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Biomedical subjects

R R Turner

Publications and source records attributed to R R Turner.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients.

PURPOSE: Detection of micrometastases in the regional tumor-draining lymph nodes is critical for accurate staging and prognosis in melanoma patients. We hypothesized that a multiple-mRNA marker (MM) reverse transcriptase-polymerase chain reaction (RT-PCR) assay would improve the detection of occult metastases in the sentinel node (SN), compared with hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC), and that MM expression is predictive of disease relapse. PATIENTS AND METHODS: Seventy-two consecutive patients with clinical early-stage melanoma underwent sentinel lymphadenectomy (SLND). Their SNs were serially sectioned and assessed for MAGE-3, MART-1, and tyrosinase mRNA expression by RT-PCR, in parallel with H&E staining and IHC, for melanoma metastases. MM expression in the SNs was correlated with H&E and IHC assay results, standard prognostic factors, and disease-free survival. RESULTS: In 17 patients with H&E- and/or IHC-positive SNs, 16 (94%) expressed two or more mRNA markers. Twenty (36%) of 55 patients with histopathologically negative SNs expressed two or more mRNA markers. By multivariate analysis, patients at increased risk of metastases to the SN had thicker lesions (P =.03), were 60 years of age or younger (P <.05), and/or were MM-positive (P <.001). Patients with histopathologically melanoma-free SNs who were MM-positive, compared with those who were positive for one or fewer mRNA markers, were at increased risk of recurrence (P =.02). Patients who were MM-positive with histopathologically proven metastases in the SN were at greatest risk of disease relapse (P =. 01). CONCLUSION: H&E staining and IHC underestimate the true incidence of melanoma metastases. MM expression in the SN more accurately reflects melanoma micrometastases and is also a more powerful predictor of disease relapse than are H&E staining and IHC alone.

Adult↗
PubMed1999

The effects of venlafaxine on social activity level in depressed outpatients.

BACKGROUND: Although most depression treatment outcome scales focus on symptoms, depression also affects daily functioning, social activity, and quality of life. We examined the effects of venlafaxine on social activity, general life functioning, and depressive symptoms in 2 placebo-controlled clinical trials of venlafaxine. METHOD: Subjects were 600 outpatients with major depression (DSM-III-R criteria). Treatment outcomes were examined separately in each study, primarily because of differing lengths of follow-up. RESULTS: Treatment with venlafaxine significantly improved activity level, general life functioning, and depressive symptoms. Treatment accounted for statistically significant changes in both activity level and general life functioning even after controlling for changes in depression. CONCLUSION: We provide evidence that social activity is a behavioral domain distinct from depressive symptoms and that venlafaxine improves social activity level and general life functioning in addition to its positive effects on depressive symptoms in outpatients with major depression.

Adolescent↗
PubMed1998

Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple-marker RT-PCR.

This study was undertaken to assess a multiple-marker RT-PCR and Southern blot assay for detection of metastases in frozen sections of sentinel lymph nodes from breast cancer patients. Sentinel lymphadenectomy was performed in 41 AJCC (American Joint Committee on Cancer) stage I-IIIA breast cancer patients and 57 sentinel nodes (SNs) were excised. The SN, which is the first node in the lymphatic basin to receive metastases from the primary tumor, was identified using isosulfan blue dye. Hematoxylin and eosin (H&E), immuno-histochemistry (IHC) and RT-PCR were performed on adjacent sections of the SN. Six consecutive 12-microm frozen sections of each SN were obtained for the RT-PCR assay to determine expression of mRNA tumor markers C-Met, beta1 --> 4GalNAc-T and P97. Metastatic breast cancer was detected by H&E in 10 of 57 (18%) SNs and by IHC in an additional 7 (12%). Only 1 of 17 (6%) SNs with metastases did not express any of the 3 tumor mRNA markers. C-Met, beta1 --> 4GalNAc-T and P97 tumor mRNA markers were expressed in 31 (78%), 21 (53%) and 25 (63%) of 40 SNs without metastases, respectively. At least 2 mRNA tumor markers were expressed in 25/40 (63%) histo-pathologically tumor-free SNs, whereas all 3 mRNA tumor markers were expressed in 17/40 (43%) SNs. Expression of all 3 mRNA tumor markers in a SN was significantly higher in patients with a family history of breast cancer (p = 0.05), prior history of breast cancer (p < 0.05), infiltrating lobular carcinoma (p = 0.06), estrogen receptor-negative (p = 0.04) tumor or a higher Bloom Richardson score (p = 0.04). The multiple-marker RT-PCR and Southern blot assay improves the detection of occult metastases in the SN when compared to conventional H&E and IHC analysis. Expression of all 3 tumor mRNA markers in the SN correlated with poor prognostic clinico-pathologic factors compared to expression of 0 to 2 markers.

