Aluminium bone disease in patients receiving plasma exchange with contaminated albumin.

Aluminium balance studies were carried out on eight patients with various immunological disorders who were receiving plasma exchange with albumin solutions known to be contaminated with aluminium. Four patients with impaired renal function (creatinine clearance less than 50 ml/min) retained between 60% and 74% of the aluminium infused during a single plasma exchange. Transiliac bone biopsy specimens from three patients in this group had a high content of aluminium and showed histological evidence of current or previous bone disease related to aluminium. Two of these patients suffered intermittent bone pain. The main route of excretion of injected aluminium was in urine, only a small proportion of the total input being removed in the "plasma bag" during plasma exchange. The extent of aluminium retention and bone deposition was not reflected by the plasma aluminium concentration before or after plasma exchange. Treatment of five patients with intravenous desferrioxamine increased the plasma aluminium concentration and urinary output of aluminium in those with evidence of aluminium retention. These studies show that patients with poor renal function receiving treatment with albumin contaminated with aluminium retain the metal and deposit it in bone, where it may eventually cause aluminium bone disease. Plasma exchange should be used with caution in patients with renal impairment.     

Human immunodeficiency viruses in patients attending a sexually transmitted disease clinic in London, 1982-7.

OBJECTIVE--To determine the prevalence of infection with the human immunodeficiency virus (HIV) in all patients attending a London sexually transmitted disease clinic over four weeks at the end of 1987 and to see how it varied from that in similar samples studied between 1982 and 1986. DESIGN--Anonymous testing of serum samples from consecutive heterosexual and homosexual patients having routine serological investigations for syphilis. Testing was for anti-HIV-I, anti-HIV-II, and hepatitis B core antibody (anti-HBc) and P24 antigen. Age, nationality, sexual orientation, and past sexually transmitted diseases were recorded for each patient. Gonorrhoea rates by quarters were analysed among homosexual and bisexual men and heterosexual men and women from 1981 to 1987. SETTING--Outpatient department of genitourinary medicine. PATIENTS--A total of 1074 patients attending consecutively for syphilis serology. Thirty five homosexual and bisexual men were excluded (these were regular attenders as part of a prospective study of the natural course of HIV infection). MEASUREMENTS AND MAIN RESULTS--The prevalence of anti-HIV-I in homosexual and bisexual men in 1987 was 25.6% (64/250). Results in the same clinic population between 1982 and 1984 had shown a rise in prevalence, which flattened out in 1985-6 and continued at that level. Among heterosexual attenders in 1987 the prevalence of anti-HIV-I was 1% (women 4/412; men 4/377), which contrasted with a prevalence of 0.5% (women 2/395; men 3/757) in January 1986. One homosexual man was seropositive for anti-HIV-II and seronegative for anti-HIV-I. Among homosexual and bisexual men the rate of gonorrhoea had declined by an average of 2.7% a year since 1981, such that by 1987--and for the first time in the clinic--there was no significant difference in the rates between these men and heterosexual men and women. CONCLUSIONS--The appearance of HIV-I infection among heterosexuals indicates a need for more aggressive education programmes and intervention strategies along the lines adopted for homosexual men. Surveillance for HIV-II infection is needed to provide information for future policy in national screening programmes.     

Growth of silver hake within the U.S. continental shelf ecosystem of the northwest Atlantic Ocean

Von Bertalanffy growth parameters were estimated for silver hake Merluccius bilinearis within four regions of the United States continental shelf ecosystem of the northwest Atlantic Ocean during 1975–1980, 1982–1987 and 1988–1992. Differences in silver hake growth were found between the Middle Atlantic and southern Georges Bank regions ( P <0–01) over all three time periods. Growth also differed between northern Georges Bank and the Gulf of Maine ( P <0–01) during 1975–1980 and 1982–1987, and significant differences between southern Georges Bank and northern Georges Bank were found only during 1982–1987. Silver hake in the Gulf of Maine exhibited larger asymptotic sizes, but attained their asymptotic size at slower rates (L₀₀= 47 cm and K =0–33) in comparison to silver hake in the Middle Atlantic ( L₀₀= 43 cm and K =0–51), while growth parameter estimates for silver hake on Georges Bank were intermediate between these. Although significant differences in growth of silver hake between the various regions are consistent with separate stocks in the U.S. continental shelf ecosystem, the growth characteristics from the different regions are inconsistent with the presently assigned stock boundaries. (c) 1996 The Fisheries Society of the British Isles     

