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At least 253 records · Page 14Linked to original sources

PubMed1992

Ifosfamide-based chemotherapy for patients with resistant germ cell tumors: the Memorial Sloan-Kettering Cancer Center experience.

Sixty-six patients with germ cell tumors (GCTs) refractory to cisplatin plus etoposide/vinblastine-based therapy were treated with cisplatin, ifosfamide, and either etoposide (VIP) (50 patients) or vinblastine (VeIP) (16 patients). Sixty-two patients were evaluable for response. Twenty-one patients (34%) achieved a complete response (CR), 18 with chemotherapy alone and an additional three following surgical resection of viable tumor. Six of these patients have relapsed, and 15 (24%) remain in CR at a median follow-up of 13 months (range, 3+ to 41+ months). Three patients who achieved an incomplete response or relapsed from CR are disease free following additional salvage therapy; one patient underwent resection of a solitary metastasis and two received high-dose chemotherapy with autologous bone marrow rescue. Ifosfamide adds efficacy to cisplatin plus etoposide or vinblastine-based salvage therapy. Ifosfamide/cisplatin-based combinations should be considered in the first-line salvage treatment of germ cell tumors. The modest proportion of patients who achieve a durable CR following salvage therapy with VIP/VeIP emphasizes the need for early identification of treatment failure and more effective salvage therapy.

Adult↗

PubMed1992

Treatment of limited-disease small cell lung cancer.

Refinements in the use of chemotherapy, both alone and in combination with chest irradiation, have prolonged the survival of patients with limited-disease small cell lung cancer in the last two decades. Based on reviews of trials of patients with both limited and extensive disease, these improvements appear to transcend adjustments made in the staging of limited disease. Alternation of chemotherapy regimens according to the Goldie-Coldman hypothesis has not proven advantageous in this setting. Etoposide combined with cisplatin has been effective as a salvage regimen for previously treated small cell lung cancer, and is particularly useful in first-line treatment approaches when given concurrently with chest irradiation. Although prophylactic cranial irradiation has reduced central nervous system recurrence in complete responders, its role remains controversial due to an unclear effect on survival and associated long-term toxicities. Our present understanding of the biology of limited-disease small cell lung cancer should lead to further refinements in treatment.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

The role of etoposide therapy in germ cell cancer.

In the last decade, etoposide has become a standard component of first-line combination chemotherapy in germ cell cancer. The replacement of vinblastine by etoposide in primary treatment came after the therapeutic efficacy of etoposide-containing regimens was determined to be equivalent or superior to vinblastine, with diminished short-term side effects. Subsequent investigations in the salvage setting have demonstrated that high-dose carboplatin and etoposide regimens coupled with autologous bone marrow transplantation can cure some patients with highly resistant disease, and that novel scheduling of etoposide using daily, oral, low-dose therapy can provide effective palliation in some patients. Although these therapeutic successes have been clouded by the demonstration of secondary acute leukemias in rare patients who have received high-dose etoposide, the challenge of the 1990s will be to capitalize on the clinical leads of dose and scheduling as well as to continue to document the long-term safety of these agents.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

[Indications for Clozapine].

Clozapine does not constitute a first-line treatment due to the occurrence of agranulocytosis. However, the benefit risk/ratio fully justifies its use in two situations: resistance to neuroleptics, intolerance to neuroleptics. There are no internationally recognized objective criteria to define resistance. The ones defined in the well-restricted methodological environment of a clinical trial are generally not applicable to daily practice. In particular, the accepted criteria do not always take into account the personal factors, the social and environmental context and rehabilitation programs. May et al. for example defined in 1988 the degree of response to therapy based on clinical improvement as well as social integration. It is widely recognized that if the severity of residual symptoms (grade 5 response) requires the hospitalization, treatment with clozapine is warranted. For partial responders to classical treatment (grade 4 response) who could benefit from clozapine, the risk ratio of clozapine needs to be further evaluated. The identification of predictive factors of response to therapy would allow a novel approach of this indication. According to certain authors, paranoid type responds best to therapy. However, the evidence collected to date needs to be confirmed. In particular, the effects of clozapine on predominantly negative symptoms require further investigations. In contrast to several european studies, intolerance to neuroleptics is rarely a reason for initiation of clozapine therapy. This would indicate that the appreciation of intolerance to neuroleptics notably varies from one country to the next. Intolerance criteria need to be further specified as well as the benefit risk/ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Clozapine↗

PubMedDate not supplied

Reassessment of the role of theophylline in the current therapy for nocturnal asthma.

BACKGROUND: Symptoms of asthma commonly increase at night for a variety of reasons. While different options are available for the management of nocturnal asthma, theophylline has maintained a prominent role in treating this problem, and it is widely promoted as a first-line agent. Very recent reports stress the use of anti-inflammatory agents as the drugs of choice for the long-term treatment of asthma. METHODS: Using the key words "asthma," "theophylline," "bronchodilators," "adrenal cortex hormones," "beclomethasone," "triamcinolone acetonide," and "disodium cromoglycate," the MEDLINE files were searched from 1982 to the present. Articles dating before 1982 were accessed from cross-reference of the more recent articles. RESULTS: Sustained-release theophylline preparations are effective in decreasing the rate of exacerbations of nocturnal asthma symptoms, but theophylline has risks of major toxicity and serum concentrations must be monitored. Inhaled corticosteroids are also useful in controlling nocturnal asthma, and they reduce inflammation, which is the basic problem in asthmatics. Inhaled anticholinergics and oral controlled-release albuterol are also helpful in reducing symptoms of nocturnal asthma. CONCLUSIONS: A suggested approach to managing nocturnal asthma includes corticosteroids inhaled through a spacer device at optimum doses, adding inhaled albuterol or oral sustained-release albuterol and then ipratropium with a spacer. If control is not maintained with this regimen, sustained-release theophylline may add benefit to inhaled steroid therapy in reducing nighttime asthma symptoms. Long-acting inhaled beta 2 agonists show promise and could be the adjunctive treatment of choice when they become available in the United States.

Adrenal Cortex Hormones↗

PubMed1992

Drugs for treatment of peptic ulcers.

Pharmacologic management of peptic ulcer disease continues to evolve with the introduction of diverse types of new therapeutic agents. The ideal aims of treatment of peptic ulcer disease are to relieve pain, heal the ulcer, and delay ulcer recurrence. This article provides a broad perspective on the pharmacology and therapeutic actions of antiulcer drugs. To date, no drug meets all goals of therapy. Drug treatment of peptic ulcers is targeted at either counteracting aggressive factors or stimulating the mucosal defense. Drugs that inhibit or neutralize gastric acid secretion include histamine H2-receptor antagonists, proton pump inhibitors, anticholinergics, prostaglandins, and antacids. H2-receptor antagonists have become first-line drugs for treatment of uncomplicated duodenal ulcers, gastric ulcers, prevention of ulcer relapse, and mild esophagitis. However, H2-receptor antagonists, like other gastric antisecretory/antiulcer drugs, have high rates of ulcer recurrence following discontinuation of therapy. They therefore need to be administered continuously in patients prone to such recurrences. Omeprazole has emerged as a major drug for the treatment of severe erosive esophagitis, refractory ulcers, and Zollinger-Ellison syndrome. The major disadvantage of proton pump inhibitors is the concern for their long-term safety. The roles of M1-antimuscarinic agents and antacids have not been fully defined. Misoprostol, effective for the treatment of gastric and duodenal ulcers, is now the only drug that prevents ulcers induced by nonsteroidal anti-inflammatory drugs. Mucosal protective drugs that do not inhibit gastric acid secretion include sucralfate and organic bismuth salts. Sucralfate is a nonsystemic, well-tolerated, effective drug for treatment of duodenal ulcers and prevention of duodenal ulcer relapse. The organic bismuth salt bismuth subcitrate is efficacious in the treatment of duodenal and gastric ulcers. Furthermore, it has also been established that it alters the course of ulcer recurrence. However, bismuth encephalopathy is a major toxicity concern that needs to be addressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Ulcer Agents↗

PubMed1992

Control of gastric acid secretion. Histamine H2-receptor antagonists and H+K(+)-ATPase inhibitors.

