Vrushali Dabak

Preferential migration of effector CD8 + T cells into the interstitium of the normal lung

The respiratory tract is a primary site of infection and exposure to environmental antigens and an important site of memory T cell localization. We analyzed the migration and retention of naive and activated CD8+ T cells within the noninflamed lungs and quantitated the partitioning of adoptively transferred T cells between the pulmonary vascular and interstitial compartments. Activated but not naive T cells were retained within the lungs for a prolonged period. Effector CD8+ T cells preferentially egressed from the pulmonary vascular compartment into the noninflamed pulmonary interstitium. T cell retention within the lung vasculature was leukocyte function antigen-1 dependent, while the egress of effector T cells from the vascular to the interstitium functions through a pertussis toxin-sensitive (PTX-sensitive) mechanism driven in part by constitutive CC chemokine ligand 5 expression in the lungs. These results document a novel mechanism of adhesion receptor- and pulmonary chemokine-dependent regulation of the migration of activated CD8+ T cells into an important nonlymphoid peripheral site (i.e., the normal/noninflamed lung).

Thrombosis in VonWillebrand disease.

OBJECTIVE To date, only a few case studies have reported occurrence of thrombosis in patients with VonWillebrand disease (VWD). No studies have looked at its incidence in this patient population. The aim of this study was to test our hypothesis that decreased VonWillebrand factor (VWF) levels confer a protective effect on arterial and venous thrombosis. METHODS This is a retrospective cohort study including patients (n=350) with the ICD-9 code of VWD who were identified from our hospital database over a period of 25 years, out of which 198 patients were included in the final sample. A parallel control sample without VWD matched for age, sex, hypertension, hyperlipidemia, atrial fibrillation and diabetes mellitus was also obtained from the hospital database. The primary outcomes were incidence of diagnosis of symptomatic arterial and venous thrombosis. The results were computed using multivariate conditional logistic regression analysis and proportions were compared using McNemers Chi - square test. RESULTS Out of 198 patients (mean age 44.2 ± 17.5, women 72%) with VWD, 170 (86%) were VWD type 1, 21 (10%) were type 2 and 7 (3%) were type 3. VWD was found to be an independent protective predictor from arterial thrombosis (OR 0.28, 95% CI 0.14-0.54, p<0.0001), more so in CAD (OR 0.28, 95% CI 0.12-0.64, p=0.002) than in CVD (OR 0.28, 95% CI 0.10-0.77, p=0.01). However this was not the case in venous thrombosis (p=0.42). CONCLUSION In a population of relatively younger individuals with VWD, our study suggests a reduced incidence of arterial thrombosis but not of venous thrombosis. This brings up the possibility that there could be other pathways or factors involved in arterial and venous thrombosis. To our knowledge, this is the first large observational study that has provided insight into the thrombotic disease in this group of patients.

Thalidomide-induced severe hepatotoxicity

Thalidomide was introduced in Europe during the 1950s as a sedative agent and was found to alleviate symptoms of morning sickness. However, it was withdrawn in 1961 due to its teratogenic properties. Around that time, the immunomodulatory eVects of thalidomide were recognized, and it became the drug of choice for erythema nodosum leprosum [1]. It is also being used to alleviate symptoms of HIVinduced cachexia, presumably via its suppression of tumor necrosis factor-a [2, 3]. In the Weld of hematology, thalidomide appeared to inhibit the growth and survival of myeloma cells via its immunomodulatory and antiangiogenic properties. It was approved by the Food and Drug Administration (FDA) in May of 2006 for use in combination with dexamethasone for treatment patients with of newly diagnosed multiple myeloma [4–6]. Common side-eVects during treatment with thalidomide are sedation, constipation, skin rash and peripheral neuropathy [7]. Less frequently bradycardia, hypotension and hypothyroidism have been described. Deep vein thromboses has been reported in patients receiving the combination of thalidomide and cytotoxic agents [8]. More severe toxicity in the form of Stevens–Johnson syndrome and toxic epidermal necrolysis has also been reported [9]. Hepatotoxicity is listed as an extremely rare adverse eVect, though a limited number of reports have demonstrated it to be a potentially serious adverse eVect [10–12]. Post marketing surveillance of thalidomide since reintroduction in 1998 has identiWed one case where the cause of death was thought to be directly due to treatment with thalidomide [13]. Thalidomide induced fulminant hepatic failure, which proved to be fatal in a 64-year-old woman has also been described in Mayo clinic proceedings [14]. Lenalidomide induced severe hepatotoxicity was recently described by Hussain et al. in Blood in 2007 [15], cautioning regarding the use of immunomodulatory group of drugs. We describe two such cases treated with thalidomide, one serious enough to be fatal.

Idiopathic erythrocytosis in dialysis patients: a case report and literature review.

Anemia is a common complication in end-stage renal disease (ESRD) patients. On the other hand, idiopathic erythrocytosis is extremely rare, with only a few cases reported in the literature. We present a case of erythrocytosis that developed after initiating hemodialysis. A 68-year-old male with a history of ESRD secondary to diabetes presented with erythrocytosis that started a few months after initiating dialysis in the absence of having received erythropoietin-stimulating agents or iron supplements. His erythropoietin level was elevated, with a negative JAK2 mutation. Blood gases showed normal oxygen and CO2, with slightly elevated carboxyhemoglobin. Tiny foci in both kidneys were noted, representing vascular calcifications or renolithiasis. There was no radiological evidence of neoplasms or cysts. After excluding secondary causes, a diagnosis of idiopathic erythrocytosis was made. The patient underwent intermittent phlebotomies during dialysis, and his hemoglobin went from 18.5 to 14 mg/dl. Erythrocytosis in ESRD patients is very rare. So far, there is no complete understanding of the underlying pathophysiology; however, there seem to be multiple possible reasons for an increased erythropoietin level. Phlebotomy is a successful and easy way to control erythrocytosis in such patients. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, currently being used in posttransplant erythrocytosis, might also be considered.

Can rituximab replace splenectomy in immune thrombocytopenic purpura

AimImmune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction. Standard practice is to initiate treatment with corticosteroids, followed by splenectomy. Most published literature for responses from rituximab is in patients with chronic refractory ITP, who have failed multiple prior treatments, including splenectomy. We therefore decided to analyze our patient population with ITP who had been treated with rituximab, mainly as a second line treatment regimen prior to splenectomy.MethodsWe performed a retrospective chart review of patients with a diagnosis of ITP who had been treated with rituximab between January 2001 and December 2006 at our institution.Results18/29 patients (62%) had a CR, 2/29 (7%) patients had a PR, representing an overall response rate of 69%. The average time to response was 5 weeks and all patients have maintained their response for more than 12 months after treatment with rituximab.ConclusionOur study shows higher CR, comparable overall response rates, but with a longer duration of response when compared to the published literature.