High-alert medications for hospitalised paediatric patients - a two-step survey among paediatric clinical expert pharmacists in Germany.

Paediatric patients are more vulnerable to be harmed by medication errors compared to adults due to pharmacokinetic and pharmacodynamic changes in their development, individual dosing calculations, and manipulation of ready to-use products intended for adult patients. According to the Institute of Safe Medication Practices, there are some "drugs that bear a heightened risk of causing significant patient harm when they are used in error"; these drugs are called high-alert medications (HAM). The two-step survey among paediatric clinical expert pharmacists presented here aimed to compile a nation-wide HAM list. To provide detailed guidance, this survey followed a drugbased approach, resulting in specific potential drug related problems (DRPs) and associated recommendations for prevention. In contrast to this approach, in the first round of the survey two drug classes were included that both were rated as HAM (i.e.chemotherapy and parenteral nutrition). Twenty single drugs were identified as HAM, 65% of which were cardiovascular or neurological drugs. The paediatric expert pharmacists mentioned in total 216 potential DRPs; in particular, they identified potential administration-related problems (28% of all DRPs), dosing-related problems (26%), and drug-choice-related problems (18%, e.g.drug confusion and drug monitoring). Moreover, they suggested 275 potential interventions to address these DRPs. Two thirds of all interventions dealt with the preparation by the hospital pharmacy, standardisation of processes (e.g.labelling), and education or training. In conclusion, this survey provided a German paediatric high-alert medication list from a paediatric pharmacist point of view. Moreover, the experts mentioned for the first time specific potential DRPs and associated interventions to guide a local multidisciplinary approach for preventing medication-related harm in children.

Length and weight of very low birth weight infants in Germany at 2 years of age: does it matter at what age they start complementary food?

BACKGROUND/OBJECTIVES: We analysed at what age parents start complementary food in very low birth weight infants, determined risk factors for early introduction of complementary food (post-term age) and analysed whether the age at introduction of complementary food influences height or weight at 2 years of age. SUBJECTS/METHODS: Parents of premature infants born in 2009-2011 answered questionnaires regarding introduction of complementary food in the first year of life (N=2262) and were followed up at a post-term age of 2 years (N=981). Length and weight were compared with full-term infants from the KiGGs study. Logistic and linear regression analyses were conducted to study predictors for early introduction of complementary food and the influence of age at introduction of complementary food on later height and weight. RESULTS: Average age at introduction of complementary food was 3.5 months post-term age. The lower the gestational age at birth, the earlier (post-term age) vegetables and meat were introduced. Age at introduction of complementary food was influenced by intrauterine growth restriction, gestational age at birth, maternal education and a developmental delay perceived by the parents. Length and weight at a post-term age of 2 years was not negatively influenced by early introduction of complementary food. CONCLUSIONS: VLBW infants are introduced to complementary food on average before a post-term age of 4 months. There was no negative effect of early introduction of complementary food on height and weight at 2 years of age.

[Combination of Excessive Weight Gain and Interleukin-8: A Possible Predictor of Necrotising Enterocolitis in Neonates?]. / Kann ein Gewichtssprung in Kombination mit einem Anstieg des Interleukin-8 eine nekrotisierende Enterokolitis bei Neonaten vorhersagen?

BACKGROUND: Weight gain before the clinical diagnosis of necrotising enterocolitis (NEC) is described as a predictive factor. HYPOTHESIS: Weight gain of more than 5% one day prior to clinical suspicion plus increase of plasma Iinterleukin-8 (IL-8) are predictive for NEC. METHODS: 48 infants with diagnosis of NEC stage II and III were enrolled in a case-control study. Oral and parenteral nutrition, diuresis and kinetics of weight and of IL-8 were documented. RESULTS: 31 infants with NEC-II and 17 infants with NEC-III were enrolled. Weight gain>5% occurred in 35.3% of NEC-III, in 0% of NEC-II and in 4.2% of the control group. IL-8 increased significantly [NEC-III (6 561.4 pg/mL) vs. NEC-II: (326.7 pg/mL) vs. control group (38.9 pg/mL); p<0.05]. Sensitivity of IL-8 in NEC-II was 87.10% (70.15-96.25) and in NEC-III 100.00% (80.33-100.00). Sensitivity of weight gain was 0.00% (0.00-11.32) in NEC-II and 35.29% (14.30-61.65) in NEC-III. CONCLUSION: Weight gain>5% was found in only 35.3% of the cases with NEC-III. Combination of weight gain and IL-8 did not improve the diagnosis of NEC.

Increased risk for bronchitis after discharge in non-vaccinated very low birth weight infants.

BACKGROUND: In very low birth weight (VLBW) infants, obstructive bronchitis is a frequent cause of hospital re-admission. For VLBW infants, early vaccinations starting at 2 months after birth have been recommended. OBJECTIVE: To analyze risk factors for bronchitis during the first year after discharge and the effects of in-hospital standard vaccination (hexavalent/pneumococci) and/or RSV immunoprophylaxis with palivizumab. METHODS: A standardized questionnaire was sent to the parents of VLBW infants 7 month after discharge. The reported episodes of bronchitis were correlated with clinically recorded parameters including risk factors for pulmonary morbidity. The effects of in-hospital vaccination were assessed in a subgroup discharged after day 60. RESULTS: A sample of 1 967 responses of infants born 2009-2011 was analyzed. Risk factors for bronchitis were male gender and older siblings. 24% of the population had episodes of bronchitis. In the subgroup discharged after day 60, episodes of bronchitis were reported for 31% of infants who were not vaccinated in-hospital. A significant reduction of the bronchitis rate was found in infants who received palivizumab±standard vaccination (17% bronchitis, p=0.003). Interestingly, in-hospital standard vaccination without RSV immunoprophylaxis was protective (20% bronchitis; p=0.037) as well. CONCLUSIONS: Non-vaccinated male VLBW infants with older siblings are at increased risk for bronchitis during the first year after discharge. Vaccination according to schedule seems to have protective effects, while underlying mechanisms are unknown. The rate of timely vaccination in preterm infants should be increased.

Diagnostic value of immature myeloid information in early-onset bacterial infection in term and preterm neonates.

BACKGROUND: For quick detection of neonatal early-onset bacterial infection (EOBI) pro-inflammatory cytokines like Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in combiantion with C-reactive Protein (CRP) have been used. Automated determination of immature myeloid information (IMI) seems to be an additional useful tool in the diagnosis of NBI. OBJECTIVE: To compare the diagnostic value of IMI, I/T-Ratio, plasma IL-6 and IL-8 levels and CRP in term and preterm neonates at time of clinical suspicion of EOBI. PATIENTS AND METHODS: 31 preterm and 123 term neonates with clinical and serological signs of EOBI were analysed. 91 preterm and 159 term neonates with risk factors but without proven EOBI served as non-infected controls. RESULTS: Neonates with EOBI showed significantly elevated IMI levels at time of first clinical suspicion of EOBI (Preterm: 1 028/µL (38-8 759) vs. 289/µL (6-3 126); Term: 1 268/µL (48-14 035) vs. 856/µL (19-5 735); p<0.05 respectively). I/T-Ratio, IL-6, IL-8 and CRP values were significantly higher in preterm and term neonates with EOBI (p<0.05). Sensitivity of IMI at a cut-off level of 650/µL was 84.2% [95%-CI: 74.0-91.6%] in preterm and 65.4% [95%-CI: 56.8-73.3%] in term infants. Specificity was 66.7% [95%-CI: 47.1-82.7%] and 53.9% [95%-CI: 43.8-63.7%], respectively. Combination of different infection parameters improved sensitivity up to 93.5% and specificity up to 98.9%. CONCLUSION: The diagnostic value of IMI in diagnosing EOBI in preterm and term neonates is not comparable to IL-6, IL-8 and CRP. Combination of IMI-Channel with IL-6, IL-8 or CRP improves their sensitivity, specificity and predictive value.

The ratio of abdominal circumference and body weight--an objective parameter for the daily ward round in a NICU?

OBJECTIVE: Feeding tolerance and the degree of abdominal distension are important factors on the ward round on a NICU. They are basis for systematic changes in enteral feeds and an early indicator of clinical deterioration. Our aim was to examine the ratio of abdominal circumference(AC) to body weight (BW) as an additional variable for abdominal distension and its relationship to feeding, the increase of feeds and CPAP. HYPOTHESIS: The AC/BW ratio of premature infants decreases in serial measurements with increasing body weight during the fi rst 28 days of life. Higher amount of enteral nutrition and CPAP cause an increase. PATIENTS AND METHODS: In 30 premature infants(mean: 27.5 weeks, SD 2.2; 16 male, 2 200 measurements),daily measurement and recording during the fi rst 28 days of life: AC (cm), BW (g),enteral/parenteral amount of fluid intake, type of formula, composition of macronutrients (breastmilk, type of formula), gastric residual volume,CPAP therapy. RESULTS: Increase of AC ratio mean value from 19.9, SD 3.2 (d1) to 25.0, SD 5.2 (d6), followed by continuous decrease to 19.9, SD 4.4 (d28). Weeks of gestation, total amount of enteral feeding had a significant eff ect (p < 0.05). With increasing total amount of enteral feeding, the AC/BW ratio decreased. Changes in enteral feeding volume,CPAP had no significant eff ect. CONCLUSION: Our aim was to provide longitudinal data from VLBW infants and to assess whether AC/BW ratio is affected by feeding, increase in feds and CPAP. In future the ratio may be a more objective parameter to avoid withholding feds or to detect early clinical deterioration.

Postoperative outcome in premature infants with open abdomen.

BACKGROUND: Premature infants treated with laparostomy in the first days of their life represent a group of complex patients with high morbidity and mortality rates. Laparostomy is a surgical treatment method in which the peritoneal cavity is opened anteriorly and deliberately left open, hence often called "open abdomen". The aim of this study was to analyze crucial factors influencing the postoperative outcome of premature infants treated this way. METHODS: Between March 2002 and August 2012, we treated 40 premature infants with a median gestational age of 29 weeks (range from 24 to 34 weeks) with open abdomen in our institution. Their data were analyzed retrospectively. They were divided into two groups depending on in-hospital survival. RESULTS: Indications for surgery were ileus (n = 16), spontaneous intestinal perforation (n = 11), gastroschisis (n = 8) and necrotizing enterocolitis (NEC, n = 5). The overall in-hospital mortality was 43 % (17 of 40 patients). Postoperative anemia was the only significant factor influencing mortality rates in our patients (10 vs. 14 patients; p = 0.028). Neither the indication of surgery, nor week of gestation, nor birth weight had any significant influence on postoperative survival. Twenty-one of the 23 surviving patients reached fascia closure. CONCLUSIONS: In our study, outcome of premature infants with open abdomen in the first days of their life seems to depend more on an operation and a postoperative course without complications than on the preoperative conditions of the children. Postoperative anemia seems to be a significant negative prognostic marker. Patients reaching fascia closure mainly survive.

Healthcare worker-related MRSA cluster in a German neonatology level III ICU: a true European story.

