Lymphocytic hypophysitis with lachrymal, salivary and thyroid gland involvement

We report on hypophysitis associated with a prominent lymphoid infiltration of salivary and lachrymal glands in a 35-year-old woman with a dramatic response to steroids. Four years later, overt Graves' disease developed. To our knowledge, pseudotumoral lymphocytic infiltration of both lachrymal and salivary glands has never been described in association with hypophysitis. Benign lymphocytic hypophysitis may belong to a spectrum that extends from low-grade lymphoid proliferation to autoimmune disease. Such a process may follow a regional tissue distribution including pituitary, thyroid, lachrymal and salivary glands.     

Maximizing the Value of Mobile Health Monitoring by Avoiding Redundant Patient Reports: Prediction of Depression-Related Symptoms and Adherence Problems in Automated Health Assessment Services

Background

Interactive voice response (IVR) calls enhance health systems’ ability to identify health risk factors, thereby enabling targeted clinical follow-up. However, redundant assessments may increase patient dropout and represent a lost opportunity to collect more clinically useful data.

Objective

We determined the extent to which previous IVR assessments predicted subsequent responses among patients with depression diagnoses, potentially obviating the need to repeatedly collect the same information. We also evaluated whether frequent (ie, weekly) IVR assessment attempts were significantly more predictive of patients’ subsequent reports than information collected biweekly or monthly.

Methods

Using data from 1050 IVR assessments for 208 patients with depression diagnoses, we examined the predictability of four IVR-reported outcomes: moderate/severe depressive symptoms (score ≥10 on the PHQ-9), fair/poor general health, poor antidepressant adherence, and days in bed due to poor mental health. We used logistic models with training and test samples to predict patients’ IVR responses based on their five most recent weekly, biweekly, and monthly assessment attempts. The marginal benefit of more frequent assessments was evaluated based on Receiver Operator Characteristic (ROC) curves and statistical comparisons of the area under the curves (AUC).

Results

Patients’ reports about their depressive symptoms and perceived health status were highly predictable based on prior assessment responses. For models predicting moderate/severe depression, the AUC was 0.91 (95% CI 0.89-0.93) when assuming weekly assessment attempts and only slightly less when assuming biweekly assessments (AUC: 0.89; CI 0.87-0.91) or monthly attempts (AUC: 0.89; CI 0.86-0.91). The AUC for models predicting reports of fair/poor health status was similar when weekly assessments were compared with those occurring biweekly (P value for the difference=.11) or monthly (P=.81). Reports of medication adherence problems and days in bed were somewhat less predictable but also showed small differences between assessments attempted weekly, biweekly, and monthly.

Conclusions

The technical feasibility of gathering high frequency health data via IVR may in some instances exceed the clinical benefit of doing so. Predictive analytics could make data gathering more efficient with negligible loss in effectiveness. In particular, weekly or biweekly depressive symptom reports may provide little marginal information regarding how the person is doing relative to collecting that information monthly. The next generation of automated health assessment services should use data mining techniques to avoid redundant assessments and should gather data at the frequency that maximizes the value of the information collected.     

Familial inflammatory inclusion body myositis

OBJECTIVE: To compare familial inflammatory inclusion body myositis (IBM) with hereditary inclusion body myopathies and sporadic IBM. PATIENTS AND METHODS: Clinical, biological, MRI, and histological data were analysed in two siblings with inflammatory IBM and compared with those of patients with sporadic and hereditary IBM. RESULTS: Both patients had a clinical phenotype of sporadic IBM, which differs from hereditary myopathies because of late age of onset--respectively 65 and 66 years, and different pattern of muscular involvement--asymmetric, mainly distal but also involving quadriceps. MRI showed selective fatty infiltration and oedema in the extensor compartment of thigh muscles. The diagnosis of IBM was confirmed by muscle biopsy, showing muscle fibres containing numerous rimmed vacuoles, a characteristic shared by all types of IBM. In contrast with hereditary IBM, histological analysis also showed inflammatory mononuclear infiltrate invading non-necrotic fibres, ragged red and oxidase c negative fibres, and positive Congo red staining. Moreover, HLA class II typing disclosed DR beta 1 0301 haplotype, which is significantly related to sporadic but not to hereditary IBM. With steroid treatment and monthly intravenous immunoglobulins, the disease was stabilised in both patients at protracted follow up. CONCLUSION: Sporadic and familial inflammatory IBM share the same clinical, biological, MRI, and histological features.     

Evaluation of erythropoiesis in long-term hamster bone marrow suspension cultures: absence of a requirement for adherent monolayer cells

In long-term hamster bone marrow cultures, proliferation and differentiation of hemopoietic stem cells occurs for several months without need for hydrocortisone or adherent stromal elements, which are requirements for bone marrow growth in all other species studied. Only the most primitive erythroid progenitors (BFU-E) are produced in the cultures. Following treatment of the cells with erythropoietin, these progenitor cells undergo differentiation into mature hemoglobinized red blood cells. Concomitant addition of erythropoietin (Epo) and prostaglandin-E1 (PGE1) results in the production of large numbers of maturing red blood cells. In cultures stimulated with Epo and PGE1, as many as 70% of the cells are benzidine-positive, while Epo alone stimulated as many as 45% of the cells to become erythroid. Epo and PGE1 do not have any apparent deleterious effect on the continuous hemopoiesis occurring in these cultures. Under identical conditions, syngeneic adherent cell cultures do not produce any erythroid elements. The development of mature red blood cells from primitive erythroid precursors occurs in the presence of Epo alone and without any apparent need for adherent stromal elements. These cultures provide a useful in vitro model for dissecting the positive and negative signals that regulate erythropoiesis.     

Antiphospholipid antibodies in a series of 25 cases of lupus without antinuclear antibodies. Comparison with a series of 91 lupus patients with antinuclear antibodies

Twenty-five patients with at least 3 of 1982 ARA criteria of SLE but without the ANA, were compared with 91 patients with 4 or more of the ARA criteria of lupus with positive ANA. The ANA-negative group was characterised by the low incidence of skin involvement, serous effusions and alopecia, and a relatively high incidence of thrombocytopaenia and venous and arterial thrombosis. Three types of antiphospholipid antibodies were looked for: the VDRL, antiprothrombinase and anticardiolipin antibodies by an immuno-enzymatic method. The VDRL was the only antibody which was significantly commoner in the ANA-negative group. Statistical studies showed that the three methods of demonstrating antiphospholipid antibodies detected crossed but not identical specificities. In the ANA-positive group only the antiprothrombinase was associated with a high incidence of venous thrombosis and stroke. In the ANA-negative group, only the anticardiolipin antibodies were associated with a high incidence of arterial or venous thrombosis. Two subgroups may be identified in the group of ANA-negative lupus patients: firstly, those with high anticardiolipin antibody titres with a high incidence of thrombotic and haematological complications, and, secondly, patients with low anticardiolipin antibody levels with a high incidence of cutaneous involvement, serous effusions and Raynaud's phenomenon.     

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.     

Pregnancy and systemic lupus erythematosus

Pregnancy is widely authorized in systemic lupus erythematosus (SLE). Fertility is similar in SLE and in the general population although the age of menarche seems higher. Some cases of sterility might be attributed to SLE because of autoimmune ovaritis or antiphospholipid antibodies (aPL). These antibodies might lead to endothelial activation and thrombosis by influencing homeostasis, complement activation, inhibition of protein C and annexin V. They might have a deleterious effect on embryonic implantation by adhesion to the trophoblast, inhibition of invasion and placentation and decreased hCG production. The most important part of sterility seems secondary to the use of cyclophosphamide and might be prevented by acetate leuprolide administration. Maternal morbidity seems correlated to SLE activity (controlled by pregnancy planning), hypertension, preeclampsia, Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP) syndrome, therapy and aPL. Hydroxychloroquine (HCQ) should be maintained throughout pregnancy. Aspirin is prescribed alone in patients with asymptomatic aPL and in addition to heparin if there is a history of thrombosis or fetal loss with aspirin. Fetal and neonatal morbidity correlate with prematurity, adverse effects or maternal steroid therapy and maternal anti-SSA antibodies with 1 to 2% risk of congenital atrioventricular block. Abnormal obstetrical echography-doppler examination is the best predictor of pregnancy outcome. Abnormal ombilical artery flow on the second trimester echodoppler examination and history of thrombophlebitis predict fetal or neonatal death. Abnormal uterine notch on the second trimester echodoppler examination predicts adverse pregnancy outcome. Except for the preventive therapy of congenital atrioventricular block, modalities of SLE pregnancy monitoring and therapy are now well established.     

Longterm course of mixed cryoglobulinemia in patients infected with hepatitis C virus

OBJECTIVE: To describe epidemiological, clinical, and immunological characteristics and the longterm course of persistent mixed cryoglobulinemia (MC) in patients infected with hepatitis C virus (HCV). METHODS: Retrospective study of HCV infected patients (HCV RNA positive) who had persistent positive MC, with 2 immunochemical typings of MC carried out after 24-month minimum interval. RESULTS: In total, 125 patients were studied, aged 52 +/- 13 years at diagnosis of MC, with duration of HCV infection of 18 +/- 10 years. At entry, 60 patients had type II MC, 53 patients had type III, and 12 patients had the oligoclonal type. At the second immunochemical typing, after a mean interval of 45 +/- 20 months, MC was type II in 72 patients, type III in 39 patients, and the oligoclonal type in 14 patients. The proportion of cases of MC with the same immunochemical type was higher among patients with type II (78%) than type III (59%) or oligoclonal MC (17%) (p < 0.01). The MC that changed turned more to type II (55.5%) than type III (29%) or the oligoclonal type (15.5%) (p = 0.0002). MC vasculitis (purpura, arthralgia, peripheral neuropathy, renal involvement) and other extrahepatic manifestations (polyarteritis nodosa, lymphoma) in 60/125 patients was associated with advanced age (p < 0.01), a longer duration of infection (p < 0.05), type II MC (odds ratio = 5, p < 0.01), and a higher MC serum level (p < 0.01). CONCLUSION: During chronic active HCV infection, type II MC is more stable over time than type III and oligoclonal MC. The oligoclonal type appears to be an intermediate stage in the course of type III changing to type II MC. Symptomatic persistent HCV MC was associated with advanced age, longer duration of HCV infection, type II MC, and a higher MC serum level.