Systematic review and assessment of systematic reviews examining the effect of periodontal treatment on glycemic control in patients with diabetes.

OBJECTIVES: There have been several systematic reviews(SRs) on whether periodontal treatment for an individual with both periodontal disease and diabetes can improve diabetes outcomes. The purpose of this investigation was to conduct a systematic review (SR) of previous meta-analyses, and to assess the methodological quality of the SRs examining the effects of periodontal treatment and diabetes. (PROSPERO Registration # CRD 42015023470). STUDY DESIGN: We searched five electronic databases and identified previous meta-analyses of randomized controlled trials published through July 2015. In cases where the meta-analysis did not meet our criteria, the meta-analyses were recalculated. General characteristics of each included trial were abstracted, analyzed, and compared. The mean difference, 95% confidence intervals (CIs) and the I2 statistic were abstracted or recalculated. The Assessment of Multiple Systematic Reviews Instrument (AMSTAR) was used to assess methodological quality. RESULTS: Of the 475 citations screened, nine systematic reviews were included. In total, 13 meta-analyses included in nine SRs were examined. In comparability analyses, meta-analyses in four SRs did not meet our criteria, and were recalcuated. Of these 13 meta-analyses, 10 suggested significant effects of periodontal treatment on HbA1c improvement. Mean differences found in the 13 meta-analyses ranged from -0.93 to 0.13. AMSTAR assessment revealed six SRs with moderate and three with high overall quality. CONCLUSIONS: We can conclude that there is a significant effect of periodontal treatment on improvement of HbA1c in diabetes patients, although the effect size is extremely small. In addition to the small effect size, not all SRs could be considered of high quality.

[The effect of celiprolol hydrochloride for lipid metabolism--especially for the low density lipoprotein particle size].

Recently, much attention has been paid to small sized low density lipoprotein (LDL) as a risk factor for ischemic heart disease. We investigated the effect of celiprolol hydrochloride (CH), which is a beta 1 selective beta-blocker with high intrinsic sympathomimetic activity (ISA), on the LDL particle size. We treated 41 hypertensive patients with CH and studied the change in LDL particle size according to the score of fast beta lipoprotein and LDL relative mobility value (LDL-Rm) measured by lipoprotein polyacrylamide gel disc electrophoresis (PAGE). We also studied changes in blood pressure, total cholesterol (TC), trygiyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and midband on PAGE. Systolic and dyastolic blood pressure and pulse significantly decreased during treatment. TC levels were significantly decreased at 8 weeks in all subjects and at 4, 8 and 12 weeks in patients with a TC value of over 220 mg/dl. TG levels were significantly decreased at 4 and 8 weeks in patients with initial levels of over 150 mg/dl, and significantly increased at 4 and 8 weeks in those with initial levels of under 150 mg/dl of TG. HDL-C levels did not significantly change during treatment. LDL-C levels were significantly decreased at 4, 8 and 12 weeks in patients with initial levels of over 150 mg/dl. Apo AI, AII, B, CII, CIII and E levels did not significantly change during treatment. Fast beta lipoprotein scores did not significantly change overall during treatment, but were significantly decreased at 4 and 8 weeks in patients initial TG levels of over 150 mg/dl and at 4 and 12 weeks in those with initial levels of over 220 mg/dl of TC. LDL-Rm scores did not significantly change during treatment. Midband scores were significantly reduced overall at 8 weeks, and after 4 and 8 weeks in patients with initial TG levels of over 150 mg/dl and at 4, 8 and 12 weeks in those with initial TC levels of over 220 mg/dl. These results indicated that CH did not change LDL particle size. It was suggested that CH might be a beneficial beta-blocker from the standpoint of prevention for atherosclerosis.

1H-NMR investigation of the influence of the heme orientation on functional properties of myoglobin.

There are two interconverting forms of myoglobin, which differ in the orientation of the heme by a 180 degrees rotation around the alpha,gamma-meso axis; the proteins possessing the same heme orientation, as found in the single crystal, and the reversed heme orientation are called the major and minor forms, respectively. Structures and functional properties of these two forms have been investigated by NMR. Heme peripheral side-chain and non-coordinated amino acid proton resonances of the minor form in its met-cyano form have been assigned and the comparison of the shift between the corresponding resonances of the two forms revealed that the heme electronic structure is not largely influenced by the heme rotation. On the other hand, the exchange rate of His E7 NepsilonH proton of the minor form is larger by a factor of 3-5 than that of the major one, indicating that the stability of the hydrogen bond between Fe-bound ligand and His E7 is slightly weaker in the minor form that in the major one. The rate of autoxidation of oxy-myoglobin and azide affinity of met-aquo myoglobin were also found to depend on the orientation of the heme.

Magnetic resonance imaging of reticulo-endothelial system in patients with idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is characterized by accelerated platelet destruction in the reticulo-endothelial system (RES). We performed magnetic resonance imaging (MRI) to estimate the degree of activated RES. MRI was performed with a Gyroscan S-15 (1.5 tesla) in 7 healthy volunteers and 22 patients with ITP. The 22 patients included 19 who were at initial diagnosis or were nonresponders to the therapy (non-DX group), and 3 who were responders. For the non-DX group, the T1 relaxation time of the spleen was initially significantly shorter than for healthy volunteers, but normalized after responding to the therapy. The initially shorter T1 values of the spleen for ITP patients correlated with a low platelet count (P < 0.05). This condition may indicate foam cells or fatty components due to platelet destruction. There was no significant relationship between the sequestration in (111)In-scan and T1 values of the liver or spleen. However, MRI is a noninvasive method, and it may be a clinically useful tool in the evaluation of RES in patients with ITP.

[First example of Hb lepore Washington-Boston trait in a Japanese].

An abnormal hemoglobin (Hb) found in a 63-year-old Japanese woman presenting with asymptomatic chronic microcytic anemia was extensively characterized by the conventional protein chemistry, restriction mapping of the genomic DNA with Bgl II digestion, and direct sequencing of a relevant segment of the mutant non-alpha-globin gene. The results identified a hybrid globin with delta- and beta-like sequences, from position 1 to 87 and from 105 to 146 (C-terminal), respectively. The delta beta fusion gene was produced by deletion of 7.4 kb involving parts of the two closely linked genes. The break point was somewhere within the homologous 58 bps, from codon 88 to IVS-II-7. The same deletion had repeatedly been reported in Hb Lepore Washington-Boston. The expression of a mild (delta beta)(+)-thalassemia trait in the present case completely agreed with previous reports on representative Hb Lepore heterozygotes. The basis for the activity of Hb Lepore gene which is several times higher than the delta-globin gene was discussed.

Changes in urinary nitrate and nitrite during treatment of ulcerative colitis.

The urinary excretion rates of nitrate (NO3) and nitrite (NO2) were monitored in 14 patients with active ulcerative colitis during treatment using hydrocortisone and sulfasalazine. During the active phase of the disease, the NO3 excretion was significantly higher in the patients than in healthy controls (n = 6, p < 0.05), although it varied considerably among the patients. During the healing phase, the NO3 excretion decreased concurrently with improvement of symptoms and colorectal ulceration, but the NO2 excretion increased. During the inactive phase of the disease, the NO3 and NO2 excretions were significantly lower than during the active phase, and the NO2/NO3 ratio resembled that in the healthy controls. In contrast, a patient who failed to respond to treatment showed continuously high NO3 and NO2 excretion rates. These results indicate that urinary NO3 and NO2 excretions vary with the disease state in ulcerative colitis.

[Prostaglandin E1 bladder instillations for late-onset hemorrhagic cystitis following allogeneic bone marrow transplantation].

Between July, 1990 and March, 1994, 31 patients with hematological malignancies or severe aplastic anemia underwent allogeneic bone marrow transplantation (BMT) at the Second Department of Internal medicine, Chiba University Hospital. Among the 29 evaluable patients who survived over 100 days after transplant, 11 patients (37.9%) developed late-onset hemorrhagic cystitis with a median time of onset of 57 days (range 11-205) from BMT. Adenovirus type 11 was isolated from the urine of 4 patients. Five patients recovered with fluid hydration and forced diuresis, while 6 patients had persistent gross hematuria with clot formation, 5 of whom also developed hydronephrosis. Seven-day courses of 500 micrograms prostaglandin E1 (PGE1) bladder instillations was initiated to control hematuria in these 6 patients. Complete resolution of gross hematuria was achieved in 4, and partial response with decreased clot formation and partial clearing of the urine was observed after 4 of 9 courses of the treatment. Although all patients experienced bladder spasm or lower abdominal pain during the PGE1 instillations, these symptoms were manageable with sedative drugs and morphine. No systemic side effect was apparent. PGE1 bladder instillations is a safe and useful treatment for severe, life-threatening late-onset hemorrhagic cystitis after allogeneic BMT.

Estimation of the total saliva volume produced per day in five-year-old children.

Fifteen boys and 15 girls were asked to record for 2 days the time spent awake, eating meals or snacks, and sleeping. The salivary flow rates elicited by chewing foods were also determined. The mean flow rate (+/- SD) of unstimulated saliva was 0.26 +/- 0.16 ml/min and that of saliva while chewing six different foods was 3.6 +/- 0.8 ml/min. The mean times spent eating, and awake but not eating, were 80.8 +/- 27.3 and 820 +/- 59 min, respectively, and the volumes of saliva produced during those periods would average about 288 and 208 ml, respectively. If the flow rate is virtually zero during sleep, the estimated total salivary volume produced per day is calculated to be about 500 ml.

Matrix mineralization and the differentiation of osteocyte-like cells in culture.

Osteocyte-like cells were prepared by sequentially treating calvaria from newborn rats with collagenase and chelating agents. On a reconstituted gel of basement membrane components, cells from the third collagenase digest displayed a round shape and expressed the highest level of alkaline phosphatase with minimal osteocalcin deposition into the matrix. On the other hand, cells derived from the interior after EDTA treatment exhibited well-developed dendritic cell processes and expressed essentially no alkaline phosphatase. The latter population also showed quite distinct characteristics such as higher extracellular activities of casein kinase II and ecto-5'-nucleotidase and the extracellular accumulation of a large amount of osteocalcin associated with mineral. These diverse phenotypic and protein expressions as well as the sites from which each population of cells were recovered strongly suggest that we have isolated osteoblastic and osteocytic cells. Bone sialoprotein II was extracellularly phosphorylated by casein kinase II in osteocytic cells but not in osteoblastic cells. We discuss the possibility that differentiation of young osteocytes from osteoblasts may facilitate the biochemical sequence of mineral deposition in the bone matrix.

[A trial use of prostaglandin E1 for prevention of hepatic veno-occlusive disease after allogeneic bone marrow transplantation].

We performed retrospective analysis of hepatic veno-occlusive disease (VOD) in 57 cases with leukemia after allogeneic bone marrow transplantation (BMT). Prostaglandin E1 (PGE1) was used to prevent VOD in 8 cases at a dose of 0.3 micrograms/kg/hr from day -8 to day 30. No VOD was noted in the PGE1 group, while the incidence of VOD was 8/49 (16.3%) in the non PGE1 group. In twelve patients with pretransplant liver dysfunction, VOD was noted in 0/3 in the PGE1 group and 4/9 (44.4%) in the non PGE1 group, respectively. However, prophylactic effects of PGE1 on VOD is not significant in this study, so further studies are needed to determine the efficacy of PGE1. One of 8 patients with PGE1 prophylaxis had edema and erythema on extremities, however, severe toxicity was not experienced.

[A combination chemotherapy of mitoxantrone, etoposide, carboplatin, and prednisolone (MECP) in recurrent or refractory non-Hodgkin's lymphomas].

Twenty-two patients with recurrent or refractory non-Hodgkin's lymphoma were treated with a combination chemotherapy of mitoxantrone, etoposide, carboplatin, and prednisolone (MECP). Of 22 evaluable patients, 11 (50%) responded to MECP and 7 (32%) achieved complete remission. Particularly in relapsed cases, 9 (75%) responded and 6 (50%) achieved complete remission. Myelosuppression was the major toxicity. Thirteen patients (59%) experienced WBC counts under 1,000/microliters, and thrombocytopenia under 50,000/microliters was seen in 12 patients (55%). During myelosuppression, 2 patients developed sepsis and 1 showed intestinal bleeding. Other gastrointestinal toxicities were well tolerated. There was no death due to chemotherapy. These results show that MECP is a well-tolerated treatment regimen, and effective for recurrent or refractory non-Hodgkin's lymphomas.

[Prostaglandin E1 bladder instillations for a patient with severe hemorrhagic cystitis after allogeneic bone marrow transplantation].

A 39-year-old female with AML (M2) underwent allogeneic bone marrow transplantation (BMT) on July 8th, 1991. The post transplantation course had been going well until day 85 post BMT, when severe hemorrhagic cystitis with right hydronephrosis and ureter stenosis developed. Adenovirus type 11 was isolated from the urine. She received instillations of prostaglandin E1 (PGE1) directly into the bladder after the appearance of clots in the urine. Complete resolution of hematuria was obtained by two courses of this treatment. PGE1 bladder instillations seem to be effective for the control of hematuria caused by severe hemorrhagic cystitis after BMT.

[Chromosomal abnormalities in Castleman's disease with high levels of serum interleukin-6].

Chromosomal abnormalities in Castleman's disease with high levels of serum IL-6 were reported. A 69-year-old male was found to have superficial lymph node swelling and polyclonal hypergammaglobulinemia, when he was admitted to the department of otolaryngology for carcinoma of the tongue in July 1991. In December, he was referred to our department after completing radiation therapy. Laboratory examination revealed 7.7 g/dl hemoglobin, 10.8 g/dl total protein, and 56.0% gamma-globulin. Serum electrophoresis revealed polyclonal hypergammaglobulinemia and no Bence-Jones protein. Bone marrow aspirates showed an increase of plasma cells to 21.8%. Serum IL-6 was 252 pg/ml. Chromosomal analysis of cells in the lymph node showed a karyotype of 46,XY,t(7;14)(p22;q22). The lymph node histology showed marked hyperplasia of plasma cells at interfollicular areas. These plasma cells were stained with both anti-kappa and anti-lambda antibody. He was diagnosed as multicentric form Castleman's disease. Treatment with prednisolone and melphalan resulted in improvement of clinical findings such as anemia, lymph node swelling and hypergammaglobulinemia in concurrence with decrease in serum levels of IL-6. Since the IL-6 gene is located on 7p21-22, the translocation 7; 14 may be related to the high level of serum IL-6.

A simple chemiluminescence method for measuring oxygen-derived free radicals generated in oxygenated rat myocardium.

We have developed a simple and reproducible method employing chemiluminescence to measure oxygen-derived free radicals generated in oxygenated myocardium. Isolated perfused rat hearts were frozen in liquid nitrogen during the control perfusion (non-ischemia), after 30 min of global ischemia (ischemia), or after 20 min of reperfusion following 30-min global ischemia (reperfusion). The frozen hearts were ground to a fine powder and then oxygenated by mixing with phosphate-buffered saline (PBS) (pH 7.4 and PO2 183-194 mmHg) containing lucigenin. The mixed solution was injected into a chemiluminescence detection flow cell. The chemiluminescence intensity increased in relation to the lucigenin and myocardium contents of the test solution. However, it was not affected by the temperature of PBS in the range of 25 degrees C to 50 degrees C. The chemiluminescence intensity of ischemic myocardium was 2.5 times larger than that of non-ischemic or reperfused myocardium (P < 0.01). Recombinant human superoxide dismutase (r-h-SOD) reduced dose-dependently the chemiluminescence intensity induced by oxygenation of ischemic myocardium, while chemically inactivated r-h-SOD did not.

[Cyclosporine-induced graft-versus-host disease in a syngeneic bone marrow transplantation].

A 33-year-old woman with AML (M4) resistant to chemotherapy received syngeneic marrow graft from her identical twin following high dose busulfan and etoposide. However, the relapse was confirmed on the 60th day after the procedure. Since she failed to achieve remission despite intensive chemotherapy, a second BMT from the same donor was performed following total body irradiation and high dose etoposide on the 126th day after the initial BMT. At this time, cyclosporine (1 mg/kg/day) was administered to induce graft-versus-host disease (GVHD). Skin rash appeared on the 18th day after the 2nd BMT, and biopsy from the rash on the 23rd day showed a typical picture of cutaneous GVHD (grade 2) and there was no evidence of viral infection. On the 36th day after the 2nd BMT, the patient died of veno-occlusive disease. Although graft-versus-leukemia effect in this patient could not be evaluated because of early death, the induction of GVHD with cyclosporine might be effective to reduce the relapse rate after syngeneic or autologous BMT. Further studies are required to confirm this effect.

[Multiple myeloma in a patient in remission from malignant lymphoma].

A 71-year-old man was admitted because of right cervical lymph node swelling in February 1986. Lymph node biopsy revealed that he suffered from diffuse, large cell malignant lymphoma. Immunological staining showed lymphoma characterized by B cell markers, IgG, kappa type. Bone marrow aspiration, revealed no evidence of lymphoma and 0.2% plasma cells. The clinical stage was IIA. The patient was treated with the CHOP regimen (doxorubicin, cyclophosphamide, vincristine and prednisolone), which achieved complete remission. In October 1988, he was re-admitted because of a subcutaneous abscess, and biopsy of the inguinal lymph node showed reactive lymphadenitis. Although he improved with antibiotic therapy, laboratory date on admission showed monoclonal gammopathy. Serum immunoelectrophoresis demonstrated a monoclonal bow of IgA kappa type, and bone marrow aspiration revealed hypercellularity with an increased number of plasma cells (76.8%). The patient was diagnosed as having multiple myeloma, and combination chemotherapy was begun. He now attends the out-patient department at our hospital. The development of multiple myeloma has not been reported previously during a course of malignant lymphoma. Although the association of these two B cell neoplasias was unknown, in this case both showed the characteristic of kappa type light chains. This case may provide information concerning tumor cell origin.

Nonenzymatic glycation alters properties of collagen as a substratum for cells.

Acid-soluble collagen from rat skin was glycated in vitro by incubating with 0.2 M D-ribose at 37 degrees C for several days, and properties of the glycated collagen as a substratum for fibroblasts 3 Y 1 were studied. The cells attached but spread poorly on the glycated collagen as compared with on the untreated collagen. Thymidine incorporation by the cells on the glycated collagen was higher than that by the cells on untreated collagen. These results indicate that the glycation significantly alters properties of collagen as a substratum for cells.