Limited effect of rituximab on thrombocytopaenia and anticardiolipin antibodies in a patient with primary antiphospholipid syndrome.
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Biomedical subjects
Publications and source records attributed to C Tommasino.
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The aim of this study was to evaluate a possible association between lymphocyte subsets and intima media thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS). We used a cross-sectional study on PAPS patients (n = 18) and healthy controls (n = 16). IgG anti-cardiolipin antibody (aCL), IgG anti-beta2glycoprotein-I (anti-beta2GPI), IgG anti-beta2glycoprotein-I complexed to oxidized low-density lipoprotein (oxLDL) and to a specific oxidized moiety of LDL (oxLig1), and beta2GPI-oxLDL were measured by ELISA. Lymphocyte immunophenotyping was performed using pairs of monoclonal antibodies directly labelled with fluorescein isothiocyanate, or phycoerythrin or phycoerythrin-Texas-red-X. Intima media thickness (IMT) of carotid arteries was determined by high-resolution sonography. Total peripheral blood lymphocytes did not differ between PAPS and controls. Memory CD4+/CD45RO + T cells were lower in PAPS than controls (P = 0.0007) as well as CD16+56+ natural killer cells (P = 0.02). In PAPS memory T CD45RO + cells positively correlated with IgG anti-beta2GPI-oxLigl (P = 0.002) and to IMT of carotid arteries (common carotid P = 0.02, bifurcation P = 0.007). Naive CD4+/CD45RA+ T cells inversely correlated with beta2GPI-oxLDL (P = 0.009). The relation between IgG anti-beta2GPI-oxLig1 and IMT of carotid arteries with memory CD45RO + T lymphocytes suggests a role for the latter in PAPS related atherogenesis.
This study evaluated whether IgG anticardiolipin antibody (aCL) titre and traditional risk factors for atherosclerosis bore any relationship to the intima media thickness (IMT) of carotid arteries of patients with idiopathic antiphospholipid antibodies (aPL). IMT was assessed by high-resolution sonography at the common carotid, carotid bifurcation and internal carotid in 42 (13 male, 29 female, mean age 31+/-10 years) aPL subjects, 29 with primary thrombotic antiphospholipid syndrome and 13 with persistence of aPL in the absence of any underlying disorder. In the same subjects the following were measured: plasma fibrinogen (FNG), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI), homocysteine (HC), total cholesterol (CHO), triglycerides (TG), high density and low density lipoprotein (HDL and LDL), platelet numbers and aCL of IgG and IgM isotype. IMT of the internal carotid was greater in males than females (0.48+/-0.03 vs 0.39+/-0.01 mm, P=0.02). IMT of the carotid bifurcation was greater in thrombotic than nonthrombotic subjects (0.50+/-0.02 vs 0.42+/-0.02 mm, P=0.04). By simple regression, IMT of the common carotids correlated with age (P< 0.0001) IgG aCL titre (P=0.001), FNG (P=0.006), LDL (0.01), CHO (0.02) and PAI (P=0.02). IMT of the carotid bifurcation correlated with age (P=0.002), IgG aCL titre (P=0.0002), FNG (P=0.0001), HC (P=0.009), CHO (P=0.02), vWF (P=0.01) and number of thrombotic events (P=0.03). IMT of the internal carotids correlated with age (P=0.002), IgG aCL titre (P=0.0001), FNG (P=0.0008), PAI (P=0.002) and HC (P=0.01). By stepwise multiple regression analysis, IgG aCL titre independently predicted IMT at all carotid segments examined (P always <0.005). In addition, plasma FNG and HC also resulted independent predictors of IMT at the carotid bifurcation (P=0.001 and P<0.0001, respectively) and internal carotid (P=0.03 and P<0.0001, respectively). These data strongly support an atherogenic role for IgG aCL in patients with aPL. Measurement of plasma HC and FNG may help define aPL subjects at higher vascular risk who may require lowering of HC and FNG by vitamin and/or pharmacologic intervention.
