A short peptide GPIGS promotes proliferation of hair bulb keratinocytes and accelerates hair regrowth in mice

The aim of this study was to discover a novel agent that promotes hair growth. We carried out a screening test in 298 types of conditioned medium (CM) from cultures of bacteria by using a hair bulb keratinocyte (HBK) growth assay. As a result, we found a HBK growth factor in the CM of Bacillus sp. M18. This HBK growth factor was purified by collecting biologically active fractions in three steps, including HP-20 batch processing, LH-20 chromatography and C18 reverse-phase high-pressure liquid chromatography, and identified as a short peptide GPIGS. GPIGS increased Akt phosphorylation in HBKs. Moreover, the GPIGS-stimulated HBK growth was inhibited by the treatment with LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI-3K). These results suggest that GPIGS promotes HBK growth via the PI-3K/Akt pathway. In addition to in vitro tests, GPIGS was found to accelerate hair regrowth in telogen mice. Our results indicate that GPIGS is a potential agent to promote hair growth.     

F-18 FDG PET/CT provides the earliest findings of enthesitis in reactive arthritis

A 31-year-old woman developed polyarthralgia and extension disorder of the right elbow of 2 months' duration without abdominal symptom. Laboratory findings revealed C-reactive protein 2.7 mg/dL. Anti-nuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) antibody were negative. F-18 FDG PET/CT showed elevated pinpoint uptakes of FDG in the entheses. In contrast, MRI revealed no specific findings. Four months after PET/CT, she developed right lower abdominal pain. Colonoscopy showed abscess in ascending colon, which the initial PET/CT finding might mean early image of infective colitis. A diagnosis of early reactive arthritis was made. Treatment with antibiotics improved colitis, colonic abscess, and enthesitis after 2 months. Moreover, F-18 FDG PET/CT showed no accumulation in colon and entheses. These findings suggest that F-18 FDG PET/CT scanning allows enthesitis in the early stage of reactive arthritis, before the possible detection by the other procedures.     

Is the Volume of the Parathyroid Gland a Predictor of Maxacalcitol Response in Advanced Secondary Hyperparathyroidism?

We evaluated the relationship between the volume of parathyroid glands estimated by ultrasonography (US) and response of 22-oxa calcitriol (Maxacalcitol, OCT) in patients with secondary hyperparathyroidism (2HPT) to evaluate whether the volume can be a predictor of the OCT response. Eleven institutes participated in this study. Ninety-four patients with advanced 2HPT were enrolled. The volume of the parathyroid glands were estimated by US before and 6 months after OCT treatment. The response of OCT treatment was classified into three groups (Group A: i-PTH < 300 pg/mL; Group B: 300 pg/mL < or = i-PTH < 500 pg/mL; Group C: i-PTH > or = 500 pg/mL). Forty-eight patients were in Group A, 28 patients in Group B, and 18 patients in Group C. The PTH levels at the beginning and 6 months were 458.3-199.1 pg/mL (P < 0.0001) in Group A, 524.6-403.2 pg/mL (P = 0.007) in Group B and 736.7-613.6 pg/mL (ns) in Group C, respectively. The volume of the largest gland in Group B was significantly larger than that in Group A (96.2 vs. 343.2 mm3: P < 0.001). Clinical factors affecting response of OCT was evaluated by logistic regression analysis and only the volume of the largest gland was a significant factor. In the patients whose volume was less than 300 mm3, the OCT response was significantly effective. We conclude that the glandular volume of the largest parathyroid gland estimated by US can be a useful factor to predict the OCT response in patients with moderate or severe renal HPT.     

Phase I/II Trial of Docetaxel and Carboplatin as a First-Line Therapy in Patients with Stage IV Non-Small-Cell Lung Cancer

A phase I/II study was conducted to determine the maximum-tolerated dose, the safety and tolerability, and the clinical efficacy of carboplatin and docetaxel in combination in patients with stage IV non–small-cell lung cancer. Patients with measurable, previously untreated, good performance status, and stage IV non–small-cell lung cancer were eligible. Increasing doses of docetaxel were given in combination with a fixed dose of carboplatin except at level 5. Cycles were repeated every four weeks. Seventy-seven patients were registered. In phase I, 27 patients were entered at five different dose levels. A docetaxel dose of 60 mg/m² and carboplatin area under the concentration time curve 6 was recommended for phase II, and an additional 50 patients were entered at this level for a total of 56 patients. Grade 3/4 neutropenia was the most common adverse event and occurred in 70% of the patients. Two patients had febrile neutropenia. Fifty-six patients were assessable for response; 21 partial responses were observed for an overall response rate of 37.5%. The median time to tumor progression was 4.0 months (range, 1.0–21.0 months), and the median survival was 12.9 months (range, 0.4–51.3 months). The one-year survival rate was 46.4%. The combination of docetaxel 60 mg/m² and carboplatin area under the concentration time curve 6 is feasible and effective in patients with stage IV non–small-cell lung cancer.     

Cyclosporin A treatment for Japanese patients with severe adult-onset Still’s disease

For over 10 years there have been no clinical studies about adult-onset Still's disease (AOSD) in Japan. We aimed to investigate recent clinical features and treatment of AOSD and to evaluate the efficacy of cyclosporin A (CyA) in the treatment of AOSD. The data from 34 patients with AOSD who were admitted to our hospital between 1994 and 2007 were analyzed retrospectively. Of several immunosuppressive agents, the efficacy of CyA given to seven patients was precisely evaluated. Clinical features observed in this study did not differ from those in our previous study, and serum ferritin levels were elevated in all the patients. Among immunosuppressive agents CyA, used concomitantly with corticosteroids (CS) for seven patients with severe AOSD, proved to be very effective. The disease was led to remission promptly by CyA in six patients, and all the patients except one experienced no recurrence. These results suggest that CyA can be one of the potent candidates to be used next to CS for patients with AOSD that is resistant to CS.     

BCMA and autoantibody-producing RP105 B cells; possible new targets of B cell therapy in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease with multiple organ disorders. Although the prognosis of SLE has been recently improved, corticosteroid and immunosuppressive agents are still main treatment used in medical practice. Refractory disease and complications by the conventional drugs still remain. RP105 (CD180) is one of the toll-like receptor associated molecules. The molecule is expressed on mature B cells. Significantly increased population of RP105-negative [RP105(-)] B cells is found in SLE. RP105(-) B cells belong to highly activated and differentiated late B cells and produce autoantibodies including anti-dsDNA antibodies. RP105(-) B cells are further divided into at least 5 subsets that include novel human B cell subsets. In active SLE, subset 1 (activated B cells) and 3 (early-plasmablasts) are significantly increased compared to inactive SLE patients. Especially, subset 3 RP105(-) B cells may play an important role in pathophysiology of SLE. RP105(-) B cells from active SLE patients express preferentially BCMA (B-cell maturation antigen) compared to BAFF-R (B-cell activating factor-receptor) than normal subjects and other autoimmune diseases. In SLE, it is suggested that BAFF/APRIL (a proliferation-inducing ligand) maintain chronic activation and survival of RP105(-) B cells. The increased RP105(-) B cells may reflect the breaking of tolerance checkpoint for autoreactive B cells and finally affect autoimmunity in SLE. For the B cell therapy, especially targeting of autoantibody-producing B cells, including subset 3 of RP105(-) B cells, BCMA and RP105(-) B cell itself may be an ideal target.     

Intraoperative ultrasound as an educational guide for laparoscopic biliary surgery

AIM： To analyze the efficacy of routine intraoperative ultrasound （IOUS） as a guide for understanding biliary tract anatomy, to avoid bile duct injury （BDI） after laparoscopic cholecystectomy （LC）, as well as any burden during the learning period. METHODS： A retrospective analysis was performed using 644 consecutive patients who underwent LC from 1991 to 2006. An educational program with the use of IOUS as an operative guide has been used in 276 cases since 1998. RESULTS： IOUS was highly feasible even in patients with high-grade cholecystitis. No BDI was observed after the introduction of the educational program, despite 72% of operations being performed by inexperienced surgeons. Incidences of other morbidity, mortality, and late complications were comparable before and after the introduction of routine IOUS. However, the operation time was significantly extended after the educational program began （P 〈 0.001）, and the grade of laparoscopic cholecystitis （P = 0.002）, use of IOUS （P = 0.01）, and the experience of the surgeons （P = 0.05） were significant factors for extending the length of operation. CONCLUSION： IOUS during LC was found to be a highly feasible modality, which provided accurate, real- time information about the biliary structures. Theeducational program using IOUS is expected to minimize the incidence of BDI following LC, especially when performed by less-skilled surgeons.     

Minimally invasive direct coronary artery bypass grafting using the gastroepiploic artery for reoperation after the cabrol procedure

Obstruction of the right coronary ostial anastomosis is a rare late complication after composite graft replacement of the ascending aorta and the aortic valve with separate Dacron coronary grafts (Cabrol method). Occlusion at the right coronary ostial anastomosis in a 36-year-old woman with aortitis syndrome who underwent a composite graft with a Dacron coronary graft is described. She underwent a third successful operation for right coronary reconstruction by minimally invasive direct coronary artery bypass grafting technique using the right gastroepiploic artery. This approach is likely to be extremely useful in avoiding resternotomy and cardiopulmonary bypass in patients requiring coronary reoperation.     

Repeated unconsciousness due to chronic carbon monoxide poisoning in an older patient: a case report

Objective: Although much is known about acute carbon monoxide (CO) poisoning, little is known about chronic CO poisoning. Chronic CO poisoning is often diagnosed based on the patient’s living environment and medical history. Herein, we report the case of an older patient who presented with repeated unconsciousness due to chronic CO poisoning.Case presentation: A 90-year-old man was brought to the emergency department after being found at home with a disturbance of consciousness. Arterial blood gas measurements in room air revealed a carboxyhemoglobin level of 18.0%. Impaired consciousness was caused by chronic CO poisoning. The patient received high-flow oxygen therapy, which promptly improved his condition. According to his family, briquette kotatsu was the cause of chronic CO poisoning.Conclusion: Although high-flow oxygen therapy has been said to be less effective than hyperbaric oxygen therapy in CO poisoning treatment, recent studies have demonstrated that high-flow oxygen has similar effects and benefits. Thus, in institutions that do not have hyperbaric oxygen, high-flow oxygen may be sufficient to treat patients with CO poisoning, as seen in the present case. It should be noted that briquette kotatsu can lead to CO poisoning. This case highlights the need for clinicians to consider patients’ living conditions.