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Introduction: Polycythemia vera (PV) accompanies the clinical course of thrombosis. Phosphatidylserine (PS) expression on the plasma membrane has been known to be one of place where the coagulation system activates. We studied the relationship between clotting factor activity and PS expression on the erythrocyte membrane in patients with erythrocytosis. Methods: The coagulation test and PS expression in 23 patients with erythrocytosis were measured. PS expression was determined indirectly by measuring annexin V binding to erythrocytes using fluorescence activated cell sorter analysis (FACS). Results: The activity of clotting factors (II, V, VII, VIII, von Willebrand factor, IX, X) was significantly lower in PV than in the mutation-negative erythrocytosis. There was a significant correlation between reduced activity of clotting factors such as V, X, and IX and increased PS expression of the erythrocyte membrane. Conclusion: Increased expression of PS on the erythrocyte membrane may reduce the activities of clotting factors in PV patients with JAK2 V617F mutation. [ABSTRACT FROM AUTHOR]

The clinical course of losartan potassium/hydrochlorothiazide (Preminent®)-induced hyponatremia has not been described. We summarized 40 patients with Preminent-induced hyponatremia. The study involved 15 (37.5%) men and 25 (62.5%) women (mean age [SD], 76.4 [8.3] years; range, 55–95). Their sodium levels before Preminent administration were 139.5 (4.9) mEq/L (range, 131–145; reference range, 135–147). The duration from the day of Preminent administration to the day with the lowest sodium level was 59.3 (64.9) days (range, 2–207; median, 24). Most patients for whom this duration was <50 days exhibited progressive symptoms, whereas most of those for whom this duration was >50 days did not exhibit progressive symptoms but exhibited symptoms after fever or appetite loss. The lowest sodium value was 114.4 (8.2) mEq/L (range, 99–133). The duration from the time of Preminent discontinuation to (1) the time of early recovery and (2) the time of final recovery was 6.8 (5.5) days (range, 1–20; median, 5) and 11.6 (7.6) days (range, 2–29; median, 7.5), respectively. Of the 40 patients, 36 (90.0%) achieved full recovery, 1 (2.5%) suffered from after-effects due to central pontine myelinolysis, 1 (2.5%) died, and 2 (5.0%) were unknown. In the analysis of other adverse effects of Preminent and the same adverse effects of other three angiotensin II receptor blocker (ARB)/thiazide combinations, hyponatremia was observed as a primary adverse effect of all ARB/thiazide combinations. However, hyperesthesia dermatitis was reported as an adverse effect of Preminent only. [ABSTRACT FROM AUTHOR]

Introduction. Concentrations of thyroid hormones, their carrier proteins, and thyroid antibodies in plasma have been extensively investigated, but those in pleural effusion have not. Patients and Medthods. In the present study, we report, for the first time, the concentrations of thyroid hormones, their carrier proteins, and thyroid antibodies in the pleural effusion of two thyrotoxicosis patients with Graves' disease. Results. The pleural effusions were transudates. The concentrations of thyroid hormone carrier proteins, such as thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (Alb) were approximately 30-50% of the plasma. The concentrations of total triiodothyronine (TT3), total tetraiodothyronine (TT4), free triiodothyronine (FT3), and free tetraiodothyronine (FT4) were approximately 15-40%, 45-55%, 45-75%, and 80-85% of the plasma, respectively. The concentration of thyroid stimulating hormone receptor antibody (TRAb) (equal to TSH-binding inhibitory immunoglobulins%; TBII%) was approximately 90% of the plasma. Conclusion. If the pleural effusions were treated with diuretics, substantial quantity of thyroid hormones and thyroid antibodies in the pleural effusion may have returned to the plasma, and might exacerbate thyrotoxicosis. For patients with thyrotoxicosis and pleural effusion, thoracentesis should be considered. The present findings will contribute to the understanding and treatment of hyperthyroidism-induced pleural effusion. [ABSTRACT FROM AUTHOR]

Bone lesions in multiple myeloma (MM) have a significant impact on the quality of life of elderly patients, but they have not been extensively investigated in the elderly. The subjects were 146 elderly MM patients (aged ≥ 65 years, median age 74) admitted to 11 institutions. Bone lesions were compared with those in 65 non-elderly MM patients. At the time of diagnosis, skeletal symptoms were present in 104 cases and bone pain in 75. Mixed type occurred more often in elderly patients (63.5%) than in controls (28.3%) ( P < 0.0001). Lumbar vertebral lesions were more common in elderly than non-elderly patients ( P < 0.0001). Bone lesions restricted physical activity in 71 elderly patients (48.6%). There was a significant difference between elderly patients with and without bone lesions in the rate of detection of plasma cells in bone marrow. Significant differences were detected in serum calcium concentration, the rate of detection of plasma cells in bone marrow, and serum β2-microglobulin concentration between patients with and without bone pain, and between those with and without fractures. No significant differences were detected in survival time between elderly patients with and without bone lesions, with and without bone pain, or with and without fractures, whereas a significant difference was seen between these subgroups of non-elderly patients. Although there were no significant differences in the incidence of bone lesions between elderly and non-elderly patients, the mixed type of bone lesions occurred more often in the elderly than in controls. Lumbar vertebral lesions were more common in elderly than non-elderly patients. There was no significant difference in prognosis between elderly patients with and those without bone lesions so the treatment strategy for bone lesions in the elderly should be aimed at improving quality of life through direct treatment of the bone lesions, with subsequent improvement of the related symptoms. [ABSTRACT FROM AUTHOR]

