[Clinical reasoning and decision making in practice. A depressive foreign woman with symptoms of malaise]. / Klinisch denken en beslissen in de praktijk. Een depressieve buitenlandse vrouw met klachten van malaise.

A 27-year-old woman was admitted to the hospital with a depression, anaemia and fatigue. She had come from Angola to the Netherlands as a refugee 2 years before this evaluation. As an explanation for her symptoms tropical infectious diseases of parasitic origin were considered, but no clues were found in this direction. The test for trypanosomiasis was considered to be suggestive for an infection in the past (persistent titre 1:200). She was discharged but readmitted 6 months later because of a deterioration of her clinical condition. Magnetic resonance imaging showed bilateral signal abnormalities within the white matter of the brain. On examination no neurological signs or abnormalities were found. Again, no definite diagnosis could be made and the patient was discharged. Because of a further deterioration of her clinical condition she was readmitted a short time later for the third time. On the MRI the white matter lesions had increased. The serum protein electrophoresis was markedly abnormal with an elevated IgM Level. Finally, at a repeated lumbar puncture mobile trypanosomes were found. The diagnosis of 'West African sleeping sickness' was made and the patient was treated with eflornithine. She recovered completely during the next 18 months.

Relative bioavailability of three newly developed albendazole formulations: a randomized crossover study with healthy volunteers.

This study of healthy volunteers shows that the relative bioavailability of albendazole formulations that use arachis oil-polysorbate 80 or hydroxypropyl-beta-cyclodextrin as an excipient was enhanced 4.3- and 9.7-fold compared to the results seen with commercial tablets. Administration of macrogol suppositories did not result in measurable plasma concentrations of albendazole sulfoxide.

[Giant diverticulum of the sigmoid]. / Reuzendivertikel van het sigmoïd.

A 77-year-old woman who had been examined 8 months previously because of chronic abdominal pain and an altered pattern of defecation presented to the emergency department with complaints of nausea, vomiting and acute pain in the abdomen. Her appetite was diminished and she had lost 10 kg in the past year. The abdominal X-ray showed a balloon-like, gas-filled intra-abdominal configuration, which proved to be a giant diverticulum of the sigmoid. She was treated by resection of the diverticulum and the sigmoid. A giant diverticulum is a rare complication of diverticulosis, a frequently occurring condition that is encountered most often in the sigmoid; the complication can easily be missed. The presenting symptoms can vary from an acute abdomen to chronic non-specific abdominal complaints. The most important complications of a giant diverticulum are perforation, obstruction or a volvulus. In view of the severity of these complications, resection of that part of the intestine in which the giant diverticulum arises is the treatment of choice.

Diagnosis and treatment of hepatic echinococcosis: an overview.

BACKGROUND: Surgery has long been considered the first-choice treatment in patients with echinococcosis of the liver. The poorly predictable outcome of older studies using mebendazole or albendazole confirmed this belief. Since the introduction of a percutaneous technique (PAIR; puncture, aspiration, injection, reaspiration) treatment policy is changing. The actual question is which treatment is preferred in which patients. METHODS: Review of recent literature. RESULTS: Laparoscopic treatment of anteriorly located hepatic cysts is a new surgical technique with high success rates (77%-100%) and low complication (0%-17%) and recurrence rates (0%-9%). Albendazole is superior to mebendazole treatment. Degenerative changes were found in 82% of patients treated with albendazole and in 56% of those treated with mebendazole. The main problem is the high relapse rate: 25% mostly within 2 years. PAIR proved to be superior to albendazole treatment (88% versus 18%) and equally effective as surgery (86% versus 76%). A combined injection of alcohol with polidocanol is a simple alternative to PAIR. Percutaneous evacuation of cyst content (PEVAC) made percutaneous treatment accessible to patients with complicated cysts. CONCLUSIONS: Albendazole is the first-choice treatment in patients with univesicular cysts. PAIR or combined injection of alcohol with polidocanol is indicated when pain is intractable or albendazole fails. In patients with multivesicular cysts, PEVAC is a better choice. Surgery is the first-choice treatment only when the expertise of percutaneous treatment is not available or when percutaneous treatment fails.

Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability.

The assumed metabolic breakdown of albendazole by mucosal CYP3A4 enzymes was studied by coadministering albendazole (10 mg/kg) with grapefruit juice. Concentrations of albendazole sulfoxide (ABZSX), the active metabolite of albendazole, were compared with those after albendazole was administered with water, a fatty meal, or grapefruit juice plus cimetidine (10 mg/kg). In comparison to water, maximum ABZSX concentration (Cmax) was enhanced 6.5-fold by a fatty meal (from 0.24 +/- 0.09 mg/l to 1.55 +/- 0.30 mg/l; mean +/- SD; P < 0.001) and 3.2-fold by grapefruit juice (from 0.24 +/- 0.09 mg/l to 0.76 +/- 0.37 mg/L; P = 0.031). When grapefruit juice was combined with cimetidine, Cmax was significantly lower than with grapefruit juice alone (0.41 +/- 0.29 mg/l and 0.76 +/- 0.37 mg/l, respectively; P = 0.022). The area under the concentration-time curve from 0 to infinity (AUC(0-omega)) followed a comparable pattern. Half-life (T(1/2)) was 8.8 +/- 4.2 hr and 8.2 +/- 4.3 hr after administration with water or a fatty meal (P = 1.000). Grapefruit juice shortened T(1/2) by 46% (P = 0.026). We hypothesize that albendazole is metabolized by CYP3A4 enzymes in the intestinal mucosa. This process can be inhibited by grapefruit juice. Cimetidine decreased albendazole bioavailability.

Percutaneous evacuation (PEVAC) of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material: first results of a modified PAIR method.

BACKGROUND: Surgery is the treatment of choice in echinococcal cysts with cystobiliary fistulas. PAIR (puncture, aspiration, injection, and reaspiration of scolecidals) is contraindicated in these cases. AIM: To evaluate a modified PAIR method for percutaneous treatment of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material. PATIENTS: Twelve patients were treated: 10 patients with multivesicular cysts which contained non-drainable material and were complicated by spontaneous intrabiliary rupture, secondary cystobiliary fistulas, cyst infection, or obstructed portal or hepatic veins; and two patients with large univesicular cysts and a ruptured laminated membrane, one obstructing the portal and hepatic veins and one a suspected cystobiliary fistula. METHODS: The methods used, termed PEVAC (percutaneous evacuation of cyst content), involved the following steps: ultrasound guided cyst puncture and aspiration of cyst fluid to release intracystic pressure and thereby to avoid leakage; insertion of a large bore catheter; aspiration and evacuation of daughter cysts and endocyst by injection and reaspiration of isotonic saline; cystography; injection of scolecidals only if no cystobiliary fistula was present; external drainage of cystobiliary fistulas combined with endoprosthesis or sphincterotomy; catheter removal after complete cyst collapse and closure of the cystobiliary fistula. RESULTS: In all 12 patients initial cyst size was 13.1 (6-20) cm (mean (range)). At follow up 17.9 (4-30) months after PEVAC, seven cysts had disappeared and five cysts had decreased to 2.4 (1-4) cm (p=0.002). In eight patients with multivesicular cysts, a cystobiliary fistula, and infection, cyst size was 12.5 (6-20) cm, catheter time 72.3 (28-128) days, and hospital stay 38.1 (20-55) days. At 17.3 (4-28) months of follow up, six cysts had disappeared and in two cysts residual size was 1 and 2.9 cm, respectively (p=0.012). In four patients without a cystobiliary fistula, cyst size was 14.4 (12.7-16) cm, catheter time 8.8 (3-13) days, and hospital stay 11.5 (8-14) days. At 19.3 (9-30) months of follow up, one cyst had disappeared and three cysts were 85 (69-94)% smaller (2.2 (1-4) cm) (p=0.068). CONCLUSION: PEVAC is a safe and effective method for percutaneous treatment of multivesicular echinococcal cysts with or without cystobiliary fistulas which contain non-drainable material.

[Physical diagnosis--ascites]. / Fysische diagnostiek--ascites.

The diagnosis of ascites can be made very likely by a good clinical history and a well-directed physical examination, if the patient suffers from a disease which can cause ascites. The physician should ask about recent weight gain, change in abdominal girth and ankle oedema. With a positive history, the likelihood of the presence of ascites may increase 3 to 4-fold. When the findings at physical examination are also positive, the likelihood may increase 10 to 20-fold. A fluid wave is the most specific but less sensitive symptom. Shifting dullness, bulging flanks and flank dullness are less specific but much more sensitive parameters. The presence of ascites is very unlikely if the prior probability is low and both the patient's answers and the findings at physical examination are negative. Abdominal ultrasound, the gold standard, is not strictly indicated for diagnosing ascites: if based on the trial tried: pretest probability, clinical history and physical examination, the diagnosis is very likely or very unlikely. Ultrasonography is always indicated, however, when ascites is suspected and a positive finding is of clinical relevance.

[Acute schistosomiasis: fever and eosinophilia, with or without urticaria, after a trip to Africa]. / Koorts en eosinofilie, al dan niet met urticaria, na een reis door Afrika: acute schistosomiasis.

Despite treatment for malaria two travellers who acquired fever in Africa continued to have complaints: a 25-year-old Dutch woman and a 25-year-old Australian man. On questioning they appeared to have swum in Lake Malawi and a diagnosis of acute schistosomiasis was made, confirmed by serological tests. This syndrome, also called Katayama fever, is characterized by fever, oedema, urticaria and eosinophilia. The aetiology is not fully elucidated but it is supposed to be caused by immune complexes initiated by maturing worms and eggs. Patients who acquired fever in an endemic area must be questioned about contact with fresh water. Serological tests are important for the diagnosis. Treatment is with praziquantel but it is advised to treat only after the acute phase. During the acute manifestations corticosteroids may be necessary. Prevention is by avoiding contact with infected water. There is no vaccine. The role of artemisinin drugs in prevention is currently being studied.

Effect of dose increase or cimetidine co-administration on albendazole bioavailability.

The low bioavailability of albendazole affects the therapeutic response in patients with echinococcosis. Cimetidine co-administration is reported to improve bioavailability. To analyze the assumed dose-dependent bioavailability of albendazole, we administered 5 to 30 mg/kg albendazole to 6 male volunteers in a randomized cross-over study. To assess the effect of cimetidine (10 mg/kg twice daily), the drug was given with albendazole (20 mg/kg). A dose-dependent bioavailability was not observed. This was due to inter-individual variability of the maximal concentration (Cmax 38%-72%) of albendazole sulphoxide (ABZSX), the active metabolite of albendazole. Cmax was 0.21+/-0.14 mg/L after 5 mg/kg and 0.39+/-0.19 mg/L after 30 mg/kg albendazole (P = 0.217). Cimetidine tended to decrease Cmax by 52% (P = 0.109) and significantly inhibited ABZSX breakdown as indicated by the prolongation of ABZSX elimination half-life from 7.4+/-3.3 hr to 19.0+/-11.7 hr (P = 0.028). Remarkably, the inter-individual variability of Cmax was significantly lower during cimetidine co-administration: 14% versus 72%.

Be aware of abdominal tuberculosis.

Abdominal tuberculosis is often diagnosed in a late stage because symptoms are aspecific. Two patients with intestinal tuberculosis and tuberculous peritonitis respectively, both from endemic countries presented with long-standing fever, abdominal pain and weight loss. Acid fast bacilli were present in aspirate and biopsy specimens obtained by colonoscopy and laparoscopy respectively; PCR was positive for M. tuberculosis complex and later M. tuberculosis was cultured. Both patients responded to antituberculous therapy. In one patient AIDS was diagnosed.

[A patient with alveolar echinococcosis (Echinococcus multilocularis infection]. / Een patiënt met alveolaire echinokokkose (infectie met Echinococcus multilocularis).

