The influence of torque and manual glide path on the defect or separation rate of NiTi rotary instruments in root canal therapy.

INTRODUCTION: One of the effecting factors in prognosis of root canal therapy is accidental procedure as broken files that may be unpreventable. Many manufacturers have designed and marketed various electromotors that can control rotational speed and torque. On the other hand, some studies have recommended applying a manual glide path to diminish contact area between the file and canal walls. The purpose of this study was evaluation of the effect of torque and a manual glide path on defects as separation of Nickel-titanium (NiTi) rotary files. MATERIALS AND METHODS: This ex vivo randomized controlled trial study was carried out on 160 canals of human's matured molars with mild curvature (15-338). After initial preparation of samples and checking for inclusion criteria, in first group, preparation was carried out with air-driven handpiece, and in group two, Endo IT was used as electromotor. In both groups, Mtwo files with simultaneous technique were used for preparation. Then all data were collected and analyzed with Mann Whitny, Mantel Cox, and t-test. RESULTS: No significant differences between two groups (P < 0.05) were observed. Based on survival analysis, safety probability of files after preparation of nine canals is 64% in group one and 69.9% in group two. There was no significant differences between this safety probability in two groups (P = 0.272). CONCLUSION: Usage of torque control handpiece is not an important factor, comparing instrumentation technique.

Functional phenotyping and genotyping of circulating tumor cells from patients with castration resistant prostate cancer.

Circulating tumor cells (CTCs) hold promise for studying advanced prostate cancer. A functional collagen adhesion matrix (CAM) assay was used to enrich CTCs from prostate cancer patients' blood. CAM ingestion and epithelial immuno-staining identified CTCs, which were genotyped using oligonucleotide array comparative genomic hybridization. The highest CTC counts were observed in men with metastatic castration resistant prostate cancer (CRPC) compared to castration sensitive prostate cancer. Copy number profiles for CRPC CTCs were similar to paired solid tumor DNA, and distinct from corresponding DNA from the residual CAM-depleted blood. CAM CTC enrichment may allow cellular and genetic analyses in prostate cancer.

Lack of association between hyperprolactinemia and colon carcinoma.

Two recent studies reported that many patients with colorectal carcinoma have elevated serum prolactin (PRL) concentrations and have suggested ectopic PRL secretion as the cause. In the present study, serum PRL was minimally elevated in 16 of 116 colon cancer patients and 2 of 25 control subjects; medications or chemotherapy appeared to be responsible for the PRL elevations in 11 of 16 cancer patients. Serum PRL was not correlated with either plasma carcinoembryonic antigen or disease stage. Preoperative and postoperative serum PRL concentrations were similar in 26 evaluated patients. None of 19 colorectal tumors was positive for PRL staining by immunohistochemistry. Thus, we could not confirm previous reports of frequent hyperprolactinemia in patients with colorectal cancer; factors such as medications, anxiety, pain, and nausea may have raised serum PRL in these earlier studies. Serum PRL is not a useful marker for colon carcinoma, at least in patients in the United States.

Pseudopulmonary embolism: acute respiratory distress in the syndrome of heparin-induced thrombocytopenia.

A 73-year-old man with myasthenia gravis was treated with daily plasmapheresis. During the course of treatment, the patient developed progressive thrombocytopenia and an episode of severe acute respiratory distress suggesting pulmonary embolism. The thrombocytopenia and respiratory impairment improved after discontinuation of heparin, and both recurred on heparin rechallenge. The presence of heparin-specific antibodies was confirmed by in vitro assay. The time frame of clinical events suggests a heparin-mediated mechanism for both the thrombocytopenia and respiratory compromise. We conclude that acute respiratory distress may be the presenting manifestation of the syndrome of heparin-associated thrombocytopenia in patients treated with dialysis or apheresis.

Elevated plasma stromelysin levels in arthritis.

