Genomic Dissection of Travel-Associated Extended-Spectrum-Beta-Lactamase-Producing Salmonella enterica Serovar Typhi Isolates Originating from the Philippines: a One-Off Occurrence or a Threat to Effective Treatment of Typhoid Fever?

One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing Salmonella enterica serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of S. Typhi. The reported strain was similar to a previously published strain harboring bla_SHV-12 from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing S. Typhi.     

Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients.

(18)F-Galacto-RGD has been developed for PET of alpha(v)beta(3) integrin expression, a receptor involved in, for example, angiogenesis and metastasis. Our aim was to study the kinetics and biodistribution of (18)F-Galacto-RGD in cancer patients. METHODS: Nineteen patients with metastases of malignant melanoma (n = 7), sarcomas (n = 10), or osseous metastases (n = 2) were examined. After injection of 133-200 MBq (18)F-Galacto-RGD, 3 consecutive emission scans from the pelvis to the thorax or dynamic emission scans of the tumor over 60 min, followed by 1 static emission scan of the body, were acquired. Time-activity curves and standardized uptake values (SUVs) were derived by image region-of-interest analysis with image-based arterial input functions. Compartmental modeling was used to derive the distribution volume for muscle tissue and tumors. RESULTS: (18)F-Galacto-RGD showed rapid blood clearance and primarily renal excretion. SUVs in tumors ranged from 1.2 to 9.0. Tumor-to-blood and tumor-to-muscle ratios increased over time, with peak ratios of 3.1 +/- 2.0 and 7.7 +/- 4.3, respectively, at 72 min. The tumor kinetics were consistent with a 2-tissue compartment model with reversible specific binding. Distribution volume values were, on average, 4 times higher for tumor tissue (1.5 +/- 0.8) than those for muscle tissue (0.4 +/- 0.1). The data suggest that there was only minimal free and bound (specific or nonspecific) tracer in muscle tissue. CONCLUSION: (18)F-Galacto-RGD demonstrates a highly favorable biodistribution in humans with specific receptor binding. Most important, this study shows that (18)F-Galacto-RGD allows visualization of alpha(v)beta(3) expression in tumors with high contrast. Consequently, this tracer offers a new strategy for noninvasive monitoring of molecular processes and may supply helpful information for planning and controlling of therapeutic approaches targeting the alpha(v)beta(3) integrin.     

Dynamic aspects of expanding cava septi pellucidi et Vergae

Summary Two paediatric patients with expanding cysts of the cava Vergae et septi pellucidi are presented. In the first patient, consecutive CT scans showed agrowing cavum thought to be responsible for his dramatic increase in head circumference. In the other patient, the expanding cavum was discovered because a routine skull X-ray after minor head trauma revealed marked impressiones digitatae.Both patients were successfully treated with stereotactically placed internal shunts from the cysts via the lateral ventricle to the subarachnoid space. During this procedure, contrast medium was instilled, and the cysts were visualized on postoperative CT scans.Some dynamic aspects of such expanding cava are discussed.     

Prognosis of fracture of the talus in children: 21 (7-34)-year follow-up of 14 cases

14 children suffering from a fracture of the talar neck or body were examined after 21 (7-34) years. The talar neck was fractured in 10 children and the talar body in 4. 3 fractures were displaced and primarily treated with reduction and immobilization. Nondisplaced fractures were treated conservatively. All fractures healed. All patients with displaced fractures had exercise-induced pain at follow-up. Of 11 patients with nondisplaced fractures only 1 had minor complaints.

CT and conventional radiographs showed arthrosis in the talocrural joint and normal subtalar joints in those with displaced fractures. The radio- graphic findings were normal after nondisplaced fractures.     

Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats.

BACKGROUND AND PURPOSE: Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed. METHODS: Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n = 5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 mg/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted. RESULTS: Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean +/- SEM baseline, 1.86 +/- 0.25 pmol/ml perfusate; during ischemia, 8.14 +/- 0.89 pmol/ml; p < 0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98 +/- 0.15 pmol/ml; ischemia, 24.4 +/- 5.93 pmol/ml; p < 0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34 +/- 16 normal-appearing neurons, middle, 52.2 +/- 22.9 neurons; lateral, 56.6 +/- 21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6 +/- 6.5 neurons; middle, 131.4 +/- 4.9 neurons; lateral, 130 +/- 7.5 neurons; p < 0.01 different from nontreated). CONCLUSIONS: Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage.     

In vivo percutaneous absorption and skin decontamination of alachlor in rhesus monkey.

The objectives of this study were to determine the percutaneous absorption of alachlor relative to formulation dilution with water, and to determine the ability of soap and water, and of water only, to remove alachlor from skin, relative to time. Alachlor is a preemergence herbicide. The in vivo percutaneous absorption of alachlor in rhesus monkeys was 17.3 +/- 3.3, 15.3 +/- 3.9, and 21.4 +/- 14.2% for 24-h skin exposure to Lasso formulation diluted 1:20, 1:40, and 1:80, respectively. In vivo, there was no support for increased alachlor skin absorption with water dilution, as previously reported for in vitro absorption. The average in vivo absorption of 18% applied dose over 24 h (0.75%/h) was similar to the maximum in vitro rate of 0.8%/h using human skin and human plasma as receptor fluid. Dose accountability in vivo was 80.6-95.2%. [14C]Alachlor in Lasso diluted 1:20 with water was placed on rhesus monkeys at concentrations of 23 micrograms/10 microliters/cm2. Skin decontamination at 0 h with soap and water (50% Ivory liquid 1:1 v/v with water) removed 73 +/- 15.8% (n = 4) of the applied dose with the first wash; this increased to a total of 82.3 +/- 14.8% with two additional washes. Decontamination after 1 h removed 87.5 +/- 12.4% with three successive washes. After 3 h decontamination ability decreased, and after 24 h only 51.9 +/- 12.2% could be recovered with three successive washes. Using water only, at 0 h 36.6 +/- 12.3% alachlor was removed with the first wash and the total increased to 56.0 +/- 14.0% with two additional washes. At 24 h the total amount decreased to 28.7 +/- 12.2% for three successive washes. Alachlor as Lasso in field-use rate (11 micrograms/cm2) and undiluted (217 and 300 micrograms/cm2) proportions were left on rhesus monkey skin for 12 h and decontaminated with soap and water (10% Ivory liquid v/v with water). Continual successive washes (6-8 in sequence) recovered 80-90% of the skin-applied alachlor. These results suggest that simple washing with soap and water is appropriate for removing some chemicals from skin. Decontamination with only water was less effective than with soap and water.     

Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists.

The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications.