Whipple's disease in a man with weight loss and diarrhea

In a 45-year-old man with diarrhoea, upper abdominal pain and malabsorption Whipple's disease was diagnosed by gastroduodenoscopy with small bowel biopsies. The disease is rare and can present with gastrointestinal problems but also with cardiac or neurological complaints. Tropheryma whippelii, the aetiological organism, can be demonstrated by pathological investigation of biopsies and with the polymerase chain reaction (PCR). Treatment with trimethoprim-sulfamethoxazole 160-800 mg twice daily is the therapy of choice: it must be continued for a year, otherwise there is a high possibility of relapse. Correct diagnosis, based mostly on gastroduodenoscopy, can lead to the right therapy and recovery of the patient.     

Whole genome sequencing identifies variants associated with sarcoidosis in a family with a high prevalence of sarcoidosis

Clinical Rheumatology - We studied genetic risk factors associated with sarcoidosis within a family with a high prevalence of this disease. We studied 41 members of a family with a high rate of...     

Long term results of pneumatic dilation in achalasia followed for more than 5 years

OBJECTIVE: We aimed to evaluate the long term therapeutic outcome in achalasia patients treated with pneumatic dilation, specifically focusing on those patients treated more than 15 yr ago. METHODS: All patients treated in our center whose records were available for review were asked to fill out a questionnaire assessing their degree of dysphagia, retrosternal pain, regurgitation, weight loss, and coughing during the night. The number of dilations was collected from the clinical records. The results of the treatment were classified into four different classes (excellent, good, moderate, poor). For those patients who had died, the cause of death was ascertained from the medical records or from the general practitioner. RESULTS: The questionnaires were distributed to 249 patients, 32 of whom had died. Of the 125 patients who completed the questionnaire, 81 (45 male and 36 female) were treated more than 5 yr ago. The mean follow-up was 12+/-1 yr. The therapeutic success rate was 50%, obtained after a median of four dilations (interquartile range = 3-6). Of this cohort, 25 patients (18 male and seven female, aged 35-84 yr) were treated more than 15 yr ago (mean follow-up = 20.5+/-0.5 yr). The median number of dilations was four (interquartile range = 3-7), with a therapeutic success rate of 40%. Two patients experienced a perforation, and seven were referred for surgery. Six patients out of 32 (19%) died of esophageal cancer. CONCLUSIONS: The long term success rate of pneumatic dilation is rather low, resulting in permanent successful treatment of achalasia in only 40-50% of patients. Achalasia is a risk factor for esophageal cancer.     

Early gastric cancer: a clinicopathologic study

We report our experience, between 1973 and 1989 of 302 patients with gastric cancer in a Dutch general hospital. In 144 (47.7%) of them gastric resection was performed. Twenty-eight patients had early gastric cancer (EGC) (9.3% of the entire series and 19.4% of the resected specimens). Multicentricity of EGC was noted in 3 patients (10.7%). The incidence of EGC decreased slightly during consecutive 8-year intervals. There were 16 men and 12 women (mean age 64 and 66 years, respectively). Standard biphasic contrast radiographic studies of the upper gastrointestinal tract diagnosed or suggested malignancy in all but one patient. Endoscopy with directed biopsy diagnosed malignancy in all patients. Twenty-one lesions (67.7%) were localized to the antral region. Type IIc was most frequent (38.7%). There were 21 intestinal-type and 10 diffuse-type EGC by the Lauren classification. The incidence of intestinal-type EGC decreased during two consecutive 8-year periods. All type I and IIa lesions were of the intestinal type, whereas all diffuse-type EGCs were either type IIc or III. Lymph node metastasis was observed in 9.7% of the lesions. The incidence of lymph node metastasis increased from 0% in mucosal cancer to 20% in submucosal cancer. The overall 5-year survival rate was 91.3%: (diffuse type 100% and intestinal type 85.7%). The 5-year survival rate was 100% in mucosal cancer and 81.8% in submucosal cancer.     

Microbial flora in the gastrointestinal tract abolishes cytostatic effects of alpha-difluoromethylornithine in vivo

Although treatment with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) leads to depletion of intracellular polyamines and to related growth inhibition in vitro, its cytostatic effects in vivo are disappointing. This may be due to abolition of DFMO-induced growth inhibition by polyamines released during normal body cell turnover, to dietary polyamines, or to putrescine synthesized by the microbial flora in the GI tract. We studied selectively (aerobic) and totally (aerobic + anaerobic) GI tract-decontaminated LI210-bearing mice fed with 3 types of diet differing in their polyamine and carbohydrate residue contents and treated with combinations of intraperitoneal DFMO and oral deuterium-labelled putrescine. Our data show that, irrespective of diet type, total decontamination markedly potentiates the moderate tumor growth inhibition that is caused by DFMO alone. During total decontamination, growth-inhibited L1210 cells accumulate in the G0/G1 phase of the cell cycle. Although orally administered deuterium-labelled putrescine gave rise to deuterium labelling of L1210 putrescine, spermidine and spermine, the polyamine levels in our diets played only a minor role.     

A patient with acute hydroxychloroquine poisoning; recommendation for treatment

We treated a 30-year-old man for whom Plaquenil (hydroxychloroquine) had been prescribed for rheumatoid arthritis, and who had taken 4 g orally to end his life. Symptoms of severe intoxication due to (hydroxy)chloroquine are rapid onset of hypoventilation, cardiovascular collapse with bradycardia, peripheral vasodilation, arrhythmias and convulsions. The lethal dose of chloroquine has been estimated at 3-5 g in adults and at 0.75-I g in young children. Acute intoxication should be treated with aspiration of gastric contents, artificial ventilation in case of hypoventilation and intravenous or intratracheal dopamine, noradrenaline or adrenaline in case of cardiovascular depression and peripheral vasodilation. Arrhythmias and convulsions should be treated symptomatically. The patient in our case survived the intoxication and is now under psychiatric treatment.     

Respiratory syncytial virus infection augments NOD2 signaling in an IFN‐β‐dependent manner in human primary cells

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants, with remarkable variability in disease severity. An exaggerated proinflammatory response and influx of leukocytes is part of the pathogenesis of severe RSV disease. Here, we show an increase in proinflammatory cytokine production by human immune cells after stimulation with RSV and muramyl dipeptide (MDP), which is recognized by nucleotide‐binding oligomerization domain containing 2 (NOD2). PBMCs from Crohn's disease patients homozygous for the 3020insC mutation in the NOD2 gene did not show a synergistic response to stimulation with RSV and MDP, suggesting that NOD2 is essential for the observed synergy. Further experiments aimed at identifying the viral ligand indicated that viral RNA plays an essential role in the recognition of RSV. Stimulation with RSV or Poly(I:C) induced IFN‐β expression, which resulted in an increased expression of the viral receptors TLR3 and RIG‐I, as well as an increased NOD2 expression. Our data indicate that IFN‐β induction by viral RNA is an essential first step in the increased proinflammatory response to MDP. We hypothesize that the enhanced proinflammatory response to MDP following RSV infection may be an important factor in determining the outcome of the severity of disease.     

Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice

Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.