Appendicular bone mass and knee and hand osteoarthritis in Japanese women: a cross-sectional study

BACKGROUND: It has been reported that there is an inverse association between osteoarthritis (OA) and osteoporosis. However, the relationship of bone mass to OA in a Japanese population whose rates of OA are different from Caucasians remains uncertain. METHODS: We studied the association of appendicular bone mineral density (second metacarpal; mBMD) and quantitative bone ultrasound (calcaneus; stiffness index) with knee and hand OA among 567 Japanese community-dwelling women. Knee and hand radiographs were scored for OA using Kellgren-Lawrence (K/L) scales. In addition, we evaluated the presence of osteophytes and of joint space narrowing. The hand joints were examined at the distal and proximal interphalangeal (DIP, PIP) and first metacarpophalangeal/carpometacarpal (MCP/CMC) joints. RESULTS: After adjusting for age and body mass index (BMI), stiffness index was significantly higher in women with K/L scale, grade 3 at CMC/MCP joint compared with those with no OA. Adjusted means of stiffness index and mBMD were significantly higher in women with definite osteophytes at the CMC/MCP joint compared to those without osteophytes, whereas there were no significant differences for knee, DIP and PIP joints. Stiffness index, but not mBMD, was higher in women with definite joint space narrowing at the CMC/MCP joint compared with those with no joint space narrowing. CONCLUSIONS: Appendicular bone mass was increased with OA at the CMC/MCP joint, especially among women with osteophytes. Our findings suggest that the association of peripheral bone mass with OA for knee, DIP or PIP may be less clearcut in Japanese women than in other populations

Basal insulin ratio of type 1 diabetes

Aims/Introduction: To investigate the basal insulin requirement in patients with type 1 diabetes who are on multiple daily injections (MDI) and to assess the patient characteristics that affect the percent of total daily basal insulin dose to the total daily insulin dose (%TBD/TDD). Materials and Methods: The subjects of this study were 67 inpatients with type 1 diabetes who were served diabetic meals of 25–30 kcal/kg standard body weight during several weeks of hospitalization. The basal insulin requirement was adjusted to keep the blood glucose level from bedtime to before breakfast within a 30 mg/dL difference. The bolus insulin dose before the meal was adjusted to keep the blood glucose level below 140 and 200 mg/dL before and 2 h after each meal, respectively. The total daily insulin dose (TDD), the percent of total daily basal insulin dose (TBD) to TDD (%TBD/TDD), and clinical characteristics were collected. Results: The median (Q1, Q3) of TDD was 33.0 (26.0, 49.0) units, and the %TBD/TDD was 24.1 ± 9.8%. The %TBD/TDD was positively correlated with the body mass index (BMI) and negatively correlated with the age at the onset and at the examination according to a univariate analysis. However, the %TBD/TDD was dependent on the BMI (β = 0.340, P = 0.004) and the age at examination (β = −0.288, P = 0.012) according to the multiple regression analysis. Conclusions: The average %TBD/TDD in patients with type 1 diabetes on MDI was approximately 24% under inpatient conditions. The basal insulin requirement was dependent on the BMI and the age at examination

Loss of Endoreduplication as Morphogenesis of Micromegakaryocytes in Myelodysplastic Syndrome.

Morphogenesis of micromegakaryocytes in MDS was investigated in a case of refractory anemia with excess of blasts by analysing megakaryocyte colonies developed from peripheral blood mononuclear cells in a semi-solid culture containing aplastic anemia patient\u27s plasma as source for megakaryocyte colony stimulating factor and thrombopoiesis stimulationg factor. Candidate megakaryocyte colonies were individually stained for glycoprotein (GP)IIb/IIIa by immunocytochemical method. Three types of colonies were distinguished ; type I composed of 10-30 large magakaryocytes with high ploidy number, type II composed of 50-200 micromegakaryocytes with single nucleus, and type III composed of 20-50 micromegakaryocytes. Type I colonies were similar to megakaryocyte colonies obtained from three control subjects. Periodic in situ observation of type II and III colonies disclosed that large megakaryocytes never appeared during 21 days\u27 culture, suggesting mitotic growth at every generation. These findings indicate that loss of endoreduplication is primary defect in micromegakaryocyte formation by MDS clone. Quantitaive aspect of platelet formation by micromegakaryocytes could not be assessed in this study, but morphological observation in situ or on GPIIb/IIIa-stained preparation suggested reduced platelet production. Biological significance of diminished endoreduplication is yet to be determined in respect to leukemic predisposition

Low Dose Cytosine Arabinoside Regimen for Overt Leukemia, Hypoplastic Leukemia and Myelodysplastic Syndromes : Hypoplastic Leukemia Responds Best.

In a series of 38 patients consisting of 13 with overt acute leukemia, 14 with hypoplastic leukemia, and 11 with myelodysplastic asyndromes (MDS), responsiveness to low dose cytosine arabinoside (LDAC) regimen was investigated to clarify the disease type most benefitted. LDAC was continuously administered intravenously at dose 0.2mg/kg/day and continued as long as possible to meet the pre-assigned target point of 5% marrow blasts which was confirmed by weekly marrow aspiration. Overall response rate was 47%; complete remission (CR) being 31% and partial remission (PR) 16%. CR rate was significantly different between the disease types ; 69% in hypoplastic leukemia, 23% in overt leukemia and 0% in MDS (p=0.01). In hypoplastic leukemia the survival time was significantly longer in the LDAC-treated cases compared with 15 historical control cases treated with supportive care only ; median survial being 750 days in the former and 250 days in the latter (p=0.01). In overt leukemia only three M2 AML cases obtained CR ; two of them were treated during hypoplastic phase induced by intensive chemotherapy. All CR cases eventually achieved the target point after 20 to 42 days (median 26) of LDAC administration. Substantial toxicity of LDAC was evident, but most cases tolerated well. The present investigation suggests that hypoplastic leukemia is the disease type most sensitive to LDAC regimen. Stratification of the elderly leukemia patients should be considered for this regimen

In Vitro Study of the Independent and Combined Effects of Recombinant Human GM-CSF and G-CSF on Normal Bone Marrow Granulocytes : GM-CSF Enhances the Growth Effect but Suppresses the Terminal Maturation-inducing Effect of G-CSF

We studied the independent and combined effects of recombinant human granulocyte colony- stimularting factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the growth and maturation of neutrophilic granulocytes. Absolute granulocyte numbers, cellular composition, and neutrophil alkailne phosphatase (NAP) activity were examined after normal nonphagocytic bone marrow cells were cultured for seven days with rhG-CSF, rhGM-CSF, and a combination of both growth factors. The numbers of band and segmented forms produced in the cultures containing rhGM-CSF were significantly lower than in control cultures or those with rhG-CSF. When both rhGM-CSF and rhG-CSF were in the culture total granulocyte production was highest, but the increment of band and segmented forms produced by rhG-CSF alone was reduced. Neutrophil alkaline phosphatase (NAP), an enzyme marking terminal maturation, was increased by rhG-CSF alone, but not by rhGM-CSF alone. Cultures containing both CSFs showed significantly lowered NAP activity compared to those containing rhG-CSF alone. The decrement in NAP activity was proportionate to the amount of rhGM-CSF added. These results indicate that terminal maturation-inducing effect is a property of rhG-CSF but not of rhGM-CSF. In the presence of both GM-CSF and G-CSF, the growth of granulocytes is maximumly stimulated but the terminal maturation-inducing effect of rhG-CSF is suppressed

A case of isolated ACTH deficiency that required 6 months for the diagnosis from onset

A 53-year-old man noticed anorexia, nausea, and arthralgia of the upper limbs in April, 201X. Since these symptoms persisted, he visited general hospital and clinic and was examined for blood chemistry, ECG, echocardiography and so on. However, he did not get a definitive diagnosis and was followed up with drip infusion of saline. The symptoms did not subside and fatigue and syncope with hypotension developed. Furthermore, he also suffered weight loss of 10 kg in few months and was referred to our hospital for more detailed examinations in October, 201X. Upon the initial examination, all his symptoms matched those of adrenal insufficiency and notable decreases of both plasma ACTH and serum cortisol level were observed. Prompt glucocorticoid supplementation improved his symptoms and the abnormal laboratory data immediately. He was diagnosed adrenal insufficiency due to isolated ACTH deficiency from the results of CRH loading test and insulin tolerance test. Since most of the symptoms and laboratory findings are non-specific, diagnosis of adrenal insufficiency is often delayed. However, adrenal insufficiency could worsen when the patient is under stress (e.g. infection) and often be life-threatening. Glucocorticoid replacement therapy should be initiated as soon as the diagnosis is confirmed. Furthermore, educating patients and his families plays a very important role in the management of chronic adrenal insufficiency, in particular to the prevention of adrenal crisis

FMD and eGFR Slope in Males and Females

Aims: It is known that there are sex differences in vascular endothelial function and the development of chronic kidney diseases; however, it remains unclear whether sex differences influence the association between vascular endothelial function and renal prognosis. Methods: To clarify the relationship between vascular endothelial function and longitudinal eGFR changes in male and female patients with cardiovascular risk factors, we retrospectively evaluated 341 patients (176 males and 165 females) with cardiovascular risk factors in whom vascular function was assessed by flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV) and in whom 24-month longitudinal eGFR values were recorded after the vascular function examinations. Associations of values of FMD and baPWV with values of eGFR slope were statistically analyzed. Results: Simple regression analysis showed that the value of FMD was positively associated with eGFR slope in females (p=0.001) and non-smoking males (p=0.033) but not in smoking males. Multiple regression analysis showed that the value of FMD remains a positive contributor for eGFR slope in females (p=0.001) and non-smoking males (p=0.045) but not in smoking males. In contrast, values of baPWV had no significant association with eGFR slope regardless of sex and cigarette smoking. Conclusions: In individuals with cardiovascular risk factors, evaluation of vascular endothelial function enables prediction of renal prognosis in females and non-smoking males

A case of Cushing’s syndrome detected by repeated fragility fractures

A ３８-year-old woman had suffered from an avulsion fracture of the left cuboid bone, a rib fracture, a fatigue fracture of the left second metatarsal bone and a pubic fracture within the last ４ years. She also realized that her face was getting rounded and became aware of edema on extremities. She had repeated fragile fractures before menopause and was referred to our department on suspicion of secondary osteoporosis. The patients showed physical signs of moon face, central obesity, and abdominal violaceous striae. Cushing’s syndrome was suspected, therefore confirmatory studies were performed. Circadian variation of cortisol : serum cortisol１９．３μg／dL（at７：００）, ２１．４μg／dL（at２３：００）, urinary free cortisol :２４７．４μg／２４h, ACTH :２．５pg／mL. Low-dose（１mg） dexamethasone did not suppress cortisol level（１８．９μg/dL）. Based on these findings, we diagnosed as Cushing’s syndrome and glucocorticoid excess seemed to be the cause of secondary osteoporosis. Abdominal CT identified a ２．７ cm tumor in the left adrenal gland, and in-phase T１‐weighted MRI showed decreased signal compared to out-phase, suggesting an adrenocortical adenoma. She underwent laparoscopic left adrenalectomy. Postoperative fasting serum cortisol decreased to２．２ μg/dL, and glucocorticoid replacement therapy was started. It is necessary to find out any secondary causes for premenopausal women with fragility fractures. It is well known that endocrine disorders including Cushing’s syndrome are the most frequent associated diseases in patients with premenopausal osteoporosis. Cushing’s syndrome should be considered as a causative disease in premenopausal women with osteoporosis

Novel method for detection of pancreatic beta cell death using cell-free DNA

In people with type１ diabetes（T１D）, biomarkers that can sensitively and quantitatively evaluate injury of pancreatic beta cell are required in order to predict the onset of the disease at an early stage and to provide interventions to prevent the progression of the disease. We developed a new method for quantifying pancreatic beta cell-derived insulin DNA in circulation that combines bisulfite conversion and Amplification Refractory Mutation System（ARMS）PCR, which can be performed using a conventional real-time PCR system. We applied this method to T１D patients and healthy adults, both could be detected in about ３０％ of cases. The results in healthy adults indicate that this method may have sensitivity to detect the turnover of pancreatic beta cells at physiological conditions. In post-onset T１D patients, there were many negatives because the amount of residual pancreatic beta cells was extremely small. However, in some cases with a short duration of the disease, pancreatic beta cell-derived insulin DNA was detected in negative correlation between the duration of the disease, that suggested the residual pancreatic beta cells continue to be slowly destroyed. It was demonstrated that the time course of pathophysiology in T１D could be understood using this method

2ガタ トウニョウビョウ カンジャ ニオケル ケットウ シヒョウ ト ゲンエン ガ モタラス ケツアツ テイカ トノ レンカン

Background : The majority of patients with type２diabetes mellitus（T２DM）have hypertension, leading to serious cardiovascular events, including acute myocardial infarction, heart failure and stroke. Therefore, blood pressure（BP）control is a critical issue in patients with T２DM. Although sodium restriction is known to reduce BP, it is unclear what factors are associated with sodium restriction-induced BP reduction in T２DM patients. Subjects and Methods : A retrospective analysis was performed in hospitalized patients with T２DM（６６males and６１females, mean age :５８．１±１４．２years, mean HbA１c :９．５±２．０％）. They received diet therapy including sodium restriction as NaCl of５to８g/day during admission. The relationship between changes in systolic BP（SBP）during admission and clinical parameters at the time of admission was statistically analyzed. Results : Mean SBP in the sodium-restricted patients was significantly reduced during admission（ from １３０．２±１６．１ to １２２．７±１３．９ mmHg, p＜０．０１）. Multiple regression analysis showed that serum creatinine levels and presence of hypertension were inversely associated with and that initial SBP value was positively associated with the change in SBP. On the other hand, no glycemic parameters, including fasting plasma glucose levels, HbA１c, M values calculated from daily blood glucose profile, duration of T２DM and duration of hospitalization, were associated with the change in SBP. Conclusion : Sodium restriction-induced BP reduction in T２DM patients was associated with presence of hypertension, serum creatinine levels and initial SBP values. Sodium restriction is a useful treatment for T２DM patients regardless of their glycemic condition