Sorption of thiotepa to polyurethane catheter causes falsely elevated plasma levels

Central venous access catheters are commonly used in clinical oncology. The double lumen variant is applied in pharmacokinetic studies for simultaneous administration and blood sampling when frequent blood collections are necessary. Occlusion of one lumen, a common complication, necessitates the investigator perform blood sampling through the administration lumen after interrupting the infusion. Plasma concentrations measured in this sample can be influenced by sorption of the previously infused compound to the catheter lumen. In this study, the quality of cyclophosphamide, thiotepa, and carboplatin plasma concentrations is investigated when sampling is performed through the administration lumen.     

The epidemiology of lifestyle and risk for type 2 diabetes

Results from ecological and migration studies indicate that a western lifestyle is associated with a higher prevalence of type 2 diabetes. In recent years, there has been a rapid accumulation of data on lifestyle and risk for type 2 diabetes from studies on an individual level. This article gives an overview of the evidence for the effect of different lifestyle factors on risk for type 2 diabetes and discusses various methodological approaches. Randomized intervention studies have shown that changes in diet and physical activity can protect against type 2 diabetes. Diet and physical activity can affect the development of type 2 diabetes through changes of body fatness, but also through other pathways. Findings from cohort studies and trials with intermediary endpoints have indicated that higher consumption of whole grain products and exchanging unsaturated fat for saturated fat may lower risk for type 2 diabetes. In addition, several new promising hypotheses about diet and the development of type 2 diabetes are currently being investigated. Light to moderate alcohol consumption may also reduce risk for type 2 diabetes, whereas high alcohol consumption and cigarette smoking may increase risk for type 2 diabetes. Prevention of weight gain by balancing energy intake and expenditure is of paramount importance to limit current increases in the prevalence of type 2 diabetes. In addition, other effects of lifestyle may play an important role in reducing risk for type 2 diabetes.     

A case of diphtheria in the Netherlands due to an infection with Corynebacterium ulcerans

A 58-year-old woman was admitted due to a pseudomembranous pharyngitis. The patient had not been vaccinated against diphtheria. Corynebacterium ulcerans was cultured from a throat swab. The production of diphtheria toxin by these bacteria was demonstrated with PCR and an immunoprecipitation test. The patient was cared for in respiratory isolation and was treated with benzylpenicillin. She quickly recovered and was discharged four days after admission. A contact investigation did not reveal any dissemination of the toxin-producing C. ulcerans and a source was not found. In spite of the large-scale vaccination against diphtheria which has taken place in the Netherlands since 1953, a physician has to consider diphtheria in the differential diagnosis of patients who present with a clinical syndrome compatible with this disease. Either Corynebacterium diphtheriae or C. ulcerans could be the pathogen responsible.     

Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction

BACKGROUND: The endoscopically placed enteral stent has emerged as a reasonable alternative to palliative surgery for malignant intestinal obstruction. This is a report of our experience with the use of enteral stents for nonesophageal malignant upper GI obstruction. METHODS: Data on all patients who had undergone enteral stent placement were reviewed. Those with a diagnosis of pancreatic cancer were compared with another similar cohort of patients who underwent palliative gastrojejunostomy. RESULTS: Thirty-one procedures were performed on 29 patients (mean age 67.7 years). Thirteen (45%) were men and 16 (55%) women. The diagnoses were gastric (13.8%), duodenal (10.3%), pancreatic (41.4%), metastatic (27.6%), and other malignancies (6.9%). Malignant obstruction occurred at the pylorus (20.7%), first part of duodenum (37.9%), second part of duodenum (27.6%), third part of duodenum (3.5%), and anastomotic sites (10.3%). Twenty-nine (93.5%) procedures were successful and good clinical outcome was achieved in 25 (80.6%). Re-obstruction by tumor ingrowth occurred in 2 patients after a mean of 183 days. The median survival time for patients with pancreatic cancer who underwent enteral stent placement compared with those who underwent surgical gastrojejunostomy was 94 and 92 days, charges were $9921 and $28,173, and duration of hospitalization was 4 and 14 days, respectively (latter 2 differences with p value < 0.005). CONCLUSION: Endoscopic enteral stent placement of nonesophageal malignant upper GI obstruction is a safe, efficacious, and cost-effective procedure with good clinical outcome, lower charges, and shorter hospitalization period than the surgical alternative.     

Age-dependent cognitive decline in the APP23 model precedes amyloid deposition

Heterozygous APP23 mice, expressing human amyloid-precursor protein with the Swedish double mutation and control littermates, were subjected to behavioral and neuromotor tasks at the age of 6-8 weeks, 3 and 6 months. A hidden-platform Morris-type water maze showed an age-dependent decline of spatial memory capacities in the APP23 model. From the age of 3 months onwards, the APP23 mice displayed major learning and memory deficits as demonstrated by severely impaired learning curves during acquisition and impaired probe trial performance. In addition to the cognitive deficit, APP23 mice displayed disturbed activity patterns. Overnight cage-activity recording showed hyperactivity in the transgenics for the three age groups tested. However, a short 2-h recording during dusk phase demonstrated lower activity levels in 6-month-old APP23 mice as compared to controls. Moreover, at this age, APP23 mice differed from control littermates in exploration and activity levels in the open-field paradigm. These findings are reminiscent of disturbances in circadian rhythms and activity observed in Alzheimer patients. Determination of plaque-associated human amyloid-beta 1-42 peptides in brain revealed a fivefold increase in heterozygous APP23 mice at 6 months as compared to younger transgenics. This increase coincided with the first appearance of plaques in hippocampus and neocortex. Spatial memory deficits preceded plaque formation and increase in plaque-associated amyloid-beta 1-42 peptides, but probe trial performance did correlate negatively with soluble amyloid-beta brain concentration in 3-month-old APP23 mutants. Detectable plaque formation is not the (only) causal factor contributing to memory defects in the APP23 model.     

