Granulomatous and lymphocytic hypophysitis – are they immunologically distinct?

Hypophysitis includes three histopathologically distinct entities – granulomatous, lymphocytic and xanthomatous forms. Etiopathogenesis and the immunological differences among these is not well characterized. This study aims to explore the immunopathogenesis of granulomatous and lymphocytic forms of hypophysitis. Demographic, clinical, endocrine function and radiological features of 33 histologically confirmed cases of hypophysitis were reviewed. Immunophenotyping of inflammatory component was performed in 13/33 cases. Visual disturbances (46%), headache (36%), polyuria/polydipsia (6%), menstrual disturbance (6%) and galactorrhoea (6%) were the frequent presenting symptoms. Endocrine abnormalities were noted in 11/18 cases evaluated (61%). Hypothyroidism was the most common endocrine abnormality (33.33%) followed by hyperprolactinaemia (22%) and hypocortisolism (16.66%). On neuroimaging, sellar mass with variable contrast enhancement was observed. On histology, granulomatous hypophysitis (GH) was more common (84.84%) than lymphocytic hypophysitis (LH) (15.15%). In GH, the infiltrate had almost equal proportions of CD3+ T cells and CD68+ histiocytes. Cytotoxic T cells (CD8+) predominated [CD4:CD8 < 1]. CD20+ B cell component ranged from <5% to 50%. Fibrosis, necrosis and giant cells accompanied GH. LH in contrast, had CD4+ T‐helper cell predominance [CD4: CD8 > 1]. CD68+ histiocytes constituted <20% and CD20+ B cells, 5–40% of the infiltrates. In conclusion, GH revealed cytotoxic T cell and histiocyte rich infiltrate in contrast to CD4+ T‐cell predominance in LH suggesting that the two forms have distinct immunological mechanisms in evolution, an autoimmune process in LH and type IV hypersensitivity response in GH.     

Effect of acute environmental heat stress on urinary water and electrolyte excretion in the rat

Plasma cortisol and urinary excretion of water, sodium, potassium, calcium and magnesium have been studied in the rat after application of heat stress. There was a significant increase in plasma cortisol level after exposure to heat. During heat stress complete cessation of urine formation was observed. In the next 30 min there was statistically significant increase in the urinary excretion of water, sodium and calcium but not of potassium and magnesium. Urinary calcium/magnesium ratio was also significantly elevated. The increase in urinary water and electrolyte excretion seemed to be mediated through prostaglandins since it could be abolished by administration of indomethacin prior to the application of heat stress. On the basis of these results, the possible role of heat stress in the genesis of urolithiasis has been discussed.     

The fludarabine,cytarabine, and granulocyte colony‐stimulating factor (FLAG) chemotherapy regimen is an alternative to anthracycline‐based therapy for the treatment of acute myeloid leukemia for patients with pre‐existing cardiac disease

We conducted a retrospective study assessing FLAG (fludarabine, cytarabine, and granulocyte colony‐stimulating factor) as first‐line treatment in 56 newly diagnosed acute myeloid leukemia patients considered ineligible for anthracycline‐based treatment due to advanced age, significant comorbidities, or pre‐existing cardiac disease. The median age was 69 (21–80); 46% received FLAG for pre‐existing cardiac disease and others due to age (32%), non‐cardiac comorbidities (20%), or previous anthracycline exposure (2%). The induction mortality was 16% and, among evaluable patients, 48% achieved a complete remission after the first induction course with an additional patient achieving a remission after a second course for a total complete remission rate of 50%. Four patients proceeded to an allogeneic stem cell transplant including two with pre‐existing cardiac disease. Among non‐transplanted patients, the relapse rate (RR) was 47%. When censored at time of stem cell transplant, the median relapse‐free survival was 14.7 months. The median overall survival was 9.3 months with 1‐ and 2‐yr survivals of 44% and 22%, respectively. There was no difference in clinical outcomes between patients treated with FLAG for cardiac reasons vs. other reasons. In conclusion, FLAG is a useful alternative to anthracycline‐based induction for Acute myeloid leukemia in those with significant comorbidities including pre‐existing cardiac disease.     

Platelet adhesion to collagen types I through VIII under conditions of stasis and flow is mediated by GPIa/IIa (alpha 2 beta 1-integrin)

Platelet adhesion to fibrillar collagens (types I, II, III, and V) and nonfibrillar collagens (types IV, VI, VII, and VIII) was investigated in the presence of physiologic concentrations of divalent cations under conditions of stasis and flow. Under static conditions, platelet adhesion was observed to collagen types I through VII but not to type VIII. Under flow conditions, platelet adhesion to collagen types I, II, III, and IV was almost independent of shear rates above 300/s. Collagen type V was nonadhesive. Platelet adhesion to collagen type VI was shear rate-dependent and optimal at a rate of 300/s. Collagen types VII and VIII showed minor reactivity and supported platelet adhesion only between shear rates 100 to 1,000/s. Monoclonal antibody (MoAb) 176D7, directed against platelet membrane glycoprotein Ia (GPIa; very late antigen [VLA]-alpha 2 subunit), completely inhibited platelet adhesion to all collagens tested, under conditions of both stasis and flow. Platelet adhesion to collagen type III at shear rate 1,600/s was only inhibited for 85%. The concentration of antibody required for complete inhibition of platelet adhesion was dependent on the shear rate and the reactivity of the collagen. An MoAb directed against GPIIa (VLA-beta subunit) partially inhibited platelet adhesion to collagen. These results show that GPIa-IIa is a major and universal platelet receptor for eight unique types of collagen.     

Prevalence of major depressive disorder in patients receiving beta-blocker therapy versus other medications

Depression is believed to be a common side effect in patients receiving beta-blocker therapy. However, diagnoses of depression defined by current diagnostic criteria may not be more common in patients receiving beta-blockers than in patients with the same medical disorder receiving other medications. Seventy-seven patients undergoing elective cardiac catheterization for evaluation of chest pain received a semi-structured diagnostic psychiatric interview. Twenty-one percent of the patients receiving beta-blockers and 33 percent of the patients receiving medications other than beta-blockers met the current American Psychiatric Association criteria for major depressive disorder (DSM-III) (p = NS). The mean heart rate and state anxiety scores for patients taking beta-blockers were significantly lower than those measured in patients taking medications other than beta-blockers. No other medical or demographic differences were observed between the two groups. Despite the methodologic limitations of the study, there does not appear to be a difference in the point prevalence of depression between patients receiving beta-blockers and those receiving other medications.     

Can the Adenoma Detection Rate Reliably Identify Low-Performing Endoscopists? Results of a Modeling Study

Background

Experts have stated that adenoma detection rates (ADR) of individual endoscopists should be measured to assess colonoscopy quality.

Aim

The purpose of this study was to quantify the reliability of the ADR as a quality marker.

Methods

We simulated a population of endoscopists and patients using published data on adenoma prevalence and adenoma miss rates. For each endoscopist, the ADR was calculated. The proportion of ADR variance attributable to endoscopist and the area under the ROC (AUROC) curve for low-performing endoscopists (lowest quartile or decile) were also calculated.

Results

In the base-case analysis (200 patients per endoscopist, miss rate 22 %, adenoma prevalence 24 %), only 13 % of ADR variance was attributable to endoscopist performance (AUROC up to 0.73). An ADR cutoff of <16.5 % identified approximately half of endoscopists in the lowest performance decile (test sensitivity = 53 %), but most (79 %) of the endoscopists identified by this cutoff were NOT low performers (i.e., false positives). In sensitivity analysis, increasing the number of patients per endoscopist, reducing the variance of adenoma prevalence between endoscopists (i.e., performing case-mix adjustment), and increasing the variance in performance between endoscopists all improved ADR test characteristics (AUROC up to 0.88). However, regardless of assumptions, a substantial proportion of endoscopists would be misclassified if a simple ADR cutoff were utilized.

Conclusions

The ADR has limited reliability as a quality marker under real-world assumptions. Simple cutoffs are likely to either be insufficiently sensitive or have high false positive rates. Future studies should identify alternative means for assessing endoscopist performance.     

Update on the Performance and Application of Basophil Activation Tests

The basophil activation test (BAT) is a flow-cytometry-based functional assay that assesses the degree of cell activation after exposure to a stimuli. Though no standardized technique currently exists, recent advances have improved the performance of this assay, including identification of new basophil-specific markers and comparisons of the expression of CD63 to CD203c during activation. The basophil activation test has also been validated for many IgE-mediated disease conditions, which have been extensively reviewed elsewhere. This review focuses on the most recent applications of this test to the diagnosis of allergy to drugs, foods, venoms, and pollens, and the evolving role of the BAT in monitoring immunotherapy.