Automated Skeletal Classification with Lateral Cephalometry Based on Artificial Intelligence.

Lateral cephalometry has been widely used for skeletal classification in orthodontic diagnosis and treatment planning. However, this conventional system, requiring manual tracing of individual landmarks, contains possible errors of inter- and intravariability and is highly time-consuming. This study aims to provide an accurate and robust skeletal diagnostic system by incorporating a convolutional neural network (CNN) into a 1-step, end-to-end diagnostic system with lateral cephalograms. A multimodal CNN model was constructed on the basis of 5,890 lateral cephalograms and demographic data as an input. The model was optimized with transfer learning and data augmentation techniques. Diagnostic performance was evaluated with statistical analysis. The proposed system exhibited >90% sensitivity, specificity, and accuracy for vertical and sagittal skeletal diagnosis. Clinical performance of the vertical classification showed the highest accuracy at 96.40 (95% CI, 93.06 to 98.39; model III). The receiver operating characteristic curve and the area under the curve both demonstrated the excellent performance of the system, with a mean area under the curve >95%. The heat maps of cephalograms were also provided for deeper understanding of the quality of the learned model by visually representing the region of the cephalogram that is most informative in distinguishing skeletal classes. In addition, we present broad applicability of this system through subtasks. The proposed CNN-incorporated system showed potential for skeletal orthodontic diagnosis without the need for intermediary steps requiring complicated diagnostic procedures.

Induction of striatal neurogenesis enhances functional recovery in an adult animal model of neonatal hypoxic-ischemic brain injury.

While intraventricular administration of epidermal growth factor (EGF) expands the proliferation of neural stem/progenitor cells in the subventricular zone (SVZ), overexpression of brain-derived neurotrophic factor (BDNF) is particularly effective in enhancing striatal neurogenesis. We assessed the induction of striatal neurogenesis and consequent functional recovery after chronic infusion of BDNF and EGF in an adult animal model of neonatal hypoxic-ischemic (HI) brain injury. Permanent brain damage was induced in CD-1 (ICR) mice (P7) by applying the ligation of unilateral carotid artery and hypoxic condition. At 6 weeks of age, the mice were randomly assigned to groups receiving a continuous 2-week infusion of one of the following treatments into the ventricle: BDNF, EGF, BDNF/EGF, or phosphate buffered saline (PBS). Two weeks after treatment, immunohistochemical analysis revealed an increase in the number of BrdU(+) cells in the SVZ and striata of BDNF/EGF-treated mice. The number of new neurons co-stained with BrdU and betaIII-tubulin was also significantly increased in the neostriata of BDNF/EGF-treated mice, compared with PBS group. In addition, the newly generated cells were expressed as migrating neuroblasts labeled with PSA-NCAM or doublecortin in the SVZ and the ventricular side of neostriata. The new striatal neurons were also differentiated as mature neurons co-labeled with BrdU(+)/NeuN(+). When evaluated post-surgical 8 weeks, BDNF/EGF-treated mice exhibited significantly longer rotarod latencies at constant speed (48 rpm) and under accelerating condition (4-80 rpm), relative to PBS and untreated controls. In the forelimb-use asymmetry test, BDNF/EGF-treated mice showed significant improvement in the use of the contralateral forelimb. In contrast, this BDNF/EGF-associated functional recovery was abolished in mice receiving a co-infusion of 2% cytosine-b-d-arabinofuranoside (Ara-C), a mitotic inhibitor. Induction of striatal neurogenesis by the intraventricular administration of BDNF and EGF promoted functional recovery in an adult animal model of neonatal HI brain injury. The effect of Ara-C to completely block functional recovery indicates that the effect may be the result of newly generated neurons. Therefore, this treatment may offer a promising strategy for the restoration of motor function for adults with cerebral palsy (CP).

Comparison of multiplex reverse transcription polymerase chain reaction and conventional cytogenetics as a diagnostic strategy for acute leukemia.

