Paediatric nodal marginal zone B‐cell lymphadenopathy of the neck: a Haemophilus influenzae‐driven immune disorder?

Many hyperplasias and lymphomas of marginal zone B‐cells are associated with infection. We identified six children and one adolescent with cervical lymphadenopathy showing prominent polyclonal nodal marginal zone hyperplasia (pNMZH) and four adolescents with monoclonal paediatric nodal marginal zone lymphoma (pNMZL). The clonality status was assessed using BIOMED‐2‐IG PCR analysis. Haemophilus influenzae was identified in all six cases of pNMZH that could be tested by direct culture (N = 3) or a very sensitive PCR for the H. influenzae gyrase gene in frozen materials (N = 5). H. influenzae was not detected in three pNMZLs and 28 non‐specific reactive cervical lymph nodes of age‐matched controls, except for a single control node that was obtained during oropharyngeal surgery for a cleft palate showing very low copy numbers of H. influenzae. pNMZH patients were younger than pNMZL patients (median age 12 versus 21 years). pNMZH showed a prominent nodular appearance with variable fibrosis without acute inflammation. Within the nodules, the expanded germinal centres and variably sized marginal zones were colonized by activated B‐cells with weak expression of IgD and lack of CD10 and/or BCL6 expression. Some areas showed skewed light chain expression in plasma cells (4/5 cases lambda). In four cases tested, this was confirmed by flow cytometry for surface Ig (3/4 cases lambda). In contrast, pNMZL showed more extensive expansion of marginal zones by centrocytoid cells and often expression of BCL2 protein. Several H. influenzae strains are known to interact with the constant part of IgD on human B‐cells, leading to their polyclonal proliferation and activation. We speculate that in vivo stimulation of IgD+ marginal zone B‐cells by this bacterium may be implicated in this particular lymphadenopathy that should be distinguished from monoclonal pNMZL. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Rectal compliance as a routine measurement

PURPOSE: The clinical impact of rectal compliance and sensitivity measurement is not clear. The aim of this study was to measure the rectal compliance in different patient groups compared with controls and to establish the clinical effect of rectal compliance. METHODS: Anorectal function tests were performed in 974 consecutive patients (284 men). Normal values were obtained from 24 controls. Rectal compliance measurement was performed by filling a latex rectal balloon with water at a rate of 60 ml per minute. Volume and intraballoon pressure were measured. Volume and pressure at three sensitivity thresholds were recorded for analysis: first sensation, urge, and maximal toleration. At maximal toleration, the rectal compliance (volume/pressure) was calculated. Proctoscopy, anal manometry, anal mucosal sensitivity, and anal endosonography were also performed as part of our anorectal function tests. RESULTS: No effect of age or gender was observed in either controls or patients. Patients with fecal incontinence had a higher volume at first sensation and a higher pressure at maximal toleration (P=0.03), the presence of a sphincter defect or low or normal anal pressures made no difference. Patients with constipation had a larger volume at first sensation and urge (P<0.0001 andP<0.01). Patients with a rectocele had a larger volume at first sensation (P=0.004). Patients with rectal prolapse did not differ from controls; after rectopexy, rectal compliance decreased (P<0.0003). Patients with inflammatory bowel disease had a lower rectal compliance, most pronounced in active proctitis (P=0.003). Patients with ileoanal pouches also had a lower compliance (P<0.0001). In the 17 patients where a maximal toleration volume<60 ml was found, 11 had complaints of fecal incontinence, and 6 had a stoma. In 31 patients a maximal toleration volume between 60 and 100 ml was found; 12 patients had complaints of fecal incontinence, and 6 had a stoma. Proctitis or pouchitis was the main cause for a small compliance. All 29 patients who had a maximal toleration volume>500 ml had complaints of constipation. No correlation between rectal and anal mucosal sensitivity was found. CONCLUSION: Rectal compliance measurement with a latex balloon is easily feasible. In this series of 974 patients, some patient groups showed an abnormal rectal visceral sensitivity and compliance, but there was an overlap with controls. Rectal compliance measurement gave a good clinical impression about the contribution of the rectum to the anorectal problem. Patients with proctitis and pouchitis had the smallest rectal compliance. A maximal toleration volume<60 ml always led to fecal incontinence, and stomas should be considered for such patients. A maximal toleration volume>500 ml was only seen in constipated patients, and therapy should be given to prevent further damage to the pelvic floor. Values close to or within the normal range rule out the rectum as an important factor in the anorectal problem of the patient.Drs. Sloots and Poen were supported by a grant from Janssen-Cilag. Presented at the meeting of the Dutch Society of Gastroenterology, Veldhoven, the Netherlands, October 7 to 8, 1999.     

