p53 as a key molecular node in the stress response pathway, including inflammation. p53 is involved in several critical pathways including cell cycle arrest, apoptosis, DNA repair, and cellular senescence, which are essential for normal cellular homeostasis and maintaining genome integrity. The alteration of the TP53 gene or posttranslational modification in the p53 protein can alter its response to cellular stress. The molecular archaeology of the TP53 mutation spectrum generates hypotheses concerning the etiology and molecular pathogenesis of human cancer. The spectrum of somatic mutations in the TP53 gene implicates environmental carcinogens, and both endogenous agents and processes in the etiology of human cancer.
Multifunctional systems must maintain homeostasis. Man is an ideal example of a system that constantly aspires to attain optimal regulation, even under the stress of severe disease. We assume that there are universal, interchangeable (as required) biologically active substances that regulate the system and try to keep it in balance. We propose that one of these substances is vitamin B12. Why vitamin B12? The list of organs and body systems in which vitamin B12 plays a functional role is constantly being added to. Vitamin B12 affects the normal growth of children, the peripheral and central nervous systems, bone marrow, skin, mucous membranes, bones, and vessels. It is possible that even when the serum cobalamin level is normal, treatment with vitamin B12 could correct defects caused by other biologically active substances. We call this phenomenon the "Master Key" effect. We suggest that this "Master Key" concept can be tested by treating diseases, such as recurrent stomatitis, various forms of hyperpigmentation, trophic ulcers, and burns, with vitamin B12, even if the B12 serum level is normal.
Combined spinal epidural anesthesia is widely used for Caesarean section. Bolus administration of an epidural initial dose introduces the risk of drug flux from the epidural space to the subarachnoid space, and the volume effect of the initial dose may cause epidural top-up and extension of subarachnoid blockade. These problems may be avoided if the initial dose is not administered. This study investigated whether epidural continuous infusion without an initial dose (continuous group) can decrease postoperative pain as well as an epidural continuous infusion with an initial dose (initial dose group). Sixty-one patients undergoing elective Caesarean section were randomly assigned to the initial dose group or the continuous group. Twenty patients undergoing emergency Caesarean section with spinal anesthesia (spinal group) were also investigated to confirm that epidural block is effective for postoperative pain. Data in this study were obtained retrospectively from each patient's records. Between the initial dose group and the continuous group, there was no significant difference in the number of times flurbiprofen or pentazocine were used for postoperative pain relief. However, the number of times that pentazocine was used was significantly higher in the spinal group than in other groups. This finding suggests that an epidural initial dose is unnecessary for postoperative pain relief in combined spinal epidural anesthesia for Caesarean section.
Background and aims: Red light phototherapy with laser sources has been used successfully for a number of indications. A new generation of quasimonochromatic 630 ± 3 nm light-emitting diode (LED) systems has recently been yielding good results for the same indications, but no study has examined changes in visible red light irradiated skin at an immunological level. This study was thus designed to examine changes in skin-homing T-cell levels induced in normal human skin by visible red LED energy. Subjects and methods: Six adult male volunteers (35∼48 years old) who satisfied all study criteria had the skin over the lateral aspect of the leg irradiated once per week for 8 weeks with a visible red (630 ± 3 nm) LED-based system, with irradiance of 105 m/cm2, 15 minutes/session, and a radiant flux of 94 J/cm2. Skin biopsies were performed after the eighth treatment session, and cultures were prepared to assay the type and quantity of skin-homing T-cells using qualitative and quantitative polymerase chain reaction (PCR) techniques. Ultrastructural changes were also assessed with transmission electron microscopy. Results: Transmission electron microscopy revealed mild fibroplastic changes in fibroblasts, with no acute inflammatory changes throughout the treatment session. Qualitative PCR showed the presence of both Th-1 and Th-2 T-cells, and quantitative PCR showed an increase in the numbers of both types of skin-homing T-cells, much more so for Th-2 than for Th-1. Conclusions: Visible red LED irradiation appears to activate the skin-homing immune system.
Background: We retrospectively identified the prognostic factors in cases of synchronous liver metastases from colorectal cancer and established a clinical strategy at our institution. Methods: One hundred eight patients with hepatic metastases from colorectal cancer underwent a first radical hepatic resection. Of these, 67 were diagnosed with hepatic synchronous metastases from colorectal primaries (S group) and 41 were diagnosed with metachronous metastases (M group). Hepatic lesions were diagnosed concurrently with the primary lesions in 45 of the 67 patients in the S group. Of these 45 patients, 37 underwent synchronous hepatectomy (SH group) and 8 underwent metachronous hepatectomy (MH group). Results: The overall 3-, 5- and 10-year survival rates were 51.4%, 41.6%, and 30.9%, respectively. There were no significant differences between the S and M groups in overall survival. Univariate analysis of the S group revealed significant differences in survival based on tumor factor, pathological lymph node metastases of the primary tumor, and the tumor-free margin. There were no significant differences between the SH and MH groups in overall survival. Conclusions: Patients with synchronous liver metastases from colorectal cancer should undergo radical resection of the primary lesion and simultaneous hepatectomy with an adequate tumor-free margin as a standard surgical course.
This case report presents a patient with advanced diffuse panbronchiolitis accompanied by chronic respiratory failure, marked cachexia, and refractory spontaneous pneumothorax. Because instillation of a pleurodesis agent and thoracoscopy were considered highly risky and invasive, we instead treated the patient with intravenous administration of a coagulation factor XIII concentrate, and the pneumothorax resolved. This case suggests refractory pneumothorax in a restrictive ventilatory disorder can be effectively treated with noninvasive intravenous administration of coagulation factor XIII concentrate.
We report on 5-month-old girl with severe autoimmune hemolytic anemia (hemoglobin 2.9 g/dl, positive direct Coombs test) in whom thrombocytopenia developed after red blood cell transfusion. The platelet count was 62.1 × 104/mm3 on admission and rapidly fell to 6.0 × 104/mm3 rapidly after transfusion of incompatible red blood cells with intravenous predonisolone administration. No increased hemolysis or alloimmunization was observed after transfusion. The platelet count and hemoglobin levels gradually improved over 8 weeks with corticosteroid therapy. We suspect that the thrombocytopenia in our patient was transfusion-induced.
A 59-year-old man with myelodysplastic syndrome who was hospitalized for evaluation of fever and generalized fatigue had elevated levels of C-reactive protein and pancytopenia. A search for a site of infection and empiric treatment with antibiotics were unsuccessful. Over 5 to 6 weeks right upper quadrant pain and rebound tenderness developed. Sonographic Murphys sign was present. Computed tomography showed thickening of the gallbladder wall, and repeated ultrasonography demonstrated changes consistent with cholecystitis. Open cholecystectomy was performed as an emergency procedure. Macroscopically the resected gallbladder showed an edematous and thickened wall. Histopathologic examination revealed transmural infiltration by atypical mononuclear cells with distinct nuclei. The cells showed immunohistochemical staining for CD15, indicating myeloid lineage. By 10 days after surgery, counts of leukocytes and leukoblasts had markedly increased, reaching 36,700/μL and 76.0%, respectively. The blast crisis was thought to indicate progression from myelodysplastic syndrome to leukemia. The patient died of progressive disease 12 days after surgery. We have described a rare case of acute cholecystitis caused by infiltration of immature myeloid cells to the gallbladder. An acute abdomen complicating hematologic disorders is life-threatening and requires prompt and appropriate treatment.
A 58-year-old man with a chief complaint of epigastralgia was admitted to our hospital. Physical examination disclosed a large, firm mass in the right hypochondrium. Abdominal computed tomography comfirmed thickening of the gallbladder wall and a 15 × 8 cm mass occupying almost all of the right lobe and medial segment of the liver. With a preoperative diagnosis of malignant gallbladder tumor infiltrating the liver, right hepatic trisegmentectomy was performed. Histopathologic examination showed atypical cells with small round to oval nuclei and sparse eosinophilic cytoplasm, proliferating in a solid and focal nesting pattern. Near this small cell proliferation was a focus of tubular adenocarinoma that showed a zone of transition from the small cell neuroendcrine pattern. The small cells demonstrated immunohistochemical reactivity for chromogranin A. Electron microscopy disclosed neurosecretory granules 150 nm in diameter, representing dense round core vesicles, confirming a neuroendocrine cell linage. The patient was diagnosed with neuroendocrine cell carcinoma combined with adenocarcinoma of the gallbladder. Tumor recurrence became evident 3 months after surgery, and he died 4 months after surgery.