Therapeutic progress I: Current treatment of rheumatoid arthritis

Over recent years the pharmacological treatment strategy for rheumatoid arthritis (RA) has changed. An early, aggressive approach has been adopted with a view to maintaining functional capacity. The changing role of nonsteroidal antiinflammatory agents is discussed in the light of the potential toxicity of this class of drugs. The current use of second-line agents is dealt with in depth and includes guidelines to patient monitoring. Particular attention has been paid to the growing use of cyclosporin A in the treatment of RA as this drug represents the newest, most potent, nonexperimental form of treatment. The questions of when to introduce second-line agents, who should receive treatment and how many drugs should be prescribed are all addressed in this review. The relative efficacy and toxicity of these agents is discussed and a treatment protocol is proposed.     

THE TREATMENT OF ACUTE AND CHRONIC VAGINAL CANDIDOSIS

Vaginal candidosis is one of the most common infections of the vagina and the first accredited record of the disease appeared in 1849. Over the years the terms ‘candidiasis’ and ‘candidosis’ have been used, but it is generally accepted now that the terms are synonymous, and the term most commonly in use today is ‘candidosis’. Mainly caused by the yeast Candida albicans, the condition is characterised by intense inflammation of the vaginal mucosa and a curdy, off-white discharge; it is often associated with severe vulval itching and possibly burning pain. The severity of symptoms seems to vary greatly from patient to patient and the reason for this is unclear. It is suggested that in some patients there may be an element of hypersensitivity. Vaginal candidosis may occur in children but is most common in adults and only sometimes affects the elderly. The majority of women will suffer at least one attack of vaginal candidosis during their lifetime, and there are several predisposing factors such as diabetes, pregnancy and antibiotics. Some authorities consider the condition more frequent in those taking oral contraceptives or other hormones.     

Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.

Fiduxosin is a new alpha(1)-adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC(50) values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC(50) values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC(50)/IUP IC(50), were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of alpha(1)-adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an alpha(1a)-/alpha(1d)-subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist.     

Diet and premenopausal bilateral breast cancer: A case-control study

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.     

Chirurgie der differenzierten Schilddrüsenkarzinome

Die 5-Jahres-überlebensrate von differenzierten Schilddrüsenkarzinomen ist generell sehr gut und betr?gt 80 – 95%. Hierbei bestehen Abh?ngigkeiten zum Alter des Patienten [15], zum prim?ren Tumorstadium, zur histologischen Differenzierung und zum Ausma? der region?ren und Fernmetastasierung [6]. Patienten mit Tumorfreiheit haben ebenfalls eine bessere Prognose gegenüber denen mit einem Resttumor. Dies spricht für ein konsequentes Vorgehen beim Prim?reingriff mit Thyreoidektomie und Entfernung der Lymphknoten des zentralen Kompartments. Stadienadaptiert schlie?t sich eine Radiojodtherapie oder die Kombination mit einer externen Radiatio an. Bei der Reoperation differenzierter Schilddrüsenkarzinome mu? zwischen der individuellen Prognose des Patienten, dem Ziel der Operation und der postoperativen Morbidit?t/Mortalit?t entschieden werden. Aufgrund des hohen Risikos sollten diese Operationen in Zentren durchgeführt werden, so da? postoperative Komplikationen (permanente Recurrensparese/Hypoparathyreoidismus) vertretbar gering gehalten werden k?nnen (Tabelle 11). Dennoch sollte nicht au?er Acht gelassen werden, da? individuell bei differenzierten Schilddrüsenkarzinomen im Stadium pT1 auch ein eingeschr?nkt radikales Vorgehen (Hemithyreoidektomie) ohne Verschlechterung der Prognose m?glich scheint. Strenge Nachuntersuchungsergebnisse und Ergebnisse weiterer klinischer Studien müssen hierzu abgewartet werden.     

SUICIDE ATTEMPT DUE TO METOCLOPRAMIDE-INDUCED AKATHISIA

Akathisia as a side-effect of metoclopramide has received increasing attention in consultation-liaison psychiatry in recent years. A case of metoclopramide-induced akathisia resulting in a suicide attempt is reported in order to highlight the suffering of such patients and the factors that lead to misdiagnosis.