IgM paraproteinemia in a patient with primary lateral sclerosis

Primary lateral sclerosis is an uncommon, distinct clinical entity. We report a patient with primary lateral sclerosis in whom investigations revealed an IgM monoclonal gammopathy, raised CSF protein and persistently high ESR. A number of reports suggest that lymphoproliferative disorders, paraproteinemia and clinico-pathological syndromes mimicking motor neuron diseases may be associated. We discuss the clinical features noted in our patient in relation to these reports, and the possible pathogenetic mechanisms.     

Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX‐68

Objective

Low‐dose weekly methotrexate therapy remains a mainstay in the treatment of inflammatory arthritis. Results of previous studies demonstrated that adenosine, acting at one or more of its receptors, mediates the antiinflammatory effects of methotrexate in animal models of both acute and chronic inflammation. We therefore sought to establish which receptor(s) is involved in the modulation of acute inflammation by methotrexate and its nonpolyglutamated analog MX‐68 (N‐[[4‐[(2,4‐diaminopteridin‐6‐yl)methyl]‐3,4‐dihydro‐2H‐1,4‐benzothiazin‐7‐yl]‐carbonyl]‐L ‐homoglutamic acid).

Methods

We studied the effects of low‐dose methotrexate (0.75 mg/kg intraperitoneally [IP] every week for 5 weeks), MX‐68 (2 mg/kg IP 2 days and 1 hour before induction of inflammation), dexamethasone (1.5 mg/kg IP 1 hour before induction of inflammation), or vehicle control on acute inflammation in an air‐pouch model in A_2A and A₃ receptor knockout mice.

Results

Low‐dose weekly methotrexate treatment increased the adenosine concentration in the exudates of all mice studied and reduced leukocyte and tumor necrosis factor α accumulation in the exudates of wild‐type mice, but not in those of A_2A or A₃ receptor knockout mice. Dexamethasone, an agent that suppresses inflammation by a different mechanism, was equally effective at suppressing leukocyte accumulation in A_2A knockout, A₃ knockout, and wild‐type mice, indicating that the lack of response was specific for methotrexate and MX‐68.

Conclusion

These findings confirm that adenosine, acting at A_2A and A₃ receptors, is a potent regulator of inflammation. Moreover, these results provide strong evidence that adenosine, acting at either or both of these receptors, mediates the antiinflammatory effects of methotrexate and its analog MX‐68.

     

Cross-sectional echocardiographic recognition of submitral left ventricular aneurysm

Three cases of annular submitral left ventricular aneurysm precisely diagnosed by cross-sectional echocardiography are reported from the Indian subcontinent. The cineangiographic findings are available in all and morphologic findings in two cases. The apical four-chamber view demonstrated a characteristically large aneurysm arising below the mural leaflet of the mitral valve extending anterolaterally and posteriorly and communicating with the left ventricular cavity in all the cases. Contrast echocardiography performed during cardiac catheterisation promises to be a good technique for the qualitative assessment of the associated mitral regurgitation. Cross-sectional echocardiography is invaluable in diagnosis and assessment of results of surgery in this entity.     

Lifestyle and testicular dysfunction: A brief update

The incidence of testicular cancer, cryptorchidism and defective spermatogenesis is increasing probably due to environmental and lifestyle-related factors. The aim of this review is to briefly describe and comment on the principal lifestyle factors. The recent findings that the electromagnetic waves following the use of the cell phone and the prolonged exposure to the noise stress cause relevant testicular dysfunction in man or animals reinforce the hypothesis of the importance of lifestyle-related factors.     

SYSTEMATIC TRAINING OF BUS,SHOPPING, AND CAFETERIA SKILLS

Four mentally handicapped adults from an ATC were systematically trained (using role-play and other techniques) to travel by bus, go shopping, and use cafés at a local shopping complex. It was hypothesised that their general social interaction skills would improve as a consequence of teaching them these three specific self-help or “community living” skills (Marholin et al., 1979). Pre- and post-measurements on the AAMD Adaptive Behavior Scales, and on an observational scale (TAF) devised by the author, showed that this prediction was fulfilled. There were also clear improvements in the three taught skills although these were not always statistically significant. The trainees' level of confidence (as measured by the TAS) also showed improvement, with increasing independence in using these public facilities. Since this study, three more groups at the ATC have started using the same assessment and training methods.