Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 25
Filter
1.
Clin Radiol ; 72(3): 266.e1-266.e6, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28341031

ABSTRACT

AIM: To determine if the rate and timing of a second breast cancer event (SBCE) in women with a personal history of breast cancer varies by disease subtype or breast imaging method. MATERIALS AND METHODS: A retrospective review was performed of women with a SBCE from January 2006 to December 2010 at a single institution. Data analysed included oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status of the primary and second breast cancers; mammographic and ultrasound (US) features from SBCE; and the time interval between both events. RESULTS: Of 207 patients diagnosed with a SBCE, the median age at first diagnosis was 50.6 years, range 24.8 to 80.2; at second diagnosis was 56.2 years, range 25.8 to 87.9. Eleven percent of SBCE were diagnosed >10 years after the primary cancer diagnosis. The median time between the first and second diagnosis for ER-positive patients was 2.7 years (range 0.7-17.4 years); and 1.9 years for ER-negative patients, (range 0.4-23.4 years; p<0.002). Patients with triple-negative breast cancer (TNBC) had a shorter time between diagnoses than others (p=0.0003). At 3, 5, and 10 years, 85%, 92%, and 97% of ER-negative and 54%, 81%, and 95% of ER-positive tumours, respectively, had recurred. ER-negative tumours and TNBC were more likely to be visible at US. CONCLUSION: There may be a role for customised imaging surveillance of women with a personal history of breast cancer (PHBC) after 10 years. Further studies are necessary to determine if US may be valuable in the surveillance of patients with ER-negative and TNBC tumours.


Subject(s)
Breast Neoplasms/diagnostic imaging , Mammography/methods , Neoplasm Recurrence, Local/diagnostic imaging , Adult , Age Factors , Aged , Aged, 80 and over , Breast/diagnostic imaging , Breast Neoplasms/blood , Female , Follow-Up Studies , Humans , Middle Aged , Population Surveillance , Receptor, ErbB-2/blood , Receptors, Estrogen/blood , Receptors, Progesterone/blood , Reproducibility of Results , Retrospective Studies , Triple Negative Breast Neoplasms/diagnostic imaging , Ultrasonography, Mammary/methods , Young Adult
2.
Bone Marrow Transplant ; 52(1): 28-33, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27595282

ABSTRACT

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.


Subject(s)
Bendamustine Hydrochloride/administration & dosage , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Transplantation Conditioning/methods , Adult , Aged , Cyclophosphamide/administration & dosage , Disease-Free Survival , Female , Humans , Male , Middle Aged , Rituximab/administration & dosage , Survival Rate , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives
3.
Clin Radiol ; 71(6): 515-22, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27012496

ABSTRACT

AIM: To determine the ability of magnetic resonance imaging (MRI) in detecting tumour-free margins from the internal os (IO). MATERIALS AND METHODS: A database search yielded 79 women with early-stage cervical cancer who underwent radical hysterectomy and preoperative MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MRI in assessment of ≤5 and >5 mm IO involvement were calculated with histopathological surgical specimen findings considered to be the reference standard. A main and subset analysis was performed. The subset analysis included only those patients who would have been considered for radical trachelectomy. RESULTS: For predicting a distance between the tumour and the IO of ≤5 mm, MRI had a sensitivity of 73%, a specificity of 98.3%, a PPV of 95%, a NPV of 88.1%, and an accuracy of 89.8% for the main analysis, and sensitivity of 81.8%, a specificity of 93.2% a PPV of 69.2% a NPV of 96.5% and an accuracy of 91.4% for the subset analysis. CONCLUSION: MRI has high specificity, NPV, and accuracy in detecting tumour from the IO, making MRI suitable for treatment planning in patients desiring trachelectomy to preserve fertility.