Biomarkers, Tumor↗
PubMed1998

Metaplastic carcinoma of the breast: report of three cases.

BACKGROUND: Metaplastic carcinoma is a rare form of breast carcinoma that often is confused with other benign and malignant entities. The diagnosis can be difficult to establish on both a clinical and conventional histopathologic basis. One report recently described clinical and mammographic features dissimilar to the authors' experience but to the authors' knowledge no other reports have been published. Therefore a review of three cases was undertaken; all patients had undergone mammography to identify and report the mammographic features of this disease, suggesting that imaging may add to the proper diagnosis of this entity. METHODS: Three clinical cases in which the diagnosis of metaplastic carcinoma was confirmed and for which mammography was performed were reviewed retrospectively. Follow-up on all three patients was available. RESULTS: Metaplastic carcinoma may be manifest as a well circumscribed mass or an irregular or spiculated mass. The latter always is highly suspicious for malignancy and the former incurs suspicion if it grows, although in this series the smooth mass was biopsied immediately. The spiculated masses were associated with delayed diagnosis and poorer prognosis because immunohistochemical studies were not performed on the original excisional biopsy specimens. CONCLUSIONS: Although spiculated masses usually are associated with invasive ductal and lobular carcinoma, they also may represent metaplastic carcinoma and immunohistochemical studies often are required to establish this diagnosis and avoid delay in proper treatment. Well circumscribed masses representing this disease may suggest benign disease but metaplastic carcinoma should be included in the differential diagnosis, especially if the mass enlarges.

Breast Neoplasms↗
PubMed1998

Prognostic implications of p53 overexpression in cutaneous melanoma from sun-exposed and nonexposed sites.

BACKGROUND: There is increasing evidence that mutations in the p53 tumor suppressor gene are among the most common genetic alterations in human malignancies. Because ultraviolet light can induce specific p53 mutations and is linked to the development of skin cancers, this study was done to determine the significance of p53 protein (p53p) overexpression in melanomas originating at different cutaneous sites varying in frequency of sunlight exposure. METHODS: Sixty-three paraffin embedded primary and metastatic melanoma biopsy specimens from 61 patients were deparaffinized and stained with the mouse monoclonal antibody DO-1 to wild-type and mutant p53p. Twenty-eight specimens were from primary tumors and 35 specimens were from lymph node, subcutaneous, or visceral metastases. The chi-square test was used to assess the significance of p53p overexpression, and the Cox proportional hazards model was used to estimate the impact of p53p overexpression on survival. RESULTS: Of the 61 patients studied, 37 had primary cutaneous melanomas arising on chronically sun-exposed head and neck sites, 12 patients on intermittently exposed extremity sites, and 12 patients on rarely exposed trunk sites. Thirteen of the 63 primary or metastatic specimens (21%) overexpressed p53p. Overexpression of p53p was not related to patient gender or age, anatomic site of the primary tumor, Clark level, or Breslow thickness. However, those patients with p53p positive primary tumors or metastases had significantly better survival than those determined to be negative for p53p overexpression (P = 0.045). The median survival was 152.4 months for p53p positive patients versus 55.7 months for p53p negative patients. The risk ratio of dying from melanoma was 0.32 for patients with tumor specimens overexpressing p53p. CONCLUSIONS: In this study, p53p overexpression was infrequent in paraffin embedded melanoma specimens and independent of the primary melanoma's anatomic site. Although p53p overexpression was not related to other prognostic features of primary or metastatic lesions, it was associated with a significantly improved survival in this group of melanoma patients.

Adult↗
PubMed1998

Quality of life and calcium channel blockade with nifedipine GITS versus amlodipine in hypertensive patients in Spain. Gastrointestinal Therapeutic System.

