[An amebic liver abscess; early suspicion, late detection]. / Een amoebenabces in de lever; vroeg vermoeden, late detectie.

Two men aged 38 and 26 years developed symptoms including pain in the (upper) abdomen, malaise and fever 1.5-5 months after visiting the Caribbean. It was only after repeated ultrasonography that liver abscesses were observed. Adequate treatment was instituted and the patients recovered. The diagnosis of 'amoebic abscess of the liver' is usually based on the clinical presentation, the serological findings and characteristic observations at ultrasonography. However, if patients are seen at an early stage of development of the abscess, the serological findings may be negative and the ultrasonographic findings normal; consequently these findings do not justify exclusion of the diagnosis.

The release of endotoxin from antibiotic-treated Escherichia coli and the production of tumour necrosis factor by human monocytes.

The influence of antibiotic-induced release of endotoxin from in-vitro grown Escherichia coli on the production of tumour necrosis factor-alpha (TNF) by human monocytes was studied. Antibiotics tested were: cefuroxime (7.5 and 75 mg/L); ceftazidime (10 and 100 mg/L); aztreonam (10 and 100 mg/L); imipenem (10 and 100 mg/L); and tobramycin (8 mg/L). The effect of the combination of cefuroxime plus tobramycin, and the effect of taurolidine, an endotoxin-binding agent, on TNF production was also tested. After incubation for 4 h, all antibiotic-treated cultures (high-dose) induced a similar rise in extracellular TNF production when compared to the controls. However, after incubation for 24 h, a significant rise in TNF production was noticed in the cefuroxime and aztreonam-treated cultures (6440 and 5969 ng/L, respectively) compared to the ceftazidime and imipenem-treated cultures (846 and 381 ng/L, respectively). The cefuroxime-induced release of TNF could be reduced by addition of tobramycin (from 6440 to 1615 ng/L). Similar differences in TNF production were noticed in cell-associated TNF. Dose-response curves did not demonstrate differences in TNF production in aztreonam or imipenem-treated cultures. However, for both cefuroxime and ceftazidime-treated cultures, low-dose treatment resulted in significantly higher production of TNF. The differences in TNF production between these antibiotics could be explained by the production of filaments following treatment with cefuroxime, aztreonam and low-dose ceftazidime, resulting in late bacterial lysis with high levels of endotoxin, whereas treatment with imipenem or high-dose ceftazidime resulted in the formation of spheroplasts, resulting in early lysis of the bacteria and much lower levels of endotoxin. The addition of taurolidine to either imipenem or aztreonam-treated cultures prevented a rise in TNF production as a result of nearly complete neutralization of the released endotoxin. It was concluded that the observed differences in TNF production by human monocytes in vitro were related to differences in the mechanisms and amount of antibiotic-induced release of endotoxin.

[Pyomyositis, not an exclusively tropical disease]. / Pyomyositis, niet alleen een tropische ziekte.

Pyomyositis is considered to be limited to tropical areas. In recent years, however, it is increasingly reported from temperate climate areas, predominantly in immunocompromised patients. Since the disease can mimic several other conditions, it may remain unrecognized for weeks. Two native patients from the Netherlands are presented, neither of them had ever travelled to the tropics. One of the patients had AIDS, the other had no predisposing factors. Pyomyositis can be difficult to diagnose, but in most cases it is easy to cure. Pyomyositis should be considered in the differential diagnosis in patients with fever and localised myalgia.

Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acute-phase proteins during the treatment of severe sepsis in humans.

OBJECTIVE: To study the patterns of plasma concentrations of endotoxin, tumor necrosis factor-alpha (TNF), interleukin-6 (IL-6), plasminogen activator inhibitor-1, C-reactive protein, and serum amyloid A during the treatment of human sepsis. DESIGN: A prospective case series study. SETTING: ICU of the Department of Internal Medicine, University Hospital Groningen, The Netherlands. PATIENTS: Twenty consecutive patients (11 female, 9 male, mean age 67 yrs) with clinically defined sepsis. Eighteen patients were admitted from the outpatient emergency ward; two patients were already inpatients. The control group (n = 7) comprised patients with nonseptic shock. MEASUREMENTS AND MAIN RESULTS: Ten (50%) septic patients had detectable endotoxemia (greater than 5 (ng/L). TNF concentrations on admission were increased in 94% of the septic patients, whereas IL-6 and plasminogen activator inhibitor plasma concentrations were increased in all septic patients. The septic group showed significantly (p less than .05) higher concentrations of TNF, IL-6, plasminogen activator inhibitor-1, C-reactive protein, and serum amyloid A compared with the nonseptic patients. In the septic group, we found a correlation of both IL-6 and plasminogen activator inhibitor concentrations with severity of illness (r2 = .33, p less than .05; r2 = .22, p less than .05, respectively). After the start of antibiotic treatment, high concentrations of TNF and plasminogen activator inhibitor persisted in the nonsurvivors in contrast to decreasing concentrations in most of the survivors. After an initial increase in seven patients, IL-6 concentrations decreased in all septic patients and also in nonsurvivors. CONCLUSIONS: This study confirms previous findings that: a) TNF is a major mediator involved in the pathogenesis of septic shock; b) plasminogen activator inhibitor activity is significantly increased in septic patients and might be involved in the pathogenesis of disseminated intravascular coagulation associated with sepsis; and c) IL-6 is involved in the pathophysiology of septic shock, although further studies are needed to determine whether IL-6 is directly involved in mediating the lethal complications of septic shock or whether it should be considered an "alarm hormone" that reflects endothelial cell injury. Our findings also suggest that the concentrations and trends of these mediators during treatment are valuable for monitoring septic patients.

Complement activation and the production of inflammatory mediators during the treatment of severe sepsis in humans.

Sepsis or septic shock is frequently associated with activation of the complement system, coagulation and fibrinolytic changes and the release of several cytokines. In this study we analyzed the relation of complement activation to the inflammatory mediators, hemodynamic and biochemical parameters and severity of illness and outcome in 20 consecutive patients with clinically defined sepsis. Levels of C3a and C3d were elevated in 90% of the patients (median levels 0.19 mg/l and 8.6 mg/l respectively) in comparison to 14% and 42%, respectively of 7 patients with non-septic shock. Levels of C4 were decreased in only 1 of the 20 septic patients. Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, Levels of TNF and IL-6 were elevated in 94% and 100% of the patients, respectively (median levels 122 ng/l and 1300 U/ml) and were clearly interrelated (r = 0.67, p less than 0.01). C3a levels correlated with the APACHE II score (r = 0.57, p less than 0.05) and high C3a levels were associated with fatal outcome (p less than 0.05). C3a was also correlated inversely with mean arterial pressure (r = 0.50, p less than 0.01). Levels of complement C3a and C3d significantly correlated with levels of plasminogen activator inhibitor-1 (PAI) and correlated inversely with AT-III levels. We found no correlation between these complement products and leukocyte counts or lactate levels, nor was there a correlation between C3a or C3d and the cytokines TNF and IL-6. Levels of C3a and C3d did not decrease significantly during the first 24 h of treatment, in contrast to a clear decrease in IL-6 levels in all patients and a decrease in TNF in the surviving patients. TNF levels remained stable or increased in the non-survivors. We conclude that both the complement system and the cytokine system are involved in the pathogenesis of septic shock and may be involved in the development of some of the fatal complications like hypotension and disseminated intravascular coagulation.

Fatal respiratory failure caused by pulmonary infiltration by pseudo-Gaucher cells.

Pseudo-Gaucher cells are reticuloendothelial cells that are found in several diseases. We report a case of pulmonary tuberculosis in which extensive pulmonary involvement with these cells resulted in fatal respiratory failure.

[Mycobacterium avium disease in AIDS patients; diagnosis and therapy]. / Mycobacterium avium-ziekte bij AIDS-patiënten; diagnostiek en therapie.

