The colitis of Behcet's disease: A separate entity?

Summary An additional case of Behcet's disease with colonic involvement has been presented. This association is rare, as only 13 prior cases with adequate data were available for comparison. Controversy exists as to whether these cases represented true involvement of the colon by Behcet's disease, coincidental inflammatory bowel disease and Behcet's disease, or merely autoimmune phenomena associated with inflammatory bowel disease. Unusual colonoscopic lesions noted in our patient and other features enumerated in the text suggested to us that at least some of these cases represented primary Behcet's disease involving the colon.     

The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity,with a special focus on dyslipidemia

We prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase in relation to levels of asparaginase activity in children with acute lymphoblastic leukemia. We also evaluated the incidence of pancreatitis, thrombosis, hyperammonemia and central neurotoxicity and their association with asparaginase activity levels. Eighty-nine patients were treated according to the Dutch Childhood Oncology Group Acute Lymphoblastic Leukemia 10 medium-risk intensification protocol, which includes 15 doses of PEGasparaginase (2,500 IU/m²) over 30 weeks. Erwinia asparaginase (20,000 IU/m²) was administered when allergy to or silent inactivation of PEGasparaginase occurred. Triglyceride, cholesterol and ammonia levels increased rapidly in children treated with PEGasparaginase and remained temporarily elevated, but normalized after administration of the last asparaginase dose. Among the patients treated with PEGasparaginase, hypertriglyceridemia and hypercholesterolemia (grade 3/4) were found in 47% and 25%, respectively. The correlation between PEGasparaginase activity levels and triglyceride levels was strongest at week 5 (Spearman correlation coefficient=0.36, P=0.005). The triglyceride levels were higher in children ≥10 years old than in younger patients (<10 years old) after adjustment for type of asparaginase preparation: median 4.9 mmol/L versus 1.6 mmol/L (P<0.001). In patients receiving Erwinia asparaginase, triglyceride levels increased in the first weeks as well, but no grade 3/4 dyslipidemia was found. Hyperammonemia (grade 3/4) was only found in patients treated with Erwinia asparaginase (9%). Thrombosis occurred in 4.5%, pancreatitis in 7%, and central neurotoxicity in 9% of patients using either of the two agents; these toxicities were not related to levels of asparaginase activity or to triglyceride levels. In conclusion, severe dyslipidemia occurred frequently, but was temporary and was not associated with relevant clinical events and should not, therefore, be considered a reason for modifying asparaginase treatment. Dyslipidemia was the only toxicity related to levels of asparaginase activity.     

Improving Confidence in the Determination of Free Fraction for Highly Bound Drugs Using Bidirectional Equilibrium Dialysis

Equilibrium dialysis has been widely used for the measurement of the fraction of unbound drug (f_u) in plasma, but it suffers from the accuracy and reliability for low f_u values. To address this concern, an orthogonal approach, called the bidirectional equilibrium dialysis, is described to simultaneously measure a pair of f_u values for each drug based on equilibration in 2 opposite dialysis directions: from plasma to buffer (f_u,p/b) and from buffer to plasma (f_u,b/p). Hypothetically, if true equilibrium is attained in both dialysis directions, the measured f_u,b/p and f_u,p/b values for a given drug should converge, and thus, the ratio of f_u,b/p to f_u,p/b becomes unity (1.0). Thus, the ratio can be used as a tangible readout for data reliability. This methodology has been extensively tested in the present study using various drugs with distinct plasma binding characteristics. Our results clearly showed that low f_u values (<0.01) could be reliably determined and verified using either the standard or dilution bidirectional equilibrium dialysis method for some known highly bound drugs; for extensively bound drugs with high logD_7.4, such as montelukast, bedaquiline, and venetoclax, only a range of f_u can be reported with confidence because of uncertainty in the true equilibrium.     

Incisional hernia after liver transplantation: risk factors and health‐related quality of life

The aim of this cross‐sectional study was to analyze the incidence of incisional hernia after liver transplantation (LT), to determine potential risk factors for their development, and to assess their impact on health‐related quality of life (HRQoL). Patients who underwent LT through a J‐shaped incision with a minimum follow‐up of three months were included. Follow‐up was conducted at the outpatient clinic. Short Form 36 (SF‐36) and body image questionnaire (BIQ) were used for the assessment of HRQoL. A total of 140 patients was evaluated. The mean follow‐up period was 33 (SD 20) months. Sixty patients (43%) were diagnosed with an incisional hernia. Multivariate analysis revealed surgical site infection (OR 5.27, p = 0.001), advanced age (OR 1.05, p = 0.003), and prolonged ICU stay (OR 1.54, p = 0.022) to be independent risk factors for development of incisional hernia after LT. Patients with an incisional hernia experienced significantly diminished HRQoL with respect to physical, social, and mental aspects. In conclusion, patients who undergo LT exhibit a high incidence of incisional hernia, which has a considerable impact on HRQoL. Development of incisional hernia was shown to be related to surgical site infection, advanced age, and prolonged ICU stay.     

Risk factors for the development of an adenocarcinoma in columnar-lined (Barrett) esophagus

Background. To evaluate the importance of the length of columnar-lined esophagus, sex, age, smoking, and drinking habits as risk factors for malignant degeneration, the authors performed a retrospective case-control study comparing patients with and without adenocarcinoma in Barrett esophagus. Methods. The records of 96 patients (53 male and 43 female; mean age, 61 years) with a benign columnar-lined esophagus and 62 patients (47 male and 15 female; mean age, 62 years) with an adenocarcinoma in columnar-lined esophagus referred to the Rotterdam Esophageal Tumor Study Group, diagnosed over the same period (1978–1985), were reviewed. A frequency distribution of the length of columnar-lined esophagus in both groups was made. Statistical analysis was performed with multivariate methods. Results. The length of columnar-lined esophagus was related significantly to carcinoma: a doubling of the length resulted in a 1.7 times increased risk. Smokers had a 2.3-fold increased risk as compared with nonsmokers. Male sex as a risk factor approached statistical significance (P = 0.06). Adjusted for these risk factors, no relation between carcinoma and age or alcohol consumption was found. Conclusions. The risk of development of an adenocarcinoma in Barrett esophagus increased with the length of Barrett epithelium. Smoking and possibly male sex were also risk factors. The identification of these risk factors may help in developing more efficient screening programs for patients with Barrett esophagus.     

Prognostic importance of gram-negative intestinal colonization preceding pancreatic infection in severe acute pancreatitis

Objectives: To establish, firstly, whether gram-negative (re)-colonization of the gut leads to an increased risk of gram-negative pancreatic infections and whether this event is time-related and, secondly, whether the difference in the quantity and quality of micro-organisms colonizing the digestive tract influences morbidity and mortality. Design: Prospective analysis of the results of systematic semi-quantitative cultures of several body areas taken from patients with severe acute pancreatitis, during a controlled multicenter trial of adjuvant selective decontamination. Setting: Surgical intensive care units of 16 hospitals. Patients: A total of 2159 semi-quantitative cultures from the oropharynx, rectum and pancreatic tissues taken from 90 patients were analyzed. Interventions: Surveillance cultures from the oropharynx and rectum were taken on admission and repeated twice weekly and from the (peri)-pancreatic devitalized tissues (i. e. necrosis) at every relaparotomy and from drainage. Measurements and results: All gram-negative pancreatic infections were preceded by intestinal colonization with the same micro-organisms. The risk of developing a pancreatic infection following gram-negative intestinal colonization (15/42 patients) was significantly higher as compared to patients without gram-negative colonization (0/10 patiens) (p < 0.001) or to patients in whom E. coli was the only intestinal micro-organism cultured (0/30 patients) (p < 0.001). The occurrence of intestinal E. coli did not increase the risk of pancreatic infection. Gram-negative colonization of the rectum and oropharynx significantly correlated with the later development of pancreatic infection: relative risks 73.7 (p < 0.001) and 13.6 (p < 0.001), respectively. However, when both areas were evaluated simultaneously, the rectum was more significant (p < 0.001). The severity of intestinal intestinal colonization until the moment of pancreatic infection showed an increase in time in all 15 patients. In 11 of 15 patients (73 %) these infections occurred within 1 week following the first isolation from the digestive tract. Gram-negative intestinal colonization was associated with a 3.7 fold increased mortality risk (p = 0.004). Conclusions: Gram-negative intestinal colonization, E. coli excepted, is an early prognostic parameter in patients in whom pancreatic infection has not yet occurred and represents a significantly increased risk of pancreatic infections and mortality. Received: 17 June 1997 Accepted: 3 March 1998