Summary:We investigated whether adjusting the oral busulfan (BU) dosage on the basis of early pharmacokinetic data to achieve a targeted drug exposure could reduce transplant-related complications in children with advanced hematologic malignancies. Twenty-five children received a preparative regimen consisting of thiotepa (250 mg/m 2 i.v. daily for 3 days), BU (40 mg/m 2 per dose p.o. every 6 h for 12 doses), and cyclophosphamide (60 mg/kg i.v. daily for 2 days) and then underwent allogeneic stem cell transplantation. Busulfan clearance and area under concentration time-curve (AUC) were determined after the first dose using a one-compartment pharmacokinetic (PK) model with first-order absorption. The initial PK analysis was successfully completed after the first BU dose in 21 patients (84%). A final AUC of 1000-1500 m × min/dose was targeted and subsequent doses were modified as necessary to achieve this value. Fourteen of the 25 patients (56%) required dose adjustment. Followup PK analysis was completed in 21 patients and 16 of these achieved the targeted BU exposure for the course of therapy. Interpatient variability in BU clearance was high (up to five-fold). The most frequent regimenrelated toxicities were cutaneous and gastrointestinal (stomatitis and diarrhea). Only one patient developed hepatic veno-occlusive disease. Our study demonstrates the feasibility of adjusting the oral BU dose in individual pediatric patients. Although toxicity associated with BU seemed to be reduced, this conclusion is tempered by the fact that the overall regimen-related toxicity (RRT) remains substantial and reflected the effects of all agents used in the preparative regimen. Bone Marrow Transplantation (2000) 26, 463-470.
The oral manifestations of chronic graft-versus-host disease (cGVHD) in eight allogeneic bone marrow transplant (BMT) paediatric recipients were studied clinically, and lip biopsies were performed in seven of them. A prominent lichenoid reaction was observed in four patients, two with accompanying ulceration. Superficial mucoceles were present in three children. Clinically obvious xerostomia was seen in seven patients. Lip biopsies were positive and correlated with the clinical manifestations. Both clinical and histological findings confirmed the diagnosis of cGVHD. In three additional children, with systemic manifestations indicating cGVHD, the oral mucosa was clinically and histologically normal, and the systemic manifestations were, thus, attributed to drug reactions. The above findings indicate the high value of oral examination in diagnosing or confirming paediatric cGVHD. Superficial mucoceles, reported for the first time in paediatric recipients, seem to be important in the early diagnosis of cGVHD.
The related literature highlighted the impact of COVID‐19 on agri‐food entrepreneurship, the government measures and support on agri‐food entrepreneurship, and the shift of agri‐food entrepreneurship towards digitization, innovative ideas, and new market solutions. Agri‐food entrepreneurship faces numerous challenges, but at the same time, the crisis can generate opportunities. The studies made so far indicate that COVID‐19 can cause transformational changes to agri‐food entrepreneurship, although further research is needed to clarify open issues.
A potato field experiment was conducted for 2 consecutive years to determine the effects of nitrogen (N) and potassium (K) fertilization rates on the yield and quality of potato cv. Spunta cultivated on soil low in N and K. A 3 × 4 complete factorial experiment was used with three rates of nitrogen (330, 495, and 660 kg N ha -1 ) and four rates of potassium (112, 225, 450, and 675 kg K 2 O ha -1 ). An additional treatment without fertilization was used as the control. On soils low in N and K, potatoes showed low yield response to K fertilizer. The greatest tuber yields for both years were achieved at 495 kg N ha -1 and 112 kg K 2 O ha -1 (29.81 t ha -1 ) and 225 kg ha -1 (27.13 t ha -1 ), respectively. Differences in mean fresh weight due to treatment application were not significant. Application of 495 kg N ha -1 significantly reduced harvest index (the ratio of tuber dry weight to the total dry weight at harvest) compared to 330 kg N ha -1 , but at 660 kg N ha -1 harvest index achieved the greatest significant value. Potassium fertilization had no significant influence on harvest index. Nitrogen rates positively influenced the number of tubers. The addition of 450 kg K 2 O ha -1 significantly enhanced the number of tubers compared to the lower K rates, and the number was significantly decreased by the application of 675 kg K 2 O ha -1 . Tuber dry-matter concentration was significantly promoted by N fertilization in both cultivation years, but it was negatively affected by K fertilization in the first year of cultivation. There was no change in tuber N with N application, but N application strongly increased nitrate (NO 3 ) concentration, which fluctuated between 360 and 1382 mg kg -1 wet mass. Tuber NO 3 was negatively correlated with tuber yield, indicating that high levels of NO 3 in tubers can adversely affect yield. Tuber response to K fertilization was not in accordance with the rate of applied nutrient.
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