Outpatient CAPD catheter salvage for persistent exit-site/tunnel infection.

BACKGROUND: Partial replantation (i.e. replacement of the extraperitoneal portion of the catheter with creation of a new subcutaneous tunnel) has been suggested to avoid catheter removal in patients with persistent exit-site/tunnel infection (ESTI). However, published experience with this technique is limited. METHODS: Partial replantation was performed on an outpatient basis under local anesthesia for seven patients with persistent ESTI of >3 months duration. All patients resumed CAPD immediately following surgery. RESULTS: One patient had dialysate leakage less than 1 week after surgery that required catheter removal. The other patients had no complications and mean catheter survival following surgery was 7. 7 months (range 3.5-13 months). There was no recurrence of ESTI after surgery, although two patients presented with exit-site infection unrelated to the initial episode (i.e. different organism, long latency). Three other patients presented with episodes of peritonitis unrelated to surgery (i.e. delay >1 month) or ESTI (i.e. different organism). CONCLUSIONS: Partial replantation allows significant prolongation of catheter survival without major complications or interruption of CAPD. This novel procedure appears to be an appropriate alternative to catheter removal for the management of persistent ESTI. However, further studies are needed to prospectively compare partial replantation with catheter removal.

Experimental observation of plasmon polariton waves supported by a thin metal film of finite width.

What are believed to be the first experimental observations of the existence of long-range plasmon-polariton waves, guided by a thin metal film of finite width, are presented. A waveguide composed of an 8-mum-wide, 20-nm-thick, 3.5-mm-long Au metal film embedded in SiO (2) was successfully excited at a free-space wavelength of 1.55 mum in an end-fire experiment. The theoretical nature of the phenomenon is described, and experimental observations of field confinement provided by this metal waveguide are presented in detail.

EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and endometrium.

Breast cancer is the most frequent cancer in women while it is the second cause of cancer death. Estrogens are well recognized to play the predominant role in breast cancer development and growth and much efforts have been devoted to the blockade of estrogen formation and action. The most widely used therapy of breast cancer which has shown benefits at all stages of the disease is the use of the antiestrogen Tamoxifen. This compound, however, possesses mixed agonist and antagonist activity and major efforts have been devoted to the development of compounds having pure antiestrogenic activity in the mammary gland and endometrium. Such a compound would avoid the problem of stimulation of the endometrium and the risk of endometrial carcinoma. We have thus synthesized an orally active non-steroidal antiestrogen, EM-652 (SCH 57068) and the prodrug EM-800 (SCH57050) which are the most potent of the known antiestrogens. EM-652 is the compound having the highest affinity for the estrogen receptor, including estradiol. It has higher affinity for the ER than ICI 182780, hydroxytamoxifen, raloxifene, droloxifene and hydroxytoremifene. EM-652 has the most potent inhibitory activity on both ER alpha and ER beta compared to any of the other antiestrogens tested. An important aspect of EM-652 is that it inhibits both the AF1 and AF2 functions of both ER alpha and ER beta while the inhibitory action of hydroxytamoxifen is limited to AF2, the ligand-dependent function of the estrogen receptors. AF1 activity is constitutive, ligand-independent and is responsible for mediation of the activity of growth factors and of the ras oncogene and MAP-kinase pathway. EM-652 inhibits Ras-induced transcriptional activity of ER alpha and ER beta and blocks SRC-1-stimulated activity of the two receptors. EM-652 was also found to block the recruitment of SRC-1 at AF1 of ER beta, this ligand-independent activation of AF1 being closely related to phosphorylation of the steroid receptors by protein kinase. Most importantly, the antiestrogen hydroxytamoxifen has no inhibitory effect on the SRC-1-induced ER beta activity while the pure antiestrogen EM-652 completely abolishes this effect, thus strengthening the need to use pure antiestrogens in breast cancer therapy in order to control all known aspects of ER-regulated gene expression. In fact, the absence of blockade of AF2 by hydroxytamoxifen could explain why the benefits of tamoxifen observed up to 5 years become negative at longer time intervals and why resistance develops to tamoxifen. EM-800, the prodrug of EM-652, has been shown to prevent the development of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat, a well-recognized model of human breast cancer. It is of interest that the addition of dehydroepiandrosterone, a precursor of androgens, to EM-800, led to complete inhibition of tumor development in this model. Not only the development, but also the growth of established DMBA-induced mammary carcinoma was inhibited by treatment with EM-800. An inhibitory effect was also observed when medroxyprogesterone was added to treatment with EM-800. Uterine size was reduced to castration levels in the groups of animals treated with EM-800. An almost complete disappearance of estrogen receptors was observed in the uterus, vaginum and tumors in nude mice treated with EM-800. EM-652 was the most potent antiestrogen to inhibit the growth of human breast cancer ZR-75-1, MCF-7 and T-47D cells in vitro when compared with ICI 182780, ICI 164384, hydroxytamoxifen, and droloxifene. Moreover, EM-652 and EM-800 have no stimulatory effect on the basal levels of cell proliferation in the absence of E2 while hydroxytamoxifen and droloxifene had a stimulatory effect on the basal growth of T-47D and ZR-75-1 cells. EM-652 was also the most potent inhibitor of the percentage of cycling cancer cells. (ABSTRACT TRUNCATED)

