Malignant evolution of Schnitzler's syndrome--chronic urticaria and IgM monoclonal gammopathy: report of a new case and review of the literature

Schnitzler's syndrome, initially described in 1974 is an uncommon condition defined by chronic urticaria and monoclonal IgM gammopathy. Additional features include fever of unknown origin, elevated ESR, bone pain and frequently a benign clinical course. We conducted a literature search of Medline, EMBASE and Cancerlit and found 56 cases of Schnitzler's syndrome reported to date. The absence of lymphoproliferative disease in this condition is typical, but nine patients have progressed to develop lymphoplasmacytic neoplasias, particularly Waldenstrom's macroglobulinemia (WM). Malignant evolution of Schnitzler's syndrome is a rare complication, but emphasizes the importance of long term follow-up and the need for these patients to undergo periodic assessment of the bone marrow and lymph nodes. Treatment of this condition is difficult, with varying response to corticosteroids and largely unsuccessful results with standard chemotherapy used for WM. We describe a case of Schnitzler's syndrome in a 50-year old man with lymphocytic aggregates in the bone marrow after 9 years of chronic urticaria, fever, arthralgias and bone pain. We review the clinical features and treatment, with emphasis on the hematologic aspects of this unusual condition.     

Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction

In a recent study on head and neck squamous cell carcinoma (HNSCC) cells we found that epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, inhibited activation of the epidermal growth factor receptor (EGFR) and related signaling pathways. Since activation of EGFR signaling pathways is associated with angiogenesis, we examined the effects of EGCG on vascular endothelial growth factor (VEGF) production by YCU-H891 HNSCC and MDA-MB-231 breast carcinoma cell lines, because we found that both of these cell lines display autocrine activation of transforming growth factor-alpha (TGF-alpha)/EGFR signaling and produce high levels of VEGF. Treatment with EGCG inhibited the constitutive activation of the EGFR, Stat3, and Akt in both cell lines. These changes were associated with inhibition of VEGF promoter activity and cellular production of VEGF. Mechanistic studies indicated that inhibition of Stat3, but not mitogen-activated protein kinase kinase (MEK)1 or phosphatidylinositol 3'-kinase (PI3K), significantly decreased VEGF promoter activity. However, the inhibitory effects of a dominant negative Stat3 on VEGF expression was not as strong as that produced by EGCG. An analysis of alternative pathways indicated that EGCG strongly inhibited the constitutive activation of NF-kappa B in both cell lines, and an NF-kappa B inhibitor strongly inhibited VEGF production. These results suggest that EGCG inhibits VEGF production by inhibiting both the constitutive activation of Stat3 and NF-kappa B, but not extracellular-signal-regulated kinase (ERK) or Akt, in these cells. Therefore, EGCG may be useful in treating HNSCC and breast carcinoma because it can exert both antiproliferative and antiangiogenic activities.     

SunghyangJungki-San Ga Pogongyoung inhibits IL-1 mediated tumour necrosis factor-alpha secretion in astrocytes

Astrocytes play an important role in initiating and modulating inflammatory responses within the central nervous system (CNS). Extensive studies in rodents have shown that substance P induces inflammatory cytokine production in astrocytes. In this study we have examined whether an aqueous extract of SunghyangJungki-San Ga Pogongyoung (SSGP) inhibits the secretion of TNF-alpha from primary cultures of rat astrocytes. SSGP (10-1,000 microg/mL) significantly inhibited the TNF-alpha secretion by astrocytes stimulated with lipopolysaccharide (LPS) and substance P (SP). Interleukin-1 (IL-1) has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-alpha secretion from primary astrocytes by SSGP. Treatment with SSGP (10-1,000 microg/mL) to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. Moreover, the secretion of TNF-alpha by LPS and SP in astrocytes was progressively inhibited with an increasing amount of IL-1 neutralizing antibody. Our results suggest that SSGP may inhibit TNF-alpha secretion by inhibiting IL-1 secretion and that SSGP has an antiinflammatory activity in the CNS.     

