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[Usefulness of converting enzyme inhibitors in the diagnosis of arterial hypertension].

Angiotensin-converting enzyme (ACE) inhibitors are now widely used as first-line treatment of essential hypertension. Their effectiveness is potentiated by a low-salt diet and, above all, by the simultaneous prescription of diuretics. When secondary hypertension is suspected, ACE inhibitors are a good pharmacological tool to study the renin-angiotensin system. Since activation of this system is the main mechanism responsible for renovascular hypertension, ACE inhibitors are very useful for diagnosis. Conversely, blood pressure is not influenced by ACE inhibitors in primary hyperaldosteronism because of the low plasma renin and angiotensin II levels. Pheochromocytoma activates the renin-angiotensin system, and ACE inhibitors combined with beta-blockers enable the hypertension to be controlled prior to surgical treatment of the tumour. Finally, ACE inhibitors can be used to explore the renin-angiotensin system in the experimental model of renovascular hypertension and therefore contribute to our knowledge of the complex pathophysiology of this most frequent type of secondary hypertension.

Adrenal Gland Neoplasms↗

[Rhabdomyosarcoma of the prostate. Diagnostic course and current therapy. Report of a case of a 17-year-old boy].

The authors report a case of rhabdomyosarcoma in a 17 year old boy which recurred after combination chemotherapy and radical prostatectomy, followed by death of the patient due to haematological complications of second-line chemotherapy. The diagnosis of these rhabdomyosarcomas is facilitated by the various immunohistochemical stains now available. Chemotherapy is undeniably effective and, combined with surgery and radiotherapy, ensures a 5-year survival of 47% to 93% depending on the stage. The first-line chemotherapy avoids the need for radiotherapy in the early stages and allows less mutilating surgical procedures, while maintaining the survival rate.

Adolescent↗

[Value (and limitations) of the RAST fx5 in pediatric allergological practice].

RAST f x 5 (CAP-system, Pharmacia), an in vitro assay testing a mixture of 6 food antigens, was systematically applied to 400 children and adolescents with respiratory pathologies possibly of allergic origin. The clinical aspects of the 293 test-negative patients were compared with those of the 107 positive cases. Furthermore, 84 positive sera were also evaluated against each of the 6 antigens regrouped in the f x 5. In this population with allergic respiratory diseases, the most frequently positive tests reacted with antigens of plant origins: wheat, peanut and soybean. From an economic point of view, first-line use of f x 5 markedly reduced the cost of a systematic study of food allergens, whose clinical justification remains to be demonstrated.

Adolescent↗

Teniposide (VM-26) and carboplatin as initial therapy for small cell lung cancer.

Forty-four patients with previously untreated histologically proven small cell lung cancer (SCLC) were treated with a combination of teniposide 60 mg/m2 intravenously (IV) on days 1 through 5 and carboplatin 400 mg/m2 IV on day 1 every 28 days for six courses. Patients with limited disease (LD) subsequently received prophylactic cranial and thoracic radiotherapy. Of the 44 patients, 40 were evaluable for response: 31 (78%) achieved an objective response; 9 of 18 patients (50%) with LD had a complete response (CR), with a partial response (PR) plus CR rate of 78%. Two of 22 patients (9%) with extensive disease achieved a CR, with a combined PR and CR rate of 77%. Median duration of response for all evaluable patients was 253 days (36 weeks). Median duration of survival for LD patients was 368 days (52 weeks). Survival of LD patients was 86% at 6 months, 52% at 12 months, and 26% at 18 months. Median duration of survival for all patients in the study was 275 days, with a survival of 79% at 6 months, 36% at 1 year, and 12% at 18 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3 or 4 infection occurring in 38% of patients. However, no patient died of sepsis or hemorrhage. Treatment was otherwise well tolerated, with no neurotoxicity or nephrotoxicity documented. The high activity of this drug combination justifies its use as first-line treatment of previously untreated SCLC.

Adult↗

Screening for cervical cancer: is there a place for incorporating tests for the human papillomavirus?

Well organized screening programmes for cervical cancer, based on exfoliative cervical cytology, are known to be effective at reducing the incidence of invasive cervical cancer and mortality from the disease. HPV testing should not replace cervical cytology as the first-line approach in screening for cervical cancer, as HPV testing is not sufficiently reliable and some cancers are not associated with HPV infection. Even though there are many unanswered questions about the validity of HPV tests, it is timely to consider whether HPV testing might improve the management of the substantial number of women whose smears are neither clearly normal nor abnormal, but are described as atypical, suspicious or mildly dyskaryotic. The efficacy and costs of incorporating HPV testing into a cervical cancer screening programme need to be evaluated in controlled trials.

Female↗

Clindamycin: an evaluation of its role in dental patients.

A review of the etiology of orofacial infections, of the pharmacology and spectrum of clindamycin and its associated complications, and a treatment plan for orofacial infections have been presented. On the basis of the data presented, it would seem that except for proved B fragilis infections, clindamycin is not a first-line drug for infections of the orofacial region. There are, however, indications for its use that have been presented. The serious complications associated with its use have also been presented. A high index of suspicion must be maintained regarding the development of these complications if clindaymcin is to be used.

Bacterial Infections↗

Sumatriptan: a new drug for vascular headache.

The role of serotonin in the pathogenesis of migraine is discussed, and the chemistry, pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage and administration of sumatriptan are reviewed. Sumatriptan, which is structurally related to the neurotransmitter serotonin, is a serotonin type-1-like-receptor agonist that has a selective but heterogeneous effect on the carotid arterial system. Sumatriptan has a rapid onset of action and a large volume of distribution. Its subcutaneous bioavailability approaches 100%, and its mean terminal half-life is two hours. Studies have shown that both subcutaneous sumatriptan and oral sumatriptan are superior to placebo in relieving migraine and cluster headaches. Studies comparing oral sumatriptan with either ergotamine tartrate plus caffeine (Cafergot) or aspirin plus metoclopramide indicated that sumatriptan relieved headache more quickly and effectively; however, the dosages of these other agents may have been suboptimal. Sumatriptan is generally well tolerated by patients, and most dose-related effects are mild and transient. The most common adverse effect is pain at the injection site. No drug interactions have been identified so far. Subcutaneous sumatriptan 6 mg and oral sumatriptan 100 mg seem to offer the best benefit-to-risk ratio, although dosage and administration information is limited. Subcutaneous and oral sumatriptan are effective in aborting moderate to severe migraine and cluster headaches and their associated symtpoms. However, more studies are necessary to compare sumatriptan's efficacy with that of other treatments before it can be recommended as first-line therapy for migraine.

Cluster Headache↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