In eight (25%) of 32 consecutive AIDS patients between 1986 and 1989, Mycobacterium avium infection was diagnosed: in seven disseminated, in one as a local lymph node process. Six patients were treated as consistently as possible with a combination of ethambutol, rifabutine, clofazimine and protionamide (or cycloserine) in relatively large dosages. Median survival of treated patients was 15.5 (4-22) months. Protionamide inhibited most M. avium strains (7 of 8) in vitro, but often caused intolerance (nausea). Treatment of disseminated cytomegalovirus infection in our opinion was necessary in 5 of 6 patients during longterm M. avium therapy. HIV therapy (Zidovudine) during M. avium treatment was not possible due to bone marrow depression. A low maintenance dose of corticosteroids was necessary in 3 of 6 patients (one with adrenal insufficiency) to suppress symptoms such as fever and malaise.

Fusobacterium pyomyositis of the shoulder after tonsillitis. Report of a case of Lemierre's syndrome.

A case of nontropical pyomyositis is reported in a young male without predisposing factors. The disease was preceded by a tonsillitis, and the presentation initially suggested a septic arthritis of the shoulder. Fusobacterium, a highly unusual pathogen in pyomyositis, was isolated from an abscess in the infraspinatus muscle. The increasing frequency of the disease in areas with a temperate climate and the pathogenesis are discussed. Our case had the classic features of Lemierre's syndrome: invasion of the bloodstream by Fusobacterium species from a tonsillitis.

[Hemorrhagic fever caused by dengue in 2 tourists]. / Hemorragische koorts door dengue bij twee toeristen.

Dengue haemorrhagic fever in two female tourists to Thailand (1990) and Indonesia (1989) respectively, is reported for the first time in the Netherlands. The main symptoms directly after return were high fever, haemorrhagic exanthema, thrombocytopenia and in one patient signs of haemoconcentration. Initially both patients were treated with antibiotics. They recovered after intravenous fluid therapy; one of them received a thrombocyte transfusion. Increasing travel to Asia and South America will result in more tourists returning with this potentially serious arboviral disease (dengue haemorrhagic shock).

Tumour necrosis factor (cachectin) and other cytokines in septic shock: a review of the literature.

The role of bacterial endotoxin in the pathogenesis of septic shock has been studied extensively. Endotoxin does not seem to exert most of its effects on the host directly, but rather it elicits the production of host factors that may in turn lead to shock and death. These factors, called cytokines, appear to be produced by cells of haematopoietic origin such as macrophages/monocytes, but can also be produced by other cells such as endothelium and fibroblasts. Three important cytokines associated with septic shock are tumour necrosis factor/cachectin (TNF), interleukin 1 (IL-1) and interleukin 6 (IL-6). The macrophage-derived TNF has been implicated as the most important host mediator in the pathogenesis of septic shock. TNF, alone or together with endotoxin or IL-1, is capable of inducing lethal shock and tissue injury resembling that of septic shock. It has also been suggested that IL-6 is involved in the pathogenesis of septic shock. The major biologic activities of IL-6 include B-cell differentiation and induction of the acute-phase proteins. In the present paper, reports addressing the current understanding of the biological, regulatory and clinical aspects of these cytokines are reviewed.

Effects of different types and combinations of antimicrobial agents on endotoxin release from gram-negative bacteria: an in-vitro and in-vivo study.

Total and free endotoxin release in time from cultures of Escherichia coli by different antibiotics was studied in vitro for 4 h in relation to the antibiotic effect on viable counts and morphological features of the test cultures. The most rapid fall in viable counts was seen after treatment with imipenem or the combination of imipenem with tobramycin, accompanied by an early, but minimal increase (1.8-fold) of the total (free plus cell-bound) endotoxin level at 1 h. Total endotoxin levels increased approximately 5-fold upon incubation with ceftazidime, tobramycin or the combination of tobramycin with cefuroxime, whereas incubation with cefuroxime or aztreonam alone caused a late 22-and 49-fold increase in total endotoxin, respectively, at 4 h. In chloramphenicol treated cultures there was still an increase in viable counts during therapy, resulting in an ultimately 78-fold increase of mean levels of total endotoxin. Free endotoxin levels increased approximately 6-fold within 1 h upon treatment with imipenem, alone or in combination with tobramycin, or ceftazidime as the result of rapid lysis of bacteria. Treatment with cefuroxime or aztreonam induced a relatively late but much higher release of free endotoxin (118-and 222-fold, respectively), which was due to the formation of long filamentous structures during the first 2 h of incubation and eventually cell lysis. Both tobramycin and the combination of tobramycin with cefuroxime caused a more gradual rise in free endotoxin, with a +/- 15-fold increase in free endotoxin at 4 h. In chloramphenicol treated cultures, as in the control cultures, the level of free endotoxin remained proportional to the amount of viable organisms. We also studied plasma endotoxin levels in 20 patients with septic shock. 10 out of these 20 patients had a detectable endotoxemia (greater than 5 ng/l) on admission. We describe the patterns of plasma endotoxin in these patients during the first 24 h of antibiotic treatment. We conclude that, in the in-vitro study, values of total endotoxin, free endotoxin, and the rate of release of endotoxin varies with the antibiotic used. We also demonstrate that in patients under treatment for septic shock endotoxin release can be related to the administration of antibiotics.

