Correlation of drug sensitivity in vitro with clinical responses in childhood acute myeloid leukemia

Clonogenic cells from 41 children with newly diagnosed acute myeloid leukemia (AML) were tested in vitro for their sensitivity to cytarabine (Ara-C) and daunorubicin (DNR). The findings were then compared with the patients' responses to induction chemotherapy that uniformly included Ara-C and DNR. Light-density marrow cells were incubated with either or both drugs for one hour and cultured over leukocyte feeder layers; clusters and colonies were scored on days 7, 10, and 14. Only the percentage of cell kill in the presence of 1.8 mumol/L DNR was significantly associated with responses to induction therapy: median of 45% (range, 0% to 98%) for patients achieving complete remission v 16% (range, 4% to 23%) for nonresponders (P = .007). The relationship between clonogenic cell kill less than or equal to 23% and clinical responses was striking. Of the 11 evaluable patients with in vitro findings in this category, ten either failed induction therapy or relapsed within 1 year after attaining remission. Kaplan-Meier analysis of relapse-free survival times indicated longer durations of remission for patients whose blast cells showed increased sensitivity in vitro to Ara-C alone, DNR alone, or a combination of the two agents. Seven of 11 patients with cell kills of greater than or equal to 49% in the presence of 1.25 mumol/L Ara-C remain free of leukemia, compared with only one of 12 whose cells were less sensitive to the drug (P = .006). We conclude that the in vitro sensitivity of clonogenic leukemic progenitors to DNR and Ara-C correlates with treatment outcome in children with newly diagnosed AML.     

Colonization, bloodstream infection, and mortality caused by vancomycin-resistant enterococcus early after allogeneic hematopoietic stem cell transplant.

Bloodstream infection caused by vancomycin-resistant enterococcus (VRE) is associated with very high mortality among allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. However, it remains unclear whether VRE bloodstream infection directly causes mortality in the early posttransplant period or is simply a marker of poor outcome. To determine the risk factors for VRE bloodstream infection and its effect on outcome, we followed 92 patients screened for stool colonization by VRE upon admission for alloHSCT. Patient records were reviewed to determine outcomes, including mortality and microbiologic failure. Colonization by VRE was extremely common, occurring in 40.2% of patients. VRE bloodstream infection developed in 34.2% of colonized patients by day +35, compared to 1.8% without VRE colonization (P < .01). VRE bloodstream infection was associated with a significant decrement in survival and frequent microbiologic failure, despite treatment with linezolid and/or daptomycin. Five (35.7%) of 14 patients with VRE bloodstream infection had attributable mortality or contributing mortality from the infection. Strain typing by pulsed-field gel electrophoresis identified 9 different VRE strains among the 37 colonized patients and 5 patients with different strains recovered from the stool and the blood. In conclusion, stool screening effectively identified patients at extremely high risk for VRE bloodstream infection. The high mortality of VRE in the early posttransplant period supports the use of empiric antibiotics with activity against VRE during periods of fever and neutropenia in colonized patients.     

Behavior of prealbumin in the acute phase of polymyalgia rheumatica treated with 6-methylprednisolone

Summary Serum levels of prealbumin, fibronectin, fibrinogen, α₁-acid glycoprotein, C-reactive protein, immunoglobulins, and white blood cell count were prospectively studied in 33 patients affected by polymyalgia rheumatica during the first 45 days of treatment with 6-methylprednisolone. Almost all parameters considered, except for fibronectin and IgM, settled within the normal range fairly quickly, while prealbumin showed a specular course compared with the other reactants. This behavior reflected the improvement of clinical symptoms registered in all patients after steroid treatment. Finally, the genesis of the low baseline prealbumin levels found in polymyalgia rheumatica/giant cell arteritis and their behavior during treatment are discussed.     

The Triad Mother-Breast Milk-Infant as Predictor of Future Health: A Narrative Review

The benefits of human milk for both mother and infant are widely acknowledged. Human milk could represent a link between maternal and offspring health. The triad mother-breast milk-infant is an interconnected system in which maternal diet and lifestyle might have effects on infant’s health outcome. This link could be in part explained by epigenetics, even if the underlining mechanisms have not been fully clarified yet. The aim of this paper is to update the association between maternal diet and human milk, pointing out how maternal diet and lifestyle could be associated with breast-milk composition, hence with offspring’s health outcome.     

Growth in the first two years of uninfected children born to HIV-1 seropositive mothers

OBJECTIVE—To assess the growth curves of uninfected infants born to type 1 human immunodeficiency virus (HIV-1) seropositive mothers by means of standardised anthropometric indices.
METHODS—The z scores (National Center for Health Statistics-World Health Organisation data) of weight for age, length for age, and weight for length of 92 uninfected full term infants born to HIV positive mothers were compared with those of 65 bottle fed full term infants born to healthy mothers at 0, 1, 2, 3, 4, 6, 9, 12,18, and (in a subgroup) 24 months of age. Confounders were also recorded.
RESULTS—The study population had a lower length for age z score at birth (95% confidence intervals (CI): 0.02, −0.58) and higher weight for length z scores at 1 (95% CI: 0.21, 0.63), 2 (95% CI: 0.25,0.66), and 3 (95% CI: 0.0, 0.48) months compared with the reference group. After a temporary recovery, the length for age z score difference increased progressively from the 4th month onwards and was significant at 18 (95% CI: −0.31, −1.05) and 24 (95% CI: −0.02, −0.91) months. The difference between the length for age z scores at birth was associated with maternal covariates, but the between group difference at 18 months was apparent even after adjustment for covariates.
CONCLUSION—Uninfected infants born to HIV positive mothers have a rapid weight gain immediately after birth. A decrease in length progression during the second year might be a result of the social risk connected with the family environment and an unfavourable programming related to the maternal HIV status.

     

Effect of rifampicin in the treatment of pruritus in hepatic cholestasis

Pruritus in hepatic cholestasis has been suggested to be secondary to a high concentration of serum bile acids. Rifampicin, which inhibits the uptake of bile acids by hepatocytes, has been used to treat pruritus. To determine the efficacy of rifampicin as a treatment for refractory pruritus, the medical records of 33 children (median age 25 months, range 4-135; 19 boys) with chronic cholestasis liver disease (21 with Alagille's syndrome, eight with progressive intrahepatic cholestasis, one with extrahepatic biliary atresia, one with an inborn error of bile acid metabolism, and one with cryptogenic cirrhosis) were reviewed retrospectively. The median dose of rifampicin was 5(4-10) mg/kg/day. The median duration of intake was 36(4-120) weeks. Complete relief of pruritus was noted in five (15%) patients and a partial response in 12 (36%). Overall, no significant difference was noted in the laboratory parameters before and after treatment with rifampicin. In the 21 patients with Alagille's syndrome, however, a significant decrease in alkaline phosphatase was seen before and after one and six months of starting treatment. No adverse side effects were seen. Rifampicin appears to be effective in the treatment of refractory pruritus. A prospective study is warranted to assess further the effect of rifampicin treatment in children with hepatic cholestasis.     

Effectiveness and safety of etodolac in treatment of rheumatoid arthritis: a multicentre two-months' open study

One hundred and seventeen outpatients (87 females and 30 males; mean age 53.5 +/- 13.2 years) encompassing the 1987 American Rheumatism Association criteria for rheumatoid arthritis were admitted into a multicentre open study. All patients were evaluated at baseline and after two months of therapy with etodolac (400 or 600 mg/die per os). Clinical evaluation was performed by using the following indicators: viso-analogic scale of global pain; index of pain on active movements; index for sleep disturbances, and duration of morning stiffness. The erythrocyte sedimentation rate was chosen for the laboratory evaluation of the activity of the disease. One hundred patients received 400 mg/die, while only 17 patients received 600 mg/die; 115 patients undertook the evaluation after treatment, whereas two patients were considered "lost to follow-up". One hundred and five patients completed the study while ten patients withdrew (seven because of inefficacy and three because of intolerance of the gastrointestinal tract). Only nine patients presented side-effects, among these: five were judged etodolac-related, whereas four were not. A complete resolution of all these side-effects was achieved in all cases. Significant improvements were registered for all the four clinical variables. At the end of the study 56.5% of patients expressed a preference for etodolac, 16.5% for one of the non-steroidal anti-inflammatory drugs previously taken and 27% did not answer or were not able to express any definite preference. Strict concordance was found between the degree of clinical improvement achieved and the preferences expressed. The laboratory parameters did not reveal any variation at the end of the study in comparison with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adverse drug reactions in newborns, infants and toddlers: pediatric pharmacovigilance between present and future

INTRODUCTION: The detection, assessment, understanding and prevention of adverse drug reactions (ADRs) are the primary aims of pharmacovigilance activities. Pediatric patients, especially all newborns and infants, are particularly at risk for experiencing drug-related adverse events. AREAS COVERED: This review briefly analyzes the physiological peculiarities of pharmacodynamic and pharmacokinetic aspects of drugs in newborns, infants and toddlers and children. It also deals with specific pediatric pharmacovigilance aspects, such as the frequent use of unlicensed and/or off-label drugs in neonatal intensive care units in European countries and in Australia. This review reports on European, American and Canadian data about the incidence and type of pediatric ADRs, particularly focusing on neonates, infants and toddlers. EXPERT OPINION: The awareness of pediatricians about the importance of reporting ADRs should be stimulated, new reporting systems should be encouraged and pediatric pharmacovigilance activities should be improved, first, by intensifying active post-marketing surveillance methods.