Systemic capillary leak syndrome

A 40-year-old woman was referred to our hospital with severe hypovolemic shock and anasarca. The laboratory findings showed marked hemoconcentration and a decrease in total serum protein with the presence of monoclonal IgG-lambda. She had had a similar episode of generalized edema 2 years previously. We diagnosed the patient as having typical systemic capillary leak syndrome (SCLS) and she improved gradually after infusion of albumin-containing fluid. SCLS is a very rare condition caused by unexplained episodic capillary hyperpermeability. Its treatment has remained largely supportive and the prognosis is generally poor. Awareness of SCLS is necessary for improvement of the outcome.     

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a ⁶⁴Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of ⁶⁴Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from ⁶⁴Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to ⁶⁴Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D₁₀ values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that ⁶⁴Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from ⁶⁴Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after ⁶⁴Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that ⁶⁴Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of ⁶⁴Cu-ATSM as a cancer treatment modality for hypoxic tumors.     

Kinetic and molecular docking studies of loganin and 7-O-galloyl-d-sedoheptulose from Corni Fructus as therapeutic agents for diabetic complications through inhibition of aldose reductase

Archives of Pharmacal Research - Aldose reductase (AR) is a key enzyme in the polyol pathway that is strongly implicated in the pathogenesis of diabetic complications. AR inhibitors have been...     

Progression from Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis Cirrhosis Confirmed by Liver Histology after 14 Years

A 44-year-old patient progressed from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) cirrhosis. She was diagnosed with NAFL via a liver biopsy. At 56 years old, she was diagnosed with NASH stage 3 via a second liver biopsy. One year later, she was diagnosed with NASH cirrhosis via a third liver biopsy. This is the first study to report the gradual deterioration of liver histology shown via three liver biopsies and fibrosis markers in a patient who progressed from NAFL to NASH cirrhosis. Following menopause, it is necessary to be aware of the rapid development of liver fibrosis.     

Unilateral active adrenal tuberculosis featuring persistent intermittent fever

The adrenal gland is one of the organs which tuberculosis infects. In most clinical settings bilateral adrenal tuberculosis has been clarified after adrenal insufficiency is overt. On the contrary, active adrenal tuberculosis is rarely detected during the survey of infectious disease. A 68-year-old man was admitted because of intermittent fever. The fever had continued for the last 3 months. The intermittent fever was accompanied with leukocytosis and elevation of C-reactive protein. Serum soluble interleukin-2 receptor was 1920 U/ml, and beta2-microglobulin was 4.0 mg/l. Bacterial cultures of blood, sputa, urine, bone marrow and cerebrospinal fluid did not show any particular bacteria. Mycobacterium tuberculosis was negative in culture of sputa, and there was no tuberculin reaction. Plasma ACTH and serum cortisol were 18.5 pmol/l and 527.0 nmol/l, respectively. Abdominal CT scan showed right adrenal mass with a size of 28 x 20 mm, which was low density and had a well-encapsulated homogenous appearance. After the adrenalectomy, histology verified active adrenal tuberculosis. The intermittent fever disappeared, and white blood cells and C-reactive protein normalized. These findings indicate an atypical, rare case of unilateral, active adrenal tuberculosis closely linked to intermittent fever, and without any other organ involvement.     

Lymphomatous polyp of mantle cell type in the duodenum complicated by gastric cancer: a case of trisomy 3 and t(11;14)(q13;q32)

We experienced a rare case of a lymphomatous polyp of mantle cell type forming a polypoid mass lesion in the duodenum bulbous together with advanced gastric cancer. A total gastrectomy was performed, and the specimen revealed atypical small- to medium-sized lymphoid cells with indented nuclei, which infiltrated the Peyer's patch and formed a nodular mass in the lamina propria and submucosa of the duodenum. The lymphoma cells also infiltrated the lymphoid follicle of the gastric mucosa, spleen, and regional lymph node with a typical mantle zone pattern. Flow cytometric analysis of the single cells of the lymph node and immunohistochemistry of a paraffin-embedded specimen revealed that the lymphoma cells expressed surface CD5, CD19, CD20, and nuclear cyclin D1. Chromosomal analysis of this single cell suspension revealed that these lymphoma cells have trisomy 3 in conjunction with t(11;14)(q13;q32), which is frequently seen in mucosa-associated lymphoid tissue lymphomas (MALToma) in the stomach and is also reported in mantle cell lymphoma as a secondary genetic alteration. Our report suggests that trisomy 3 may be a common chromosomal abnormality in lymphomatous polyps of mantle cell type.     

IL6 trans-signaling promotes functional recovery of hypofunctional phagocytes through STAT3 activation during peritonitis

Objective

The role of high interleukin 6 (IL6) levels has not been clearly explained in severe sepsis. We show that the augmentation of the IL6 signal by recombinant IL6 receptors (rIL6R) delivery allows the functional recovery of phagocytes in a peritonitis mouse model.

Materials and Methods

Mice were challenged intraperitoneally (i.p.) with live Staphylococcus aureus for effect of IL6R delivery on the 24 h-survival, bacterial clearance and cellular responses. In additional experiments to assess the effect of IL6R delivery on phagocytosis, the model was i.p. inoculated with heat-killed S. aureus with or without rIL6R and the peritoneal lavage fluid and cells were collected at 1 h after the i.p. inoculation of S. aureus.

Results

The IL6R delivery tended to improve 24 h survival and increase bacteria clearance from the septic mice. The rIL6R treatment to heat-killed bacteria challenged mice augmented the uptake of bacteria and phagosome acidification, inducing the phosphorylation of STAT3 in peritoneal cells within 1 h after the IL6R delivery. Furthermore, the rIL6R delivery prevented the extracellular release of neutrophil elastase activity and myeloperoxidase (harmful factors).

Conclusions

These results indicate that augmentation of IL6 signaling appears to be critical for the effective management of hypofunctional neutrophils during severe inflammation, such as sepsis.     

Carcinoma of the fallopian tube: Results of a multi-institutional retrospective analysis of 127 patients with evaluation of staging and prognostic factors

The aim of this study was to determine the impact of prognostic factors in primary fallopian tube carcinoma (PFTC). All cases of PFTC diagnosed between 1990 and 2010 were retrieved from the files of 6 academic centers. The cases were staged according to a modification of the International Federation of Obstetrics and Gynecology staging system proposed by Alvarado-Cabrero et al (Gynecol Oncol 1999; 72: 367–379). One hundred twenty-seven PFTC cases were identified. The mean age of the patients was 64.2 years. Stage distribution was as follows: 72 (57%), stage I; 19 (15%), stage II; 28 (22%), stage III; and 8 (6.2%), stage IV. Depth of infiltration of the tubal wall was an independent prognostic factor in stage I cases (P < .001). Carcinomas located in the fimbriated end even without invasion had a worse prognosis than did carcinomas involving the tubal portion of the organ. The presence of vascular space invasion correlated with the depth of tubal wall invasion (P = .001) and the presence of lymph node metastases (P = .003). Tumor grade significantly correlated with survival (P < .0001), but histologic type was of marginal significance and only if it was grouped as nonserous/non–clear cell vs serous/clear cell (P = .04). The depth of invasion of the tubal wall and the presence of carcinoma in the fimbriated end even without invasion are important prognostic indicators. The modified International Federation of Obstetrics and Gynecology staging system should be used on a routine basis in all carcinomas of the fallopian tube.