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Three oral explanations took place during the meeting. The COMP noted that four applications for orphan medicinal product designation were withdrawn by sponsors. Overview of orphan designation procedures The European Commission granted ten positive decisions on orphan designation1 since the last COMP meeting on 14-15 June 2005 see Annex 1 ; . The status of orphan designation procedures, to date for 2005, is summarised below.
We have recently shown that conservation and differentiation of primitive human hematopoietic progenitors in in vitro long-term bone marrow cultures LTBMC ; occurs t o a greater extent when hematopoietic cells are grown separated from the stromal layer than when grown in direct contact with the stroma. This finding suggests that hematopoiesis may depend mainly on soluble factors produced by the stroma. To define these soluble factors, w e examine here whether a combination of defined early-acting cytokines can replace soluble stroma-derived biologic activities that induce conservation and differentiation of primitive progenitors. Normal human Lineage- CD34 + HLA-DRcells DR- ; were cultured either in the absence of a stromal layer "stroma-free" ; or in a culture system in which DR- cells were separated from the stromal layer by a microporous membrane "stroma-noncontact" ; . Both culture systems were supplemented three times per week with or without cytokines. These studies show that culture of DR- cells for 5 weeks in a "stroma-free" culture supplemented with a combination of four early acting cytokines Interleukin-3 [IL-31, stem cell factor [SCF], leukemia-inhibitory factor [LIF], and granulocyte colony-stimulating factor [G-CSF] ; results in a similar cell expansion as when DR- cells are cultured in "stroma-noncontact" cultures supplemented with the same cytokines. However, generation of committed progenitors and conservation of the more primitive long-term bone marrow culture initiating cells LTBMC-IC ; was far superior in "stroma-noncontact" cultures supplemented with or without IL-3 than in "stroma-free" cultures supplemented with IL-3 alone or a combination of IL-3, LIF, G-CSF, and SCF. These studies indicate that human BM stroma produces soluble factors that can either alone or in synergy with defined cytokines 1 ; conserve primitive LTBMC-IC, 2 ; induce early differentiation of a fraction of the primitive progenitors, and 3 ; prevent their terminal differentiation. We show here that these stroma-derived factors are not likely t o be the known early acting cytokines IL-3, SCF, LIF, or G-CSF. Characterization of the stroma-derived factor s ; may have important implications for clinically relevant studies, such as in vitro stem cell expansion in cancer treatment and gene therapy. 0 1993 by The American Society of Hematology.

Paul Roufail, Therapeutic Products Directorate, Health Canada, Ottawa, Ontario, Canada The Therapeutic Products Directorate has been developing guidance documents on several areas related to topically administered formulations. The objectives of these guidance documents are to assist the pharmaceutical industry in the development and filing of submissions and ensure consistency in the procedures used for the evaluation of these formulations. This presentation will give an update on the status of these activities and discuss some of the issues related to each of them.

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The magnitude and persistence of informality is one emblematic aspect of urban land markets in Third-world cities. It seems to be both an effect and a cause of high land prices. A number of factors limit access to land. Land prices are just too high compared to average family incomes and equivalent prices in developed countries. The latter may be attributed to informality growing more rapidly than poverty despite large scale government-sponsored regularization programs and citywide settlement upgrading programs. It is apparent we are losing ground on generating more socially responsible alternatives for informality and slum formation. The growth rate of informal settlements is still higher than the solutions provided through formal programs. This event will focus on the two complementary sides of the response to this problem A discussant mentioned that t-butyl hydroperoxide given to rabbits causes an increase in thromboxane but no change in pulmonary pressure. if the rabbits are pretreated with the antioxidants, vitamin E, or butylated hydroxyanisole, is both an increase in thromboxane and pulmonary The with medial The are not vascular implication reduces observation in point. None. RATIONALE: The intent of the criteria is to ensure that patients follow selection elements noted in labeling and the clinical guidelines for the treatment of obesity set by the National Institutes of Health, National Heart, Lung and Blood Institute NHLBI ; , and American Association of Clinical Endocrinologists AACE ; . The purpose of weight loss and weight maintenance is to reduce health risk. Only patients who are at increased medical risk should use weight loss medications. Weight loss programs should begin with a basic regimen of low calorie diet, increased physical activity, and behavioral therapy. After at least 6 months on the basic weight loss program, if a patient has not lost the recommended one pound per week, careful consideration may be given to phamacotherapy. Organic causes of obesity e.g., untreated hypothyroidism ; should also be excluded before prescribing pharmacotherapy. The major role of medications is to help with patient compliance to weight loss plan. Therefore, drugs should be used as part of a comprehensive weight loss program and should never be used without concomitant lifestyle modification. Drugs may be used as an adjunct to diet and physical activity for patients with a BMI that is 30 kg other risk factors are present e.g., hypertension, diabetes, hyperlipidemia ; . Patient should be monitored regularly while on a weight loss regimen. People with high blood pressure, symptomatic cardiovascular disease, hyperthyroidism, glaucoma, history of drug abuse, or have taken a monoamine oxidase inhibitor in the previous 14 days should not take anorectic therapy. In addition, patients should be informed of the potential risks versus the benefits of pharmacotherapy. For renewal after one month of therapy, in order to limit unwarranted exposure and risks, therapy should be continued only if the patient has satisfactory weight loss with in the first four weeks of treatment. The patient must lose at least one pound per week 4 pounds in 4 weeks ; . Anorectic drugs have a narrow FDA labeling which reflects on the importance of prevention of inappropriate usage. The approval duration is limited to 3 months because labeling and guidelines support up to 12 weeks of therapy. The safety of long-term anorexiant therapy has not been established conclusively beyond 12 weeks of administration. To be considered for therapy, the patient must be at least 16 years of age. Even though benzphetamine and phendimetrazine are approved for use in children at least 12 years of age or greater, the treatment guidelines do not recommend the use of pharmacotherpy in children or adolescents. ADDITIONAL INFORMATION Dosage and Administration Diethylpropion Immediate Release One 25 mg tablet three times daily, one hour before meals, and in mid-evening if desired to overcome night hunger. Controlled Release One 75 mg tablet, swallowed whole, in the morning. Didrex Dosage should be individualized according to the response of the patient. The suggested dosage ranges from 25 mg to 50 mg one to three times daily. Treatment should begin with 25 mg to 50 mg once daily with subsequent increase in individual dose or frequency according to response. A single daily dose is preferably given in midmorning or mid-afternoon, according to the patient's eating habits. In an occasional patient it may be desirable to avoid late afternoon administration. Use of benzphetamine is not recommended in individuals under 12 years of age. Bontril One slow-release capsule 105 mg ; in the morning, taken 30 minutes to 60 minutes before the morning meal. Phendimetrazine is not recommended for use in children under 12 years of age and benztropine.

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Follow-up of TCRBV expansions during therapy with IFN- . In two patients the TCRBV domain expression before and during IFN- therapy was measured. Results are shown in Table 2. Patient A was analyzed after 3 years and showed a complete hematologic response with normalization of the leukocyte differential disappearance of circulating hairy cells, reappearance of monocytes ; . The very high percentage of BV3 cells decreased from 24.6% to 7.5% normal, 3.3% 1.2% ; . By RT-PCR a faint TCRBV band was still visible 3 years after the start of IFN- Fig 3 ; . Also, the increased percentages of BV17 10%; normal, 5.4% 1.3% ; and BV18 6.8%; normal, 1.2% 0.6% ; normalized during IFN- . This normalization was also seen for the absolute BV17 and BV18 cell counts Table 3 ; . In contrast, patient B, who was assessed after. A total of 485 patients were recruited and randomized in 29 GEICAM-affiliated centers. A flowchart of main features of the study design and execution is shown in Figure 1. Of the 485 patients, 11 2.26% ; were non-evaluable because of major protocol deviations; six patients were ineligible because of metastatic disease, two patients were in stage IIIB, two patients were premenopausal and one patient did not have documented nodal involvement. Analysis of results was performed according to the intent-to-treat principle and, as such, patients with minor protocol deviations or treatment noncompliance were not excluded. At a median follow-up of 54 months, seven patients were lost to follow-up in the SEQ treatment arm and five patients in the CON arm. Additionally, three and one patient, in the two treatment arms, respectively, opted to withdraw from the study. Minimum time of follow-up was 22 months and the maximum time was 83 months. Patient characteristics are depicted in Table 1. As expected after stratification and randomization, the main demographic characteristics and prognostic factors were well balanced in the two treatment groups. Hormone receptor determination was by immunohistochemistry in all participating centers. Local criteria for positive or negative status were respected when results were expressed unambiguously. A threshold of 10% positive cells was preferred when this quantitative information was available. Compliance with treatment was generally good, with 87% and 90% chemotherapy cycles administered on time for SEQ and CON treatment arms, 11% and 9%, respectively, were delayed 5 days, with only 2% and 1%, respectively, being delayed 5 days. As per protocol, delayed chemotherapy administration was justi and bepridil.

