Clinical characteristics of muscle cramps in hereditary angiopathy with nephropathy, aneurysms, and muscle cramps syndrome associated with a novel COL4A1 pathogenic variant: A family case study.

BACKGROUND: Muscle cramps are a common problem characterized by a sudden, painful, and involuntary contraction of a muscle or muscle group. Most muscle cramps develop in the calf muscles, particularly in situations of prolonged exercise; however, some may be related to underlying systemic conditions such as the hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome. Muscle cramps appear to be the initial symptom of the HANAC syndrome; however, the clinical characteristics of these muscle cramps have rarely been described in detail. CASE PRESENTATION: We report a familial case of autosomal-dominant muscle cramps in four members of a Japanese family spanning across three generations. The muscle cramps were recognized as systemic symptoms of the HANAC syndrome associated with a novel COL4A1 pathogenic variant, NM_001845:c.1538G > A, p.(Gly513Asp). The four affected individuals indicated that the first episodes of the muscle cramps occurred in early childhood. In addition, they reported that the muscle cramps are characterized by an abrupt onset of severe pain without muscle contraction. The painful recurrent attacks occurred spontaneously in various muscles throughout the body, but rarely in the calf muscle. The muscle pain lasts for several minutes, cannot be ameliorated by stretching the affected muscle, and leaves a feeling of discomfort that lasts for 24-48 h. The serum creatine kinase levels of the patients were persistently elevated; however, their electromyography results did not reveal any specific abnormalities. CONCLUSIONS: Recognition of the clinical characteristics of the muscle cramps in the HANAC syndrome may facilitate early diagnosis of the syndrome and enable proper treatment of the patients, improve their long-term outcomes, and facilitate the design and adaption of appropriate genetic counseling.

Chloride Selective Macrocyclic Bisurea Derivatives with 2,2'-Binaphthalene Moieties as Spacers.

A cyclic bisurea derivative 2a has been successfully prepared from the corresponding diamine and diisocyanate in the presence of tetrabutylammonium chloride as a template. A more soluble cyclic bisurea 2b has also been prepared by introduction of sterically bulky tert-butyl groups. X-ray crystal analyses of [2a·Cl]- and [2b·Cl]- revealed that overall structure was saddle like and the chloride anion was located in the center of the cavity. The bound chloride anion was hydrogen bonded by four N-H of urea groups and weakly hydrogen bonded by four 1-C-H of naphthyl groups, respectively. After removal of the bound chloride anions of [2b·Cl]- with silver nitrate, two different X-ray crystals of free 2b were obtained; one was intermolecular hydrogen bonded shrunken structure and the other was extended structure. Receptor 2b showed large binding ability for Cl-, however, the selectivity for Cl- against basic anions, such as AcO- and F-, has been insufficient. In aqueous MeCN, the association constant of 2b for Cl- was reduced but still large, and the selectivity for hydrophobic Cl- was greatly improved. In this solvent, 2b also selectively recognized alkaline metal chloride salts. Therefore, cyclic bisurea 2b is highly selective and effective Cl- selective receptor.

An adult case of kawasaki disease in a pregnant Japanese woman: a case report.

Kawasaki disease is an acute febrile disease predominantly seen in young children. We report a case of Kawasaki disease in a 32-year-old pregnant woman. She developed a generalized erythematous skin rash accompanied by high fever. Bilateral conjunctival congestion, tender cervical lymphadenopathy, an edematous lower lip and peripheral edema followed by desquamation were observed. She was successfully treated with aspirin and intravenous gammaglobulin (1 g/kg/day). Her course was not complicated by coronary artery aneurysm and she delivered a healthy baby. To the best of our knowledge, this is the first case of Kawasaki disease in a pregnant woman. We suggest that Kawasaki disease should be included in the differential diagnosis of a generalized, erythematous skin rash accompanied by high fever in adults.

Three patients with cancer who developed rapid-eye-movement sleep behavior disorder.

This article discusses the clinical significance of differentiating parasomnia, such as rapid-eye-movement (REM) sleep behavior disorder (RBD), from delirium in patients with advanced cancer. We describe three patients with advanced cancer who presented with aberrant behavior at night. All three patients developed violent behaviors when they were administered opioids and/or chemotherapy. Polysomnography (PSG) showed REM sleep with tonic electromyography. Previous treatment with neuroleptics had failed to improve their problematic behaviors. Diagnosis was made using criteria for REM behavior disorder of the International Classification of Sleep Disorders, 2nd edition, and PSG. Clonazepam (0.5 mg/day) was administered orally once at night. After treatment with clonazepam, aberrant and violent behaviors were improved. It should be noted that it is not rare for patients with advanced cancer to present with parasomnia, such as RBD, although organic brain syndrome, such as delirium, is more prevalent. Therefore, it is necessary to provide adequate assessment and treatment of aberrant behaviors in cancer patients.

The efficient prevascularization induced by fibroblast growth factor 2 with a collagen-coated device improves the cell survival of a bioartificial pancreas.

OBJECTIVES: The subcutaneous transplantation of a bioartificial pancreas is a very attractive cure for diabetes mellitus. We recently developed a new immunoisolatory device that has the ability to induce neovascularization for subcutaneous transplantation. We applied the newly developed device to subcutaneous transplantation of a bioartificial pancreas. METHODS: We investigated the prevascularization-inducing activity of the device in diabetic rats by histologic analysis and evaluated the permeability of the device to insulin and BSA. We also evaluated the survival of cells enclosed in a bioartificial pancreas, which was composed of the device, from the viewpoint of the effects of prevascularization by semiquantitative RT-PCR. RESULTS: The devices induced prevascularization more efficiently than fibroblast growth factor 2 impregnated in gelatin microspheres alone did and had more useful permeability than a noncollagen-coated device. Significantly higher expression of insulin mRNA was detected in the RT-PCR amplicons from cells retrieved from the bioartificial pancreas transplanted at the prevascularization-induced site as compared with at a nonprevascularization-induced site. CONCLUSION: We demonstrated that our newly developed device has a superior ability to induce prevascularization in diabetic rats, and the prevascularization improves the initial cell survival of the implanted cells following transplantation.

An extremely low frequency magnetic field attenuates insulin secretion from the insulinoma cell line, RIN-m.

In this study, we investigated the effects of exposure to an extremely low frequency magnetic field (ELFMF) on hormone secretion from an islet derived insulinoma cell line, RIN-m. We stimulated RIN-m cells to secrete insulin under exposure to an ELFMF, using our established system for the exposure of cultured cells to an ELFMF at 5 mT and 60 Hz, or under sham exposure conditions for 1 h and observed the effects. In the presence of a depolarizing concentration of potassium (45 mM KCl), exposure to ELFMF significantly attenuated insulin release from RIN-m cells, compared to sham exposed cells. Treatment with nifedipine reduced the difference in insulin secretion between cells exposed to an ELFMF and sham exposed cells. The expression of mRNA encoding synaptosomal associated protein of 25 kDa (SNAP-25) and synaptotagmin 1, which play a role in exocytosis in hormone secretion and influx of calcium ions, decreased with exposure to an ELFMF in the presence of 45 mM KCl. These results suggest that exposure to ELFMF attenuates insulin secretion from RIN-m cells by affecting calcium influx through calcium channels.

The development of new immunoisolatory devices possessing the ability to induce neovascularization.

The transplantation of a bioartificial pancreas has been regarded as a potential method for successful islet transplantation without any immunosuppressive agents. The subcutaneous site is a very attractive site for transplantation of a bioartificial pancreas because of its advantage of an easy operation site. Our group has been reporting that transplantation of a bioartificial pancreas to the subcutaneous site can reverse hyperglycemia in diabetic recipients. Regarding shapes of a bioartificial pancreas, it is believed that a bag form has an advantage because it is easy to prepare a large quantity. Our group previously reported successful transplantation of a bioartificial pancreas in bag form, a mesh-reinforced polyvinyl alcohol bag (MRPB), implanted in the peritoneal cavity. We also reported that the effect of subcutaneous islet transplantation can be greatly improved with prevascularization treatment. In the present study, we attempted to combine MRPB to our protocol of subcutaneous prevascularization. The main problem of this trial is that the procedure of MRPB implantation injures the prevascularized blood vessel networks. To solve this problem, we made a slight alternation in our protocol, and designed new devices on the basis of MRPB. The new devices, possessing the ability to induce neovascularization, were prepared by collagen coating on the surface of MRPB and were implanted with/without different doses of FGF-2 impregnated in gelatin microspheres. When using 5 microg of FGF-2, more blood vessels were observed on the surface of type I/IV collagen-coated MRPB compared with the original MRPB and type I collagen-coated MRPB. Quite a few blood vessels were observed either around the injection site of 50 microg of FGF-2 impregnated in gelatin microspheres alone or around the implantation site of FGF-2-free gelatin microspheres and type I collagen-coated MRPB or type I/IV collagen-coated MRPB. Here we demonstrated that the combination of both FGF-2 impregnated in gelatin microspheres and collagen-coated MRPB could give an effective system of neovascularization suitable for subcutaneous implantation of a bioartificial pancreas.

Bioartificial pancreas transplantation at prevascularized intermuscular space: effect of angiogenesis induction on islet survival.

INTRODUCTION: Bioartificial pancreas (BAP) transplantation offers a potential treatment of diabetes mellitus. The optimal site for BAP transplantation has not yet been established. AIM: To monitor the effect of induction of neovascularization at the intermuscular space on islet survival after allogenic transplantation of BAP. METHODOLOGY: Angiogenesis was induced at the intermuscular space of diabetic Lewis rats by implanting a polyethylene terephthalate (PET) mesh bag, which enclosed a collagen sponge and biodegradable gelatin microspheres containing basic fibroblast growth factor. After confirmation of angiogenesis, BAP was prepared by mixing of 5% agarose with approximately 2,800 isolated rat (Sprague-Dawley) islets and transplanted into the prevascularized PET mesh bag. RESULTS: Neovascularization was observed in and around the PET mesh bag within 10 days after implantation as confirmed by macroscopic and microscopic examinations. In the presence of a collagen sponge, new blood vessels penetrated into the PET mesh bag and formed a vascular bed. After transplantation, normoglycemia was achieved in the rats within 3 days and maintained for >35 days. The rats gradually gained body weight, and the results of intravenous glucose tolerance test showed normal patterns of blood glucose clearance 1 month after transplantation. CONCLUSION: It can be concluded that the prevascularized PET mesh bag enabled transplanted BAP to survive and maintain function, thus indicating a potential site for BAP transplantation.