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Neurol Res. 2000 Sep;22(6):588-96.
Bloody cerebrospinal fluid from patients with subarachnoid hemorrhage alters intracellular calcium regulation in cultured human vascular endothelial cells.
Nakagawa K, Hirai K, Aoyagi M, Yamamoto K, Hirakawa K, Katayama Y.
Department of Neurosurgery, Tokyo Medical and Dental University, Japan. nakagawoshima-hp.metro.tokyo.jp
Endothelial cell dysfunction may contribute to cerebral vasospasm and aggravation of ischemic brain damage following subarachnoid hemorrhage (SAH). It has been suggested that oxyhemoglobin derived from subarachnoid blood clots might be a prime candidate for cerebral vasospasm. In this study, cisternal bloody cerebrospinal fluid (bCSF) was collected from SAH patients four and seven days after aneurysmal rupture, and the effects of bCSF on the cell growth and intracellular calcium ion ([Ca2+]i) dynamics were investigated in cultured human umbilical vein endothelial cells. CSF collected from patients undergoing other intracranial surgeries was used as a control. Pre-treatment with bCSF4 significantly facilitated cell proliferation and DNA synthesis in the cultured endothelial cells, and significantly enhanced histamine-induced [Ca2+]i increase, while acute treatment of the bCSF elicited no [Ca2+]i change. Pre-treatment with interleukin-1 beta showed a similar significant enhancement of the histamine-induced [Ca2+]i response, while pre-treatment with high concentrations of serum or interleukin-6 did not change the [Ca2+]i response. It is concluded that bCSF collected from SAH patients contains some substances which enhance endothelial cell proliferation and sensitivity to inflammatory mediator.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11045021&dopt=Abstract hemorrhage
Neurol Res. 2000 Sep;22(6):634-41.
Prevention of cerebral vasospasm by nicardipine prolonged-release implants in dogs.
Kawashima A, Kasuya H, Sasahara A, Miyajima M, Izawa M, Hori T.
Department of Neurosurgery, Tokyo Women's Medical University, Japan.
The purpose of this study was to determine the efficacy of nicardipine prolonged-release implants for preventing vasospasm in a canine SAH model in a dose-escalating placebo-controlled blind fashion. Drug-release kinetics of copoly(lactic/glycolic acid) pellet containing nicardipine were evaluated in vitro. In vivo, 18 dogs were randomly assigned to one of three groups, i.e. placebo, low-dose (0.8 mg), or high-dose (8 mg) nicardipine. Angiography was performed, followed by right craniectomy, the induction of subarachnoid hemorrhage, and the placement of the pellets in the Sylvian fissure. On Day 7 and Day 14, the angiography was repeated. In the first four days, 61.9% of the actual nicardipine loaded was released and within 10 days, 96%. The average percent reductions of vessel diameters in the middle cerebral artery on Day 7 were 43%, 14% and 7% in the placebo, low-dose, and high-dose groups, respectively (p = 0.0319). The mean concentration of nicardipine in the clots on Day 14 was 9.7 x 10(-7) mol-1 l-1 and 5.1 x 10(-6) mol-1 l-1 in the low-dose and high-dose group, respectively. This drug delivery system prevented vasospasm in dogs significantly even at low dose, while maintaining an appropriate concentration of nicardipine in the clot adjacent to the arteries.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11045030&dopt=Abstract hemorrhage
Adv Perit Dial. 2000;16:170-3.
Peritoneal dialysis is the therapy of choice for end-stage renal disease patients with hereditary clotting disorders.
Bajo MA, del Peso G, Jimenez V, Aguilera A, Villar A, Jimenez C, Selgas R.
Servicio de Nefrologia, Hospital Universitario La Paz, Madrid, Spain.
Chronic renal failure is an unusual complication of hereditary clotting disorders (HCDs), but this situation could change in the near future. The modality of dialysis for end-stage renal disease (ESRD) in patients with an HCD is a difficult choice. Hemodialysis (HD) may be considered, but intensive treatment with coagulation factors is required for vascular access execution and for each HD procedure. Peritoneal dialysis (PD) has been infrequently proposed. However, PD requires coagulation replacement therapy only during peritoneal catheter placement. The aim of this paper is to describe our experience of three patients with ESRD and HCD, successfully treated with chronic PD in the medium term. Case 1 was a 58-year-old man with moderate hemophilia A, type 2 diabetes mellitus, and hepatitis C virus (HCV) infection. His ESRD was secondary to glomerulonephritis. A double-cuff peritoneal catheter was surgically placed with pre-emptive factor VIII administration. He began treatment with continuous ambulatory peritoneal dialysis (CAPD). An inguinal hernia was repaired without complications. After eleven months of follow-up, no hemorrhage episodes have been observed and clinical outcome is optimal. Case 2 was a 46-year-old man with severe hemophilia A, type 2 diabetes mellitus, and HCV and human immunodeficiency virus (HIV) infections. He developed a diabetic nephropathy that required renal replacement therapy. A permanent silicone catheter was inserted in the left internal jugular vein, and the patient started HD treatment. Later on, PD therapy was proposed. A peritoneal catheter was implanted with simultaneous factor VIII infusion. Minimal bleeding was observed at the subcutaneous tunnel over the following 48 hours. The patient started PD treatment without complications, and two months later, remaining asymptomatic, transferred to another center. Case 3 was a 41-year-old woman diagnosed with von Willebrand disease type 2A, HCV infection, and polycystic kidney disease, who presented with ESRD. An internal arteriovenous fistula was performed under coagulation factor cover. During a fistulography, and despite coagulation factor substitutive treatment, the patient showed an important hematoma. Afterwards, PD was considered. A peritoneal catheter was implanted under coagulation factor cover. The postoperative course was uncomplicated, and the patient started CAPD treatment. During follow up, she suffered two hemoperitoneum episodes that were resolved with cold dialysate. After nine months, she uneventfully continued on PD. In conclusion, PD is the therapy of choice for patients with hereditary clotting disorders and ESRD requiring dialysis. Peritoneal dialysis therapy avoids many of the complications related to HD therapy.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11045286&dopt=Abstract hemorrhage
Arch Gynecol Obstet. 2000 Sep;264(2):99-100.