Survival after diagnosis of AIDS: a prospective observational study of 2625 patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

OBJECTIVE: To estimate median survival and changes in survival in patients diagnosed as having AIDS. DESIGN: Prospective observational study. SETTING: Clinics in two large London hospitals. SUBJECTS: 2625 patients with AIDS seen between 1982 and July 1995. MAIN OUTCOME MEASURES: Survival, estimated using lifetable analyses, and factors associated with survival, identified from Cox proportional hazards models. RESULTS: Median survival (20 months) was longer than previous estimates. The CD4 lymphocyte count at or before initial AIDS defining illness decreased significantly over time from 90 x 10(6)/1 during 1987 or earlier to 40 x 10(6)/1 during 1994 and 1995 (P < 0.0001). In the first three months after diagnosis, patients in whom AIDS was diagnosed after 1987 had a much lower risk of death (relative risk 0.44, 95% confidence interval 0.22 to 0.86; P = 0.017) than patients diagnosed before 1987. When the diagnosis was based on oesophageal candidiasis or Kaposi''s sarcoma, patients had a lower risk of death than when the diagnosis was based on Pneumocystis carinii pneumonia (0.21 (0.07 to 0.59). P = 0.0030 and 0.37 (0.16 to 0.83), P = 0.016). Three months after AIDS diagnosis, the risk of death was similar in patients whose diagnosis was made after and before 1987 (1.02 (0.79 to 1.31), P = 0.91). There were no differences in survival between patients diagnosed during 1988-90, 1991-3, or 1994-5. CONCLUSIONS: In later years, patients were much more likely to survive their initial illness, but long term survival has remained poor. The decrease in CD4 lymphocyte count at AIDS diagnosis indicates that patients are being diagnosed as having AIDS at ever more advanced stages of immunodeficiency.     

Declining incidence of AIDS dementia complex after introduction of zidovudine treatment.

OBJECTIVE--To assess the incidence of the AIDS dementia complex and the presence of HIV I p24 antigen in cerebrospinal fluid in relation to zidovudine treatment. DESIGN--Retrospective study of a consecutive series of patients with AIDS from 1982 to 1988. SETTING--An academic centre for AIDS. PATIENTS--196 Patients with AIDS and neurological symptoms examined from 1982 to 1988. INTERVENTIONS--Zidovudine treatment, which was introduced to The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (Centers for Disease Control groups IVA, B, C, and D). MAIN OUTCOME MEASURES--Diagnosis of AIDS dementia complex and presence of HIV I p24 antigen in cerebrospinal fluid. RESULTS--The AIDS dementia complex was diagnosed in 40 of the 196 (20%) patients with AIDS. Thirty eight of 107 patients with AIDS (36%) not taking zidovudine developed the AIDS dementia complex compared with two of the 89 (2%) taking the drug (p less than 0.00001). The incidence of the AIDS dementia complex increased to 53% in the first half of 1987, after the introduction of zidovudine in May 1987, decreasing to 10% in the second half of 1987 and to 3% in 1988. Dementia was diagnosed before definition of the AIDS dementia complex (1986) according to DSM-III criteria and there was good agreement between diagnosis before and after 1986. Sixteen of 61 samples of cerebrospinal fluid (26%) from patients with AIDS (10 with the AIDS dementia complex) not taking zidovudine were positive for HIV I p24 antigen, whereas none of 37 cerebrospinal fluid samples from patients with AIDS (two with the AIDS dementia complex) taking zidovudine were positive. CONCLUSIONS--The incidence of AIDS dementia complex in patients with AIDS declined after the introduction of systematic treatment with zidovudine; the AIDS dementia complex might be prevented by inhibiting viral replication in the central nervous system.     

Thrombotic thrombocytopenic purpura treated with plasma exchange or exchange transfusions.

