The clinical results

Clinical Results Items 6-12 of Form 356h are all related to the clinical results. These are perhaps the most important sections of the submission to demonstrate the safety and efficacy of the drug for treating the target disease. Detailed analyses of clinical data are presented to support the application. Some of these analyses include the following ... 

The observations of Battermann et al. [32] on lung metastases indicate that slowly growing tumors (well differentiated) could benefit from high-LET treatment (Fig. 9). The clinical results accumulated over more than 25 years confirmed these observations. 

Between 1974 and 1994, 1100 patients were treated with negative pions at three centers. These particles, which provide a mixture of high- and low-LET components and some physical selectivity advantage, were very expensive to generate and the clinical results were unconvincing. All three facilities have now been closed down [5]. 

A summary of the clinical results obtained with neon ions in Berkeley is presented in Table 7 [4,47]. Some fast neutron therapy results are also presented. Although the recruitments are not comparable, it should be pointed out that tumor types or sites for which an advantage was found with neon ions are those for which an advantage was also found with fast neutrons. This suggests a specific high-LET effect. 

Some of the clinical results are summarized in Table 8. More detailed information on lung cancers [nonsmall cell lung cancer (NSCLC)] is given in Table 9, in particular, about patient selection and treatment conditions [48]. The possibility of hypofractionation has been investigated especially for lung and liver cancers with no increase in toxicity. 

Table 6 Summary of the Clinical Results Obtained with Helium Ions and Neon Ions at Berkeley...

BNCT using thermal neutron beams was started in the United States in 1951 at the Massachusetts Institute of Technology (MIT) and at the Brookhaven National Laboratory (BNL). The clinical results were very poor. The technique was introduced in Japan by Hatanaka in 1968, and some promising results were obtained. 

Historically, the progress in radiation therapy has been linked mainly to technological developments. The physical selectivity of the irradiations was significantly increased when 200-kV x-rays were progressively replaced by cobalt-60, betatrons, and linear accelerators. As a consequence, the clinical results were dramatically improved. 

The introduction of proton beams aims at further improving the physical selectivity of the irradiation. The clinical results obtained by the pioneers in proton therapy, with machines in physics laboratories, were sufficiently convincing to justify building and buying dedicated hospital-based proton machines. 

An issue which may seem an obvious qualification for selection for portfolio is the clinical results that the product has demonstrated to date in its development. Despite even dramatic clinical evidence in anecdotal studies it is sometimes difficult to establish the worth of a product without strong comparative clinical... 

Repeated injection of local anesthetics can result in loss of effectiveness (ie, tachyphylaxis) due to extracellular acidosis. Local anesthetics are commonly marketed as hydrochloride salts (pH 4.0-6.0). After injection, the salts are buffered in the tissue to physiologic pH, thereby providing sufficient free base for diffusion through axonal membranes. However, repeated injections deplete the buffering capacity of the local tissues. The ensuing acidosis increases the extracellular cationic form, which diffuses poorly into axons. The clinical result is apparent tachyphylaxis, especially in areas of limited buffer reserve, such as the cerebrospinal fluid. 

The clinical utility of this approach will depend on the results of these initial clinical trials evaluating l7(3-estradiol and the outcomes of current DESs in higher-risk patients, Speculations about the clinical results are that an improved healing and re-endothelialization, although not completely abolishing neointima formation, will allow a controlled... 

We would like to acknowledge many years of fruitful collaboration with Jeppe Sturis and Kenneth Polonsky in the area of insulin-glucose feedback regulation. Christian Binder provided the clinical results applied in our analysis of insulin absorption from subcutus. Brian Lading, Yuri Maistrenko, and Sergiy Yanchuk contributed to our study of bifurcation and synchronization phenomena in pancreatic -cells. 

Editor s comment This article is taken in large part from a review article published more than twenty years ago in Interdisciplinary Science Reviews, Vol. 3, No. 2, pp 134-147 (1978). It tells the story of the discovery of cisplatin and reflects on its possible mode of action as an antitumor agent. While some of the ideas may have been revised or discarded today, the article represents a unique personal account of the discovery and at the same time is a beautiful example of science history. The chapter on the clinical results has been deleted, since the present status is covered in an up-to-date manner in this book s contribution by O Dwyer and co-workers. The editor wishes to thank John Wiley Sons Limited for permission to reproduce this work. 

