Plasma exchange therapy for severe Graves' ophthalmopathy

The authors report on the treatment of 11 Graves' disease patients with severe ophthalmopathy by the use of intensive plasma exchange followed by immunosuppression. Results were evaluated by comparing the ophthalmopathy index and the orbital CT scan performed before and after plasmapheresis. Favorable results were obtained in 91% of the patients. The best positive effects of plasmapheresis were observed for soft tissue involvement, proptosis, tonometry, and visual acuity. Furthermore, a significant reduction in the size and density of enlarged extraocular muscles was also found. Six months after withdrawal of immunosuppression, 4 patients presented a moderate recurrence of ophthalmopathy and were treated successfully by a second course of plasmapheresis, followed by short immunosuppression. In conclusion, the use of intensive plasma exchange associated with immunosuppression is an effective approach to the treatment of severe Graves' ophthalmopathy. It yields rapid and dramatic improvements that are maintained in most patients after withdrawal of immunosuppression. Recurrences are still responsive to the beneficial effects of this combined treatment.     

Cellular hyperviscosity as a cause of neurological symptoms in leukaemia.

Six patients with various forms of leukaemia had neurological signs and symptoms associated with an extremely high white blood cell count and increased whole blood (but not plasma) viscosity. All were treated by leucapheresis with an Aminco Celltrifuge. Rapid and complete reversal of all symptoms occurred in three patients and partial recovery in one. One patient died shortly after leucapheresis and another (from cerebral intravascular coagulation) two days later. It is concluded that a cellular hyperviscosity syndrome may cause neurological dysfunction in patients with extremely high white cell counts, and that leucapheresis, in carefully selected patients, can be an effective method of treatment.     

Diagnosis and management of meningococcal disease: the need for centralized care

Meningococcal infection remains a significant health problem in children, with a significant mortality and morbidity. Prompt recognition and aggressive early treatment are the only effective measures against invasive disease. This requires immediate administration of antibiotic therapy, and the recognition and treatment of patients who may have complications of meningococcal infection such as shock, raised intracranial pressure (ICP) or both. Encouragingly, its mortality has fallen in recent years. This is the result of several factors such as the centralization of care of seriously ill children in paediatric intensive care units (PICUs), the establishment of specialized mobile intensive care teams, the development of protocols for the treatment of meningococcal infection, and the dissemination by national bodies and charities of guidance about early recognition and management. We will review the pathophysiology and management of the different presentations of meningococcal disease and examine the possible role of adjunctive therapies.     

Hemostasis disorders after transfusions

Disturbances of haemostasis caused immunologically and non-immunologically were observed after transfusion of blood and blood derivatives. Transfusion of heparin blood increased the bleeding susceptibility only in case of pre-existing high-degree defects of haemostasis or if they were performed as massive or exchange transfusions. Massive transfusions with blood stored for a long time will induce complex defects. Under intensive substitution therapy of haemophilia A the so-called paradoxical bleeding will occur in spite of a high factor VIII level. These bleedings are supposed to be disturbances of the thrombocyte function and are caused by fibrin(ogen) derivatives. Post-transfusional thrombocytopenias may be brought to remission by repeated plasmapheresis. Factor specific inhibitory bodies will appear after substitution in a small percentage of haemophilic patients. 5 to 7 days after the onset of therapy an anamnestic reaction can be observed as a titre increase by leaps. Usually, the inhibitory titre will decrease to a mostly low basal value in the course of three to five months. The therapy with cyclophosphamide simultaneously started with the substitution will more frequently prevent the anamnestic reaction or reduce it. Titres with more than 5 units cannot be overcome at the beginning even by higher concentrations of preparations. The substitution therapy should be preceded by exchange transfusions or plasmapheresis of up to 25 units. With still higher titres only procedures of inhibitor-bypassing are possible with factor VIII preparations of animal origin or better with activated prothrombin complex preparations, such as FEIBA. Recent reports give evidence that permanent substitution with factor VIII concentrates at a highest dosage can eliminate the production of inhibitors completely.     

Harvesting of granulocytes for granulocyte transfusion by means of continuous flow centrifugation or filtration leukapheresis]

More than 10(10) viable granulocytes are necessary for a therapeutical effective granulocyte transfusion. This number of cells can be harvested from normal donors by two techniques basing on different principles: continuous flow centrifugation (CFC) and filtration leucapheresis (FL). Our studies demonstrated that, under certain special conditions, the separation potentials of both methods are comparable yielding 2.5 to 3.0 X 10(10) granulocytes within 4 hrs. Granulocyte collection rate was optimal if donors were treated with dexamethasone during 16 hrs prior to the state of the procedure. However, the costs of CFC exceed those of FL by a factor of about two. The increased occurrence of side effects attributed to the transfusion of FL-granulocytes can be reduced to the level of CFC-granulocytes by repetitive filtration-elution leucapheresis minimizing cell damage. The studies define the efficiency spectrum of CFC which in addition to granulocyte separation includes collection of thrombocytes, cells for immunotherapy, and plasmapheresis.     

Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.     

Method of Removing Abnormal Protein Rapidly from Patients with Malignant Paraproteinaemias

On 48 occasions large quantities of abnormal protein were removed from the blood of 11 patients with malignant paraproteinaemias (plasmacytomas) by exchanging their plasma with reconstituted blood bank plasma. The IBM continuous flow blood cell separator was used to exchange the plasma, a procedure that is safe, very rapid, and with clinical benefits which are much better than can be obtained by conventional plasmapheresis. In addition, the constituents of reconstituted plasma correct deficiencies in normal immunoglobulins found in these patients. Clearly for the management of some patients with paraproteinaemia a cell separator is essential.     

Antibody response to Staphylococcus aureus whole cell, lipase and staphylolysin in patients with S. aureus infections

Abstract Three assays to measure antibodies against Staphylococcus aureus whole cells, lipase and staphylolysin were used to try to discriminate between complicated and uncomplicated S. aureus septicaemia. Sera were examined from 8 patients with S. aureus endocarditis, 23 patients with complicated S. aureus septicaemia, 12 patients with uncomplicated S. aureus septicaemia and 93 febrile non-septicaemic controls. No single assay could distinguish between complicated and uncomplicated S. aureus septicaemia. If the criterion for a positive result is defined as positive antibody level in the anti-lipase ELISA as well as in at least 1 of the other 2 assays, 10/31 patients with S. aureus endocarditis or complicated septicaemia were positive compared to 0/93 non-septicaemic patients and 0/12 patients with uncomplicated S. aureus septicaemia. Therefore, the combined use of serological assays in the diagnosis of complicated S. aureus septicaemia, one of which is the anti-lipase ELISA, is recommended.     

供浆者多次献浆后sdLDL-C和ox-LDL水平的测定

目的探讨多次献浆后,对供浆者体内血浆小而密低密度脂蛋白胆固醇(sdLDL-C)、氧化低密度脂蛋白(ox-LDL)水平变化的影响。方法分别检测100例多次献血浆者和100例初次献血浆者的血浆sdLDL-C和ox-LDL水平,同时检测其血脂及血浆蛋白水平。结果多次献血浆者的血浆sdLDL-C、ox-LDL以及血脂水平略有下降,但与初次献浆者之间无显著性差异;多次献血浆者的血浆总蛋白(TP)、白蛋白(ALB)与初次献浆者的水平相当,两者之间也无显著性差异。结论多次献血浆是安全的,不会增加动脉粥样硬化性心血管疾病的风险。     

Continuous-flow plasmapheresis in management of severe rhesus disease.

Eight patients with severe rhesus disease and expected fetal loss were treated by intensive plasmapheresis using a continuous-flow cell separator. Plasmapheresis was started at 16-27 weeks'' gestation, and continued until planned intrauterine transfusion or until the infant was delivered or the rhesus disease became uncontrolled again. Altogether 24 to 2371 of plasma was exchanged over periods ranging from seven to 16 weeks. In seven of the eight patients the anti-D concentration fell during the period of plasmapheresis. Amniotic fluid spectrophotometry values remained below those recorded in the preceding pregnancy in six out of seven women. In five patients an attempt was made to control the rhesus disease by plasmapheresis alone, and two of these women delivered infants who survived. In the other three cases the infants died, one from the idiopathic respiratory distress syndrome and the other two in utero. These preliminary findings suggest that intensive plasmapheresis with a cell separator may reduce fetal haemolysis is delivered. Nevertheless, plasmapheresis may best be used to reduce haemolysis until intrauterine transfusions may be given more safely after 30 weeks'' gestation.     

Liver and kidney functions after therapeutic plasmaphereses in the treatment of acute destructive diseases of the lungs and pleura

Liver and renal functions were assessed after classical discrete plasmapheresis (DP) and different variants of low-volume discrete plasmapheresis (LVDP) in the combined treatment of patients with acute destructive lung and pleural diseases (ADLPDs). LVDP associated with modification of erythrocytes to be autotransfused significantly decreased alanine and aspartate aminotransferase activities and blood contents of bilirubin, urea, and creatinine, whereas similar changes were less pronounced after classical DP. Thus, in patients with ADLPDs, LVDP with autotransfusion of erythrocytes modified by shortwave ultraviolet or washed with Hemodez efficiently improved the functions of the liver and the kidneys, providing for prevention of intoxication-caused renal and hepatic failure, whereas the hepato-and renoprotective effects of other types of plasmapheresis were weaker.     

