TWNK Gene Associated Perrault Syndrome Patient with Neurological Features

Perrault syndrome 5 is a rare autosomal recessive disorder that is characterized by the association of sensorineural hearing loss and ovarian dysgenesis in females with diversity of neurologic deficits due to variants of twinkle mtDNA helicase (TWNK) gene. Since neurologic deficits develop gradually, patient is often misdiagnosed with other neurological disease during early age. Herein, we report a case of genetically diagnosed Perrault syndrome 5.

Melatonin and melatonergic drugs in sleep disorders

Melatonin is an endogenous chronobiological regulator secreted mainly from the pineal gland, which has been used as a dietary supplement in the treatment of sleep problems, including insomnia, parasomnia, and circadian rhythm sleep disorders. However, the short half-life and rapid metabolism of melatonin limit its suitability as a drug. There are many melatonergic drugs used in the treatment of sleep disorders and several drugs are under investigation for approval. Ramelteon was the first melatonergic agonist approved as hypnotic agent by U.S. Food and Drug Administration for the treatment of insomnia. It exhibits higher selective affinity for melatonin 1a (MT1) receptor than melatonin 1b (MT2) receptor. This selectivity suggests that it targets sleep onset with no significant adverse effect or dependency. Agomelatin, naphtahalenic compound, act as a potent MT1/MT2 melatonergic receptor agonist and serotonergic receptor antagonist was approved for treatment of depression in 2009. This dual action drug is the first melatonergic agent used in depression. Another melatonergic agonist, tasimelteon has high affinity for the MT1/MT2 receptors in humans. It was approved for the treatment of non-24 hours sleep-wake rhythm disorder. The newly developed melatonin and melatonergic drugs have the potential to be used extensively in various clinical situations and substitute the old benzodiazepine and its derivatives in the treatment of insomnia. However, the efficacy and safety of newly developed melatonergic drugs should be elucidated through long-term clinical trials.

Influence of clozapine on neurodevelopmental protein expression and behavioral patterns in animal model of psychiatric disorder induced by low-level of lead

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35–56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

Clinical characteristics of intentional self-harm inpatient with lethal methods

OBJECTIVE: The aim of this study was to identify the latent class, according to the risk factors, of the patients hospitalized due to intentional self-harm by lethal means. METHODS: The risk factors were derived by categorizing the intentional self-harming measures by lethal (hanging, pesticide poisoning, jumping, and drowning) and non-lethal (drug poisoning and stab) measures and comparing the demographics, diseased state, and suicide-related characteristics. Latent class analysis was performed to identify the type of intentional self-harm. RESULTS: Male (sex), elderly (age), rural (residing location), and comorbid diseases were found to be the risk factors for fatal injuries. For this, four latent classes were modeled. Factors, such as the age group between 20 to 40 years, women, and family conflict were included in the first class. The second class included the age group between 30 to 50 years, men, and financial problems. The third class covered the age group between 60 to 70 years and comorbidity. The fourth class contained the age group of 10 to 50 years, women, and mental problems. The rate of suicide and choice of fatal suicide was ranked in the order of 3 (62.7%, 21.5%), 2 (59.8%, 13.9%), 4 (36.8%, 5.7%), and 1 (29.5%, 5.9%). CONCLUSION: A lethal mean access control policy needs to be established for the high-risk group of self-harm. Moreover, establishing an emergency room-community link prevention policy could help reduce the re-suicide attempt among suffering patients.

Effects of Tianeptine on Adult Rats Following Prenatal Stress

OBJECTIVE: Exposing a pregnant female to stress during the critical period of embryonic fetal brain development increases the risk of psychiatric disorders in the offspring. The objective of this study was to investigate the effect of antidepressant tianeptine on prenatally stressed (PNS) rats. METHODS: In this study, a repeated variable stress paradigm was applied to pregnant rats during the last week of gestation. To investigate the effects of antidepressant tianeptine on PNS rats, behavioral and protein expression analyses were performed. Forced swim test, open field test, and social interaction test were performed to determine changes in PNS rats compared to non-stressed offspring. Haloperidol was used as a positive control as an antipsychotic drug based on previous studies. RESULTS: Behavioral changes were restored after treatment with tianeptine or haloperidol. Western blot and immunohistochemical analyses of the prefrontal cortex revealed downregulation of several neurodevelopmental proteins in PNS rats. After treatment with tianeptine or haloperidol, their expression levels were increased. CONCLUSION: Downregulation of several proteins in PNS rats might have caused subsequent behavioral changes in PNS rats. After tianeptine or haloperidol treatment, behavioral changes in PNS rats were restored. Therefore, tianeptine might decrease incidence of prenatal stress related-psychiatric disorders such as depression and schizophrenia.

Nocturnal Restless Arms and Face Improved by Dopamine Agonist: Is It a Variant of Restless Legs Syndrome?

The symptoms of restless legs syndrome (RLS) usually involve legs and can extend to other body parts. However, isolated body parts other than leg have rarely been involved. A 32-year-old woman had abnormal sensations of both forearms and face during night, which caused a difficulty falling in sleep. The symptoms were relieved by shaking and rubbing. She experienced a clear benefit from pramipexole, but a recurrence of restlessness was followed in both arms subsequent to pramipexole withdrawal. Finally, she had been prescribed a dose of 0.375 mg, which was well tolerated for 6 years. We report a case of nocturnal restless arms and face without leg involvement, which was like RLS in terms of clinical criteria except lesion site.

Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model

Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

Toxicokinetics of paraquat in Korean patients with acute poisoning

To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1+/-6.8 h. Cmax and AUCinf were 20.8+/-25.7 mg/l and 172.5+/-160.3 h.mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9+/-61.3 l/kg and 173.4+/-111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data

BACKGROUND/AIMS: This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis. METHODS: Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals. RESULTS: Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9+/-30.2 months (mean+/-SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality. CONCLUSIONS: A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.

Early Bile Duct Cancer Detected by Direct Peroral Cholangioscopy with Narrow-Band Imaging after Bile Duct Stone Removal

Cholangioscopy not only enables the direct visualization of the biliary tree, but also allows for forceps biopsy to diagnosis early cholangiocarcinoma. Recently, some reports have suggested the clinical usefulness of direct peroral cholangioscopy (POC) using an ultra-slim endoscope with a standard endoscopic unit by a single operator. Enhanced endoscopy, such as narrow band imaging (NBI), can be helpful for detecting early neoplasia in the gastrointestinal tract and is easily applicable during direct POC. A 63-year-old woman with acute cholangitis had persistent bile duct dilation on the left hepatic duct after common bile duct stone removal and clinical improvement. We performed direct POC with NBI using an ultra-slim upper endoscope to examine the strictured segment. NBI examination showed an irregular surface and polypoid structure with tumor vessels. Target biopsy under direct endoscopic visualization was performed, and adenocarcinoma was documented. The patient underwent an extended left hepatectomy, and the resected specimen showed early bile duct cancer confined to the ductal mucosa.

Bile-Duct Stone Removal under Direct Transnasal Cholangioscopy Using an Ultraslim Upper Endoscope

The transnasal endoscopic examination using an ultraslim upper endoscope may be more comfortable and less stressful than the peroral approach. Transnasal endoscopic retrograde cholangiopancreatography (ERCP), endoscopic nasobiliary drainage, and direct peroral cholangioscopy using an ultraslim upper endoscope have recently been reported. An 82-year-old woman with a previous history of endoscopic sphincterotomy and stone removal was admitted with acute cholangitis. Instead of conventional ERCP, we performed direct transnasal cholangioscopy (TNC) using an ultraslim upper endoscope for biliary decompression and stone removal because of her unstable vital signs. Direct TNC using an ultraslim upper endoscope may be useful in selected patients with biliary disease.

A Case of Locally Invasive Obstructive Jejunal Cancer with Curative Resection after Stenting and Chemotherapy / 대한소화기학회지

Small bowel adenocarcinoma is a relatively rare malignancy. In Korea, 13.1% of small bowel adenocarcinoma occurs in the jejunum. The absence of effective screening methods and relatively obscure symptoms contribute to the higher percentage of advanced cases at the time of diagnosis. Although curative resection is the mainstay of treatment, it is often impossible. Chemotherapy and radiotherapy have shown a disappointing treatment result for advanced staged small bowel adenocarcinoma. We report a 54-year-old woman with locally invasive jejunal cancer who underwent curative resection after stent insertion with enteroscopy and chemotherapy.

Effect of Transdermal Fentanyl Patches on the Motility of the Sphincter of Oddi

BACKGROUND/AIMS: Pain is one of the most troublesome symptoms of pancreatitis. Transdermal fentanyl patches (TFPs) are long-acting analgesics with a reduced risk of dependency. This prospective study evaluated the effect of TFPs on sphincter of Oddi (SO) motility for the management of pain in pancreatitis. METHODS: SO manometry (SOM) was performed using triple-lumen catheters anterogradely inserted through the percutaneous transhepatic route during cholangioscopy in 16 patients. The basal pressure, amplitude, and frequency of the SO were assessed before and after applying a TFP at 24 hour at doses of 25 and 12.5microgram/hr, respectively. RESULTS: Two of 16 patients receiving a 25microgram/hr. TFP were excluded because of adverse side effects (headache and/or nausea). The mean basal pressure, amplitude, and frequency of SOM did not change significantly in the 25microgram/hr TFP group (n=4 patients). Parameters of SO function also did not significantly change in the 12.5microgram/hr TFP group (n=11 patients). CONCLUSIONS: TFPs below a dose of 25microgram/hr may not affect the motility of the SO. Administration of TFPs at lower dosages seems to be a safe analgesic treatment for the pain control of patients with pancreatitis without affecting the function of the SO.

Endoscopic Management of Acute Cholecystitis and Cholangitis Caused by Limy Bile

Limy bile is a relatively rare condition in which a radiopaque material is visible in the gallbladder, extending rarely into the bile duct, on plain radiography. Acute cholangitis or cholecystitis caused by limy bile is a very rare condition. There are no definite treatment guidelines for limy bile, but in most cases with cholangitis or cholecystitis, laparoscopic cholecystectomy has been the preferred treatment. We report a case of limy bile with biliary symptoms that was treated only with an endoscopic procedure.

Peritonitis due to spontaneous rupture of the urinary bladder in an end stage renal disease patient with anuria / 대한내과학회지

Patients with nonfunctioning bladders, such as found in anuric renal failure, are prone to a severe form of urinary tract infection called pyocystis. Pyocystis is the accumulation of pus in the bladder. Anuric patients are often believed to be incapable of acquiring a urinary pathogen; thus, the urinary tract may be mistakenly discounted as a possible source of sepsis and bladder rupture. Although bladder rupture is normally associated with trauma, spontaneous bladder rupture may occur, especially in patients with mental disabilities, alcohol abuse and urinary tract infection. We report a rare case of a spontaneous intraperitoneal bladder rupture, probably precipitated by pyocystis. Symptoms and signs were atypical and included pain and vomiting with fever, abdominal distension and ascites. An abdominal CT and retrograde cystography showed a large quantity of intraperitoneal fluid and tearing in the dome of the bladder. Repair of the rupture site of the bladder after laparotomy was performed. However,, the patient expired due to peritonitis and pulmonary infection.

Asymtomatic Giant Benign Schwannoma Involving Cervical Vertebral Body: A Case Report-

Benign Schwannoma rarely involves the vertebral bodies extensively. Despite of huge amount of neoplastic mass and severe destructive bony changes, the neurologic deficits could not be discovered. The authors discussed the findings of plain X-rays, cervical CT, MRI, pathology as well as surgical procedure, and reviewed the literatures.

Acute Growing Skull Fracture: Case Report

Growing skull fracture is a rare complication of injury during infancy and childhood. About 90% of them occur in childhood under the age of 3 years. Growing skull fracture or leptomeningeal cyst was known to be formed through the bony erosion of fractured site by cerebrospinal fluid pulsation of the leptomeninges, impacted into the fractured bone by trauma. Most growing skull fractures are located in the parietal region. A growing fracture commonly presents as a progressive, often pulsatile, scalp mass that appears several months to years after head injury sustained during infancy or early childhood. The authors report a case of acute growing skull fracture in 4-year-old male patient, which developed 3 weeks after fall down injury.

Safety and Immunogenicity of a Pseudomonas aeruginosa Outer Membrane Protein Vaccine(CFC-101) : a Phase I/IIa Clinical Trial / 감염

BACKGROUND: We developed a Pseudomonas aeruginosa outer membrane protein(OMP) vaccine, CFC-101, and the prophylactic efficacy of which has been demonstrated in animal models. In order to evaluate the safety and immunogenicity of the P. aeruginosa vaccine, we carried out a phase I/IIa clinical trial in healthy male volunteers. METHODS: Groups of eight volunteers, including two placebo subjects, were vaccinated intramuscularly with three doses of 0.25, 0.5 or 1.0 mg of the vaccine at one week intervals. Signs of systemic and local reactions observed after vaccination were recorded for each vaccinee for 5 days. Physical examinations were performed on days 0, 1, 7, 8, 14, 15, 21, and 42, and clinical laboratory tests were done on days 0, 3, and 21. Blood samples for assay of serum antibody levels were obtained up to 42 days after the first vaccination. RESULTS: The vaccine was generally well tolerated by all vaccinees, showing no significant side effects. In the three dosage groups, all vaccinees, except one receiving the 0.25 mg dose, showed significant elevation in serum IgG antibody titers against the vaccine proteins, indicating 100% seroconversion in 0.5 and 1.0 mg groups. The human antibodies induced by the vaccine were specific for P. aeruginosa OMPs, as confirmed by western blot analysis and immunoprecipitation assays. The capacity of the human antisera to enhance opsonophagocytic killing activity by polymorphonuclear leukocytes and to confer protection against P. aeruginosa infections indicates that the antibodies elicited by the vaccine have protective efficacy. CONCLUSION: We conclude that the P. aeruginosa OMP vaccine is safe and effective for human use and its optimal dose to be 0.5 or 1.0 mg.

Two Cases of Langerhans' Cell Histiocytosis: Report of Two Cases

The authors encountered two cases of Langerhans' cell histiocytosis. One, a three-year-old male, had persistent epiphora and showed exophthalmos of the left eye. A mass was detected in the left orbit and was removed subtotally; pathologic examination revealed Langerhans cell histiocytosis. The other case, a 24-year-old male, presented with a gradually growing palpable mass in the parietal area; the skull defect was punched out in shape. The mass, which was tightly attached to the outer layer of the dura mater, was completely removed. On the basis of pathologic findings, Langerhans' cell histiocytosis was diagnosed, and the patient subsequently underwent radiotherapy.

An Arachnoid Cyst in Cervical Spinal Canal: Case Report

The authors have experienced a case of an arachnoid cyst within the cervical canal. The patient suffered from right upper extremity pain and numbness for 1 month. On cervical MRI, intradural extramedullary mass was detected. A total laminectomy of C5, C6 and C7 was performed. We could diagnose by radiological and pathological findings.