Platelet-derived growth factor concentrations in platelet-poor plasma and urine from patients with myeloproliferative disorders

Our enzyme-linked immunosorbent assay (ELISA) for measuring human platelet-derived growth factor (PDGF) detects nanogram quantities (ranging from 0.007 to 16 ng/100 microL) in purified PDGF standards. This assay is sensitive enough for studying plasma and urine. The range in normal volunteers was 0.6 to 2.3 micrograms/L for platelet-poor plasma and 1.4 to 3.3 micrograms/L for urine. We determined PDGF levels in the circulation (outside platelets) in patients with myeloproliferative diseases. Platelet-poor plasma and urine PDGF were significantly elevated in patients with myelofibrosis (6.2 +/- 2.0 micrograms/L for plasma; 7.8 +/- 2.4 micrograms/L for urine) and essential thrombocythemia (5.5 +/- 1.5 micrograms/L for plasma; 11.4 +/- 2.2 micrograms/L for urine), but not in patients with chronic myelogenous leukemia (2.1 +/- 0.4 micrograms/L for plasma; 2.8 +/- 1.2 micrograms/L for urine). Polycythemia vera produced an intermediate pattern: although plasma PDGF was within the normal range (2.1 +/- 0.2 micrograms/L), urine levels were increased (3.7 +/- 0.6 micrograms/L). These results show that PDGF is increased in the circulation in some but not all myeloproliferative diseases, and suggest that this is due to abnormal in vivo release from either megakaryocytes in the bone marrow or circulating platelets.     

High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors

Eight-five consecutive patients with relapsed or refractory Hodgkin's disease (HD) underwent high-dose chemotherapy or chemo/radiotherapy followed by autologous bone marrow (ABMT) and/or peripheral blood stem cell (PBSC) transplantation. Two preparative regimens were used. Twenty- two patients (26%) without prior radiation received fractionated total body irradiation (FTBI) 1,200 Gy in combination with high-dose etoposide (VP-16) 60 mg/kg and cyclophosphamide (CTX) 100 mg/kg. Sixty- three patients (74%) with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. The median age was 32 years (range, 16 to 56). The median number of prior chemotherapy regimens was three (range, 1 to 7). Forty-three patients (51%) received transplants in first relapse or second complete remission (CR), whereas 33 (39%) received transplants after second or subsequent relapse. All relapsed patients, except one, received conventional salvage chemotherapy and/or radiotherapy in an attempt to reduce tumor bulk before transplant. At the time of analysis in April 1994, fifty-seven patients (67%) are alive, including 44 (52%) in continuous CR, with a median follow-up for the surviving patients of 28 months (range, 7 to 66). Thirty patients (35%) relapsed at a median of 9 months (range, 1 to 43). Eleven patients (13%) died of transplant-related complications including veno- occlusive disease of the liver (VOD) in five, acute and late interstitial pneumonitis in three, graft failure in one, cerebral hemorrhage in one, and therapy-induced myelodysplasia (MDS)/acute leukemia in one patient. At a median follow-up of 25 months (range, 0.6 to 66), the cumulative probability of 2-year overall and disease-free survival (DFS) of all 85 patients is 75% (95% confidence interval [CI] 64% to 84%) and 58% (95% CI 47% to 69%), respectively. Three independent prognostic variables were identified by univariate analysis: number of prior chemotherapy regimens, prior radiotherapy, and extranodal disease at ABMT. Multivariate stepwise Cox regression identified the number of prior chemotherapy regimens as the only significant prognostic factor predicting for both relapse and DFS. There were no significant differences in the outcome of the treatment between the two preparative regimens. Our results confirm that high- dose therapy and ABMT is an effective therapy for patients with relapsed or refractory HD. Earlier transplantation is recommended before the development of drug resistance and end organ damage that results from repeated attempts of salvage therapy.     

Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa

Alterations in phenotype and function of intestinal macrophages occur in inflammatory bowel disease (IBD) but it is unclear whether these changes result from the recruitment of circulating monocytes to the intestine or from proliferation of resident intestinal macrophages. We sought to demonstrate the arrival of blood monocytes, the precursors of macrophages, in IBD mucosa. Peripheral blood mononuclear cells were isolated from 23 patients with clinically active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two infective colitis), then radiolabelled with ^99mtechnetium (Tc)-stannous colloid (n=13) or ¹¹¹indium (In)-oxine (n=10) before re-injection and abdominal scanning. Four patients had demonstrable intestinal monocyte uptake using [^99mTc]-stannous colloid, while six [¹¹¹In]-oxine-labelled monocyte scans were positive. Uptake sites correlated with actively inflamed regions. Patients demonstrating monocyte uptake had been treated with corticosteroids for a significantly (P < 0.02) shorter duration (median 3 vs 20 days) than those with negative scans. There was no significant difference between positive and negative scans for disease category, clinical or histological disease activity, or radioisotope used. Biopsies of inflamed mucosa from two patients suffering ulcerative colitis who had positive scans showed a high proportion of CD14-positive macrophages, 4–9% of which contained autoradiographic grains. These results demonstrate that blood monocytes are recruited to the mucosa of actively inflamed bowel, and suggest that this process may be inhibited by corticosteroids. Moreover, the phenotype of the recently-arrived monocytes indicates their susceptibility to stimulation by lipopolysaccharide, and suggests a mechanism for the continuing inflammation in the bacterial product-rich milieu of IBD.     

Factor VIII/von Willebrand factor protein: sensitivity of periodic acid Schiff stain to carbohydrate deficiency

We have investigated the periodic acid Schiff (PAS) Coomassie staining ratio of the human factor VIII/von Willebrand factor (fVIII/vWf) protein. The PAS-Coomassie staining ratio is consistent over 8 days. The PAS-Coomassie ratio of fVIII/vWf protein purified from different starting materials does not appear to be significantly different. The PAS stain can detect as little as 300 ng of carbohydrate in the fVIII/vWf protein. Desialation did not affect the PAS-Coomassie ratio, while removal of penultimate galactose resulted in a marked reduction in the PAS-Coomassie ratio. This reduction was further accentuated with the removal of N-acetylglucosamine. The smaller multimers of the fVIII/vWf protein have a reduced sialic acid and PAS-Coomassie staining ratio. This difference does not appear to be related to the sialic acid deficiency but may be related to the distribution or organization of the carbohydrate moieties on the smaller fVIII/vWf multimers.     

目平湖洲滩钉螺的消长及影响因素

目的探讨目平湖洲滩钉螺的消长及影响因素,为控制或消灭钉螺提供科学依据。方法选择目平湖五一村垸外洲滩为试点,收集当地2002-2007年的气象、水位资料,现场观察各年度的钉螺分布、消长及环境变化情况,分析钉螺分布的特点及其与气象、水位、环境变化的关系。结果钉螺分布服从负二项分布,活螺平均密度和年降雨量有显著相关关系（r=0．822,P〈0．01）,其回归方程为Y活螺密度=-24．552＋0．066X降雨量。2003-2005年,各年度气温、湿度、降雨量和日照时间无明显变化,钉螺密度无显著性差异（P〉0．05）。2006年气温、湿度、日照时间与2003-2005年无明显差异（P〉0．05）,但降雨量减少（3、8～9月）、水位明显下降（8～11月）;同时,2005年洲滩进行了开沟抬垅、封洲植树等人工改造。2006年开始钉螺密度显著下降、钉螺死亡率明显上升（P〈0．01）。结论目平湖（西洞庭湖）每年的气温、湿度、日照时间相对稳定,影响本地洲滩钉螺分布及消长的主要因素是降雨量和地理环境变化。     

