Recombinant growth hormone therapy for prepubertal children with idiopathic short stature in Korea: a phase III randomized trial.

PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.

First Report of Powdery Mildew Caused by Cystotheca wrightii on Quercus glauca in Korea.

Quercus glauca Thunb. (syn. Cyclobalanopsis glauca (Thunb.) Oerst.), known as ring-cupped oak or Japanese blue oak, is a dominant tree species commonly found in evergreen forests in East Asia (2). In May 2012, hundreds of Q. glauca were found heavily affected by a powdery mildew in several locations of Jeju Islands, Korea. Symptoms on overwintered leaves appeared as circular to irregular blackish violet to dark brown felt-like growths with numerous chasmothecia on abaxial leaf surfaces. New infections on current-year leaves started in early summer and were characterized by typical white patches with abundant sporulation on abaxial leaf surfaces. In early autumn, with formation of special aerial hyphae and without further sporulation, the patches turned light brown to brown. Formation of chasmothecia was noticed from late autumn. The adaxial leaf surface was free of powdery mildew growths and exhibited yellowing and discoloration. Voucher specimens were deposited in the Korea University Herbarium (KUS). Special aerial hyphae were falcate to curved, aseptate, at first hyaline, later deep brown to purplish brown, thick-walled, and 80 to 140 × 6 to 15 µm. Conidiophores were 175 to 245 × 10 to 12 µm, and produced 2 to 4 immature conidia in chains with a sinuate outline. Foot-cells of conidiophores were cylindrical and 80 to 120 µm long. Conidia were lemon- to barrel-shaped, 26 to 35 × 17 to 24 µm with a length/width ratio of 1.2 to 1.6, and devoid of fibrosin bodies. Primary conidia were apically conical and basally subtruncate. Germ tubes produced in the lateral to perihilar position of conidia were long and slender (3 µm wide). Chasmothecia were scattered or gregarious, partly embedded with special aerial hyphae, dark brown, spherical, 55 to 70 µm in diameter, and contained a single ascus. Chasmothecial peridia consisted of two layers. Exoperidia (outer layer) were composed of dark brown, polygonal cells 10 to 20 µm wide. Endoperidia (inner layer) consisted of hyaline, polygonal cells 10 to 15 µm wide. Appendages were basally attached, mycelioid, rare or few, and pale brown to rusty brown. Asci were short stalked, 55 to 72 × 35 to 46 µm, had a terminal oculus 10 to 20 µm wide, and contained 8 ascospores. Ascospores were oblong-elliptical, 22 to 27 × 10 to 12.5 µm, subhyaline, and contained 1 or 2 oil drops. The specific measurements and characteristics (especially falcate aerial hyphae) were consistent with those of Cystotheca wrightii Berk. & M.A. Curtis (1). Fungal DNA was extracted by the Chelex method. The internal transcribed spacer (ITS) region of rDNA of KUS-F27309 was amplified with primers ITS5/P3 and sequenced directly (4). The resulting 589-bp sequence was deposited in GenBank (Accession No. KF735066). A BLAST search in GenBank showed that the Korean isolate had 100% homology with C. wrightii on Q. glauca from Japan (AB000932). Powdery mildews of Q. glauca associated with C. wrightii have been known in Japan, Taiwan, and China (1,3), but not in Korea. Finding of C. wrightii on Q. glauca could pose a potential threat to other evergreen oak species in southern part of Korea. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No. 11, CBS, Utrecht, Netherlands, 2012. (2) X. Y. Chen et al. Acta Bot. Sin. 39:149, 1997. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, retrieved 21 October, 2013. (4) S. Takamatsu et al. Mycol. Res. 113:117, 2009.

First Confirmed Report of Powdery Mildew Caused by Podosphaera xanthii on Farfugium japonicum in Korea.

Farfugium japonicum (L.) Kitam., known as Japanese silver leaf, is native to Japan, Korea, and Taiwan. It is grown as an ornamental plant for garden plantings and containers not only in East Asia but more recently also in Europe and North America. Since 2003, powdery mildew infections of F. japonicum 'Gigantea' have been consistently found in the southern part of Korea, including the districts of Jeju, Seogwipo, Busan, Wando, and Ulleungdo. Specimens have been deposited in the Korea University Herbarium (KUS). Signs of powdery mildew first appeared as circular to irregular white patches on both sides of the leaves. The infections were usually severe on young leaves and caused malformation and browning. Appressoria on the mycelium were nipple-shaped or nearly absent. Conidiophores, measuring 160 to 280 × 10 to 12.5 µm, were simple and produced 2 to 12 immature conidia in chains, followed by 2 to 3 cells. Foot-cells in conidiophores were relatively short, 50 to 95 µm long, and constricted at the base. Conidia were hyaline, ellipsoid to ovate, 32 to 48 × 17.5 to 25 µm (length/width ratio = 1.4 to 2.3), had distinct fibrosin bodies, and produced germ tubes on the lateral position. No chasmothecia were observed. The morphology and dimentions of reproductive structures were compatible with those of Podosphaera xanthii (Castagne) U. Braun & Shishkoff (1). To confirm the identity of the causal fungus, the complete ITS region of rDNA from isolate KUS-F26469 was amplified with primers ITS5 and P3 (4) and directly sequenced. The resulting sequence of 475 bp was deposited in GenBank (Accession No. KC155426). A GenBank BLAST search of this sequence revealed 100% identity (475/475 bp) with those of many P. fusca isolates on plants in the Aster family plants including Calendula officinalis, Euryops pectinatus, Syneilesis palmata, and F. japonicum from Japan (e.g., AB040346). The P. fusca isolates listed above are now placed in P. xanthii (1). Pathogenicity was confirmed through inoculation by gently pressing diseased leaves onto leaves of three healthy potted plants of the same cultivar. Three non-inoculated plants served as controls. Plants were maintained in a greenhouse at 25 ± 2°C. Inoculated plants developed typical signs and symptoms of powdery mildew after 8 days, whereas the control plants remained symptomless. The fungus present on the inoculated leaves was morphologically identical to that originally observed on diseased plants. Powdery mildew infections of F. japonicum caused by P. fusca (syn. P. fuliginea) have been reported previously in both Japan and Korea (2). In Korea, it was listed simply as a host fungus of Ampelomyces quisqualis, which is hyperparasitic to powdery midlews, without any data on its identity (3). To our knowledge, this is the first confirmed report of powdery mildew caused by P. xanthii on F. japonicum in Korea. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (2) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved November 14, 2012. (3) M. J. Park et al. Fungal Biol. 114:235, 2010. (4) S. Takamatsu et al. Mycol. Res. 113:117, 2009.

First Report of Leaf Spot Caused by Pseudocercospora subsessilis on Melia azedarach in Korea.

