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M Thanikachalam

Publications and source records attributed to M Thanikachalam.

7 recordsLinked to original sources

A clinically relevant CTLA4-Ig-based regimen induces chimerism and tolerance to heart grafts.

BACKGROUND: We determined whether a nontoxic CTLA4-Ig-based conditioning regimen effected mixed chimerism and donor-specific tolerance when heart and bone marrow were transplanted simultaneously. METHODS: Fully mismatched rat strain combinations were used. Recipients received total-body irradiation (300 centigrays), bone marrow (10(8) cells), and cardiac transplants from the donor on day 0. Subsequently, recipient animals received CTLA4-Ig (2 mg/kg, every other day, x 5 doses), tacrolimus (1 mg/kg/day; days 0 to 9), and one dose (10 mg) of antilymphocyte serum on day 10. RESULTS: All bone marrow recipients (n = 7) developed mixed chimerism (mean = 25% +/- 9% at 1 year) and accepted cardiac allografts permanently (> 375 +/- 32 days). Recipients that received conditioning regimen but no bone marrow (n = 5) rejected donor hearts within 51 +/- 13 days (p < 0.01). Recipients that accepted heart grafts also permanently accepted (> 180 days) donor-specific skin grafts, but rapidly rejected (< 10 days) third-party skin grafts. CONCLUSIONS: A nontoxic CTLA4-Ig-based conditioning regimen effects mixed chimerism and donor-specific tolerance when heart and bone marrow are transplanted simultaneously. This regimen may have clinical application.

Abatacept↗

Combined host-conditioning with CTLA4-Ig, tacrolimus, anti-lymphocyte serum, and low-dose radiation leads to stable mixed hematopoietic chimerism.

The toxic dose of irradiation required to achieve stable mixed hematopoietic chimerism is the major limitation to its clinical application in transplantation and other nonmalignant conditions such as hemoglobinopathies. This study examines the additive effect of costimulatory blockage, to our previously described tacrolimus-based conditioning regimen, in further reducing the dose of total-body irradiation to achieve stable mixed chimerism in rats. Fully mismatched, 4- to 6-week-old ACI and Wistar Furth rats were used as donors and recipients, respectively. Recipients were administered CTLA4-Ig 2mg/kg/day (alternate days) in combination with tacrolimus 1 mg/kg/day (daily) from day 0 through day +10, anti-lymphocyte serum 10 mg at day +10 (single dose), and total-body irradiation ranging from 100-600 cGy, prior to bone marrow transplantation (day 0) with 100 x 10(6) of T-cell-depleted bone marrow cells. Levels of donor chimerism were determined over a period of 12 months. The short course of CTLA4-Ig, tacrolimus, and ALS led to dramatic engraftments at reduced doses of irradiation: 100% (5/5) and 93% (13/14) of the animals developed mixed chimerism at 400 cGy and 300 cGy, respectively. At 300 cGy, recipients exhibited durable, multilineage mixed chimerism at 365 days with donor cells ranging from 19-42% (mean 23.4%) with no evidence of graft-vs-host disease. These mixed chimeras exhibited in vitro (mixed lymphocyte reaction) and in vivo (skin grafts) donor-specific tolerance. This study suggests that addition of costimulatory blockade to a tacrolimus-based conditioning regimen reduces the dose of irradiation required to achieve stable multilineage chimerism in rats.

Abatacept↗

Retroperitoneal and abdominal wall emphysema after transanal excision of a rectal carcinoma.

The use of transanal excision to remove rectal carcinomas is a relatively new application of this surgical procedure, which may require full thickness excision. Retroperitoneal and abdominal wall emphysema are potential complications of surgical procedures that breach the wall of the colon and rectum. Computed tomographic scans provide the clearest diagnostic picture of developing emphysema, and prompt diagnosis through accurate interpretation of the scans is essential to minimize morbidity and mortality. When the diagnosis is made early and no active infection accompanies the emphysema, the preferred approach to initial treatment is nonsurgical. This article presents a case in which local transanal excision was performed on a 70-year-old male to remove a superficial adenocarcinoma from the lower rectal wall. He developed postoperative retroperitoneal and abdominal wall emphysema. Conservative treatment is discussed.

Abdominal Muscles↗

Avulsion fracture of the anterior superior iliac spine presenting as acute-onset meralgia paresthetica.

Avulsion fracture of the anterior superior iliac spine is rare. Most cases occur in adolescents involved in competitive sports or vigorous exercise in which the sartorius and tensor fascia lata muscles are contracted strongly and suddenly against a hyperextended trunk. Patients who sustain this injury usually experience acute pain in the anterior pelvic region. We describe a patient with avulsion of the anterior superior iliac spine who presented with meralgia paresthetica. The symptoms resolved with conservative treatment.

Adolescent↗