Low-resolution brain electromagnetic tomography (LORETA) identifies brain regions linked to psychometric performance under modafinil in narcolepsy

Low-resolution brain electromagnetic tomography (LORETA) showed a functional deterioration of the fronto-temporo-parietal network of the right hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil. The aim of this study was to determine the effects of modafinil on cognitive and thymopsychic variables in patients with narcolepsy and investigate whether neurophysiological vigilance changes correlate with cognitive and subjective vigilance alterations at the behavioral level. In a double-blind, placebo-controlled crossover design, EEG-LORETA and psychometric data were obtained during midmorning hours in 15 narcoleptics before and after 3 weeks of placebo or 400 mg modafinil. Cognitive investigations included the Pauli Test and complex reaction time. Thymopsychic/psychophysiological evaluation comprised drive, mood, affectivity, wakefulness, depression, anxiety, the Symptom Checklist 90 and critical flicker frequency. The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were performed too. Cognitive performance (Pauli Test) was significantly better after modafinil than after placebo. Concerning reaction time and thymopsychic variables, no significant differences were observed. Correlation analyses revealed that a decrease in prefrontal delta, theta and alpha-1 power correlated with an improvement in cognitive performance. Moreover, drowsiness was positively correlated with theta power in parietal and medial prefrontal regions and beta-1 and beta-2 power in occipital regions. A less significant correlation was observed between midmorning EEG LORETA and the MSLT; between EEG LORETA and the ESS, the correlation was even weaker. In conclusion, modafinil did not influence thymopsychic variables in narcolepsy, but it significantly improved cognitive performance, which may be related to medial prefrontal activity processes identified by LORETA.     

Langzeiteffekte der Unterkieferprotrusionsschiene IST®

Background

Mandibular advancement devices (MAD) are well established in the treatment of snoring (SN) and sleep-disordered breathing (SDB). The aim of the present study was to investigate the long-term effects and side effects of the IST® (intra-oral snoring therapy) device in SN and SDB as well as patients’ compliance.

Methods

A total of 60 patients, who had received the IST® device in the sleep laboratory, were sent questionnaires after 2 years of treatment.

Results

The questionnaires were returned by 44 patients (33 males), aged 43–83 years (m±sd 63±10), who had been using the IST® for 24–75 (32±17) months; 77% were still using it regularly. Based on a grading system (1=best, 5=worst), 34% rated the tolerability of the IST® with 1, 25% with 2, 29.5% with 3, 4.5% with 4, and 7% with 5. Snoring heard by the partner was reported by 26%—compared to 93% before treatment. The following scores that had already been evaluated in the sleep lab were significantly improved (p<0.01) by the IST®: Pittsburgh Sleep Quality Index (7.6±3.6 to 5.1±2.7), Epworth Sleepiness Scale (9.1±4.3 to 8.4±4.0; n.s.), SAS anxiety scale (30.6±6.4 to 26.5±4.6), SDS depression scale (32.3±7.7 to 28.7±6.9), and the IRLSSG restless legs syndrome scale (7.2±8.5 to 3.8±5.3). Transient side effects comprised salivation (59%), dry mouth (53%), temporo-mandibular joint pain (38%), toothache (35%), gingival pain (27%), muscular pain (21%), occlusive changes (21%), mandibular joint clicks (18%), and earache (15%).

Conclusion

The IST® device is reported as still being used by 77% of the patients after an average of 32 months. The patients describe a clinically relevant improvement in SN as well as a normalization of sleep quality and clinical symptoms with only occasional side effects.     

The use of opioids at the end of life: the knowledge level of Dutch physicians as a potential barrier to effective pain management

Background  

Pain is still one of the most frequently occurring symptoms at the end of life, although it can be treated satisfactorily in most cases if the physician has adequate knowledge. In the Netherlands, almost 60% of the patients with non-acute illnesses die at home where end of life care is coordinated by the general practitioner (GP); about 30% die in hospitals (cared for by clinical specialists), and about 10% in nursing homes (cared for by elderly care physicians).