Melia azedarach L., called chinaberry, is native to Southeast Asia and Australia. The trees are commonly planted as ornamentals in the southern part of Korea. In October 2010, a leaf spot disease was observed on trees for the first time in Wando, Korea. Further surveys conducted from 2010 to 2012 showed that the disease occurs on trees in Jeju, Seogwipo, and Tongyeong cities as well as Wando county with nearly 100% incidence. Leaf spots were circular to semicircular, later becoming angular, small, pale brown in the center with a dark brown margin, and later becoming milky white. Leaf spots sometimes coalesced to blight the entire leaf and were capable of rapidly defoliating whole trees in late September. Fruiting was amphigenous, but mostly hypogenous. Stromata were substomatal, globular, dark brown, and 25 to 70 µm in diameter. Conidiophores were densely fasciculate, pale olivaceous to pale brown, substraight to mildly curved, not geniculate, 10 to 30 µm long, 2.5 to 4.5 µm wide, and aseptate or uniseptate. Conidia were pale olivaceous, generally darker than conidiophores, cylindric to obclavate, substraight in shorter ones, curved to mildly sinuous in longer ones, obconically truncate at the base, obtuse at the apex, 2- to 14-septate, 16 to 120 × 3 to 5 µm, guttulate, and had inconspicuous hila. Morphological characteristics of the fungus were consistent with the previous descriptions of Pseudocercospora subsessilis (Syd. & P. Syd.) Deighton (2). Voucher specimens (n = 6) were deposited in the Korea University Herbarium (KUS). An isolate from KUS-F25395 was deposited in the Korean Agricultural Culture Collection (KACC45688). The complete internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1/ITS4 (3) and sequenced. The resulting sequence of 517 bp was deposited in GenBank (Accession No. JX993904). A BLAST search in GenBank revealed that the sequence shows >99% similarity (1 bp substitution) with a sequence of P. subsessilis ex M. azedarach from Cuba (GU269815). For pathogenicity tests, hyphal suspensions were prepared by grinding 3-week-old colonies grown on potato dextrose agar with distilled water using a mortar and pestle. Five 3-year-old chinaberry trees were inoculated with hyphal suspensions using a fine haired paint brush. Three healthy trees of the same age, serving as controls, were sprayed with sterile water. The plants were covered with plastic bags to maintain 100% relative humidity for 24 h and then transferred to a greenhouse. Typical symptoms of necrotic spots that appeared on the inoculated leaves 10 days after inoculation were identical to the ones observed in the field. P. subsessilis was reisolated from symptomatic leaf tissues, confirming Koch's postulates. No symptoms were observed on control plants. The disease has been reported in several Asian countries as well as in Cuba and the United States (1). To our knowledge, this is the first report of leaf spot on chinaberry caused by P. subsessilis in Korea. The observed high incidence and severity suggest that this disease can be a limiting factor in utilizing this tree species as ornamentals in public areas. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved October 22, 2012. (2) Y. L. Guo and W. H. Hsieh. The genus Pseudocercospora in China. International Academic Publishers, Beijing, China, 1995. (3) T. J. White et al. PCR Protocols. Academic Press, San Diego, CA, 1990.

First Report of Powdery Mildew Caused by Podosphaera xanthii on Hibiscus mutabilis in Korea.

Hibiscus mutabilis L., known as cotton rose, is a deciduous shrub native to China. Horticultural varieties of the species are widely planted throughout the world (4). In September 2012, typical powdery mildew symptoms on the cotton rose were observed in a public garden of Jeju City, Korea. Powdery mildew colonies were circular to irregular white patches on both sides of the leaves and also on young stems and sepals. As the disease progressed, white mycelial growth covered the entire shoot portion, causing leaf distortion. In the middle of November, numerous chasmothecia were formed on the lesions. Voucher specimens (n = 4) were deposited in the Korea University Herbarium (KUS). Hyphal appressoria were only swollen part of hyphae or occasionally nipple-shaped. Conidiophores were 140 to 275 × 10 to 11.5 µm and produced 2 to 8 immature conidia in chains with a crenate outline. Foot-cells of conidiophores were straight, 30 to 65 µm long, and cylindric. Conidia were hyaline, ellipsoid-ovoid, and measured 27 to 42 × 17.5 to 21 µm with a length/width ratio of 1.5 to 2.4, and had distinct fibrosin bodies. Chasmothecia were amphigenous, cauligenous, 85 to 110 µm in diameter, and contained one ascus each. Peridium cells of chasmothecia were irregularly polygonal, large, and 15 to 38 µm wide. Appendages were mycelioid, 1- to 6-septate, brown at the base, and becoming paler. Asci were sessile, oval to broadly fusiform, with terminal oculus of 15 to 20 µm wide. Ascospores numbered eight per ascus were ellipsoidal, 19 to 25 × 14 to 16 µm. The morphological characteristics were consistent with previous records of P. xanthii (Castagne) U. Braun & Shishkoff (1). To confirm the identification, the complete internal transcribed spacer (ITS) region of rDNA from isolate KUS-F27134 was amplified with the primers ITS5 and P3 and sequenced (3). The resulting sequence of 477 bp was deposited in GenBank (Accession No. KC460208). The Korean isolate showed >99% similarity with dozens of sequences of P. xanthii ex cucurbitaceous hosts (e.g., JQ912061, JQ409565, HM070403, etc.) as well as Podosphaera sp. ex H. mutabilis from Japan (AB040308). Pathogenicity was confirmed through inoculation tests by gently pressing diseased leaves onto young leaves of three asymptomatic, potted 2-year-old seedlings. Three non-inoculated seedlings were used as controls. Plants were maintained in a greenhouse at 24 to 30°C. Inoculated leaves developed symptoms after 7 days, whereas the control plants remained symptomless. The fungus present on the inoculated leaves was morphologically identical to that observed on the original diseased leaves, fulfilling Koch's postulates. Powdery mildew infections of H. mutabilis associated with P. xanthii (including P. fuliginea in broad sense) have been known in China, Japan, and Taiwan (1,2). To our knowledge, this is the first report of powdery mildew caused by P. xanthii on H. mutabilis in Korea. Since Jeju, the southmost island of Korea, is the only habitat of cotton rose in Korea and is the northmost natural habitat in Asia, powdery mildew is a new threat to the health of wild populations of cotton rose. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (2) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, retrieved January 18, 2013. (3) S. Takamatsu et al. Mycol. Res. 113:117, 2009. (4) D. A. Wise. J. Hered. 64:285, 1973.

Is there a clinical difference in paediatric congenital cholesteatoma according to age?

OBJECTIVE: This study aimed to analyse surgical outcomes of paediatric patients with congenital cholesteatoma according to age. METHOD: This was a retrospective study reviewing the records of 186 children (136 boys and 50 girls) from August 1993 to January 2016. Patients were divided into three age groups (equal to or less than 3 years, over 3 and less than 7 years, and 7 to 15 years). RESULTS: There were significant differences in chief complaints, location of cholesteatoma in the middle ear, computed tomography findings, operation methods, ossicular erosion and type of cholesteatoma sac among the three groups. In addition, older age, open type cholesteatoma, ossicular erosion and mastoid invasion of cholesteatoma increased the recurrence rate after surgery. However, despite higher pre-operative air-bone gap in older children, hearing can be improved enough after proper surgery with ossicular reconstruction. CONCLUSION: Delayed detection of paediatric cholesteatoma can lead to extensive disease and the need for an aggressive operation, which can result in worse hearing outcomes and an increased recurrence risk.

Risk factors for osteoporosis in long-term survivors of intracranial germ cell tumors.

SUMMARY: We measured bone mineral densities in 28 intracranial germ cell tumor long-term survivors. There was the high prevalence of osteoporosis and osteopenia, 25.0% and 42.9%, respectively, and three additional risk factors, male sex, a low lean mass, and adult growth hormone replacement, were identified. INTRODUCTION: Intracranial germ cell tumor long-term survivors (iGCTLS) have many risk factors for osteoporosis, including irradiation from cancer therapy and multiple hormone deficiencies. However, no study of bone mineral density (BMD) has been conducted in iGCTLS because these tumors are rare. The aims of this study were to evaluate the prevalence of osteoporosis and to identify risk factors associated with reduced bone mass in iGCTLS. METHODS: We evaluated BMD and body composition of 28 iGCTLS (10.9 ± 5.2 years after cancer treatment; 13 males) using dual-energy X-ray absorptiometry. To determine risk factors, we analyzed the medical history, including the nature of the tumor, treatment modality, endocrine status, hormone replacement therapy, lifestyle, and biochemical parameters. RESULTS: Twenty-five percent of iGCTLS were diagnosed with osteoporosis and 42.9% with osteopenia. Most males (92.3%) had low BMD. Lean mass (LM) was positively correlated with BMD in all regions of interest, and the starting age of adult growth hormone (GH) replacement was negatively correlated with the BMD Z-score at the femur neck. In logistic regression analysis, male sex and low LM were related to low BMD. CONCLUSIONS: The iGCTLS had a high prevalence of low BMD. We found that male sex, low LM, and delayed start of adult GH replacement were risk factors for osteoporosis. Therefore, the BMD of all iGCTLS should be evaluated, and if it is low, proper management should be started early.

HBEGF promotes gliomagenesis in the context of Ink4a/Arf and Pten loss.

Heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) is a ligand for the EGF receptor (EGFR), one of the most commonly amplified receptor tyrosine kinases (RTKs) in glioblastoma (GBM). While HBEGF has been found to be expressed in a subset of malignant gliomas, its sufficiency for glioma initiation has not been evaluated. In this study, we demonstrate that HBEGF can initiate GBM in mice in the context of Ink4a/Arf and Pten loss, and that these tumors are similar to the classical GBM subtype observed in patients. Isogenic astrocytes from these mice showed activation not only of Egfr but also the RTK Axl in response to HBEGF stimulation. Deletion of either Egfr or Axl decreased the tumorigenic properties of HBEGF-transformed cells; however, only EGFR was able to rescue the phenotype in cells lacking both RTKs indicating that Egfr is required for activation of Axl in this context. Silencing of HBEGF in vivo resulted in tumor regression and significantly increased survival, suggesting that HBEGF may be a clinically relevant target.

