Nortriptyline: a model drug in geriatric depression.
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Aged↗
Biomedical subjects
R C Young
Publications and source records attributed to R C Young.
Mania in late life: focus on age at onset.
The authors review current understanding of manic syndromes and bipolar disorders in the elderly, emphasizing the limited number of systematic studies available. Discussion is focused on the validity of late age at onset as a nosologic distinction in geriatric patients. This issue is contrasted with possible age-associated effects on early-onset illness. Data regarding incidence and prevalence in the elderly are assessed, and the high average age at onset of mania is noted. The review cites evidence that relatively low rates of familial affective disorder and increased frequency of certain diseases and drug use are associated with late age at onset. Aspects of psychopathology in the elderly, course of illness, and outcomes including chronicity, mortality, and cognitive impairment/dementia are considered. Management of these elderly patients is briefly discussed, highlighting questions concerning response to lithium salts.
Adult↗
Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure.
PURPOSE: The study was undertaken to evaluate clinical prognostic factors, probability of response to therapy, duration of response, and overall survival of patients with Hodgkin's disease relapsing from a chemotherapy-induced complete remission. PATIENTS AND METHODS: Study population comprised 107 patients with Hodgkin's disease treated with combination chemotherapy at the National Cancer Institute who relapsed after achieving a complete remission. RESULTS: Half of the relapses occurred within the first year of achieving complete remission; among patients in remission 5 years or longer, only 4% relapsed. The overall survival of the relapsed patients is projected to be 17% at 20 years, calculated from the date of relapse. Primary treatment regimen, presence of B symptoms, stage, sex, liver involvement, pleural involvement, marrow involvement, and histologic subtype did not affect the survival of relapsed patients. Only age at diagnosis (older or younger than 30 years) and length of initial remission (shorter or longer than 1 year) made a significant impact on survival. Patients whose initial remission was longer than 1 year had significantly higher complete response rates to salvage therapy, significantly more durable second remissions, and significantly longer survival than patients whose initial remission was shorter than 1 year. Survival beyond 11 years from relapse of patients with long initial remissions was 24%; for those with short initial remissions, 11% (P2 = .027). Despite the fact that with salvage therapy, patients with long initial remission had an 85% complete response rate to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) with a disease-free survival of 45% at 20 years, acute leukemia and other treatment-related complications combined to lower the survival rate of this more favorable subset. CONCLUSIONS: These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.
Adolescent↗
Dose-intensive induction therapy with cyclophosphamide, cisplatin, and consolidative abdominal radiation in advanced-stage epithelial ovarian cancer.
PURPOSE: The primary goal of this trial was to evaluate the clinical activity of a high-dose cisplatin-based induction regimen for women with advanced-stage ovarian cancer. A secondary goal was to assess the use of whole-abdominal radiation as consolidative therapy in the subset of women left with less than 5 mm residual disease after completion of chemotherapy. PATIENTS AND METHODS: Fifty consecutive patients with newly diagnosed, advanced-stage ovarian cancer received cisplatin 40 mg/m2/d and cyclophosphamide 200 mg/m2/d intravenously (IV) for 5 days, every 4 to 6 weeks. After three to four cycles of chemotherapy, patients who still had residual disease less than 5 mm in greatest diameter at second-look surgery were given whole-abdominal radiotherapy. RESULTS: The overall response rate in 49 patients assessable for response was 61.3% (24.5% pathologic complete responses [pCRs], 32.7% pathologic partial responses [pPRs], and 4.1% clinical partial responses [cPRs]). Median survival for all patients was 23.4 months, and actuarial 4-year survival was 33.7% (95% confidence interval [CI], 21.8% to 48.1%). Multivariate analysis showed stage III and serous histology as independent favorable prognostic factors for survival. Median survival for stage III patients was 36.5 months, with an actuarial 4-year survival of 41.6% (95% CI, 25.5% to 59.6%). Median survival for stage IV patients was 12.0 months, with actuarial 4-year survival of 22.9% (95% CI, 9.5% to 45.5%). The major acute toxicities encountered were myelosuppression and peripheral neuropathy. Patients who received consolidative radiotherapy were at increased risk of developing late-onset enteropathy. CONCLUSIONS: This regimen is active against advanced-stage ovarian cancer, but the associated toxicity is severe. Consolidative whole-abdominal radiation did not appear to prolong survival in the subset of women left with less than 5 mm residual disease after chemotherapy.
Adolescent↗
Radiation therapy is better than chemotherapy in early-stage Hodgkin's disease? Not so fast.
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Antineoplastic Combined Chemotherapy Protocols↗
Gynecological malignancies.
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Endometrial Neoplasms↗
Etoposide in the treatment of non-Hodgkin's lymphomas.
