Ehrlich II –2nd World Conference on Magic Bullets

Randomized Controlled Clinical Trial of Day-Care Based and Hospitalized Management of Severe Childhood Pneumonia by Injection Ceftriaxone in Dhaka, Bangladesh ASHRAF H^1, ALAM NH^1, GYR N^2 ^1International Centre for Diarrhoeal Disease Research (ICDDR,B), Dhaka, Bangladesh, ^2University of Basel, Switzerland Background: Although hospital-based treatment of severe pneumonia in children is desirable, but practical barriers often prevent children in areas with the highest rates from receiving hospital care. We have shown recently in an uncontrolled trial a success in day-care treatment of severe pneumonia in children; however, a randomized, controlled trial is recommended. Methods: The study was conducted at the Radda Clinic, Mirpur, Dhaka and Mirpur Shishu (Paediatric) Hospital, Mirpur, Dhaka as the two primary sites for the day-care management and inpatient management, respectively. Children of either sex aged 2-59 months with severe pneumonia according to World Health Organization (WHO) criteria without associated co-morbidities were randomized to receive either day-care treatment at the Radda Clinic, or hospitalized treatment at Mirpur Shishu Hospital. Children at the clinic received day-care management with appropriate antibiotics like injection ceftriaxone, feeding and supportive care from 08:00-17:00 every day, while mothers were educated on continuation of care at home during the night. Children at the hospital received hospital care with similar antibiotics like injection ceftriaxone, feeding and supportive care for 24 hours every day rather than 9 hours at the clinic until improvement. Results: From September 2006 to December 2007, 251 children (125 at clinic as day-care, 126 at hospital as hospital care) with severe pneumonia without associated co-morbidities were enrolled, 83 (33%) were hypoxaemic with a mean (SD) oxygen saturation of 94 (5)%, which increased to 98 (1)% on oxygen therapy. Day-care management was successful in 109 children [87% (95% CI 80% to 92%)], as opposed to the success rate of 98% (95% CI 94% to 100%) by hospital management. Fifteen [12% (95% CI 7% to 19%)] children in the day-care group had to be referred to hospital for supportive management, but none in the hospital group. Conclusion: Most (87%) children with severe pneumonia without associated co-morbidities can be successfully managed on a day-care basis at a day-care clinic. However, few (12%) children required referral to hospital.

Transcription of Major Histocompatibility Complex Class I (K^b) and Transporter Associated with Antigen Processing 1 and 2 genes is up-regulated with age. ASSOUNGA AG^1,2, WARNER CM^1 ^1. Department of Biology, Northeastern University, Boston, MA 02115. ^2. Department of Medicine, University of KwaZulu-Natal, Durban, South Africa. Background: The transporter associated with antigen processing 1 and 2 (TAP1 and TAP2) genes belong to the ATP-binding cassette family of transporter genes. They provide peptides necessary for the assembly of MHC class I molecules by transporting these peptides into the endoplasmic reticulum. As MHC class I protein expression increases with age, we have explored the effect of age on the transcription of MHC class I (K^b), TAP1 and TAP2 genes in C57BL/6 mice. Methods: Blood and spleen lymphocytes were isolated and from mice aging from 3 months to over 24 months. RNA was extracted and mRNA for K^b, TAP1, TAP2 were quantified using slot-blot hybridization followed by a densitometry. Results: There is a parallel age related increase (1.5-fold) in blood lymphocyte mRNA of these genes from 3 months to 21 months. In mice over 24 months old there is a decrease in K^b and TAP1 mRNA, but an increase in TAP2 mRNA. In spleen lymphocytes an age-related increase in all three mRNA species occurs throughout life. While MHC class I and Tap genes follow about the same age related changes, MHC class I mRNA is about 50 times more abundant than either TAP1 or TAP2 mRNA. Conclusion: Transcription of MHC class I (K^b) and peptide transporter (TAP1 and TAP2) genes is up-regulated with age. It is possible that coordinated expressions of MHC class I and TAP1 or TAP2 may predispose an animal to better antigen presentation and a longer life.

The changes in renal function after a single dose of intravenous furosemide in patients with compensated liver cirrhosis ASSY N^1,2,5, KAYAL M,^3 MEJIRISKY Y,^3 GORENBERG M,^4 HUSSEIN O,^2 AND SCHLESINGER S^2 ^1Liver Unit, Sieff Hospital, Safed, Israel, ^2Department of Internal Medicine A, Sieff Hospital, Safed, Israel ^3Department of Internal Medicine B, Sieff Hospital, Safed, Israel. ^4Department of Nuclear Medicine, Sieff Hospital, Safed, Israel. ^5Faculty of Medicine, Technion Institute of Technology, Haifa, Israel Background:Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment. Aim: To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis. Methods: Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 ± 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic) were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 ± 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic) were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d) and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT) were performed for all patients. Results: Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% ± 3.8 to 15.2% ± 2.2, p < 0.001 in Gr I as compared to 10.6% ± 4.6 to 13.5% ± 3.6 in Gr 2, p < 0.001). In 8 patients (45%, 3 pts from Gr 1 and 5 pts from Gr 2) DMSA uptake remain unchanged. The mean 8 hrs UNa excretion after intravenous furosemide was above 80 meq/l and was higher in Gr 2 as compared to Gr 1 respectively (136 ± 37 meq/l) VS 100 ± 36.6 meq/l, P = 0.05). Finally, basal global renal DMSA uptake was decreased in 80% of patients; 22.5 ± 7.5% (NL > 40%), as compared to normal calculated creatinine clearance (CCT 101 ± 26), and measured CCT of 87 ± 30 cc/min (P < 0.001). Conclusion: A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined.

How to avoid drug—drug interactions ÅSTRAND B^1, MONTELIUS E^2, ANTONOV K^3, HOVSTADIUS B^1 AND PETERSSON G^2 ^1 School of Pure and Applied Natural Sciences, University of Kalmar, Kalmar, Sweden 2 School of Human Sciences, University of Kalmar, Kalmar Sweden 3 The Association of Pharmaceutical Industry, Stockholm, Sweden Background: It may be favorable to use a combination of drugs, if the combination is well documented, to enhance the effect or to reduce adverse effects. However, in the case of patients visiting several different physicians, who are prescribing less appropriate combination of drugs due to being unaware of each other, the outcome may be negatively influenced. The polypharmacy may even result in serious adverse drug events. Methods: In Sweden, the government has legislated and funded a nationwide mandatory database for all dispensed prescriptions. The information content is available during 15 months for prescribers and dispensing pharmacists, as well as for the registered individual. Prior to the launch of the nationwide database in Sweden, studies were performed to estimate the prevalence of potential drug—drug interactions (DDI) in a general population and to evaluate the historical change in risk over three decades. Results: On average each individual filled 14.6 prescriptions during a 15 month study period (2003-2004). The risk of receiving a potential DDI was estimated as the cumulative incidence 0.26 overall. The relative risk for women was estimated as 1.3. For more severe potential DDIs the cumulative incidence was estimated as 0.02. The risk of receiving a potential DDI was positively correlated to age and polypharmacy. The change in risk over three decades increased for type C (relative risk RR 1.18), but decreased (RR 0.71) for the more severe type D interactions. Polypharmacy increased with more than 60% during the three decade study period. Fifteen months after launch of the new National Pharmacy Register in Sweden, the prevalence of individuals with dispensed drugs was 71% (6,424,487/9,047,752). For elderly (80-89 years) the mean number of dispensed prescriptions was 27.8 during the first 15 months. Conclusions: The new National Pharmacy Register will provide health care professionals with a powerful tool to systematically review all prescriptions. Alert systems integrated in electronic healthcare records may be used to detect potential DDIs. To gain approval among physicians, the alerting should focus on the more severe and clinically relevant DDIs. More individual-oriented information (laboratory, genetic, allergies) may in the future be processed before prescribing of drugs, to better customize the therapy for the single individual.