Impaired Postoperative Hyperglycemic Stress Response Associated with Increased Mortality in Patients in the Cardiothoracic Surgery Intensive Care Unit

ObjectiveTo describe the association of tight glycemic control with intensive insulin therapy and clinical outcome among patients in the cardiothoracic surgery intensive care unit.MethodsAll patients who underwent cardiothoracic surgery and were admitted to the cardiothoracic surgery intensive care unit between September 13, 2007, and November 1, 2007, were enrolled. Clinical and metabolic data were prospectively collected. All patients received intensive insulin therapy using a nurse-driven dynamic protocol targeting blood glucose values of 80 to 110 mg/dL. Four stages of critical illness were defined as follows: acute critical illness (intensive care unit days 0-2), prolonged acute critical illness (intensive care unit 3 or more days), chronic critical illnesss (tracheotomy performed), and recovery (liberated from ventilator).ResultsOne hundred fourteen patients were enrolled. Seventy-three (64%) recovered during acute critical illness, 26 (23%) recovered during prolonged acute critical illness, and 15 (13%) progressed to chronic critical illness. All 6 deaths were among patients in chronic critial illness. Admission blood glucose and average blood glucose values for the first 12 hours were lower in patients who developed chronic critical illness and died and were higher in patients who developed chronic critical illness and survived (P = .007 and P = .007, respectively). Severe hypoglycemia (blood glucose < 40 mg/dL) occurred once (0.03% of all measurements). Lower initial blood glucose values, which reflect an impaired stress response immediately after surgery, were associated with increased mortality, and a significant delay in achieving tight glycemic control with intensive insulin therapy was associated with prolonged intensive care unit course, but no increase in mortality.ConclusionThe study findings suggest that acute postoperative hyperglycemia and its prompt correction with intensive insulin therapy are associated with favorable outcomes in patients in the cardiothoracic surgery intensive care unit. (Endocr Pract. 2010;16:798-804)     

Hematologic and oncologic complications in the critically ill child

Admission of a patient to an intensive care unit for management of direct consequences of a hematologic or oncologic disease is occasionally necessary. Such problems included exchange transfusion, sepsis, compression of vital structures by malignant tumor, metabolic derangements, leukostasis, post-operative care, major sickling episodes in vital organs, and disseminated coagulopathy. More often, however, hematologic complications arise in the child critically ill from other causes, such as trauma or infections. The first two sections of this review address blood transfusion and hemostasis, topics likely to have wide application in the care of critically ill children. The last portion discusses problems unique to patients with sickling or malignant disease.     

Inhibitor factors in the serum of patients with the AIDS-related complex

The data on the presence of factors blocking the reaction of E-rosette formation and leukocyte chemotaxis in the blood sera of patients with AIDS-related complex (ARC) and HIV-positive donors are presented. Most frequently the blocking of E-rosette formation coincided with the presence of a inhibiting effect on the migration capacity of leukocytes. This blocking activity was not linked with the presence of C-reactive protein in the circulation stream. The treatment of ARC patients with plasmapheresis and/or travolol was accompanied either by the disappearance of blocking activity or by the appearance of activity stimulating E-rosette formation.     

Prevalence and Clinical Course in Invasive Infections with Meningococcal Endotoxin Variants

Background

Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.

Methods

A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The lpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records.

Results

Of 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95%CI 0.09–0.58) and were less often admitted to intensive care (OR 0.21; 95%CI 0.07–0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics.

Conclusions

In adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course.     

Serum magnesium, copper, and zinc alterations following spinal fusion

Changes in serum magnesium, copper and zinc values were evaluated in spinal fusion patients at four monitorings. For magnesium and copper individually, a significant difference was found between the mean values at each monitoring (p<0.05), whereas the changes of zinc values between four monitorings were insignificant. There was no statistical difference between the changes of each trace element values and gender, age, operative time, intraoperative blood loss, blood replacement, number of the vertebral levels fused, and antibiotic type used. As a result, magnesium can be suggested to be more important than the other two elements in the postoperative period. Alterations of serum magnesium, copper, and zinc values do not have any correlation with the fusion of the spinal column, either with the width of the fused area or operative time and blood loss. This study cannot confirm the exact reason for this entity and the etiology remains speculative. There is no need for magnesium, copper, or zinc supplementation during the surgical period for the patients. It will be worthy to evaluate the patients who were sent to the intensive care unit after spinal surgery and compare their results with the other intensive care patients.     

Prevention of secondary cases of meningococcal disease in household contacts by vaccination.

Household contacts of patients with group A meningococcal infection were vaccinated with either meningococcal vaccine or tetanus toxoid. Five of the 523 subjects who received tetanus toxoid developed meningococcal meningitis and another four probably had meningococcal disease. Only one possible case of meningococcal infection occurred among 520 contacts vaccinated with meningococcal vaccine. Vaccination had no effect on nasopharyngeal carriage of meningococci. Vaccination of household contacts of patients with group A meningococcal infections is an effective way of using limited supplies of meningococcal vaccine, though its value would be limited in an epidemic. Secondary cases of meningococcal infection often occur within a few days of the index case, and, although vaccine alone seemed to provide adequate prophylaxis in these Nigerian subjects, additional chemoprophylaxis may be needed to cover this critical period.     

Cost effectiveness of self monitoring of blood glucose in patients with non-insulin treated type 2 diabetes: economic evaluation of data from the DiGEM trial

Objective To assess the cost effectiveness of self monitoring of blood glucose alone or with additional training in incorporating the results into self care, in addition to standardised usual care for patients with non-insulin treated type 2 diabetes.Design Incremental cost utility analysis from a healthcare perspective. Data on resource use from the randomised controlled diabetes glycaemic education and monitoring (DiGEM) trial covered 12 months before baseline and 12 months of trial follow-up. Quality of life was measured at baseline and 12 months using the EuroQol EQ-5D questionnaire.Setting Primary care in the United Kingdom.Participants 453 patients with non-insulin treated type 2 diabetes.Interventions Standardised usual care (control) compared with additional self monitoring of blood glucose alone (less intensive self monitoring) or with training in self interpretation of the results (more intensive self monitoring).Main outcome measures Quality adjusted life years and healthcare costs (sterling in 2005-6 prices).Results The average costs of intervention were £89 (€113; $179) for standardised usual care, £181 for less intensive self monitoring, and £173 for more intensive self monitoring, showing an additional cost per patient of £92 (95% confidence interval £80 to £103) in the less intensive group and £84 (£73 to £96) in the more intensive group. No other significant cost difference was detected between the groups. An initial negative impact of self monitoring on quality of life occurred, averaging −0.027 (95% confidence interval−0.069 to 0.015) for the less intensive self monitoring group and −0.075 (−0.119 to −0.031) for the more intensive group.Conclusions Self monitoring of blood glucose with or without additional training in incorporating the results into self care was associated with higher costs and lower quality of life in patients with non-insulin treated type 2 diabetes. In light of this, and no clinically significant differences in other outcomes, self monitoring of blood glucose is unlikely to be cost effective in addition to standardised usual care.Trial registration Current Controlled Trials ISRCTN47464659.     

Imaging of disease dynamics during meningococcal sepsis

Neisseria meningitidis is a human pathogen that causes septicemia and meningitis with high mortality. The disease progression is rapid and much remains unknown about the disease process. The understanding of disease development is crucial for development of novel therapeutic strategies and vaccines against meningococcal disease. The use of bioluminescent imaging combined with a mouse disease model allowed us to investigate the progression of meningococcal sepsis over time. Injection of bacteria in blood demonstrated waves of bacterial clearance and growth, which selected for Opa-expressing bacteria, indicating the importance of this bacterial protein. Further, N. meningitidis accumulated in the thyroid gland, while thyroid hormone T4 levels decreased. Bacteria reached the mucosal surfaces of the upper respiratory tract, which required expression of the meningococcal PilC1 adhesin. Surprisingly, PilC1 was dispensable for meningococcal growth in blood and for crossing of the blood-brain barrier, indicating that the major role of PilC1 is to interact with mucosal surfaces. This in vivo study reveals disease dynamics and organ targeting during meningococcal disease and presents a potent tool for further investigations of meningococcal pathogenesis and vaccines in vivo. This might lead to development of new strategies to improve the outcome of meningococcal disease in human patients.     

The artificial endothelium

As the world of critical care medicine advances, extracorporeal therapies (ECC) have become commonplace in the management of the high risk intensive care patient. ECC encompasses a wide variety of technologies from hemodialysis, continuous renal replacement therapy (CRRT) and plasmapheresis, to cardiopulmonary bypass (CPB), extracorporeal life support (ECLS) and hepatic support. The development of internal man made organs is the next step with ventricular assist devices and artificial lungs. As we advance the technologies with smaller devices, and more intricate circuitry, we lack the keystone necessary to control the blood-biomaterial interface. For the last 50 years much has been learned about surface induced thrombosis and attempts have been made to prevent it with alternative systemic anticoagulation, circuitry surface modifications, or a combination of both. Despite these efforts, systemic or regional anticoagulation remain necessary for both laboratory and clinical application of ECC. As such, the development of an endothelial-like, biomimetic surface to reduce or perhaps even eliminate the blood activation/thrombus formation events that occur upon exposure to artificial surfaces is paramount.