The sounds of silence.
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Antineoplastic Agents↗
Biomedical subjects
R C Young
Publications and source records attributed to R C Young.
Executive dysfunction and long-term outcomes of geriatric depression.
BACKGROUND: This study investigated the relationship of executive and memory impairment to relapse, recurrence, and course of residual depressive symptoms and signs after remission of geriatric major depression. METHODS: Fifty-eight elderly subjects remitted from major depression received continuation nortriptyline treatment (plasma levels 60-150 ng/mL) for 16 weeks and then were randomly assigned to either nortriptyline maintenance therapy or placebo for up to 2 years. Diagnosis was made using the Research Diagnostic Criteria and the DSM-IV criteria after an interview using the Schedule for Affective Disorders and Schizophrenia. Executive dysfunction and memory were assessed with the Dementia Rating Scale, disability and social support were rated with the Philadelphia Multiphasic Instrument, and medical burden was assessed with the Cumulative Illness Rating Scale. RESULTS: Abnormal initiation and perseveration scores, but not memory impairment, were associated with relapse and recurrence of geriatric depression and with fluctuations of depressive symptoms in the whole group and in subjects who never met criteria for relapse or recurrence during the follow-up period. Memory impairment, disability, medical burden, social support, and history of previous episodes did not significantly influence the outcome of depression in this sample. CONCLUSIONS: Executive dysfunction was found to be associated with relapse and recurrence of geriatric major depression and with residual depressive symptoms. These observations, if confirmed, will aid clinicians in identifying patients in need of vigilant follow-up. The findings of this study provide the rationale for investigation of the role of specific prefrontal pathways in predisposing or perpetuating depressive syndromes or symptoms in elderly patients.
Age Factors↗
Age and nortriptyline concentrations in plasma ultrafiltrate.
OBJECTIVES: Since plasma protein binding of tricyclic antidepressants may be relevant to treatment effects and can be influenced by age-associated factors, we examined both plasma ultrafiltrate and total concentrations of nortriptyline (NT) in patients and compared these to age. We hypothesized negative associations with age of both ultrafiltrate NT and the ratio of ultrafiltrate NT to total plasma NT. METHODS: Patients with major depression at a psychiatric service treated with a stable dose of NT were studied. Trough plasma ultrafiltrate NT concentrations and total plasma NT concentrations were measured by high performance liquid chromatography. Concentrations were corrected for dose. RESULTS: Eighty-seven patients aged 26 - 88 years were studied. Ultrafiltrate NT concentrations and the ratio of ultrafiltrate NT to total NT concentrations were both significantly negatively associated with age. Total NT concentrations were not significantly associated with age. CONCLUSIONS: Relatively low ultrafiltrate NT concentrations in older patients may reflect lower tissue exposure at a given total plasma NT concentration. This could be relevant to toxic and therapeutic effects. Studies of relationships between non-bound drug concentrations and NT treatment outcomes across the age span are needed.
Adult↗
Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF.
PROBLEM: Over-expression of epidermal growth factor-receptors (EGF-R) has been described in a variety of cancers, including cervical cancer. Nicotine may increase cellular proliferation rates through a mechanism involving EGF or EGF-R. In this study, we ascertain the effect of EGF antibodies on nicotine-enhanced proliferation rates in two cervical cancer cell lines. METHOD OF STUDY: We studied (a) nicotine-induced increase in the cellular expression of EGF-R in human papillomavirus (HPV)-positive ME-180 and HPV-negative HT-3 cervical cancer cell line cultures, using a semi-quantitative immunofluorescent antibody assay; (b) alterations in cellular proliferation in association with changes in EGF-R levels; and (c) the EGF-R mediation by EGF. RESULTS: Nicotine exposure at physiologically attainable plasma concentrations caused increased expression of EGF-R in both cervical cancer cell lines. Up-regulation of EGF-R was associated with increased cellular proliferation. Decreased expression of EGF-R was associated with decreased cellular proliferation. These data were consistent with EGF-R expression as a mechanism for the control of proliferation of the cervical cancer cells. The action of nicotine was abrogated when antibodies to EGF were added, implying that nicotine up-regulation of EGF-R may be mediated by EGF. CONCLUSIONS: Our data show that nicotine-induced proliferation of cervical cancer cells is mediated through EGF-R over-expression and that this action of nicotine utilizes EGF.