Here we investigated a cluster of eight newly Methicillin-resistant Staphylococcus aureus (MRSA)-colonized neonates at an ICU, and present data on molecular strain characterization as well as the source identification process in which we analyze the impact of MRSA-colonized HCWs. Molecular strain characterization revealed a unique pattern which was identified as spa-type t 127--an extremely rare strain type in Germany. Environmental sampling and screening of parents of colonized neonates proved negative. However, staff screening identified one healthcare worker (HCW; 1/134) belonging to a group of recently employed Romanian HCWs who was colonized with the spa 127 strain. Subsequent screening also detected MRSA in 9/51 Romanian HCWs (18%) and 7/9 (14% of all) isolates showed the same molecular pattern as the index case (spa/PFGE type). All carriers were successfully decolonized, after which no new patient cases occurred. As a result, we have now implemented a universal screening programme of all new employees as part of our infection control management strategy. MRSA-colonized HCWs can act as a source for in hospital transmission. Since HCWs from high endemic countries are particular prone to being colonized, they may pose a risk to patients.

Influence of smoking and alcohol during pregnancy on outcome of VLBW infants.

BACKGROUND: Nicotine and alcohol consumption have been associated with premature delivery and adverse neonatal outcome. We wanted to analyze the influence of self-reported nicotine and alcohol consumption on outcome of VLBW infants. MATERIAL AND METHODS: In an ongoing multicenter study 2475 parents of former very low birth weight (VLBW) infants born between January 2009 and December 2011 answered questionnaires about maternal smoking habits and alcohol consumption during pregnancy. 2463 (99.5%) completed questions on alcohol consumption and 2462 (99.5%) on smoking habits. These infants were stratified to reported maternal smoking and alcohol consumption during pregnancy. We compared the reasons for premature delivery, neonatal outcome and parental reports on bronchitis during the first year of life, as well as growth and development at age 2 years to pregnancy exposure. RESULTS: In nicotine exposed infants intrauterine growth restriction (31 vs. 21%, p<0.01), a birth weight below the 10th percentile (26 vs. 17%, p<0.01) and placenta abruption (9.2 vs. 5.8%, p<0.05) was seen more often. Premature rupture of membranes (24 vs. 30%, p<0.05) or HELLP syndrome (6 vs. 11%, p<0.01) was less frequent. A birth weight below the 3rd percentile was seen more frequently in mothers with reported alcohol consumption (13 vs. 6%, p<0.05). We noted an increased rate of BPD and ROP if mothers reported smoking during pregnancy (p<0.05). Growth parameters and scores on Bayley Sscales of infant development at age 2 years did not differ. CONCLUSION: Smoking during pregnancy results in a high rate of growth restricted VLBW infants. Prenatal exposition to nicotine seems to increase postnatal complications such as BPD und ROP.

Ballantyne syndrome and congenital anaemia associated with Parvovirus B19 infection: case report and review.

Acute maternal Parvovirus B19 infection affects about 1% of all pregnancies worldwide. Diaplacental transmission of Parvovirus B19 during the second trimester can cause complications like foetal hydrops, premature delivery or foetal loss in about 20-30% of these pregnancies, whereas the majority of maternal infections remain clinically silent. In individual cases, foetoplacental hydrops (of various origins) can trigger a rare form of Preeclampsia in the pregnant woman. The developing maternal oedema in this situation apparently "mirrors" the hydropic state of the foetus. The symptom triad of foetal hydrops, foetoplacental oedema and maternal anasarca defines Ballantyne syndrome. We report a case of Parvovirus-induced Ballantyne syndrome including a 10-year follow-up of mother and child. While the mother recovered rapidly after (preterm) delivery, the infection complicated the first months of life of the neonate. Congenital transfusion-dependent red cell aplasia and cholestatic hepathopathy took a chronic course but resolved under IVIG treatment. Follow-up now finds both the former neonate and the mother entirely recovered. Current knowledge on Ballantyne syndrome as well as perigestational Parvovirus infections including congenital anaemia is briefly reported and pathophysiological hypotheses are discussed.

[Hyperglycaemia and preterm infants: a chapter of its own]. / Hyperglykämie und Frühgeborene: Ein Kapitel für sich.

Antenatally, glucose maintenance takes place via transplacental transfer from mother to fetus. In the third trimester, the amount of glucose transported increases, while glycogen and fat stores are developed. After delivery a continuous and sufficient glucose supply for vital organs and brain is essential. In term infants hormonal and metabolic adaption is well-coordinated, involving adrenal gland, pancreas and liver. However, in preterm infants, mainly during first week of life, there is a high risk of abnormalities in glucose homeostasis. Due to limited glycogen and fat stores, hypoglycaemia may occur which is avoided by continuous glucose infusion. An underestimated risk is hyperglycaemia due to a combination of relative insulin deficiency and insulin resistance, associated with increased mortality and morbidity. Management of hyperglycaemia is one of the topics in neonatology and is still being discussed controversially. This review approaches different therapeutic strategies and gives an overview about the current recommendations in the literature.

Thermoregulation of Premature Infants during and after Skin-to-Skin Care.

OBJECTIVE: Providing normothermia is an important issue in daily routine care of premature neonates. We recently found with infrared thermography (IRT) a drop in skin temperature of premature babies after they were positioned from skin-to-skin care (SSC) back into the incubator. Since this did not disappear within 10 min, we wanted to find out how long it takes until the baby has fully warmed up after SSC and if the IRT measurements correlate with conventional rectal temperature? STUDY DESIGN: A prospective observational study was undertaken with 5 premature infants [3 male, median gestational age 28 weeks (25-29), median age at study 34 d (28-52), median birth weight 898 g (400-1095), median weight at study 1263 g (790-1465)], temperature was determined with IRT (leg, back, arm, head, upper abdomen; diameter 1 cm, scale 0.00°C), comparison with 2 conventional sensors and rectal temperature. Temperatures were recorded every 2 min and displayed for 4 time points, namely at the beginning and the end of skin-to-skin care (SSC1, SSC2), as well as at the beginning and the end of a subsequent 60 min incubator period (I). RESULTS: A significant rise during SSC occurred while the cooling after SSC persisted during the complete incubator measurement time (I; p<0.05). Rectal temperature remained stable through the whole measuring period. CONCLUSION: While SSC in our setting led to an increase in temperature, the lack of compensation of peripheral heat loss in the incubator after 60 min may express an inadequate peripheral regulation of body temperature. This should be taken into account before routine care after SSC.

Diagnostic value of an interleukin-6 bedside test in term and preterm neonates at the time of clinical suspicion of early- and late-onset bacterial infection.

BACKGROUND: For quick detection or exclusion of neonatal early-onset bacterial infection (EOBI) or late-onset bacterial infection (LOBI), interleukin (IL)-6 is used. Its clinical use is sometimes limited due to prolonged recall times. Therefore, an IL-6 bedside test was established. OBJECTIVE: To compare the diagnostic value of plasma IL-6 and an IL-6 bedside test at the time of clinical suspicion in the course of EOBI and LOBI. METHODS: Eighteen term (mean gestational age 40.2 weeks, SD 1.3) and 88 preterm (mean gestational age 30.1 weeks, SD 4.2) neonates with clinical and serological signs of bacterial infection were analysed. Eight had an EOBI, and 24 had a LOBI, of whom 13 were blood culture positive. Twelve term and 62 preterm neonates with risk factors but without proven EOBI/LOBI served as a non-infected group. RESULTS: At the time of clinical suspicion, the sensitivity of the IL-6 bedside test in comparison to plasma IL-6 was 69 versus 75% (p = 0.7744, McNemar's test), and specificity was 77 versus 81% (p = 0.6476, McNemar's test; cutoff level 50 ng/l). For LOBI, both the sensitivity (75%) and specificity (82%) of the bedside test exceeded values calculated for EOBI (sensitivity 50%, specificity 75%). CONCLUSION: No significant difference between the bedside and established plasma IL-6 test was detected for LOBI. For detection of EOBI, the bedside test was not sensitive enough. Larger studies are needed to verify our findings before IL-6 bedside tests can be recommended routinely.

Impact of skin to skin care, prone and supine positioning on cardiorespiratory parameters and thermoregulation in premature infants.

BACKGROUND: Skin to skin care (SSC), prone (PP) and supine (SP) positions are standard positions in daily care for premature infants. Their influence on cardiorespiratory parameters and thermoregulation is discussed controversially. OBJECTIVES: We compared SSC with PP, the recommended position for preterm infants, and SP, the safest position for term infants, and tested the hypothesis that SSC has no impact on cardiorespiratory parameters and thermoregulation. METHODS: In 18 spontaneously breathing premature infants [median gestational 28 weeks (24-32); chronological age 36 days (7-64), and weight 1,543 g (750-2,100)], heart and respiratory rate, breathing pattern, episodes of desaturation (<85 but >or=80 and <80%), oxygen saturation and rectal temperature were analyzed with polygraphy (Alice 3(R) and 3.5(R)) in a 6-hour measuring cycle of three subsequent series (120 min each in SP, SSC and PP) and compared (Wilcoxon test). RESULTS: During SSC, we found no increase in apneic attacks and bradycardic episodes and no difference in respiratory rate, breathing pattern, oxygen saturation, episodes and duration of desaturation compared to SP and PP. Episodes of desaturation <85 but >or=80 and <80% were more frequent in SP compared to PP (p = 0.0421 and p = 0.0319). Heart rate increased in SSC and PP compared to SP (154.86 bpm, SD 11.55, and 153.33 bpm, SD 15.95 vs. 150.25 bpm, SD 14.64; p = 0.0013 and p = 0.0346). Temperature level was not significantly higher during SSC and PP compared to SP except a rise between the start and the end of the 6-hour measuring cycle (37.05 degrees C, SD 0.2 vs. 37.30 degrees C, SD 0.3; p = 0.0436). CONCLUSION: We found no significant SSC-mediated changes in quality and quantity of desaturations and in body temperature compared to PP in preterm infants.

Lipopolysaccharide-binding protein in noninfected neonates and those with suspected early-onset bacterial infection.

OBJECTIVES: To investigate postnatal lipopolysaccharide-binding protein (LBP) kinetics in term neonates and to test its diagnostic accuracy for early-onset bacterial infection (EOBI). STUDY DESIGN: A total of 99 neonates with clinical and serological signs of EOBI comprised the study group; 198 neonates with risk factors, but without EOBI, served as controls. LBP, C-reactive protein (CRP) and interleukin-8 (IL-8) were determined. RESULTS: LBP in the noninfected group increased until 24 h after birth (P < 0.05 vs 6 h). LBP and CRP correlated strongly in neonates with suspected EOBI (r = 0.63). Although LBP reached a higher sensitivity than CRP 6 and 12 h after clinical suspicion (45 (24-68) and 79% (54-94) vs 9 (0-24) and 39% (17-64); P < 0.05)), EOBI was most reliably detected by IL-8. CONCLUSION: LBP kinetics were age-dependent. LBP was not sufficiently sensitive in the prediction of EOBI.

Hydrops fetalis in three male fetuses of a female with incontinentia pigmenti.

OBJECTIVES: Careful investigation of hydrops fetalis (HF) is important with regard to genetic counselling and prenatal diagnosis. HF is known to be associated with various genetic disorders. To date there has been only one report of a male fetus in whom incontinentia pigmenti (IP) was associated with generalised oedema. We describe a family who had a girl with clinical signs of IP after three consecutive miscarriages of three male fetuses due to HF. RESULTS: Molecular genetic analysis showed a mutation in the NEMO/IKK(chi) gene in the girl and the mother, which confirmed the diagnosis of IP in both cases. In the two fetuses that could be investigated, inheritance of the affected maternal X chromosome could be demonstrated retrospectively by linkage analysis. CONCLUSION: The present findings suggest that IP might be an X-linked dominant trait causing HF in male fetuses. In cases of recurrent HF in male fetuses, minimal signs of IP in the maternal line should therefore be carefully investigated in order to be able to perform mutational analysis and to offer appropriate genetic counselling.

Dexamethasone inhibits CD4 T cell deletion mediated by macrophages from human immunodeficiency virus-infected persons.

Prednisolone slows the loss of CD4 T cells in individuals with human immunodeficiency virus (HIV) disease and inhibits antigen-induced apoptosis of recently HIV-infected CD4 cells in vitro. This study investigated whether dexamethasone inhibits the ability of macrophages to delete CD4 T cells via anti-CD4 antibody or immune-complexed HIV envelope protein gp120. Peripheral blood mononuclear cells from HIV-negative persons were incubated with CD4-reactive ch412 monoclonal antibody or with gp120/IgG immune complexes and resident macrophages, with and without dexamethasone. Dexamethasone inhibited CD4 cell deletion in a dose-dependent manner. The deletion of normal CD4 cells by macrophages from HIV-infected patients also was inhibited by dexamethasone. Furthermore, up-regulation of CD95 expression on T cells exposed to anti-CD4 and gp120/IgG, which predisposes T cells to CD95-mediated apoptosis, is inhibited by dexamethasone in a dose-dependent fashion. Dexamethasone inhibits the macrophage-mediated deletion of CD4 lymphocytes in HIV-infected persons.

Polyspecific self-reactive antibodies in individuals infected with human immunodeficiency virus facilitate T cell deletion and inhibit costimulatory accessory cell function.

Self-reactive polyspecific IgG antibodies (PSAs) arise in human immunodeficiency virus (HIV)-seropositive subjects before they develop AIDS. Self-reactive PSA levels correlate with the destruction of CD8 T cells in HIV-infected individuals and mediate the antibody-dependent cellular toxicity-based destruction of human T cells in tissue culture. PSAs react across the species barrier and bind to T cell antigens in mice. Such reactivity with mouse lymphocytes was not detected in normal human serum. Injection of human PSA IgG causes massive T cell depletion in the spleen, lymph nodes, and thymus in mice: evidence that PSA IgG facilitates T cell destruction in vivo. In addition to facilitating macrophage cytotoxicity, self-reactive PSA IgG inhibits the macrophage-mediated activation of T cells with antigen receptor-specific monoclonal antibody or with antigen. Exogenous costimulatory stimuli or interleukin (IL)-12 can reverse the inhibition. In contrast, exogenous IL-10 mimics this inhibition. These data implicate PSA IgG as a pathogenic factor in the development of HIV disease.

Functional analysis of P-glycoprotein and multidrug resistance associated protein related multidrug resistance in AML-blasts.

Despite the high effectiveness of various P-glycoprotein (P-gp) modulating substances in vitro their clinical value e.g. for combination treatment of acute myelogenous leukemias (AML) remains still unclear. This might be explainable by recent findings that other factors than P-gp (e.g. the multidrug resistance associated protein (MRP)) may also be involved in clinical occurring drug resistance. To study P-gp and MRP mediated MDR in AML blasts from patients with relapses at the functional level we measured rhodamine 123 (RHO) efflux in combination with a P-gp specific (SDZ PSC 833) or a MRP specific (MK571) modulator, respectively. Furthermore, direct antineoplastic drug action was monitored by determination of damaged cell fraction of a blast population using flow cytometry. We generally found strongly modulated RHO efflux by SDZ PSC 833 but slight RHO-efflux modulation by MK571 in blasts from relapsed states of AML expressing MDR1 or MRP mRNA at various levels. We could not demonstrate, though, significant PSC 833 or MK571 mediated modulation of the cytotoxic effects of etoposide. The results point to the possibility that combination of etoposide and a modulator might not improve responses to chemotherapy by targeting P-gp or MRP exclusively.