Evidence for a polyclonal nature of the cell infiltrate in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

Summary. Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease, is rare histiocytic disorder of known origin which shares several cell markers with Langerhans'cell histiocytosis (LCH). Although Rosai-Dorfman cells exhibit an aberrant immunophenotype, the indolent clinical course of SHML suggests a reactive disorder rather than a neoplastic process. Until recently this was prevailing opinion concerning LCH also, but recent studies have detected clonal histiocytes in all forms of this latter condition, which is therefore considered a clonal neoplastic disorder with highly variable biologial behaviour. To determine whether the histiocytic proliferation in SHML is polyclonal or clonal we used X-linked polymorphic loci to assess clonality in lesional tissues in two women. Polymorpic regions of the human androgen receptor (HUMARA) locus were amplified by polymerase chain reaction (PCR) analysis. The HUMARA locus was informative in both cases and, following digestion with methylation-sensitive enzymes, typical polyclonal X-inactivation patterns were observed. Since abnormal cells accounted for >90% lesional tissue cells, we conclude that Rosai-Dorfman histiocytic proliferation was polyclonal in the women studied.     

Molecular basis of non-alcoholic fatty liver disease and metabolic syndrome in a subset of South Asians

International Journal of Diabetes in Developing Countries - Metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are emerging threats in Pakistan. The prevalence of MetS is...     

Isolated H. pylori duodenal colonization and idiopathic duodenal ulcers

OBJECTIVE: To evaluate whether some duodenal ulcers (DU) classified as idiopathic according to standard criteria may be causally related to isolated duodenal colonization by H. pylori. METHODS: We studied consecutive ambulatory patients undergoing upper gastrointestinal endoscopy in a secondary care setting. Gastric and duodenal biopsies for diagnosing H. pylori infection were taken from all patients. Independently from the findings of duodenal biopsies, DU patients without gastric infection were classified as having idiopathic ulcers, and underwent urea C13 breath test and subsequent eradication therapy. Endoscopy was repeated 6 months after eradication treatment. RESULTS: Among 608 DU patients, 42 (6.9%) were classified as idiopathic: 24 (3.9%) were free from gastric and duodenal infection (group A) and 18 (3.0%) (group B) had isolated duodenal colonization. Urea C13 breath test was positive in one (4.2%) group A patient and in 3 (16.7%) group B patients. After eradication therapy, DU were detected in 14 out of 20 group A patients (70%) (four patients did not perform control endoscopy) and in 2 group B patients (11.1%): OR 18.66, 95% CI 3.23-107.82, P= 0.002. The difference was still detectable after multivariate analysis taking into account possible confounding factors: OR 15.79, 95% CI 2.48-100.53, P= 0.001. CONCLUSIONS: Isolated duodenal colonization by H. pylori is detectable in a substantial proportion of patients with so-called idiopathic DU, and eradication therapy is effective in these patients.     

Improvement in patient‐reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti–tumor necrosis factor therapy

Objective

To assess the effects of treatment with rituximab plus methotrexate on patient‐reported outcomes in patients with active rheumatoid arthritis (RA) who experienced inadequate response to anti–tumor necrosis factor therapy.

Methods

Patients with active RA were randomly assigned to rituximab (1,000 mg on days 1 and 15) or placebo. The primary end point was the proportion of patients with an American College of Rheumatology 20% response at week 24. Additional goals were to assess treatment effects on pain, fatigue, functional disability, health‐related quality of life, and disease activity by comparing mean changes between groups. The analysis was conducted in the intent‐to‐treat population. The proportion of patients who achieved the minimum clinically important difference on the Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐F), and Short Form 36 (SF‐36) was determined.

Results

Rituximab patients had statistically significantly greater pain relief. The FACIT‐F showed significantly greater improvement in rituximab patients than placebo patients from weeks 12 through 24. Mean improvement from baseline in functional disability (measured by the HAQ DI) was significantly greater in rituximab patients from weeks 8 to 24. The mean ± SD change from baseline for the SF‐36 Physical Component Score was 6.64 ± 8.74 for rituximab patients and 1.48 ± 7.32 for placebo patients (P < 0.0001). The mean change from baseline for the SF‐36 Mental Component Score was 5.32 ± 12.41 for rituximab patients and 2.25 ± 12.23 for placebo patients (P = 0.0269).

Conclusion

Rituximab produced rapid, clinically meaningful, and statistically significant improvements in patient‐reported pain, fatigue, functional disability, health‐related quality of life, and disease activity. These effects were sustained throughout the study.     

Evidence for a physiological reduction in brain dopamine but not norepinephrine metabolism during the preovulatory phase in normal women

To investigate the role of brain catecholamine (CA) activity in the mechanisms related to physiological ovulatory function, we used high-performance liquid chromatography with electrochemical detector to measure the levels of urinary dopamine (DA), norepinephrine (NE), epinephrine (E), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and total 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a group of 12 normal women during both the early follicular and pre-ovulatory phases of the menstrual cycle. The mean (+/- SEM) concentrations of HVA and DOPAC were significantly lower (P less than 0.001) during the pre-ovulatory phase than during the early follicular phase, whereas those of DA, NE, E, VMA and total MHPG were unaltered. A significant negative correlation between urinary HVA and plasma LH (r = -0.70, P less than 0.01) was also found during the pre-ovulatory period, whereas no significant negative correlations were found between urinary HVA and plasma PRL, progesterone and oestradiol. These data show: 1) reduced brain DA activity and 2) unchanged brain NE activity at the time of the midcycle surge in normal women, suggesting a physiological variation of the central DA metabolism in ovulatory function.