Cell Division↗
Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer.
PROBLEM: To ascertain if cervical epithelial epidermal growth factor receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. METHOD OF STUDY: We tested cervical biopsies obtained from 18 controls, 3 women with cervical intraepithelial neoplasia (CIN) I, 17 women with CIN II and III, and 12 women with cervical cancer for EGF-R using a quantitative immunofluorescent antibody assay. We measured serum IGF-II levels using an enzyme-linked immunosorbent assay in 20 controls, 26 CIN patients, 12 with cervical cancer before therapy, 5 with cervical cancer for < 1 year, and 9 others > 1 year after therapy. RESULTS: The levels of cervical EGF-R in women with CIN and cervical cancer were significantly higher (P<0.05 for CIN I; P<0.001 for patients with CIN II and III or cervical cancer) than in controls. Women with cervical cancer (P<0.001 vs. controls) or advanced CIN (P = 0.03) had elevated levels of serum IGF-II, while the women with CIN I had levels similar to controls. Women with cervical cancer in the post-therapy period had significantly lower serum IGF-II levels than the women with cervical cancer before therapy (P<0.001). CONCLUSION: Cervical epithelial EGF-R and serum IGF-II levels may be used for the diagnosis and prognosis of cervical cancer.
Biomarkers, Tumor↗
Fox Chase Network: Fox Chase Cancer Center's community hospital affiliation program.
Fox Chase Cancer Center developed a format for affiliation with community providers in 1986. Fox Chase Network was formed to establish hospital-based community cancer centers to increase access to patients involved in clinical research. Under this program, the Fox Chase Network now contributes 500 patients per year to prevention and clinical research studies. As relationships with community providers form, patient referrals have increased at Fox Chase Cancer Center and for each Fox Chase Network member. A dedicated staff is required to operate the central office on a day-to-day basis as well as at each affiliate. We have found this to be a critical element in each program's success. New challenges in the cancer business-increasing volumes with declining revenue-have caused us to reconfigure the services offered to affiliates, while maintaining true to our mission: to reduce the burden of human cancer.
Cancer Care Facilities↗
Three cycles versus six cycles of adjuvant paclitaxel (Taxol)/carboplatin in early stage ovarian cancer.
The optimal management of early stage ovarian cancer with poor prognostic features remains controversial. On the basis of results of studies in advanced ovarian cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a platinum agent has become part of adjuvant chemotherapy trials in early stage disease. Because the optimal number of chemotherapy cycles has not been determined, the Gynecologic Oncology Group is conducting a study comparing three cycles with six cycles of adjuvant paclitaxel/carboplatin in high-risk patients with early stage ovarian cancer. At a median follow-up period of 3 years, 290 (88%) of the 331 evaluable patients on both arms of the trial were alive and recurrence free. Regimen B (treatment groups have not yet been unblinded) was associated with a somewhat higher incidence of grade 3/4 leukopenia and a markedly higher frequency of grade 2-4 neurologic toxicity. Final results from this study will reveal any difference in overall or progression-free survival between the two regimens.
Adult↗
Automated oxyhemoglobin dissociation curve construction to assess sickle cell anemia therapy.