OBJECTIVE: Compliance with hypertension treatment is affected by treatment-related factors (complexity, side effects), efficacy and compound-specific effects that impact on quality of life. This study examined the differences in quality of life produced by two once-daily calcium channel blockers using different delivery systems: nifedipine gastrointestinal therapeutic system (GITS) and amlodipine. DESIGN: This was a double-blind, double-dummy, randomized clinical trial comparing nifedipine GITS (30 mg) and amlodipine (5 mg) for 24 weeks following a placebo run-in. Clinical, laboratory evaluations and quality-of-life data were assessed at screening, baseline randomization and three times during active therapy. SETTING: The study was conducted in 13 medical clinics in Spain. PATIENTS: The sample comprised 430 screened and 356 randomized patients with mild to moderate hypertension (diastolic blood pressure 95-114 mmHg). MAIN OUTCOME MEASURES: Change in systolic and diastolic blood pressure and in health-related quality of life were the main outcome measures. RESULTS: There were no significant differences between active treatment groups in the blood pressure changes (systolic blood pressure: nifedipine GITS -15.5 mmHg; amlodipine -15.7 mmHg). Spontaneous adverse events consistent with calcium channel blockage were not different. The nifedipine GITS group improved in all quality-of-life measures except Sexual Symptom Distress and showed a significantly greater improvement than amlodipine in overall Quality of Life (P< 0.05), General Perceived Health (P < 0.026) and its subscale Vitality (P < 0.019). The amlodipine group declined in overall Quality of Life, General Perceived Health, Vitality and Sleep Disturbance, and significantly in Sexual Symptom Distress (P < 0.045). However, this group improved in self-reported Cognitive Functioning (P=0.036), Mental Acuity (P < 0.005) and Detachment/disorientation (P=0.01). CONCLUSIONS: These results suggest compound-specific effects on quality of life that may be due to differences in the delivery system. Nifedipine GITS is short-acting (2 h half-life) and is delivered continuously over a 24 h period, while amlodipine has a half-life of 40 h, which may produce more sustained low-level effects. While a more beneficial profile was observed for nifedipine, amlodipine demonstrated potential positive effects on cognitive functioning.

Adolescent↗
PubMed1998

Valuing quality of life and improvements in glycemic control in people with type 2 diabetes.

Outcomes research is used increasingly for assessing the health economic benefits of new therapeutic programs and interventions. The measurement properties of the outcomes assessment tools are important. If overlooked, they can mislead health care administrators and caregivers regarding the importance and value of these programs and interventions. We reviewed the literature and conducted two analyses to determine the absolute, relative, and operative quality-of-life ranges for people with type 2 diabetes. Quality of life and fasting blood glucose and HbA1c concentrations were measured at baseline and at 4, 8, and 12 weeks of treatment in 569 men and women randomized to either glipizide gastrointestinal therapeutic system (GITS) or placebo in a double-blind, multicenter clinical trial. A subgroup of 290 patients completed a diabetes-specific health states questionnaire at endpoint (week 12 or early termination) rating 10 health-state descriptions on a health thermometer scale ranging from 0 (death) to 100 (full health). Health losses at the higher end of the scale had a greater negative utility than did comparable losses at lower health states, indicating patients' strong preferences for maintaining asymptomatic or mildly symptomatic conditions. Patients rated their current health state at 83.4 +/- 0.8% of full health and indicated that a loss of 27 points below this value would prevent them from living and working as they currently do. The calibration analysis applied to the quality-of-life scales suggested that the targeted range for clinical investigation and quality-of-care evaluation must be more narrowly focused. Effect sizes as seemingly small as 2% (0.25 responsiveness units) on the absolute scale can correspond to quality-of-life losses of 15-20% on the personal operative scale. Differences in glycemic control clearly affected quality of life. Those patients with the best HbA1c responses (decreasing 1.5% or more from baseline) versus those with the worst responses (increasing 1.5% or more from baseline) were separated by 0.6 responsiveness units for the overall quality-of-life summary measure. The calibration analysis suggested that this degree of better glycemic control provides a nearly 50% gain in quality of life according to personal expectations within the operative range. In conclusion, general measures of quality of life may be too crude and insensitive to capture the important gains in health outcomes due to new therapeutic interventions and programs in diabetes. Quality-of-care evaluations for diabetes are at risk of favoring inferior programs with lower costs simply because gains or losses in health outcomes go undetected.

Adult↗
PubMed1997

Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma.

BACKGROUND AND OBJECTIVE: The sentinel node hypothesis assumes that a primary tumor drains to a specific lymph node in the regional lymphatic basin. To determine whether the sentinel node is indeed the node most likely to harbor an axillary metastasis from breast carcinoma, the authors used cytokeratin immunohistochemical staining (IHC) to examine both sentinel and nonsentinel lymph nodes. METHODS: From February 1994 through October 1995, patients with breast cancer were staged with sentinel lymphadenectomy followed by completion level I and II axillary dissection. If the sentinel node was free of metastasis by hematoxylin and eosin staining (H&E), then sentinel and nonsentinel nodes were examined with IHC. RESULTS: The 103 patients had a median age of 55 years and a median tumor size of 1.8 cm (58.3% T1, 39.8% T2, and 1.9% T3). A mean of 2 sentinel (range, 1-8) and 18.9 nonsentinel (range, 7-37) nodes were excised per patient. The H&E identified 33 patients (32%) with a sentinel lymph node metastasis and 70 patients (68%) with tumor-free sentinel nodes. Applying IHC to the 157 tumor-free sentinel nodes in these 70 patients showed an additional 10 tumor-involved nodes, each in a different patient. Thus, 10 (14.3%) of 70 patients who were tumor-free by H&E actually were sentinel node-positive, and the IHC lymph node conversion rate from sentinel node-negative to sentinel node-positive was 6.4% (10/157). Overall, sentinel node metastases were detected in 43 (41.8%) of 103 patients. In the 60 patients whose sentinel nodes were metastasis-free by H&E and IHC, 1087 nonsentinel nodes were examined at 2 levels by IHC and only 1 additional tumor-positive lymph node was identified. Therefore, one H&E sentinel node-negative patient (1.7%) was actually node-positive (p < 0.0001), and the nonsentinel IHC lymph node conversion rate was 0.09% (1/1087; p < 0.0001). CONCLUSIONS: If the sentinel node is tumor-free by both H&E and IHC, then the probability of nonsentinel node involvement is <0.1%. The true false-negative rate of this technique using multiple sections and IHC to examine all nonsentinel nodes for metastasis is 0.97% (1/103) in the authors' hands. The sentinel lymph node is indeed the most likely axillary node to harbor metastatic breast carcinoma.

Adult↗
PubMed1997

Effects of dissolved organic carbon and salinity on bioavailability of mercury.

Hypotheses that dissolved organic carbon (DOC) and electrochemical charge affect the rate of methylmercury [CH3Hg(I)] synthesis by modulating the availability of ionic mercury [Hg(II)] to bacteria were tested by using a mer-lux bioindicator (O. Selifonova, R. Burlage, and T. Barkay, Appl. Environ. Microbiol. 59:3083-3090, 1993). A decline in Hg(II)-dependent light production was observed in the presence of increasing concentrations of DOC, and this decline was more pronounced at pH 7 than at pH 5, suggesting that DOC is a factor controlling the bioavailability of Hg(II). A thermodynamic model (MINTEQA2) was used to select assay conditions that clearly distinguished among various Hg(II) species. By using this approach, it was shown that negatively charged forms of mercuric chloride (HgCl3-/HgCl(4)2-) induced less light production than the electrochemically neutral form (HgCl2), and no difference was observed between the two neutral forms, HgCl2 and Hg(OH)2. These results suggest that the negative charge of Hg(II) species reduces their availability to bacteria and may be one reason why accumulation of CH3Hg(I) is more often reported to occur in freshwater than in estuarine and marine biota.

Biological Availability↗
PubMed1997

Cell-density-dependent sensitivity of a mer-lux bioassay.

The sensitivity of a previously described assay (O. Selifonova, R. Burlage, and T. Barkay, Appl. Environ. Microbiol. 59:3083-3090, 1993) for the detection of bioavailable inorganic mercury (Hg2+) by the activation of a mer-lux fusion was increased from nanomolar to picomolar concentrations by reducing biomass in the assays from 10(7) to 10(5) cells ml-1. The increase in sensitivity was due to a reduction in the number of cellular binding sites that may compete with the regulatory protein, MerR, for binding of the inducer, Hg2+. These results show that (i) the sensitivity of the mer-lux assay is sufficient for the detection of Hg2+ in most contaminated natural waters and (ii) mer-specified reactions, Hg2+ reduction and methylmercury degradation, can be induced in natural waters and may participate in the geochemical cycling of mercury.

Bacterial Proteins↗
PubMed1995

Form of mercury in stream fish exposed to high concentrations of dissolved inorganic mercury.

The form of mercury predominating in mercury-contaminated fish from both pristine and industrialized waters in North America and Europe has almost universally been methylmercury. Sunfish (Lepomis auritus) living in a stream contaminated with 0.5-1 micrograms/L dissolved inorganic mercury accumulated greater concentrations of total mercury at headwater sites, where the dissolved mercury concentrations were greatest, than they did at downstream sites. However, despite evidence from laboratory studies that dissolved inorganic mercury is rapidly accumulated by fish without transformation to methylmercury, methylmercury constituted 85% or more of the total mercury concentration in fish at all sites.

Animals↗
PubMed1995

Improved axillary staging of breast cancer with sentinel lymphadenectomy.

OBJECTIVE: The authors evaluated the effect of intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) on the axillary staging of patients with carcinoma of the breast. SUMMARY BACKGROUND DATA: The accurate staging of patients with breast cancer is essential to guide management and determine prognosis. The authors previously reported the feasibility and accuracy of SLND in breast carcinoma. Sentinel lymphadenectomy identifies the first ("sentinel") axillary lymph node draining the site of a primary tumor; because this node is the most likely site of axillary metastasis, histopathologic examination of the sentinel node correlates well with examination of the entire axillary contents. The current study compares SLND with standard axillary lymphadenectomy (ALND) for the staging of breast carcinoma. METHODS: The incidence of axillary node metastasis and micrometastasis in SLND and ALND specimens from patients undergoing operative treatment of a primary breast carcinoma was compared prospectively. Multiple sections of each sentinel lymph node in SLND specimens were examined by hematoxylin and eosin (H&E) staining and by immunohistochemical techniques using antibodies to cytokeratin. One or two sections of each nonsentinel lymph node in ALND specimens were examined by routine H&E staining. RESULTS: One hundred thirty-four patients underwent ALND (ALND group), and 162 underwent successful SLND followed by completion ALND (SLND group). Both groups were similar with respect to age (median, 55 and 54 years, respectively), palpable primary tumors (54.5% and 59.3%, respectively), palpable axillary nodes (5.2% and 7.4%, respectively), size of primary tumor (median, 1.5 cm in each group), and total number of axillary lymph nodes examined (median, 19 and 21, respectively). The number of patients with axillary metastasis was 39 (29.1%) in the ALND group and 68 (42.0%) in the SLND group (p < 0.03). Of these, 4 of 39 (10.3%) ALND patients (3.0% of all ALND patients) and 26 of 68 (38.2%) SLND patients (16.0% of all SLND patients) had micrometastasis (< or = 2 mm), a highly significant difference (p < 0.0005) CONCLUSIONS: Sentinel lymphadenectomy with multiple sectioning and immunohistochemical staining of sentinel nodes increases the accuracy of axillary staging in breast cancer and can identify significantly more patients with lymph nodes metastases, especially micrometastases, than can ALND with routine histopathologic processing of lymph nodes.

Adult↗
PubMed1995

Evaluation and quality-of-life assessment of amlodipine and enalapril in patients with hypertension.

In this multicentre, double-blind trial in 461 patients with essential hypertension, amlodipine (5-10 mg once daily) and enalapril (10-40 mg once daily) were compared in terms of quality of life, efficacy and tolerability after 1 year of treatment (part 1). In part 2, 177 patients successfully treated with amlodipine in part 1 continued in an open evaluation of efficacy and safety of antihypertensive treatment with amlodipine for a further 2 years. In part 1, both drugs were similarly effective in lowering blood pressure (BP) (although significantly more enalapril patients required a diuretic) while maintaining quality of life. Apart from class-typical effects, such as oedema for calcium antagonists and cough for angiotensin-converting enzyme inhibitors, both drugs were equally well tolerated, with few adverse effects of clinical significance. Only a few patients (eight amlodipine (4%), nine enalapril (4%)) were withdrawn from the trial because of drug-related adverse events, demonstrating that the tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. The BP reduction seen in the amlodipine patients after part 1 was maintained during part 2. Also, blood lipids and safety variables remained virtually constant. It is concluded that, at similar BP reduction, quality of life is equally well maintained on amlodipine and enalapril therapy. Thus, amlodipine compares favourably with enalapril as an effective and well-tolerated anti-hypertensive agent over the first year. Additionally, amlodipine patients evaluated over a 2-year extension maintained good BP control and the drug was well tolerated.

Adult↗
PubMed1994

Changes in concentrations of selenium and mercury in largemouth bass following elimination of fly ash discharge to a quarry.

Elimination of slurried fly ash discharges to a water-filled quarry was followed by a steady increase in concentrations of mercury in the axial muscle of resident largemouth bass (Micropterus salmoides). Average mercury concentrations in bass (adjusted for covariance with fish weight) increased from 0.02 micrograms/g to 0.17 micrograms/g in three years. Aqueous selenium concentrations in the quarry decreased from 25 micrograms/L to < 2 micrograms/L after elimination of fly ash discharges, but selenium concentrations in bass remained about three times background levels. Previous studies have shown selenium addition to be a viable means of ameliorating mercury contamination in fish in low alkalinity, low pH waters of northern Europe and Canada. These results suggest that selenium may also be effective at blocking the accumulation of methylmercury in harder, more alkaline waters.

Animals↗