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P3.18.16 STUDY ON THE MANAGEMENT OF SIL OF THE UTERINE CERVIX M.Oda 1 ; , M. Ohmura 1 ; , Y. Ishii 2 ; , N. Ishida 2 ; , 1 ; Tokyo Metropolitan Cancer Detection Center, 2-5 Kandasurugadai, Chiyodaku, Tokyo, Japan, 101-0062, 2 ; Tokyo Kenbikyou-In Foundation, Chiyoda-ku, Tokyo, Japan. Objective: Establishment of a following-up system for squamous intraepithelial lesion SIL ; of the uterine cervix by retrospective study. Method: Between 1984 and 1994, we have been mass-screened 177, 340 subjects for uterine cervical cancer, and detected 798 cases of low SIL and high SIL excluding cases of CIS ; of the uterine cervix at the Tokyo Metropolitan Cancer Detection Center detection rate 0.45% ; . We followed 860 cases, including cases that were referred to us. The following criteria were used in evaluating the outcome of SIL. Cases in which both cytological and colposcopical results were negative at least 3 times and continuously for at least 2 years were evaluated as regressing. Cases in which intraepithelial carcinoma or worse was confirmed histologically were evaluated as progressing. Cases which did not progress nor regress during at least 2 years of follow-up were evaluated as persisting. The average follow-up period for SIL was 49.8 months. Results: 1 ; Out of 383 cases of low SIL, 12 cases 3.1% ; progressed, 97 cases 25.3% ; persisted and 274 cases 71.4% ; regressed. 2 ; Out of 194 cases of high SIL, 39 cases 20.1% ; progressed, 68 cases 35.1% ; persisted and 87 cases 44.8% ; regressed. 3 ; Of the 361 cases that regressed, 301 did so within 2 years of followup. 4 ; Of the 51 cases that progressed, the operative histologic diagnosis was established in 44 cases. The breakdown was; CIS, 31 cases; MIC, 5 cases; SCC 1b, 4cases. Conclusion: High SIL is a lesion that progresses at a rate of approximately six times that of low SIL. Closely controlled follow-up of high SIL is possible, but medical treatment is indicated if there is no regression within 2 years. P3.19 ULTRASOUND P3.19.01 COMPARISON OF MATERNAL MIDDLE CEREBRAL ARTERY BLOOD FLOW VELOCITY AS MEASURED IN PREECLAMPTIC, HEALTHY PREGNANT AND NON-PREGNANT WOMEN BY TRANSCRANIAL DOPPLER SONOGRAPHY. J. Zatik 1 ; , J. Aranyosi 1 ; , T. Major 1 ; , L. Ovari 2 ; , D. Pall 3 ; , B. Fulesdi 1 ; , 1 ; Dept. OB GYN, 2 ; Dept. Int. Med. 3 ; Dept. Anesth. and Intensive Care, University Medical School of Debrecen, Hungary. Objectives: The aim of the study was to test the hypothesis that cerebral blood flow velocity is altered in preeclamptic pregnant women as compared to healthy pregnant and non-pregnant women. Study Methods: Preeclamptic n 21 ; and healthy pregnant n 17 ; , as well as non-pregnant n 29 ; women had undergone transcranial Doppler blood flow velocity measurements of the middle cerebral artery. Mean blood flow velocities of the middle cerebral artery MCAV ; were compared between the different groups. Results: MCAV values was significantly higher in non-pregnant women as compared to healthy pregnant women. Preeclamptic women showed significantly higher MCAV values compared to non-pregnant females. Same to the non-pregnant women, healthy pregnant patients showed lower MCAV values compared with preeclamptic women. Conclusions: We detected increased resting cerebral flow velocities in the middle cerebral arteries of pregnant patients with preeclampsia. In our opinion this finding refers to arteriolar dilation of the resistance vessels of the brain.

4.6.3 Sport-Specific Protocols Sport-specific protocols governing medical intervention during competition are listed below. Local rules may vary, however, and the following should be used as a guide only: 1. Alpine Skiing There are no specific regulations. Skiing can be considered relatively high risk and a physician and emergency personnel should be scheduled to cover the races. The local ski patrol should also be on duty. 2. Athletes with a Disability A list of the medical problems of each athlete should be made available to those covering this venue. This information should be collected on the registration forms. 3. Badminton If a participant is injured during play, the Umpire will signal the referee who will request the medical personnel enter the court to assess the injured athlete. 4. Baseball Medical personnel must wait until the umpire interrupts the play in order to attend injuries on the field. Pitchers cannot wear white bandages or tape on their arms, wrists or fingers on the throwing hand ; . Bandages must be skin colour or a long sleeve shirt must cover the bandages. Pitchers also are forbidden to wear batting gloves underneath their catching gloves. 5. Basketball Medical and paramedical personnel cannot go onto the court until play has been stopped by the official's whistle. 6. Boxing Weigh-In In the morning of the competition day, and in conjunction with the official weigh-in, all competitors must undergo a medical inspection. In addition, all referees must also undergo a physical examination prior to the beginning of a bout. These medical inspections are the responsibility of the attending physician. The equipment required includes: opthalmoscope, otoscope, stethoscope, and blood pressure cuff. The athletes generally have a medical book which must be initialed by the medical officer prior to the fight. If they have been knocked out in the preceding 30 60 90 days depending upon the severity ; , they are not allowed to fight Boxing Commission of BC ; . Items to include in the pre-fight history include: History of recent headaches History of any recent visual disturbances Recent nausea History of ever being knocked out Recent illnesses and diovan.
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Shionoiri H, Kosaka T, Kita E, et al. Comparison of long-term therapeutic effect of an ACE inhibitor, temocapril, with that of a diuretic on microalbuminuria in non-diabetic essential hypertension. Hypertens Res. 2000; 23; 593-600. Stein JH, McBride PE. Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment. Arch Intern Med. 1998; 158: 1301-1306. Thom DH, Grayston JT, Siscovick DS, et al. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. JAMA. 1992; 268: 68-72. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med. 1998; 338: 1042-1050. Cardio CRPTM Clinical Use: This test is used to determine the relative risk of cardiovascular disease CVD ; and to assess risk of recurrent cardiovascular event in patients with coronary heart disease CHD ; . 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However, mild CRP elevation within the normal, non-acute-phase range ; has recently emerged as a valuable marker of cardiovascular risk.1 Mildly elevated CRP eg, 10 mg L ; has been linked with risk for CVD, including first and recurrent coronary events1 and stroke; 2 vascular events after stroke; 3 myocardial infarction or angina in patients with peripheral vascular disease; 4 poor outcome in acute coronary syndromes1, 5 and congestive heart failure; 6 restenosis after coronary angioplasty; 7 sudden cardiac death; 8 hypertension; 9 dementia; 10 and type 2 diabetes mellitus.11 Prospective studies with highly sensitive assays such as Cardio CRP have consistently shown CRP to be a strong predictor of increased cardiovascular risk in both men and women.1 The predictive value of CRP is independent of other established risk factors, including LDL-cholesterol, and screening with both CRP and LDL may provide a better risk assessment than using either test alone.12 Additionally, evidence suggests patients with high CRP normal LDL are at greater risk than those with normal CRP high LDL.12 Many therapies aimed at reducing cardiovascular risk act through antiinflammatory pathways. Aspirin and statins both yield the greatest preventive effect in patients with the highest CRP levels.1, 13 Statin therapy reduces the risk of first acute coronary events14 and stroke15 associated with elevated CRP, and recent evidence suggests patients who have low CRP levels after statin therapy have better clinical outcomes regardless of the resultant LDL level.16 Statin therapy also appears to reduce the risk of major adverse cardiac events after stent implantation in patients with elevated CRP levels.17 Furthermore, evidence from multiple studies indicate that intensive statin therapy leads to an early reduction in cardiac events, sustained for over 2 years, in patients with acute coronary syndrome.18 Such reduction is likely related to diminished inflammation as evidenced by greater decreases in CRP levels observed after statin therapy than observed after placebo.19 Weight loss20 and regular physical activity, 21 both associated with reduced cardiovascular risk, appear to have anti-inflammatory effects as well reduced CRP, fibrinogen, and white blood cell levels ; . 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The chloride concentration in Table 1 of Diuretics Bulletin 8, July 2001, page 369 ; after loop and thiazide diuretics, should have been shown as decreasing rather than increasing. The Editor and authors apologise for this error. According to new study results published in the August issue of Urology, women with mixed incontinence, a combination of stress incontinence and urge incontinence due to overactive bladder OAB ; , reported a greater treatment benefit for OAB symptoms from DETROL LA than placebo. DETROL LA is manufactured by Pfizer Inc. By demonstrating a reduction in the number of urgency episodes in a 24-hour period and a reduction in weekly urge episodes, the study showed that DETROL LA treats the urge incontinence component of mixed incontinence, where symptoms of urge predominate. There is not a single drug on the market that treats all symptoms of mixed incontinence. ACCEPTABLE BUT NOT OPTIMAL ; P.O. ALTERNATIVES.

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HISTORY Plethora was founded to exploit, modify and or improve the clinical effects of established and late stage drugs to satisfy under-served medical needs within the field of urology. The Group will manage a portfolio of development projects comprising three drug candidates in clinical development for the treatment of different urological disorders and three medical devices at differing development stages. The Company is a newly incorporated company which has been formed for the purpose of acquiring Plethora and to seek admission to trading on AIM. The Company has never traded or carried on any activities save that on 17 March 2005 the Company agreed to acquire all of the shares in Plethora for an aggregate consideration of approximately 20 million comprising the issue of the Consideration Shares, conditional only on the Placing Agreement becoming unconditional, details of which are set out in paragraph 10 of Part IX of this document. The Company intends to raise approximately 8.9 million net of expenses ; by way of the Placing. Further details in relation to the Placing are set out in the paragraph titled "Details of the Placing" below. MARKET OPPORTUNITY The Group is focused on exploiting novel formulations of established and innovative pharmaceuticals, together with complementary delivery systems and devices, for the diagnosis, treatment and management of urological disorders. Urology is the branch of medicine dealing with diseases of the urinary tract and urogenital system. This speciality treats a spectrum of disorders including urinary incontinence, sexual dysfunction, prostatic diseases, infections and malignancies of the urinary tract. Extrapolating from US National Institutes for Health prevalence figures, the Directors estimate that over 40 million men and women in North America and the major European nations France, Germany, Italy, Spain and the United Kingdom ; suffer from incontinence and in a recently reported survey of men from Italy, Germany and the USA the prevalence of premature ejaculation was found to be over 25 per cent. for each of the participating countries. Treatment of these urological conditions constitutes a significant pharmaceutical opportunity. A number of urology drugs had global sales approaching, or in excess of, US$1 billion in 2004. Sales of the incontinence drug, Detrok LA Pfizer ; exceeded US$900 million a 66 per cent. increase on the 2003 worldwide sales ; , while global sales of the benign prostatic hyperplasia treatments, Flomax Alna Boehringer Ingelheim ; and Proscar Merck ; were US$1.06 billion in 2003 a 35 per cent. increase on 2002 sales ; and US$733 million a 21 per cent. increase on 2003 sales ; , respectively. The leading erectile dysfunction drug, Viagra Pfizer ; had sales of US$1.67 billion in 2004. While this represented an 11 per cent. decline in sales over 2003, global sales of a competitor drug, Cialis Lilly ICOS ; rose from US$203 million in 2003 to US$552 million in 2004, an increase of 272 per cent. Total sales of oral prescription drugs for erectile dysfunction were close to US$2.5 billion in 2004. Major drivers of the urology market include: Changing demography: The commonest urological disorders predominantly affect older adults and this target population is projected to grow in the developed world along with increasing life expectancy. Increasing acceptance and demand for "lifestyle" drugs: Lifestyle drugs are drugs used for non-health problems or for conditions that lie at the boundary between a health need and a lifestyle wish. The last decade has seen the growth of market opportunities in the treatment of non-life threatening but distressing conditions such as male baldness and erectile dysfunction. A number of drugs are in late stage clinical development for the treatment of female sexual dysfunction. 13.

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