Case of hemorrhagic shock due to hypermenorrhea during anticoagulant therapy.
Minakuchi K, Hirai K, Kawamura N, Ishiko O, Kanaoka Y, Ogita S.
Department of Obstetrics and Gynecology, Osaka City University Medical School, Japan.
We report the case of a patient with uterine myoma who developed uncontrollable massive hemorrhage from the uterus during anticoagulant therapy after cardiac valve replacement and required hysterectomy. There was a discrepancy between the laboratory findings regarding the blood coagulation system and the clinical manifestations, suggesting a combination of multiple factors, such as a hormonal imbalance. This was a case that demanded strict attention to the management of the uterine lesions during the conduct of anticoagulant treatment.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11045334&dopt=Abstract hemorrhage
Transplantation. 2000 Oct 15;70(7):1094-8.
Hydrophobic extracts of a Chinese herb (CMX-13) exhibit potent immunosuppressive properties and prevent acute rejection in a highly histoincompatible model of rat lung transplantation.
Zuo XJ, Okada Y, Toyoda M, Yap HK, Marchevsky A, Matloff JM, Jordan SC.
Department of Pediatrics, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA 90048, USA.
BACKGROUND: The potential of higher plants as sources for new immunosuppressive medications is well recognized. In our experiments we investigated the immunosuppressive effect of a highly refined and potent extract of a Chinese herbal preparation, CMX-13, on inhibiting acute allograft rejection (AR) in a highly histoincompatible rat lung transplant model, BN-->LEW, and on lymphocyte activation and cytokine gene expression in vitro. METHODS: Left lung transplants: the control group (group 1) received only dimethylsulfoxide (DMSO) which is the solvent for CMX-13. Group 2 received intramuscular cyclosporin A (CsA, 25 mg/kg) on day 2 posttransplant. Group 3 and 4 received i.p. CMX-13 (0.5 mg/day, low dose and 5 mg/day, high dose, respectively) on day 1, 2, and 3 posttransplant. All animals were killed on day 6 posttransplant. Several pathological categories of inflammation were examined. In vitro experiments: rat spleen cells were incubated with Con A or irradiated stimulator cells with/without serial dilutions of CMX-13 or CsA. Cell proliferation was measured by 3H-thymidine incorporation. mRNA expression of interleukin-2 and interferon-gamma was examined by reverse transcriptase-polymerase chain reaction. RESULTS: The severity of AR in animals receiving high dose CMX-13 was significantly reduced (stage II, P<0.05) compared with controls (stage IV). Significant differences were also seen when more specific parameters of inflammation were examined (necrosis, 0 vs. 1.7+/-1.0, P<0.05; interalveolar hemorrhage, 0 vs. 3.0+/-0.9, P<0.05). The responses seen in the animals treated with high dose CMX-13 were similar to those in the CsA group. CMX-13 inhibited T cell proliferative responses induced by Con A and alloantigen stimulation in a dose-dependent manner that were similar to CsA. Interleukin-2, and interferon-gamma mRNA expression in Con A-stimulated spleen cells was not inhibited by CMX-13 although CsA showed significant inhibition. CONCLUSIONS: 1) CMX-13 significantly reduces the stage of AR and parameters of inflammation in a highly histoincompatible rat lung transplant model. 2) CMX-13 has equal potency to CsA in the inhibition of Con A and alloantigen stimulated rat spleen cell proliferation. 3) CMX-13 showed no inhibitory effects on IL-2 and gamma-IFN mRNA expression, suggesting that its mechanism of action is different from CsA. 4) CMX-13 or derivatives may have potential utility as an immunosuppressive agent(s) in modulation of AR and management of other inflammatory and immunological disorders.
Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11045648&dopt=Abstract hemorrhage
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