Pirongia School is staging an outdoor movie night this Friday. Live band entertainment starts at 6pm, followed by a `mystery' family movie on the big screen.Entry is by way of a gold coin donation. The greater availability of solvent protons in the latter protein is probably responsible for the uncoupling and that a highly orchestrated protonation of the iron-peroxy intermediate must occur at the active site to generate the iron-oxene species. A recent study by Miller and White 47 ; suggests that P450 2B4 retains water in the active site even in the presence of a hydrophobic substrate, which may account for the partial uncoupling observed with this enzyme. Alternatively, the solvent may serve as a protic source for cleavage of the O-O bond, partially substituting for threonine-302 in 2B4 A2-27 ; T302A. This may account for the remaining slight activity in the benzphetamine and cyclohexane hydroxylation reactions catalyzed by the mutant enzyme. In the case of 1-phenylethanol oxidation to acetophenone, however, a reaction known to occur via hydroxylation of the benzylic carbon 40 ; , as much as one-half of the activity is retained by our T302A mutant. It may be noted in this connection that P450EryF, which is highly unusual in lacking the conserved threonine in the active site, is competent in the hydroxylation of the erythromycin precursor 6-deoxyerythronolide B 26 ; . From such substrate structure-function relationships and analysis of the crystal structure of P45OEryF 48 ; , Poulos and colleagues 49 ; have suggested that a novel substrate-assisted acid catalysis is used in the oxygen activation step. Presumably, a substrate hydroxyl group in conjunction with ordered water in the active site may provide the necessary hydrogen bonding network between the active site and the bulk solvent such that a proton can be provided for cleavage of the iron-peroxo complex to generate the iron-oxene species. Thus, we propose that in a similar way the hydroxyl group of 1-phenylethanol in conjunction with water molecules in the active site may replace the proton delivery network disrupted by the T302A mutation in P450 2B4 A2-27 ; . It should also be noted that while the oxidation of 1-phenylethanol was demonstrated to proceed by a stepwise hydrogen atom abstraction and oxygen rebound mechanism, the oxidant was assumed to be an iron-oxenoid species 40 ; . From our results it is apparent that threonine-302, while influencing the generation of the active oxidant for hydroxylation reactions, appears not to be uniquely responsible for promoting cleavage of the O-O bond of the iron-peroxo intermediate to the iron-oxenoid species. In sharp contrast to the decreased oxidation of benzphetamine, cyclohexane, and 1-phenylethanol by the T302A mutant, the deformylation of cyclohexane carboxaldehyde to yield cyclohexene was increased about 10-fold over that of truncated 2B4 and more than 5-fold over that of intact 2B4 Table 2 ; . On the basis of this finding and that of previous studies with H202 and artificial oxidants 14 ; , we conclude that the reaction and betaseron.

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Table 2. Subject Demographics by Group.

Isolated factor VII deficiency and the relatively mild bleeding diathesis associated with factor XI deficiency. Combined deficiency of factors VII and XI may have more serious clinical consequences. We are not aware of any reports of such a congenital deficiency state or adverse reactions after the administration of vitamin K antagonists to factor XI-deficient patients. Such studies could be performed such animals We suggest in XIare that deficient animals, not available at patients tor VII possible but unfortunately the present time and betaxolol. Predictable response with the development of one or two mature follicles and a significantly reduced risk for OHSS and multiple gestation. To achieve multiple ovulation, the addition of FSH to the AI is likely necessary.

Induced ejaculation delay in the rat. Br J Pharmacol 2003; 138 suppl.1 ; : PO32. de Jong TR, Pattij T, Veening JG, et al. Citalopram combined with a silent 5-HT1A receptor antagonist strongly inhibits male rat sexual behavior and ejaculation-related Fos expression. Neuroscience Poster. Second Dutch Endo-Neuro-Psychomeeting. Doorwerth. The Netherlands, June 2003. Ludovico GM, Corvasce A, Pagliarulo G, Cirillo-Marucco E, Marano A, Pagliarulo A. Paroxetine in the treatment of premature ejaculation. Br J Urol 1996; 77: 881-82. Waldinger MD, Hengeveld MW, Zwinderman AH. Ejaculationretarding properties of paroxetine in patients with primary premature ejaculation: a double-blind, randomized, dose-response study. Br J Urol 1997; 79: 592-5. Giammusso B, Morgia G, Spampinato A, Motta M. Paroxetine in the treatment of premature ejaculation. Arch Ital Urol Androl 1997; 69: 11-3. McMahon CG, Touma K. Treatment of premature ejaculation with paroxetine hydrochloride. Int J Impot Res 1999; 11: 241246. Waldinger MD, Zwinderman AH, Olivier B. On-demand treatment of premature ejaculation with clomipramine and paroxetine: A randomized, double-blind fixed-dose study with stopwatch assessment. Eur Urol 2004; 46: 5106. Mendels J, Camera A, Sikes C. Sertraline treatment for premature ejaculation. J Clin Psychopharmacol 1995; 15: 3416. Roblin D. Premature ejaculation: diagnosis and pharmacotherapy. Int J Pharm Med 2000; 14: 313318. Kim SC, Seo KK. Efficacy and safety of fluoxetine, sertraline and clomipramine in patients with premature ejaculation: a doubleblind placebo controlled study. J Urol 1998; 159: 425427. McMahon G. Treatment of premature ejaculation with sertraline: a single blind placebo controlled crossover study. J Urol 1998; 159: 1935-1938. Yilmaz U, Tatlisen A, Turan H, Arman F, Ekmekcioglu O. The effects of fluoxetine on several neurophysiological variables in patients with premature ejaculation. J Urol. 1999; 161 1 ; : 107-11. Cantor JM, Binik YM, Pfaus JG. Chronic fluoxetine inhibits sexual behavior in the male rat: reversal with oxytocin. Psychopharmacology 1999; 144: 355-62. Kara H, Aydin S, A argn MY, Odabas , Yilmaz Y. The efficacy of fluoxetine in the treatment of premature ejaculation: a doubleblind placebo controlled study. J Urol 1996; 156: 1631-2. Murray MJ, Hooberman D. Fluoxetine and prolonged erection. J Psychiatry 1993; 150: 167-8. Manasia P, Pomerol J, Ribe N, Gutierrez del Pozo R, Alcover Garcia J. Comparison of the efficacy and safety of 90 mg versus 20 mg fluoxetine in the treatment of premature ejaculation. J Urol. 2003; 170 1 ; : 164-5. Palmer KJ, Benfield P. Fluvoxamine: an overview of its pharmacological properties and review of its therapeutic potential in non-depressive disorders. CNS Drugs. 1994; 1: 5787. Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B. Effect of SSRI antidepressants on ejaculation: A double-blind, randomized, placebocontrolled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J Clin Psychopharmacol 1998b; 18: 27481. Waldinger MD, van De Plas A, Pattij T, et al. The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment. Psychopharmacology 2002; 160: 283-9 Segraves RT, Saran A, Segraves K, Maguire E. Clomipramine vs placebo in the treatment of premature ejaculation: a pilot study. J Sex Marital Ther 1993; 19: 198200. Riley AC, Riley EJ. Pharmacotherapy for sexual dysfunction: current status. In AJ Riley, M Peet, and C Wilson, eds. Sexual Pharmacology. Oxford: Clarendon, 1993; 21126. Colpi GM, Fanciullacci F, Aydos K, Grugnetti C. Effectiveness mechanism of clomipramine by neurophysiological tests in subjects with true premature ejaculation. Andrologia 1990; 23: 45-7. Kilic S, Ergin H, Baydinc YC. Venlafaxine extended release for the treatment of patients with premature ejaculation: a pilot, singleblind, placebo-controlled, fixed-dose crossover study on short-term administration of an antidepressant drug. Int J Androl 2005; 28 1 ; : 47-52 and bevacizumab.

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Tell your doctor if you are taking, have recently taken, or plan to take any of the following prescription and non-prescription medications: certain other antidepressants including amitriptyline elavil ; , amoxapine, clomipramine anafranil ; , desipramine norpramin ; , doxepin sinequan ; , imipramine tofranil ; , maprotiline, mirtazapine remeron ; , nortriptyline pamelor ; , protriptyline vivactil ; , and trimipramine surmontil amphetamines such as amphetamine in adderall ; , benzphetamine didrex ; , dextroamphetamine dexedrine, dextrostat, in adderall ; , and methamphetamine desoxyn bupropion wellbutrin, zyban buspirone buspar caffeine no-doz, quick-pep, vivarin cyclobenzaprine flexeril dexfenfluramine redux ; not available in the dextromethorphan robitussin, others duloxetine cymbalta epinephrine epipen, primatene mist guanethidine ismelin ; not available in the levodopa larodopa, in sinemet medications for allergies, cough and cold symptoms, hay fever; anxiety, sinus problems, or weight loss diet pills, appetite suppressants medications for seizures such as carbamazepine tegretol narcotic medications for pain; nasal decongestants, including nose drops and sprays; other maois such as isocarboxazid marplan pargyline not available in the ; , procarbazine matulane ; , tranylcypromine parnate ; , and selegiline eldepryl, emsam, zelapar meperidine demerol methyldopa aldomet 'pep pills'; sedatives; selective serotonin reuptake inhibitors such as citalopram celexa ; , escitalopram lexapro ; , fluoxetine prozac ; , fluvoxamine luvox ; , paroxetine paxil ; , and sertraline zoloft sleeping pills; tranquilizers; venlafaxine effexor and medications containing alcohol nyquil, elixirs, others. Diverse microhabitats Ros et al. 1985 ; . Their conservation may be important to maintain healthy fisheries of some species in the area. The purpose of this paper is to examine variation in 3 population parameters condition, feeding and reproductive potential ; of the white seabream Diplodus sargus as indicators of habitat quality in the northwestern Mediterranean. Specifically, we aim to explore the impact of reserve protection, substrate type and depth on condition, feeding and reproductive potential to evaluate the effectiveness of a marine reserve and the importance of certain types of substrates. We hypothesize that bottom type, protection and depth might be important for condition. The effect of sex, maturity and length on condition will be also analyzed because these biological parameters have been shown to affect condition of many fish species see Shulman & Love 1999 ; . The condition of a fish is affected by interactions among habitat characteristics e.g. food and habitat availability, competition, physical factors, parasitic infections and pollution ; and the physiology of the fish Chellappa et al. 1989, Kerrigan 1994, Griffiths & Kirkwood 1995, Parrish & Mallicoate 1995, Guderley et al. 1996, Francis 1997, Lee & Khan 2000, Lloret & Rtz 2000, Yaragina & Marshall 2000 ; . As a measure of energy reserves, condition indices can have major consequences for the health of individual fish and influence survival and population success Kjesbu et al. 1992, Lambert & Dutil 1997, Marshall & Frank 1999, Shulman & Love 1999 ; . Inadequate energy reserves have been implicated in the reduced reproductive potential of several fish species through reduced fecundity and or quality of eggs and larvae Kjesbu et al. 1992, Adams 1999, Marshall et al. 1999, Lambert & Dutil 2000 ; . Poor condition i.e. lower available energy reserves ; may also lower the chances of survival of big fish, leading to an increase of natural mortality Krivobok & Tokareva 1972, Love 1974, Adams 1999, Shulman & Love 1999 ; . Starvation due to exhaustion of energy reserves, particularly in smaller individuals and during the nonfeeding periods, weakens fish and also renders them more susceptible to predation and to a variety of environmental stressors e.g. parasites, thermal and contaminant effects ; . The condition of a fish can be assessed by a variety of criteria ranging from morphometric to physiological and biochemical e.g. lipid content ; measurements. Lipids play a critical role in the health of benthic and planktonic animals and plants Adams 1999 ; . They are known to play a role as energy reserves especially during nonfeeding periods ; and as regulators of body density, cellular metabolism, detoxification, behavior swimming performance and migration ; and reproduction Planes et al. 1997, Adams 1999, Shulman & Love and bexarotene.

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Cholinomimetic activities of minaprine. Naunyn-Schmiedeberg Arch. Pharmacol. 340: 411418, 1989. XU, M., MIZOBE, F., YAMAMOTO, T. AND KATO, T.: Differential effects of M1 and M2-muscarinic drugs on striatal dopamine release and metabolism in freely moving rats. Brain Res. 495: 232236, 1989. YAMANISHI, Y., KOSASA, T. AND KANEKO, T.: E2030, a novel acetylcholineasterase inhibitor 1 ; : Neurochemical studies on the central nervous system Abstract ; . Neuroscience 18: 340, 1992. ZHU, X. D., GIACOBINI, E. AND HORNSBERGER, J. M.: Effect of MDL 73, 745 on acetylcholine and biogenic amine levels in rat cortex. Eur. J. Pharmacol. 276: 9399, 1995. Send reprint requests to: Dr. Craig P. Smith, Hoechst Marion Roussel, Inc., Neuroscience TD, PO Box 6800, Routes 202206, Bridgwater, NJ 08807-0800 and benzphetamine. CHEMICALS KNOWN TO THE STATE TO CAUSE REPRODUCTIVE TOXICITY Chemical Acetazolamide Acetohydroxamic acid Actinomycin D All-trans retinoic acid Alprazolam Altretamine Amantadine hydrochloride Amikacin sulfate Aminoglutethimide Aminoglycosides Aminopterin Amiodarone hydrochloride Amitraz Amoxapine Anabolic steroids Angiotensin converting enzyme ACE ; inhibitors Anisindione Arsenic inorganic oxides ; Aspirin NOTE: It is especially important not to use aspirin during the last three months of pregnancy, unless specifically directed to do so physician because it may cause problems in the unborn child or complications during delivery ; Atenolol Auranofin Azathioprine Barbiturates Beclomethasone dipropionate Benomyl Benzene Benzodiazepines Benzphetamine hydrochloride Bischloroethyl nitrosourea BCNU ; Carmustine ; Type of Reproductive Toxicity developmental developmental developmental developmental developmental developmental, male developmental developmental developmental developmental developmental, female developmental, female, male developmental developmental female, male developmental developmental developmental developmental, female CAS No. 59665 546883 50760 --54626 19774824 33089611 14028445 -117373 --50782 Date Listed August 20, 1999 April 1, 1990 October 1, 1992 January 1, 1989 July 1, 1990 August 20, 1999 February 27, 2001 July 1, 1990 July 1, 1990 October 1, 1992 July 1, 1987 August 26, 1997 March 30, 1999 May 15, 1998 April 1, 1990 October 1, 1992 October 1, 1992 May 1, 1997 July 1, 1990 and bidil.
FEBRUARY February 1. Lithuania established diplomatic relations with Belize. February 2. Lithuanian Foreign Minister Antanas Valionis and Polish Foreign Minister Adam Daniel Rotfeld met in Vilnius. February 3-4. Lithuanian Foreign Minister Antanas Valionis paid a visit to Ireland and met with Irish Prime Minister Bertie Ahern, Foreign Minister Dermot Ahern, parliamentary committees for Foreign and European affairs. February 7. Lithuanian Foreign Minister Antanas Valionis met with Georgian Foreign Minister Salome Zourabichvili in Vilnius. The Ministers discussed Georgia's relations with the EU and NATO.

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An observational, multicenter study was performed in 29 general hospitals from several regions in Spain. These hospitals comprised a total of 20, 250 beds for acute patients and served a population of 9, 716, 880 inhabitants. All of the patients with HIV and R equi infection from the beginning of the AIDS epidemic until September 1998 were included. Information from every patient was collected by a previously designed form. The follow-up of each patient was carried out for as long as possible, and it was finished in December 1998. In those cases diagnosed before the beginning of this study, this information was collected retrospectively. Isolation, identification, and susceptibility tests of the R equi strains were performed in the microbiology laboratory of each hospital. AIDS was diagnosed using the diagnostic criteria in force in Europe at the time of diagnosis of the R equi infection.14 16 Definitions Outcome of R equi Infection: This was assessed at the end of the follow-up period using three categories: cure, disappearance of the initial lesions and absence of manifestations of infection 1 month after withdrawing antimicrobial treatment; regression, reduction of the initial lesions and or improvement of symptoms attributable to R equi infection during the course of antimicrobial therapy; and progression, increase of the lesions or exacerbation of symptoms attributable to R equi infection during the course of treatment, as well as the recurrence of infection after withdrawing treatment. Survival: Survival was evaluated using the following categories: 1 ; death associated with R equi infection related mortality ; , when the patient's death occurred due to causes directly attributable to the infection, to complications of the infection or to the therapy used; 2 ; death not associated with the infection, when and benztropine.

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