LOW MOLECULAR WEIGHT IgM IN B CELL LYMPHOPROLIFERATIVE DISORDERS

Circulating low molecular weight (LMW) IgM was demonstrated in five of 38 patients with B cell lymphoproliferative disorders. These five patients all had malignant disease and could be subdivided into two groups. In the first group were three patients, each with an associated serum IgM paraprotein; two had Waldenstrom's macroglobulinemia. and one lymphocytic lymphoma. The two patients of the second group did not have IgM paraproteins; one had lymphocytic lymphoma and one chronic lymphocytic leukemia. Both these patients also had acquired C1 esterase inhibitor deficiency, a previously recognised association with circulating LMW IgM. None of the 16 patients with benign IgM macroglobulinemia had circulating LMW IgM. In those positive sera with LMW IgM this moiety contributed between 10.5% and 37.5% of the total IgM. There was no apparent association between LMW IgM and total IgM levels, kappallambda typing or the presence of Bence Jones proteinuria. but rheumatoid factor, immune complexes and cryoglobulins occurred in many of the sera which contained LMW IgM. Pokeweed mitogen stimulated peripheral blood mononuclear cells from two patients with circulating LMW IgM secreted considerable quantities of this moiety in vitrobut this did not occur in two patients with benign IgM macroglobulinemia. We conclude that LMW IgM is found in the malignant but riot the benign forms of B cell lymphoproliferative disorders and is frequently associated with other serological abnormalities. The basic abnormality causing defective IgM polymerisation in these disorders is obscure.     

Splenectomy as an adjuvant measure in the treatment of severe aplastic anaemia

The role of splenectomy in aplastic anaemia (AA) is controversial. The hazards of operating on a severely pancytopenic patient, the fear of compromising the patient’s immune function, and the improvement of non-surgical treatment have made splenectomy unpopular in this disease. We have evaluated positive and adverse effects of splenectomy in 80 patients with severe aplastic anaemia (SAA) treated with antilymphocyte globulin (ALG) (group A), using 52 nonsplenectomized ALG patients as controls (group B). All patients survived the operation. Nonfatal complications of surgery occurred in 10 (12.5%). Splenectomy induced a significant increase of peripheral blood neutrophils, reticulocytes and platelets within 2 weeks, followed by a continuous increase of all values over the following weeks. 28/132 patients (21%) developed a late clonal disorder of haemopoiesis, paroxysmal nocturnal haemoglobinuria (PNH) or myelodysplastic syndrome (MDS), or both. Their incidence was identical in groups A and B. 13/28 (59%) died, 10/17 (59%) in group A and 3/11 (27%) in group B (not significant (n.s.)). Overall probability of survival at 18 years after ALG was 51 ± 6% for group A and 61 ± 7% for group B (n.s.). We conclude that splenectomy in AA is safe. It induces an immediate increase of peripheral blood counts and, thereafter, a continuous improvement of haemopoiesis. It does not increase the incidence of late clonal complications but has a borderline effect on mortality from these disorders. Splenectomy should be reconsidered in selective nontransplanted patients who have prolonged transfusion requirements despite otherwise optimal treatment.     

Adult “idiopathic” extrahepatic venous thrombosis

The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a latent myeloproliferative disorder has been reported in adults with idiopathic EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The idiopathic group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17–70) with a median follow up of 96 months (19–372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance.Supported by R Farini Foundation for Gastroenterology Research.     