Subject(s)
Cervix Uteri/diagnostic imaging , Cervix Uteri/pathology , Magnetic Resonance Imaging/methods , Margins of Excision , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/pathology , Adult , Cervix Uteri/surgery , Female , Humans , Image Interpretation, Computer-Assisted/methods , Neoplasm Grading , Preoperative Care/methods , Reproducibility of Results , Sensitivity and Specificity , Uterine Cervical Neoplasms/surgery , Young Adult
4.
Invest New Drugs ; 32(5): 969-75, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24875133

ABSTRACT

BACKGROUND: Melanoma cell lines treated with decitabine show upregulation of cancer antigens, and interferon-α upregulates MHC Class I antigens in cancer cells, leading to enhanced T-cell recognition and T-cell mediated tumor apoptosis. We evaluated the synergy between the hypomethylating effects of decitabine and the immunomodulatory effects of interferon in a combination regimen administered to advanced melanoma patients in a phase 1 trial. METHODS: Patients with one prior systemic therapy were eligible. Using a modified 3 + 3 design, patients received escalating doses of decitabine and pegylated interferon α-2b (PEG-IFN) during every 28-day treatment cycle. Global DNA methylation was measured on days 1 and 5 of cycles 1 and 3. Cytokine profiling and quantification of T-cell subpopulations by FACS were performed at baseline and cycle 3. RESULTS: Seventeen patients were assigned to one of four dose levels. Decitabine 15 mg/m2/d + PEG-IFN 3 µg/kg was the maximum tolerated dose (MTD). Grade 3/4 cytopenias were seen across all dose levels: anemia (1), neutropenia (7), and thrombocytopenia (2). One patient remained progression-free for 37 weeks. The other 16 patients progressed at or before 12 weeks. Median overall survival was 39 weeks. Hypomethylation was seen at all dose levels. Due to treatment-induced lymphocytopenia, absolute changes in T-cell populations post-treatment were too small to be meaningfully interpreted. CONCLUSIONS: The response to this combination regimen was characterized by significant myelosuppression, particularly neutropenia. Although disappointing efficacy and slow accrual led to early closure of the trial, hypomethylation showed pharmacodynamic evidence of a therapeutic effect of decitabine at all dose levels.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Melanoma/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/administration & dosage , Azacitidine/adverse effects , Azacitidine/analogs & derivatives , DNA Methylation , Decitabine , Female , Humans , Interferon alpha-2 , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Leukocyte Count , Male , Maximum Tolerated Dose , Melanoma/immunology , Melanoma/metabolism , Middle Aged , Neutropenia/chemically induced , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , T-Lymphocyte Subsets/immunology
5.
Br J Dermatol ; 169(3): 549-54, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23627639

ABSTRACT

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in the white population. It is an important driver of healthcare costs and causes significant morbidity. Topical imiquimod is a good noninvasive treatment alternative for surgical excision in superficial BCC (sBCC). However, there are currently no uniform histological definitions of sBCC. A definition based on tumour thickness might be a good alternative. OBJECTIVES: To determine whether tumour thickness in sBCC is a predictor of treatment failure. METHODS: We retrospectively examined 127 histological biopsy specimens of sBCC treated primarily with imiquimod five times a week for 6 weeks. Mean follow-up was 34 months (range 3-91). Recurrence was evaluated clinically with histological verification. RESULTS: Among nonrecurrent cases the median tumour thickness was 0·26 mm (range 0·09-0·61), while for recurrent cases the median tumour thickness was 0·57 mm (range 0·41-1·41, P < 0·0001). Among lesions ≤ 0·40 mm in thickness, none recurred, whereas for lesions > 0·40 mm the recurrence rate was 58% (P < 0·0001). CONCLUSIONS: We recommend the use of tumour thickness to define the superficial pattern in pathology reports for BCC as this can help to determine treatment response of sBCC to imiquimod.


Subject(s)
Aminoquinolines/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Basal Cell/drug therapy , Skin Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/pathology , Female , Humans , Imiquimod , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Skin Neoplasms/pathology , Treatment Failure , Treatment Outcome
6.
Breast Cancer Res Treat ; 131(1): 41-8, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21331622

ABSTRACT

Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I-III MSC of the breast were patient age > 50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I-II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥ 95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I-III MSC had decreased disease-free survival (two-sided log rank, P = 0.018). Five-year disease-free survival was 44 ± 8% versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.


