Severe hypocalcemia after denosumab treatment leading to refractory ventricular tachycardia and veno-arterial extracorporeal membrane oxygenation support: a case report.

BACKGROUND: Severe hypocalcemia may lead to life-threatening arrhythmias. Denosumab is an effective treatment for osteoporosis that allows long intervals between doses. However, there is a risk of hypocalcemia in some patients. Due to the long half-life of denosumab, emergency physicians caring for patients presenting with symptoms of hypocalcemia may not be aware of the medication, and adverse effects may last longer. CASE PRESENTATION: A 55-year-old woman with a history of systemic lupus erythematosus (SLE) and anxiety disorder called for an ambulance for symptoms of hyperventilation and muscle cramps. After evaluation at the local hospital, she developed pulseless ventricular tachycardia and was resuscitated by defibrillation by the hospital staff. After conversion to sinus rhythm, she was transported to a tertiary center. Upon arrival, pulseless ventricular tachycardia occurred again, and veno-arterial extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pumping (IABP) were implemented. Laboratory results showed severe hypocalcemia (corrected calcium level of 5.3 mg/dL) whereupon intravenous calcium supplementation was started. She had received the first dose of denosumab (60 mg) by subcutaneous injection 24 days prior to hospitalization. She was eventually weaned from ECMO and IABP support. CONCLUSION: Cardiac arrest due to hypocalcemia is relatively rare but can be fatal. In the present case, hyperventilation may have acutely exacerbated pre-existing hypocalcemia, leading to ventricular tachycardia. The patient had a slightly decreased serum calcium level prior to denosumab. Close monitoring may be preferable after the primary dose of denosumab in selected patients. Emergency physicians caring for patients who may be suffering from symptoms/signs of hypocalcemia must be mindful of medications that have long half-lives and affect electrolyte balance when treating fatal arrhythmia due to hypocalcemia.

Histologic and electrophysiological study of nerve regeneration using a polyglycolic acid-collagen nerve conduit filled with collagen sponge in canine model.

OBJECTIVES: To determine the rate of achieving electrophysiologically proved functional recovery by autonomic nerve regeneration, with the aid of an artificial nerve conduit. METHODS: A polyglycolic acid (PGA) collagen nerve conduit filled with collagen sponge was interposed in a 10-mm-long gap of the right hypogastric nerve (HGN) in 16 dogs. Histologic evaluation of nerve regeneration and electrophysiological analysis at 2 weeks and 2, 3, 4, 5, 6, 7, and 8 months (n = 2, each) after surgery was performed, measuring the responses for the spermatic ducts (SD), bladder neck (BN), and prostate contraction, by stimulating the right lumbar splanchnic nerves (LSNs) from L2 to L4, after transection of the left HGN to eliminate substitutive pathways. RESULTS: Two months after implantation, the regenerated neurofilaments were successfully extended through the graft from the proximal-to-distal direction. In 2 control dogs, electrostimulation of the right LSNs induced elevation of the intraluminal pressure of the SD, elevation of the BN pressure, and prostate contraction. No responses were observed in all dogs up to 6 months of follow-up after implantation. In 1 dog with a 7-month follow-up, electrostimulation elicited elevation of BN pressure alone. In both dogs with an 8-month follow-up, electrostimulation induced similar responses to control in all SD, BN, and prostate; however, after excision of the area of the interposed right HGN, no response was observed. CONCLUSIONS: These results proved that regeneration of a 10-mm gap of the HGN, using a novel PGA-collagen nerve conduit could be achieved within 8 months.

Marked production of ginsenosides Rd, F2, Rg3, and compound K by enzymatic method.

The hydrolysis of protopanaxadiol-type saponin mixture by various glycoside hydrolases was examined. Among these enzymes, crude preparations of lactase from Aspergillus oryzae, beta-galactosidase from A. oryzae, and cellulase from Trichoderma viride were found to produce ginsenoside F(2) [3-O-(beta-D-glucopyranosyl)-20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], compound K [20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], and ginsenoside Rd {3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol}, respectively, from protopanaxadiol-type saponin mixture in large quantities. Moreover, the crude preparation of lactase from Penicillium sp. having a high producing activity of ginsenoside Rh(1) (6-O-beta-D-glucopyranosyl-20(S)-protopanaxatriol) from protopanaxatriol-type saponin mixture gave ginsenoside Rd as a main product, ginsenoside Rg(3) {3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20(S)-protopanaxadiol}, and compound K from protopanaxadiol-type saponin mixture. The hydrolytic pathways of ginsenosides Rb(1), Rb(2), and Rc to ginsenosides Rd, Rg(3), and F(2), and compound K by crude preparations of four glycoside hydrolases were also studied. This is the first report on the enzymatic preparation of an intestinal bacterial metabolite, ginsenoside F(2), in quantity, and a considerable amount of a minor saponin, ginsenoside Rg(3), from a protopanaxadiol-type saponin mixture.

Sign and speech: amodal commonality in left hemisphere dominance for comprehension of sentences.

The neural basis of functional lateralization in language processing is a fundamental issue in systems neuroscience. We used functional MRI (fMRI) to examine hemispheric dominance during the processing of signed and spoken sentences. By using tasks involving comprehension of sentences (Sc) and sentential non-word detection (Sn), we compared different groups and stimulus conditions. Under the sign condition with sentence stimuli in Japanese Sign Language (JSL), we tested two groups of subjects: Deaf signers (Deaf) of JSL, and hearing bilinguals (children of Deaf adults, CODA) of JSL and Japanese (JPN). Under the speech condition, we tested hearing monolinguals (Mono) of JPN with auditory JPN stimuli alone (AUD), or with an audiovisual presentation of JPN and JSL stimuli (A&V). We found that the overall bilateral activation patterns under the four experimental conditions of Deaf, CODA, AUD and A&V were almost identical, despite differences in stimuli (JSL and JPN) and groups (Deaf, CODA and Mono). Moreover, consistently left-dominant activations involving frontal and temporo-parietal regions were observed across all four conditions. Furthermore, irrespective of the modalities of sign and speech, the main effects of task (Sc-Sn) were found primarily in the left regions: the ventral part of the inferior frontal gyrus (F3t/F3O), the precentral sulcus, the superior frontal gyrus, the middle temporal gyrus, the angular gyrus and the inferior parietal gyrus. Among these regions, only the left F3t/F3O showed no main effects of modality condition. These results demonstrate amodal commonality in the functional dominance of the left cortical regions for comprehension of sentences, as well as the essential and universal role of the left F3t/F3O in processing linguistic information from both signed and spoken sentences.

Enzymatic preparation of ginsenosides Rg2, Rh1, and F1.

During investigation of the hydrolysis of a protopanaxatriol-type saponin mixture by various glycoside hydrolases, crude preparations of beta-galactosidase from Aspergillus oryzae and lactase from Penicillium sp. were found to produce two minor saponins, ginsenoside Rg(2) [6-O-(alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl)-20(S)-protopanaxatriol] and ginsenoside Rh(1) (6-O-beta-D-glucopyranosyl-20(S)-protopanaxatriol), respectively, in high yields. Moreover, a naringinase preparation from Penicillium decumbens readily gave an intestinal bacterial metabolite, ginsenoside F(1) (20-O-beta-D-glucopyranosyl-20(S)-protopanaxatriol), as the main product, with a small amount of 20(S)-protopanaxatriol from a protopanaxatriol-type saponin mixture. Also, a hesperidinase from Penicillium sp. selectively hydrolyzed ginsenoside Re into ginsenoside Rg(1). This is the first report on the enzymatic preparation of minor saponins, ginsenosides Rg(2) and Rh(1), and of an intestinal bacterial metabolite, ginsenoside F(1), with high efficiency from a protopanaxatriol-type saponin mixture.

An event-related fMRI study of explicit syntactic processing of normal/anomalous sentences in contrast to implicit syntactic processing.

Using event-related functional magnetic resonance imaging (fMRI), we examined activation of cortical language areas for explicit syntactic processing. In a syntactic decision (Syn) task, the participants judged whether the presented sentence was syntactically correct, where syntactic knowledge about the distinction between transitive and intransitive verbs was required. In a semantic decision (Sem) task, lexico-semantic knowledge about selectional restrictions was indispensable. In a phonological decision (Pho) task, phonological knowledge about accent patterns was required. The Sem and Pho tasks involved implicit syntactic processing, as well as explicit semantic and phonological processing, respectively. We also tested a voice-pitch comparison (Voi) task in which no explicit linguistic knowledge was required. In the direct comparison of Syn - (Sem + Pho + Voi), we found localized activation in the left inferior frontal gyrus (F3op/F3t), indicating that activation of the left F3op/F3t is more prominently enhanced in explicit syntactic processing than in implicit syntactic processing. Moreover, we determined that its activation is selective to syntactic judgments regarding both normal and anomalous sentences. These results suggest that explicit information processing in the syntactic domain critically involves the left F3op/F3t, which is functionally separable from other regions.