A prospective randomized trial comparing a virtual reality simulator to bedside teaching for training in sigmoidoscopy

BACKGROUND AND STUDY AIMS: Clinical investigation using endoscopy simulators is now possible due to recent advances in virtual reality technology. A prospective randomized trial was conducted to compare the exclusive use of a virtual reality endoscopy simulator with bedside teaching for training in sigmoidoscopy. MATERIALS AND METHODS: Internal medicine residents were randomly assigned to training exclusively using a virtual reality simulator (group 1) or via bedside teaching (group 2). Residents were then observed performing five sigmoidoscopic procedures in asymptomatic patients referred for colorectal cancer screening. Endoscopic examinations were evaluated for procedure duration, completion, ability to perform retroflexion, and level of patient comfort/discomfort. Each examination was scored from 1 (inability to insert the endoscope beyond the rectum) to 5 (able to complete the entire examination independently in less than 20 min). RESULTS: Sixty-six sigmoidoscopic examinations were completed by nine residents in group 1 (simulator-trained group) and seven residents in group 2 (traditional teaching group). Participants in group 1 had more difficulty with initial endoscope insertion and negotiation of the rectosigmoid junction (mean score +/- SEM 2.9 +/- 0.2) than those in group 2 (3.8 +/- 0.2) ( P < 0.001). The splenic flexure was reached independently in 10 of 34 examinations (29 %) in group 1, compared with 23 of 32 examinations (72 %) in group 2 ( P = 0.001). Retroflexion was successfully performed by 19 of 34 (56 %) in group 1 compared to 27 of 32 (84 %) in group 2 ( P = 0.02). The average procedure time, patient satisfaction, and discomfort associated with the procedure did not differ statistically between the two groups. CONCLUSIONS: The use of a state-of-the-art virtual reality-based endoscopy simulator is inferior to traditional bedside teaching techniques when used exclusively for training medical residents to perform sigmoidoscopy.     

Immunomodulating effects of 3-thia fatty acids in activated peripheral blood mononuclear cells

BACKGROUND: 3-thia fatty acids such as tetradecylthioacetic acid (TTA) are modified fatty acids that have been suggested to change the plasma profile from atherogenic to cardio protective. Because of its interaction with peroxisome proliferator activated receptor (PPAR) we hypothesized that TTA also could have immunomodulatory properties. Based on the suggested role of inflammation in atherogenesis, any immunomodulating effects of TTA would be of particular interest for the potential use of this fatty acid in atherosclerotic disorders. MATERIALS AND METHODS: We examined if TTA could modulate proliferation and the release of cytokines from peripheral mononuclear cells (PBMCs) taken from five healthy blood donors. RESULTS: Our main findings were: (i) TTA had several effects on cytokine release from activated PBMCs with a marked increase in interleukin (IL)-10 accompanied by a reduction in IL-2 possibly favouring anti-inflammatory net effects. (ii) These cytokine-modifying effects were found in both T cells and monocytes when cultured separately. (iii) Tetradecylthioacetic acid increased the cytokine stimulating effects of tumour necrosis factor alpha with a particularly enhancing effect on IL-10. (iv) Tetradecylthioacetic acid significantly suppressed PBMC proliferation, and this antiproliferative property did not involve enhanced apoptosis or necrosis. (v) These immunomodulatory effects of TTA were accompanied by a marked down-regulation of PPARoad mRNA expression, the most abundant PPAR subtype in PBMCs. CONCLUSIONS: Our findings show potent immunomodulatory effects of TTA in activated PBMCs, possibly involving PPAR-related mechanisms.     

Results with the M. E. Müller cemented, straight-stem total hip prosthesis: a 10-year historical cohort study in 180 women

In 1986, 242 M. E. Muller (MEM) cemented, straight-stem total hip arthroplasty prostheses were implanted in 229 patients; 15 hips (13 patients) were lost to follow-up. Of the remaining 227 implants, 180 were placed in women, and 47 were placed in men (each with mean age, 71 +/- 7.7 years). After 10 years, 66 patients had died, and 152 implants were still in situ. As a result of aseptic loosening, 9 hips were revised (5 femoral and 4 acetabular components); two of these patients had a Girdlestone as a result of postoperative infection. Because 50% of the men died during follow-up, further analysis was performed with the 180 implants in women. The incidence of revision for aseptic loosening was 5.9 per 1,000 implants. The cumulative survival rate after 10 years was 94%. Survival was not influenced significantly by age, indication for operation, or having a contralateral hip prosthesis. The 10-year follow-up results for the MEM straight-stem total hip prosthesis in our hospital are satisfactory despite the probability that the cement mantle produced with this stem is not uniform in thickness.     

Definition of 'quack' in the public debate on alternative medicine

In May 1999 the Amsterdam Court of Justice decided that a retired internist and propagandist of his own alternative cancer therapy, could rightfully be called a quack by his critics. Recently this judgment was reversed on appeal. The first court used the medical definition of quackery: a treatment of which the supposed benefits are unsubstantiated. The court of appeal, however, took into consideration that to the general public calling someone a quack is an indication that this person is a swindler and practises medicine unlawfully. This definition is supported by the most authoritative Dutch dictionary. Apparently a different semantic interpretation of the term quack has led to these strongly diverging verdicts. The terms quack and quackery are indispensable in the public debate on alternative medicine.