Cepharanthin, a bisbenzylisoquinoline (biscolaurine) alkaloid drug, has been reported to improve the symptoms of intractable or steroid-resistant chronic idiopathic thrombocytopenic purpura (ITP). To clarify the mechanism by which the cepharanthin is beneficial to ITP, we examined the effects of cepharanthin on thrombocytopenia in (NZW × BXSB) F1 (W/B F1) mice and on the formation of colony forming unit of megakaryocyte (CFU-MK) derived from human CD34-positive progenitor cells. The decrease in platelet numbers in W/B F1 was diminished by the administration of 5 mg/kg cepharanthin for 6 weeks as well as by 2 mg/kg prednisolone. Furthermore, the administration of over 0.2 mg/kg cepharanthin enhanced the therapeutic effect of prednisolone. From the data in this animal model, it is suggested that cepharanthin may prolong the platelet lifespan. The treatment of CD34-positive progenitor cells isolated from cord blood with cepharanthin (over 5 × 10[sup -10]g/ml) caused an increase in the formation of CFU-MK induced by the cocktail of thrombopoietin, interleukin (IL)-6 and IL-3. The addition of 0.1% normal human serum dramatically increased the number of CFU-MK. In contrast, the serum isolated from patients with ITP at the same concentration decreased the number of CFU-MK. However, the simultaneous addition of 5 × 10[sup -8]g/ml cepharanthin recovered the number of CFU-MK to the level induced by normal serum. These findings indicate that cepharanthin has the potent therapeutic activity not only on the platelet destruction process, but also on the platelet production process of thrombocytopenia in chronic ITP. [ABSTRACT FROM AUTHOR]

While CHOP therapy is effective for malignant lymphoma, the optimum schedule for elderly patients remains controversial. The present study investigated the usefulness of reduced-dose CHOP therapy for elderly patients. Previously untreated patients aged 65 years or older with intermediate to high-grade non-Hodgkin's lymphoma were given up to 6 courses of reduced-dose CHOP therapy at 3-week intervals. Group A patients were given 5/6 of the standard dose and Group B received 7/12 of the standard dose. Filgrastim was administered when the white blood cell count fell below 2,000/μL. Fifty-seven patients were évaluable and the scheduled therapy was completed in 37. For patients aged from 65 to 79 years and for patients older than 80 years, the complete response rate was 79.5% and 46.2%, overall 3-year survival was 58.2% and 30.4%, and event-free 3-year survival was 49.3% and 44.4%, respectively. Major toxicities (> grade 3) included leukopenia in 42 patients and documented infection in 7 patients. Grade 3 cardiac plus renal failure, grade 3 peritonitis due to small bowel perforation, and grade 3 liver dysfunction occurred in 1 patient each. One patient died of toxicity (grade 4 hematological toxicity and pneumonia). In conclusion, it seems that in the elderly patients with non-Hodgkin's lymphoma, response to reduced-dose (5/6 dose) CHOP therapy is comparable to that for standard CHOP in younger adults, mainly because of improved dose-intensity. [ABSTRACT FROM AUTHOR]

Abstract: DiGeorge syndrome – a component of the 22q11 deletion syndrome – causes a disturbance in cervical neural crest migration that results in parathyroid hypoplasia. Patients can develop hypocalcemia-induced seizures. Spina bifida is caused by failure of neurulation, including a disturbance in the adhesion processes at the neurula stage. Spina bifida has been reported as a risk factor for epilepsy. We report, for the first time, the case of a patient with DiGeorge syndrome with spina bifida and sacral myelomeningocele, who developed both hypocalcemia-induced seizures and epilepsy. The patient had spina bifida and sacral myelomeningocele at birth. At the age of 13 years, he experienced a seizure for the first time. At this time, the calcium concentration was normal. An electroencephalogram (EEG) proved that the seizure was due to epilepsy. Antiepileptic medications controlled the seizure. At the age of 29, the patient''s calcium concentration began to reduce. At the age of 40, hypocalcemia-induced seizure occurred. At this time, the calcium concentration was 5.5mg/dL (reference range, 8.7–10.1mg/dL). The level of intact parathyroid hormone (PTH) was 6pg/mL (reference range, 10–65pg/mL). Chromosomal and genetic examinations revealed a deletion of TUP-like enhancer of split gene 1 (tuple1)—the diagnostic marker of DiGeorge syndrome. Many patients with DiGeorge syndrome have cardiac anomalies; however, our patient had none. We propose that the association among DiGeorge syndrome, spina bifida, epilepsy, cardiac anomaly, 22q11, tuple1, and microdeletion inheritance should be clarified for appropriate diagnosis and treatment. [Copyright &y& Elsevier]

Background: Nitric oxide (NO) is an important physiological mediator of vascular tone and is involved in pathophysiology of septic shock. Although plasma nitrite is a stable end product of NO oxidation derived from endogenous NO, the plasma nitrite level is also easily affected by the intake of various foods, bacterial products and renal functional status. Aims: We propose an excellent alternative assay technique for measuring endogenous NO production. Methods: We measured the nitrite level in cultured vascular smooth muscle cells (SMC) treated with serum obtained from patients with sepsis (4 patients), by means of a chemiluminescence detector. Results: The nitrite concentrations in such cells were significantly higher as compared to those in the cells treated with normal serum. Moreover, the increased nitrite levels in the SMC treated with the sera obtained from patients with sepsis were completely inhibited by L-nitroarginine (1 m m ol/L), a nitric oxide synthase inhibitor. Conclusion: These data suggest that this assay method enable us to know the ability of endogenous NO production in each patient. [ABSTRACT FROM AUTHOR]