In a 45-year-old Swiss male, who had been living in the Netherlands for 20 years, alveolar echinococcosis was diagnosed. He had probably been infected during his youth in Switzerland. His illness became symptomatic more than 20 years later. The diagnosis was reached by microscopic examination of material obtained from a necrotic mass in the liver. Imaging revealed that the disease had spread diffusely throughout the liver, spleen and abdomen. Curative resection was impossible. Percutaneous drainage of the hepatic necrotic mass was complicated by a bacterial infection for which he was treated with antibiotics. Treatment with high doses of albendazole resulted in considerable improvement. The patient represents the first case of Echinococcus multilocularis infection diagnosed in the Netherlands.

[Diagnosis and treatment of unilocular hydatid disease (Echinococcus granulosus infection)]. / Diagnostiek en behandeling van cysteuze echinokokkose (infectie met Echinococcus granulosus). Nederlandse Echinococcose Werkgroep.

Unilocular hydatid disease occurs in humans after oral intake of eggs of the dog tapeworm, Echinococcus granulosus. Cysts develop mostly in the liver, but sometimes also in the lung. The diagnosis of Echinococcus infection is based on history-taking, physical examination, ultrasound and CT examination and serological testing; the diagnosis is confirmed by parasitological examination of cystic fluid. Treatment until some 15 years ago consisted in operation. Subsequently, treatment with initially mebendazole, later with albendazole or with percutaneous drainage (puncture, aspiration, injection of a scolicidal, respiration (PAIR)), or with combinations of the same, became accepted forms of management. The PAIR method is reported to give high proportions of success, low proportions of recurrence and few complications. However, adequate evaluation is not yet possible because of the short follow-up period. For the prevention of leakage it is recommended to perform the PAIR method with a transhepatic puncture under continuous ultrasonographic or CT guidance; for avoidance of recurrences, one week's pretreatment and 1-4 weeks' after-treatment with albendazole are recommended. The results of albendazole monotherapy are hard to predict and highly variable: success: 30-88% (median: 71%); failure: 22-32% (median: 25%); recurrences: 9.5-31% (median: 16%). Both albendazole therapy and the PAIR management should be followed by protracted follow-up to check regression of cysts and detect recurrences. It is not clear which treatment is the best one.

First Trimester Listeria monocytogenes Septicemia.

BACKGROUND: Little is known about fetal outcome after Listeria monocytogenes septicemia in the first trimester of pregnancy. CASE: A primigravida with L. monocytogenes septicemia at 9 weeks gestation was treated with amoxicillin. At 40 weeks gestation a healthy female infant was born. CONCLUSION: This case shows that fetal outcome can be normal after appropriate treatment of maternal L. monocytogenes septicemia during embryogenesis.

[Immunotherapy using the anti-endotoxin antibody HA-1A in patients with sepsis syndrome; good results in relation to treatment with placebo]. / Immunotherapie met de anti-endotoxine-antistof HA-1A bij patiënten met het sepsissyndroom; gunstige resultaten ten opzichte van behandeling met placebo.

Passive immunization with a human anti-endotoxin monoclonal IgM antibody (Centoxin, HA-1A) was recently studied in patients with suspected Gram-negative sepsis. Comparison of the results obtained in the Amsterdam subpopulation with those in a larger international study population of which the Amsterdam patient group was a part, showed that it had been possible to select a patient population in which HA-1A has an 'intention-to-treat' effect based upon clinical criteria (a decrease in mortality compared with placebo by 42% (p = 0.04) and in the larger study by 9% (p = 0.24). Until a clinically useful test becomes available, identification of patients who have a high likelihood of Gram-negative sepsis and who would benefit from anti-endotoxin immunotherapy with HA-1A should be based upon the history and evaluation of underlying disease, infection status, severity and progression of the disease. The severely ill patients thus selected should receive treatment as early as possible.

