[A rare cause of swelling of the little finger]. / Een snelgroeiende zwelling van de top van de pink.

A 71-year-old man presented with a painful swelling of the tip of his little finger. Infection was considered, but antibiotics and incision did not give relief. Biopsy showed metastasis of anal carcinoma, for which he had been treated 7 years earlier with curative chemoradiotherapy. He underwent amputation of the finger.

[A woman with nausea and epigastric pain]. / Een vrouw met misselijkheid en pijn in epigastrio.

An 48-year old woman presented at the emergency room with epigastric pain and nausea. 6 months earlier she had a distended ascending colon, which resolved quickly after conservative treatment with nasogastric tube. Now she had similar complaints. A plain abdominal radiograph was not conclusive; barium enema examination demonstrated a cecal volvulus. Patient required right hemicolectomy. She recovered uneventfully.

White Matter Lesions Are Not Related to ß-Amyloid Deposition in an Autopsy-Based Study.

Population-based studies have investigated the relation between ß-amyloid levels in cerebrospinal fluid or plasma and white matter lesions (WMLs). However, these circulating levels of ß-amyloid in cerebrospinal fluid or plasma may not reliably reflect the actual degree of amyloid present in the brain. Therefore, we investigated the relation between WMLs and ß-amyloid plaques and amyloid angiopathy in brain tissue. WML on MRI or CT were rated in 28 nondemented patients whose neuroimaging was available prior to death. ß-amyloid in plaques and arterioles were immunohistochemically stained and quantified in postmortem brain necropsies. WMLs were present in 43% of the total population. Both cortex and periventricular region showed no differences for ß-amyloid deposition in either plaques or blood vessel walls in patients with WMLs compared to those without WMLs. Thus, our results indicate that there is no relation between the degree of WMLs and ß-amyloid deposition in the brain.

Effects of the α7 nicotinic acetylcholine receptor agonist GTS-21 on the innate immune response in humans.

The vagus nerve can reflexively attenuate the innate immune response via binding of the vagal neurotransmitter acetylcholine (ACh) to the α7 nicotinic ACh receptor (α7nAChR). We recently reported potent anti-inflammatory effects of the α7nAChR agonist GTS-21 in human leukocytes. In the present work, we investigated the anti-inflammatory effects of GTS-21 on the innate immune response during experimental human endotoxemia. We performed a double-blind placebo-controlled pilot study in 14 healthy nonsmoking male volunteers. Subjects received 150 mg GTS-21 (n = 7) or placebo (n = 7) orally three times per day during 3 days before endotoxin administration and on the day of the human endotoxemia experiment. This GTS-21 dosage scheme is the highest reported to be safe in humans. Subsequently, subjects were i.v. administered 2 ng/kg endotoxin (LPS derived from Escherichia coli O:113). Serial blood withdrawals were performed to determine GTS-21 plasma concentrations and inflammatory mediators. Plasma concentrations of GTS-21 and its active metabolite 4-OH-GTS-21 were highly variable between subjects. LPS administration resulted in a transient inflammatory response. There were no differences in the LPS-induced cytokine response between the GTS-21- and placebo-treated groups. However, within the GTS-21-treated group, higher GTS-21 plasma concentrations correlated with lower levels of TNF-α (r = -0.78, P = 0.03), IL-6 (r = -0.76, P = 0.04), and IL-1RA (r = -0.86, P = 0.01), but not IL-10 (r = -0.35, P = 0.25). In conclusion, although higher GTS-21 plasma concentrations significantly correlated with lower cytokine levels, the highest dose tested to be safe in humans did not result in significant differences in inflammatory mediators between the GTS-21- and placebo-treated groups.