Cloning of a cysteine proteinase cDNA of adult Paragonimus westermani by polymerase chain reaction.

Cysteine proteinase cDNA fragment from adult mammalian trematode, Paragonimus westermani was amplified by reverse transcription-polymerase chain reaction (RT-PCR) using degenerate oligonucleotide primers derived from conserved cysteine proteinase sequences. The 5' and the 3' regions of the cysteine proteinase gene were amplified using the PCR protocol for the rapid amplification of cDNA ends (RACE). It has an open reading frame of 804 bp. The deduced amino acid sequence consists of 268 amino acids. Sequence analysis and alignment showed significant sequence similarity to other eukaryotic cysteine proteinases and conservation of the cysteine, histidine, and asparagine residues that form the catalytic triad. The cysteine proteinase cDNA fragment was also subcloned in the expression vector pET and expressed as a C-terminal His-tag fusion protein in Escherichia coli.

Mutation analysis of Korean patients with citrullinemia.

Citrullinemia is an autosomal recessive disease due to the mutations in the argininosuccinate synthetase (ASS) gene. Mutation analysis was performed on three Korean patients with citrullinemia. All of the three patients had the splicing mutation previously reported as IVS6-2A>G mutation. Two had Gly324Ser mutation and the other patient had a 67-bp insertion mutation in exon 15. The IVS6-2A>G mutation was reported to be found frequently in Japanese patients with citrullinemia, but Caucasian patients showed the extreme mutational heterogeneity. Although a limited number of Korean patients were studied, the IVS6-2A>G mutation appears to be one of the most frequent mutant alleles in Korean patients with citrullinemia. The Gly324Ser mutation identified in two patients also suggests the possible high frequency of this mutation in Korean patients as well.

Sequence variation of mitochondrial DNA control region in Koreans.

The sequencing data for two mtDNA segments in control region I and II, 385 and 341 nucleotides long, respectively, for 306 unrelated Koreans are presented. In regions I and II, 139 and 58 polymorphic sites, respectively, were noted. These were distributed evenly along the control region, though the frequency of each site was variable. Nucleotide substitution rather than insertion/deletion was the prevalent pattern of variation. A total of 265 different mtDNA lineages in region I and 154 in region II were revealed. This result represents a substantial level of polymorphism in a defined population, and presents the possibility that mtDNA polymorphism could be used as an individual identification marker, especially when nuclear DNA is not available. In view of the complex pattern of variation, meticulous test-sequencing is thought to be more appropriate than RFLP analysis using restriction endonuclease or hybridization using an SSO probe. Racial differences with genealogical usage are also described.

An unusual case of shoulder pain.

Shoulder pain is a common musculoskeletal ailment. The process of determining the etiology of shoulder pain can be difficult. The differential diagnoses include: both intracapsular and extracapsular lesions; and neurologic, vascular, postural, and visceral causes. We present an unusual case of shoulder pain accompanied by loss of shoulder range of motion (ROM), initially thought to be caused by an intrinsic shoulder disorder. However, it ultimately was determined that a cervical radicular disorder caused both the impaired ROM and the patient's shoulder pain.

[Mismatches in the treatment for gastric cancer and their correction].

Mismatches in the treatment of gastric cancer to date in Japan are as follows: 1. Difference in the definitive pathological diagnosis even among well-known, experienced pathologists. The case of a patient who was successfully treated by the authors is reported in this paper. 2. The insufficient number of medical oncologists for gastric cancer. 3. The administration of adjuvant chemotherapy after surgery without obvious evidence that it is needed. 4. Inadequate preventive measures, i.e. refrainment from smoking and eradication of Helicobacter pylori. 5. The application of standard surgery, which is designed basically to treat advanced gastric cancer with serosal and nodal involvement, in cases of early gastric cancer. These mismatches have been corrected recently by the adoption of modified surgery and an endoscopic approach to the early gastric cancer. These modifications could be attained through our pioneering effort to find a balance between the two contradictory approaches of radical treatment and preservation of organic function, which are often irreconcilable in cancer treatment in general, after the accumulation of sufficient data on early gastric cancer in a Japanese nationwide study.

Factors affecting growth and final adult height after pediatric renal transplantation.

BACKGROUND: Growth retardation is a common problem for children with chronic kidney disease. Although renal transplantation (RTx) resolves endocrine metabolic and uremic disturbances, growth continues to be suboptimal. This study aims to describe changes in height from diagnosis to final adult height (FAH) in Korean renal allograft recipients and determine factors associated with posttransplantation growth. METHODS: We retrospectively reviewed 63 renal allograft recipients who underwent RTx at <15 years of age with regular follow-up for >3 years afterwards. Pre- and post-RTx growth was analyzed by height Z scores (Ht_Z) at RTx, 2 and 5 years follow-up, and at FAH. RESULTS: Ht_Z decreased from diagnosis to dialysis by -0.8 (P = .009) and from dialysis to RTx by -0.46 (P < .001). The mean baseline Ht_Z at RTx was -1.62 ± 1.36. The change in Ht_Z at 2 and 5 years after transplantation was 0.68 ± 0.88 and 0.48 ± 0.86, respectively. Both variables were negatively correlated with baseline age at RTx. Mean FAH was -1.22 ± 1.11 and was positively correlated with baseline height at RTx. Height at start of dialysis and dialysis duration were significant determinants of baseline height at RTx (P < .001). CONCLUSIONS: Although there is significant posttransplant catch-up growth among younger recipients and among those with greater baseline height deficit, catch-up growth is not sustained and greater FAH is attained in those who are taller at RTx. Achieving greater height before dialysis and decreasing dialysis duration leads to maximal height at RTx as well as greater FAH.

Clinical implications of N epsilon-(carboxymethyl)lysine, advanced glycation end product, in children and adolescents with type 1 diabetes.

AIM: The aim of this study was to investigate the relationship between serum levels of the glycoxylation product N(epsilon)-(carboxymethyl)lysine (CML) and development of chronic diabetic complications and degree of diabetic control in children and adolescents with type 1 diabetes. METHODS: The serum levels of CML were measured in 87 patients with uncomplicated type 1 diabetes mellitus (12.7 +/- 4.6 years of age) and in seven patients with background retinopathy, microalbuminuria or neuropathy (18.2 +/- 5.2 years of age) and compared with those in 64 normal control subjects (12.6 +/- 5.2 years of age). The mean durations of diabetes in uncomplicated and complicated patients were 5.0 +/- 3.4 years (0.1-14 years), and 8.6 +/- 5.0 years (3.1-18 years), respectively. The serum levels of CML were measured by enzyme-linked immunosorbent assay using a monoclonal anti-CML antibody (6D12). RESULTS: The serum levels of CML were significantly higher in the patient group than those in the control group; 0.85 +/- 0.37 (0.37-1.93) U/ml vs. 0.56 +/- 0.23 (0.15-1.05) U/ml (p < 0.001) and significantly higher in the patient group with chronic complications than those in patient group without chronic complications; 1.06 +/- 0.39 (0.72-1.78) U/ml vs. 0.83 +/- 0.36 (0.37-1.93) U/ml (p < 0.05). Weak, but statistically significant relationship between CML levels and haemoglobin A(1c) levels at the measurement of CML was observed (r = 0.29, p < 0.05). CONCLUSIONS: Our data are suggesting that higher serum levels of CML are involved in the development of chronic diabetic complications, and serum levels of CML reflect the degree of diabetic control for a long duration in type 1 diabetic children and adolescents.

Stable semiconductor laser with a 7-Hz linewidth by an optical-electrical double-feedback technique.

A semiconductor laser with a linewidth of 7 Hz locking to a supercavity was achieved by using an optical-electrical double-feedback technique. The emitted power concentration within the stabilized field spectrum was 81%. The minimum value of the square root of the Allan variance for the frequency stability was 2.4 x 10(-14) at the integration time of 70 msec.

Two-stage operation for treatment of a large dissecting popliteal cyst after failed total knee arthroplasty.

A symptomatic popliteal cyst after total knee arthroplasty (TKA) is rare, occurring most frequently as a result of intra-articular knee pathology. We present a case of a large dissecting popliteal cyst 7 years after TKA with symptoms of severe calf pain and functional disability. The symptomatic cyst was excised completely in a first-stage operation, and the severely worn TKA was corrected by a second-stage surgical procedure. The patient in this report was pain free and had satisfactory range of knee motion 5 years after the index revision TKA, without recurrence of effusion or popliteal cyst formation.

Olecranon fractures treated with tension band wiring techniques--comparisons among three different configurations.

Retrospective comparisons were conducted among 3 different configurations of tension band wiring techniques for adult olecranon fractures. The follow-up period was at least one year (average 26 months). All 3 configurations achieved high union rates with an average of 3.4 months to achieve union. However, the olecranon screw group or Kirschner wire group had a relatively higher satisfactory rate than the Rush pin group, even though there was no significance in statistics (P > 0.05). Complications were few, and implant migration occurred in the Rush pin or Kirschner wire group. The complications were not difficult to manage. The authors conclude that for olecranon fractures with a large fragment, olecranon screw or Kirschner wire can be chosen. For olecranon fractures with a small fragment, Kirschner wire should be utilized.

Conservative management of adenocarcinoma in situ of the cervix.

OBJECTIVE: The purpose of this study was to determine the method of treatment and outcome of women with cervical adenocarcinoma in situ (AIS). METHODS: Following institutional review board approval, all women diagnosed with cervical AIS from 1987 to 1999 were identified. Data were retrospectively collected by record review and correspondence with medical providers. RESULTS: Of 132 women treated with cone biopsy for AIS, 95 (72%) were managed conservatively after cold knife cone or loop electrical excisional procedure alone; 37 (28%) eventually underwent hysterectomy. The median age of diagnosis was 29 years (range, 17-47) in the conservative management group and 40 years (range, 25-72) in the hysterectomy group (P < 0.0001). Seventy-four percent were nulliparous in the conservative group compared with 27% in the hysterectomy group (P < 0.0001). Of the 95 conservatively managed patients, 92 obtained negative margins; three were followed despite positive or unevaluable margins. During a median follow-up of 30 months, 9 women required evaluation for follow-up abnormalities after cone biopsy with negative margins. None had pathologic evidence of recurrent AIS. Twenty-three infants were delivered. Hysterectomy was generally performed for undesired fertility or persistently positive cone margins. One woman required hysterectomy for recurrent AIS. Thirteen (62%) of twenty-one hysterectomy specimens had residual AIS following cone biopsy with positive or unevaluable margins; 1 (6%) of 16 had residual AIS following cone biopsy with negative margins (P < 0.0001). No patient developed invasive adenocarcinoma. CONCLUSIONS: Younger women with cervical AIS may be effectively treated with cone biopsy alone if negative margins can be achieved.

Analysis of the STR myelin basic protein locus in Koreans.

Allele und genotype frequencies and the mutation rate of a short tandem repeat locus, the myelin basic protein (MBP) gene, were studied in 973 unrelated Koreans. The alleles were distributed in two discrete regions, one in a high molecular weight region (A) above 190 bp and the other in a low molecular weight region (B) below 150 bp. In a heterozygote, two alleles were found in each region. In region A 13 alleles were found and in region B 7 alleles. Most alleles showed a difference of 4 bp, but three interalleles were found in region A. Allele frequencies in Koreans differed from those reported for Germans and Portuguese. Sets of alleles, one from each region, were linked and transmitted to the offspring. A total of 36 haplotypes and 148 genotypes was identified. In 763 gametes of 550 families, whose parent-child relationship was confirmed using other serological and DNA systems, all alleles were transmitted in a Mendelian fashion, and no mutations were observed. The polymorphism information content (PIC) in Koreans was calculated as 0.833 for region A and 0.718 for region B. The power of discrimination (PD) was 0.959 for region A and 0.901 for region B. No significant deviation from Hardy-Weinberg equilibrium could be observed for this system.