[Immunotherapy using the anti-endotoxin antibody HA-1A (Centoxin) in patients with sepsis syndrome; fair results following protocol selection of patients]. / Immunotherapie met de anti-endotoxine-antistof HA-1A (Centoxin) bij patiënten met het sepsissyndroom; matige resultaten na geprotocolleerde selectie van patiënten.

OBJECTIVE: Evaluation of HA-1A treatment in patients with the sepsis syndrome. DESIGN: Descriptive. SETTING: Department of intensive care, Academic Medical Centre, Amsterdam. PATIENTS AND METHODS: Intensive-care patients with the sepsis syndrome and shock or organ failure with a presumptive diagnosis of Gram-negative infection were eligible for treatment with HA-1A. We analysed and compared the results with those of the double-blind, randomized HA-1A study by Ziegler et al. RESULTS: Between May 1991 and March 1992, 27 patients were treated with HA-1A. The mortality rate was 59% (16/27). Among the 11 patients with a Gram-negative bacteraemia mortality was 7/11, much higher than in the Ziegler study (30%). In comparison with the HA-1A study we selected sicker patients: the mean APACHE II score was higher, 93% of our patients were in shock and 85% had organ failure. More patients presented with an intra-abdominal sepsis and mortality in this group was very high (11/14). In patients with a Gram-negative bacteraemia the delay between the onset of the sepsis syndrome and the administration of HA-1A was longer (median 22 h versus 14.3 h in the Ziegler study, mean 30 versus 20 h). CONCLUSION: HA-1A does not appear to be beneficial in critically ill patients with a longstanding sepsis syndrome, especially not if an intra-abdominal sepsis is apparent. Therefore, we decided not to use H-1A until additional data become available. Additional objective inclusion criteria are needed to improve the identification of the patient group that may benefit from treatment with HA-1A.

Peripheral venous nutrition: the equal relevance of volume load and osmolarity in relation to phlebitis.

This study aimed to investigate the peripheral vein tolerance for total parenteral nutrition (TPN) and to point out the factors which induce phlebitis. TPN was administered from 'all-in-one' bags. Five different types of TPN were investigated, wherein the amounts of amino-acids, dextrose, lipids, osmolarity and volume were varied. Type I (829 mOsm/l) was a low energy (1570 NPE kcal) nutritive mixture of 2425 ml with 9.5 g N. Type II (842 mOsm/l) was an intermediate energy (1800 NPE kcal) mixture of 2525 ml with 9.5 g N. Type III (860 mOsm/l) contained 1800 NPE kcal and 13.5 g N in 2775 ml. Type IV (790 mOsm/l) was only a dilution of Type III with 250 ml water. Type V (1044 mOsm/l) covered normal energy needs (2000 NPE kcal) and 13.5 g N in 2580 ml. All bags contained standard amounts of electrolytes, vitamines, trace elements and heparin (1.000 IE/l). The infusion site was not changed until phlebitis developed or oral feeding could be started. Type I, II, III and IV were given to at least 30 patients, and Type V to only 11 patients because of an unacceptable high phlebitis rate (91% after 2.8 days). The phlebitis rate for Type I, II, III and IV was 4%, 12%, 24% and 27% respectively after 48h increasing to 14%, 37%, 55% and 73% respectively after 14 days. The mean infusion time and phlebitis rate were related to each component of the nutritive mixture. A poor relation was found between the phlebitis rate and the amount of amino-acids, dextrose or lipid respectively. Both osmolarity (with variabl volume) and volume (with variable osmolarity) correlated poorly with the phlebitis rate (r = 0.37 and 0.29 respectively). However, the osmolarity rate, defined as the number of milliOsmols infused per hour, correlated well with the phlebitis rate (r = 0.95). Our results demonstrate that the peripheral route can be used as a practical alternative for central venous administration, if the osmolarity rate is limited.

Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors.

Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single-photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurements with the volume of the resected liver mass. The correlation coefficient between these methods was 0.899 (P less than 0.01). Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days the liver had regenerated maximally to a volume of 75 +/- 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 +/- 10% for the caffeine clearance and to 100 +/- 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. Our study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy.