Variation in the histological pattern of nodal involvement by gamma/delta T-cell lymphoma

AIMS: Gamma-delta (gammadelta) T-cell non-Hodgkin's lymphomas (NHLs) usually present with liver, spleen and marrow infiltration. Lymph node involvement by gammadelta T-cell NHL has been rarely documented so far; its histological pattern needs to be further defined. METHODS AND RESULTS: Two cases of nodal gammadelta T-cell NHL are reported: case 1, a 44-year-old man, presented with cytomegalovirus retinitis and superficial lymphadenopathies. Histological analysis of an inguinal lymph node showed complete destruction by a diffuse pleomorphic lymphoid proliferation, which was positive for CD2, CD3, CD43, CD45, TIA-1 and granzyme B, and displayed a gammadelta phenotype (deltaTCR1+, Vdelta1+, Vdelta2-, Vdelta3-, betaF1-). Bone marrow was normal. Case 2, a male 24-year-old patient with a history of renal transplantation, presented with hepatosplenomegaly and supraclavicular lymph node enlargement. Lymph node architecture was globally preserved. Peripheral sinuses contained scattered nests of medium-sized irregular lymphoid cells. Bone-marrow was infiltrated. Phenotype showed positivity for CD2, CD3, CD45 and TIA1 and expression of gammadelta TCR (deltaTCR1+, deltaV1+, deltaV2-, deltaV3-, betaF1-). Both patients died a short time after diagnosis. CONCLUSIONS: These observations suggest that at least two forms of nodal gammadelta T-cell NHL may be encountered: one mimicking classical alphabeta T-cell NHL, with diffuse pleomorphic cell proliferation, and one displaying sinusoidal neoplastic infiltration suggesting a close relationship with hepatosplenic gammadelta T-cell NHL.     

Hepatic MALT lymphoma disclosing a nodal extension

We report a case of a 50-year-old man with chronic viral hepatitis B presenting with a primary hepatic lymphoma of mucosa-associated lymphoid tissue, revealed clinically by a pedicular nodal mass. The liver biopsy showed an active chronic hepatitis and a dense portal lymphoid infiltrate with centrocyte-like cells inducing typical biliary lympho-epithelial lesions. The lymph-node biopsy revealed a marginal zone lymphoma pattern. A monoclonal rearrangement of the immunoglobulin heavy chain gene was detected in the lymph node by polymerase chain reaction. This case of primary hepatic mucosa-associated lymphoid tissue lymphoma confirms that the liver also contains mucosa-associated lymphoid tissue, in which low grade lymphoma can arise.     

Teratological studies on the TCDD congener 3,3′,4,4′-tetrachloroazoxybenzene in sensitive and nonsensitive mouse strains: Evidence for direct effect on embryonic tissues

The teratogenicity of 3,3,4,4-tetrachloroazoxybenzene (TCAOB), a TCDD congener, was studied in Ah-responsive (C57BL and NMRI) and non-responsive (DBA/2J and AKR/NBom) strains of mice. In the responsive strains, the TCAOB produced cleft palate and hydronephrosis in 50–90% of the offspring at a dose level of 6–8 mg/kg b.w. in the absence of apparent maternal toxicity. Day 11 was shown to be the day of highest sensitivity (palatal closure occurs at day 14) in the C57BL strain. Higher doses (16 mg/kg b.w.) produced high rate of fetal death both in responsive (C57BL; 60%) and non-responsive (DBA; 40%) strains. These doses induced cleft palate in 95% of the surviving C57BL fetuses but failed to do so in the DBA strain. The non-sensitivity of the DBA and AKR strains appeared to segregate as a dominant trait. Backcrosses between NMRI x DBA F₁ generation and NMRI showed an intermediate sensitivity. It was shown that the genotype of the embryo was of ultimate importance for the development of cleft palate. There appeared however to be an additional host (maternal) factor as well, because the offspring of NMRI females mated with NMRI x DBA F₁ males showed a higher rate of cleft palate as compared to those of the crossing between NMRI x DBA F₁ females and NMRI males. Light and scanning electron microscopy indicated that the apical epithelial cells of the secondary palates failed to follow the normal pattern of programmed cell death, suggesting a similar mechanism of pathogenesis as previously described for TCDD.     

Embryotoxicity of chromium: Distribution in pregnant mice and effects on embryonic cells in vitro

The embryonic and fetal uptake of Na₂ ⁵¹Cr₂O₇(Cr VI) was about 10 times higher than that of ⁵¹CrCl₃(Cr III) when these two were given in the same doses i. v. to pregnant C57BL mice. On day 13 of gestation, embryonic concentrations were 12% (Cr VI) and 0.4% (Cr III) of the maternal serum concentration 1 h after injection to the mother. After injection of Cr(III) radioactivity was not detectable in embryonic structures in early gestation, when autoradiographic techniques were used. In late gestation, administration of both forms of Cr resulted in an accumulation in the calcified areas of the fetal skeleton. The radioactivity after administration of Cr(VI) may represent Cr(III) after reduction in the tissues. When added to chick limb bud mesenchymal cells in vitro, Cr(VI) inhibited chondrogenesis at a concentration of about 0.1 g/ml medium, which is around 1/10 of the embryonic concentration achieved after giving teratogenic doses to pregnant mice. Cr(III) on the other hand did not show any overt cytotoxicity even at 15 g/ml ( 500 times higher than the in vivo embryonic concentrations after teratogenic doses). Especially Cr(III) accumulated strongly in the visceral yolk sac, probably after binding to and transport by maternal serum proteins. The possibilities that Cr(III) excerts its teratogenic action by inhibiting embryotrophic nutrition is discussed.     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

Ceftaroline fosamil as first-line versus second-line treatment for acute bacterial skin and skin structure infections (ABSSSI) or community-acquired bacterial pneumonia (CABP)

The Clinical Assessment Program and Teflaro^® Utilization Registry (CAPTURE) is a multicenter registry study of acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) patients treated with ceftaroline fosamil in the US. Data for this analysis were collected between August 2011 and February 2013 at US study centres by randomly ordered chart review. Clinical success rates among ABSSSI patients were >81% when ceftaroline fosamil was used as first- or second-line therapy, including monotherapy and concurrent therapy. Among CABP patients, clinical success rates were >77% among first-line and second-line patients and patients who received first-line concurrent therapy or second line monotherapy or concurrent therapy. For CABP patients treated with ceftaroline fosamil as first-line monotherapy, the clinical success rate was 70%. Ceftaroline fosamil is an effective treatment option for patients with ABSSSI or CABP with similar clinical success rates when used as first-line or second-line treatment.     

The prevalence of Type 2 Diabetes Mellitus in the United Arab Emirates: justification for the establishment of the Emirates Family Registry

To study the prevalence of Type 2 Diabetes Mellitus (T2DM) in a population of United Arab Emirates (UAE) residents through the creation of the ??Emirates Family Registry?? (EFR). Major hospitals and diabetes centres in the UAE were contacted to establish a bio-banking facility referred to as the EFR. Through assistance made available by the Ministry of Health and collaborators of this network, demographic data of T2DM patients were collected and collated in a database for analysis and longitudinal studies. Clinical specimens were collected for biochemical profiling (such as; glucose, lipids, HbA_1c levels). In the first 24?months of the operation the EFR recruited 23,064 adult volunteers from three major hospitals and nine primary care centres throughout the UAE. Within this cohort, 88% were patients classified as T2DM patients from the medical records. The cohort was divided into age categories with 59% of T2DM patients aged between 40 and 59?years old. UAE nationals comprised 30% of the database of which 21% were diagnosed with T2DM. However the percentage of adults with T2DM was higher in other ethnic groups effecting almost 33% of the Indians who live in the UAE. A total of 741 UAE Nationals consented to donate blood; in phase I of the study; for biochemical testing after which 23% were diagnosed with T2DM, 30% with pre-T2DM and 47% were healthy. This study is consistent with the previously reported high prevalence of T2DM in the UAE. Furthermore, analyses of the factors that predispose to the disease have revealed that obesity, a large waist circumference, consanguineous marriage, family history, lack of physical activity, unhealthy dietary practices, high total cholesterol, and high triglycerides levels were more prevalent in T2DM patients. The classification of these features will contribute to defining more effective and specific plans to screen for and manage diabetes and its complications in UAE and other developing countries.