The prevalence of prothrombin (PT) G20210A and methylenetetrahydrofolate reductase (MTHFR) C677 <-- T was assessed in 40 patients with primary antiphospholipid syndrome (APS) (14 male, 26 female; mean age, 37 +/- 14 years) and in 27 persistent carriers of antiphospholipid antibodies (aPL) (five male, 22 female; mean age, 40 +/- 16 years) without underlying diseases. Non-APS thrombotic patients (n = 100; 47 female, 53 male; mean age, 40 +/- 10 years) and healthy subjects (n = 100; 46 female, 54 male; mean age, 56 +/- 16 years) served as control groups. Plasma homocysteine (HC) (enzyme-linked immunosorbent assay) was measured in all aPL patients and in 51 subjects from the healthy control group (mean age, 38 +/- 16 years). Heterozygous prothrombin PT G20210A was more frequent in the thrombotic group without APS (18%) than in the control (4%), APS (12%) or aPL (11%) groups, whereas homozygous MTHFR C677 <-- T was equally distributed. After genotype sub-grouping, plasma HC was higher in APS patients with homozygous MTHFR C677 <-- T compared with non-homozygous APS patients (22 +/- 5.4 versus 11 +/- 1.3 micromol/l; P < 0.01) and with homozygous MTHFR C677 <-- T controls (22 +/- 5.4 versus 15 +/- 2.0 micromol/l). In the APS group, mean age at first event was lower in homozygous MTHFR C677 <-- T patients than in non-homozygous patients (26 +/- 7.5 versus 36 +/- 13 years; P = 0.008). In the same group, homozygous MTHFR C677 <-- T patients suffered an increased average number of events per person than non-homozygous patients (1.9 versus 1.3; P = 0.04). Heterozygous PT G20210A contributes little to the thrombotic tendency of primary APS whereas plasma HC may influence age at first event and number of events. Measurement of plasma HC in aPL subjects may identify patients at increased thrombotic risk requiring HC lowering.
Summary Idiopathic autoimmune haemolytic anaemia developed in a patient with hereditary spherocytosis. The behaviour of some osmotic fragility tests throughout the illness and the efficacy of intravenous immunoglobulins in controlling autoimmune haemolysis which recurred post splenectomy are discussed
We prospectively evaluated the effects of pneumoperitoneum and reverse Trendelenburg position on cardiopulmonary function in 20 ASA physical status II-III morbidly obese patients (body mass index > 35 kg m(-2)) undergoing laparoscopic gastric banding. After general anaesthesia was induced, patients' lungs were ventilated using intermittent positive pressure ventilation (at measurement times, the following parameters were used: tidal volume 12 mL kg(-1) ideal body weight, respiratory rate of 12 bpm, an inspiratory to expiratory time ratio of 1:2). Haemodynamic variables, blood gas parameters, and lung/chest compliance were recorded: in the supine position, after induction of general anaesthesia (T0, baseline) and induction of pneumoperitoneum (T1); after placing the patient in a 25 degree reverse Trendelenburg position (T2); during the surgical time (T3); before deflating the abdomen (T4); after pneumoperitoneum resolution (T5), and before the end of anaesthesia, with the patient supine (T6). The PaO2, PaO2/FiO2 ratio, and lung/chest compliance decreased during the study. After the pneumoperitoneum had been resolved, lung/chest compliance but not oxygenation parameters returned to baseline values. The arterial to end-tidal CO2 tension difference progressively increased from 0.38+/-0.3 kPa (2.85+/-2.25 mmHg) (T0) to 0.63+/-0.3 kPa (4.73+/-2.25 mmHg) (T6). In morbidly obese patients, undergoing laparoscopic gastric banding, a CO2 pneumoperitoneum markedly affected gas exchange and lung/chest compliance, while positioning the patient in a 25 degree reverse Trendelenburg position had no beneficial effects.