Personality profiles of patients with dissociative trance disorder in Singapore

This report studies the personality of individuals who suffer from dissociative trance disorder and examines whether the personality profiles could predict the individual's frequency of trance states. A total of 58 cases were given the Eysenck Personality Questionnaire (EPQ) and their personal information harvested from the case notes and through subsequent interviews. The subjects were also reassessed 1 year later to obtain their frequency of trance states. For both sexes, there were lower extraversion scores and higher psychoticism, neuroticism, and lie scores in the sample compared to the Singapore norms. Of the 47 subjects traced, total episodes of trances that occurred over the 1-year period was positively correlated with neuroticism and negatively with extraversion scores. The high lie scores in individuals with dissociative trance disorder could be a reflection of their concern of how others perceive them. The motivation could be that of restoration of self-esteem or "face." The profiles in the EPQ could be used to predict the individual's frequency of trance states. Subjects with personality traits like nervousness, excitability, and emotional instability were more likely to have a higher frequency of trance states.     

Migraine and isolated recurrent vertigo of unknown cause

Chronic recurrent attacks of vertigo, not associated with any auditory or neurological symptoms, are a common reason for referral to our neurotology clinic. Even after an extensive neurotological evaluation, some cases remain undiagnosed. We prospectively evaluated 72 consecutive patients who presented to the clinic with isolated recurrent vertigo of unknown cause. All patients underwent diagnostic evaluation to exclude identifiable causes of isolated recurrent vertigo. We compared the prevalence of migraine, according to the International Headache Society (IHS) criteria, in the isolated recurrent vertigo group, with a sex- and age-matched control group of orthopedic patients. The prevalence of migraine according to IHS criteria was higher in the isolated recurrent vertigo group (61.1%) than in the control group (10%; p < 0.01). Only 16.7% of patients had an abnormal vestibular function test. The most common abnormal finding was a unilateral vestibular weakness to caloric stimulation. Our results suggest that migraine should be considered in the differential diagnosis of isolated recurrent vertigo of unknown cause.     

Effect of transfusion of fresh-frozen plasma on recipients' antibodies to hepatitis B surface antigen and hepatitis B surface antigen status in countries where hepatitis B virus is endemic

BACKGROUND AND OBJECTIVES: Antibodies to hepatitis B virus (HBV) that are passively acquired through transfusions may lead to confusion and inappropriate clinical decisions. We evaluated the effects of transfusing fresh-frozen plasma (FFP) on serological tests for HBV antibodies in patients without such antibodies. MATERIALS AND METHODS: Tests for HBV surface antigen (HBsAg), and for antibodies to HBV surface antigen (anti-HBs) and HBV core antigen (anti-HBc), were carried out using enzyme immunoassay on the FFP and sera of 50 patients transfused with FFP containing anti-HBs. RESULTS: After FFP transfusion, the incidences of 'false' positivity for anti-HBs and anti-HBc were 64% (32/50) and 100% (seven of seven), respectively, and of 'false' negativity for HBsAg was 18.8% (three of 16) in previously positive patients. The post-transfusion seropositivity for antibodies results from passive transmission, whereas the inability to detect HBsAg is the result of decreased detectable levels. CONCLUSIONS: Laboratory staff and clinicians alike should be cautious in interpreting the results of the HBV marker tests in patients who have recently been transfused, and in obtaining specimens for such studies.     

Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction

The vascular endothelium maintains a relatively vasodilated state via the release of nitric oxide (NO), a process that could be disrupted by hyperhomocysteinaemia. Since endothelial dysfunction is associated with increased systemic vascular resistance that is the hallmark of sustained arterial hypertension, we hypothesised that in patients with both hypertension and coeliac disease with hyperhomocysteinaemia (via malabsorption of essential cofactors), treatment of the latter disease could improve blood pressure (BP) control. A single patient with proven sustained hypertension and newly-diagnosed coeliac disease had baseline and post-treatment BP and endothelial function assessed by ambulatory BP monitoring (ABPM) and brachial artery forearm occlusion plethysmography respectively. This 49 year-old woman had uncomplicated sustained hypertension proven on repeated ABPM carried out 6 weeks apart (daytime mean 151/92 mm Hg and 155/95 mm Hg), and sub-clinical coeliac disease (gluten-sensitive enteropathy). Initial assessments revealed raised homocysteine levels with low normal vitamin B(12) level. It was likely that she had impaired absorption of essential cofactors for normal homocysteine metabolism. She adhered to a gluten-free diet and was give oral iron, folate and B(6) supplementations as well as B(12) injections for 3 months. Her BP had improved by 6 months and normalised by 15 months (daytime ABPM mean 128/80 mm Hg). There was parallel restoration of normal endothelial function with normalisation of her homocysteine levels. These observations suggest that sub-clinical coeliac disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of aetiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.