Subject(s)
Breast Neoplasms/pathology , Metaplasia/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Disease-Free Survival , Female , Humans , Metaplasia/therapy , Middle Aged , Neoplasm Metastasis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism
7.
Spinal Cord ; 47(6): 496-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19172154

ABSTRACT

STUDY DESIGN: Cross-sectional pilot study. OBJECTIVES: To explore correlates of body image among women with spinal cord injury (SCI), within the framework of Cash's cognitive behavioral model of body image. SETTING: Hamilton, Ontario, Canada. METHODS: Women with SCI (N=11, 64% with tetraplegia) reported their functional and appearance body image (Adult Body Satisfaction Questionnaire). A 3-day recall of leisure time physical activity (LTPA), three measures of body composition (that is, weight, waist circumference, body fat) and several demographic variables were assessed as potential correlates. RESULTS: Appearance satisfaction was negatively correlated with all three measures of body composition and positively correlated with years postinjury. Functional satisfaction was positively correlated with years postinjury, and negatively correlated with various LTPA variables. CONCLUSION: Functional and appearance body image may improve with time following SCI. Body composition may impact satisfaction with physical appearance for some women. The negative relationship between LTPA and functional satisfaction merits further examination, as functional dissatisfaction may motivate individuals to engage in certain types and intensities of LTPA. Correlates of body image differ between appearance and functional satisfaction. Future research should examine appearance and functional satisfaction separately among women with SCI.


Subject(s)
Body Image , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/psychology , Adult , Body Composition/physiology , Female , Humans , Motor Activity , Pilot Projects , Statistics, Nonparametric , Surveys and Questionnaires
8.
Spinal Cord ; 47(3): 252-6, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18794904

ABSTRACT

STUDY DESIGN: Cross-sectional. OBJECTIVES: To examine the relationship between body image and leisure time physical activity (LTPA) among men with spinal cord injury (SCI). Specifically, to examine the moderating function of the perceived impact of body image on quality of life (QOL). SETTING: Ontario, Canada. METHODS: Men with SCI (N=50, 50% paraplegic) reported, (a) their functional and appearance body image (Adult Body Satisfaction Questionnaire), (b) their perceived impact of body image on QOL and (c) LTPA performed over the previous 3 days. RESULTS: Body image was in the 'normal' range compared with the general population. Linear regression analysis found a significant LTPA x body image impact on QOL interaction beta=0.39, P<0.05. Post hoc analysis showed that among individuals who reported a negative effect of body image on QOL, those who engaged in LTPA were less satisfied with their physical function than those who did not. For those who did not perceive their body image to negatively impact their QOL, there was generally no difference in functional body image between those who engaged in LTPA and those who did not. CONCLUSION: Appearance body image is not related to LTPA for men with SCI. It has been suggested that body dissatisfaction may motivate some individuals to engage in LTPA. However, for men living with SCI, functional body image may be associated with LTPA only when a negative effect on QOL is perceived. Future research should consider the moderating function of the perceived impact of body image on QOL when examining the relationship between LTPA and body image among men living with SCI.


Subject(s)
Body Image , Motor Activity/physiology , Quality of Life , Self Concept , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/psychology , Adaptation, Psychological/physiology , Adult , Body Composition , Cross-Sectional Studies , Humans , Male , Middle Aged , Surveys and Questionnaires
9.
Ground Water ; 46(3): 372-83, 2008.
Article in English | MEDLINE | ID: mdl-18266731

