Can Surface Neuromuscular Electrical Stimulation of the Wrist and Hand Combined With Routine Therapy Facilitate Recovery of Arm Function in Patients With Stroke?

Rosewilliam S, Malhotra S, Roffe C, Jones P, Pandyan AD. Can surface neuromuscular electrical stimulation of the wrist and hand combined with routine therapy facilitate recovery of arm function in patients with stroke?ObjectiveTo investigate whether treatment with surface neuromuscular electrical stimulation to the wrist extensors improves recovery of arm function in severely disabled patients with stroke.DesignSingle blinded randomized controlled trial.SettingAcute stroke unit and stroke rehabilitation wards of a university hospital.ParticipantsPatients with no upper limb function (Action Research Arm Test [ARAT] score 0) (N=90; mean age ± SD, 74±11y; 49% men) were recruited to the study within 6 weeks of stroke. Only 67 participants were alive at the end of the study and data from 66 of these people were analyzed.InterventionsParticipants were randomized to surface neuromuscular electrical stimulation using surface electrical stimulators for 30 minutes, twice in a working day for 6 weeks in addition to standardized upper limb therapy or just standardized upper limb therapy.Main Outcome MeasureThe primary outcome measure was the ARAT score. Assessments were made at baseline and at 6, 12, 24, and 36 weeks after recruitment.ResultsThere were statistically significant improvements in measures of wrist extensor (mean difference 0.5; 95% confidence interval [CI], 0.0–1.0) and grip strength (mean difference 0.9; 95% CI, 0.1–1.7) over the treatment period. Arm function (ARAT score) was not significantly different between the groups over the treatment period at 6 weeks (mean difference 1.9; 95% CI, ?2.9 to 6.8) or over the study period at 36 weeks (mean difference 6.4; 95% CI, ?1.8 to 14.7), and the rate of recovery was not significantly different (mean difference 0.7; 95% CI, ?0.2 to 1.6).ConclusionsIn patients with severe stroke, with no functional arm movement, electrical stimulation of wrist extensors improves muscle strength for wrist extension and grip, and larger studies are required to study its influence on arm function.     

Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors

OBJECTIVE: Endothelial progenitor cells (EPCs) are used for angiogenic therapies or as biomarkers to assess cardiovascular disease risk. However, there is no uniform definition of an EPC, which confounds EPC studies. EPCs are widely described as cells that coexpress the cell-surface antigens CD34, AC133, and vascular endothelial growth factor receptor-2 (VEGFR-2). These antigens are also expressed on primitive hematopoietic progenitor cells (HPCs). Remarkably, despite their original identification, CD34+AC133+VEGFR-2+ cells have never been isolated and simultaneously plated in hematopoietic and endothelial cell (EC) clonogenic assays to assess the identity of their clonal progeny, which are presumably the cellular participants in vascular regeneration. METHODS: CD34+AC133+VEGFR-2+ cells were isolated from human umbilical cord blood (CB) or granulocyte colony-stimulating factor-mobilized peripheral blood and assayed for either EPCs or HPCs. RESULTS: CD34+AC133+VEGFR-2+ cells did not form EPCs and were devoid of vessel forming activity. However, CD34+AC133+VEGFR-2+ cells formed HPCs and expressed the hematopoietic lineage-specific antigen, CD45. We next tested whether EPCs could be separated from HPCs by immunoselection for CD34 and CD45. CD34+CD45+ cells formed HPCs but not EPCs, while CD34+CD45- cells formed EPCs but not HPCs. CONCLUSIONS: Therefore, CD34+AC133+VEGFR-2+ cells are HPCs that do not yield EC progeny, and the biological mechanism for their correlation with cardiovascular disease needs to be reexamined.     

Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease

The objective of this study was to examine the potential of oral interleukin-10 (IL-10) gene therapy for the treatment of inflammatory bowel disease (IBD). Nanoparticles-in-microsphere oral system (NiMOS) was formulated with murine IL-10-expressing plasmid DNA in type-B gelatin nanoparticles, which were further encapsulated in poly(epsilon-caprolactone) microsphere matrix. Upon oral administration in an acute colitis model, IL-10 expression in the large intestine was measured by quantitative real-time PCR and ELISA. The locally expressed IL-10 was able to suppress the levels of proinflammatory cytokines, such as IFN-gamma, TNF-alpha, IL-1alpha, IL-1beta and IL-12, as well as certain chemokines. The therapeutic benefits of transfected IL-10 were further demonstrated by an increase in body weight, favorable clinical activity score, restoration in colon length and weight, and suppression of inflammatory response as assessed by tissue histological analysis and myeloperoxidase activity. The results of this study provide highly encouraging evidence of oral gene delivery and transfection and potential utility in IBD therapy.     

Expression of interferon-γ and tumor necrosis factor-α in bone marrow T cells and their levels in bone marrow plasma in patients with aplastic anemia

Immune-mediated stem cell damage has been postulated to be responsible for disease initiation and progression in aplastic anemia (AA). It is hypothesized that T lymphocytes play a major role in destroying the bone marrow (BM) stem cells of AA patients by infiltrating the BM and secreting excessive levels of anti-hematopoietic cytokines, interferon-gamma (IFN-), and tumor necrosis factor-alpha (TNF-). We undertook this study to assess the pathogenic significance of anti-hematopoietic cytokines such as IFN- and TNF- in BM T cells and plasma of AA patients. Significantly elevated levels of IFN- and TNF- were found in the BM plasma of AA patients compared to controls (p=0.05 and 0.006, respectively). Intracellular IFN- and not TNF- in BM CD3⁺ T cells of AA patients was significantly higher compared to controls (p=0.04 and p=0.2, respectively). A follow-up analysis of expression of these cytokines in BM T cells and their levels in BM plasma in five AA patients before and 180 days (6 months) after antithymocyte globulin (ATG) and cyclosporin A (CsA) therapy showed a decline 180 days after therapy compared to pre-therapy. We thus conclude that increased production of both IFN- and TNF- in the BM may contribute to disease pathogenesis in AA and ATG therapy may induce hematological remission by suppressing the elevated levels of IFN- and TNF- in AA BM.     

Spontaneous bacterial empyema in a noncirrhotic patient: an unusual scenario

Spontaneous bacterial empyema (SBEM) is infection of a preexisting pleural effusion without evidence of pneumonia. It has been reported mostly in patients with hepatic hydrothorax. Only 1 case of SBEM in a noncirrhotic patient has been reported. We present an unusual case of bilateral SBEM from Streptococcus pneumoniae bacteremia in a noncirrhotic patient. A 52-year-old man presented with bilateral pleuritic chest pain and dyspnea for 2 days. His medical history included congestive heart failure, hemodialysis-dependent renal failure and known bilateral pleural effusions. No ascites or hepatosplenomegaly was noticed. Bilateral pleural effusions were again present on physical examination and confirmed by a chest computed tomography scan. Cardiac medical treatment and hemodialysis failed to improve his condition. Bilateral thoracentesis revealed purulent pleural fluid that was culture-positive for Streptococcus pneumonia as were blood cultures. There was no clinical or radiographic evidence of pneumonia. The detailed clinical course, treatment and highlighted points are described.     

First trimester bleeding evaluation

First trimester bleeding is a common presentation in the emergency room. Ultrasound evaluation of patients with first trimester bleeding is the mainstay of the examination. The important causes of first trimester bleeding include spontaneous abortion, ectopic pregnancy, and gestational trophoblastic disease; 50% to 70% of spontaneous abortions are due to genetic abnormalities. In normal pregnancy, the serum beta hCG doubles or increases by at least 66% in 48 hours. The intrauterine GS should be visualized by TVUS with beta hCG levels between 1000 to 2000 mIU/mL IRP. Visualization of the yolk sac within the gestational sac is definitive evidence of intrauterine pregnancy. Embryonic cardiac activity can be identified with CRL of >5 mm. A GS with a mean sac diameter (MSD) of 8 mm or more without a yolk sac and a GS with an MSD of 16 mm or more without an embryo, are important predictors of a nonviable gestation. A GS with a mean sac diameter of 16 mm or more (TVUS) without an embryo is a sonographic sign of anembryonic gestation. A difference of <5 mm between the mean sac diameter and the CRL carries an 80% risk of spontaneous abortion. Approximately 20% of women with first trimester bleeding have a subchorionic hematoma. The presence of an extra ovarian adnexal mass is the most common sonographic finding in ectopic pregnancy. Other findings include the tubal ring sign and hemorrhage. About 26% of ectopic pregnancies have normal pelvic sonograms on TVUS. Complete hydatidiform mole presents with a complex intrauterine mass with multiple anechoic areas of varying sizes (Snowstorm appearance). Twenty-five percent to 65% of molar pregnancies have associated theca-leutin cysts. Arteriovenous malformation of the uterus is a rare but life-threatening cause of vaginal bleeding in the first trimester. The sonographic findings in a patient with first trimester bleeding should be correlated with serum beta hCG levels to arrive at an appropriate clinical diagnosis.     

Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma

RATIONALE AND OBJECTIVES: Patients with severe asthma have a poor therapeutic response to corticosteroid therapy, and corticosteroid responsiveness cannot be easily measured in these patients. We hypothesized that this poor response is associated with a reduced effect of corticosteroids to inhibit cytokine release from activated peripheral blood mononuclear cells (PBMCs). METHODS: Patients with severe asthma were defined by American Thoracic Society criteria. We compared the suppression of LPS-induced cytokine release (monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein [MIP] 1alpha, RANTES, tumor necrosis factor alpha, interleukin 1beta (IL-1beta), IL-8, IFN-gamma, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) by dexamethasone from PBMCs of patients with severe asthma (n = 16), patients with nonsevere asthma (n = 19), and normal volunteers (n = 10). RESULTS: There was no difference in baseline spontaneous or stimulated release of these cytokines among groups. LPS-induced release of 10 cytokines was less suppressed by dexamethasone (10(-6) M) in patients with severe asthma compared with patients with nonsevere asthma, with statistical significance achieved for IL-1beta (p < 0.03), IL-8 (p < 0.03), and MIP-1alpha (p < 0.003), and borderline significance for IL-6 (p = 0.054). There was less difference between the two groups for dexamethasone at 10(-8) M. Nuclear histone deacetylase (HDAC) and histone acetyltransferase activities were reduced in patients with severe asthma compared with patients with nonsevere asthma (p < 0.01). HDAC activity reduction correlated directly to the degree of steroid insensitivity of GM-CSF (r = 0.57, p < 0.01) and IFN-gamma (r = 0.56, p < 0.05) release. Reduction in histone acetyltransferase activity related to corticosteroid use rather than asthma severity. CONCLUSIONS: Patients with severe asthma have diminished corticosteroid sensitivity of PBMCs when compared with patients with nonsevere asthma, associated with a reduction in HDAC activity that parallels the impaired corticosteroid sensitivity.     

Retroperitoneal cystic lymphangioma in an adult: A case report and review of the literature

Lymphangiomas are rare benign cystic tumors of the lymphatic system. Retroperitoneal lymphangiomas account for 1% of all lymphangiomas, and approximately 186 cases have been reported. They may clinically present as a palpable abdominal mass and can cause diagnostic dilemmas with other retroperitoneal cystic tumors, including those arising from the liver, kidney and pancreas. This report describes the rare case of a cystic retroperitoneal lymphangioma in a 54-year-old male patient. The lymphangioma had progressed to the point of inducing clinical symptoms of abdominal distention, abdominal pain, anorexia, fever, nausea and diarrhea. Radiological imaging revealed a large multiloculated cystic abdominal mass with enhancing septations involving the upper retroperitoneum and extending into the pelvis. Surgical removal of the cyst was accomplished without incident. A benign cystic retroperitoneal lymphangioma was diagnosed on histology and confirmed with immunohistochemical stains.     

A comparative study of insulin resistance for Saudi and Caucasian subjects across a range of glycaemic categories

AimSaudi and Caucasian subjects, matched for adiposity, and of differing glycaemic status were compared using several insulin sensitivity indices and to also to assess insulin, glucose and insulin-like growth factor binding protein-1 (IGFBP-1) responses to intravenous glucose.MethodsSubjects with normal glucose tolerance (NGT; n = 24), impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 12), and type 2 diabetes (DM; n = 13) were recruited from Saudi (n = 33) and Caucasian (n = 28) populations. All had specimens taken in the context of a standard oral glucose tolerance test at their first visit and had the insulin sensitivity parameter (Si) determined by frequently-sampled intravenous glucose tolerance test (FSIVGTT) at a second visit.ResultsSaudis in the NGT and pooled glucose intolerance categories had significantly higher diastolic blood pressure (p < 0.001, p < 0.05 respectively) and HbA1c (p < 0.01, p < 0.05 respectively) compared to Caucasians. Caucasians in the NGT category had significantly higher Si, fasting and 2 h IGFBP-1 (p < 0.01, p < 0.05 and p < 0.01 respectively) compared to Saudis. Two hours following oral or intravenous glucose serum IGFBP-1 decreased to 44% (p < 0.001) and 50% (p < 0.05) of baseline levels respectively.ConclusionsOur data suggest that adult Saudis with normal glucose tolerance appear to be more insulin resistant than Caucasians matched for adiposity. In normal individuals at 2 h the IGFBP-1 level will be about half the baseline level regardless of the route of glucose administration.