Gastric acid secretion is regulated by an intricate interplay of neural (acetylcholine), hormonal (gastrin), and paracrine (histamine, somatostatin) mechanisms. Receptors for each of these agents and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of acetylcholine and gastrin is mediated by an increase in cytosolic calcium, whereas that of histamine is mediated by activation of adenylate cyclase and generation of cAMP. Strong potentiation between histamine and either gastrin or acetylcholine reflects postreceptor interaction between the distinct pathways as well as the ability of acetylcholine and gastrin to release histamine from mucosal ECL cells. The inhibitory effects of somatostatin on acid secretion are mediated by receptors coupled by guanine nucleotide-binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+K(+)-ATPase, the proton pump of the parietal cell. Precise information on the mechanisms involved in gastric acid secretion has led to the development of potent drugs capable of inhibiting acid secretion. These include competitive antagonists that interact with stimulatory receptors (e.g., histamine H2-receptor antagonists) as well as noncompetitive inhibitors of H+K(+)-ATPase (e.g., omeprazole). The histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, and nizatidine) continue as first-line therapy for peptic ulcer disease and are effective in preventing relapse. Although they are generally well tolerated, histamine H2-receptor antagonists may cause untoward CNS, cardiac, and endocrine effects as well as interference with the absorption, metabolism, and elimination of various drugs. Omeprazole is a weak base that reaches the parietal cell through the bloodstream, diffuses through the cytoplasm, and becomes activated and trapped as a sulfenamide in the acidic canaliculus of the parietal cell. It covalently binds to H+K(+)-ATPase, thereby irreversibly blocking acid secretion in response to all modes of stimulation. The main drawback to its use is its extreme potency, which leads to virtual anacidity, gastrin and ECL cell hyperplasia, hypergastrinemia, and, in rats, to the development of carcinoid tumors.

Absorption↗

PubMed1992

[Sulfasalazine in the treatment of rheumatoid arthritis. A multicenter open study of 150 patients during 6 months].

One hundred and fifty patients with rheumatoid arthritis were given sulfasalazine in a daily dosage of 2 g during an open-label, multicenter, six-month trial. Improvements were apparent as early as four weeks after initiation of the drug. Improvements in clinical parameters and erythrocyte sedimentation rate were statistically significant. In the patients who remained on the study protocol, clinical and biological improvements continued over time and were more marked after six months. Overall clinical safety was satisfactory: 30 patients were withdrawn from the trial for adverse events, all of which resolved after discontinuation of the study drug. Most of these adverse events (93%) developed within two months of initiation of the drug, demonstrating the need for hematologic and hepatic tests at regular intervals during the first three months of sulfasalazine therapy. Thirty-four patients had not previously received maintenance therapy; in this subgroup, only one patient was withdrawn for ineffectiveness. In view of its favorable risk/benefit ratio and fast action, sulfasalazine may be a useful first-line drug in patients with rheumatoid arthritis.

Aged↗

PubMed1992

Isradipine in the treatment of mild-to-moderate hypertension in Portugal.

A short-term trial of isradipine was conducted to assess its effectiveness and tolerability in the treatment of mild-to-moderate hypertension. The study was carried out by general practitioners and involved 2,702 patients, aged 18-70 years, who had diastolic blood pressures (DBP) of 95-114 mm Hg. Patients completed a pretreatment phase of up to 4 weeks for antihypertensive drug washout and placebo run-in, before entering a 12-week active-treatment phase with 1.25 mg of isradipine twice daily, which was increased after 4 weeks to 2.5 mg twice daily, depending on the blood pressure response. At the end of 12 weeks, the mean systolic blood pressure (SBP) and DBP were 148.1 and 86.7 mm Hg compared with 169.0 and 103.0 mm Hg after placebo, respectively. The majority of patients (89.6%) had a DBP reduction greater than 10 mm Hg, and 86.2% had normalized DBP (less than or equal to 90 mm Hg) at the end of treatment. Adverse events were reported by 2.8% of patients, and 90% of patients and general practitioners reported satisfaction with the treatment. Thus, our results indicate that isradipine is effective and well tolerated, and may deserve a place as first-line treatment in mild-to-moderate hypertension.

Adolescent↗

PubMed1992

Etoposide, ifosfamide, and methotrexate combination chemotherapy for aggressive non-Hodgkin's lymphomas after failure of the LNH 84 regimen.