Although etoposide has become one of the most active drugs for the treatment of non-Hodgkin's lymphoma, its optimal use remains to be determined. Nevertheless, it has been used judiciously in a wide variety of treatment settings, including management of aggressive non-Hodgkin's lymphoma, in combinations testing an aggressive approach for the treatment of advanced indolent lymphomas, integrated combined-modality therapy for localized aggressive lymphoma, salvage therapy, and induction regimens with autologous bone marrow transplantation. It has also been used in assorted combinations attempting to maximize antitumor efficacy while minimizing toxicity in elderly patients with lymphomas. This paper reviews the studies using etoposide in these various management situations.
Antineoplastic Combined Chemotherapy Protocols↗
Environmental health concerns of the Persian Gulf War.
Environmental health concerns in the Persian Gulf are peculiar to the geography of the region. Prevention of heat and solar injury deserves primary consideration, but cold injury also may occur in the desert. Immunizations are recommended against a number of diseases, while malarial chemoprophylaxis is necessary in Iraq and Kuwait. In addition to malaria, other parasitic diseases deserve consideration. Diarrheal diseases, diseases from the desert dust, and products of infected desert animals are of concern. Additional natural hazards are venomous bites from scorpions and desert snakes. Finally, threats of enemy action necessitated protection from nuclear biological and chemical weapons and LASER eye/skin injury. Unexploded ordinance will constitute a continuing hazard into the future.
Environmental Health↗
Management of early-stage ovarian cancer.
Approximately 30% of patients with epithelial ovarian cancer present with localized or early-stage disease. Accuracy of staging is dependent on careful surgical staging. Subsets of patients with specific prognostic factors have now been identified who do not require additional therapy after proper primary surgical staging. Poor prognosis patients do require adjuvant therapy. Whole abdominal irradiation, intraperitoneal P32, and single agent and combination chemotherapy have been utilized. The optimal therapy or whether any therapy is truly effective remains unknown.
Carcinoma↗
Smoking is a factor in causing acute chest syndrome in sickle cell anemia.
A link between cigarette smoking and "acute chest syndrome" in sickle cell anemia is suggested. Acute chest syndrome in the patient with sickle cell anemia is characterized by fever, leukocytosis, cough, chest pain, and pulmonary infiltrates in the chest radiograph. This article describes the results of a study of 69 adolescent and young adult sickle cell anemia patients. Twenty-nine of these patients were smokers, three were former smokers, and 37 were nonsmokers. Patients completed respiratory questionnaires that focused on smoking habits and included a history of chest syndrome. Information obtained was confirmed by review of clinical records. The chi-square test demonstrated a strong relationship between cigarette smoking and chest syndrome in sickle cell anemia. All 29 smokers had a history of chest syndrome, but only 24 of 37 nonsmokers had such a history. Although the exact mechanism of the relationship between smoking and the development of acute chest syndrome remains speculative, cigarette smoking joins infection, hypoxia, acidosis, infarction, dehydration, and analgesics as a causative factor in adolescent and adult patients with sickle cell anemia. Behavioral modification of the smoking habit in patients with sickle cell anemia may decrease the frequency of acute chest syndrome and sequelae of sickle cell lung disease.
Acute Disease↗
Geriatric mania.
Some general themes emerge from available information concerning manic states and bipolar disorders in late life: heterogeneity of both clinical features of the manic episode and of antecedent illness course; late average age at illness onset; lower rate of affective illness in families of late-onset cases; association of medical and neurologic illness and drug treatments with late-onset cases; utility of lithium salts for acute, continuation, and maintenance treatment; changes in lithium pharmacokinetics associated with aging, disease, and drugs resulting in increased plasma concentration/dose ratios. Geriatric manic states and bipolar disorders present opportunities for research. Investigation may illuminate the nature of mood disorders across the age spectrum, lead to better diagnosis and management in the elderly, and suggest strategies for prevention based on insights into pathophysiologic and pathogenetic mechanisms. Strategies that can be pursued include: longitudinal studies to evaluate differences in affective, cognitive, and other outcomes in geriatric patients with late-onset compared with early-onset illness; studies of psychopathology, family history, and illness course in organic mood disorder, manic; retrospective categorization when cognitive impairment accompanies acute episodes; studies of mania occurring in the context of dementing illness; application of neuroimaging and other laboratory measures to geriatric manic states; contrast of clinical and laboratory findings in early-onset geriatric patients and young adult patients to assess effect of age; definition of lithium concentration-effect relationships in regard to efficacy and toxicity in patients with and without cognitive impairment/dementia.
Aged↗
Patterns of coal workers' pneumoconiosis in Appalachian former coal miners.
To aid in diagnostic chest film interpretation of coal workers' pneumoconiosis, a composite profile of common radiologic patterns was developed in 98 Appalachian former coal miners who were diagnosed as having coal miner's pneumoconiosis and who applied for black lung benefits. The mean age was 61 years, with a lifetime coal mine dust exposure of 18.7 years. Results showed that chest radiographs of coal workers' simple pneumoconiosis contained small irregular linear opacities more frequently (47%) than small rounded opacities. Sparse profusion of all small opacities was the rule. Small opacities involved two out of six lung zones simultaneously 39% of the time while other combinations occurred less frequently. Lower zones were involved more frequently than upper ones. Thickened pleura occurred in 18% of radiographs. Other frequent radiographic abnormalities were parenchymal calcifications (19%), marked emphysema (12%), and inactive tuberculosis (12%). Calcification of the aortic knob, a degenerative process reflecting age, occurred in 9%. Only one instance of complicated coal workers' pneumoconiosis (progressive massive fibrosis) was encountered (0.7%). Many of the descriptive features of coal workers' pneumoconiosis noted in the literature were not observed in this study. Only one instance of complicated pneumoconiosis was encountered.
Appalachian Region↗
Trait-state artifacts and the diagnosis of personality disorders.
The multiaxial nature of DSM-III has stimulated interest in the personality disorders. There are also indications that it has produced an increase in their diagnosis. However, there is clinical and psychometric evidence that a personality evaluation undertaken while a patient is in a dysphoric mental state may distort or misrepresent traits, the so-called trait-state problem in personality assessment. The present study appears to be the first to investigate this phenomenon with a clinical interview rather than with personality tests. It examined the effect of anxiety, depression, and level of global impairment on the diagnosis of personality disorder and the assessment of the criteria for the individual Axis II disorders. Eighty-four patients, most of whom had current Axis I diagnoses, were evaluated by seven experienced clinicians with a new semistructured interview, the Personality Disorder Examination. The sample evidenced a trend toward acknowledging fewer maladaptive personality traits at follow-up than at entry. There was no evidence, however, that anxiety or depression had affected either the diagnosis of a personality disorder or the criteria associated with most of the individual personality disorders.
Adolescent↗
Passive membrane properties and inward calcium current of human uterine smooth muscle cells.
Human myometrium was obtained at the time of cesarean delivery by means of excisional biopsy from the upper margin of the uterine incision through the lower uterine segment. Isolated smooth muscle cells were obtained by collagenase treatment. With the whole-cell patch clamp technique, voltage-clamp and current-clamp experiments were performed. Regenerative action potentials were seen in 3 mmol/L calcium bathing solution. Voltage-clamp experiments demonstrated the presence of transient inward currents and large outward currents. Inward currents were isolated with the use of tetraethylammonium ion as a blocking agent of outward current. In 3 mmol/L calcium inward current began at -60 mV and maximum inward current occurred at -40 mV. Maximum inward current density during the rising phase of the action potential was 1.0 microA/cm2 in 3 mmol/L calcium and was unaffected by reduction of sodium concentration in the bathing solution.
Action Potentials↗
Characterization of sodium channels in cultured human uterine smooth muscle cells.
Voltage-clamp studies using the whole-cell patch clamp technique were performed on single cells of cultured human uterine smooth muscle obtained from term pregnancies. The small size of the cells allowed time resolution of transient ionic currents as short as 3 msec. A large, voltage-activated inward current was identified as a sodium channel conductance by the following criteria: (1) Removal of sodium from the bath eliminated the current; (2) current was blocked by the sodium-channel-blocking agent tetrodotoxin; (3) current was observed in the absence of calcium. The sodium current was large (maximal inward current 7.2 microA/cm2) and of short duration (decayed within 10 msec). The onset of activation of this current was -40 mV, with peak inward current at -10 mV. Steady-state voltage inactivation of this channel demonstrated half-maximal inactivation at -67 mV, indicating that this channel is largely inactivated at normal resting potentials.
Cells, Cultured↗
Advances in the management of early stage ovarian cancer.
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Clinical Trials as Topic↗
Hexamethylmelamine (altretamine): early National Cancer Institute trials.
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Altretamine↗
A case of late-onset crack dependence and subsequent psychosis in the elderly.
While rapidly spreading "crack" addiction is a major concern in our community, current research in this area is focused mainly on adolescents and young adults. We discuss a case of crack addiction developing for the first time in an elderly person and subsequent complications. We believe no such cases have been previously reported. We hope this will be helpful to practicing clinicians and stimulate research to understand cocaine and crack abuse patterns in the elderly.
Crack Cocaine↗