Of 40 patients with thrombotic thrombocytopenic purpura, 17 were treated with plasma exchange, 15 with exchange transfusions, and 6 with both types of therapy. One patient died before being treated and another patient was seen but not treated. Plasma exchange was performed daily for a mean of seven exchanges per patient. The replacement fluid during plasma exchange was fresh frozen plasma in all cases. The complete response rates for each type of treatment were as follows: 88% for plasma exchange (15 patients), 47% for exchange transfusions (7 patients), and 67% for exchange transfusions and plasma exchange (4 patients). Clinical and laboratory factors were examined for any statistically significant association with therapy response. Treatment with plasma exchange was statistically the initial factor most strongly associated with prognosis. Paresis, paresthesias, seizures, mental status change, and coma showed no association with response to treatment. Some of the laboratory factors that did not show significant association with treatment response were the initial creatinine, hemoglobin, platelet count, lactate dehydrogenase, and total bilirubin. This study supports the hypothesis that plasma exchange has significantly improved the prognosis of patients with thrombotic thrombocytopenic purpura. These patients should be treated aggressively regardless of the severity of their symptoms.     

The modified primary succession following sand mining: A validation of the use of chronosequence analysis

Changes in small mammal succession along a forested coastal dune system in the Myall Lakes-National Park, New South Wales, during 15 years of regeneration after sand mining, were determined by surveys in 1982 and 1987. The results clearly demonstrate a wave of succession moving along the mining path, and confirm that over the intervening 5 year period to 1987, small mammal succession has followed a path indicated by that of the 1982 chronosequence. The house mouse, Mus musculus quickly recolonizes disturbed areas, and peak abundance occurred on plots with a regeneration age of 3.7 years in 1982 and 3.4 years in 1987 (i.e. the 3.0–4.5 age class). Colonization by the New Holland mouse. Pseudomys novaehollandiae was first recorded on plots with 4.6 years regeneration in 1982 and 5.4 years in 1987. Peak Pseudomys numbers occurred on plots in the 7.5–9.0 age class in both 1982 and 1987. The common dunnart, Sminthopsis murina appears to be the third species to enter the succession. This modified primary succession closely resembles the mammalian secondary succession following fire where additional evidence suggests that the use of chronosequence analysis may also be appropriate.     

Inpatient deaths from acute myocardial infarction, 1982-92: analysis of data in the Nottingham heart attack register.

OBJECTIVE: To assess longitudinal trends in admissions, management, and inpatient mortality from acute myocardial infarction over 10 years. DESIGN: Retrospective analysis based on the Nottingham heart attack register. SETTING: Two district general hospitals serving a defined urban and rural population. SUBJECTS: All patients admitted with a confirmed acute myocardial infarction during 1982-4 and 1989-92 (excluding 1991, when data were not collected). MAIN OUTCOME MEASURES: Numbers of patients, background characteristics, time from onset of symptoms to admission, ward of admission, treatment, and inpatient mortality. RESULTS: Admissions with acute myocardial infarction increased from 719 cases in 1982 to 960 in 1992. The mean age increased from 62.1 years to 66.6 years (P < 0.001), the duration of stay fell from 8.7 days to 7.2 days (P < 0.001), and the proportion of patients aged 75 years and over admitted to a coronary care unit increased significantly from 29.1% to 61.2%. A higher proportion of patients were admitted to hospital within 6 hours of onset of their symptoms in 1989-92 than in 1982-4, but 15% were still admitted after the time window for thrombolysis. Use of beta blockers increased threefold between 1982 and 1992, aspirin was used in over 70% of patients after 1989, and thrombolytic use increased 1.3-fold between 1989 and 1992. Age and sex adjusted odds ratios for inpatient mortality remained unchanged over the study period. CONCLUSIONS: Despite an increasing uptake of the "proved" treatments, inpatient mortality from myocardial infarction did not change between 1982 and 1992.     

Plasma therapy for severe hemolytic-uremic syndrome in children in Atlantic Canada.

Clinical reports have suggested that therapy with fresh frozen plasma is a useful adjunct in the management of the hemolytic-uremic syndrome (HUS). We reviewed the charts of 36 children with severe HUS who were treated at the Izaac Walton Killam Hospital for Children, Halifax, over 10 years to assess the effectiveness of plasma therapy. All children who required specific supportive therapy for renal dysfunction, hemolysis or serious extrarenal complications were included. We compared the outcome of 18 children who received plasma therapy from 1982 to 1987 with that of 18 children who did not. The two groups were similar with regard to the severity of HUS, the length of hospital stay, the duration of renal dysfunction and the incidence of disease-related complications, such as seizures, enterocolitis and cardiomyopathy. At discharge the prevalence of hypertension was higher in the plasma therapy group than in the control group. Plasma therapy did not demonstrate any benefit that would outweigh the risk of fluid overload, hyperproteinemia and transmission of viral infection.     

Haemorrheological response to plasma exchange in Raynaud's syndrome.

Eight patients with Raynaud''s syndrome were treated by weekly plasma exchange for four weeks using a Haemonetics Model 30 Blood Processor. The mean whole-blood viscosity at a shear rate of 0.77/s was significantly lower after treatment, and the mean index of red-cell deformability was significantly improved. In four patients studied serially the mean percentage fall in whole-blood viscosity after a single plasma exchange was 49% at 0.77/s but only 14% at 91/s. All patients noticed symptomatic improvement including healing of ischaemic digital ulcers. In six patients the number of digital arterial segments containing detectable blood flow was measured by directional Doppler; in all six the number increased. It is concluded that plasma exchange is an effective means of haemorrheological treatment and may be beneficial in patients with digital ischaemia.     

Substance P plasma levels in pregnancy and in various clinical disorders.

Using radioimmunoassay, immunoreactive SP (iSP) has been measured in the plasma of 162 hospital patients with various disorders and in the plasma of 67 pregnant women. In pregnancy, iSP was undetectable in 40% women as compared to 12% in other hospital patients. The mean iSP plasma level in pregnancy was 37.8 +/- 4.6 (SEM) as compared to 77.1 +/- 4.9 (SEM) pg/ml in other hospital patients. The results support earlier observations based on bioassay, suggesting that the blood of pregnant women contains higher concentrations of a SP-inactivating factor. Of the hospital patients, elevated levels of iSP were found in patients with chronic leukaemia, in one patient with a basaloid carcinoma of the anus, and in one patient with toxic liver damage and pancreatic insufficiency. No correlation was found between thyroid function and iSP plasma levels. ISP plasma levels in various gastrointestinal disorders were similar to those found in normal subjects.     

The incidence of Encephalitozoon cuniculi in a commercial barrier-maintained rabbit breeding colony.

Between 1982 and 1987 sera from 4952 New Zealand White rabbits (Oryctolagus cuniculus) obtained from a single commercial supplier were tested for the presence of antibodies to Encephalitozoon cuniculi. A commercially available carbon immunoassay test kit was used. Initially 32.9% of the rabbits were seropositive with the number progressively decreasing to 2.3% by 1987. The reason for the significant decline in the incidence of infection was most likely due to a selection process for breeding stock instituted by the supplier based upon productivity, posture and weight of each animal.     

Prerequisites for recruitment of Kittiwakes Rissa tridactyla

Observations at the North Shields Kittiwake colony between 1982 and 1984 showed over 100 potential recruits (birds of breeding age) associated with the colony, only about 40% of which were actually recruited. In addition, there were younger birds which visited the colony. The origins, age structure and intercolony movements of members of the pool of prospectors have been examined. Porter & Coulson (1987) demonstrated that recruits are heavier than prospectors, implying that they are in better body condition. Three further prerequisites for breeding in Kittiwakes are recognized: the age of recruits is at least three years; all birds which recruit are present at the colony at least one year prior to breeding; and recruits show a high degree of attachment to colony as illustrated by their colony and nest site tenacity, attendance and early arrival. The results suggest that there is considerable selection of individuals at the time of recruitment; the mechanism for this has yet to be examined.     

Prospective pricing and DRGs.

In the Congenital Heart Program at San Diego Children''s Hospital, alterations in medical practice have reduced costs without impairing quality or access. Pediatric cardiac catheterization was done in 483 consecutive elective patients without overnight hospital stay. Hospital readmission was required in one patient for psoas tendinitis. Avoiding overnight hospital stay minimized attendant risks of hospital care, lessened psychosocial trauma and reduced the average hospital bill by $493 (29%). Hospital stay was also reduced for elective surgical correction of congenital heart disease on a case-by-case basis. Review of 151 consecutive cases (1978 through 1982) showed a decrease in both preoperative days in hospital and postoperative days in an intensive care unit. The duration of the postoperative stay was shortened from 6.8 days in 1978-1979 to 4.4 days in 1982 (P <.05). No increase in morbidity and no mortality resulted from the shortened perioperative hospital stay. Financial savings from this process averaged $991 per procedure.Diagnostic tests were reassessed and many precatheterization laboratory tests were eliminated. Without change in new patients seen or surgical volume, the use of cardiac catheterization decreased from 241 procedures in 1981 to 161 in 1982 and the number of operations without catheterization increased (11 to 22, 1981 to 1982). No increase in surgical morbidity or mortality was found comparing those diagnosed only by echocardiography with those who had preoperative cardiac catheterization. The decrease of 80 catheterizations in one year resulted in a savings of $188,800.True cost containment (reducing cost without reducing quality) can be accomplished in congenital heart programs. Similar cost containments in other disciplines may also be achieved.     

Genetic mapping of a highly variable norovirus GII.4 blockade epitope: potential role in escape from human herd immunity

Noroviruses account for 96% of viral gastroenteritis cases worldwide, with GII.4 strains responsible >80% of norovirus outbreaks. Histo-blood group antigens (HBGAs) are norovirus binding ligands, and antigenic and preferential HBGA binding profiles vary over time as new GII.4 strains emerge. The capsid P2 subdomain facilitates HBGA binding, contains neutralizing antibody epitopes, and likely evolves in response to herd immunity. To identify amino acids regulating HBGA binding and antigenic differences over time, we created chimeric virus-like particles (VLPs) between the GII.4-1987 and GII.4-2006 strains by exchanging amino acids in putative epitopes and characterized their antigenic and HBGA binding profiles using anti-GII.4-1987 and -2006 mouse monoclonal antibodies (MAbs) and polyclonal sera, 1988 outbreak human sera, and synthetic HBGAs. The exchange of amino acids 393 to 395 between GII.4-1987 and GII.4-2006 resulted in altered synthetic HBGA binding compared to parental strains. Introduction of GII.4-1987 residues 294, 297 to 298, 368, and 372 (epitope A) into GII.4-2006 resulted in reactivity with three anti-GII.4-1987 MAbs and reduced reactivity with four anti-GII.4-2006 MAbs. The three anti-GII.4-1987 MAbs also blocked chimeric VLP-HBGA interaction, while an anti-GII.4-2006 blocking antibody did not, indicating that epitope A amino acids comprise a potential neutralizing epitope for GII.4-1987 and GII.4-2006. We also tested GII.4-1987-immunized mouse polyclonal sera and 1988 outbreak human sera for the ability to block chimeric VLP-HBGA interaction and found that epitope A amino acids contribute significantly to the GII.4-1987 blockade response. Our data provide insights that help explain the emergence of new GII.4 epidemic strains over time, may aid development of norovirus therapeutics, and may help predict the emergence of future epidemic strains.     

Changing disease patterns in patients with AIDS in a referral centre in the United Kingdom: the changing face of AIDS.

OBJECTIVE--To study the changes in morbidity, mortality, and survival patterns in a population of patients with AIDS in the United Kingdom from 1982 to 1989. DESIGN--A retrospective analysis of inpatient and outpatient records of patients with AIDS. SUBJECTS--347 Patients with AIDS, predominantly homosexual or bisexual men. SETTING--Departments of immunology and genitourinary medicine, St Mary''s Hospital, London. MAIN OUTCOME MEASURES--Presenting diagnosis of AIDS, occurrence of other opportunist diseases, cause of death, and survival since AIDS was diagnosed, in particular for those patients with Pneumocystis carinii pneumonia or Kaposi''s sarcoma. RESULTS--The overall proportion of patients who developed P carinii pneumonia dropped from 56% (20/36) in 1984 to 24% (46/194) in 1989, although it has remained the index diagnosis in about half of new patients. Kaposi''s sarcoma has decreased as index diagnosis from 30% (20/67) to 20% (15/74) over the same period, though the prevalence has remained constant at around 35%. P carinii pneumonia accounted for 46% (16/35) of known causes of death in 1986 but only 3% (1/31) in 1989. Conversely, deaths due to Kaposi''s sarcoma rose from 14% (1/7) to 32% (10/31) between 1984 and 1989. Lymphoma accounted for an increased proportion of deaths among these patients with 16% (5/31) of deaths in 1989. Their median survival increased from 10 months in 1984-6 to 20 months in 1987. CONCLUSIONS--The changing patterns of disease in patients with AIDS have important implications both for health care provision and future medical research. Medical and nursing provision must be made for the increased morbidity of these diseases and the increased survival of these patients. Research should now be directed towards developing effective treatments for the opportunist infections which are currently more difficult to treat, the secondary malignancies of AIDS, as well as more effective immunorestorative treatments. Future changes in disease patterns must be recognised at an early stage so that resources can be adequately planned and allocated.     

High affinity divalent cation exchange on actin. Association rate measurements support the simple competitive model

Each actin molecule has one high affinity site which binds a divalent cation. It has been proposed that an isomerization of the actin molecule is involved in divalent cation exchange at this site ("isomerization model," Frieden, C. (1982) J. Biol. Chem. 257, 2882-2886); we have maintained that exchange is by a simple competitive mechanism (Estes, J. E., Selden, L. A., and Gershman, L. C. (1987) J. Biol. Chem. 262, 4952-4957). Here, using fluorescent-labeled actin, we measure the apparent rate constant for exchange (kapp) as a function of the ratio of free Ca2+ and Mg2+ concentrations, ([Ca]/[Mg]), and show that both models are consistent with the data. The major parameter controlling this relationship in the simple competitive exchange model, the ratio of the association rate constants for Ca2+ and Mg2+ to actin (kCa/kMg), is found to have a value of about 90. We have verified this parameter by direct measurements of kCa and kMg, finding that kCa = 1.9 x 10(7) M-1 s-1 and kMg = 2.3 x 10(5) M-1 s-1, consistent with the characteristics of the Ca2+ and Mg2+ aquo ions. The corresponding parameter derived from the isomerization model is not verifiable. We conclude that high affinity divalent cation exchange on actin proceeds by a simple competitive mechanism.     

Neglected markers: altered serum proteome in murine models of disease

More than a decade ago our groups pioneered the analysis of serum proteins of laboratory animals with up-to-date proteomic techniques. We were, and still are, convinced that conforming animal procedures to the minimally invasive approaches typical of clinical biochemistry focuses attention on the actual conditions under which any finding arrived at on animal models of disease may eventually be applied to human patients for screening/diagnosis. We are also convinced that, besides the proteins present in trace level as a result of tissue leakage during disorders affecting specific peripheral organs, changes in the concentration of some of the major serum proteins as part of an acute-phase response may be taken as biological end-points during a number of experimental procedures. When reviewing literature data about proteomic investigations on plasma or serum of mice, we realized that not much work has been done in the direction we favor. In addition, we noticed that sometimes information about serum proteome has been coarsely treated and in a few cases even misunderstood/misused. In the following, we present current findings on serum/plasma proteome of the laboratory mouse not only under control conditions and during an experimentally induced acute-phase reaction, but also in a number of models of disease, mainly related to cancer and to metabolic disorders.     

Why are diabetic patients treated at rheumatological hospitals?]

Retrospective analysis included 316 case histories of diabetic patients treated at the Silesian Rheumatology Hospital in 1987-1988. An analysis included causes of disorders, calcium-phosphorus metabolism disturbances, lipid and purine disorders. Statistical parameters were compared with the type of diabetes mellitus, duration of the disease, sex, age and obesity. There were 10% of inflammatory rheumatic disorders (6.4% rheumatic arthritis, 1.7% of rheumatoid spondylosis and 2% of other disorders) in the analysed case histories, and 32% of degenerative disorders (19% of vertebral column joints and 12.7% of other joints). Degenerative disorders were noted more frequently in patients with diabetes mellitus type 2, treated with insulin, while spondylopathies were particularly frequent in female patients of this group. Biochemical disorders in the form of hypocalcemia and hypophosphatemia, hypertriglyceridemia, hyperuricemia, signs of lesions to the liver and kidneys were more increasing with the duration of the disease and the degree of insulin-dependence. Locomotive system disorders are not related only to primary articular lesions. They depend also on diabetic neuro-vascular complications and osteopenia.     

Meningococcal septicaemia treated with combined plasmapheresis and leucapheresis or with blood exchange.

Mortality among patients suffering from meningococcal septicaemia has reached nearly 50% in parts of northern Norway despite intensive care. The activation of complement and blood cells by endotoxin is assumed to be the cause of most of the associated pathophysiological changes. Consequently, it would seem logical to remove such constituents either by combined plasmapheresis and leucapheresis or by blood exchange in patients with a fatal prognosis. Three patients were treated with plasmapheresis and leucapheresis and one with blood exchange. All recovered without sequelae, and no complications or serious problems caused by these procedures were observed. It is concluded that either combined leucapheresis and plasmapheresis or blood exchange is well tolerated and a valuable supplement to conventional intensive care in fulminant meningococcal septicaemia.