ABSTRACT

Water resources in the arid southwestern United States are frequently the subject of conflict from competing private and public interests. Legal remedies may remove impasses, but the technical analysis of the problem often determines the future success of legal solutions. In Owens Valley, California, the source of water for the Los Angeles Aqueduct (LAA) is flow diverted from the Owens River and its tributaries and ground water from valley aquifers. Future management of ground water delivered to the LAA needs technical support regarding quantity available, interconnection of shallow and confined aquifers, impact on local springs, and rate of recharge. Ground water flow models and ground water composition are tools already in use, but these have large uncertainty for local interpretations. This study conducted targeted sampling of springs and wells to evaluate the hydrologic system to corroborate conceptual and numerical models. The effort included measurement of intrinsic isotopic composition at key locations in the aquifers. The stable isotopic data of boron (delta(11)B), sulfur (delta(34)S), oxygen (delta(18)O), hydrogen (delta D), and tritium ((3)H) supported by basic chemical data provided rules for characterizing the upper and the lower aquifer system, confirmed the interpretation of ground water flow near faults and flow barriers, and detected hydraulic connections between the LAA and the perennial springs at key locations along the unlined reach of the LAA. This study exemplifies the use of forensic isotopic approaches as independent checks on the consistency of interpretations of conceptual models of a ground water system and the numerical hydrologic simulations.


Subject(s)
Environmental Monitoring , Isotopes/analysis , Models, Theoretical , Water Movements , Water Supply/analysis , California , Geologic Sediments/analysis , Geologic Sediments/chemistry , Isotopes/chemistry , Los Angeles , Rivers , Southwestern United States
10.
Ground Water ; 46(3): 489-501, 2008.
Article in English | MEDLINE | ID: mdl-18266732

ABSTRACT

The salinization of rivers, as indicated by salinity increases in the downstream direction, is characteristic of arid and semiarid regions throughout the world. Historically, salinity increases have been attributed to various mechanisms, including (1) evaporation and concentration during reservoir storage, irrigation, and subsequent reuse; (2) displacement of shallow saline ground water during irrigation; (3) erosion and dissolution of natural deposits; and/or (4) inflow of deep saline and/or geothermal ground water (ground water with elevated water temperature). In this study, investigation of salinity issues focused on identification of relative salinity contributions from anthropogenic and natural sources in the Lower Rio Grande in the New Mexico-Texas border region. Based on the conceptual model of the system, the various sources of water and, therefore, salinity to the Lower Rio Grande were identified, and a sampling plan was designed to characterize these sources. Analysis results for boron (delta(11)B), sulfur (delta(34)S), oxygen (delta(18)O), hydrogen (delta(2)H), and strontium ((87)Sr/(86)Sr) isotopes, as well as basic chemical data, confirmed the hypothesis that the dominant salinity contributions are from deep ground water inflow to the Rio Grande. The stable isotopic ratios identified the deep ground water inflow as distinctive, with characteristic isotopic signatures. These analyses indicate that it is not possible to reproduce the observed salinization by evapotranspiration and agricultural processes alone. This investigation further confirms that proper application of multiple isotopic and geochemical tracers can be used to identify and constrain multiple sources of solutes in complex river systems.


Subject(s)
Environmental Monitoring , Isotopes/analysis , Rivers/chemistry , Sodium Chloride/analysis , Water Movements , Water Pollutants, Chemical/analysis , Geological Phenomena , Geology , Isotopes/chemistry , Models, Biological , New Mexico , Texas
11.
Int J Gynecol Cancer ; 18(1): 146-51, 2008.
Article in English | MEDLINE | ID: mdl-17466036