OBJECTIVE: To determine whether plasma concentrations of stromelysin-1 and gelatinase A are increased in patients with various forms of arthritis. METHODS: A sensitive and specific sandwich enzyme linked immunosorbent assay (ELISA), which employs a murine monoclonal antibody and a rabbit polyclonal antibody to human stromelysin-1, was used to measure plasma stromelysin-1 in 53 healthy subjects, 113 patients with various forms of arthritis and connective tissue diseases, and 65 patients with cancer. Gelatinase A was also measured in these patients using specific polyclonal and monoclonal antibodies to gelatinase A in an ELISA: RESULTS: The plasma concentration of stromelysin-1 (X +/- SEM) was significantly increased (p < 0.001) in patients with rheumatoid arthritis (RA) (187 +/- 14 ng/ml) and systemic lupus erythematosus (SLE) (258 +/- 35 ng/ml) as compared to both healthy control subjects (50 +/- 4 ng/ml) or patients with cancer (61 +/- 20 ng/ml). Plasma stromelysin-1 was also significantly increased in smaller groups of men with osteoarthritis (OA) and gout. In contrast, plasma concentrations of gelatinase A were not significantly increased in patients with RA, OA or gout. In healthy subjects, the concentration of stromelysin-1 was significantly higher in men than women. No correlation was noted between plasma stromelysin-1 levels and age. CONCLUSION: The detection of elevated plasma levels of stromelysin-1 in patients with RA is consistent with increased stromelysin-1 concentrations in inflamed synovial tissues in this disease. The origin of increased plasma stromelysin-1 in SLE is speculative. Measurement of plasma stromelysin-1 may be useful in the diagnosis and management of patients with various forms of arthritis.

Characteristics of human immunodeficiency virus and chlorpromazine induced antiphospholipid antibodies: effect of beta 2 glycoprotein I on binding to phospholipid.

OBJECTIVE: To investigate the nature of the target epitope for human immunodeficiency virus (HIV) and chlorpromazine (CPZ) induced antiphospholipid antibodies (aPL) by evaluating the effect of the aPL cofactor (beta 2 glycoprotein I) on phospholipid binding and to compare this with known binding patterns of infection induced and autoimmune aPL. METHODS: aPL positive sera from 17 patients with HIV and 16 patients with schizophrenia treated with CPZ were tested and compared with aPL positive sera from 20 patients with syphilis and 35 with autoimmune disease. Both the sera and either IgG fractions prepared by affinity chromatography or IgM fractions prepared by euglobulin precipitation and gel filtration were tested for binding to cardiolipin (CL) in ELISA in the presence and absence of purified human beta 2 glycoprotein I (beta 2-GPI). Competition studies evaluated biotinylated CPZ IgM aPL binding and the effect on this of added aPL, placental anticoagulant protein I--a phospholipid binding protein that inhibits autoimmune aPL--and CL vesicles. RESULTS: HIV IgG aPL binding to CL was inhibited by beta 2-GPI (51-53%), like syphilis IgG aPL and in contrast to autoimmune IgG aPL. CPZ IgM aPL, like autoimmune IgM aPL, bound more efficiently in the presence of beta 2-GPI, with binding increases of 31-149%. Binding of biotinylated CPZ IgM aPL to CL was competitively inhibited by autoimmune IgG aPL (47%) and CPZ aPL (92%) but not by HIV IgG aPL or normal IgG. Placental anticoagulant protein I and CL vesicles completely prevented binding of CPZ IgM aPL to CL (100 and 96% inhibition, respectively). CONCLUSIONS: Findings indicate that CPZ aPL resembles the autoimmune aPL, whereas aPL found in HIV infection do not appear to be of autoimmune type.

M(r) 92,000 type IV collagenase is increased in plasma of patients with colon cancer and breast cancer.

Overproduction of matrix metalloproteinases (MMPs) is a common characteristic of metastatic cancer cells. Since MMPs can be identified in plasma, we proposed that enhanced MMP-9 secretion by invasive cancer cells may be detected by plasma assay. To this end, we developed a specific sandwich enzyme-linked immunosorbent assay which uses two mouse monoclonal antibodies to human M(r) 92,000 type IV collagenase (MMP-9). The plasma concentration of MMP-9 (mean +/- SD) in 60 healthy subjects (9 +/- 11 ng/ml), 136 patients without cancer, and 179 patients with cancer of the lung, genitourinary tract, or lymphomas-leukemias did not differ significantly. In contrast, plasma MMP-9 was significantly increased (P < 0.01) in 122 patients with gastrointestinal tract cancer and breast cancer (18 +/- 23 and 21 +/- 22 ng/ml, respectively). Whereas carcinoembryonic antigen levels were significantly increased in patients with stage IV gastrointestinal cancer, MMP-9 concentrations were not significantly increased in patients with metastatic disease as compared to those with nonmetastatic cancer. Combining both assays improves sensitivity of detection of colon cancer. MMP-9 was also significantly increased during pregnancy which is consistent with the extensive ongoing tissue remodeling and the leaching of the tissue proteinase into plasma.

