[Three patients with weight loss as a result of sarcoidosis presenting as liver disease]. / Drie patiënten met gewichtsverlies door sarcoïdose, zich uitend als leverziekte.

Sarcoidosis presenting as a liver disease is uncommon. Hepatic sarcoidosis was diagnosed in three male patients aged 80, 64 and 69 years. They all presented with aspecific symptoms such as weight loss. Further investigation revealed liver disease, and liver biopsies demonstrated the presence of non-caseating granulomas. However, non-caseating granulomas can be associated with a great number of disorders and are therefore not specific. Other causes were excluded before the diagnosis of hepatic sarcoidosis was established with reasonable certainty. The diagnosis was finally confirmed on the basis of medical history, laboratory tests and histology. Sarcoidosis presenting as symptomatic liver disease can be treated with corticosteroids and probably with ursodeoxycholic acid as well. These three patients were treated with corticosteroids. The first patient died a year later from a cerebral infarct, the second one after a few months from a (non-sarcoidotic) cerebral haemorrhage and the third one after eight years from hepatic failure.

Saquinavir soft-gel capsules (Fortovase) give lower exposure than expected, even after a high-fat breakfast.

BACKGROUND: The soft-gel capsule (sgc) of saquinavir has been developed in order to improve the poor oral bioavailability of the original hard-gel capsules. However, in a Dutch study population using saquinavir-sgc plasma levels were lower than expected. We hypothesised that this was caused by differences in the amount of fat in the meals of the study populations. METHODS: 8-h steady-state plasma curves after observed ingestion of 1200 mg saquinavir-sgc were recorded, concomitantly with a normal breakfast (600 kcal, 33% fat) on the first day, and a high-fat breakfast (1040 kcal, 54% fat) on the second day. Additionally, a comparison was made between saquinavir hard-gel capsules and saquinavir-sgc with or without grapefruit juice (n = 1). Furthermore, a comparison between saquinavir-sgc and ritonavir + saquinavir-sgc 400/400 mg bid was made (n = 1). RESULTS: Although saquinavir exposure was improved by fat, grapefruit juice or ritonavir, exposure to saquinavir for all recorded curves was lower than expected. A large proportion of trough concentrations was below the efficacy threshold. CONCLUSION: Intake of squinavir-sgc with high-fat meals or grapefruit juice may improve the pharmacokinetic profile. However, plasma concentrations may then still be lower than expected and insufficient for good antiviral efficacy. Probably the only way to reach adequate saquinavir concentrations is by combining saquinavir with ritonavir.

Culture negative endocarditis combined with glomerulonephritis caused by Bartonella species in two immunocompetent adults.

Two cases of culture negative endocarditis are presented. In both, Bartonella species could be identified as the causative agent and in one of them Bartonella henselae was very likely. Both cases were accompanied by glomerulonephritis, in one case proven by a kidney biopsy. A nephrotic syndrome may be the first presentation of an endocarditis caused by Bartonella species.

Effects of peritoneal dialysis with an overnight icodextrin dwell on parameters of glucose and lipid metabolism.