Influenza vaccine in chronic lymphoproliferative disorders and multiple myeloma

OBJECTIVE: Vaccination against influenza in patients with chronic lymphoproliferative disorders (CLPD) and multiple myeloma (MM) is still a matter of clinical uncertainty. The aim of this study was to determine the safety, immunogenicity and clinical response to a commercially available vaccine against influenza in a group of such patients. METHODS: Thirty-four patients with CLPD and MM and 34 immunologically normal subjects were vaccinated with the same vaccine against influenza. Patients were observed during the epidemic season from October 1999 to April 2000, and monitored for side-effects of the vaccine, seroprotection and seroconversion after vaccination. The prevaccination level of immunoglobulins was also determined. Occurrence of influenza episodes was demonstrated with the positive isolation of a viral strain from a pharyngeal swab. RESULTS: No patient had untoward reactions to the vaccine used. Seroconversion and seroprotection were up to the standard established by the European Agency for the Evaluation of Medicinal Products. Only one patient developed influenza during follow-up. CONCLUSIONS: Influenza vaccine is effective and well tolerated in patients with CLPD and MM. No contraindications exist for its use, and it should become a routine practice, in order to prevent serious complications during the influenza epidemic season.     

Treatment of coagulation inhibitors with extracorporeal immunoadsorption (Ig-Therasorb)

Coagulation inhibitors may occur as alloantibodies in patients with congenital factor deficiencies or as autoantibodies in patients with a previously normal coagulation. We treated 10 patients with factor VIII inhibitors (three haemophiliacs and seven patients with acquired factor VIII inhibitors) and one patient with a factor V inhibitor using extracorporeal immunoadsorption to immobilized antibodies against human immunoglobulins (Ig-Therasorb). The initial inhibitor titre was between 18 BU/ml and 540 BU/ml. Nine patients had signs of bleeding. Eighty-nine immunoadsorption sessions were performed in the 11 patients (8.1 +/- 5.1 per patient), each processing 6980 +/- 880 ml of plasma in 3.8 +/- 0.5 h. The mean reduction of the inhibitor titre was 71.9 +/- 19.4% per session. Serum IgG, IgA and IgM levels decreased by 68.7 +/- 10.1%, 55.7 +/- 12.7% and 48.6 +/- 11.1% respectively. In two haemophiliac patients, an initial titre reduction prior to an immune tolerance protocol was performed. Another haemophiliac patient was treated because of acute cerebral bleeding. In six out of eight patients with acquired inhibitors, a durable elimination was achieved within a median of 18 d. Treatment was safe and well-tolerated and seems to be a promising method in the treatment of patients with coagulation inhibitors, especially when a fast inhibitor titre reduction is necessary.     

神经精神狼疮的诊断和治疗

目的对神经精神狼疮患者的诊断和治疗进行临床总结。方法对83例SLE患者进行回顾性分析总结。42例为神经精神狼疮(NPSLE)患者;41例为无临床神经精神症状的SLE对照组。对两组病人实验室检查,包括血液:细胞计数、电解质、肝肾功能、血糖、血脂、血沉;免疫学检测:补体、抗dsDNA抗体、可提取的核抗原(ENA)、间接荧光抗核抗体(IFANA)、抗磷脂抗体等;尿:尿常规、24h尿蛋白;脑脊液:常规、生化、脑脊液压力、细菌、霉菌学检查、免疫球蛋白检测;影像学检查:脑电图(EEG)、脑CT、脑核磁共振。治疗:对于昏迷、癫痫大发作、急性意识障碍的重症NPSLE患者治疗的甲泼尼龙(MP)起始剂量约200~500mg/d;对于一般认知障碍、磷脂抗体综合征、局灶性NPSLE(FNPSLE)的泼尼松剂量约1~2mg·kg-1·d-1。当MP剂量渐减至100mg/d应及时适当应用环磷酰胺(CTX)、甲氨蝶呤(MTX)、硫唑嘌呤(AZA)等免疫抑制剂。统计学分析:Fisher's精确试验和t检验。结果临床症状方面,NPSLE和SLE对照组比较,面部红斑(71%∶44%)和皮肤/胃肠道血管炎的发生率(67%∶27%)差异有显著性(P<0.001)。血清学检测,两组比较,仅抗磷脂抗体(aCL)和/或抗β2糖蛋白1(β2GP1)差异有显著性,其发生率分别为43%和22%(P<0.05)。42例NPSLE患者,其中33例为弥漫性NPSLE(DNPSLE),9例为F     

Barrett's esophagus: Pathogenesis,epidemiology, functional abnormalities,malignant degeneration,and surgical management

Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125-fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials.     

Platelet-rich plasma serotonin levels in chronic myeloproliferative disorders: evaluation of diagnostic use and comparison with the neutrophil PRV-1 assay

In a prospective study of 109 subjects, an enzyme-linked immunosorbent assay (ELISA) was used to measure platelet-rich plasma (PRP) serotonin levels in patients with polycythaemia vera (PV; n = 27), essential thrombocythaemia (ET; n = 14), myelofibrosis with myeloid metaplasia (MMM; n = 30), secondary or spurious polycythaemia (SP; n = 22) and controls (n = 16). Nine study subjects who were taking a selective serotonin reuptake inhibitor (SSRI) all displayed a markedly decreased PRP serotonin level (median, 24.2 ng/10(9) platelets; range, 0-49.3) and were therefore excluded from further analysis. Among the remaining 100 subjects, the median and range of PRP serotonin levels, in ng/10(9) platelets, was significantly lower in MMM (89.5; 0-278.3), PV (204.8; 0-496.0) and ET (385.3; 136.8-1025.7) compared with both SP (608.8; 369.0-1780.1) and controls (567.2; 359.9-1071.1). Neutrophil polycythaemia rubra vera-1 (PRV-1) expression was concurrently assayed by real-time polymerase chain reaction in 69 patients (23 PV, 17 SP, 12 ET, seven MMM, 10 controls). PRP serotonin measurement performed as well as the PRV-1 assay in distinguishing PV from SP (93% vs. 86% test accuracy). The current study suggests that PRP serotonin concentration might be considered as one of the several biological markers that complement each other for the diagnosis of PV.     

Expiratory-Synchronized Sleep in a Quadriplegic Patient Using Inspiratory Neck Muscles To Breathe

In a patient with C3 quadriplegia causing complete diaphragm paralysis who developed inspiratory neck muscles (INM) hypertrophy to sustain ventilation, spontaneous breathing deeply altered sleep architecture, relegating sleep to the expiratory phase of the ventilatory cycle. A polysomnographic recording performed during mechanical ventilation (without INM activity), showed that sleep was abnormal but unaffected by the respiratory cycle. During spontaneous breathing, the polygraphic recordings showed expiratory microsleep episodes, with inspiratory arousals synchronous to bursts of INM activity. This case report illustrates the powerful adaptability of the respiratory and sleep control systems to maintain each vital function.     

Hair analysis of antidepressants and antipsychotics—Overview of quantitative data

Antidepressant and antipsychotic drugs are regularly encountered in different aspects of forensic toxicology, and some cases require the examination of hair samples. In this study, common antidepressant and antipsychotic drugs regarding hair concentrations over the past decades were reviewed. Although numerous publications around method validations, case reports, or controlled dose studies were found, apparently there is a lack of comprehensive data for many substances. Information on the hair length and dosage across the publications varied largely, and case numbers were generally low except for several retrospective controlled dose studies. Many substances were described only in method validations or case reports, and data were obtained from small case numbers. On the contrary, clozapine, haloperidol, amitriptyline, nortriptyline, risperidone and its metabolite, methylphenidate, citalopram, chlorpromazine, chlorprothixene, and quetiapine had a well‐founded database as these substances were investigated in controlled dose studies with higher case numbers. Given the advancements made in analytical techniques over the past years, gas chromatography–mass spectrometry and liquid chromatography with tandem mass spectrometry techniques were the methods of choice and allowed the detection of chemical compounds at low concentrations. The controversy around a potential use of hair analysis to estimate the dosage remains as dose‐concentration studies provided divergent results. A harmonization on the investigated hair length as well as on the extraction protocol would be of favor to achieve better comparability. Although hair analysis research focused mainly on drug abuse, availability of more data on antidepressants and antipsychotics would help to gain better knowledge and assist other forensic investigators.