Oxyhemoglobin dissociation curves measure the most important function of red blood cells - the affinity for oxygen and its delivery to the tissues. This function may be deranged in sickle cell anemia and some other hemoglobinopathies. An automated oxyhemoglobin dissociation curve analyzer constructed dissociation curves in 55 patients with hemoglobinopathies and in 24 control subjects while maintaining constant temperature and pH. Sigmoid curves were converted to rectilinear ones using the Hill equation. Oxygen affinity of red cells was assessed by calculation of P50 (the PO2 at which hemoglobin is half saturated). Results revealed separation of oxyhemoglobin dissociation Hill plots according to phenotype but with wide variability. Mean oxygen affinity of fetal hemoglobin was greatest, whereas that of sickle hemoglobin was least. Other hemoglobins were intermediate. A positive correlation between decreased oxygen affinity and carboxyhemoglobin confirmed the decreased oxygen affinity of sickle hemoglobin and decreased oxygen affinity and increased diphosphoglycerate in red cells. Hill plots are less sensitive discriminators of oxygen affinity than traditional sigmoid dissociation curves and offer no particular advantage. Serial studies in a subset of three sickle cell anemia patients treated conservatively suggest automated oxyhemoglobin dissociation curves may be useful in assessment of effectiveness of newer therapies of sickle cell anemia after refinement of the method and studies of larger populations.
Adult↗
Brain computed tomography in geriatric manic disorder.
BACKGROUND: Excess brain changes in geriatric manic patients have been hypothesized. Few neuroimaging studies are available. METHODS: Brain computed tomography scans in geriatric patients with manic disorder (n = 30) were compared to those in same-age control subjects (n = 18). Ratings of cortical sulcal widening (CSW), lateral ventricle-brain ratio (VBR), and related linear measures were determined. RESULTS: Patients had greater CSW scores (Exact p = .002) and VBR (t = 2.51, df = 46, p < .02) compared to control subjects. CSW was positively associated with age at illness onset (rs = .46, p < .01) and age at first manic episode (rs = .53, p < .005). VBR was poorly correlated with CSW and was not associated with these indices of illness course. CONCLUSIONS: These findings support the need for further investigation of relationships between brain structure and clinical features in geriatric mania.
Aged↗
Three-dimensional structure of the smooth muscle in the term-pregnant human uterus.
OBJECTIVE: To identify the structural elements and describe the three-dimensional microanatomy of the term-pregnant human uterus. METHODS: Biopsy specimens were taken from the funduses and the lower uterine segments of two term-pregnant uteri. Tissue was sectioned serially and stained with Masson trichrome. Microscope images were captured with a digital camera, aligned, and computer-processed. Computer-assisted three-dimensional reconstruction of structures was performed. RESULTS: Five structures were identified: 1) fasciculus-the macroscopic organization of myocytes and connective tissue, 2) cylindric bundle-300+/-100-microm diameter cylinder of densely packed myocytes, 3) sheet-like bundle-densely packed sheet of myocytes, 4) fiber bundle-a loosely packed bundle of small numbers of myocytes, and 5) communicating bridge-a large cylindric bundle that bridges adjacent fasciculi. The cylindric bundles merged, dichotomized, and intertwined with each other and with sheet-like bundles. Essentially all myocytes except those in fiber bundles were contiguous. CONCLUSION: The microanatomy of the term-pregnant human uterus contains clearly defined structural elements. These structures merge with each other and potentially form an interlacing network, connecting the vast majority of the myocytes of the uterus in a contiguous pathway.
Female↗
Calcium-calmodulin mediates bradykinin-induced MAPK phosphorylation and c-fos induction in vascular cells.
The vasoactive peptide bradykinin (BK) has been implicated in the pathophysiology of a number of vascular wall abnormalities, but the cellular mechanisms by which BK generates second messengers that alter vascular function are as yet undefined. Exposure of vascular smooth muscle cells (VSMC) to BK (10(-7) M) produced a rapid and transient rise in intracellular calcium, which preceded an increase in tyrosine phosphorylation of mitogen-activated protein kinase (MAPK). MAPK activation by BK was observed as early as 1 min, peaked at 5 min, and returned to baseline by 20 min. Treatment of cells with the intracellular calcium chelator EGTA-acetoxymethyl ester inhibited BK-stimulated MAPK activation, suggesting that intracellular calcium mobilization contributes to the activation of MAPK. The calmodulin inhibitor W-7 also markedly inhibited BK-induced MAPK phosphorylation in the cytoplasm as well as in the nucleus. Moreover, the BK-induced increase in c-fos mRNA levels was significantly inhibited by the calmodulin inhibitor, indicating that calmodulin is required for BK signaling leading to c-fos induction. These results implicate the calcium-calmodulin pathway in the mechanisms for regulating MAPK activity and the resultant c-fos expression induced by BK in VSMC.
Animals↗
On and off the playing field: ethics in medicine.
The sportscasters' metaphor, "on and off the playing field," is used to describe the altruistic demeanor of good ethical and moral behavior and empathy toward patients that is required of medical students and physicians. It has been noted that these altruistic qualities often compete unsuccessfully with scientific skills and scholarly pursuits. Many schools hold the "White Coat Ceremony" annually and host a chapter of the Honor Medical Society to instill these traits in students. Teaching of altruistic demeanor is most successful using a combination of techniques, which include philosophy, virtue theory, small-group discussions using case vignettes, and the structured objective clinical examination with "standardized patients." On the playing field, current major issues are intellectual honesty, mandatory testing/treatment for HIV/AIDS, abortion, end-of-life issues, and gene therapy. Off the playing field, family, religion, community service, and leadership will immortalize medical students in the mythical Health Care Hall of Fame.
Altruism↗
Brain morphology and response to nortriptyline in geriatric depression.
In geriatric patients with major depression (N=15), the authors compared response to treatment with nortriptyline as it relates to brain morphology assessed by computed tomography. There was a significant negative association between ventricle-brain ratio and response to nortriptyline (rs=-0.63; P=0.015).
Aged↗
Are sociodemographic factors important in sarcoidosis?
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Adult↗
Alpha(1)-acid glycoprotein, age, and sex in mood disorders.
Serum alpha(1)-acid glycoprotein (AAG) reportedly can increase with age in the normal population, especially among women. In 33 patients with unipolar major depression or bipolar disorder, serum AAG was measured by age. The authors noted a positive association with age, particularly in depressed female patients (n=18; r(s)=0.61; P<0.01). The authors discuss implications for drug pharmacokinetics. Investigation of AAG in mood disorders needs to take age and sex into consideration.
Adult↗
Metastatic renal-cell carcinoma: what causes occasional dramatic regressions?
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Adjuvants, Immunologic↗
Teasing in hierarchical and intimate relations.
Following E. Goffman's (1967) face threat analysis of social interaction, it was hypothesized that the aggressive, playful content of teasing would vary according to social status and relational satisfaction, personality, role as teaser or target, and gender. These 4 hypotheses were tested in analyses of the teasing among fraternity members (Study 1) and romantic couples (Study 2). Consistent with a face threat analysis of teasing, low-status fraternity members and satisfied romantic partners teased in more prosocial ways, defined by reduced face threat and increased redressive action. Some findings indicate that disagreeable individuals teased in less prosocial ways, consistent with studies of bullying. Targets reported more negative emotion than teasers. Although female and male romantic partners teased each other in similar ways, women found being the target of teasing more aversive, consistent with previous speculation.
Aggression↗
P300 latency in geriatric depression.
OBJECTIVE: The purpose of this study was to determine if P300 latency is prolonged in geriatric depression and if longer P300 latency and deficits in initiation and errors of perseveration in depressed elderly patients are related to risk factors for vascular disease. METHOD: Geriatric patients with unipolar depression (N = 43) and elderly comparison subjects (N = 24) were assessed for depressive symptoms, cognitive functions, risk factors for vascular disease, and P300 latency. RESULTS: Depressed elderly patients had longer P300 latency than normal elderly subjects. In the depressed patients, P300 latency was related to deficits in initiation and errors in perseveration. Risk factors for vascular disease were associated not only with P300 latency but also with deficits in initiation and errors in perseveration. CONCLUSIONS: Functional impairment of the cortico-striato-pallido-thalamo-cortical pathways from vascular disease, implicated in late-life depressive disorders, may explain not only deficits in initiation and errors in perseveration but also longer P300 latency in depressed elderly patients. These results are preliminary and need further examination with brain imaging and more sensitive neuropsychological measures.
Aged↗