Type IV collagenase/gelatinase (MMP-2) is not increased in plasma of patients with cancer.

We have developed a sensitive and specific sandwich-type enzyme-linked immunosorbent assay to detect M(r) 72,000 type IV collagenase [matrix metalloproteinase 2 (MMP-2)] in human plasma. As a result of the linkage between MMP-2 production by cancer cells and the metastatic phenotype, we undertook this study to compare plasma MMP-2 levels in healthy individuals, patients with various types of cancer, and hospitalized patients with chronic diseases other than cancer. The results demonstrate that MMP-2 levels are not increased in cancer patients regardless of the extent of disseminated malignancy. In an effort to explain this data, we compared MMP-2 secretion by human umbilical vein endothelial cells and lung cancer cells passaged as cell lines. Endothelial cells secreted higher levels of MMP-2 than did lung cancer cells propagated in vitro. We propose that blood vessel lining cells make a sizable contribution to plasma levels of MMP-2 and may thereby obfuscate the detection of increased levels of MMP-2 originating from extravascular sources such as solid tumors.

Cyclosporine and prednisone therapy for pure red cell aplasia in patients with chronic lymphocytic leukemia.

We describe the characteristics of response to treatment with cyclosporine (CYA) plus prednisone in seven episodes of pure red cell aplasia (PRCA) in four patients with B cell chronic lymphocytic leukemia (CLL). Fourteen episodes of PRCA occurred in four patients with CLL. Eleven episodes were treated with conventional therapies which included an alkylating agent and prednisone. Four episodes that failed to respond to conventional therapies and an additional three episodes were treated with CYA and prednisone. Six of the seven episodes, including three of four which had failed conventional therapies, responded to CYA plus prednisone compared with six of eleven episodes treated with conventional therapies. Response to CYA and prednisone occurred without a reduction in leukemic mass. In contrast, PRCA remission did not occur until after leukemic mass reduction in three of four patients treated successfully with conventional therapies. Time to response was shorter (14 +/- 3 days) with CYA plus prednisone than with conventional therapies (154 +/- 97 days) in three of four patients. These results indicate that CYA plus prednisone is an effective therapy for the induction of remission from PRCA in patients with CLL.

Immunoassay of type IV collagenase/gelatinase (MMP-2) in human plasma.

We have developed a sensitive and specific sandwich type enzyme-linked immunosorbent assay (ELISA) to detect type IV collagenase (MMP-2) in human plasma which employs the combination of affinity purified rabbit polyclonal antibodies and mouse monoclonal antibodies to human MMP-2. The MMP-2 ELISA detects latent and activated MMP-2, MMP-2 complexed with TIMP and MMP-2 complexed with alpha 2 macroglobulin (65% efficiency). To determine whether physiologic conditions associated with increased connective tissue turnover are accompanied by increased MMP-2 levels in plasma, we compared enzyme levels in pregnant and nonpregnant women. Plasma MMP-2 (mean +/- standard deviation) was significantly increased (p less than 0.05) in the second half of pregnancy (650 +/- 312) as compared to early pregnancy (356 +/- 139) or the nonpregnant state (387 +/- 193). As a result of the linkage between type IV collagenase production by cancer cells and the metastatic phenotype, the assay of MMP-2 in plasma is of potential clinical value in cancer.

Proteinase-alpha 2 macroglobulin complexes are not increased in plasma of patients with cancer.

Alpha 2-macroglobulin, a major glycoprotein component of plasma, is unique in its capacity to bind and inhibit the proteolytic activities of all classes of proteinases. Since proteinases implicated in cancer dissemination (type-IV collagenase, plasminogen activator, cathepsins B) are normal constitutents of blood, we have explored the hypothesis that elevated tissue levels of activated proteinases bound to alpha 2M might be detected in plasma of patients with cancer. To test this premise, blood was collected from 149 subjects (33 healthy controls, 31 patients with infections and non-malignant diseases, 16 with myeloproliferative disease, 10 with gastrointestinal cancer, 7 with genito-urinary cancer, 16 with lung cancer, 14 with lymphoma, 11 with miscellaneous cancers and 11 with chronic lymphocytic leukemia and myeloma). Plasma was assayed for alpha 2M-proteinase complexes using a sandwich ELISA which employs a mouse monoclonal antibody (MAb) that binds to a neo-antigenic determinant on complexed alpha 2M and a rabbit polyclonal anti-native human alpha 2M antibody. The concentration of complexed alpha 2M in healthy controls was 14.2 +/- 9.8 micrograms/ml (mean +/- standard deviation). No significant differences in complexed alpha 2M were noted between normal and cancer groups (range 7.4-14.6 micrograms/ml). On the basis of these data, we propose that, in patients with cancer, activated proteinases are bound locally to inhibitors in the tissues and are not available to form complexes with plasma alpha 2M. An alternative explanation is that proteinases are not secreted in excess by cancer cells in vivo.

