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Biomedical subjects

R C Young

Publications and source records attributed to R C Young.

At least 73 records · Page 4Linked to original sources
PubMed1996

Recovery in geriatric depression.

BACKGROUND: Clinical characteristics of depression, age at illness onset, medical burden, disability, cognitive impairment, lack of social support, and poor living conditions may influence the course of depression. This study investigates the timetable of recovery and the role of the above factors in predicting recovery in elderly patients with major depression. METHODS: Recovery was studied in 63 elderly (age >63 years) and 23 younger patients with depression who were followed up for an average of 18.2 months (SD, 13.1 months) under naturalistic treatment conditions. Diagnosis was assigned according to Research Diagnostic Criteria after administration of the Schedule for Affective Disorders and Schizophrenia. The Longitudinal Follow-up Interval Examination was used to identify recovery. RESULTS: The recovery rate of depressed elderly patients was similar to that of younger depressed patients. In the elderly patients, age, antidepressant treatment, age at onset, and chronicity of episode were significantly associated with time to recovery since entry. Among these parameters, late age at onset was the strongest predictor of slow recovery. In younger patients, long time to recovery was predicted by weak social support, younger age, cognitive impairment, and low intensity of antidepressant treatment. In the elderly, the intensity of antidepressant treatment began to decline within 16 weeks from entry and approximately 10 weeks prior to recovery. CONCLUSIONS: These findings challenge the view that geriatric depression has a worse outcome than depression in younger adults. However, depressed patients with onset of first episode in late life may be at higher risk for chronicity. Antidepressant treatment prescribed by clinicians may decline prior to recovery despite evidence that high treatment intensity is effective in preventing relapse.

Adult↗
PubMed1996

Intra-and intercellular calcium waves in cultured human myometrium.

Intracellular calcium waves were observed in cultured human myometrium using confocal laser scanning microscopy in the epifluorescence mode. Intracellular calcium waves were observed following stimulation of the cells with 10 mU ml-1 oxytocin in physiological bathing solution, or following substitution of tetraethylammonium chloride for NaCl. Intracellular wave speeds were 18.9 +/- 8.2 microns s-1 in physiological bathing solution. Intracellular calcium waves were also observed in cells bathed in calcium-free solutions, with no significant differences in wave speeds. Calcium waves that crossed cell boundaries were also observed. Some intercellular calcium waves travelled large distances (> 500 microns). Wave speeds for intercellular waves were 7.8 +/- 1.6 microns s-1. Attempts to use octanol to determine the contribution of gap junctions to intercellular calcium wave propagation were unsuccessful because of direct effects of 2 mM octanol on calcium oscillations. These data demonstrate that intra- and intercellular calcium waves are a means of tissue level communication in myometrium that is distinct from action potentials with regard to mechanisms of action, propagation speeds, responses to stimuli, and responses to inhibitors.

Calcium↗
PubMed1996

Disability in geriatric depression.

OBJECTIVE: The authors' purpose was to identify the relationship of disability to clinical measures that are part of a comprehensive psychiatric examination of depressed elderly patients. METHOD: The disability of 75 elderly inpatients and outpatients with major depression whose cognitive function ranged from normality to mild dementia was assessed with the Philadelphia Multilevel Assessment Instrument. Age at onset of depression, chronicity of depression, severity of depression, cognitive impairment, medical burden, social support and living environment were assessed with standardized instruments. RESULTS: Impairment in instrumental activities of daily living was significantly associated with advanced age, severity of depression, and medical burden. The relationship of depressive symptoms to impairment in instrumental activities of daily living was not influenced by age or medical burden. Anxiety and depressive ideation as well as retardation and weight loss were significantly associated with impairment in instrumental activities of daily living. Interviewer-rated global disability was associated with advanced age at onset of depression, medical burden, and overall cognitive impairment. Specifically, a disturbance in initiation and perseveration was significantly related to global disability. CONCLUSIONS: Impairment in instrumental activities of daily living appears to be a relatively independent dimension of health status that is related to depressive symptoms, particularly anxiety and depressive ideation as well as retardation and weight loss. Global disability may be associated with impairment in initiation and perseveration and with late onset of depression. These findings provide a basis for studies investigating whether psychotherapy aimed at depressive ideation and rehabilitation efforts focused on instrumental activities of daily living can improve the outcome of geriatric depression.

Activities of Daily Living↗
PubMed1996

Phase I trial of buthionine sulfoximine in combination with melphalan in patients with cancer.

PURPOSE AND METHODS: Resistance to alkylating agents and platinum compounds is associated with elevated levels of glutathione (GSH). Depletion of GSH by buthionine sulfoximine (BSO) restores the sensitivity of resistant tumors to melphalan in vitro and in vivo. In a phase I trial, each patient received two cycles as follows: BSO alone intravenously (i.v.) every 12 hours for six doses, and 1 week later the same BSO as cycle one with melphalan (L-PAM) 15 mg/m2 i.v. 1 hour after the fifth dose. BSO doses were escalated from 1.5 to 17 g/m2 in 41 patients. RESULTS: The only toxicity attributable to BSO was grade I or II nausea/vomiting in 50% of patients. Dose-related neutropenia required an L-PAM dose reduction to 10 mg/m2 at BSO 7.5 g/m2. We measured GSH in peripheral mononuclear cells (PMN), and in tumor biopsies when available, at intervals following BSO dosing. In PMNs, GSH content decreased over 36 to 72 hours to reach a nadir on day 3; at the highest dose, recovery was delayed beyond day 7. The mean PMN GSH nadirs were approximately 10% of control at BSO doses > or = 7.5 g/m2; at 13 and 17 g/m2, all but two patients had nadir values in this range. GSH was depleted in sequential tumor biopsies to a variable extent, but with a similar time course. At BSO doses > or = 13 g/m2, tumor GSH was < or = 20% of starting values on day 3 in five of seven patients; recovery had not occurred by day 5. We measured plasma concentrations of R- and S-BSO by high-performance liquid chromatography (HPLC) in 22 patients throughout the dosing period. Total-body clearance (CLt) and volume of distribution at steady-state (Vss) for both isomers were dose-independent. The CLt of S-BSO was significantly less than that of R-BSO at all doses, but no significant differences in Vss were observed between the racemates. Harmonic mean half-lives were 1.39 hours and 1.89 hours for R-BSO and S-BSO, respectively. CONCLUSION: A biochemically appropriate dose of BSO for use on this schedule is 13 g/m2, which will be used in phase II trials to be conducted in ovarian cancer and melanoma.

Adult↗
PubMed1996

Gynecological malignancies.

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)

Antineoplastic Agents↗
PubMed1996

Pulmonary disability in former Appalachian coal miners.

A prospective case-control study was undertaken to assess respiratory disability in 133 former coal miners who were claimants for "black lung" benefits. Consecutive assignment was made to either case or control group based on their chest radiograph having shown coal workers' pneumoconiosis or no coal workers' pneumoconiosis. A respiratory occupational survey was completed with physical examination that placed special emphasis on the cardiorespiratory systems. Subjects underwent pulmonary function testing while 92 of these also received arterial blood gases to assess respiratory disability and pulmonary insufficiency. Arterial blood gases were superior to spirometry in assessment of pulmonary insufficiency/disability. Smoking interacts with coal workers' pneumoconiosis to cause pulmonary insufficiency. The most frequent spirometric pattern was obstructive. Disability was caused by occupational injuries and comorbidities, both of which occurred with greater frequency in miners with coal workers' pneumoconiosis than in controls. Pulmonary insufficiency appears to be a better discriminator than respiratory disability in coal miners, suggesting that arterial blood gases replace spirometry in their evaluation. Greater emphasis on smoking intervention among coal miners should be given.

Appalachian Region↗
PubMed1995

Age at onset of geriatric depression and sensorineural hearing deficits.

Comorbidity of sensorineural hearing deficits and both depressive states and dementia in late life provided the rationale for this investigation. Cognitively intact geriatric major depressives (n = 43) were assessed for depressive symptoms, cognitive performance, and delusions while symptomatic, and following treatment, when audiometry was performed. Late-onset depressed patients (LOD) had more hearing deficits compared to early-onset depressives (EOD). Age at onset of depression was found to have a significant effect on Pure-Tone Thresholds for 0.5-4.0 kHz and on Word Recognition in Noise in the better ear (0.001 < p < 0.031; ANCOVA). Criteria for neural deficit were met more frequently in LODs compared to EODs, although this was attributable to the older age of LOD. Additional investigations can contribute to our understanding of the relationship between forms of hearing loss and both the course of geriatric depression and its relationship to dementia.

Age of Onset↗
PubMed1995

Maitotoxin increases voltage independent chloride and sodium currents in GH4C1 rat pituitary cells.

Maitotoxin (MTX) is a 3,424 dalton polyether marine toxin that causes influx of calcium through type L voltage-dependent calcium channels (L-VDCC) in GH4C1 rat pituitary cells, presumably as the result of membrane depolarization. In this study we have investigated the ionic conductances responsible for MTX-induced depolarization under voltage clamp conditions using the perforated and ruptured patch methods. MTX-induced steady-state voltage independent currents of nearly 400 pS/pF within seconds of addition to the bath. Ion substitution experiments demonstrated these currents are consistent with the conductance of sodium and chloride, but not calcium, ions. MTX induction of the voltage-independent chloride conductance in GH4C1 cells occurred concurrently without modification of L-VDCC currents. Pretreatment with nimodipine eliminated voltage activation of L-VDCC, and reduced by two thirds the voltage independent current. Analysis as a function of time of MTX exposure revealed that the first 60 sec of MTX-induced currents were not affected by nimodipine pretreatment, but subsequent additional currents were prevented. This indicates that the initial currents induced by MTX occur independently of L-VDCC mediated calcium entry, but full activation of these currents by MTX likely requires the involvement L-VDCC. Taken together this work identifies a voltage-independent sodium/chloride conductance as an initial action of MTX, one that may promote the sequence of ionic events leading to activation of L-VDCC and massive calcium entry.

Action Potentials↗
PubMed1995

Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem.

PURPOSE: To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem. PATIENTS AND METHODS: Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection. RESULTS: Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile-associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients. CONCLUSION: Ceftazidime and imipenem are both effective in the management of fever and chemotherapy-related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity.

Acyclovir↗
PubMed1995

The treatment of early stage ovarian cancer.

Approximately one third of women with ovarian cancer present with localized disease. A series of recent studies have identified a population of patients who require only comprehensive surgical staging for optimal results and another group that may benefit from adjuvant therapy. A series of national and international studies are evaluating a variety of adjuvant treatments in prospective randomized trials that may enhance long-term survival in poor-prognosis early ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

The management of early ovarian cancer.

Approximately one third of patients with epithelial ovarian cancer present with localized or early-stage disease. Prognostic features identify certain subsets of patients with good risk characteristics who do not require adjuvant treatment after comprehensive surgical staging and cytoreduction. Only a minority of patients undergo such a complete procedure, which often results in understaging of these patients. In the United States, patients with poor prognostic features, such as stage IC to II disease, poorly differentiated histologic grade, clear cell histology, dense adhesions, and large volume ascites, have received adjuvant chemotherapy. Single-agent or combination chemotherapy, whole abdominal irradiation, and intraperitoneal phosphorus 32 have been evaluated, although no modality has been shown to improve overall survival. Randomized trials investigating the optimal therapy or whether any therapy is truly effective are in progress. Until the completion of these trials, the most common postoperative adjuvant therapy in these patients in this country remains combination chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination chemotherapy.

PURPOSE: To review the efficacy of cyclophosphamide, doxorubicin, etoposide, methotrexate with leucovorin, and prednisone (ProMACE)-based combination chemotherapy programs in the treatment of patients with diffuse small noncleaved-cell non-Burkitt's lymphoma. PATIENTS AND METHODS: Thirty-three patients with diffuse small noncleaved-cell non-Burkitt's lymphoma were accrued: eight with localized disease were treated with modified ProMACE-mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus involved-field radiation therapy, and 25 with advanced-stage disease were treated with ProMACE/MOPP flexitherapy (n = 8), ProMACE-MOPP (n = 9), or ProMACE-cytarabine, bleomycin, vincristine, and methotrexate with leucovorin (CytaBOM) (n = 8). The median follow-up duration is 10 years. RESULTS: All eight patients with localized disease achieved a complete response, none have relapsed, and one died of intercurrent illness. Among patients with advanced-stage disease, five of eight (63%) flexitherapy-treated patients, six of nine (67%) ProMACE-MOPP-treated patients, and eight of eight (100%) ProMACE-CytaBOM-treated patients achieved a complete response. If the two ProMACE-MOPP-based groups are considered together, disease-free and overall survival rates at 15 years are projected at 61% and 35%, respectively. In contrast, only one patient has relapsed from a ProMACE-CytaBOM-induced complete remission, and overall survival of ProMACE-CytaBOM-treated patients (88%) is significantly higher than that for flexitherapy and ProMACE-MOPP (P2 = .04). CONCLUSION: Adult patients with diffuse small non-cleaved-cell non-Burkitt's lymphoma may be effectively treated with regimens that are effective in other aggressive lymphomas (eg, diffuse large-cell lymphoma).

Adult↗
PubMed1994

Mood disorders associated with acoustic neuromas.

OBJECTIVE: The primary purpose of this article is the presentation of three cases of manic and mixed states associated with an acoustic neuroma, and review of the literature on psychiatric symptoms accompanied by the tumor. METHODS: The cases were identified from 830 consecutive inpatient psychiatric admissions over age fifty-five years. Patients were assessed using a Structured Clinical Interview (SCID-R), and met DSM-III-R criteria for the diagnosis of bipolar disorder. The psychopathology seen in acoustic neuroma patients and the pathophysiologic mechanisms proposed to explain them are reviewed. RESULTS: The cases we report differ from other cases in the literature in that psychiatric symptoms began pre-operatively and remained for long periods post-operatively. The psychiatric signs and symptoms reported in acoustic neuroma patients are usually described as transient, and these include mood changes, agitation, persecutory delusions, hallucinations, and memory loss and confusional episodes. The disruption of brainstem structures including the auditory pathways, the cerebellum and the ascending reticular system may contribute to mood changes. Systematic studies are necessary to examine their relationship. Although psychological reactions attributable to surgery and facial paralysis may serve as contributory factors the evidence for their role was not striking in the cases we report.

Aged↗