Clinical characteristics and treatment status of pustulotic arthro-osteitis: A single-center study involving 51 cases.

Pustulotic arthro-osteitis (PAO) is a major complication of palmoplantar pustulosis (PPP). In orthopedic surgery outpatient clinics, PPP patients with osteoarticular symptoms are seen frequently, but PAO's clinical features remain not well known. To determine Japanese patients' clinical features and treatment status with PAO, we conducted a single-center retrospective epidemiologic survey. Clinical features, including gender, age, smoking habit, the onset pattern, interval between skin manifestation and osteoarticular symptoms, and the incidence of sternoclavicular joint lesions, axial and peripheral joint lesions, were examined. The association between physical status and image findings by X-ray, computed tomography, bone scintigraphy with Technetium99 , or magnetic resonance imaging was evaluated. The distribution pattern of peripheral joint lesions and the treatment status were evaluated. We identified 51 patients, 10 men and 41 women, with PAO. The average age was 48 years and 59% were smokers. The frequency of onset patterns was skin-leading type (63%), simultaneous onset (18%), and osteoarticular leading type (16%). The average interval between skin involvement and osteoarticular involvement in skin-leading type was significantly longer than that in osteoarticular leading type (7.1 years vs. 2.0 years). A sternoclavicular joint (SCJ) lesion was detected in 65% cases, and the physical findings of SCJ were significantly related to the image findings. Axial and peripheral joint lesions were detected in the same ratio (23 cases, 45%). In the peripheral joints, the finger joint was the most common (26%), followed by the shoulder joint (21%). Patients were treated with nonsteroidal anti-inflammatory drugs (76%), followed by conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (29%) and biological DMARDs (9.8%). Tonsillectomy was performed in 11 cases. In conclusion, PAO more frequently involves SCJ in middle-aged women who smoke. Given that osteoarticular leading type was detected in 16% cases, seronegative oligoarthritis patients should be monitored for PPP, leading to a diagnosis of PAO.

Evaluation of salivary melatonin concentrations as a circadian phase maker of morning awakening and their association with depressive mood in postpartum mothers.

The disruption of circadian rhythm is closely related to mood disorders in night-shift workers, and a similar situation may occur in postpartum mothers. However, the situations of postpartum mothers remain largely unknown because of a lack of an appropriate circadian phase marker in the clinical setting. This study aimed to evaluate whether salivary melatonin concentration at awakening can identify misalignment between awakening time and the biological clock system, which might be associated with depressive mood in some mothers. Ninety-eight healthy mothers who were currently the primary parental caregivers were recruited at 1 month after delivery. All mothers completed the Edinburgh Postnatal Depression Scale (EPDS) and wore an actigraphy watch at home for 3 consecutive days to determine nocturnal sleep variables. While wearing the actigraphy watch, they also collected saliva samples during the awakening period for a melatonin concentration assay. The results indicated that daily salivary melatonin levels after 30 min of awakening (hereafter, melatonin levels) were positively correlated with sleep onset time and negatively correlated with sleep offset time and total sleep time. Six mothers with an EPDS score of ≥9 (the cutoff value for Japanese women at high risk for postnatal depression) had an average melatonin level of either <4 pg/ml or >16 pg/ml for 3 d. Mothers with melatonin levels <4 pg/ml or >16 pg/ml tended to have elevated EPDS scores (4.93 ± 2.95 or 4.20 ± 2.93, mean ± standard deviation) compared with mothers with melatonin levels between 4 and 16 pg/ml (3.00 ± 2.12, p = .053). Mothers whose melatonin levels were >16 pg/ml had relatively later sleep onset time and shorter nocturnal sleep duration. Backward stepwise regression demonstrated that such high/low levels of melatonin were a significant predictor of EPDS scores. These results suggest that elevated melatonin levels after 30 min of awakening could identify a phase-delayed circadian rhythm in postpartum mothers, and that relatively higher or lower melatonin levels could be associated with increased depressive mood.

Management of Acquired Hemophilia A in Elderly Patients.