The pathogenesis of antiphospholipid antibody (aPL) related thrombosis is multifactorial and includes, amongst others, enhanced coagulation activation measured as prothrombin fragment 1 + 2 (F1 + 2), elevated plasma levels of von Willebrand factor (vWF), plasminogen activator inhibitor (PAI) and endothelin-1 (ET-1) as well as heightened thromboxane generation and lipid peroxidation. To evaluate the antioxidant susceptibility of some of the above pathways, probucol (500 mg/d orally, a cholesterol lowering agent bearing antioxidant properties) was administered for a three week period to 14 subjects with aPL and to seven healthy controls. At baseline aPL participants showed higher plasma levels of vWF (P = 0.006), ET-1 (P = 0.0002) and enhanced urinary excretion of 11-dehydro-thromboxane-B2 (TXB2) (P = 0.0004), F2-isoprostanes (marker of lipid peroxidation) (P = 0.02) and albumin (P = 0.04) than controls. In the aPL group baseline IgG anticardiolipin (aCL) titre positively related with urinary TXB2 (r2 = 0.43, P = 0.01) and inversely with urinary NOx (r2 = -0.6, P = 0.005) whereas urinary NOx and TXB2 were negatively correlated (r2 = -0.42, P = 0.01). After the treatment period significant decreases from baseline values were noted for PAI (P = 0.01), ET-1 (P = 0.006), TXB2 (P = 0.02), F2-isoprostanes (P = 0.01) and albuminuria (P = 0.01) in aPL participants but not in controls. These pilot data support oxidative sensitive mechanisms and a potential role for antioxidant treatment in the pathogenesis of aPL induced vasculopathy.
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The etiology, diagnosis, pathology and treatment of rhabdomyolysis due to intraoperative malpositioning and the medico-legal implications of physicians involved in the surgical treatment and anesthesia of the patient are described. According to the Italian law, the anesthesiologist is the only physician of the surgery-anesthesia team responsible for the patient's positioning. The anesthesiologist must assume primary responsibility for protecting the patient from iatrogenic injuries due to improper positioning, and/or inadequate preventive measures.
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To evaluate the significance of common thrombophilic genotypes in subjects with idiopathic antiphospholipid antibodies (aPL) we determined the methylenetetrahydrofolate reductase C677-->T (MTHFR) and factor V A506-->G (FV Leiden) polymorphisms in 49 subjects with idiopathic aPL (57% of whom suffered spontaneous vein thrombosis), in 70 subjects with a history of spontaneous vein thrombosis and in 193 healthy subjects. The prevalence of MTHFR C677-->T+/+ (homozygotes) was 25%, 18% and 17% respectively amongst aPL thrombotics, non aPL thrombotics and controls and that of MTHFR C677-->T+/- (heterozygotes) was 53%, 59% and 53% respectively in the same groups. The prevalence of FV Leiden was higher in aPL thrombotics (14%) and in non aPL thrombotics (18%) than in controls (4%) (p < or = 0.05). APL thrombotics with MTHFR C677-->T+/+ had a lower mean age at first thrombotic event (22 +/- 6 years) than aPL thrombotics with MTHFR C677-->T+/- and non mutated considered together (38 +/- 14 years, p = 0.0004) and than non aPL thrombotics with MTHFR C677-->T+/+ (38 +/- 14 years, p = 0.003). FV Leiden may contribute to the hypercoagulability of a small, albeit significant proportion of thrombotic aPL subjects, whereas the association between MTHFR C677-->T+/+ and aPL may have an impact on age at first occlusive event and suggests a possible pathogenetic interaction.
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Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, has been used in two randomized, double-blind, vehicle-controlled trials in Europe, Australia, New Zealand, and in North America in patients with aneurysmal subarachnoid hemorrhage. The first trial has been concluded, enrolled 1023 patients, and demonstrated a dramatic reduction in mortality from 27% to 3% (p = 0.01) in males receiving 6 mg/kg/day tirilazad for 10 days, when compared to vehicle-treated patients. There was also a less incidence of symptomatic vasospasm, and the frequency of hypertensive-hypervolemic-hemodilution therapy was significantly reduced. The reduction in mortality rate was remarkable, however the benefits of treatment with tirilazad were predominantly shown in men rather than in women. This clinical trial suggest that tirilazad mesylate, at a dosage of 6 mg/kg/day, improves overall outcome in aneurysmal subarachnoid hemorrhage patients. Further data from the North America trial and the trial in women receiving higher doses of tirilazad are still pending.
Cerebral vasospasm following aneurysmal subarachnoid hemorrhage is one of the most important causes of cerebral ischemia, and is the leading cause of death and disability after aneurysmal rupture. The optimal treatment of vasospasm awaits development of agents for blocking or inactivating spasmogenic substances, or blocking arterial smooth muscle contraction. Rheological and/or hemodynamic manipulation using triple-H (hypertensive-hypervolemic-hemodilution) therapy to prevent or reverse ischemic consequences are relatively effective, but complicated and hazardous, and should be viewed principally as interim measures awaiting development of more specific therapies for arterial narrowing.
Recent evidence indicates that the relationship between "brain protection" and the degree of hypothermia is not linear, and even mild reduction of body temperature (i.e. 2-5 degrees C) may provide protection against cerebral ischemia. The protective effects of mild hypothermia have been demonstrated in various animal models of cerebral ischemia, and are encouraging in human studies. At the present time, although there is no randomized clinical trial assessing the benefits of mild hypothermia for intracranial aneurysm clipping, some neurosurgical centers are routinely instituting mild hypothermia before vascular occlusion.
Undiagnosed esophageal intubation is still prominently in anesthesia-related morbidity and mortality. Three cases of undiagnosed esophageal intubation taken into consideration for possible anesthesiologic malpractice are presented. A review of the international anesthetic-related morbidity and mortality statistics indicates that this misadventure remains a problem even among anesthesia personnel, a medical population specifically trained in such a procedure. It is not only the frequency of this misadventure but the potential catastrophic consequences for the patient that underline the importance of being able to recognise and correct an esophageal intubation. The reliability of commonly prescribed methods of assessing tracheal tube position is reviewed and the conclusion is drawn that continuous end-tidal carbon dioxide measurement during anesthesia is perhaps the most reliable means under all circumstances for determining proper tube position and should be employed routinely whenever possible.
This prospective randomized clinical study was designed to compare the effects of equal volumes of 7.5% hypertonic saline solution (HS) or 20% mannitol (M) on brain bulk and lumbar cerebrospinal fluid pressure (CSFP) during elective neurosurgical procedures (aneurysm, arteriovenous malformation, or tumor). After informed consent, 50 American Society of Anesthesiologists physical Status I (ASA I) patients were randomly assigned to M (n = 25) or HS (n = 25) groups. Anesthesia protocol was identical for both, and variables monitored included mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP), CSF pressure (CSFP), arterial blood gases (PaCO2 30-35 mm Hg), serum sodium, potassium, and osmolality, and diuresis. The study period started before hypertonic solution administration (T0) and ended at the opening of the dura mater or 60 min after T0. Data were assessed with repeated measures analysis of variance and Student t test with Bonferroni correction (p < or = 0.05). MAP and CVP were the same in the two groups. After treatment, osmolality increased, and the increase at T15 was higher in HS-treated patients [316.6 +/- 9.3 vs. 304.0 +/- 12.0 (SD) mOsmol/kg; p < 0.001]. Sodium decreased after M and increased after HS. During the study, brain bulk was always considered satisfactory. CSFP was not different between M and HS groups and significantly decreased overtime (p = 0.0056) with no difference between treatments. The results of the present study demonstrate that hypertonic saline is as effective as mannitol in reducing the brain bulk and the CSFP during elective neurosurgical procedures under general anesthesia.