Nontropical pyomyositis as a cause of subacute, multifocal myalgia in the acquired immunodeficiency syndrome.

We report a case of nontropical pyomyositis in a patient with acquired immunodeficiency syndrome and disseminated Mycobacterium avium infection, in which severe myalgia was the presenting symptom over several weeks. Multifocal muscle lesions were identified by gallium scanning and magnetic resonance imaging techniques. The epidemiology, possible pathogenesis, clinical features, diagnostic imaging, and therapy are reviewed. Early suspicion of nontropical pyomyositis in severely immunocompromised patients with "cryptic" myalgia is recommended.

Cytomegalovirus antigenemia.

The cytomegalovirus (CMV) antigenemia test is a new direct method of diagnosing active CMV infection. The test is based on immunocytochemical detection of CMV immediate early antigens in blood leukocytes. Technical aspects and pitfalls are discussed. The diagnostic merits of the test are compared with those of other methods, such as isolation of virus from blood, serologic determinations, and the polymerase chain reaction. Overall, active CMV infection can be diagnosed by the detection of CMV antigenemia with a sensitivity and specificity of greater than or equal to 90%, whereas sensitivity is 100% in symptomatic patients. On average, the test provides diagnostic information at least 1 week earlier than other established methods. Moreover, the level of CMV antigenemia appears to be related to the severity of disease and to be inversely related to the level of host immunocompetence. It is concluded that (1) the test is useful for the early and rapid diagnosis of life-threatening CMV infection in immunodeficient patients, (2) the test could be a useful tool in the study of the immunopathophysiology of CMV disease, and (3) the antigenemia test may be a promising marker for monitoring disease activity and its response to specific chemotherapy.

Relapse Pneumocystis carinii pneumonitis and adverse reaction to current therapy in patients with AIDS: trimetrexate as an alternative.

This is a case report of a 31-yr-old homosexual male with AIDS, admitted to our clinic with a relapse P. carinii pneumonitis (PCP) and a previous history of severe adverse reactions to currently used therapy. He was treated successfully with trimetrexate (TMTX), a dihydrofolate reductase inhibitor combined with leucovorin rescue. Adverse reactions, current therapy and prophylaxis of PCP in AIDS are discussed.

Familial increased serum intestinal alkaline phosphatase: a new variant associated with Gilbert's syndrome.

Investigation of mild, inherited increased serum alkaline phosphatase activity partially combined with Gilbert's syndrome in one family showed, apart from a normal liver fraction, an intestinal isoenzyme pattern and an extra band in the agar electrophoresis. Analysis by agarose electrophoresis before and after incubation of neuraminidase showed that the extra fraction was an intestinal variant isoenzyme. The precise genetic background of the two disorders in this family could not be determined from the available data. Abnormal activities of (regular) intestinal alkaline phosphatase isoenzyme caused the increase in serum alkaline phosphatase in the absence of disease.

Lymphoedema of the legs as a result of lymphangiomyomatosis. A case report and review of the literature.

Leg lymphoedema is described as an unusual presenting feature of lymphangiomyomatosis. MRI scanning revealed typical lesions. Possible sex hormonal manipulation as a therapy for pulmonary or abdominal involvement is reviewed.