Neutrophil Phagocytosis of Platelets in the Early Phase of 2,4,6-trinitro-1-chlorobenzene (TNCB)-induced Dermatitis in Mice

Activated platelets form platelet–leukocyte aggregates in the circulation in inflammatory diseases. We investigated whether activated platelets in inflamed skin tissues are phagocytized and removed by neutrophils. To investigate the kinetics of platelets and neutrophils, we immunohistochemically examined the spatiotemporal distribution of them in a murine model of 2,4,6-trinitro-1-chlorobenzene (TNCB)-induced dermatitis by using confocal and structured illumination microscopy. Four hours after elicitation, aggregates of CD41-positive platelets were adhered to CD31-positive endothelial cells within the vessels, and CD62P and PF4, markers of activated platelets, were expressed on platelet aggregates. At 8 hour post-elicitation, fragmented CD41-positive platelets were located both inside and outside vessels. Twenty-four hours after elicitation, the number of Ly-6G-positive neutrophils ingesting fragmented CD41-positive platelets outside vessels was increased, and CD62P and PF4 expression on the phagocytosed platelets was no longer observed. Disc-shaped CD41-positive platelets were not found outside vessels at any time during the experiment. Our data revealed that aggregates of activated platelets inside vessels were ingested and removed by neutrophils in the early stage of TNCB-induced dermatitis, suggesting that the process of removal of activated platelets by neutrophils may play an important role not only in the early phase of skin inflammation but also in other types of acute inflammation.     

Ulcerative colitis with hepatitis B virus infection treated successfully by granulocyte monocyte apheresis

Ulcerative colitis (UC) is a major type of idiopathic inflammatory bowel disease (IBD). Immunosuppressive therapies are used to treat IBD patients. Clinicians have strong concerns about using immunosuppressive therapies for IBD patients with hepatitis B virus (HBV) infection because aggressive immunosuppressive therapy can promote reactivation of HBV. For that reason, physicians hesitate to use steroids or other immunosuppressive drugs for IBD patients with HBV infection. Granulocyte monocyte apheresis (GMA) is a safe and effective therapy for UC patients. In Japan, a maximum of 11 sessions of GMA are allowed for moderate‐to‐severe, steroid‐resistant UC patients. However, the effects of GMA on HBV remain unclear. This case report describes a 39‐year‐old man with active UC complicated by HBV infection. Although his symptoms improved with steroid treatment while under entecavir therapy, clinical remission could not be maintained after the steroid dosage was decreased, so GMA was started. After GMA initiation, the frequency of diarrhea decreased and his symptoms improved, and the steroid dosage could be decreased. During the course of GMA, the patient did not experience deterioration in his hepatitis and the HBV DNA level gradually decreased, although GMA itself did not affect the HBV DNA level during each session of GMA. Results show that GMA is a safe and efficacious strategy against UC complicated by HBV without affecting hepatitis because GMA had no remarkable effect on HBV activity. J. Clin. Apheresis 31:584–586, 2016. © 2015 Wiley Periodicals, Inc.     

Asian variant of intravascular large B cell lymphoma causes patients to frequently develop the syndrome of inappropriate antidiuretic hormone secretion

The Asian variant of intravascular large B cell lymphoma is a special type of intravascular lymphoma with hemophagocytic syndrome and hypercytokinemia including interleukin-6, which stimulates antidiuretic hormone synthesis in the hypothalamus. We present here that the syndrome of inappropriate antidiuretic hormone secretion frequently occurs in patients with the Asian variant of intravascular large B cell lymphoma. The syndrome of inappropriate antidiuretic hormone secretion was found in eight of 118 (6.8%) lymphoma patients at the first diagnosis. Although there were six (5.1%) among 118 lymphoma patients with the Asian variant of intravascular large B cell lymphoma, four of the six patients (66.7%) developed the syndrome of inappropriate antidiuretic hormone secretion. In four patients with the Asian variant of intravascular large B cell lymphoma with the syndrome of inappropriate antidiuretic hormone secretion, elevated serum interleukin-6 and low sodium levels were almost normalized after chemotherapy. The Asian variant of intravascular large B cell lymphoma patients frequently develop the syndrome of inappropriate antidiuretic hormone secretion, and interleukin-6 might play a role in the occurrence of this disease. We should pay attention to hyponatremia caused by the syndrome of inappropriate antidiuretic hormone secretion in patients with the Asian variant of intravascular large B cell lymphoma.     