We assessed the efficacy and tolerability of VIM (etoposide/ifosfamide/methotrexate) combination therapy in 24 patients who were failing the treatment protocol of the Lymphomes Non Hodgkiniens (LNH) 84 study. Eight patients were refractory to the LNH 84 induction cycles, but ten achieved a partial response (PR). The six remaining patients attained complete response (CR) after LNH 84 induction, but relapsed either during consolidation therapy or after completing the whole program. Twenty-three patients are evaluable for response. The VIM regimen provided a CR rate of 43% and a PR rate of 17%. Treatment failed in nine cases (39%). The CR rate was particularly high (67%) in the group of patients who had PR with LNH 84 induction treatment. Of the ten who had attained CR, five relapsed after 4 to 42 months and five are still alive with no evidence of disease after 29 to 62 months. VIM therapy was well tolerated. A total of 101 VIM courses were given. Myelotoxicity was the most common side effect. Grade 3 or 4 cytopenia was recorded after 11% of the cycles. Among eight infectious episodes recorded, one was fatal. This study demonstrates that CR and long disease-free survival are obtainable with the VIM regimen in a small number of patients failing a high-dose doxorubicin-containing first-line treatment.

Adult↗

PubMed1992

Angiotensin converting enzyme inhibitors and the cardiovascular system.

OBJECTIVE: To show that angiotensin converting enzyme (ACE) inhibitors benefit the cardiovascular system to a greater extent than other antihypertensive agents. DATA EXTRACTION: An extensive literature search has shown that ACE inhibitors can induce regression of left ventricular hypertrophy, which may improve systolic and/or diastolic function in the left ventricle; increase in arterial compliance; and improve clinical signs of congestive heart failure and reduce mortality in patients with severe heart failure. In addition, ACE inhibitors have either a neutral or a beneficial effect on blood lipids and lipoproteins. These agents also have potential anti-ischaemic and anti-arrhythmic activity but do not depress resting cardiac function. CONCLUSION: ACE inhibitors are uniquely valuable first-line antihypertensive agents, especially in patients with cardiovascular risk.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Recent developments in endocrine treatment of prostate cancer.

Cancer of the prostate gland is the most frequently occurring malignant lesion in men. Because most prostate cells depend on androgen for growth, removal of testosterone by either orchiectomy or medical castration using diethylstilbestrol or a luteinizing hormone-releasing hormone (LHRH) analogue is first-line treatment for patients with symptomatic Stage D2 disease. The trend in hormonal therapy has been toward long-acting minimal-dosing high-compliance regimens, capitalizing on the recent availability of the long-acting LHRH analogues, which require only monthly injections to maintain castration levels of testosterone, and the nonsteroidal antiandrogen ICI 176,334, which (in early clinical trials) appears to block intracellular testosterone activity with a once-a-day oral regimen. To eliminate the rapid LH increase that can occur during early agonist therapy, combinations of LHRH analogues and antiandrogens (total androgen blockade) have been tested and appear promising. The effects of hormonal treatment in patients with symptomatic Stage D2 prostate cancer have been studied extensively and are relatively well understood. By contrast, hormonal treatment has not been explored in contemporary randomized Phase III trials of asymptomatic Stage D2, D1, or C disease, localized Stage B or A disease, or before prostate surgery or radiation treatment. Research must continue to determine the optimal regimen that suppresses testosterone activity with the least amount of toxicity.

Androgen Antagonists↗

PubMed1977

Drug prescribing in rheumatoid arthritis in Otago.

The drug therapy prescribed for a group of 50 patients with rheumatoid arthritis in Otago prior to specialist referral was examined. Thirty-two patients were receiving some first-line anti-inflammatory drugs and six were receiving no therapy at the time of their first hospital clinic visit. Salicylates had been prescribed first in only 16 of the 50 patients while this drug had been withdrawn because of side effects in about one-third of the patients who had been treated with it prior to specialist referral. Seven patients had received phenylbutazone and six corticosteroids as the first treatment for their rheumatoid arthritis. About one-third of the patients were receiving more than one anti-inflammatory drug at the time of their initial clinic visit.

Adult↗

PubMed1979

Bretylium tosylate: a review.

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, drug interactions and dosage of bretylium tosylate, a recently approved antiarrhythmic agent, are reviewed. Bretylium tosylate is used to treat life-threatening ventricular arrhythmias, principally ventricular fibrillation and ventricular tachycardia, that have not responded to treatment with first-line antiarrhythmic agents. The drug has a direct positive inotropic effect on the myocardium and blocking effect on postganglionic sympathetic nerve transmission. The drug is poorly absorbed orally, requiring either i.m. or i.v. administration. Drug excretion occurs primarily through the kidney, necessitating dosage modification in renal disease. Hypotension is the most commonly observed adverse reaction to bretylium tosylate. Rapid i.v. administration may cause severe nausea and vomiting, and i.m. injection at the same site may cause atrophy and necrosis of muscle tissue. Quinidine and procainamide may potentiate the hypotensive effects of bretylium. Bretylium will aggravate digitalis-induced arrhythmias. Bretylium's use in resistant ventricular tachyarrhythmias requires close clinical monitoring.