Haemophilus influenzae type b conjugate vaccine stability: catalytic depolymerization of PRP in the presence of aluminum hydroxide.

The structural stability of the Haemophilus influenzae type b (Hib) capsular polysaccharide, polyribosylribitolphosphate (PRP) in an aluminum hydroxide adsorbed, polysaccharide-protein conjugate vaccine was monitored using modifications of an HPLC assay developed by Tsai et al. [Tsai C-M, Gu X-X, Byrd RA. Quantification of polysaccharide in Haemophilus influenzae type b conjugate and polysaccharide vaccines by high-performance anion-exchange chromatography with pulsed amperometric detection. Vaccine 1993;12:700-706.]. As applied to products containing PRP conjugated to the outer membrane protein complex (OMPC) from Neisseria meningitidis, this assay allows direct measurement of the total PRP content in very complex samples including commercial vaccine products. In addition, with the use of a high-speed centrifugation step, the assay can be used to directly quantify any PRP that is not conjugated to the OMPC carrier protein. These results provide evidence of what appears to be a catalytic reaction taking place between the phosphodiester bond of PRP and the aluminum hydroxide adjuvant that results in hydrolysis of the PRP polymer into smaller chain lengths and liberation of PRP oligomers from the conjugate particle. The reaction approaches an asymptotic limit after approximately two years at 2-8 degrees C. Clinical studies which span this time period confirm that the modest decrease in conjugated PRP content over time does not impact the overall clinical effectiveness of PRP-OMPC-containing vaccines.

Treatment of external auditory canal exostoses.

Exostoses of the external auditory canal can occur in patients living in coastal, southern California communities with a history of cold-water aquatic activities such as ocean surfing and swimming. Although most canal exostoses are asymptomatic, patients with canal obstruction greater than 80% can have recurrent episodes of external otitis and a related conductive hearing loss. In most cases, medical treatment resolves the symptomatic external otitis and related hearing loss. Patients recalcitrant to medical treatment are candidates for surgical removal of the exostoses. This report reviews the authors' surgical experience with 18 patients (27 ears) who have undergone surgical removal of exostoses. Their preferred surgical technique of transmeatal removal of exostoses with a specialized mallet and thin chisel under local anesthesia is described.

Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells.

The adenovirus type 5 243R E1A protein induces p53-dependent apoptosis in the absence of the 19- and 55-kDa E1B polypeptides. This effect appears to result from an accumulation of p53 protein and is unrelated to expression of E1B products. We now report that in the presence of the E1B 55-kDa polypeptide, the 289R E1A protein does not induce such p53 accumulation and, in fact, is able to block that induced by E1A 243R. This inhibition also requires the 289R-dependent transactivation of E4orf6 expression. E4orf6 is known to form complexes with the E1B 55-kDa protein and to function both in the transport and stabilization of viral mRNA and in shutoff of host cell protein synthesis. We demonstrated that the block in p53 accumulation is not due to the generalized shutoff of host cell metabolism. Rather, it appears to result from a mechanism targeted specifically to p53, most likely involving a decrease in the stability of p53 protein. The E1B 55-kDa protein is known to interact with both E4orf6 and p53, and as demonstrated recently by others, we showed that E4orf6 also binds directly to p53. Thus, multiple interactions between all three proteins may regulate p53 stability, resulting in the maintenance of low levels of p53 following virus infection.

Expression of p53 in Saos-2 osteosarcoma cells induces apoptosis which can be inhibited by Bcl-2 or the adenovirus E1B-55 kDa protein.

Studies were carried out to determine the effects of introducing p53 using an adenovirus gene transfer vector into p53 null human Saos-2 osteogenic carcinoma cells. Expression of p53 led to cell death within 30-40 h. The morphology of these cells as determined by electron microscopy indicated that death was by apoptosis. Such death was significantly reduced in Saos-2 variants that express high levels of the Bcl-2 suppressor of apoptosis. It was also found that the E1B-55 kDa protein of human adenovirus type 5, which was known to bind and inactivate p53, blocks Saos-2 cell death following expression of p53. These results thus directly demonstrate that this viral protein is able to inhibit p53-induced apoptosis.

Pharmacokinetics of epidural butorphanol in isoflurane-anaesthetized dogs.

Sixteen healthy male dogs were used at random in this protocol. The dogs were anaesthetized with isoflurane in oxygen. Eight of the dogs received 0.25 mg/kg of butorphanol (group B) and the others an equal volume of isotonic saline (group S) administered by a catheter inserted in the lumbosacral epidural space. Butorphanol concentrations in plasma and cerebrospinal fluid (CSF) were measured using high-performance liquid chromatography with electrochemical detection. Maximum concentration of butorphanol and time to obtain this concentration were 42.28 ng/mL at 13.88 min in blood, and 18.03 ng/mL at 30 min in CSF. Volume of distribution, clearance, mean distribution and elimination half-lives were respectively 4.39 L/kg, 2.02 L/h.kg, 16.5 min and 189.1 min. Mean isoflurane minimal alveolar concentration values for group B obtained following hind- or forelimb stimulation decreased by 31% after epidural butorphanol. Cutaneous analgesia (to pin-prick test) persisted for 3 h after the end of isoflurane anaesthesia in group B and was in correlation with the plasmatic analgesic dose of butorphanol (9 ng/mL). These results suggested that analgesia was predominantly obtained by action of butorphanol on the supraspinal structures following its vascular systemic absorption.

Postdialysis urea rebound: determinants and influence on dialysis delivery in chronic hemodialysis patients.

We measured postdialysis urea rebound (PDUR) 30 minutes after dialysis in 92 chronic hemodialysis patients. The impact of PDUR on the estimation of dialysis delivery assessed by urea reduction ratio and Kt/V was evaluated. Total recirculation, access plus cardiopulmonary, was measured at the end of dialysis with the two-needle low blood flow method. The mean age of the 92 patients (49 men and 43 women) was 59.6 +/- 1.4 years. Thirty-eight patients had been receiving erythropoietin therapy for more than 3 months. Fifteen patients had central venovenous access and 77 had peripheral arteriovenous access. Sixty-five patients were dialyzed using hemophan membranes and 27 were dialyzed using polyacrylonitrile membranes. The mean blood flow rate was 240 +/- 28 mL/min and the mean length of the hemodialysis sessions was 3.6 +/- 0.1 hours. Kt/V was calculated with Daugirdas' second-generation formula. The mean PDUR was 16.6% +/- 0.8% (range, 2% to 44%) (n = 92), and significantly decreased the mean urea reduction ratio from 61.7% +/- 0.8% to 55.5% +/- 0.9%, the mean Kt/V from 1.14 +/- 0.03 to 0.97 +/- 0.02, and the mean protein catabolic rate from 1.06 +/- 0.04 to 0.98 +/- 0.02 (P = 0.0001). The effective Kt/V at 30 minutes postdialysis was well predicted by using a recently proposed equation: eKt/V30 = Kt/Vsp - (0.6 x Kt/Vsp/t) + 0.03, with a mean value corresponding also to 0.97 +/- 0.02. However, this estimation was less predictive in patients with very high PDUR. Moreover, PDUR showed only a weak negative correlation with dialysis session length (r = -0.28) and predialysis patient weight (r = -0.29), and showed no correlation with predialysis serum urea level or with blood flow rate. However, dialysis efficiency, as assessed by K/V, presented a correlation of 0.54 with both PDUR and the difference in Kt/V when using urea immediately postdialysis and at 30 minutes. The mean total recirculation was 7.4% +/- 0.6% (n = 86). Postdialysis urea rebound, calculated between 30 or 120 seconds and 30 minutes after dialysis to deduce the influence of recirculations, was reduced but remained important with a mean of 11.8% +/- 0.7%. Thus, total recirculation contributed to nearly 30% of PDUR. The 24 patients with PDUR > or = 20% were compared with the 68 patients with PDUR lower than 20%: women and patients with higher K/V and higher total recirculation presented greater PDUR. Because of relatively few predictive factors for PDUR, its potential considerable impact on dialysis delivery estimation, and the influence of recirculations on the total PDUR amount, total recirculation and PDUR should be determined on an individual basis in chronic hemodialysis patients. The equation proposed to estimate effective Kt/V at 30 minutes is accurate in most patients with PDUR lower than 30% and is a simple alternative.

Effect of ionizing dose rate on the radioresistance of some food pathogenic bacteria.

Food pathogenic bacteria including Listeria monocytogenes (1A1 and ATCC 19111), Staphylococcus aureus (GD13 and ATCC 13565), Escherichia coli O157:H7 (ATCC 35150), Salmonella typhimurium, Yersinia enterocolitica, Vibrio parahaemolyticus, and Campylobacter jejuni were exposed to various rates of ionizing radiation (0.78, 2.6, and 22 kGy/h) emitted by three different 60Co irradiators. D10 values (D10 is the radiation dose required to eliminate 90% of a bacterial population (one logarithmic cycle reduction)) were calculated for the various strains and growth conditions tested. A covariance analysis of these results revealed that the dose rates studied had no significant influence on the radiosensitivity of these bacteria. At all dose rates, the bacteria were more radiosensitive when irradiated in a saline solution (0.85% NaCl) than in a chicken breast meat suspension. The growth phase of the bacterial population had a variable influence on its radioresistance. For L. monocytogenes 1A1, Staphylococcus aureus ATCC 13565, E. coli O157:H7, Y. enterocolitica, and V. parahaemolyticus, radioresistance was not significantly different in the exponential and stationary phases. Populations of L. monocytogenes ATCC 19111 and Staphylococcus aureus GD13 were significantly more resistant in the stationary phase (D10 = 0.23 and 0.12 kGy, respectively) than in the exponential phase (D10 = 0.17 and 0.09 kGy, respectively). Among the pathogenic bacteria investigated in this study, the most radioresistant was L. monocytogenes (D10 = 0.16-0.38 kGy, Gram-positive bacilli) and the most radiosensitive was V. parahaemolyticus (D10 = 0.03-0.04 kGy, halophilic Gram-negative bacilli).

Functional interactions within adenovirus E1A protein complexes.

The transforming potential of adenovirus E1A oncogene products derives largely from the formation of complexes with cellular proteins, including the p105Rb tumor suppressor and a related p107 species, p130 and p300 proteins, and cyclin A (p60cycA). Extensive quantitative analyses using E1A deletion mutants identified unique binding patterns for each of these polypeptides within the amino terminus and conserved regions 1 and 2 (CR1 and CR2) of E1A proteins. A novel protein, termed p400, was found by peptide mapping to be related to p300, and, like p300, to require the E1A amino terminus and a portion of CR1 for binding. p130 was shown to be related to p107, and like p107, to associate with p60cycA. p107, p130 and p105Rb all interacted primarily with CR2, however, sequences within CR1 and the amino terminus were capable of weak interactions and appeared to function cooperatively with CR2 to bind these proteins. Protein kinase activity present in E1A complexes probably derives at least in part from p60cycA-linked p33cdk2 associated with p107 and p130. In vitro phosphorylation of complexes purified by immunoprecipitation resulted in labeling of several proteins. p60cycA was phosphorylated to about the same extent in cyclin A complexes prepared from either AD5- or mock-infected KB cells, however, that of p130 and p107 was dramatically higher in p60cycA complexes from infected cells. p300 was also phosphorylated in complexes prepared using E1A-specific antibodies. Thus one role of E1A proteins in signal transduction and regulation of the cell cycle may be to control the biological activity of p107, p130 and p300 by enhancing their phosphorylation through complex formation.

Improvement of shelf-life and wholesomeness of ground beef by irradiation-2. Chemical analysis and sensory evaluation.

Lean ground beef was exposed to three dose levels of gamma radiations (Cobalt-60) (1·0, 2·5 and 5·0 kGy). Chemical indices monitored throughout the storage period (16 days, 4°C) included pH, free fatty acids and peroxides. Irradiation clearly contributed to a diminution of the pH and an increase of the peroxides. Free fatty acids were not affected. The 10 non-expert panellists indicated a noticeable effect of irradiation on the odour and colour of the raw product. The odour and flavour of the irradiated cooked ground beef was slightly disliked while no difference was perceived in the colour and texture of the cooked irradiated ground beef. Following these considerations, it is recommended that ground beef be treated with a low dose (such as 1 kGy).

Isolation of chicken phosphotyrosyl phosphatase cDNA sequences and identification of a brain-specific species related to human PTP zeta.

The first example of a chicken cDNA sequence encoding a phosphotyrosyl phosphatase (PTPase) has been identified and found to contain coding sequences for the entire cytoplasmic and membrane spanning domains as well as a portion of the extracellular region of a transmembrane PTPase resembling human PTP zeta. Like HPTP zeta, chicken PTP zeta contained two phosphatase domains (D1 and D2), and D2 lacked a critical cysteine residue required for catalytic activity. The entire intracellular portion of CPTP zeta was expressed in bacteria and shown to be capable of dephosphorylating both p-nitrophenylphosphate and reduced carboxyamidomethylated and maleyated lysozyme but not phosphoseryl casein. Genetic analysis indicated that the presence of D2 was required for full activity. CPTP zeta mRNA was identified as a single large transcript expressed exclusively in the brain of chick embryos at both early and late stages of embryogenesis. These results suggested that CPTP zeta may perform a brain-specific function and have a role in development.

In vivo and in vitro gastric emptying of protein fractions of milk replacers containing whey proteins.

In vivo and in vitro gastric emptying of protein fractions of three milk replacers containing either milk protein (control), a mixture (50:50 on a CP basis) of milk protein and native whey protein concentrate, or a mixture (50:50 on a CP basis) of milk protein and heated whey protein concentrate was studied. In vivo gastric emptying was measured in three preruminant calves fitted with reentrant duodenal cannulas and used in a 3 x 3 Latin square design. In vitro gastric emptying was determined after enzymatic digestion in an artificial stomach. In vivo and in vitro flow rates of protein N (12% TCA-insoluble N) and total N were higher for milk replacers containing whey proteins than for control. Gastric emptying of NPN (12% TCA-soluble N) was slightly higher for diets containing whey proteins than for that containing milk proteins. Gastric emptying of all protein fractions was similar for the two milk replacers containing whey proteins. In vivo and in vitro results were significantly correlated, suggesting that the in vitro method reproduced conditions for proteolysis and could be used to predict gastric digestion of protein fractions.

Improvement of shelf-life and wholesomeness of ground beef by irradiation 1. Microbial aspects.

Various doses of ionizing radiation (cobalt-60) were used to improve the microbiological quality of commercial ground beef. The study included the isolation and identification of the natural microbial flora. The radioresistance of the individual strains was investigated. D(10) values, obtained in a saline solution, showed values ranging from 0·035 to 1·827 kGy. Treatment of ground beef with gamma radiation at doses of 1·0, 2·5 and 5·0 kGy resulted in extended shelf-life at 4°C of 4, 10 and 15 days, respectively while the control samples already exceeded 10(7) colony forming units (CFU)/g on day 0. Dominant groups of bacteria shifted from Gram-negative bacilli to Gram-positive cocci as the irradiation dose increased. Gram-negative cocci as well as yeasts and moulds also developed in greater proportion during storage of the irradiated samples.