To clarify the usefulness of multiplex reverse transcription polymerase chain reaction (mRT-PCR) in diagnosing acute leukemia, mRT-PCR detecting 28 different translocations was performed on bone marrow aspirates of 156 patients with acute leukemia, and the results were compared with conventional chromosomal karyotypes. About 113 of 156 patients had acute myeloid leukemia (AML), and 36 had acute lymphoid leukemia (ALL) with patients' ages ranging from 1 to 84 (median: 34.5). Concordance rate between karyotyping and mRT-PCR was 50% (51% in AML and 44% in ALL). Karyotype revealed chromosomal abnormalities in 70 patients (45%) while mRT-PCR showed some aberrations in 59 patients (38%). mRT-PCR detected t(1;19), t(4;11), t(9;11), t(10;11), t(11;19), t(12;21), and TAL1d, which were not detected by G-banding. In addition, 10 patients with t(15;17), one patient with t(8;21), and four patients with t(9;22) detected by mRT-PCR revealed normal karyotypes. However, mRT-PCR did not detect numerical abnormalities, deletions, and translocations other than the 28 translocations included in the assay as expected. In conclusion, although it cannot be a substitute of the conventional chromosome analysis, mRT-PCR could be a complementary diagnostic strategy of acute leukemia.

Effects of confluent, roscovitine treatment and serum starvation on the cell-cycle synchronization of bovine foetal fibroblasts.

The present study was designed to examine the effects of cell-cycle synchronization protocols, such as confluent, roscovitine treatment and serum starvation, in bovine foetal fibroblasts on synchronization accuracy at G0/G1, viability, apoptosis, necrosis and ploidy for use as a nuclei donor. The cells in 5-10 passages were randomly allocated into three treated groups. Cells were cultured either in Dulbecco's modified Eagle's medium (DMEM) + 10% foetal bovine serum (FBS) until 90% confluent (group 1, confluent), in DMEM + 10% FBS + 30 microM roscovitine for 12 h (group 2, roscovitine), or in DMEM + 0.5% FBS for 5 days (group 3, serum starvation). Most of the cells (>80%) in all groups were arrested at the G0/G1 stage. Although the rates did not differ, cells in group 1 showed an increased cell population arrested at the G0/G1 phase. Significantly (p < 0.05) higher rates of apoptosis occurred in group 3 than in group 1 and 2 (10% vs 6% and 6%, respectively). No differences in chromosomal abnormality were observed among groups. However, by increasing the number of cell culture passages up to 15, significantly (p < 0.05) higher chromosomal abnormality was observed than in 5 and 10 passages (39% vs 28% and 23%, respectively) in group 1. The results clearly indicated that bovine foetal fibroblasts could be effectively synchronized at G0/G1 stages by all the three different treatments, confluent, roscovitine and serum starvation. However, cells in confluent showed reduced apoptosis and necrosis when they underwent 5-10 passages, exhibiting increased percentage of cells with stable chromosome diversity. Hence, cells in confluent merit further studies before they could be used as nuclear donors.

A chronic heart failure model by coronary artery ligation in the goat.

The availability of a reliable heart failure model in large animals is important. We report upon our efforts to develop a chronic heart failure model in seven goats using sequential ligation of the left anterior descending (LAD) coronary artery and its diagonal branch. After anesthesia and left thoracotomy, the LAD artery was ligated, and the diagonal vessel at the same level was ligated one hour later. Cardiac measurements were performed with a thermodilution catheter and by ultrasonography. Two months after the operation, the same measurements were made and animals were sacrificed for postmortem examinations of their hearts. Hemodynamic measurements, except cardiac output, showed no significant changes immediately after the coronary artery ligation. Echocardiographic measurements showed significant changes in the ejection fraction and fractional shortening without changes in left ventricular dimensions. Wall motion analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all animals immediately after coronary artery ligation. Five animals have undergone hemodynamic and ultrasonographic studies 2 months after coronary artery ligation. The results obtained from these animals showed significant increases in central venous pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary artery capillary wedge pressure, and a significant decrease in cardiac output. Increases in left ventricular dimensions and decreases in ejection fraction with fractional shortening in ultrasonographic studies were also observed. Pathologically, well-demarcated thin-walled anteroseptal infarcts, with chamber enlargement, were clearly seen with dilatation of the heart chambers in all specimens. Based on this study, we conclude that goats, like sheep, can provide a reliable model of chronic heart failure by coronary artery ligation and in view of the many advantages offered by goats, we believe that this animal model will be useful for cardiac experimentation.

Localization of cytoskeletal proteins in Pneumocystis carinii by immuno-electron microscopy.

Pneumocystis carinii causes serious pulmonary infection in immunosuppressed patients. This study was undertaken to observe the cytoskeletal proteins of P. carinii by immuno-electron microscopy. P. carinii infection was experimentally induced by immunosuppression of Sprague-Dawley rats for seven weeks, and their lungs were used for the observations of this study. The gold particles localized actin, tropomyosin, and tubulin. The actin was irregularly scattered in the cytoplasm of the trophic forms but was much more concentrated in the inner space of the cell wall of the cystic forms called the inner electron-lucent layer. No significant amount of tropomyosin was observed in either trophic forms or cystic forms. The tubulin was distributed along the peripheral cytoplasm and filopodia of both the trophic and cystic forms rather than in the inner side of the cytoplasm. Particularly, in the cystic forms, the amount of tubulin was increased and located mainly in the inner electron-lucent layer of the cell wall where the actin was concentrated as well. The results of this study showed that the cell wall of P. carinii cystic forms is a structure whose inner side is rich in actin and tubulin. The location of the actin and tubulin in P. carinii suggests that the main role of these proteins is an involvement in the protection of cystic forms from the outside environment by maintaining rigidity of the cystic forms.

Purification of a 68-kDa cysteine proteinase from crude extract of Pneumocystis carinii.

The present study intended to verify activities of cysteine proteinase of Pneumocystis carinii from rats and to purify the enzyme. In order to exclude the contamination of host-derived enzymes, concentrates of P. carinii was primarily treated with a mixture of proteinase inhibitors before lysis of P. carinii. A 68-kDa cysteine proteinase was finally purified from the crude extract of P. carinii by 4 sequential chromatographic methods. The enzyme showed an optimal activity at pH 5.5 in 0.1 M sodium acetate, and its activity was specifically inhibited by L-trans-epoxy-succinylleucylamido (4-guanidino) butane (E-64) and iodoacetic acid, suggesting that the enzyme is a cysteine proteinase. The 68-kDa proteinase weakly digested macromolecules such as collagen, hemoglobin and fibronectin. The present study demonstrated the activity of cysteine proteinase at the 68-kDa band of P. carinii, and purified and characterized the molecule.

Genetic heterogeneity of Pneumocystis carinii from rats of several regions and strains.

Pneumocystis carinii is a major opportunistic pathogen which has been found in the lungs of a wide variety of mammalian host species, and the fact suggests the possibility of intraspecific variation. Until now, P. carinii from different mammalian species are differentiated as subspecies, and the rats are known to be infected by two subspecies. The present study investigated genetic heterogeneity of P. carinii isolates from two strains of rats in Korea and China by molecular karyotyping, RFLP and sequencing analysis. Karyotypes of P. carinii were grouped into three, two from two strains of rats in Korea and one from rats in China. However RFLP of PCR product of ribosomal and MSG gene of the P. carinii isolates showed same pattern. The sequence homology rates of alpha-tubulin DNA of the P. carinii isolates were 96% in Seoul Wistar rats, 93% in Seoul Sprague-Dawley rats, and 85% in Chinese Sprague-Dawley rats. The present finding confirmed that P. carinii from rats in Korea are grouped into two karyotype strains which are different from that of P. carinii from rats in China. The Chinese isolate shows a little different sequences of alpha-tubulin DNA.

Clinical and molecular biological analysis of a nosocomial outbreak of vancomycin-resistant enterococci in a neonatal intensive care unit.

Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial pathogens since 1988. We report here an outbreak of VRE between April 1997 and May 1997 in our neonatal intensive care unit (NICU). All isolates from four patients were identified as Enterococcus faecium positive and were resistant to vancomycin and teicoplanin. All of the patients with VRE were isolated for at least 5 d after admission to the unit and the positive cultures lasted between 13 and 31 d. There were no cases of sepsis or mortality in the patients with VRE. Two cases had previously received vancomycin therapy. All isolates were shown to have the vanA gene and had the same band pattern on repetitive PCR. After the four episodes, all equipment used to care for the patients were decontaminated and the staff engaged in therapy used disposable gloves and gowns. There were no more episodes. However, the NICU is no longer a safety area with regards to vancomycin-resistant enterococcal infection.

Usefulness of IgG4 subclass antibodies for diagnosis of human clonorchiasis.

The present study analyzed serum IgG subclass antibody reaction to major antigenic bands of Clonorchis sinensis to investigate improvement of its serodiagnosis. Of the four subclass antibodies, IgG1 and IgG2 antibodies were produced but not specific, IgG3 antibody was least produced, and IgG4 antibody was prominent and specific. The serum IgG antibody reaction to any of 43-50, 34-37, 26-28, and 8 kDa bands was found in 65.5% of 168 egg positive cases while IgG4 antibody reaction was found in 22.0% of them. The positive rates of IgG and IgG4 antibodies were directly correlated with the intensity of infection. All of the sera from heavily infected cases over EPG 5,000 showed positive reaction for specific IgG and IgG4 antibodies. The specific serum IgG4 antibody disappeared within 6 months after treatment. The bands of 35 kDa and 67 kDa cross-reacted with IgG antibodies but not with IgG4 antibodies in sera of other trematode infections. The present findings suggest that serum IgG4 antibody reaction to 8 kDa band is specific but not sensitive. Any method to increase its sensitivity is required for improved serodiagnosis.

Karyotypes of Pneumocystis carinii derived from several mammals.

Pneumocystis carinii is the most important opportunistic pathogen of humans in the world. Pneumocystis carinii is experimentally detected in the lungs of rats, mice, rabbits, and monkeys, however, the organisms from different mammals are identical in microscopic morphology. The present study tried to find out more mammalian hosts of P. carinii and also to differentiate the organisms from different mammals by karyotyping. Rats, mice, hamsters, rabbits, cats, and dogs were successfully infected by P. carinii, but guinea pigs and pigs were not. Karyotype of P. carinii from rabbits showed similar size range of chromosomes with that of the prototype, but in different pattern. The patterns from cats and dogs were also different from that of rats. The present study confirms that cats and dogs are infected by P. carinii and at least total three karyotype strains of P. carinii are proven in Korea.

The effect of heterogeneous hyperimmune IgG antibody on prophylaxis and treatment of Pneumocystis carinii infection in rats.

Immunotherapy has been used in support of trimethoprim-sulfamethoxazole treatment for Pneumocystis carinii pneumonia. The present study investigated the therapeutic or preventive effects of heterogeneous hyperimmune IgG antibody (HIA) in experimental rats. Their immunity was suppressed by steroid injection, and they were also injected peritoneally with HIA which reacted with 40-55, 92, 116, and 200 kDa bands of the crude antigen. All rats were infected by P. carinii and the cystic forms on lung impression smears were counted. The count was 20.5-76.5 (mean 52.5 + 19.3) in those which received steroid only, but decreased to 6.0-21.0 (mean 13.5 + 10.6) in those of group 3 which received HIA for the same duration. In other groups, the mean count ranged from 29.9 + 32.9 to 54.1 + 47.7, and in those which received 13.7 mg HIA the reduction effect was greater than in those which received 6.8 mg or 20.5 mg HIA. The present finding confirmed that in rats during the early stage of infection, the heterogeneous HIA to MSG antigen bands had a partial effect on P. carinii pneumonia, both prophylactically and therapeutically.

Short-course doxycycline treatment versus conventional tetracycline therapy for scrub typhus: a multicenter randomized trial.

To assess the clinical efficacy of short-course doxycycline in the treatment of scrub typhus, we compared conventional 7-day tetracycline therapy with 3-day doxycycline therapy in 116 patients. Patients were randomized to receive either tetracycline (500 mg four times daily; n = 50) or doxycycline (100 mg twice daily; n = 66) and were followed for 4 weeks after the completion of treatment. The cure rate was 100% in the tetracycline group and 93.9% in the doxycycline group (P > .05). The two groups did not differ significantly in terms of the interval required for defervescence or for the alleviation of symptoms. There were no relapses in either group. These data suggest that 3-day doxycycline therapy is as effective as conventional 7-day tetracycline therapy for the cure of scrub typhus and the prevention of relapses.

[Infection status of the sea eel (Astroconger myriaster) purchased from the Noryangjin fish market with anisakid larvae].

Although the sea eel (Astroconger myriaster) is suspected as one of the most important fish host for human anisakiasis in Korea, no report has been made on the infection status of the sea eel with anisakid larvae. In the present study, 26 sea eels (Astroconger myriaster) were purchased from the Noryangjin fish market in Seoul, and anisakid larvae were collected from their viscera, muscle, head and skin. The collected larvae were classified by their morphological types. A total of 1,351 anisakid larvae were collected from 15 of 26 fish examined. Among them, 1,269 were recovered from the viscera, 66 from the muscle, and 16 from the head and skin. Morphologically, most of the anisakids were classified into 6 known larval types, Anisakis type I (564 larvae) of Berland (1961), Contracaecum type A (409) and type D (5) of Koyama et al. (1969), Contracaecum type C' (83) and type D' (117) of Chai et al. (1986), and Contracaecum type V (1) of Yamaguti (1935). Remaining 172 specimens were new in the available literature, hence, designated as Contracaecum type A' (new type). The present results revealed that the sea eels caught in the Korean waters are heavily infected with anisakid larvae, not only in their viscera but also in the muscle, and Anisakis type I was the most common among the 7 larval types.

Percutaneous retrieval of a broken Lunderquist guidewire from the pelvicalyceal system.

The stiff Lunderquist guidewire may occasionally be needed during percutaneous insertion of a nephrostomy catheter, especially in patients with a large amount of subcutaneous fat or with a hard renal capsule. This wire may fracture at the junction of its stiff portion with the flexible tip. We have reported such an occurrence, in which an operative procedure was avoided by successful percutaneous retrieval of the broken wire tip, using the loop-snare technique.

Treatment of biliary obstruction caused by metastatic cancer.

Over an 8-year period, among 41 patients with obstructive jaundice caused by metastases to the liver or lymph nodes adjacent to the porta hepatis, palliative biliary decompression was established surgically in 11, by percutaneous transhepatic biliary drainage (PTBD) in 25, and by both methods in 2. Three patients had no drainage procedure performed. Early mortality after drainage occurred in 6 of 38 patients, and the median survivals (actuarial) for the remaining 32 patients were 4.5 months for the surgical group (range 2 to 21 months) and 4 months for the PTBD group (range 2 to 14 months). Although there were trends toward more frequent hospital readmissions and episodes of cholangitis in the PTBD group, the only statistically significant difference was in the number of catheter manipulations required. We concluded that when patients develop obstructive jaundice as a manifestation of metastatic cancer, useful palliation can be achieved by either surgical or percutaneous decompression.

Treatment of peripheral arterial obstruction with streptokinase: results in arterial vs graft occlusions.

A retrospective study of the efficacy of local low-dose intraarterial streptokinase for the treatment of peripheral arterial occlusion was performed in 60 cases. The results of treatment of occlusion of native arterial and arterial graft occlusions were compared. Twenty-two (73%) of 30 cases of arterial occlusion showed complete or partial angiographic resolution, compared with 16 (53%) of 30 cases of arterial graft occlusion. Ten (71%) of 14 patients with venous arterial grafts were successfully treated vs only six (38%) of 16 patients with prosthetic arterial grafts. These results suggest that streptokinase is an effective fibrinolytic agent for the treatment of arterial occlusion and arterial graft occlusion. Its effectiveness in arterial graft obstruction is comparatively low, although patients with venous grafts respond much more favorably than those with synthetic conduits.

Transcatheter embolotherapy of massive bleeding after surgery for benign gynecologic disorders.

Transcatheter embolotherapy is a well-established technique for control of bleeding in patients with pelvic trauma and pelvic malignancies, but it has been rarely used in massive vaginal bleeding after surgery for benign gynecologic disorders. We report five patients with massive post-operative vaginal hemorrhage following total abdominal hysterectomy (n = 3), repeated dilatation and curettage (n = 1) and cesarean section (n = 1), all successfully controlled with transcatheter embolization after many operative procedures had failed to stop the hemorrhage. The age of the patients ranged from 21 to 36 years. All patients underwent embolization of both internal iliac arteries with Gelfoam alone or in combination with stainless steel coils. The bleeding stopped immediately in all patients. Four patients recovered completely and one patient died of disseminated intravascular coagulation and multi-organ failure.