OBJECTIVE: To examine whether a reduced daily glucose load by overnight application of the less-absorbed glucose polymer icodextrin would have favorable effects on lipid profiles of continuous ambulatory peritoneal dialysis (CAPD) patients. STUDY DESIGN: Randomized crossover study with two subsequent periods of 6 weeks. SETTING: Home PD unit of a secondary-care hospital. PATIENTS: Twenty-one nondiabetic CAPD patients (15 male, 6 female; mean age 50.3+/-11.8 years). INTERVENTION: Participants were randomly assigned to receive an overnight dwell with either standard glucose solution or with a 7.5% icodextrin-containing solution. MAIN OUTCOME MEASURES: Relation between reduction in the total amount of intraperitoneal infused glucose and parameters of glucose (plasma glucose, insulin, and HbA1C) and lipid metabolism [free fatty acids, plasma lipids, lipoproteins, and low density lipoprotein (LDL) subfraction profile]. RESULTS: After the icodextrin dwells, a reduction of plasma total cholesterol (from 5.43+/-0.85 to 4.86+/-0.70 mmol/L, p < 0.001) and LDL cholesterol (from 3.38+/-0.87 to 2.93+/-0.73 mmol/L, p = 0.001) was observed. Also, high density lipoprotein (HDL) cholesterol (from 0.95+/-0.27 to 0.90+/-0.24 mmol/L, p = 0.029) was reduced, but the plasma total cholesterol-to-HDL ratio remained similar. Plasma free fatty acids and triglyceride levels tended to decrease (from 0.16+/-0.10 to 0.13+/-0.08 mmol/L, p= 0.06, and from 2.14+/-1.96 to 1.92+/-1.03 mmol/L, respectively). Evaluation of LDL subfraction profiles after ultracentrifugation showed a more buoyant LDL subfraction profile with fewer dense LDL particles in 6 patients and no changes in 14 patients after icodextrin. The effects on lipids were not accompanied by a decrease in fasting plasma glucose (from 5.76+/-1.29 to 5.86+/-0.80 mmol/L) or insulin levels (from 19.5+/-14.4 to 20.3+/-13.0 mU/L). CONCLUSION: These results suggest a beneficial effect on lipid profiles of CAPD patients with the use of an overnight dwell with icodextrin.

Hepatic steatosis and lactic acidosis caused by stavudine in an HIV-infected patient.

Lactic acidosis and hepatic steatosis caused by mitochondrial toxicity of nucleoside reverse transcriptase inhibitors (NRTI) is a rare cause of liver disease with a high mortality rate. This report describes a male, HIV-positive patient with a 4-week history of nausea, vomiting and abdominal pain. His medication consisted of prednisone 5 mg od (because of auto-immune thrombocytopenia), didanosine (for 2 years) and stavudine (for 3 months). Laboratory studies showed cholestasis and elevation of aminotransferases. Lactic level was not measured. Liver biopsy revealed steatosis and cholestatic hepatitis. In the absence of other causes of liver disease a probable diagnosis of stavudine-induced hepatic toxicity was made. After discontinuation of NRTI, he recovered completely. Because lactic acidosis had not been confirmed, stavudine was restarted and within 1 week the lactate level increased significantly. Therefore stavudine was discontinued again. One year later the patient is doing well on a double protease inhibitor regimen. In conclusion, clinicians treating patients with NRTI should be aware of the risk of lactic acidosis and hepatic steatosis. When this is suspected, all NRTI must be stopped. The diagnosis can be made when elevated lactate levels and hepatic steatosis are present in the absence of other causes of liver disease.

[Acute renal insufficiency due to vomiting or diarrhea: the Achilles heel of medical support for heart failure]. / Acute nierinsufficiëntie door braken of diarree: de achilleshiel bij medicamenteus ondersteund hartfalen.

Morbidity and mortality of heartfailure are decreasing because of improved medical treatment. The recompensation balance can however be very fragile, which is illustrated by three patients. A woman aged 73 and a man aged 62, both known with heart failure, became seriously ill after diarrhoea; examination revealed uraemia, hyperpotassaemia and raised digitalis levels. A man aged 72, also with heart failure and diarrhoea, developed sensory disorders in both feet. He, also, was found to suffer from renal insufficiency. All patients used an angiotensin converting enzyme inhibitor or an angiotensin-II-antagonist and an aldosterone receptor blocker as well. During the (innocent) intercurrent disease by which their intravascular volume diminished they developed a severe renal insufficiency which needed clinical, intensive treatment. After haemodialysis, all three recovered well. Renal function plays an essential role in the fragile treatment balance that exists in recompensated cardiac patients. The medication that is beneficial for the cardiac functioning may at the same time compromise the renal perfusion. Good monitoring and good instructions about what to do in case of intercurrent diseases are of vital importance in these patients.