ABSTRACT

The objective of our study was to evaluate the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p27, and mammalian target of rapamycin (mTOR) expressions in women with progesterone-responsive and refractory endometrial hyperplasia (EH) samples and to determine if these markers could be associated with response or used as potential targets for treatment. Thirty-eight matched pre- and posttreatment pairs of paraffin-embedded endometrial biopsies were obtained from patients with EH. Immunohistochemical analysis for PTEN, p27, and phospho-mTOR were performed on all samples. Median age at diagnosis was 49 years (20-79 years). Median treatment interval was 3 months (1-12 months). Sixteen patients (42.1%) had complete resolution of their hyperplasia (responders), and 22 (57.9%) had persistent hyperplasia (nonresponders) after treatment with progesterone. In the pretreatment samples, no markers were found to predict nonresponders. In posttreatment samples, loss of PTEN expression with phospho-mTOR expression was observed in more nonresponders than responders (40.9% vs 6.3%; P= 0.03). Phospho-mTOR overexpression was found in 63.6% of nonresponders. We found that persistent hyperplasia refractory to progesterone therapy was associated both with the loss of PTEN and with the loss of phosphorylation of mTOR. In select cases of non-responsive progesterone refractory EH, a rational target for treatment may involve the mTOR pathway.


Subject(s)
Chromosomes, Human, Pair 10/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Endometrial Hyperplasia/drug therapy , Gene Deletion , PTEN Phosphohydrolase/genetics , Progesterone/therapeutic use , Progestins/therapeutic use , Protein Kinases/metabolism , Adult , Aged , Endometrial Hyperplasia/genetics , Endometrial Hyperplasia/pathology , Female , Humans , Immunoenzyme Techniques , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Phosphorylation/drug effects , TOR Serine-Threonine Kinases
12.
AIDS ; 14(11): 1553-61, 2000 Jul 28.
Article in English | MEDLINE | ID: mdl-10983642

ABSTRACT

OBJECTIVE: To compare the virologic activity of continued lamivudine (3TC) versus a switch to delavirdine (DLV) when initiating protease inhibitor therapy in nucleoside-experienced patients. DESIGN: Randomized, open-label, multi-center study. SETTING: Adult AIDS clinical trials units. PATIENTS: Protease and non-nucleoside reverse transcriptase inhibitor-naive patients who had received 3TC plus zidovudine (ZDV), stavudine (d4T), or didanosine (ddl) for at least 24 weeks. INTERVENTIONS: Patients with plasma HIV-1 RNA levels > 500 copies/ml who previously received d4T + 3TC or ddI + 3TC were randomized to ZDV + 3TC + indinavir (IDV) or ZDV + DLV + IDV. MAIN OUTCOME MEASURES: Primary endpoints were the proportion of patients with plasma HIV-1 RNA levels < or = 200 copies/ml at 24 weeks, and occurrence of serious adverse events. The proportion of patients with plasma HIV-1 RNA levels < or = 200 copies/ml at week 48 was a secondary endpoint. RESULTS: At week 24, 58% of subjects in the ZDV + 3TC + IDV arm and 73% in the ZDV + DLV + IDV arm had plasma HIV-1 RNA levels < or = 200 copies/ml (P = 0.29). At week 48, plasma HIV-1 RNA levels were < or = 200 copies/ml in 48% and 83%, respectively (P = 0.007). Rash and hyperbilirubinemia occurred more frequently in the DLV arm than in the 3TC arm. Steady-state plasma IDV levels were higher among patients in the DLV arm as compared with the 3TC arm. CONCLUSIONS: Substituting DLV for 3TC when adding IDV improved virologic outcome in nucleoside-experienced patients. This result might be explained, in part, by the positive effect of DLV on IDV pharmacokinetics.


Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Anti-HIV Agents/therapeutic use , Delavirdine/therapeutic use , HIV Protease Inhibitors/therapeutic use , Indinavir/therapeutic use , Lamivudine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Stavudine/therapeutic use , Zidovudine/therapeutic use , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/virology , Adult , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Female , HIV Protease Inhibitors/blood , Humans , Indinavir/blood , Male , Time Factors , Viral Load
13.
N Engl J Med ; 339(18): 1261-8, 1998 10 29.
Article in English | MEDLINE | ID: mdl-9791141

