Lymphocyte interleukin 2 production and responsiveness are altered in patients with primary myelodysplastic syndrome

Immunoregulatory T and B cell functions in 15 patients with primary myelodysplastic syndrome (MDS) were studied by measuring the proliferative and the stimulatory capacity of T and B cells, respectively, in autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR). T cell proliferation in the auto MLR was 25% of the control (P less than .02), whereas proliferation in the allo MLR was normal. When control T cells were stimulated by MDS B cells, their proliferative response was only 57% of the control (P less than .01). The mechanism responsible for these abnormalities was studied by determining the capacity of MDS and normal T cells to produce interleukin 2 (IL 2) and to generate IL 2 receptors (IL 2R) following stimulation with control and MDS B cells. In the auto MLR of MDS patients, only 3% +/- 2% of T cells developed IL 2R positivity, whereas in control cultures 12% +/- 2% of T cells were positive, as determined by immunofluorescence, using a monoclonal antibody (MoAb) directed against the IL 2R, and FACS analysis. When MDS T cells were stimulated by control B cells, IL 2R generation and the production of IL 2 were within normal limits. In contrast, when control T cells were stimulated by MDS B cells or control B cells, the MDS B cells induced production of only 26% of IL 2 as compared with control B cells. In parallel experiments, IL 2R generation in control T cells stimulated by either MDS or control B cells was similar. We conclude that in the primary MDS, T and B cell interactions are impaired. Although MDS T cells develop normal quantities of IL 2R and produce normal amounts of IL 2 when stimulated by control B cells, they are markedly impaired when stimulated by self B cells. Similarly, MDS B cells can induce IL 2R generation in control T cells but not in MDS T cells. Myelodysplastic B cells are also defective in inducing IL 2 production by normal T cells in an allo MLR. These in vitro abnormalities strongly suggest that generation of lymphocytes with immunoregulatory functions is impaired in patients with MDS.     

Mixed germ cell tumour of the pineal region: a case report

An intracranial mixed germ cell tumour with germinoma and teratoma components is reported. The patient presented with parinaud's syndrome and precocious puberty. The treatment involved partial surgical debulking followed by whole brain radiotherapy (4500 cGY in 25 fraction over 5 weeks) and chemotherapy (consisting of cisplatin and etoposide). Post treatment MRI showed no residual lesion. The controversies in the management are discussed.     

Carcinoma of the maxillary antrum — A 10 year experience

A retrospective analysis was performed of 250 cases of carcinoma of the maxillary antrum seen over a 10 years period (1975–1984). 98.24% patients were seen in T3 and T4 stages (UICC 1985). 40.7% patients presented with clinically palpable nodes. 42.9% patients were treated by radical radiation and 18.6% by a combination of preoperative radiation followed by surgery. Rest 38.5% patients were treated with palliative intention. Three year disease free survival was 39.58% with radiation alone and 51.91% with combined modality treatment which includes patients salvaged by surgery. Failures were mainly at the local site, 75.86% with radiation alone and 60% with combined modality treatment. Combined modality treatment, preferably preoperative radiation followed by radical surgery, gives the best results in the management of carcinoma of the maxillary antrum.     

Irritable bowel syndrome in Asia: Pathogenesis,natural history,epidemiology, and management

Historically, the epidemiology of gastrointestinal diseases in Asia was different from that in Western countries. Early studies suggested a low prevalence of irritable bowel syndrome (IBS) in Asia. As the diagnosis of IBS is symptom‐based and as symptom perception, expression, and interpretation are influenced by sociocultural perspectives including language, the presentation of IBS is expected to vary in different communities. Furthermore, the pathogenesis is multifactorial with psychosocial (stress, illness, behavior, and diet) and biological (infection, gut microbiota, and immune activation) variables interacting, and so, the present study can anticipate that the development of IBS will vary in different environments. In recognition of this aspect of functional gastrointestinal disorders, the recently published Rome IV documents have provided greater focus on cross‐cultural factors. In this review, the present study seeks to highlight Asian perspectives by identifying historical trends and recent publications from the region and comparing these with the observations from Western societies.     

A randomized double-blind placebo-controlled trial showing rifaximin to improve constipation by reducing methane production and accelerating colon transit: A pilot study

Objective

Gut microbe-derived methane may slow colon transit causing chronic constipation (CC). Effect of rifaximin on breath methane and slow-transit CC was evaluated.

Method

Bristol stool form, frequency, colon transit time (CTT), and breath methane were evaluated in 23 patients with CC (10 patients with constipation-predominant irritable bowel syndrome [IBS-C], 13 functional constipation, Rome III) and m-ethane production compared with 68 non-constipating IBS. Methane-producing CC (basal ≥?10 PPM and/or post-lactulose rise by >?10 PPM) was randomized (double-blind) to rifaximin (400-mg thrice/day, 2-weeks) or placebo. Stool forms, frequency, breath methane, and CTT were recorded afterward.

Results

CC patients tended to be methane producer more often (13/23 [56.5%] vs. 25/68 [36.5%], p?=?0.07) and had greater area under curve (AUC) for methane (2415 [435–23,580] vs. 1335 [0–6562.5], p?=?0.02) than non-constipating IBS. Methane producers (8/13 [61.5%]) and 5/10 (50%) non-producers had abnormal CTT (marker retention: 36-h, 53 [0–60] vs. 19 [8–56], p?=?0.06; 60-h, 16 [0–57] vs. 13 [3–56], p?=?0.877). Six and 7/13 methane producers were randomized to rifaximin and placebo, respectively. Rifaximin reduced AUC for methane more (6697.5 [1777.5–23,580] vs. 2617.5 [562.5–19,867.5], p?=?0.005) than placebo (3945 [2415–12,952.5] vs. 3720 [502.5–9210], p?=?0.118) at 1 month. CTT normalized in 4/6 (66.7%) on rifaximin (36-h retention, 54 [44–57] vs. 36 [23–60], p?=?0.05; 60-h, 45 [3–57] vs. 14 [11–51], p?=?0.09) but none on placebo (p?=?0.02) (36-h, 31 [0–60] vs. 25 [0–45], p?=?0.078; 60-h, 6 [0–54] vs. 12 [0–28], p?=?0.2). Weekly stool frequency (3 [1–9] and 7 [1–14], p?=?0.05) and forms improved with rifaximin than placebo.

Conclusion

Rifaximin improves CC by altering methane production and colon transit.

Trial registration

Clinical Trial Registry, India: REF/2012/01/003216

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