Arrhythmias, Cardiac↗

PubMed1979

[Current chemotherapy of pulmonary tuberculosis].

Tuberculosis has today lost much of its dread for mankind: in 1976, 1823 persons contracted tuberculosis and 182 died of pulmonary tuberculosis in Switzerland. In contrast, 1375 died of pneumonia, 1309 of non-specific airway disease and 2202 of bronchial cancer in the same year. The present data on morbidity and mortality in Switzerland resemble those of the other industrial European countries or the USA. The decrease in morbidity and mortality of pulmonary tuberculosis was caused-among other factors-by chemotherapy. Chemotherapy not only profoundly changed the infectivity of tuberculous patients and made ambulatory, domiciliary treatment possible, but cured pulmonary tuberculosis. The introduction of the bactericidal rifampicin led to the latest major landmark in the chemotherapy of tuberculosis in the past 20 years: namely, short-course chemotherapy. Together with the other first-line drugs (isoniazid, streptomycin, ethambutol), rifampicin shortened the duration of chemotherapy from 18--24 to 9--12 months. Short-course chemotherapy is today the therapy of choice for most patients with pulmonary tuberculosis.

BCG Vaccine↗

PubMed2026

[Tics and Tourette Syndrome].

Tics disorders and Tourette syndrome (TS) are neurodevelopmental conditions characterized by motor and/or vocal tics with onset in childhood. Their clinical presentation is heterogeneous and fluctuating over time, with exacerbations related to emotional, environmental, and medical factors. Diagnosis is clinical and based on medical history and neurological examination, following DSM-5-TR criteria, with ancillary testing rarely required. The prevalence of TS is estimated at 0.7%, while transient tic disorders affect up to 10% of children. The natural history is generally favorable, with symptom improvement during adolescence, although a subset of patients continues to experience tics into adulthood. Most individuals with TS present psychiatric comorbidities, particularly attention-deficit/hyperactivity disorder and obsessive-compulsive disorder, which significantly impact quality of life and should be prioritized in management decisions. Treatment is recommended only when tics cause functional impairment and follows a stepwise approach including psychoeducation, behavioral interventions, and individualized pharmacological therapy. Comprehensive behavioral intervention for tics is considered first-line treatment when available. Alpha-2 adrenergic agonists and dopamine antagonists are the most commonly used pharmacological options. Neuromodulation therapies are reserved for severe, refractory cases. These recommendations from the Ibero-American Academy of Pediatric Neurology summarize current evidence and provide a practical, updated framework for the diagnosis and management of tic disorders and Tourette syndrome in pediatric patients.

Humans↗

PubMed1978

Rheumatoid arthritis.

Management should help relieve symptoms, increase or maintain function, produce few side effects and keep the cost to a minimum. Aspirin remains the first-line drug; other nonsteroidal anti-inflammatory drugs may be useful when aspirin cannot be tolerated. Symptoms and signs of rheumatoid disease may be suppressed by corticosteroids, but only gold compounds, penicillamine and cytotoxic therapy have been shown to decrease disease activity and lessen permanent joint damage.

Adrenal Cortex Hormones↗

PubMed1976

Role of DTIC (NSC-45388) in the chemotherapy of sarcomas.

DTIC was one of the first of several new agents evaluated by the Southwest Oncology Group (SWOG) and the M.D. Anderson Hospital and Tumor Institute (MDAH) in the therapy of adult patients with metastatic sarcomas. It yielded an overall response rate of 17%. This is similar to that seen in a review of 138 patients who represent the total number reported in either published or unpublished data. The subsequent addition of DTIC to adriamycin in several studies carried out at the MDAH and in the SWOG has increased the complete and partial remission rate over that seen with adriamycin alone, and more importantly has increased remission duration and survival. DTIC is currently used in combination with adriamycin in the first-line therapy of patients with metastatic sarcomas and should be considered for patients who have relapsed on primary therapy not including DTIC.

Clinical Trials as Topic↗