New test for AIDS.

PIP: Initial results of research indicate that the Program for Appropriate Technology in Health (PATH) in Washington, D.C. has developed an HIV-1 screening test, the HIV ImmunoDot Test, appropriate to conditions in developing countries. This means it's affordable, quick, simple, and can be manufactured in developing countries. The need for such a test is based on the occurrence of HIV transmission through blood transfusions to anemic women and children, which is a leading cause of hospitalization. It is reported that in the hospital Mama Yemo of Kinshasa, Zaire that 12,800 transfusions were performed annually in 1985/6, of which 560 children contracted the AIDs virus that same year. The rate is 15% of patients compared to 2% for Europe. Although the number of transfusions in this hospital have declined, blood from donors is frequently contaminated by hepatitis, malaria, syphilis, or HIV-1. The HIV ImmunoDot Test produces results in 20 minutes. It is highly sensitive; easy to interpret, requires no refrigeration, special equipment or instruments; and costs 25 US cents. Manufacturing plans are being developed for its manufactured in developing countries. The test consists of 8 teeth or tabs on a comb activated by a synthetic peptide derived from the GP41 molecule and allows for testing 8 serum samples simultaneously. The comb may be cut to test fewer samples. The procedure involves setting the comb in the blood specimens for 10 minutes at ambient temperature. Then it is washed in a saline solution and set to incubate for 10 minutes in an indicator reagent. After this, it is washed again in a saline solution, and read after it has dried. A red dot indicates contact with HIV positive serum. The cost for a production run of 500,000 is 12 US cents per unit test compared to the ELISA test of 207 US dollars per unit test. The PATH ImmunoDot Test is stable for up to a year at ambient temperatures typical in Equatorial Africa. The test occasionally shows positive results when it is not (98.2% specificity). Such tests are rare enough that followup with ELISA or Western Blot can confirm accurate results. It is preferable to discard a unit of blood than to transmit the virus. The research was part of an international collaborative effort.^ieng

[Dilatation of bile ducts in polycystic kidney disease in adults]. / Dilatation des voies biliaires au cours de la polykystose rénale de l'adulte.

We report the cases of 4 adult patients with polycystic kidney disease and dilatation of bile ducts. Dilatation involved the extra-hepatic bile ducts in all 4 cases and also affected the intra-hepatic bile ducts in 3 cases. A prospective ultrasonographic study in search of biliary tract abnormalities was undertaken in 40 patients with dominant polycystic kidney disease. No bile duct dilatation was found in this series, which indicates that the lesion is rare. The 4 cases reported here increase the collection of hepatobiliary lesions associated with polycystic kidney disease of adults.

Specific role of endopeptidases in modulating the nature of protein digestion products.

The impact of various endopeptidases on the nature of protein digestion products was measured with the digestion cell technique. After a 30 min pepsin pre-digestion, casein and rapeseed concentrates were hydrolyzed with various amounts of pancreatin, trypsin and/or chymotrypsin. This hydrolysis was performed in a dialysis tube (molecular weight cut-off 1000) with continuous collection of the digested material. The addition of pure trypsin or chymotrypsin to pancreatin (Enzyme:Substrate 1:25) did not change the digestibility of casein. Only a higher pancreatin level (Enzyme:Substrate 1:12.5) increased the total protein digestibility without affecting the amino acid spectra. Rapeseed digestibility was markedly increased by the addition of pure trypsin to pancreatin. Lysine and arginine, target amino acids of trypsin, were favored at the expense of chymotrypsin and elastase target amino acids. Supplementation of pancreatin with chymotrypsin enhanced rapeseed digestibility without affecting the relative amino acid digestibility. The impact of a higher pancreatin ratio (Enzyme:Substrate 1:12.5) was similar to that of enriched pancreatin but the rate of amino acid release was modified. The differences between protein sources were mainly attributed to protein structure.

Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease.

Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials.