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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↗

PubMed1992

Fractured-nose reduction under local anaesthesia. Is it acceptable to the patient?

This article examines patients' acceptance of fractured-nose reduction under local anaesthesia, both objectively and subjectively. At each stage of the reduction the level of the discomfort, the patients' experiences were recorded. The success rate of complete reduction of the nasal fracture was found to be 71% and this was similar to that obtained in other studies that have used general anaesthesia. An overall level of discomfort for the procedure in terms a layman can understand was obtained by comparing the manipulation with that of having a tooth filled at the dentist. Sixty-three percent of the patients said that the nasal fracture reduction was no worse or the same as a dental filling. Our study showed that 96% of patients would be willing to undergo the same local anaesthetic procedure if they fractured their nose a second time. We conclude that it is possible to reduce the majority of fractured noses adequately with little inconvenience to the patient under local anaesthesia, and so we recommend that this procedure should be considered in the first-line treatment of the displaced fractured nose.

Adolescent↗

PubMed1992

Carboplatin in the treatment of carcinoma of the ovary: the National Cancer Institute of Canada experience. Ovarian Cancer Subcommittee.

The National Cancer Institute of Canada Clinical Trials Group has used carboplatin in two studies in women with ovarian carcinoma. In a phase II study, carboplatin produced a clinical response rate of 28% among patients with tumor persistence or recurrence following one prior cisplatin-containing regimen. Carboplatin was most efficacious in those with smaller tumors, in those who had the best responses to prior cisplatin therapy, and in those with longer intervals between the primary cisplatin treatment and the secondary carboplatin course. In this setting, a starting dose of 320 mg/m2 is suggested. A phase III randomized trial of first-line therapy compared the efficacy of cyclophosphamide/cisplatin with cyclophosphamide/carboplatin. Four hundred eighteen eligible patients were enrolled. The regimens demonstrated comparable efficacy; however, the carboplatin-based regimen was more easily administered and caused less symptomatic toxicity. The long-term results in this population with macroscopic residual disease remain disappointing.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Replacement of cisplatin with carboplatin in combination chemotherapy against ovarian cancer: long-term treatment results of a study of the Gynaecological Cancer Cooperative Group of the EORTC and experience at The Netherlands Cancer Institute.

Carboplatin-based chemotherapy has been evaluated in three studies of ovarian cancer patients. In the first, combination cisplatin and carboplatin plus doxorubicin/hexamethylmelamine/cyclophosphamide were compared as first-line treatment of ovarian cancer in 341 women with stage IIB to IV disease. There were no observed differences in results between the two treatment groups. In the second study, conventional doses of intravenous carboplatin (350 mg/m2, given on day 1) plus oral cyclophosphamide (100 mg/m2 days 2 to 6) were given to late-relapsing patients (12 to 72 months) previously treated with cisplatin. Mature data showed a 55% overall response rate, acceptable toxicity, and an absence of additive neurotoxicity. Finally, 65 patients with refractory disease or in early relapse after cisplatin therapy (within 12 months) were treated with high-dose carboplatin (800 mg/m2). Toxicity was severe, but the 45% combined response rate was considered encouraging and worthy of further evaluation. It was concluded that carboplatin is an appropriate replacement for cisplatin in the treatment of ovarian cancer.

Adult↗

PubMed1992

Teniposide in lymphomas and leukemias.

The epipodophyllotoxins, etoposide and teniposide, have been used in leukemias and malignant lymphomas for the past 15 years. Although etoposide has acquired a place in many first-line protocols for lymphomas and, more recently, for leukemias, the role of teniposide has remained limited. Teniposide is a more potent inhibitor of topoisomerase II than etoposide, and has a less toxic effect on hematopoietic progenitor cells. Both drugs have been regarded as equitoxic and cross-resistant. The role of teniposide in front-line treatment of leukemias has only been established in childhood acute lymphoblastic leukemia (ALL). Some promising results have been obtained in small numbers of patients with refractory adult ALL and acute monoblastic leukemia. However, the remission rates and remission duration were not significantly different from those of other combination regimens. Data on teniposide in untreated acute nonlymphoblastic leukemia are very scarce. In non-Hodgkin's lymphoma, the antineoplastic activity of teniposide has been demonstrated in studies by the European Organization for Research and Treatment of Cancer and in two large studies conducted by the Australian and New Zealand Lymphoma Co-operative Chemotherapy Study Group. In these studies, teniposide had comparable but not significantly better activity than vincristine. The dose-dependent antineoplastic activity of teniposide has led to its use in several conditioning regimens in bone marrow transplantation for leukemias and lymphomas. The limited clinical data currently available on teniposide seem to warrant further clinical trials with this agent in leukemias and lymphomas.

Adult↗

PubMed1992

Gamma-vinyl GABA (vigabatrin): clinical experience in adult and adolescent patients with intractable epilepsy.

Clinical experience with gamma-vinyl GABA (GVG, vigabatrin) has accumulated mainly in Europe, where the drug has been licensed in several countries since 1989. Short-term efficacy studies in adolescent and adult patients with intractable drug-resistant epilepsy have shown that approximately 50% exhibit a reduction in seizure frequency of one-half or more but rarely complete seizure control. The best results are in patients with partial seizures with or without secondarily generalization. GVG responders have been followed for periods of up to 5 years, and overall 10-20% may exhibit subsequent seizure breakthrough, as probably occurs with any drug in such chronic patients. The most common side effect is drowsiness. Reversible behavior disorders, psychoses, and depression rarely occur in predisposed individuals. No new long-term side effects have been reported but vigilance is necessary. Studies of GVG as a first-line drug in newly diagnosed epileptic patients are proceeding.

Adolescent↗

PubMedDate not supplied

Therapy with Anagrelide in patients affected by essential thrombocythemia: preliminary results.

BACKGROUND: Anagrelide, an imidazo-quinazolin compound first proposed as a potent inhibitor of platelet function, was subsequently recognized as a drug able to lower the platelet number both in normal subjects and in myeloproliferative syndromes with thrombocytosis. We report our experience with Anagrelide therapy in 20 patients affected by essential thrombocythemia (E.T.). PATIENTS AND METHODS: Twenty consecutive patients with E.T. entered the study from June, 89 to July, 91. Therapy schedule was as follows: 0.5 mg every 12 hours for 7 days; subsequently the daily dose was increased by 0.5 mg/day every week until a response was obtained (a decrease of the platelet count to less than 500 x 10(9)/l = complete response; to less than 600 x 10(9)/l = partial response). RESULTS: Of 19 evaluable patients, complete response (CR) was obtained in 13 (68%) and partial response (PR) in 3 (16%). For all responders, the mean time to response was 5.2 months: mean daily dose of Anagrelide 2 mg. Side effects were recorded in 8/20 patients (40%): tachycardia (n = 4), gastrointestinal distress (n = 3), perimalleolar edema (n = 1). In 6 cases therapy was discontinued definitively. DISCUSSION: Response rate to therapy with Anagrelide is similar to that with alkylating agents and alpha 2b-recombinant interferon; furthermore, Anagrelide is a drug without cytotoxic properties. The mean daily dose able to obtain a response is 2 mg, but maintenance therapy at similar doses is always necessary. In conclusion, we can say that Anagrelide is an effective drug in the treatment of patients with E.T., but its side effects must be seriously considered. A larger study may show whether it should be considered as a "first-line" drug for all patients with E.T.

Adult↗

PubMedDate not supplied

Ultrastructural, immunologic and clinical follow-up of five patients with HCL treated with interferon (IFN) for more than three years.

BACKGROUND: Treatment results in HCl have been improved by the use of alpha-IFN, which is now the standard first-line therapy for this disease, but the mechanism of IFN action is still unclear. It is known, however, that IFN is able to induce hematologic, immunological and phenotype membrane changes which parallel the patients' (pts) clinical response. The aim of our study was to correlate the clinical response to IFN treatment with ultrastructural and phenotype membrane changes in hairy cells (HCs), in order to elucidate the mechanism of IFN action at the cell level. METHODS: We assessed the phenotype membrane and ultrastructural changes induced in HCs by long-term alpha-IFN treatment in five pts with HCL; membrane-bound Il 2-R on PHA-stimulated PBL, the release of IL 2-R by PHA-stimulated PBL and the serum levels of s-IL 2-R were also determined in one pt. RESULTS: The surface immunological phenotype, mainly the HCL-related surface antigen CD25, changed after IFN treatment, dropping from abnormally high to normal values. Furthermore, IFN treatment induced ultrastructural changes in HCs, consisting mainly of a sharp reduction in, up to the almost complete disappearance of, the hairy projections: very few, if any, short, thick villi persisted. The ultrastructural changes in HCs paralleled clinical and hematologic response to IFN treatment in such a way that IFN alone may be considered the cause of these changes. As far as detection of the membrane-bound IL 2-R p55 chain on PHA-stimulated PBL is concerned, the expression of p55 is very high on the membrane of HCs; a high level of serum s-IL 2-R was also found in the HCL pt studied before IFN treatment, whereas the release of IL 2-R by PHA-stimulated PBL was higher than normal, but not significantly. Two of our pts, who did not respond or responded very poorly clinically to IFN treatment, should probably be considered cases of HCL "variants". CONCLUSIONS: The phenotype membrane and the ultrastructural changes in HCs very closely paralleled the patients' clinical responses to IFN, suggesting that both the immunologic and the morphologic changes induced in HCs by in vivo IFN treatment are a direct counterpart of its biologic effect.

Aged↗

PubMed1992

Introduction to large artery properties as a target for risk reduction by antihypertensive therapy.

AIM: To review the effect of antihypertensive drugs on pulsatile stress and shear stress. RESULTS OF DATA REVIEW: Mortality and morbidity in hypertension are better correlated with systolic than diastolic blood pressure, indicating a pulsatile stress effect. Distensibility and compliance are large artery properties and important determinants of pulsatile stress. beta-Blockers with vasodilating properties, several selective beta 1-blockers, angiotensin converting enzyme inhibitors and calcium antagonists are first-line antihypertensive drugs that improve these properties of large arteries. The impact of shear stress on the ill effects associated with hypertension is not clear. CONCLUSION: Some but not all classes of antihypertensive drugs can improve large artery properties, and thereby alleviate pulsatile stress.

Antihypertensive Agents↗

PubMed1992

[Grand mal epilepsy in childhood].

Generalized tonic-clonic seizures are the most common type of convulsive disorders in children. They are always a sign of an epileptogenic cerebral dysfunction and present either acutely, predominantly as a single event with detectable origin, or chronically, recurring as an epileptic syndrome. In view of the etiology and classification of convulsions it is important to differentiate between primarily and secondarily generalized seizures. This distinction is first of all based on an exact description of the very beginning and of the course of the seizures, on the EEG findings and on any connection between the seizures and a particular time of day. Primarily generalized tonic-clonic seizures with and without associated petit mal seizures are manifestations of an idiopathic epilepsy and are most probably genetically determined, secondarily generalized seizures on the other hand are often signs of a central nervous lesion or of another symptomatic form of epilepsy. Benign idiopathic partial seizures, however, take the from of secondarily generalized convulsions during the morning sleep. Prolonged tonic-clonic seizures of any origin require vigorous treatment with anticonvulsants, if necessary in an intensive care unit. Recurrent seizures are treated with long-term anticonvulsant medication. The first-line treatment is valproic acid or phenobarbitone (or if necessary, a bromide) in primarily generalized seizures and carbamazepine or phenytoin in secondarily generalized convulsions. The recommended duration of this therapy and the risk of recurrence of seizures vary widely with the underlying etiology and the type of epilepsy.

Anticonvulsants↗

PubMed1992

Imipenem-cilastatin.

Imipenem-cilastatin, with its broad spectrum of activity and relative safety, offers an excellent alternative for the treatment of many obstetric and gynecologic infections. In addition, the possibilities for intramuscular administration give clinicians additional treatment options. Because of the relatively high cost of imipenem-cilastatin, it should not be considered "first-line" therapy for most obstetric and gynecologic infections at present. Misuse and overuse of imipenem-cilastatin will result in the further development of resistant organisms, as has already been seen with many other antibiotics, and continued monitoring of susceptibility patterns is necessary.

Animals↗

PubMed1992

[The treatment of hemifacial spasm using botulinum toxin].

Hemifacial spasm is a disagreeable disturbance with involuntary unilateral twitching of the facial muscles. Its most common form is supposedly due to an irritation of the facial nerve at its proximal intracranial segment by vascular structures. Various forms of treatment including surgical procedures are employed, very often without satisfactory results but frequently involving the risk for severe complications. For a few years a new method has been using injection of botulinum toxin into the affected muscles, which in the majority of patients relieves the abnormal movements for about half a year; therefore, this very effective and secure procedure is recommended as first-line treatment of hemifacial spasm.

Adult↗

PubMed1992

[Asthma and sleep].

In asthmatics, nocturnal cough and dyspnea are much more common than generally known. Therefore, patients with asthma must be asked specifically whether they suffer from symptoms of asthma at night. Usually, nocturnal wheezing is a sign of a badly controlled asthma. Nocturnal bronchoconstriction appears to be an exaggeration of the normal circadian changes in airway calibre. The cause of this exaggeration is not well understood, and it's origin is presumably multifactorial. Careful treatment of nocturnal asthma is particularly important because many deaths due to asthma occur at night and because regular disturbance of sleep impairs performance during the day. Inhaled corticosteroids and beta 2 agonists, especially the new long-acting beta agonists, are first-line drugs for therapy.

Airway Resistance↗

PubMed1992

[Visceral leishmaniasis in HIV infection. A totally opportunistic infection].

Visceral leishmaniasis occurring in immunocompromised patients, and in particular during HIV infection, has been described in recent years and differs from the usual Mediterranean kala-azar as encountered in France. In order to define the clinical, diagnostic and therapeutic features of the HIV-Leishmania spp. co-infection, we report 8 new cases and compare them with data from the literature. The co-infection occurs at any stage of HIV infection, usually in drug addicts using intravenous injections. Clinical manifestations, such as fever, weight loss, liver and spleen enlargement and polyadenopathy, and laboratory findings (cytoponia, inflammatory syndrome) are generally present but not specific during the HIV infection course. Moreover, some gastrointestinal and pleuropulmonary forms of the co-infection are misleading. Leishmaniasis serology is negative in 50 percent of the patients. In most cases the diagnosis is provided by detection of the parasite in bone marrow samples. Culture must be systematic, and samplings must be repeated if they are negative. The first-line treatment consists of pentavalent antimony. Almost 80 percent of the patients respond to this treatment, but relapses occur in 50 percent of the cases. This high risk of relapse and the opportunistic behaviour of leishmaniasis justify a prophylaxis of relapses.

AIDS-Related Opportunistic Infections↗

PubMed1992

Antiepileptic drugs and their psychotropic effects.

Antiepileptic drugs (AEDs) are still the main treatment for epilepsy. The first drugs such as the bromides, phenobarbital (PB), and related barbituates were all found to be anticonvulsant by chance. They also all carried to some extent the disadvantages of slowing thinking and motor behavior. Bromides are now seldom used and (PB) is only used when other drugs fail, although it is an important drug in the third world because of its low cost. Carbamazepine (CBZ), valproate (VPA), and phenytoin (PHT) are the current first-line AEDs. All of these drugs vary in the extent of their effect on mood. These drugs have also all been used in the treatment of psychiatric disorders. CBZ has been used mainly as a mood normalizer and has had some success in treating hypermanic episodes. VPA has been used successfully in the treatment of cyclical psychoses, whereas PHT, although it had a vogue in the 1940s for the treatment of psychosis, is little used as a psychological treatment now.

Affect↗

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↗