Patients with mild cases of HS often do not need any treatment. However, these patients should be watched carefully for the development of hemolytic or aplastic crisis. Splenectomy is the treatment of choice in moderate-to-severe HS cases. In general, splenectomy is indicated in patients who are continuously anemic or who have a history of gallstone colic or repeated crises. The clinical results of splenectomy for HS are almost uniformly excellent. However, splenectomy in very young children should be postponed to later in childhood because splenectomized infants are more susceptible to serious and potentially lethal infections than are older children and adults. At the time of splenectomy, it is important to identify and remove any accessory spleen otherwise, the operation will... 

Steatorrhea, the clinical result of insufficient intraluminal lipid hydrolysis, is the most important digestive malfunction in pancreatic exocrine insufficiency. As a rule, concomitant malabsorption of the lipid-soluble vitamins A, D, E, and K must be suspected in these patients. Naturally, potential differential diagnoses have to be considered in patients who present with steatorrhea (Table 26-1). The pivotal role of fat malabsorption in chronic pancreatitis is due to several interacting mechanisms ... 

The LD50 value of rivastigmine can be raised by the muscarinic blocker atropine almost 11-fold, while the value for the other carbamates in this series is usually about 3 (except for 5.8 for the dimethyl derivative). The quaternary drug atropine methylnitrate, which cannot penetrate the brain, raises the value about two-fold in all cases. This not only adds a safety feature to the use of rivastigmine, but also indicates that rivastigmine s activity - even at high and toxic doses - is more focused than the others in central mechanisms that either directly or indirectly stem from activation of muscarinic receptors. This might contribute to the clinical results if it is assumed that those unexplored nonmuscarinic effects are mostly detrimental to the AD treatment. 

Prozac s pharmacological mechanism for suppressing dopamine is more indirect than that of the neuroleptics. However, the clinical result can be very similar. Prozac can cause akathisia (agitation with hyperactivity), parkinsonism ( Fluoxetine, 1990), and dystonia (muscle spasms) (Meltzer et al., 1979 Reccoppa et al., 1990). 

Most generally, a first laboratory process is kept for the early clinical stages however, as soon as the clinical results are promising and there is evidence that the process would have to be scaled up, a novel phase in the design of an efficient and cost effective process should start. 

In order to determine the statistical distribution of amniotic fluid samples taken at different gestation weeks, two relations are studied rupture of foam films (VP = 0) and development of RDS, and formation of a bilayer foam film (W = 1) and normal respiratory status of neonates. These correlations allowed to develop a new diagnostic method for estimation of lung maturity [20]. The function of the threshold dilution of various amniotic fluid samples (corresponding to C,) on the gestation age and the clinical results (i.e. yes/no RDS in neonates) is given in Fig. 11.5. The respiratory status of the neonates is studied with the screening system of Masson et al. [26], modified by Hobel et al. [29]. 

The way in which hyperosmotic preparations are administered may affect the clinical results. Because vision is nsnally worse on arising, several instillations during the first waking hours can prove helpful. On hot dry days, eyes may require less medication, because tear film evaporation is enhanced. 

We are all aware of the substantial benefits patients have derived from the use of botanical derivatives to treat medical conditions (digitalis comes to mind immediately). The clinical results with feverfew, which has benefits as an anti-migraine agent, is but one example [4]. However, the acceptability of these plant extracts arose only after safety and efficacy was assured. An example is research conducted by the Chinese on... 

MAO-B inhibitor, is one of the few agents that has been examined in this regard and the clinical results are mixed (reviewed in ref 206). 

Dynamic wrinkles respond well to a combination of botulinum toxin and peels the peels restructrue the epidermis and the dermis on an unmoving base and the clinical results are better when these two treatments are combined than when used alone. 

It is still very difficult, however, to tally the clinical results and the histological changes of the different types of peels the formulations, adjuvants and concentrations are different, as are the methods of preparation and application of the various active agents used. Each patient has different cell characteristics, either in the quality or the quantity of phospholipids, sterols and proteins embedded in the cell membranes. Doctors are guided by their own experiences and follow the application protocol they have gradually developed in the course of their practice. This disparity makes it difficult to compare the results of different studies. Some general principles can, however, be drawn we can consider that all peels produce comparable histological effects. The differences arise from the extent of the inflammation caused and how this inflammation is controlled, as well as the relative depth reached. As far as... 

The clinical results with both Celebrex and VicKx suggest that inhibition of COX-2 is an effective treatment for the pain that is associated with surgery, osteoarthritis, and rheumatoid arthritis. 

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