Mumbai disease in far western Nepal: HIV infection and syphilis among male migrant-returnees and non-migrants

OBJECTIVE: To measure the seroprevalence of human immunodeficiency virus (HIV) infection and syphilis, and to assess the behavioural risk factors for these infections among migrant-returnees and non-migrants in far western Nepal. METHODS: In April 2001, we recruited 97 male migrant-returnees and 40 non-migrants from five rural villages in Doti district where migration to Mumbai is common. For data collection, we conducted a serological examination for HIV and syphilis, and a perception and behaviour survey on HIV and other sexually transmitted infections. RESULTS: We found that 11 of 137 men (8%) were positive for HIV infection and 30 men (22%) for syphilis. The respondents, especially the migrant-returnees from Mumbai, were engaging in risky behaviours such as pre- or extramarital sex, and sex with multiple partners, including sex workers. CONCLUSIONS: This study revealed high HIV and syphilis prevalence among the male migrant-returnees and non-migrants in far western Nepal where migration to Mumbai is common. The prevalent behaviours, particularly among the migrant-returnees, imply urgent needs of the behavioural modification programme in this area to prevent the spread of HIV infection to general population.     

Increased bone resorption may play a crucial role in the occurrence of osteopenia in patients with type 2 diabetes: Possible involvement of accelerated polyol pathway in its pathogenesis

In order to investigate the underlying mechanism of alterations in bone mineral metabolism in patients with type 2 diabetes, we determined circulating levels of bone functional markers along with urinary excretion of sorbitol (SOR) and bone mineral density (BMD), and also examined their mutual interrelationship. A total of 151 male type 2 diabetic patients were examined in this study. Forty-eight age-matched male healthy subjects were also studied as the controls. A significant reduction of serum intact osteocalcin (i-OC) was found in the diabetic groups (p<0.01). On the other hand, circulating levels of tartrate resistant acid phosphatase (TRAP) in the diabetic patients were significantly higher than those in the controls (p<0.01). Interestingly, a significantly negative relationship was observed between BMD and serum TRAP (p<0.01), although no significant relationship was noted between BMD and serum i-OC in diabetic patients. Urinary excretion of SOR was significantly elevated in the diabetic patients when compared with the controls (p<0.01). In addition, a significantly positive correlation was observed between serum TRAP and urinary SOR (p<0.01), but not between serum i-OC and urinary SOR. Elevated serum TRAP in diabetes was reduced after the administration of aldose reductase inhibitor (p<0.05). It seems most likely that the increase in osteoclastic function probably due to accelerated polyol pathway plays a crucial role in the pathogenesis of decreased bone mineral content in male patients with type 2 diabetes.     

Compressive optic neuropathy (CON) in Graves’ disease caused by hypertrophy of levator and superior rectus muscles: A case report

Rationale:Enlargemento of the medial rectus is the most predominant factor of compressive optic neuropathy (CON) in Graves‘ disease. This case report indicates that CON could develop only from the hypertrophic superior levator and superior rectus (SL/SR) muscle in a patient with poorly controlled Graves‘ disease, and described the possible risk of FT₃-thyrotoxicosis with a prominent goiter to develop the current rare case with a review of the literature.Patient concerns:A 66-year-old woman undergoing endocrine management of hyperthyroidism with prominent goiter visited the Department of Ophthalmology due to right-eye upper-eyelid retraction.Diagnoses:At initial presentation, the right and left margin reflex distance-1 (MRD-1) was 3.2 mm and 2.1 mm, respectively, and no proptosis or visual dysfunction was observed. Despite insufficient hormonal regulation, she refused to undergo goiter removal. The upper eyelid retraction gradually worsened to 7.7 mm of MRD-1, followed by the onset of 20 prism diopters (PD) of the right hypertropia, resulting in right-eye CON after 6 months. Her free thyroxin level was 3.88 ng/dl and free triiodothyronine was 24.90 pg/ml. Computed tomography and magnetic resonance imaging showed only SL/SR enlargement in the right orbit.Interventions:Intravenous steroid and radiation therapy resulted in visual improvement; however, a prominent upper eyelid retraction and 35PD of hypertropia remained in her right eye. Orbital decompression, upper retraction repair, and superior rectus recession were performed to prevent the recurrence of CON and correct any disfigurement.Outcomes:The combination of conventional intravenous steroid pulse therapy, radiotherapy, and orbital decompression was effective, and no recurrence was observed for more than 1.5-years postoperatively.Lessons:Enlargement of the SL/SR muscle complex may independently induce the CON. We believe that strict attention should be paid to patients with triiodothyronine thyrotoxicosis with progressive eyelid retraction and hypertropia.