Second neoplasms in Hodgkin's disease: current controversies.

Aggressive, multimodal treatment of Hodgkin's disease has led to dramatic increases in survival but not without significant early toxicity and late complications. The most serious late complication is the development of a secondary neoplasm. These secondary cancers include acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, and various solid tumors.

Secretion of creatine kinase MB isoenzyme by an immature teratoma with predominant rhabdomyosarcomatous elements.

A 37-year-old man with metastatic immature (malignant) teratoma with prominent rhabdomyosarcomatous elements had markedly increased activity of creatine kinase (EC 2.7.3.2) MB in serum. There was no electrocardiographic evidence of infarction or ischemia, and autopsy revealed no myocardial infarction, significant coronary atherosclerosis, myocarditis, or invasion of the heart by tumor. A high proportion of the creatine kinase activity in a homogenate of the tumor was attributable to the MB isoenzyme. Persistent increases of creatine kinase-MB and an unusually high MB isoenzyme activity, out of proportion to total creatine kinase activity, may indicate a nonmyocardial origin of this isoenzyme.

Hemolytic uremic syndrome in a patient with small cell lung cancer.

Hemolytic uremic syndrome is a rare entity in patients with carcinoma and presents with a triad of renal insufficiency, microangiopathic hemolytic anemia, and thrombocytopenia. We report this syndrome for the first time in a patient with small cell lung carcinoma. Spontaneous platelet aggregation of washed normal platelets was demonstrated using patient plasma. Circulating immune complex levels were not elevated. The entity completely resolved after treatment with plasma, vincristine, aspirin, and dipyridamole.

Pregnancy outcome in cancer patients. Experience in a large cooperative group.

To evaluate the potential teratogenicity and mutagenicity of modern cancer treatment, the authors enumerated from a cooperative clinical trial group 133 pregnancies in 66 women with malignant neoplasms (53% with Hodgkin's disease, 26% with other lymphomas and leukemia, and 21% with solid tumors). The gestations were divided into the following groups: Group 1, 43 pregnancies ending before therapy; Group 2, therapy given at conception or during 32 pregnancies; and Group 3, 58 pregnancies after therapy. Although the total frequencies of abnormalities were similar in Groups 1 and 2 (23% of 35 pregnancies not electively aborted and 28% of 25, respectively), there were slightly more elective abortions and birth defects related to radiation exposure at a susceptible time of gestation in Group 2. Still, there were eight normal infants among the ten fetuses who were liveborn and had first trimester exposure to chemotherapy alone; so, drug therapy early in pregnancy is not inevitably teratogenic. The apparent and surprising excess of abnormal outcomes in Group 3, 40% of 50 pregnancies, was due to low birth weight and premature terminations of pregnancy, rather than an excess of congenital anomalies. The type of unfavorable outcomes in Group 3 and their concentration in the first year posttherapy suggested they could represent defects in factors (e.g., uterine or hormonal) that normally maintain gestations, and not genetic damage to oocytes. Limitations of the data, collected by mail from physicians and their patients, included biases of self-reporting and low statistical power. Prospective study, probably through interinstitutional collaboration, seems necessary, if accurate estimates are to be made of the frequency of certain outcomes, such as spontaneous abortion and minor anomalies.

Acute nonlymphocytic leukemia after thiotepa instillation into the bladder: report of 2 cases and review of the literature.

We report 2 cases of acute nonlymphocytic leukemia after thiotepa instillation into the bladder for superficial bladder carcinoma and review 4 additional cases from the literature. Intravesical thiotepa is absorbed systemically in patients with bladder carcinoma and such treatment may be associated with the rare occurrence of acute nonlymphocytic leukemia and/or the myelodysplastic syndrome.