Peculiar histopathological features in minor salivary gland in lupus erythematosus.

Salivary glands (SGs) can be affected by lupus erythematosus (LE). Many authors debate whether this condition is a secondary manifestation of Sjögren syndrome (SS) or a glandular aspect of LE. The present study investigated the histopathological aspects of biopsied minor salivary glands from LE patients to analyze their peculiar features that lead to xerostomia. Twenty-three minor labial salivary gland (MLSG) cases were included in the study; the diagnosis of LE was rendered according to the American College of Rheumatology criteria. Twenty-three healthy MLSGs were used as a control, for comparison. Regarding lupus MLSG, the presence of hyalinization and thickening of ductal basement membrane, perivascular inflammatory infiltrate, epithelial spongiosis with no ductal lymphocytic aggression, vacuolar degeneration of the ductal cells and acinar serous metaplasia were statistically significant compared to the control group. In the LE group, there was a statistically significant correlation between acinar atrophy and acinar fibrosis; acinar atrophy and ductal ectasia; acinar fibrosis and ductal ectasia; ductal atrophy and ductal spongiosis with no lymphocytic focus, interstitial inflammatory infiltrate intensity and vasculitis as well as vascular thrombi and vasculitis. There were no morphological differences between the three subtypes of lupus analyzed. Minor salivary glands from patients diagnosed with LE present peculiar histopathological changes and may be a multisystemic presentation.

ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial.

BACKGROUND: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. PATIENTS AND METHODS: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥ baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. RESULTS: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P = 0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). CONCLUSION: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP.

The lip in lupus erythematosus.

Lupus erythematosus (LE) frequently compromises the skin, lips and oral mucosa. There is a large body of medical and dental literature about the cutaneous and mucosal lesions of LE, but very little has been written specifically about labial lupus. The lip has a peculiar anatomical and histological architecture, and LE lesions at this site may have some distinct features. This article reviews the existing data and adds some new concepts to the issue of labial lupus in all of its presentations, comparing such lesions to the well-established characterization of cutaneous LE (in acute, subacute and chronic lesions), and highlighting some special clinical features that may enable a better diagnosis and differential diagnosis of lip diseases.

Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B).

BACKGROUND: The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. PATIENTS AND METHODS: Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. RESULTS: A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686). CONCLUSION: In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone.

Hyperhomocysteinemia in patients with Crohn's disease.

BACKGROUND: Thromboembolic complications have been reported in patients with Crohn's disease. Among the contributing factors, hyperhomocysteinemia has been described, although controversial data exist. The aim of our study was to assess the incidence of hyperhomocysteinemia in a nonselected group of patients with Crohn's disease and to determine whether it might represent a risk marker for thrombosis in such patients. METHODS: Fifty consecutive patients were recruited, and clinical and laboratory variables were compared between those without and those with hyperhomocysteinemia. In the latter, gene mutations in N5-N10-methyltetrahydrofolate reductase were searched for, and clinical and laboratory variables were related to hyperhomocysteinemia. The presence/absence of thrombotic episodes in both groups was determined. RESULTS: Both groups had similar clinically active disease, with higher C-reactive protein values found in those with hyperhomocysteinemia. Hyperhomocysteinemia was found in 46 % of patients. Of these, 74 % had moderate, 13 % intermediate, and 13 % severe increase in serum homocysteine levels. No relationship was found between homocysteine levels, and age, vitamin B12 levels, folic acid levels, Crohn's Disease Activity Index score, and CRP values. Gene mutations were found in 5 (22 %) patients, 2 homozygotes and 3 heterozygotes. None of the patients with or without hyperhomocysteinemia had episodes of venous or arterial thrombosis, or stroke. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients with Crohn's disease, and it could be a cofactor for the pathogenesis of thrombotic episodes.

Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial.

BACKGROUND: To evaluate the activity and safety of nonpegylated liposomal doxorubicin (Myocet) when substituted for doxorubicin in the R-CHOP regimen (R-COMP). PATIENTS AND METHODS: Seventy-five elderly patients with diffuse large B-cell lymphoma (DLBCL) were studied. Only patients with left ventricular ejection fraction (LVEF) > or =50% were allowed. R-COMP regimen was administered every 3 weeks for three cycles, followed by additional five cycles in case of complete response (CR) or partial response. RESULTS: From November 2002 to April 2005, 75 patients were registered, of which 72 were evaluated. Median age was 72 years (range 61-83); 56% of patients had high or high-intermediate International Prognostic Index score. Median LVEF at baseline was 61%. Thirty-eight patients had history of abnormal cardiovascular conditions. The overall response rate was 71%, with a CR rate of 57%. After a median follow-up of 33 months, the 3-year overall survival, failure-free survival, and progression-free survival rates were 72%, 39%, and 69%, respectively. Neutropenia (54%) was the most frequent grade 3-4 adverse event (AE); 21% of patients experienced cardiac AEs, graded as 3-4 in 4% of the cases. CONCLUSION: R-COMP is an effective regimen for the treatment of DLBCL in elderly patients, with an acceptable tolerability profile.

Oral manifestations of inflammatory bowel disease: a review based on the observation of six cases.

Inflammatory bowel disease (IBD) comprises two chronic, tissue-destructive, clinical entities: Crohn's disease (CD) and ulcerative colitis (UC), both immunologically based. Bowel symptoms are predominant, but extra-intestinal complications may occur, including involvement of the oral cavity. Oral involvement during IBD includes several types of lesions: the most common are aphthae; uncommon lesions include, among others, pyostomatitis vegetans and granulomatous lesions of CD. Starting with a presentation of six patients with oral manifestations, which were crucial for the final diagnosis of IBD, a review on the subject is presented. Oral involvement in IBD may be previous or simultaneous to the gastrointestinal symptoms. However, in the majority of cases, bowel disease precedes the onset of oral lesions by months or years. In many patients, the intestinal symptoms may be minimal and can go undetected; thus, most authors believe that the bowel must be thoroughly examined in all patients with suspected IBD even in the absence of specific symptoms. Usually, the clinical course of oral lesions is parallel to the activity of IBD; therefore, oral manifestations are a good cutaneous marker of IBD.

Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study.

Acute lymphoblastic leukemia (ALL) in the elderly is characterized by its ominous prognosis. On the other hand, imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), which prompted us to assess the use of imatinib in previously untreated elderly patients. ALL patients aged 55 years or older were given steroids during 1 week. Ph+ve cases were then offered a chemotherapy-based induction followed by a consolidation phase with imatinib and steroids during 2 months. Patients in complete response (CR) after consolidation were given 10 maintenance blocks of alternating chemotherapy, including two additional 2-month blocks of imatinib. Thirty patients were included in this study and are compared with 21 historical controls. Out of 29 assessable patients, 21 (72%, confidence interval (CI): 53-87%) were in CR after induction chemotherapy vs 6/21 (29%, CI: 11-52%) in controls (P=0.003). Five additional CRs were obtained after salvage with imatinib and four after salvage with additional chemotherapy in the control group. Overall survival (OS) is 66% at 1 year vs 43% in the control group (P=0.005). The 1-year relapse-free survival is 58 vs 11% (P=0.0003). The use of imatinib in elderly patients with Ph+ ALL is very likely to improve outcome, including OS.

[High fetal irradiation: about one pregnant woman receiving infradiaphragmatic radiotherapy for Hodgkin lymphoma]. / Irradiation foetale élevée: à propos d'une femme dont la grossesse était méconnue irradiée en sous-diaphragmatique pour un lymphome hodgkinien.

We report the case of a 19-year-old young woman for whom was discovered a pregnancy at the end of the irradiation for a Hodgkin lymphoma (stage IV bone Bb), initially treated by chemotherapy. The radiotherapy delivered 36 Gy in infra-diaphragmatic volumes (lombo-aortic, spleen, L5), beginning in a pregnant patient for less than 4 amenorrhea weeks. The calculated received fetal dose (literature data, measurement with software TPS, measurement on phantom) is high: it's between 2.8 and 5 Gy. With a current follow-up of 4 years since the radiotherapy's end, the patient is in complete remission and her child presents with a normal development for the age, in spite of the infradiaphragmatic irradiation.

Adrenal lymphoma: presentation, management and prognosis.

AIM: This study aimed to identify the clinical, radiological and prognostic features of primary adrenal lymphoma (PAL) in order to diagnose the disease more accurately. MATERIALS AND METHODS: A retrospective multi-centre study was conducted on the clinical, biological and radiological features as well as the treatment and overall survival outcomes in PAL. RESULTS: Between 1994 and 2014, 28 patients from five regions of eastern France were diagnosed with primary adrenal lymphoma. The revealing symptoms were a worsening general state (77%), weight loss (77%) and abdominal pain (42%). Biological features of PAL were almost omnipresent: increased LDH, ß2 microglobulin, CRP or ferritinaemia levels. The PAL was bilateral in 20 cases (71%), adrenal insufficiency was searched for in 11 patients and found in eight (73%). CT scans showed masses of various sizes measuring up to 180 mm. On MRI, the lesions were hypointense in T1 and hyperintense in T2. When done, positron emission tomography with fluorodeoxyglucose (FDG-PET) showed locations not seen on the CT and revealed extra-adrenal locations in 70% of examinations. Adrenalectomy brought no benefit. The overall survival rate was poor (61.9% at 2 years) despite polychemotherapy. CONCLUSION: The clinical presentation of PAL comprised major general symptoms. Adrenal insufficiency was very common in patients with bilateral involvement but was not systematically tested. PET was an efficient examination to visualize extra-adrenal locations. The preliminary results of MRI to distinguish between PAL and adrenocortical carcinoma should be confirmed. Further studies are needed to establish an optimal strategy for the management of these primary adrenal lymphomas.

[A case of de novo acute basophilic leukaemia: diagnostic criteria and review of the literature]. / A propos d'un cas de leucémie à basophiles de novo: critères diagnostiques et revue de la littérature.

We report a case of a de novo acute basophilic leukaemia, revealed by an infectious pneumopathy in a 73 year old man. The full blood count revealed an hyperleucocytosis associated with an unregenerative normocytic normochrom anaemia and a thrombocytopenia. The blood and bone marrow smears showed a mixture of undifferentiated blast cells and basophiloblasts (high nucleo-cytoplasmic ratio, coarse basophilic cytoplasmic granules), along with basophilic precursors and basophilic polymorphonuclears. All the blasts were MPO negative but positive for the toluidine blue metachromatic coloration, which is considered as consistent with basophilic lineage. Immunophenotypic studies showed myeloid blasts, without maturity marker, CD 117 negative and CD203 cytoplasmic positive, the latter known to be highly representative of the basophilic lineage. This very clear-cut phenotype, associated with the morphology of cells, were arguments to ascertain the basophilic lineage of the blasts without the need of electron microscopic study. Cytogenetic and RNA analysis revealed the presence of a Philadelphia chromosome and of a BCR-ABL transcript with the unusual junction e6a2. Thus, imatinib was added to the conventional chimiotherapy and the patient is currently in complete remission. This clinical prompted allows us to review the literature on acute basophilic leukaemia and to state on the different diagnostic criteria of this rare disorder.

Helicobacter pylori-negative duodenal ulcer.

UNLABELLED: PURPOSE PATIENTS AND METHODS: Helicobacter pylori (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in those patients with DU who are HP-negative compared with those who are HP-positive, we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease. At esophagogastroduodenoscopy, antral biopsy specimens were obtained for urease test, culture, and Warthin Starry staining for HP in all patients with DU who did not have active bleeding. RESULTS: Compared with HP-positive patients who had DU, HP-negative patients with DU were more likely to be aspirin users and less likely to have had prior ulcers. HP-positive patients with DU had more severe antral inflammation than HP-negative patients. Whites were more likely to be HP-negative than blacks. HP-negative patients with DU most commonly presented with bleeding, whereas HP-positive patients with DU presented with pain. CONCLUSIONS: Our findings suggest a different mechanism for DUs in patients who are HP-positive versus those who are HP-negative, and this difference might have a bearing on treatment. The absence of HP should lead to a more thorough search for nonsteroidal anti-inflammatory drug/aspirin use, Zollinger-Ellison syndrome, and other potential causes of DUs.

Ulcer risk factors: interactions between Helicobacter pylori infection, nonsteroidal use, and age.

PURPOSE: To evaluate the influence of Helicobacter pylori, nonsteroidal anti-inflammatory drug (NSAID) use, tobacco and alcohol use, age, gender, ethnic group, and the indication for endoscopy on the frequency of gastric and duodenal ulcers in patients referred for upper endoscopy. PATIENTS AND METHODS: One thousand eighty-eight consecutive patients without prior antrectomy or active bleeding at endoscopy who were able to provide a history were interviewed prior to endoscopy, and antral biopsies were performed for H. pylori at endoscopy. Variables were tested for univariate association with duodenal or gastric ulcer and those variables with p < 0.25 were included in the logistic regression model building. RESULTS: One hundred seven patients had duodenal ulcer, 97 had gastric ulcers, and 5 had both. Significant risk factors in the final model for duodenal ulcer were H. pylori, history of previous ulcer, male gender, bleeding, and pain at presentation (p < 0.001), whereas alcohol was associated with a decreased risk (p = 0.026). H. pylori presence (p = 0.011), aspirin use (p = 0.009), and bleeding (p = 0.012) were associated with gastric ulcer in the final model; esophageal symptoms were associated with decreased risk of gastric ulcer (p = 0.003). NSAID use was associated with gastric ulcers only in those over 55 (p < 0.05), especially whites, and in nonwhites without prior ulcer. There was no interaction between H. pylori and NSAIDs. CONCLUSIONS: H. pylori was associated with an increased risk of duodenal and gastric ulcers. Aspirin increases the risk for gastric ulcer in patients of all ages, whereas nonaspirin, nonsteroidal use increases the risk for gastric ulcers to varying degrees in patients over age 55, depending on race and history of ulcer.

Multiphoton switching dynamics of single green fluorescent proteins.

Multi-photon driven photo-switching between dark and bright (fluorescent) states of a green fluorescent protein (GFP) mutant is demonstrated. A single-protein investigation shows the existence of two distinct bright states that display sharp two-photon cross-section bands peaked at 780 nm and at 870 nm. Fluorescence of these two species can be independently switched on and off. These results highlight a new photoconversion pathway for photochromic GFPs and can have significant applications in multi-photon confocal microscopy and in optical data-storage architectures.

Selective fluorescence recovery after bleaching of single E2GFP proteins induced by two-photon excitation.

We report the two-photon excitation and emission or a recently developed green fluorescent protein (GFP) mutant, E(2)GFP. Two main excitation bands are found at 780 and 870 nm. Blinking and irreversible and reversible bleaching were observed. Fluorescence blinking occurs in the millisecond range and has been ascribed to conversions between the neutral, anionic and dark zwitterionic states. Bleaching is observed after approximately 10 to 400 ms depending on the excitation power, and it is probably due to a conversion to a dark state. The striking feature of this GFP mutant is that the fluorescence can be recovered with very high efficiency only upon irradiation at 720 +/- 10 nm. This GFP mutant therefore seems promising as an almost permanent chromophore for two-photon excitation (TPE) microscopy or for applications in single-molecule memory arrays.

Covert versus overt self-recognition in late stage Alzheimer's disease.

Some persons with Alzheimer's disease (AD) lose the ability to recognize themselves, as when they cannot overtly recognize their reflection in a mirror. There is evidence, however, that covert or unconscious self-recognition might be displayed in such individuals. In this study, 3 persons with AD lacking the ability to overtly self-recognize demonstrated multiple instances of unconscious or covert self-recognition. A variety of interventions, inspired by research with prosopagnosics, was implemented to remediate this loss. Interventions enabled all participants to exhibit overt self-recognition, though each did so with the aid of a different intervention. In addition, successful overt self-recognition required a verbal probe and was entirely intervention-dependent: When the intervention was removed, overt self-recognition was lost. Results support a dissociation between explicit-declarative versus implicit-nondeclarative memory systems, and extends this dissociation into the realm of self-recognition in AD.

[Influence of pyridoxal-5'-phosphate on the responses of isolated coronary arteries to adrenaline, in the presense of pyrogallol]. / Influenza del piridossal-5'-fosfato sulle risposte di arterie coronarie isolate all'adrenalina, in presenza di pirogallolo.

The effect of PLP on the adrenaline-induced relaxation of coronary arteries was studied in vitro, after known inhibitor of COMT, Pyrogallol. Relaxation of response to adrenaline were increased by PLP. Pyrogallol potentiated responses of coronary strips to adrenaline and also reduced or abolished the enhancing effects of PLP. It is concluded that PLP enhances the response of coronary smooth muscle to adrenaline by inhibiting a enzymatic pathway for the inactivation of catecholamines.