[Open lung biopsy in severely ill patients with unrecognized pulmonary infiltrates]. / Open longbiopsie bij ernstig zieke patiënten met onbegrepen longinfiltraten.

In three patients, a man aged 34 with aids, a woman aged 67 with recurrent major dyspnoea and a woman aged 73 with chronic lymphatic leukaemia, examination revealed progressive dyspnoea while the chest X-rays showed infiltrative lesions in both lungs. In view of the inadequate response to the treatment administered, an open lung biopsy was performed, following which the diagnosis could be made. Adequate treatment was then started and followed by clinical recovery. It is not clear if open lung biopsy carries higher risks of mortality and morbidity than biopsy by means of flexible bronchoscopy. Open lung biopsy more often leads to a classifying diagnosis. For collection of endobronchial or transbronchial biopsy samples in ununderstood diffuse interstitial lung diseases, flexible bronchoscopy is the method of first choice. Open lung biopsy is a justified supplementary examination, at any rate in severely ill, immunocompromised patients who require adequate therapy without delay.

Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV-seropositive patients with Pneumocystis carinii pneumonia.

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.

[Chronic hepatitis C in hemodialysis patients]. / Chronische hepatitis C bij hemodialysepatiënten.

Hepatitis C virus (HCV) is an important cause of chronic hepatitis in dialysis patients. With regard to epidemiology, the time on haemodialysis, the (previous) use of intravenous drugs as well as the number of blood transfusions received are important risk factors. There are strong indications suggesting nosocomial transmission of HCV. Strict application of infection prevention procedures in haemodialysis units is mandatory to restrain spread of HCV infection. Preliminary results show equal efficacy of alpha-interferon in normalisation of serum transaminases in dialysis patients and in patients with normal kidney function. However, in both groups relapses occur often, despite induction of remission. Antiviral therapy (with interferon and ribavirin) is emerging as a valid option to induce HCV eradication in dialysis patients. Thereafter, transplantation may be considered.

Treatment of poor prognosis epidemic Kaposi's sarcoma with doxorubicin, bleomycin, vindesine and recombinant human granulocyte-monocyte colony stimulating factor (rh GM-CSF).

The efficacy and toxicity of doxorubicin, bleomycin and vindesine in epidemic Kaposi's sarcoma, and the role of rh GM-CSF in chemotherapy-induced neutropenia were evaluated in this Phase II study. Patients with progressive Kaposi's sarcoma were eligible, and were staged according to ACTG criteria. Treatment consisted of 20 mg/m2 doxorubicin, and a fixed dose of 15 mg bleomycin and 4 mg vindesine every 2 weeks. All patients continued antiretroviral medication with severe myelosuppression, patients received subcutaneous 5 micrograms/kg rh GM-CSF (Leucomax) from days 2-12. Response and toxicity were measured according to ACTG and WHO criteria. 27 patients were evaluable, 25 patients classified as having a poor prognosis. The response rate was 70% (3 CR, 16 PR), the duration of response was 18 weeks (range 8-25) and the median survival 30 weeks (range 4-63+). The cause of death was mostly opportunistic infection. 4 patients died of pulmonary Kaposi's sarcoma. The toxicity of this regimen was mainly myelosuppression and 13 patients were treated with rh GM-CSF. Complete recovery of the white blood cells occurred in seven of the 27 courses of rh GM-CSF (26%). No bacterial infections were recorded, but 5 patients (19%) developed an opportunistic infection during treatment. Peripheral neuropathy occurred in 16% of patients. Combination chemotherapy is effective in poor prognosis Kaposi's sarcoma but has a shortlasting effect. The main toxicity of this treatment is severe myelosuppression which can be ameliorated by rh GM-CSF. It remains to be established whether rh GM-CSF is also able to reduce the incidence of opportunistic infections.

Successful renal autotransplantation for renal failure with prolonged oliguria in a Jehovah's Witness with fibromuscular dysplasia of the renal arteries.

A young female presented with hypertension and oliguric renal insufficiency caused by fibromuscular dysplasia of the renal arteries. There was a left kidney remnant and a normal-sized right kidney with a retrograde blood supply through capsular arteries. Reconstruction of the occluded right renal artery with autotransplantation of the kidney after 60 days of oliguric renal insufficiency was followed by complete functional repair. Erythropoietin treatment was a great help in the management of this patient who refused blood transfusions because she was a Jehovah's Witness.

The incidence of subclavian vein stenosis using silicone catheters for hemodialysis.

Complications related to the use of silicone subclavian catheters for hemodialysis were prospectively studied in 21 consecutive patients with acute and chronic renal failure. Between July 1991 and December 1992, 34 double-lumen silicone catheters (Medcomp; 12 French; 20 or 24 cm) were inserted in 21 patients. The mean duration of catheterization was 20 days (range, 2-58 days). Venograms were performed in 16 patients (22 subclavian veins) within 6 months following removal of the catheter. Excluded from angiography were patients whose catheters had been in place less than 1 week or who underwent fewer than 3 dialysis sessions because of minor risk of stenosis. Patients who had ipsilateral repeated catheters were also excluded. Two angiographies showed subclavian vein stenosis, both occurring in the same patient. One showed 50% stenosis with collaterals; one showed 50% stenosis without collaterals. One other complication was a pneumothorax. Catheter thrombosis was observed in 3 patients; catheter sepsis did not occur. We conclude that use of silicone catheters for subclavian cannulation is safe and effective to provide temporary vascular access for acute hemodialysis. The incidence of subclavian vein stenosis is lower compared with polytetrafluoroethylene and polyurethane catheters.

Vascular access in continuous arteriovenous hemodiafiltration.

We describe experiences with the use of silicone catheters for continuous arteriovenous hemodiafiltration (CAVHD) in 43 patients in the Intensive Care Unit from July 1991 through March 1993. There were no serious complications with regard to the use of these widebore catheters at introduction, during therapy, or at removal. All patients who needed renal replacement therapy could be treated with CAVHD. This low complication rate is probably due to a very strict CAVHD protocol and the fact that only a few people supervise this therapy.

Identification of the component part in an epoetin alfa preparation that causes pain after subcutaneous injection.

The subcutaneous administration of epoetin alfa preparations may cause pain at the injection site. To identify the pain-causing substance in these formulations we performed two double-blind, placebo-controlled, randomized order, cross-over studies. Differences in pain experienced after subcutaneous injection of an epoetin alfa solution and its vehicle were assessed in 36 patients. The vehicle and its component parts, albumin and citrate, were compared in 36 volunteers. Normal saline served as a placebo control in both studies. Pain scores were obtained from visual analogue pain scales with no divisions and from five point verbal descriptive pain scales. Both the epoetin alfa solution and its vehicle caused significantly more pain than normal saline (P < 0.0001) in the patients studied. In volunteers the pain scores with the vehicle or its citrate component were significantly higher (P < 0.0001) when compared with normal saline or with the albumin component of the vehicle. In conclusion, the local pain experienced after subcutaneous administration of epoetin alfa preparations is mainly caused by the citrate component of the buffered solution. Epoetin alfa and the albumin component of the preparation do not play a role in this phenomenon.

[Surgical complications in treatment with continent ambulatory peritoneal dialysis; 9-year experience]. / Chirurgische complicaties bij behandeling met continue ambulante peritoneale dialyse; 9 jaar ervaring.

OBJECTIVE: To determine the number of surgical complications in patients treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective (1980-1989), partially prospective (1987-1989). SETTING: Rijnstate Hospital, Arnhem, the Netherlands. METHOD: In 1978 CAPD was introduced in the Netherlands. Since 1980 we have used this technique in our clinic. Over the period 1980-1989 we studied the number of surgical complications of CAPD and the loss of catheter caused by these complications. With these numbers the probability of having a functioning Tenckhoff double cuff catheter was calculated with the Kaplan-Meier method. RESULTS: 101 patients (54 men (mean age 52.5 years), 47 women (mean age 49.6 years)) with terminal renal insufficiency were treated during the study period. 123 catheters were implanted of which 33 had to be removed afterwards. The probability of having a functioning catheter after one year was 85%, after two years 64% and after three years 53%. Peritonitis was the main cause of temporary or final loss of the catheter. The number of observed cases of peritonitis was 187. CONCLUSION: Methods to improve the survival of the catheter are prevention of peritonitis by using an appropriate system for the fluid exchanges, screening patients for the existence of diverticulosis before starting CAPD, and prevention of exit site and tunnel infections.

[9-year experience with continuous ambulatory peritoneal dialysis in one center]. / Ervaringen met continue ambulante peritoneale dialyse in één centrum gedurende 9 jaar.

The experience gained with CAPD in a group of 101 patients with terminal renal failure and a subgroup of 19 patients with diabetes mellitus was analysed. The actuarial patient survival was 81% after two years and 50% after five years. The combined patient-technique survival after two years was 48.8%. The most important reasons for drop-out were transplantation (25%) and death (24%). Death was method-related in 4 patients and caused by peritonitis in 2 of them. More often peritonitis was the cause of morbidity and temporary interruption (10 x) or of permanent abandoning of the method (11 x ). The peritonitis frequency during the whole period of nine years was 1 : 11.3 months. Use of the Y-connector Twinbag system and a U.V.-light system reduced the incidence substantially. However, faecal peritonitis remains a dangerous situation which cannot be prevented in this way. The mortality in patients with diabetes mellitus is high but not method-related. The incidence of peritonitis is not significantly different from that among patients without diabetes mellitus.

[Experience with continuous arteriovenous hemodiafiltration for acute kidney insufficiency in intensive care patients]. / Ervaringen met continue arterioveneuze hemodiafiltratie als behandeling voor acute nierinsufficiëntie bij intensive care-patiënten.

Acute renal failure is a frequent complication at the Intensive Care Department. For this complication dialysis is often necessary. In our Intensive Care Department we have opted for continuous arteriovenous hemodiafiltration (CAVHD) as the treatment of first choice for patients with acute renal failure. We describe the results in 18 patients treated with CAVHD. In all patients an arterious and a venous catheter were placed, in most cases in the femoral artery and vein. A capillary hemofilter was placed between the catheters. In the filter a counterflow mechanism took place. All patients were successfully treated with CAVHD. Haemodynamic instability as an effect of the treatment did not appear. The fluid and electrolyte balance was perfectly under control. Renal function was recovered in 7 patients. Twelve patients died. The cause of death was never associated with the renal failure or with the CAVHD treatment.

Continuous ambulatory peritoneal dialysis (CAPD) in patients with diabetic nephropathy.

A 3-centre study was done to analyse the results of 70 patients with end-stage renal disease caused by diabetic nephropathy and treated with CAPD. Fifty patients had insulin-dependent diabetes (mean age 42, mean duration of diabetes 24 yr); 20 had non-insulin-dependent diabetes (mean age 61, mean duration 15 yr). Total treatment time was 1563 months and ranged from one to 83 months (median 18). Patient survival was 86% at 1 yr and 33% at 4 yr. Technique survival was 87% and 63%. Cox's multiple hazard regression analysis showed that age above 45 yr (relative risk 2.2), systolic hypertension (2.6) and cardiac disease (2.2) at the start of CAPD were associated with shorter patient survival. Metabolic control was good. Haemoglobin rose during the first 3 months. Plasma creatinine concentration increased with time, probably due to the loss of residual renal function. HbA1c levels were in the normal range for 60% of the patients. Mean hospital stay was 42 days per year, 26 as a consequence of vascular complications and 16 due to peritonitis and catheter-related problems. We conclude that CAPD is a good renal replacement modality for patients with diabetic renal failure. The patient survival is dependent on age, systolic hypertension and cardiac disease at the start of CAPD.