Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphoblastic leukaemia : a case report.

A 12 year old boy with acute lymphoblastic leukaemia had received prophylactic cranial irradiation (2000 cGy/15 days) and intrathecal methotrexate. Six years later he was diagnosed to have glioblastoma in left temporoparietal region. There is a strong possibility that the glioma may have been radiation and/or chemotherapy induced.     

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.

     

Patterns of relapse in stage I–II uterine papillary serous carcinoma treated with adjuvant intravaginal radiation (IVRT) with or without chemotherapy

Objective

To evaluate patterns of relapse in early stage uterine papillary carcinoma (UPSC) patients receiving adjuvant intravaginal radiotherapy (IVRT) with or without chemotherapy.

Methods

From 1/1996 to 12/2010, 77 women with stage I–II UPSC underwent surgery followed by IVRT (median 21 Gy). Stage IA patients without residual disease at surgery were excluded. IVRT and chemotherapy (carboplatin/taxane) was given to 61 (79%) patients and IVRT alone to 16 (21%). The median follow-up was 62 months for surviving patients.

Results

Of the 77 patients, 11 (14%) relapsed as follows: vaginal 2 (3%), pelvic 5 (6%), para-aortic 5 (6%), peritoneal 6 (8%), and other distant sites 8 (10%). Of the 5 pelvic relapses, 2 were isolated and were salvaged. In those treated without chemotherapy, only 1/16 developed recurrence (mediastinal). The 5-year vaginal, pelvic, para-aortic, peritoneal, and distant recurrence rates were 2.7% (C.I. 0–6.2%), 5.8% (C.I. 0.6–11.0%), 5.4% (C.I. 0.6–10.1%), 5.3% (C.I. 0.5–10.1%) and 6.6% (C.I. 1.4–11.8%), respectively. The 5-year disease-free survival (DFS), and overall survival (OS) were 88% (C.I. 81–95%), and 91% (C.I. 84–97%), respectively. The only predictor of worse 5-year pelvic control was stage (96.2% stage IA vs 87.7% for stage IB-II, p = 0.043).

Conclusions

In stage I–II UPSC patients who predominantly receive adjuvant chemotherapy, IVRT as the sole form of adjuvant RT provides excellent locoregional control. The risk of isolated pelvic recurrence is too low to warrant routine use of external pelvic RT.     

Implementation science for the adductor canal block: A new and adaptable methodology process

BACKGROUNDFollowing the successful Perioperative Surgical Home (PSH) practice for total knee arthroplasty (TKA) at our institution, the need for continuous improvement was realized, including the deimplementation of antiquated PSH elements and introduction of new practices. AIMTo investigate the transition from femoral nerve blocks (FNB) to adductor canal nerve blocks (ACB) during TKA. METHODSOur 13-month study from June 2016 to 2017 was divided into four periods: a three-month baseline (103 patients), a one-month pilot (47 patients), a three-month implementation and hardwiring period (100 patients), and a six-month evaluation period (185 patients). In total, 435 subjects were reviewed. Data within 30 postoperative days were extracted from electronic medical records, such as physical therapy results and administration of oral morphine equivalents (OME). RESULTSOur institution reduced FNB application (64% to 3%) and increased ACB utilization (36% to 97%) at 10 mo. Patients in the ACB group were found to have increased ambulation on the day of surgery (4.1 vs 2.0 m) and lower incidence of falls (0 vs 1%) and buckling (5% vs 27%) compared with FNB patients (P < 0.05). While ACB patients (13.9) reported lower OME than FNB patients (15.9), the difference (P = 0.087) did not fall below our designated statistical threshold of P value < 0.05.CONCLUSIONBy demonstrating closure of the “knowledge to action gap” within 6 mo, our institution’s findings demonstrate evidence in the value of implementation science. Physician education, technical support, and performance monitoring were deemed key facilitators of our program’s success. Expanded patient populations and additional orthopedic procedures are recommended for future study.     

The effects of maternal protein deprivation on the fetal rat pancreas: major structural changes and their recuperation

There is evidence that low birth weight and poor growth in early life cause a long-term predisposition to non-insulin-dependent diabetes. Morphological changes were assessed in fetal rat pancreas subjected to both pre- and post-natal maternal protein deprivation (LP). Further groups were subjected to purely prenatal maternal protein deprivation (preLP) and purely postnatal maternal protein deprivation (postLP), as well as a control group. The results show that the LP and postLP groups had fewer but larger islets than the control group, while the preLP group had more numerous, smaller islets. All three low protein groups had more irregularly shaped islets than the control group. There was a reduction in the amount of beta cells within each islet in all three protein-deprived groups. The LP and postLP groups showed a reduction in the percentage of islet tissue and beta cells per pancreas, but the percentage of islet tissue expressed per unit body weight was similar in all four groups. These results show that in maternal protein deprivation, homeostatic mechanisms ensure a constant amount of pancreatic endocrine tissue per unit of body weight. However, there remain major structural changes in the size, shape, and composition of the islets. These results support the theory that early development profoundly affects the structure of the pancreas and may play a role in the later development of adult diseases, such as non-insulin-dependent diabetes mellitus. © 1997 by John Wiley & Sons, Ltd.