This report describes six elderly patients with acquired hemophilia A (AHA), including four individuals aged ≥90 years. Bleeding symptoms were subcutaneous or intramuscular hemorrhage (n=4), hematuria (n=1), and hemorrhagic shock after tooth extraction (n=1). Factor VIII (FVIII) activity ranged from <1.0% to 3.0%, and anti-FVIII inhibitor titers ranged from 8.8 to 240 BU/mL. Treatment was administered at the discretion of the responsible physician. Hemostatic agents applied in the six patients comprised rFVIIa (NovoSeven®) (n=4), APCC (Feiba®) (n=2), and fresh frozen plasma/plasma exchange (n=1). Agents employed for inhibitor eradication comprised prednisolone only (n=3), prednisolone with cyclophosphamide (n=1), prednisolone with cyclosporine (n=1), and prednisolone with rituximab (n=1). In five patients, management was successful, with complete response. Treatment failed in the patient with the highest inhibitor level (240 BU/mL) in whom treatment with APCC (Feiba®; 100 U/kg/dose, three doses) and prednisolone (0.5 mg/kg/day) was followed by several episodes of relapse. The present data demonstrate that AHA severity shows wide variation in elderly subjects, indicating the necessity of individualized management.

Waldenstrom's Macroglobulinemia: A Report of Two Cases, One with Severe Retinopathy and One with Renal Failure.

We report here two cases of Waldenstrom's macroglobulinemia (WM), one with central nervous system (CNS) symptoms and severe retinopathy and one with renal failure. In both cases, the serum IgM levels exceeded 3,000 mg/dL and monoclonal IgM-kappa was observed in the blood. At onset, Case 1, a 63-year-old female, developed CNS symptoms-namely, drowsiness and syncope. Case 2, a 58-year-old male, had nausea and dysgeusia on admission associated with renal failure, which is quite rare in patients with WM. Both patients exhibited hyperviscosity-related retinopathy, but it was particularly severe in Case 1: she suddenly lost her vision after admission. However, her vision recovered completely during treatment. Case 2 required hemodialysis immediately after admission. Needle biopsy of his kidney revealed tubulointerstitial nephritis with marked infiltration with CD20-positive lymphoplasmacytic lymphoma cells. After treatment, Case 1 has been in a remission longer than 8 years, but Case 2 died of pneumonia in 6 months. Since the initial symptoms of WM are ambiguous and vary significantly and hyperviscosity-related ophthalmological problems or severe renal dysfunction can arise, it is essential to promptly measure serum IgM levels and to institute appropriate care immediately when WM is confirmed in a patient.

Successful Treatment of Leukemic Mature B-Cell Lymphoid Neoplasm with Similar Features to Splenic Marginal Zone Lymphoma Possessing Aberrant Myeloid Markers.

In splenic marginal zone lymphoma (SMZL), there are cases that cannot accurately be classified as such because of overlapping morphologic and/or immunophenotypic features. We report here a 76-year-old Japanese female, who showed leukemic B-cell lymphoproliferative disease possessing characteristic features identified for SMZL. The patient was leukemic with white blood cell counts 49,400/µL (abnormal cells, 78.5%) and neoplastic cells were characterized by aberrant expression of myeloid markers with CD19(+)CD13(+) (64.2%) and CD20(+)CD11c(+) (25.1%). Considering her history of previous chemotherapy and systemic leukemic phase of the disease, we treated the patient without performing splenectomy, with successful use of a combination of rituximab/bendamustine hydrochloride and of rituximab/cladribine. The patient has been in a complete remission longer than 44 months, with no detectable M-protein.

Two cases of primary cold agglutinin disease associated with megaloblastic anemia.

We report two cases of primary cold agglutinin disease (CAD) associated with megaloblastic anemia in Japanese elderly patients. Case 1 was a 67-year-old male and Case 2 was a 55-year-old male. Both patients were diagnosed with primary CAD, with continuously high cold agglutinin titers (1 : >8,192 and 1 : 16,834, resp.), monoclonal IgM-kappa light chains, and no underlying disease. In addition, both patients had megaloblastic anemia due to vitamin B12 deficiency. One patient received rituximab and both received vitamin 12 supplementation. To date, no cooccurrence of primary CAD and megaloblastic anemia has been emphasized. Thus, the association of these hematological diseases may be incidental; however, given that CAD is an autoimmune disease which may show antibodies against intrinsic factor and gastric parietal cells, this association was thought to be probably not a coincidence. Clinicians should be aware of the possible simultaneous presence of autoimmune hemolytic/megaloblastic anemia in patients with primary CAD.

Expansion of natural killer cells in peripheral blood in a Japanese elderly with human T-cell lymphotropic virus type 1-related skin lesions.

Natural killer (NK) cells were proposed to play an important role in the pathogenesis of human T-cell lymphotropic virus type 1- (HTLV-1-) associated neurologic disease. Our patient was a 77-year-old Japanese man, who had been treated for infective dermatitis associated with HTLV-1 for nearly 10 years. When referred to us, he had facial eczema/edema as well as extensive dermatitis at the neck/upper chest and nuchal area/upper back regions. Dermal lesions had CD3+CD4+ cells, but no NK cells. Flow cytometry of his peripheral blood showed a phenotype of CD2+ (97%), CD3+ (17%), CD4+ (12%), CD7+ (94%), CD8+ (6%), CD11c+ (70%), CD16+ (82%), CD19+ (0%), CD20+ (0%), CD56+ (67%), HLA-DR+ (68%), and NKp46+ (36%). Absolute numbers of CD56+NK cells in the peripheral blood were in a range of 986/µL-1,270/µL. The expanded NK cells in the peripheral blood are considered to be reactive, to maintain the confinement of the HTLV-1-positive CD4+ cells in the skin, and to prevent the progression of the disease.

Heart rate variability biofeedback intervention for reduction of psychological stress during the early postpartum period.

This study examined the effectiveness of heart rate variability (HRV) biofeedback intervention for reduction of psychological stress in women in the early postpartum period. On postpartum day 4, 55 healthy subjects received a brief explanation about HRV biofeedback using a portable device. Among them, 25 mothers who agreed to implement HRV biofeedback at home were grouped as the biofeedback group, and other 30 mothers were grouped as the control group. At 1 month postpartum, there was a significant decrease in total Edinburgh Postnatal Depression Scale score (P < 0.001) in the biofeedback group; this change was brought about mainly by decreases in items related to anxiety or difficulty sleeping. There was also a significant increase in standard deviation of the normal heartbeat interval (P < 0.01) of the resting HRV measures in the biofeedback group after adjusting for potential covariates. In conclusion, postpartum women who implemented HRV biofeedback after delivery were relatively free from anxiety and complained less of difficulties sleeping at 1 month postpartum. Although the positive effects of HRV biofeedback may be partly attributable to intervention effects, due to its clinical outcome, HRV biofeedback appears to be recommendable for many postpartum women as a feasible health-promoting measure after childbirth.

Chlamydia pneumoniae infection-associated erythema multiforme.

There is a well-known correlation between Herpes simplex (HSV) infection and erythema multiforme (EM). More recently, in Japan, it was found that Chlamydia pneumoniae (Cp) may promote the development of EM. All cases of Cp infection-associated EM that had been diagnosed in our clinic over the past two years (from 2011 to 2012) were analyzed. Cp infection was diagnosed on the basis of a significant increase (>2.00) in anti-Cp IgM titers, as measured by the HITAZYME-ELISA test. There were 7 cases of Cp-EM, one male and 6 females. Median age was 13 years (range 3-29 years). It is recommended that the possible involvement of Cp infection, besides HSV or Mycoplasma pneumoniae infections, should be considered in all cases of EM.

Severe hypernatremia and hyperchloremia in an elderly patient with IgG-kappa-type multiple myeloma.

A 77-year-old male was admitted to hospital after suffering a pelvic bone fracture in a road traffic accident and was incidentally found to have IgG-kappa-type multiple myeloma with hypercalcemia. The patient was also noted to be hypokalemic and had low HCO3 (-), with possible damage to the distal tubules in the kidneys. When the treatment was begun with bortezomib/dexamethasone/elcatonin and sodium bicarbonate (NaHCO3) in normal saline (equivalent to a daily sodium dose of 200 millimoles per liter [mmol/L]), the patient was in a state of poor oral fluid intake. The patient developed hypernatremia and hyperchloremia, with a peak serum sodium and chloride levels of 183 mmol/L and 153 mmol/L, respectively, at the sixth day after the start of treatment. Following the switch of the intravenous infusions from normal saline to soldem 1 and soldem 3 solutions, these high-electrolyte levels gradually returned to normal over the next 7 days. Although the patient showed disturbed consciousness (Japan Coma Scale = JCS-I-3) during the period of electrolyte abnormality, he eventually fully recovered without sequelae. In this patient, we successfully managed the severe hypernatremia/hyperchloremia, caused by the combined effects of intravenous saline burden in a state of poor oral fluid intake, during the treatment for IgG-kappa type multiple myeloma.

Rituximab for managing acquired hemophilia A in a case of chronic neutrophilic leukemia with the JAK2 kinase V617F mutation.

BACKGROUND: Acquired hemophilia A is rarely found in association with myeloproliferative neoplasms, such as the JAK2 kinase V617F mutation-positive chronic neutrophilic leukemia (CNL). CASE REPORT: An 80-year-old Japanese male was diagnosed with acquired hemophilia A. He had compartment-like symptoms due to soft tissue hemorrhage in his left forearm and right lower extremity. A blood examination showed neutrophilia with a white blood cell count of 31,900/µL (91.9% neutrophils), an activated partial thromboplastin time of 69.0 seconds, coagulation factor VIII (FVIII) < 1.0%, and anti-FVIII inhibitor, 190 BU/mL. The bleeding episodes were controlled with intravenous activated prothrombin complex concentrate (FEIBA(®)) followed by recombinant factor VIIa (NovoSeven(®)). In addition, oral prednisolone (maximum dose, 30 mg/day) plus four doses of rituximab effectively suppressed anti-FVIII inhibitor levels while simultaneously reducing the neutrophil count. CNL with the JAK2 kinase V617F mutation was identified as the underlying disease. CONCLUSION: This report describes the effectiveness of a combination of prednisolone and rituximab in managing acquired hemophilia A in an elderly man with a rare case of JAK2 kinase V617F mutation-positive CNL.

Spontaneous resolution of macrocytic anemia: old disease revisited.

We report here on a 60-year-old male with alcohol-related macrocytic anemia. He was hospitalized on three occasions with hemoglobin < 9.0 g/dL and mean corpuscular volume > 130 fL. Careful history taking and observation of his blood status led us to make a correct diagnosis. At the time of each of his admissions, only with bed rest and abstinence from alcohol did our patient dramatically show spontaneous recovery of anemia in association with a rapid decline of serum γ-glutamyl transpeptidase values. It is well recognized that marrow abnormalities in alcoholic patients are reversible. Physicians should be aware that there is a subset of patients with macrocytic anemia that could be improved without medication.

Concurrence of thyrotoxicosis and Gitelman's syndrome-associated hypokalemia-induced periodic paralysis.

A 16-year-old Japanese boy with a history of truancy had been treated at a psychiatric clinic. When the patient was referred to us for hypokalemia-associated paralysis, the diagnosis of thyrotoxic hypokalemic periodic paralysis was made, common in Asian men. Subsequently, the patient was found to have persistently high plasma renin and aldos-terone levels. Thus, solute carrier family 12 member 3 gene (SLC12A3) analysis was performed. A novel missense homozygous mutation CTC->CAC at codon 858 (L858H) was found for which the patient was homozygous and his non-consanguineous parents heterozygote. These findings indicated that the patient developed hypokalemia-associated paralysis concurrently with thyrotoxicosis and Gitelman's syndrome. This case underscores the importance of careful examinations of adolescents with complaints of truancy as well as of precise determinations of the causes of hypokalemia-associated paralysis.

[Retrospective study on intravenous compound injection of cancer pain patients with oxycodone and hydrocotarnine preparation in comparison with subcutaneous administration].

In Japan, although oral oxycodone is widely used for cancer pain treatment, there is no injection preparation of oxycodone used as a single ingredient. Only the compound injection of oxycodone and hydrocotarnine has received approval. Subcutaneous administration of the drug is approved, but there are few efficacy and safety reports about its intravenous administration. We compared 245 patients(187 intravenous administration patients and, 58 subcutaneous administration patients)to whom the compound injection of oxycodone and hydrocotarnine was administered from April, 2008 to September, 2011, in order to investigate the drug's efficacy and safety. The reasons for injection were the impossibility of oral administration in 105 patients, a need for dose adjustment in 56 patients, and that other drugs were not as effective in 37 patients, and side effect reduction in 33 patients. The average change in the numeric rating scale(0-10)was 3. 7→1. 8 in intravenous administration, and 3. 4→1. 2 in subcutaneous administration. The incidence of main adverse events(intravenous administration/subcutaneous administration)were constipation(37%/28%), vomiting(31%/34%), and somnolence(52%/50%). There was no significant difference in efficacy and safety. The conversion ratio differed in a case due to a change, and about 20 to 40% of addition was needed within four days after the start. It is considered that compound injection of oxycodone and hydrocotarnine is effective for cancer pain treatment.

Persistent thrombocytosis in elderly patients with rare hyposplenias that mimic essential thrombocythemia.

When elderly patients present with persistent thrombocytosis, myeloproliferative disease, iron-deficiency anemia or post-splenectomy status are suspected along with autoimmune diseases. Reported here are the cases of two elderly patients with persistent thrombocytosis due to hyposplenia, which is very rarely diagnosed in old age. Case 1 was a 72-year-old man whose thrombocytosis was due to non-familial type isolated congenital asplenia. Case 2 was a 74-year-old man whose thrombocytosis was caused by an atrophied spleen resulting from perforated stomach ulcer-related panperitonitis that had been treated 20 years previously. Both patients had thrombocyte counts exceeding >500,000/µl in association with small vestigial spleen tissue on a computed tomography scan and positive Howell-Jolly bodies on the blood smear. A correct diagnosis is essential for the management of persistent thrombocytosis.

Treatment of patients with hypothalamic-pituitary lesions as adult-onset Langerhans cell histiocytosis.

We report four cases of adult-onset Langerhans cell histiocytosis (LCH) with central nervous system (CNS) lesions in the hypothalamic-pituitary region. The first clinical symptoms were diabetes insipidus (two patients), hypothyroidism (one patient), and decreased libido/erectile dysfunction (one patient). Diagnosis was delayed as the CNS lesion was not initially suspected to be secondary to LCH, with a median time from symptom onset to treatment of 3.0 (range <1-5.3) years. In three patients, the tumor mass was effectively reduced by chemotherapy; however, all patients continue to exhibit hypopituitarism. Early diagnosis and initiation of treatment are required to improve the outcome of CNS-LCH in adult patients.

Excess iodide decreases transcription of NIS and VEGF genes in rat FRTL-5 thyroid cells.

Although it is well known that an excess of iodide suppresses thyroid function and blood flow in vivo, the underlying molecular mechanisms are not fully known. The functional effect of iodide occurs at multiple steps, which include inhibition of sodium/iodide symporter (NIS) expression, transient block of organification, and inhibition of hormonal release. The vascular effect likely involves suppression of the vascular endothelial growth factor (VEGF) gene. In this report, we show that excess iodide coordinately suppresses the expression of the NIS and VEGF genes in FRTL-5 thyroid cells. We also demonstrate that the mechanism of iodide suppression of NIS gene expression is transcriptional, which is synergized by the addition of thyroglobulin. Based on the findings of reporter gene assays and electrophoretic gel mobility shift analysis, we also report two novel DNA binding proteins that responded specifically to iodide and modulated NIS promoter activity. The results suggest that excess iodide affects thyroid vascular function in addition to iodide uptake. This study provides additional insights into the mechanism of action of excess iodide on thyroid function.

Serum CA 125 expression as a tumor marker for diagnosis and monitoring the clinical course of epithelioid sarcoma.

PURPOSE: We report here, our experience of seven patients with epithelioid sarcomas and their serum CA 125 levels, as well as the results of an in vitro and in vivo study of CA 125 expression in epithelioid sarcoma cells and xenografts using three epithelioid sarcoma cell lines. METHODS: In the clinical study, the serum CA 125 levels of seven epithelioid sarcoma patients were examined at multiple time points. Expression of the MUC16 gene that encodes the CA 125 sequence was examined using RT-PCR methods in three epithelioid sarcoma cell lines, FU-EPS-1, SFT-8606 and NEPS, and the CA 125 protein in each cell lysate was examined by Western blot using anti-CA 125 clone OC125 antibody. The concentration of CA 125 in the conditioned medium of each cell line was also measured. RESULTS: In five of the seven epithelioid sarcoma patients, CA 125 levels reflected regression and progression of their disease. The CA 125 concentrations in the conditioned medium of FU-EPS-1, SFT-8606 and NEPS cells were 259, 252, and 6 U/ml, respectively. Strong expression of MUC16 mRNA was shown in FU-EPS-1 and SFT-8606 cells: correspondingly, a thick band was observed by Western blot analysis in only FU-EPS-1 and SFT-8606 cells. CONCLUSION: We concluded that epithelioid sarcoma cells produce and secrete CA 125 into the blood serum and that the elevation of serum CA 125 correlates with disease progression. Therefore, measuring the serum CA 125 level should provide an useful index for diagnosing and monitoring the course of epithelioid sarcoma.