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101.
NC Mkandawire E Chipofya G Likoleche M Phiri L Katete 《Malawi medical journal : the journal of Medical Association of Malawi》2003,15(3):99-101
The efficacy of the Ponseti method of clubfoot treatment at Queen Elizabeth Central Hospital (QECH) was analysed from December 2000 to December 2001. Ninety one patients, 60 boys and 31 girls were prospectively and consecutively enrolled. 31 patients had a unilateral clubfoot and 60 had bilateral clubfeet. 77 patients had primary idiopathic clubfoot and 14 patients had clubfeet associated with other congenital anomalies such as arthrogryposis. 32 patients (35%) were lost to follow up; records were inadequate for 6 patients leaving 54 patients (59%) available for analysis. Three main groups were assessed. Group 1 (24 patients): virgin previously untreated primary idiopathic clubfeet: Ponseti method used from outset. Group 2 (19 patients): complex, primary idiopathic clubfeet: Ponseti method introduced after other manipulation techniques. Group 3 (11 patients): clubfeet associated with other congenital anomalies. In group 1, the mean age at start of treatment was 9.7 weeks and the mean time to correction of deformity was 7.4 weeks. 20 out of 24 patients (84%) had correction of deformity and remained corrected. 4 patients had recurrence of deformity mainly due to non compliance with treatment and correction was achieved once treatment restarted. In group 2, 19 patients had been on treatment for a mean period of 32 weeks prior to commencement of Ponseti treatment. In 17 of these patients the deformity was still uncorrected. Ponseti treatment was commenced at a mean age of 36 weeks and correction was achieved in all 17 patients after a mean treatment duration of 7.1 weeks. In group 3, correction of deformity was initially achieved in only 60%. The period to achieve correction was long and incidence of recurrence of deformity was high.The success of conservative treatment of clubfeet using the Ponseti method has resulted in large decrease in the number of surgical procedures performed under general anaesthaesia such as posteromedial releases in the treatment of clubfeet at QECH. This method has now been adopted as the Standard treatment of clubfoot and is being advocated nationwide. 相似文献
102.
Gene Probe Analysis in an Informative Family with Multiple Endocrine Neoplasia Syndrome Type 2A (MEN 2A). Improvement in Carrier Risk Estimation 总被引:2,自引:0,他引:2
MORRISON PJ; HADDEN DR; HUGHES AE; KENNEDY L; RUSSELL CJF; NEVIN NC 《QJM : monthly journal of the Association of Physicians》1991,80(1):597-603
Gene probe analysis of the MEN 2A locus on chromosome 10 hasbeen undertaken using the markers TB10.163, RBP 3 and TB14.34in a large kindred with familial medullary thyroid carcinomas,with or without phaeochromocytomas or primary hyperparathyroidism.A maximum LOD score of 2.97 gave strong evidence of close linkagewith zero recombination. For 12 members of the family so far not known to be affectedby any form of the disease the estimated risk of carrying thegene has been considerably decreased in all but one, whose riskhas been greatly increased. 相似文献
103.
104.
Paton NI; Cheong IK; Kong NC; Segasothy M 《QJM : monthly journal of the Association of Physicians》1996,89(7):531-538
To determine the incidence, types and risk factors for infection in
systemic lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we
retrospectively reviewed the medical records of 102 patients with definite
SLE attending a specialist clinic. Details of major infections (pneumonia
or severe infection requiring intravenous therapy) and minor infections,
and their time of onset in relation to immunosuppressive therapy and
disease flares were recorded. There were 77 major and 163 minor infections
during 564 patient-years of follow-up. In the month following a course of
pulse methylprednisolone, the incidence of major infection was 20 times
higher and the incidence of minor infection was 10 times higher than at
other periods (p<0.0001). In the month after disease flare, the
incidence of major infection was 10 times higher and the incidence of minor
infection six times higher than at other times (p<0.0001). After
allowing for methylprednisolone therapy and disease flares, there was no
increase in the rate of infections during treatment with azathioprine, oral
or intravenous cyclophosphamide. There was no effect of renal involvement
on infection rate.
相似文献
105.
Detection of fetal red cells in fetomaternal hemorrhage using a fetal hemoglobin monoclonal antibody by flow cytometry 总被引:4,自引:0,他引:4
BACKGROUND: The laboratory determination of the level of fetal cells in maternal circulation remains an important support in the obstetrical management of women with suspected uterine trauma and in the proper dose administration of anti-D for prevention of Rh hemolytic disease of the newborn. Limitations in the sensitivity and precision of the widely used manual Kleihauer-Betke test have prompted an increased utilization of flow cytometric methods for fetal cell detection in maternal blood samples. STUDY DESIGN AND METHODS: Murine monoclonal antibodies directed against fetal hemoglobin (HbF) were developed, conjugated to fluorescein isothiocyanate, and used in a multiparametric flow cytometric assay developed for the quantitation of fetal red cells. A rapid intracellular staining method using brief glutaraldehyde fixation and Triton X-100 permeabilization prior to monoclonal antibody incubation was developed, along with optimization of the flow cytometric analysis protocol for the analysis of 50,000 cells. The performance of the assay was assessed for linearity and precision and correlated with the Kleihauer-Betke acid elution method. RESULTS: The anti-HbF flow cytometric method showed good correlation with the Kleihauer-Betke method (r2 = 0.86) and superior precision with a CV < 15 percent for blood samples with > 0.1 percent fetal cells. Analysis of 150 blood samples from nonpregnant adults, including individuals with elevated HbF due to hemoglobinopathies and hereditary persistence of HbF, gave a mean value of 0.02 percent fetal cells, and all results were less than 0.1 percent. CONCLUSIONS: The anti-HbF flow cytometric method for detection of fetal cells offers a simple, reliable, and more precise alternative to the Kleihauer-Betke manual technique for the assessment of fetomaternal hemorrhage. The method has additional potential applications for the study of HbF levels or frequency of adult red cells with low levels of HbF (F cells) in individuals with hemoglobinopathies. 相似文献
106.
Hideshima T Chauhan D Hayashi T Podar K Akiyama M Gupta D Richardson P Munshi N Anderson KC 《Molecular cancer therapeutics》2002,1(7):539-544
Stromal cell-derived factor (SDF)-1alpha mediates migration of normal hematopoietic stem cells, but its role in hematological malignancies is undefined. In this study, we detected SDF-1alpha in bone marrow (BM) plasma from 10 patients with MM (multiple myeloma; 2.6 +/- 1.5 ng/ml) and BM stromal cell culture supernatants from 5 patients with MM (0.6 +/- 0.2 ng/ml). We show that SDF-1alpha promotes proliferation, induces migration, and protects against dexamethasone-induced apoptosis in MM cells, but these effects are only modest. In MM cell lines and patient MM cells, SDF-1alpha induces phosphorylation of p42/44 mitogen-activated protein kinase, as well as Akt and its downstream target Bad, and also activates nuclear factor-kappaB. In the BM milieu, SDF-1alpha up-regulates secretion of interleukin 6 and vascular endothelial growth factor in BM stromal cells, which promote tumor cell growth, survival, and migration. These data demonstrate that SDF-1alpha promotes growth, migration and drug resistance of MM cells in the BM microenvironment, but these effects are only modest, SDF-1alpha therefore does not represent a target for novel therapeutics in this disease. 相似文献
107.
Expression of a free gamma heavy chain in serum following autologous stem cell transplantation for IgG kappa multiple myeloma 总被引:1,自引:0,他引:1
A 41-year-old male with IgG kappa multiple myeloma is described. He developed a free gamma heavy chain without an accompanying light chain following high-dose chemotherapy and autologous peripheral blood stem cell transplantation. The free gamma heavy chain was detected in serum and urine specimens 2 months after transplant, and eventually evolved into an IgG kappa monoclonal protein with electrophoretic properties similar to the original myeloma protein. Although the origin of the free gamma heavy chain remains uncertain, it was most likely related to the underlying plasma cell malignancy and, therefore, was an early sign of disease relapse. 相似文献
108.
Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance 总被引:3,自引:2,他引:3
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Chauhan D Li G Hideshima T Podar K Mitsiades C Mitsiades N Catley L Tai YT Hayashi T Shringarpure R Burger R Munshi N Ohtake Y Saxena S Anderson KC 《Blood》2003,102(9):3379-3386
Smac, second mitochondria-derived activator of caspases, promotes apoptosis via activation of caspases. Heat shock protein 27 (Hsp27) negatively regulates another mitochondrial protein, cytochrome c, during apoptosis; however, the role of Hsp27 in modulating Smac release is unknown. Here we show that Hsp27 is overexpressed in both dexamethasone (Dex)-resistant multiple myeloma (MM) cell lines (MM.1R, U266, RPMI-8226) and primary patient cells. Blocking Hsp27 by an antisense (AS) strategy restores the apoptotic response to Dex in Dex-resistant MM cells by triggering the release of mitochondrial protein Smac, followed by activation of caspase-9 and caspase-3. Moreover, AS-Hsp27 overcomes interleukin-6 (IL-6)-mediated protection against Dex-induced apoptosis. These data demonstrate that Hsp27 inhibits the release of Smac, and thereby confers Dex resistance in MM cells. 相似文献
109.
110.
T Hideshima F Cottini H Ohguchi J Jakubikova G Gorgun N Mimura Y-T Tai N C Munshi P G Richardson K C Anderson 《Blood cancer journal》2015,5(5):e312
Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities. 相似文献