Hypothenar hammer syndrome is a rare and often incorrectly diagnosed form of secondary Raynaud's phenomenon in workers who use their hand as a hammer. We report 17 documented cases with long-term follow-up after diagnosis made on the basis of arteriography. Clinical findings include male sex, unilaterality, sudden onset, and severe Raynaud's phenomenon. Angiography indicated that the 17 patients had either ulnar thrombosis or ulnar aneurysm; most of them also had embolic occlusions of the digital arteries. Main pathologic findings were thrombosis on the intima and fibrosis in the media. We adopted a surgical procedure consisting of resection with end-to-end reconstruction for patent aneurysms to avoid downstream emboli and more conservative treatment when the ulnar artery was thrombosed. No patient required digital amputation and all except one improved and were able to live and work normally with only a moderate disability, consisting of Raynaud's phenomenon during the cold season only.

Hypothenar hammer syndrome is a rare and often incorrectly diagnosed form of secondary Raynaud's phenomenon in workers who use their hand as a hammer. We report 17 documented cases with long-term follow-up after diagnosis made on the basis of arteriography. Clinical findings include male sex, unilaterality, sudden onset, and severe Raynaud's phenomenon. Angiography indicated that the 17 patients had either ulnar thrombosis or ulnar aneurysm; most of them also had embolic occlusions of the digital arteries. Main pathologic findings were thrombosis on the intima and fibrosis in the media. We adopted a surgical procedure consisting of resection with end-to-end reconstruction for patent aneurysms to avoid downstream emboli and more conservative treatment when the ulnar artery was thrombosed. No patient required digital amputation and all except one improved and were able to live and work normally with only a moderate disability, consisting of Raynaud's phenomenon during the cold season only.

Small clinical trials are trials in which the number of patients does not enable the objective of the study to be appropriately met with the usual methodological rules. This situation is common in the case of rare diseases, in paediatrics, in certain cancer pathologies or when the number of patients exposed to the treatment needs to be limited. The principal methodological problems are initially identified, and the classical methods (controlled, randomised, double-blind trial using parallel groups, crossover trial, factorial design, trial performed with several measures repeated over time, add-on design, randomised withdrawal design or early-escape design) and more uncommon methods (sequential approaches, meta-analyses, the 'N of 1' method and other methods that facilitate decision making or modelling) are then discussed. Subsequently, recommendations are made to ensure that the results obtained are not a matter of chance, and to increase the level of proof. Keywords: small trials, statistical methods, level of proof Small clinical trials are trials conducted and analysed using patient numbers lower than is required to meet the aims of the study according to the more common methodological rules. This paper therefore does not concern the standard phase I and II trials where the number of patients included in the study, although quantitatively small, is methodologically adapted to the aims of the study. It concerns all trials that aim to establish the proof of whether any given effect, be it of efficacy or tolerance, is present. PHARMACOLOGIE CLINIQUEThis situation is often the case with rare diseases, in paediatrics or in cancer treatment, when the external limitations of patient availability do not enable the recruitment of patient numbers that meet the usual assessment criteria. It is also the case when the number of patients exposed to the investigational treatment methods needs to be limited, either because of constraints regarding the particular protection of individuals (children, pregnant women), or because of the toxicity of the product (cancer treatment), or even its lack of efficacy (placebo, weak doses). The methodological issue in 'proof of concept' studies, the results of which lead to the decision on whether or not to continue developing a molecule, although based on a different context, can be related to this field.The main issue surrounding these small trials is the level of proof provided by the results of these studies, which reflects the relevance of using non-standard methods.Conducting a small trial through necessity reveals various levels of difficulties, some of which are not entirely specific to small trials, but are increased because of the reduced patient numbers. These include the following:1. The risk of not reaching a conclusion, even though there is a real difference between the therapeutic regimens being compared, because of the great variability in random fluctuations. Only a quantitatively important effect is likely to be given prominence.2. The caution necessary when extr...

SummarySixty nine patients were treated with local intra-arterial urokinase (37,500 U/CTA. hr-1) for recent severe ischemia of lower limbs: 27 (40%) ultimately required amputation. The difference of amputation rate between the groups with and without thrombolysis was not significant (33% v. 42%). A biological study in 6 patients showed that local arterial plasminemia occurred in only 1 patient. Local urokinase does not strongly stimulate “endogenous” thrombolysis and enhances “exogenous” thrombolysis only very inconstantly. A better adaptation of urokinase dosage or the use of an agent with a higher affinity for fibrin might improve the efficiency of local thrombolytic therapy.

In recent years, two key concepts having numerous interrelationships were advanced for the understanding of various cardiovascular diseases: the "endothelial dysfunction" and the "arterial remodelling". Both endothelial dysfunction and arterial remodelling occur in various pathologies including essential hypertension, heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension, and have modified the therapeutic approach by offering new pharmacological targets: specific receptors not only at the site of the vascular smooth muscle cells but also on the endothelial cells, growth factors that stimulate proliferation of smooth muscle, and receptors and enzymes of the extra-cellular matrix. Among the various substances under research, the present review will discuss angiotensin II receptor antagonists, endothelin receptor antagonists, nitrates-NO donors, potassium channel activators, and substances interfering with proteoglycans and other components of the extra-cellular matrix.

The increasing counterfeiting of medicinal drugs is a very worrying phenomenon, especially in developing countries. The risk for public health is quite real, particularly as these products are often sold out of any controlled distribution channel.

-The integrity of the data from clinical trials and of its use is an essential element of the scientific method, and of the trust one can have in this method. There are many examples of fraud, and they recur regularly. The objective of this round table was to work on the definition of fraud, on its recognition and prevention especially in the institutional system. Fraud involves an active decision to cheat, and ranges from trying to hide incompetence to wholesale invention of data, patients or studies. Its frequency is difficult to evaluate but might be as high as 1% of all studies or publications. Fraud can involve ethics (post-hoc IRB [institutional review board] approval, IRB requests not applied, lack of consent), or any of the steps from realisation to interpretation of studies or trials. Identification of fraud is made harder by the usual risk for the whistleblowers, who must be protected. Seeking fraud is implicit in Good Clinical Practices (GCP) that all industry sponsors must apply, but that are less often applied by institutional sponsors. It might be useful to install procedures to detect fraud in studies, especially institutional. Various statistical methods can be used to identify unusual data patterns that could suggest fraud. Once fraud is identified, its management is often not foreseen. Here again, clear procedures or recommendations would be of help.

Selective intra-arterial urokinase (UK) is effective in treating recent arterial thromboembolism. However, usually only partials lysis is achieved and this treatment seems less effective than intravenous streptokinase. At a dose of 37,500 UCTA/hour it does not produce systemic fibrinolysis. This protocol substantially reduces the risk of systemic bleeding and embolism and extends its applicability to operative patients. The combination of surgery and UK seems particularly promising in patients with atherosclerotic arterial thrombosis.