Achondroplasia (ACH) is the most common form of short-limbed skeletal dysplasia. Patients with ACH sometimes undergo lower limb lengthening to get functional and psychological achievements. The periosteal resection (PR) is a known mechanism to increase longitudinal bone growth without osteotomy, although the results are not predictable. It could be alternative for limb lengthening in a minimally invasive technique. The purpose of this study is to evaluate the effect of PR on acceleration of bone growth in a mouse model of ACH (Fgfr3ach). We performed a circumferential resection of periosteum on the proximal tibia to both wild-type and Fgfr3ach mice at the age of four weeks. The second PR was done one week later in each mouse, which was subsequently sacrificed at the age of six weeks for micro-computed tomography (micro-CT) scan and histological examinations. We measured tibial bone length, bone volume, and metaphyseal trabecular bone parameters, including bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) by reconstructed micro-CT images. We also quantified the entire width of the growth plate of the proximal tibial from the sections stained with hematoxylin and eosin. Tibial bone length and bone volume of the PR side were significantly larger than the sham side in wild-type mice, while they were not statistically significant in Fgfr3ach mice. The BV/TV and Tb.N in the metaphysis were significantly decreased in the PR side of both mice. The histological analysis revealed that the growth plate of the proximal tibia was significantly wider in the PR side of wild-type mice while it showed no difference in width between the PR side and the sham side in Fgfr3ach mice. PR promoted longitudinal bone growth in wild-type mice, but it exhibited only a marginal effect on bone growth in Fgfr3ach mice.
Problem: Tumor necrosis factor (TNF)‐α is a major cytokine involved in inflammatory and immune function. The aim of this study was to investigate whether polymorphisms at positions −1031, −863 and −857 in the TNF gene promoter region ( TNFA ) and TNF receptor type 2 gene (TNFR2 ) are responsible in part for genetic susceptibility to endometriosis. Methods of study: TNFA and TNFR2 polymorphisms were determined in 123 patients with endometriosis and 165 fertile healthy women by the polymerase chain reaction (PCR) – preferential homoduplex formation assay and PCR‐restriction fragment length polymorphism, respectively. Results: The frequency of the TNFA‐U01 haplotype was increased significantly in patients with endometriosis compared with controls ( P = 0.045, OR = 1.45). The TNFA‐U01 haplotype was strongly associated with HLA‐B*0702. No difference was found in TNFR2 polymorphism between patients and controls. Conclusion: Our results indicated that TNFA promoter polymorphism was associated with susceptibility to endometriosis. However, this association was not independent of HLA‐class I polymorphisms.
We measured the high-field magnetization and de Haas–van Alphen (dHvA) oscillations for YbIr 2 Zn 20 with a cubic crystal structure, together with the electrical resistivity and magnetic susceptibility. The magnetic susceptibility χ with an effective magnetic moment of Yb 3+ becomes temperature-independent at low temperatures, with a broad peak at T χmax =7.4 K for H ∥<110>. The corresponding magnetization indicates a metamagnetic transition at H m =120 kOe, consistent with a T χmax vs H m relation in the Ce- and U-based heavy fermion compounds. The large cyclotron masses of 4–27 m 0 are detected in the dHvA experiment, and are found to be reduced at magnetic fields higher than H m =120 kOe. The resistivity follows the Fermi liquid relation ρ=ρ 0 + A T 2 under magnetic field, and the \(\sqrt{A}\) value is also found to have a maximum at H m as a function of magnetic field. From the present experimental results, together with the results of 4 f -itinerant energy band calculations, the 4 f electrons are found to contribute to the heavy fermion state in YbIr 2 Zn 20 .
Coronal angular deformities of the lower limbs are common in young children with skeletal dysplasia . The guided growth technique has been applied to correct deformities in children, but there are few comprehensive reports on the effectiveness of the procedure in skeletal dysplasia. We reviewed 44 limbs of 22 patients with various types of skeletal dysplasias who underwent guided growth surgery. Fifteen varus and 29 valgus limbs were treated with 102 epiphysiodesis. The average age at surgery, at implant removal, and at the latest examination was 10.4 ± 3.6 years, 11.8 ± 3.7 years and 14.1 ± 4.4 years, respectively. The mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (mMPTA), lateral distal tibial angle (mLDTA) and mechanical axis deviation (MAD) were measured from standing anteroposterior radiographs of both lower limbs. The mLDTA, mMPTA and MAD were successfully improved after surgery. Moderate or severe deformities were observed in 100% of the varus and 83% of the valgus limbs preoperatively, whereas only 14% of the varus and 20% of the valgus limbs had residual deformities at the latest examination. Correction of deformities was limited in some older children. Fifteen limbs (34%) required repeated implantations due to recurrence or inverted deformity. The guided growth surgery is effective in correcting coronal angular deformities in children with skeletal dysplasia with a limited risk of complications. The timing of surgery and implant removal is critical in obtaining satisfactory correction and preventing recurrence or inverted deformities.
Achondroplasia (ACH), the most common form of short-limbed skeletal dysplasia, is caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. More than 97% of patients result from a heterozygous p.G380R mutation in the FGFR3 gene. We present here a child who had two de novo variants in the FGFR3 on the same allele, a common p.G380R mutation and a novel p.S378N variant.A 3-year-old Japanese girl born from non-consanguineous healthy parents showed more severe clinical and radiological phenotypes than classic ACH, including severe short-limbed short stature with marked ossification defects in the metaphysis and epiphysis, hydrocephalus and cervicomedullary compression due to foramen magnum stenosis, prolonged pulmonary hypoplasia, and significant delay in the gross motor development. Genomic DNA was extracted from the proband and whole-exome sequencing was performed. The variants were subsequently confirmed by Sanger sequencing.Mutation analysis demonstrated that the proband had p.S378N (c.1133G>A) and p.G380R (c.1138G>A) variants in the FGFR3 gene. Both variants were not detected in her parents and therefore considered de novo. An allele-specific PCR was developed in order to determine whether these mutations were on the same allele (cis) or on different alleles (trans). The c.1138G>A mutation was found in the PCR product generated with the primer for the mutant 1133A, but it was not detected in the product with the wild-type 1133G, confirming that p.S378N and p.G380R variants were located on the same allele (cis).This is the second case who had two FGFR3 variants in the transmembrane domain on the same allele. The p.S378N variant may provide an additive effect on the activating receptor with the p.G380R mutation and alter the protein function, which could be responsible for the severe phenotype of the present case.
A 70-year-old man was admitted to a local hospital with epigastric pain and diagnosed with type-2 gastric cancer. Contrast-enhanced CT scan showed metastases in S3 and S8 of the liver, and the tumor was classified as type cT4aN2H1, cStage ⅣB. Nivolumab monotherapy was initiated after failure of treatment with S-1 plus oxaliplatin and ramucirumab. After 6 courses, the primary tumor, lymph nodes, and liver metastases had shrunk to a remarkable degree. The patient underwent a proximal gastrectomy with D2 lymph node dissection and partial liver resection. Histopathological examination revealed no remaining tumor cells, with a histological response Grade 3.
For 197 adults and adolescents in four villages of three small islands in the Admiralty Islands, Papua New Guinea, antimalarial antibody titers were examined using the indirect fluorescent antibody test (IFAT) and malaria parasites were detected by the microtiter plate hybridisation (MPH) method using polymerase chain reaction (PCR) technique. The parasite rate (either Plasmodium falciparum or P. vivax, or both) averaged 39.2 %, varying from 31.1 % to 44.8 % among the four villages due to natural and artificial microenvironmental conditions related to breeding sites of mosquitoes ( Anopheles farauti). The lack of flat zones owing to geomorphological formation contributed to the lowest parasite rate in the extremely small island. However, human-modified environments such as a wet-land (naturally formed but artificially reformed) and an open well played significant roles in other inter-village differences. The present findings imply significant roles of microenvironment in diversified malaria prevalence and suggest some ways of mitigation of malarial hazards. Asia Pac J Public Health 2001; 13(2): 85-90
We studied whether the diameter of the saphenous vein graft affects the result of femoro-popliteal bypass surgery.Thirty-eight patients with bypasses from the femoral artery to the above knee popliteal artery were studied. Bypasses without a patent anterior or posterior tibial artery were excluded. The great saphenous vein was used as a bypass graft in 20 extremities and Dacron grafts (6 mm or 8 mm diameter) were used in 18 arteries. The smallest diameter of the saphenous vein was measured preoperatively with ultrasonography. Vein grafts were divided into two groups: small vein graft (< or =3 mm) and large vein graft (> or =3.5 mm). The ankle brachial pressure index (ABI) was measured at 1 week and 3 months after operation.The diameter of the vein graft (2.5 to 4 mm, 3.4+/-0.5 mm) was positively correlated with postoperative ABI (R2 0.607, P<0.0001). The postoperative ABI at 1 week was significantly lower in the small vein graft group (0.72+/-0.09) than in the large vein graft group (0.95+/-0.11) and in the Dacron graft group (1.05+/-0.16). The ABI at 3 months was still significantly lower in small vein graft group (0.78+/-0.07).The diameter of the vein graft was positively correlated with postoperative ABI after femoro-popliteal above knee bypass. Postoperative ABI was lower using a vein graft with a diameter of < or =3 mm than that using a bigger vein graft or a Dacron graft.
