vacinadas com vacina polivalente]

O presente estudo avaliou o efeito da suplementação com OmniGen-AF® na proliferação de linfócitos e títulos de anticorpos após vacinação em bovinos leiteiros. Amostras de sangue periférico foram coletadas de 32 vacas leiteiras para quantificação dos títulos de anticorpos anti-Leptospira, e amostras de sangue periférico de 16 vacas leiteiras foram também coletadas para avaliação da proliferação de linfócitos. Observou-se que a suplementação com OmniGen-AF® aumentou a proliferação basal de linfócitos (sem estímulos) 21 dias após a vacinação (P=0,03), apesar de reduzir a proliferação de linfócitos B quando estimulada com Leptospira borgpetersenii serovar Hardjo inativada pelo calor (P=0,03). Ademais, nenhum efeito da suplementação sobre a proliferação de linfócitos no momento imediatamente anterior à vacinação e nos títulos de anticorpos anti-Leptospira foi encontrado. Além disso, a proliferação de linfócitos estimulada com lipopolissacarídeos foi maior em vacas multíparas que em primíparas 21 dias após a vacinação (P=0,03). Desse modo, o presente estudo demonstra que a suplementação com OmniGen-AF® não afetou de forma robusta a proliferação de linfócitos e os títulos de anticorpos anti-Leptospira após vacinação em vacas leiteiras sadias.(AU)

Differential effects of phototherapy, adalimumab and betamethasone-calcipotriol on effector and regulatory T cells in psoriasis.

BACKGROUND: Psoriasis is a chronic T-cell-mediated skin disease with marked social and economic burdens. Current treatments are unsatisfactory, with unpredictable remission times and incompletely understood modes of action. Recent advances in our understanding of the pathogenesis of psoriasis have identified the imbalance between CD4+ T effector cells, particularly the T helper (Th)17 subset, and regulatory T cells (Tregs) as key to the development of psoriatic lesions, and therefore a novel therapeutic target. OBJECTIVES: To quantify in patients the effects of three commonly used psoriasis treatment modalities on the Th1, Th2, Th17 and Treg subsets, and to test whether any change correlates with clinical response. METHODS: Flow cytometry was used to enumerate Th1, Th2, Th17 and Treg subsets in blood and skin of patients with psoriasis before and after receiving any of the following treatments: narrowband ultraviolet B (NB-UVB), adalimumab and topical betamethasone-calcipotriol combination (Dovobet® ) RESULTS: All patients responded clinically to the treatments. NB-UVB significantly increased the numbers of circulating and skin Tregs, while, by contrast, adalimumab reduced Th17 cells in these compartments, and Dovobet had dual effects by both increasing Tregs and reducing Th17 cells. CONCLUSIONS: The differential effects reported here for the above-mentioned treatment modalities could be exploited to optimize or design therapeutic strategies to overcome the inflammatory drivers more effectively and restore the Th17-Treg balance in psoriasis.

Japanese herbal medicine-induced pneumonitis: A review of 73 patients.

BACKGROUND: The number of reports concerning Japanese herbal medicine (JHM)-induced pneumonitis has increased. However, comprehensive data are lacking in this regard, and the clinical characteristics of the disease remain unclear. METHODS: A literature review was performed using PubMed and Ichushi-Web-the database of the Japan Medical Abstracts Society-to identify articles published between 1996 and 2015 describing patients with JHM-induced pneumonitis. The final cohort included 73 patients in 59 articles (7 in English; 52 in Japanese). RESULTS: Among the various JHMs reported, sho-saiko-to was the most frequently used drug (26%), followed by sairei-to (16%), seishin-renshi-in (8%), and bofu-tsusyo-san (8%). These drugs commonly contain ougon (skullcap) and kanzo (liquorice). The mean age at pneumonitis diagnosis was 63.2 ± 15.5 years (range: 7-89 years). The male/female ratio was 44/29. Sixty-five patients (89%) developed pneumonitis within 3 months of beginning JHM treatment. Bilateral ground-glass attenuations on chest computed tomography, as well as lymphocytosis with a low CD4/CD8 T-cell ratio in bronchoalveolar lavage fluid, were common findings. Twenty-six patients (36%) recovered from the pneumonitis after simply discontinuing the causative JHM. However, the remainder required immunosuppressive therapy, and 13 patients (18%) received mechanical ventilation. Importantly, three patients (4%) did not survive, with two showing pathological diffuse alveolar damage upon autopsy. CONCLUSIONS: Clinicians should be cautious regarding JHM-induced pneumonitis, particularly when using drugs/ingredients known to cause this complication, and during the early treatment period. Although most events are non-severe, critical cases should be recognized.

Alterações hematológicas em cães (Canis lupus familiaris) após tratamento com eletroacupuntura / Haematological changes in dogs (Canis lupus familiaris) after treatment with electroacupuncture

A acupuntura, é uma terapia que cada vez mais adquire uma credibilidade no mundo ocidental, a sua indicação pode ser para pacientes anêmicos e imunossuprimidos, e outras afecções. O experimento foi realizado com oito cães adultos, sendo 4 fêmeas e 4 machos. O estudo consistiu em análise das concentrações das células vermelhas e brancas avaliado em 4 tratamentos: controle (T0), acupuntura (T1), eletroacupuntura unilateral (T2) e eletroacupuntura bilateral (T3). Os acupontos utilizados foram intestino grosso 4, intestino grosso 11 e estômago 36. Todos os animais passaram por todos os tratamentos com um intervalo de 7 dias para cada tratamento. Os hemogramas séricos foram verificados 20 minutos antes do início do tratamento (M0), logo após o tratamento (M1), e 60 minutos (M2) e 120 minutos (M3) após o tratamento. O resultado da série vermelha não foi significativo, mas notou-se somente uma diminuição significativa da concentração média corpuscular (CHCM) (p<0,05) no tratamento T1 no M1 em comparação aos outros tratamentos; notou-se também uma redução significativa (p<0,05) na concentração plaquetária de T1, T2 e T3 em comparação ao grupo controle. A eletroacupuntura pode levar a uma trombocitopenia, quando estimulado estes pontos, provavelmente por um estímulo parassimpaticomimético.

Acupuncture is an alternative therapy which increasingly acquires credibility in the Western Hemisphere and it is indicated for anemic and immunosuppressed patients, as well as for other diseases. The experiment was performed with 8 adult dogs, 4 females and 4 males. The study consisted to analyze the concentrations of white and red cells evaluated at four treatments: controls (T0), acupuncture (T1), unilateral electroacupuncture (T2), and bilateral electroacupuncture (T3). The acupoints utilized were: 4 large intestine, 11 small intestine and 36 stomachs. All animals experienced all treatments with an interval of 7 days to each treatment. The serum hemograms were verified 20 minutes prior to initiation to treatment (M0), at the end of the treatment (M1), 60 minutes after treatment (M2) and 120 minutes post-treatment (M3). The results revealed that the red series was not significant, but there was only a significant decrease in medium corpuscular concentration (p<0.05) at T1 of M1 as compared to the other treatments; also there was a significant reduction (p<0.05) in the platelet concentration at T1, T2 and T3 as compared to controls. The electro-acupuncture may lead to thrombocytopenia, when stimulating these points, probably by a parasympathetic stimulus.

[Pulsed dye laser treatment for Jessner's lymphocytic infiltration of the skin]. / Infiltrat lymphocytaire de Jessner et Kanof traité par laser à colorant pulsé

BACKGROUND: Jessner's lymphocytic infiltration of the skin (LIS) is a chronic, benign T-cell infiltrative disorder, usually manifesting as erythematous papules or plaques on the face, neck and back. PATIENTS AND METHODS: five patients presented LIS with numerous skin lesions on the face and back characteristic of this disease. Histological examination showed a lymphocytic infiltrate in the dermis without any modification of the epidermis. Direct immunofluorescent study was negative in all cases. Response to dermocorticoids proved inconsistent or negative in all patients. An excellent outcome was achieved in all five patients with pulsed dye laser. In one case, further skin lesions appeared at 1 year and responded to the same treatment. Following a single treatment session with 6-8 J/cm(2), three of five patients showed normal skin. Regression occurred in the other two cases after two to three sessions. Pulsed dye laser appeared to be the best treatment for Jessner-Kanof disease for three patients at 4-8 years of follow-up. DISCUSSION: only one case of Jessner-Kanof disease treated by pulsed dye laser has been reported. Pulsed dye laser has been used in cutaneous lupus and annular granuloma. Selective photothermolysis allows photocoagulation of dilated vessels. CONCLUSION: pulsed dye laser at 595nm could offer a valuable therapeutic alternative, and even a first-line treatment with no side effects.

Acute bacterial meningitis in a patient receiving ibuprofen.

We report an atypical presentation of meningitis due to Neisseria meningitidis in a patient who received large doses of ibuprofen. Anti-inflammatory therapy such as NSAIDs could reduce CSF inflammation and modify the clinical outcome in patients with bacterial meningitis. However, the use of NSAIDs is not recommended in bacterial meningitis due to a lack of studies.

A patient of migraine-like headache with amnesia, pleocytosis and transient hypoperfusion of cerebral blood flow.

Pseudomigraine with pleocytosis (PMP) is an uncommon disease in Japan. The diagnostic criteria include at least one episode of transient neurological deficit accompanied or followed by migraine-like severe headache, cerebrospinal fluid (CSF) lymphocytosis, and normal neuroimaging. Both the etiology and the pathophysiology of PMP is not yet well defined. We report a 40-year-old man with a PMP-like syndrome. He came to our clinic because of severe throbbing headache and amnesia, and the examination showed CSF lymphocytosis of 23/mm3, a transient decrease of cerebral blood flow in the left thalamus. All the symptoms were completely resolved within 2 months.

Microscopic colitis: an underdiagnosed cause of chronic diarrhoea--the clue is in the biopsies.

Microscopic forms of colitis (collagenous colitis and lymphocytic colitis) are uncommon but important causes of chronic diarrhoea that are often overlooked. The clinical features of these disorders are similar, and they are more common in middle-aged females, although the female predominance is greater in collagenous colitis. Although their cause is unclear, both are associated with a variety of autoimmune diseases. Colonoscopy and barium enema are typically normal, so that the diagnosis depends on the demonstration of characteristic changes on histopathological examination of colorectal biopsies. These should be taken in all patients undergoing colonoscopy for the investigation of chronic diarrhoea. There are no large controlled trials of therapy available. Treatment is empirical, generally using the same agents as for inflammatory bowel -disease. Assessment of therapy is also difficult as spontaneous remissions occur often.

CD28 costimulation is critical for experimental allergic asthma in HLA-DQ8 transgenic mice.

The objective of this study was to investigate the contribution of the CD28 costimulatory molecules to allergen-induced primary and chronic inflammatory responses. To this end, we have developed and characterized a short ragweed allergen-induced asthma model involving sensitization of HLA-DQ transgenic mice followed by intranasal challenge with allergen. Forty-eight hours after primary challenge, sensitized DQ8 mice developed pulmonary eosinophilic inflammation, airway hyperreactivity, Th2 cytokines, and IgE/IgG1 Ab. This allergic inflammatory response was absent in H-2Abeta(0) and DQ8/CD28(0) mice. Secondary rechallenge with allergen 4 weeks later induced even greater inflammatory changes in the airways of DQ8 mice with eosinophils being the predominant inflammatory cells while only pulmonary lymphocytosis was observed in DQ8/CD28(0) mice. No inflammation was detected in H-2Abeta(0) mice. Proliferation and cytokine profile studies demonstrated that CD28 regulates T-cell activation and effector function. Therefore, CD28 is essential for the extrinsic asthma and can be a target for immunotherapy.

30-day intravenous administration of VRCTC-310-ONCO in rabbits.

VRCTC-310-ONCO, an agent based on the snake phospholipase A2 (crotoxin), is currently under clinical development. After phase I study in patients by intramuscular administration, the interest of intravenous (IV) dosing arose. To evaluate IV administration of VRCTC-310-ONCO in rabbits, ten animals were subjected to surgical implant of fixed jugular catheter, by which they received daily IV doses of 0.03 mg/kg body weight of VRCTC-310-ONCO for 30 days (n = 8) or saline (n = 2). The procedure was well tolerated in all rabbits. One of the animals died after the sixth dose of VRCTC-310-ONCO with CNS involvement; two additional rabbits required dose-reduction. All other rabbits achieved 30 days of treatment and were sacrificed. All rabbits (even controls) developed lymphocytosis and mild anaemia, without changes in blood neutrophils. No changes were found in serum transaminases (GOT and GPT), cholesterol, triglycerides, and y-glutamyl transpeptidase. At necropsy, chronic granulation tissue was found surrounding the implant in all rabbits. VRCTC-3 10-ONCO-treated rabbits presented generalised and marked swelling of hepatocytes, with areas of cytoplasmic vacuolisation. No abnormalities were found in kidney, heart, lung, spleen, adrenal gland, uterus, testes and ovary. Additional studies with IV route for VRCTC-310-ONCO, including humans, are required to define its toxicity in the clinical setting.

Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 1. Hematological and population level assessment.

Sunfish were collected from coal ash effluent-receiving streams and Ohio River watershed reference sites to assess the effects of exposure to low-level selenium concentrations. Selenium, copper, and arsenic concentrations were statistically higher in tissue samples from exposed fish than in reference fish. Leukopenia, lymphocytosis, and neutropenia were evident in exposed fish and were indicative of metal exposure and effect. White blood cell counts and percent lymphocyte values were significantly correlated with liver selenium concentrations. Plasma protein levels were significantly lower in exposed fish than in fish from the Ohio River, indicating that exposed fish may have been nutritionally stressed. Condition factors for fish from the ash pond-receiving streams were the same as, or lower than, those of fish from the reference sites. There was no evidence that the growth rate of fish in the receiving streams differed from that of fish in the reference streams. Despite liver selenium concentrations which exceeded reported toxicity thresholds and evidence of significant hematological changes, there were no significant differences in fish condition factors, liver-somatic indices, or length-weight regressions related to selenium.

Alteraçöes metabólicas e funcionais em células e órgäos do sistema imunológico de ratos induzidas pela administraçäo intragástrica do óleo de peixe / Metabolic and functional changes in cells and organs of immune system of rats due to the fish oil administrated by gavage

O consumo de cápsulas de óleo de peixe (OP) por humanos visa a atenuaçäo dos sintomas e prevençäo de várias patologias. As alteraçöes metabólicas e funcionais em células e órgäos do sistema imunológico causadas pelo OP pela administraçäo intragástrica (AIG) foram avaliadas. Ratos recém-desmamados (50-70 g) foram submetidos a AIG diária com óleo de peixe, óleo de soja ou manteiga de cacau (0,4 por cento do peso), por 28 dias. Os dados da AIG do OP foram também comparados com os da dieta enriquecida com OP. Foram avaliados: aumento de permeabilidade vascular (reaçäo anafilática), funcionalidade de macrófagos (produçäo de 'H IND. 2O IND. 2', 'O IND. 2' e fagocitose), proliferaçäo de linfócitos, a atividade máxima das enzimas: hexoquinase, glicose-6-fosfato desidrogenase, citrato sintase (metabolismo de glicose), catalase, glutationa peroxidase e superóxido dismutase (antioxidantes) no baço, linfonodo mesentérico e timo. A concentraçäo de TBARs nos mesmos órgäos e no plasma e a capacidade antioxidante do plasma foram também determinadas

Catecholamine-induced leukocytosis: early observations, current research, and future directions.

Recent studies demonstrate that acute psychological stress in man affects lymphocyte circulation. It has been suggested that catecholamines are responsible for these changes. The present review summarizes findings regarding catecholamine-induced lympho- and leukocytosis, starting with observations dating back to the beginning of this century. Particular attention is given to the mechanisms of this phenomenon and the potential site of origin of newly appearing leukocytes. Characteristically, two phases are recognized after catecholamine administration: a quick (<30 min) mobilization of lymphocytes, followed by an increase in granulocyte numbers with decreasing lymphocyte numbers. Many studies have shown that catecholamines predominantly affect natural killer (NK) cell and granulocyte circulation, whereas T- and B-cell numbers remain relatively unaffected. The changes in lymphocyte circulation seem to be mainly mediated via activation of beta2-adrenoceptors, whereas granulocyte increases involve alpha-adrenoceptor stimulation. Results further indicate that the marginal pool and the spleen are the major sources for freshly recruited lymphocytes, whereas granulocytes are predominantly released from the marginal pool and the lung. Results from acute psychological stress or physical exercise models corroborate the results obtained with catecholamine administration. Together, the data demonstrate that components of the innate immune system participate in the classical fight/flight response.

[Segmental ischemic colitis in lymphocytic thrombotic venulitis]. / Colite ischémique segmentaire sur veinulite lymphocytaire thrombosante.

This case illustrates the difficulty of diagnosing a colonic stenosis of ischemic origin. A 70-year-old lady presents with abdominal pain, fever and melaena. Lc are 15.2, ESR 39 mm, CEA 2.7 ng/ml. A barium enema shows a stenosis of the transverse colon that is suspicious of neoplasia. At time of operation, an induration of the transverse colon is found with edema of the corresponding mesocolon but no tumour is palpated. A resection of this area is performed and an end to end anastomosis performed. Pathology shows an ischemic colitis secondary to a lymphocytic thrombotic venulitis. The patient is discharged home one month postoperatively. 4 weeks later she is readmitted with the same symptoms. A gastrograffin enema shows a similar stenosis in the transverse colon including the anastomosis. The diagnosis is made of a recurrent ischemic stenosis. The patient improves over a 10-day period of conservative treatment (anticoagulation, TPN, steroids). A control barium enema shows a near resolution of the stenosis. The majority of ischemic colitis are of arterial origin nevertheless ischemic colitis of venous origin exists. The factor causing venous ischemia are not known. It is though thought to be associated with hypersensitivity vasculitis of drug origin. Its initial diagnosis versus neoplasia is difficult but once made there is a good response to a conservative treatment.

Dual mechanisms involved in development of diverse biological activities of islet-activating protein, pertussis toxin, as revealed by chemical modification of lysine residues in the toxin molecule.

Islet-activating protein (IAP), pertussis toxin, is an oligomeric protein composed of an A-protomer and a B-oligomer. There seem to be at least two molecular mechanisms by which IAP exerts its various effects in vivo and in vitro. On the one hand, some of the effects were not significantly affected by acetamidination of the epsilon-amino groups of the lysine residues in the molecule. These include the activities in vitro (1) catalyzing ADP-ribosylation of one of the membrane proteins directly, (2) enhancing membrane adenylate cyclase activity in C6 cells, (3) reversing receptor-mediated inhibition of insulin or glycerol release from pancreatic islets or adipocytes, respectively, and the activities in vivo (4) inhibiting epinephrine-induced hyperglycemia, (5) potentiating glucose-induced hyperinsulinemia, (6) reducing hypertension and increasing the heart rate in genetically hypertensive rats. These activities are concluded to develop as a result of ADP-ribosylation catalyzed by the A-protomer which is rendered accessible to its intramembrane substrate thanks to the associated B-oligomer moiety. Thus, neither the enzymic activity of the A-protomer nor the transporting activity of the B-oligomer needs free amino groups of the lysine residues in the IAP molecule. On the other hand, additional effects of IAP, such as (1) mitogenic, (2) lymphocytosis-promoting, (3) histamine-sensitizing, (4) adjuvant and (5) vascular permeability increasing, were markedly suppressed by acetamidination of the intrapeptide lysine residues. The free epsilon-amino group of lysine would play an indispensable role in the firm (or divalent) attachment of the B-oligomer of IAP to the cell surface that is responsible for development of these activities.

[Clinical course of Haemonchus infection in experimental invasion in lambs]. / Klinichno protichane na khemonkhozata pri eksperimentalno invazirani agneta

Eight 2-month-old lambs, divided into two groups, were experimentally infected with 5000 and 2500 larvae of H. contortus. It was found that the infection assumes a course with well manifested clinical symptoms, diarrhea, lowered appetite, stunted bodily growth, anemia, eosinophilia and lymphocytosis. Both the clinical symptoms and the parasitologic aspects are dependent on the extent of the infection. The total content of Ca and of the blood serum drops, and the amount of Mg fluctuates within the normal range.