ABSTRACT

BACKGROUND: Combination antiretroviral therapy with indinavir, zidovudine, and lamivudine can suppress the level of human immunodeficiency virus (HIV) RNA in plasma below the threshold of detection for two years or more. We investigated whether a less intensive maintenance regimen could sustain viral suppression after an initial response to combination therapy. METHODS: HIV-infected subjects who had CD4 cell counts greater than 200 per cubic millimeter, who had been treated with indinavir, lamivudine, and zidovudine, and who had less than 200 copies of HIV RNA per milliliter of plasma after 16, 20, and 24 weeks of induction therapy were randomly assigned to receive either continued triple-drug therapy (106 subjects), indinavir alone (103 subjects), or a combination of zidovudine and lamivudine (107 subjects). The primary end point was loss of viral suppression, which was defined as a plasma level of at least 200 copies of HIV RNA per milliliter on two consecutive measurements during maintenance therapy. RESULTS: During maintenance treatment, 23 percent of the subjects receiving indinavir and 23 percent of those receiving zidovudine and lamivudine, but only 4 percent of those receiving all three drugs, had loss of viral suppression (P<0.001 for the comparison between triple-drug therapy and the other two maintenance regimens). Subjects with greater increases in CD4 cell counts during induction therapy, higher viral loads at base line (i.e., at the beginning of induction therapy), and slower rates of viral clearance were at greater risk for loss of viral suppression. The presence of zidovudine-resistance mutations in HIV RNA at base line was strongly predictive of the loss of viral suppression in subjects treated with zidovudine and lamivudine. CONCLUSIONS: The suppression of plasma HIV RNA after six months of treatment with indinavir, zidovudine, and lamivudine is better sustained by the continuation of these three drugs than by maintenance therapy with either indinavir alone or zidovudine and lamivudine.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1/isolation & purification , Indinavir/therapeutic use , Lamivudine/therapeutic use , Zidovudine/therapeutic use , Adult , Double-Blind Method , Drug Therapy, Combination , Female , HIV Infections/virology , HIV-1/genetics , Humans , Male , Multivariate Analysis , RNA, Viral/blood , Remission Induction , Treatment Failure , Viral Load
14.
N Engl J Med ; 334(16): 1011-7, 1996 Apr 18.
Article in English | MEDLINE | ID: mdl-8598838

ABSTRACT

BACKGROUND: In patients with human immunodeficiency virus (HIV) infection, combined treatment with several agents may increase the effectiveness of antiviral therapy. We studied the safety and efficacy of saquinavir, an HIV-protease inhibitor, given with one or two nucleoside antiretroviral agents, as compared with the safety and efficacy of a combination of two nucleosides alone. METHODS: In this double-blind trial, patients with HIV infection were randomly assigned to receive either saquinavir (1800 mg per day) plus both zidovudine (600 mg per day) and zalcitabine (2.25 mg per day) or zidovudine plus either saquinavir or zalcitabine. The 302 patients enrolled had CD4+ counts of 50 to 300 cells per cubic millimeter and had previously received zidovudine for a median of 27 months. The study lasted 24 weeks, with an optional double-blind extension period of an additional 12 to 32 weeks. RESULTS: Ninety-six percent of the patients completed the 24-week study. In all three treatment groups, CD4+ cell counts rose at first and then fell gradually. The normalized area under the curve for the CD4+ count was greater with the three-drug combination than with either saquinavir and zidovudine (P=0.017) or zalcitabine and zidovudine (P<0.001). There were significantly greater reductions in plasma HIV with the three-drug combination than with the other regimens when peripheral-blood mononuclear cells were cultured for HIV and HIV RNA was assessed, and there were greater decreases in serum neopterin and beta2-microglobulin levels. There were no major differences in toxic effects among the three treatments. CONCLUSIONS: Treatment with saquinavir, zalcitabine, and zidovudine was well tolerated. This drug combination reduced HIV-1 replication, increased CD4+ cell counts, and decreased levels of activation markers in serum more than did treatment with zidovudine and either saquinavir or zalcitabine. Studies are warranted to evaluate whether the three-drug combination will reduce morbidity and mortality.


Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Isoquinolines/therapeutic use , Quinolines/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Zalcitabine/therapeutic use , Zidovudine/therapeutic use , Adult , CD4 Lymphocyte Count/drug effects , Double-Blind Method , Drug Therapy, Combination , Female , HIV/drug effects , HIV/isolation & purification , HIV Infections/blood , HIV Infections/immunology , Humans , Male , RNA, Viral/blood , Saquinavir , Treatment Outcome
16.
Clin Orthop Relat Res ; (220): 237-40, 1987 Jul.
Article in English | MEDLINE | ID: mdl-3594996

ABSTRACT

A total of 191 patients (representing 194 skin lacerations) hospitalized for clenched-fist injuries were evaluated for deep structure involvement. Tendon, joint, cartilage, and/or bone were damaged in 75%. Tendon involvement occurred in 28 of 138 (20.3%), joint capsule violation in 99 of 146 (67.8%), free articular cartilage fragments in 8 of 139 (5.8%) and articular-bone indentations in 23 of 139 (16.5%). All patients with clenched-fist lacerations or puncture wounds over joints should be treated by surgical debridement and exploration of the deep structures, including the joint, at the time they first seek medical care.


Subject(s)
Debridement , Hand Injuries/surgery , Wounds, Penetrating/surgery , Adolescent , Adult , Cartilage, Articular/injuries , Female , Fractures, Bone/surgery , Humans , Male , Metacarpophalangeal Joint/injuries , Middle Aged , Osteomyelitis/surgery , Tendon Injuries
17.
Clin Orthop Relat Res ; (214): 148-52, 1987 Jan.
Article in English | MEDLINE | ID: mdl-3791736

ABSTRACT

The treatment of intraarticular fractures of the distal radius has been dramatically altered over the past decade. Investigations into the pathomechanics of these injuries highlight the problems of arthritis, pain, swelling, weakness, limited range of motion and instability associated with nonanatomic reduction of both intraarticular fragments and their associated ligaments. Factors affecting the prognosis for these injuries include degree and location of articular involvement and the energy of the precipitating force as well as the anatomy of reduction. Operative treatment is reserved for displaced intraarticular fractures. Those extremely comminuted fractures are best fixed with distraction and external fixation. The operative approach to these fractures is dependent on the anatomy. Ligamentous instability, in particular with radial styloid fractures, must be sought and treated. Kirschner wires can be used as "joy sticks" to control unstable carpal bones or fracture fragments prior to fixation. Plates and screws are useful in the stabilization of volar and dorsal rim fractures. The use of intraoperative radiographs is emphasized. Postoperative early range of motion, when possible, greatly improves the long-term results.


Subject(s)
Radius Fractures/therapy , Fracture Fixation/methods , Fracture Fixation, Internal/methods , Humans , Orthopedic Fixation Devices , Wrist Injuries/therapy , Wrist Joint
20.
J Hand Surg Am ; 10(1): 118-24, 1985 Jan.
Article in English | MEDLINE | ID: mdl-3968392

ABSTRACT

This article describes the isolated occurrence of Dupuytren's pathologic fascial cords within digits of the hand. Thirty-seven cords were found in 32 patients with nearly half (45.6%) occurring in digits other than the small finger. Almost all patients (97.3%) had other clinical evidence of Dupuytren's disease. Cords were either single (83.8%) or double (16.2%) and originated from the periosteum at the base of the proximal phalanx in conjunction with adjacent ligaments and intrinsic tendons. They proceeded in an oblique direction to displace and then cross the neurovascular bundles before inserting on the bone and/or flexor tendon sheath of the middle phalanx. The average loss of extension of the proximal interphalangeal joint that resulted from these cords was 46 degrees, and surgical excision of the involved cords resulted in an average improvement of 24 degrees (53%).


Subject(s)
Dupuytren Contracture/pathology , Fascia/pathology , Adult , Aged , Dupuytren Contracture/physiopathology , Dupuytren Contracture/surgery , Fasciotomy , Female , Finger Joint/pathology , Humans , Male , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL