scholarly journals Efficiency of Sophora flavescens-Fructus Ligustri Lucidi Drug Pairs in the Treatment of Liver Fibrosis Based on the Response Surface Method

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Shuhan Chu ◽  
Hongxu Zhang ◽  
Lixin Ding
Keyword(s):  
Liver Fibrosis ◽  
Response Surface ◽  
Low Dose ◽  
Interaction Analysis ◽  
Three Dimensional ◽  
Optimal Dose ◽  
High Dose ◽  
Sophora Flavescens ◽  
Index Method ◽  
Fructus Ligustri Lucidi

The pairing of Sophora flavescens and Fructus Ligustri lucidi is taken from Shi Jinmo Medicine. The idea behind this pairing was inspired by the similarity in pharmacological effects of the two herbal drugs, both of which are known to be effective in the treatment and protection against liver fibrosis. To quantitatively study the extent of the interaction between these drugs and the effect of pairing on the treatment of liver fibrosis, an animal model of liver fibrosis mice was established by intraperitoneal injection of low-dose carbon tetrachloride. The drugs were then administered individually, or in predefined compatibility ratio pairs, by gavage, and the effects on indexes of liver fibrosis were observed. The multisynthetic index method was adopted using Matlab software in order to construct a three-dimensional response surface map of the integration effect and conduct interaction analysis of Sophora flavescens and Fructus Ligustri lucidi. The quadratic surface fitting pattern was designed by quadratic regression to determine the optimal range of each drug. The obtained results show that when the compatibility ratio of Sophora flavescens-Fructus Ligustri lucidi drug pairs is less than or equal to 1:1, their therapeutic effect is enhanced by synergy (interaction value ranging between -0.2 and -1). Overall, the synergy of the high-dose drug pairs is stronger than that of the low-dose drug pairs. The optimal dose ranges are 6~12 g and 8~17 g for Sophora flavescens and Fructus Ligustri lucidi, respectively.

scholarly journals Dose-Response Effects of Strawberries on Atherogenic Lipoproteins: A Randomized Controlled Crossover Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 75-75
Author(s):  
Ann Skulas-Ray ◽  
Chesney Richter ◽  
Trent Gaugler ◽  
Stacey Meily ◽  
Kristina Petersen ◽  
...  
Keyword(s):  
Low Dose ◽  
Optimal Dose ◽  
Serum Lipoprotein ◽  
High Dose ◽  
Funding Sources ◽  
Supplementation Period ◽  
Freeze Dried ◽  
Middle Aged Adults ◽  
Post Hoc ◽  
Main Effects

Abstract Objectives Previous research indicates that consumption of strawberries may provide benefits for reduction of atherogenic lipoproteins but has not identified an optimal dose. Our objective was to evaluate effects of 2 doses of strawberry powder, approximately equivalent to 1 and 3 servings of strawberries per day, on serum lipoprotein concentrations. Methods Middle-aged adults (n = 40, age 49 ± 1 year) with elevated LDL-C (140 ± 4 mg/dL) and elevated BMI (29.4 ± 0.4 kg/m2) consumed 0 g/d (control), 13 g/d (low-dose), and 40 g/d (high-dose) of freeze-dried strawberry powder in a randomized crossover design (4-week supplementation periods separated by a 2 week compliance break). Fasting blood samples were obtained on two separate days (and averaged) at study-entry baseline and following each supplementation period. Results There were significant main effects of treatment (P ≤ 0.05) for calculated LDL-C, nonHDL-C, and total cholesterol (TC). In post hoc tests, the low-dose resulted in 5% lower LDL-C vs. the high-dose (P = 0.01), 4% lower nonHDL-C vs. control (P = 0.04), and 3% lower TC for the low-dose vs. control and high-dose (P ≤ 0.04). Compared to baseline, low-dose strawberry supplementation also significantly reduced direct LDL-C (−6.8 mg/dL, P = 0.02), but there was not a main effect of treatment. Conclusions Our results suggest that low-dose supplementation with freeze dried strawberry powder, roughly equivalent to one serving of strawberries per day, was superior to high-dose supplementation for improving atherogenic lipoproteins in overweight adults. Funding Sources California Strawberry Commission.

scholarly journals High Dose and Low Dose Oxytocin Regimen as Determinants of Successful Induction: A multicenter comparative study

2019 ◽  
Author(s):  
MELESE GEZAHEGN TESEMMA ◽  
Demisew Amenu Sori ◽  
Desta Hiko Gemeda
Keyword(s):  
Low Dose ◽  
Optimal Dose ◽  
Cross Sectional Study ◽  
Induction Of Labor ◽  
P Value ◽  
High Dose ◽  
Bishop Score ◽  
Delivery Time ◽  
Cross Sectional ◽  
Successful Induction

Abstract Background Induction of labor by Oxytocin is a routine obstetric procedure. However, little is known regarding the optimal dose of oxytocin so as to bring successful induction. This study is aimed at comparing the effect of high dose versus low dose oxytocin regimen on success of induction.Methods Hospital based comparative cross-sectional study was conducted in four selected hospitals in Ethiopia from October 1, 2017 to May 30, 2018. A total of 216 pregnant women who undergo induction of labor at gestational age of 37 weeks and above were included. Data was entered into Epi-data version 3.1 and then exported to SPSS version 20 for cleaning and analysis. Chi-square test and logistic regression were done to look for determinants of successful induction. The result is presented using 95% confidence interval of crude and adjusted odds ratios. P-value < 0.05 was used to declare statistical significance.Result Mean “Induction to delivery time” was 5.9 hours and 6.3 hours for participants who received high dose Oxytocin and low dose Oxytocin respectively. Higher successful induction (72.2% versus 61.1%) and lower Cesarean Section rate (27.8% vs. 38.9) was observed among participants who received low dose Oxytocin compared to high dose. Favourable bishop score [AOR 4.0 95% CI 1.9, 8.5], elective induction [AOR 0.2 95% CI 0.1, 0.4], performing artificial rupture of membrane [AOR 10.1 95% CI 3.2, 32.2], neonatal birth weight of < 4Kg [AOR 4.3, 95% CI 1.6, 11.6] and being parous [AOR 2.1 95% CI 1.1, 4.0] were significantly associated with success of induction. Conclusions : In this study, oxytocin regimen didn’t show significant association with success of induction. But, high dose oxytocin regimen is significantly associated with slightly shorter induction to delivery time. Favourable bishop score, emergency induction, performing artificial rupture of membrane and delivery to non-macrosomic neonate are positive determinants of successful induction. Thus, we recommend ripening cervix when condition allows, estimating fetal weight and performing artificial rupture of membrane. We also recommend researchers to conduct more strong research that controls confounders to see the real effect of different oxytocin regimen on induction success.

Phase I study of concurrent high-dose three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7546-7546
Author(s):  
I. Sekine ◽  
M. Sumi ◽  
Y. Ito ◽  
H. Nokihara ◽  
N. Yamamoto ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Optimal Dose ◽  
Stage Iii ◽  
High Dose ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Three Dimensional Conformal Radiotherapy ◽  
3D Crt

7546 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. Methods: Eligible patients (unresectable stage III NSCLC, age ≥ 20 years, PS 0–1, V20 ≤ 30%) received cisplatin (80mg/m2 day 1) and vinorelbine (20mg/m2 days 1 and 8) repeated every 4 weeks for 3–4 cycles. The dose of 3D-CRT was 66 Gy in 33 fractions, 72 Gy in 36 fractions, and 78 Gy in 39 fractions at levels 1–3, respectively. The dose-limiting toxicity (DLT), defined as grade ≥3 esophagitis, pneumonitis, myelitis, dermatitis and heart injury, and early stop of protocol treatment, was evaluated in 6–12 patients at each level. Results: Of the 17, 16 and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled into levels 1–3, respectively, of the study. A total of 26 patients were excluded because of V20 > 30% (n=10), overdose to the esophagus (n=8) and brachial plexus (n=2), comorbidity (n=3), or patient refusal (n=3). There were 26 men and 5 women with a median (range) age of 60 (41–75) years. Of these, 23 (74%) had adenocarcinoma and 20 (65%) had stage IIIA disease. The full planned dose of radiotherapy could be administered in all the patients, and more than 80% of the patients received 3–4 cycles of chemotherapy. Grade 3–4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, grade 3 esophagitis and grade 3 pulmonary toxicity were noted in one, two and one patients, respectively. DLT was noted in 17% of the patients at each level. Two (6%) complete and 27 (87%) partial responses were obtained. In a preliminary survival analysis, the median progression-free and overall survivals were determined to be 15.0 months and 37.6 months, respectively. Conclusions: At the level of 78Gy, only 25% of the patients assessed for eligibility were actually eligible. Toxicity was relatively mild up to 78 Gy in this highly selective patient group. Thus, we determined that the recommended dose of 3D-CRT administered concurrently with cisplatin and vinorelbine chemotherapy was 72Gy. [Table: see text]

High- versus low-dose leucovorin in 5-fluorouracil-based oxaliplatin- or irinotecan-containing regimen in metastatic colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15054-e15054
Author(s):  
E. Song ◽  
N. Lee ◽  
J. Kwak ◽  
H. Yhim ◽  
K. Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Large Scale ◽  
Low Dose ◽  
Palliative Chemotherapy ◽  
Optimal Dose ◽  
Phase Iii ◽  
High Dose ◽  
Significant Difference ◽  
Gastrointestinal Side Effects

e15054 Background: Although leucovorin (LV) is widely used as a modulator of 5-fluorouracil (5-FU) for the chemotherapy of advanced colorectal cancer, the optimal dose has not yet been established. Low-dose LV appears to be as active as high-dose LV in the several studies. So, we tried to compare the efficacy of high-versus low-dose LV in the commonly used palliative chemotherapy regimen. Methods: Between May 2003 and May 2008, 40 patients with metastatic colorectal cancer were randomly treated with high-LV (200mg/m2/i.v.) or low-LV (20mg/m2/i.v.) in 5-FU based oxaliplatin (FOLFOX-4) or irinotecan (FOLFIRI) containing regimen. The primary endpoint of the study was the comparison of response rates and the secondary endpoint was the assessment of survival and tolerability. Results: The response rate was 40% in low-LV group with 2 CR and 6 PR, and 35% in high-LV group with 2 CR and 5 PR, without any significant difference (P = 0.89). The median overall survival was 24.3 months in low-LV group and 25.2 months in high-LV group, with no difference between treatments. Toxicity mainly consisted of gastrointestinal side effects, which were rare and similar in the two groups. Conclusions: In this randomized phase II study, the low and high doses of LV appeared to be equivalent in palliative chemotherapy of metastatic colorectal cancer although large-scale phase III study are necessary. No significant financial relationships to disclose.

Multicenter phase II study of concurrent high-dose (72Gy) three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7070-7070 ◽  
Author(s):  
Hidehito Horinouchi ◽  
Ikuo Sekine ◽  
Minako Sumi ◽  
Miyako Satouchi ◽  
Hiroshi Isobe ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Optimal Dose ◽  
Distant Recurrence ◽  
Stage Iii ◽  
High Dose ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
3D Crt

7070 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. We previously concluded that the recommended dose for further trial was 72Gy in a phase I study (Sekine et al., Int J Radiat Oncol Biol Phys. 953-959, 2012). Methods: Eligible patients (unresectable stage III NSCLC, age between 20 and 74, PS 0-1, V20 ≤ 30%) received cisplatin (80 mg/m2 day 1) and vinorelbine (20 mg/m2 days 1 and 8) repeated every 4 weeks for 3-4 cycles. The 3D-CRT started at the first day of chemotherapy at a total dose of 72 Gy in 36 fractions. The primary endpoint was a 2-year survival rate and the planned sample size was 60 to reject the rate of 45% under the expectation of 65% with a power of 90% and an alpha error of 5%. Results: Thirty-one patients from 4 institutions were enrolled between May 2009 and March 2010. This trial was terminated early due to slow accrual and grade 5 pulmonary toxicities in 2 patients. There were 25 men and 6 women with a median (range) age of 59 (32-72) years. Of these, 23 had adenocarcinoma and 21 had stage IIIA disease. The median (range) V20 value was 20 (9-30). The full planned dose of radiotherapy could be administered in 30 (97%) patients, and 26 (84%) of the patients received 3-4 cycles of chemotherapy. During the chemoradiotherapy, grade 3-4 febrile neutropenia, infection and esophagitis were noted in 5, 4 and 1 of the 31 patients, respectively. After completion of the planned chemoradiotherapy, 5 patients had grade 3 or higher radiation pneumonitis, and 2 (6%) of these patients died at 6.6 and 7.3 months after the treatment started. The overall response rate was 97% (95% confidence interval: 83.3-99.9). Twenty-four patients are alive and thirteen patients experienced recurrence (2 had loco-regional recurrences, 7 had distant recurrence and 4 had mixed recurrence pattern) at a median follow up of 16.4 months. Conclusions: Concurrent high-dose (72Gy) 3D-CRT with chemotherapy using cisplatin and vinorelbine may have a too excessive incidence of pulmonary toxicities to warrant any further evaluation.

scholarly journals Gadoxetate-enhanced dynamic contrast-enhanced MRI for evaluation of liver function and liver fibrosis in preclinical trials

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jimi Huh ◽  
Su Jung Ham ◽  
Young Chul Cho ◽  
Bumwoo Park ◽  
Bohyun Kim ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Clinical Research ◽  
Low Dose ◽  
Correlation Coefficients ◽  
High Dose ◽  
Dce Mri ◽  
Contrast Enhanced ◽  
Preclinical Trials ◽  
Icg R15 ◽  
And Control

Abstract Background To facilitate translational drug development for liver fibrosis, preclinical trials need to be run in parallel with clinical research. Liver function estimation by gadoxetate-enhanced dynamic contrast-enhanced MRI (DCE-MRI) is being established in clinical research, but still rarely used in preclinical trials. We aimed to evaluate feasibility of DCE-MRI indices as translatable biomarkers in a liver fibrosis animal model. Methods Liver fibrosis was induced in Sprague-Dawley rats by thioacetamide (200 mg, 150 mg, and saline for the high-dose, low-dose, and control groups, respectively). Subsequently, DCE-MRI was performed to measure: relative liver enhancement at 3-min (RLE-3), RLE-15, initial area-under-the-curve until 3-min (iAUC-3), iAUC-15, and maximum-enhancement (Emax). The correlation coefficients between these MRI indices and the histologic collagen area, indocyanine green retention at 15-min (ICG-R15), and shear wave elastography (SWE) were calculated. Diagnostic performance to diagnose liver fibrosis was also evaluated by receiver-operating-characteristic (ROC) analysis. Results Animal model was successful in that the collagen area of the liver was the largest in the high-dose group, followed by the low-dose group and control group. The correlation between the DCE-MRI indices and collagen area was high for iAUC-15, Emax, iAUC-3, and RLE-3 but moderate for RLE-15 (r, − 0.81, − 0.81, − 0.78, − 0.80, and − 0.51, respectively). The DCE-MRI indices showed moderate correlation with ICG-R15: the highest for iAUC-15, followed by iAUC-3, RLE-3, Emax, and RLE-15 (r, − 0.65, − 0.63, − 0.62, − 0.58, and − 0.56, respectively). The correlation coefficients between DCE-MRI indices and SWE ranged from − 0.59 to − 0.28. The diagnostic accuracy of RLE-3, iAUC-3, iAUC-15, and Emax was 100% (AUROC 1.000), whereas those of RLE-15 and SWE were relatively low (AUROC 0.777, 0.848, respectively). Conclusion Among the gadoxetate-enhanced DCE-MRI indices, iAUC-15 and iAUC-3 might be bidirectional translatable biomarkers between preclinical and clinical research for evaluating histopathologic liver fibrosis and physiologic liver functions in a non-invasive manner.

Preterm newborn lamb renal and cardiovascular responses after fetal or maternal antenatal betamethasone

1997 ◽  
Vol 272 (6) ◽  
pp. R1972-R1979 ◽  
Author(s):  
L. M. Berry ◽  
D. H. Polk ◽  
M. Ikegami ◽  
A. H. Jobe ◽  
J. F. Padbury ◽  
...  
Keyword(s):  
Low Dose ◽  
Cardiovascular Responses ◽  
Optimal Dose ◽  
Sodium Reabsorption ◽  
High Dose ◽  
Preterm Newborn ◽  
Short Term ◽  
To Receive ◽  
Renal Sodium Reabsorption ◽  
Dose Dependent

The optimal dose, route of administration, and treatment-to-delivery interval necessary to induce beneficial extrapulmonary effects of glucocorticoids are not known. Pregnant ewes (127 days gestation) were randomized to receive maternal or fetal intramuscular injections of betamethasone (0.2 or 0.5 mg/kg body wt) or saline 24 h before cesarean delivery of their lambs. Three hours after delivery, low-dose maternal vs. control lamb mean arterial pressure [64 +/- 4 vs. 47 +/- 2 (SE) mmHg], glomerular filtration rate (1.7 +/- 0.2 vs. 0.7 +/- 0.1 ml.min-1.kg-1), and total renal sodium reabsorption (219 +/- 31 vs. 85 +/- 12 mueq.min-1.kg-1) were increased. Comparable increases were observed in the high-dose maternal and fetal groups without effects in the low-dose fetal group. This study provides the first quantitative data demonstrating that even short-term (24-h) antenatal betamethasone exposure alters preterm newborn cardiovascular and renal functions. These responses are route and dose dependent and are comparable to glucocorticoid-induced maturational effects after longer-term antenatal exposure.

scholarly journals Safety and immunogenicity of a new inactivated polio vaccine made from Sabin strains: a randomized, double-blind, active-controlled, phase 2/3 seamless study

2020 ◽  
Author(s):  
Maria Rosario Capeding ◽  
Grace Devota Gomez-Go ◽  
Peninnah Oberdorfer ◽  
Charissa Borja-Tabora ◽  
Lulu Bravo ◽  
...  
Keyword(s):  
Low Dose ◽  
Seroconversion Rate ◽  
Optimal Dose ◽  
Stage I ◽  
Stage Ii ◽  
High Dose ◽  
Phase 2 ◽  
Double Blind ◽  
Inactivated Polio Vaccine ◽  
Polio Vaccine

Abstract Background A new inactivated polio vaccine made from Sabin strains (sIPV) was developed as part of the global polio eradication initiative. Methods This randomized, double-blind, active-controlled, phase 2/3 seamless study was conducted in two stages. Healthy infants aged 6 weeks were randomly assigned to receive three doses of one of four study vaccines at 6, 10, and 14 weeks of age (336 received low-, middle-, or high-dose sIPV, or conventional IPV [cIPV] in Stage I, and 1086 received lot A, B, or C of the selected sIPV dose, or cIPV in Stage II). The primary outcome was the seroconversion rate 4 weeks after the third vaccination. Results In Stage I, low-dose sIPV was selected as the optimal dose. In Stage II, consistency among the three manufacturing lots of sIPV was demonstrated. The seroconversion rates for Sabin and wild strains of the 3 serotypes after the three-dose primary series were 95.8% to 99.2% in the lot-combined sIPV group and 94.8% to 100% in the cIPV group, proving the non-inferiority of sIPV compared to cIPV. No notable safety risks associated with sIPV were observed. Conclusions Low-dose sIPV administered as a three-dose vaccination was safe and immunogenic compared to cIPV.

Protective Effects of Ginkgo biloba, Panax ginseng, and Schizandra chinensis Extract on Liver Injury in Rats

2007 ◽  
Vol 35 (06) ◽  
pp. 995-1009 ◽  
Author(s):  
Hsin-Fang Chang ◽  
Yun-Ho Lin ◽  
Chia-Chou Chu ◽  
Shu-Ju Wu ◽  
Ya-Hui Tsai ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Panax Ginseng ◽  
Ginkgo Biloba ◽  
Antioxidant Status ◽  
Low Dose ◽  
Herbal Extract ◽  
High Dose ◽  
Schizandra Chinensis ◽  
Tgf Β1

This study investigated the effects of the combined extracts of Ginkgo biloba, Panax ginseng, and Schizandra chinensis at different doses on hepatic antioxidant status and fibrosis in rats with carbon tetrachloride ( CCl 4)-induced liver injury. Male Sprague-Dawley rats ( n = 8–12 per group) were divided into the control, CCl 4, CCl 4 + silymarin (0.35%), CCl 4 + low-dose herbal extract (0.24% of Ginkgo biloba, Panax ginseng, and Schizandra chinensis extract at 1:1:1; LE), and CCl 4 + high-dose herbal extract (1.20% of the same herbal extract; HE) groups. Silymarin or herbal extract was orally given to rats a week before chronic intraperitoneal injection with CCl 4 for 6 weeks. The pathological results showed that herbal extract suppressed hepatic bile duct proliferation, and low-dose herbal extract inhibited liver fibrosis. Hepatic superoxide dismutase (SOD) activity was lower in the CCl 4 group, but there was no difference in the silymarin or herbal extract treated groups compared to the control group. Hepatic catalase activity and the ratio of reduced to oxidized glutathione were significantly higher ( p < 0.05) in the HE group than those in the CCl 4 group. Silymarin and herbal extract reversed the impaired hepatic total antioxidant status ( p < 0.05). Herbal extract partially reduced the elevated hepatic lipid peroxides. Hepatic transforming growth factor-β1 (TGF-β1) level decreased significantly ( p < 0.05) in the LE group. Therefore, high-dose herbal extract improved hepatic antioxidant capacity through enhancing catalase activity and glutathione redox status, whereas low-dose herbal extract inhibited liver fibrosis through decreasing hepatic TGF-β1 level in rats with CCl 4-induced liver injury.

Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the bisphosphonate AHPrBP.

1988 ◽  
Vol 6 (5) ◽  
pp. 762-768 ◽  
Author(s):  
D Thiébaud ◽  
P Jaeger ◽  
A F Jacquet ◽  
P Burckhardt
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
Optimal Dose ◽  
Urinary Calcium ◽  
Plasma Calcium ◽  
High Dose ◽  
Initial Plasma ◽  
Plasma Calcium Concentration ◽  
Dose Dependent Decrease

Fifty-two patients with malignant hypercalcemia were treated with a single dose of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose-response in humans, patients were divided into four groups receiving 30 mg, 45 mg, 60 mg, or 90 mg, respectively, as a 24-hour infusion. Initial plasma calcium was similar in all groups, except in the group receiving 90 mg, of which some patients had higher initial values. All patients responded to AHPrBP with a rapid decrease of plasma calcium concentration from 3.47 +/- 0.10 mmol/L at day 0 to 2.43 +/- 0.06 at day 6 (P less than .001). Plasma calcium became normal within four to six days in 43 patients. Eight of the nine patients whose calcium did not become normal were in the low-dose (30 and 45 mg of AHPrBP) groups. Slight and asymptomatic hypocalcemia occurred in only tow of the 26 patients in the low-dose groups, but in six of the 26 patients in the high-dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 1 month in five of ten patients in the group receiving 30 mg, in three of ten patients in the group receiving 45 mg, and in one of 20 patients in the groups receiving 60 and 90 mg, whereas mortality was almost identical in all four groups. In all groups, plasma phosphate, plasma creatinine, urinary calcium, and hydroxyproline excretion decreased significantly. In conclusion, when administered as a single-day infusion in the treatment of tumor hypercalcemia, AHPrBP leads to a dose-dependent decrease in plasma calcium. To prevent transient hypocalcemia and early relapse, the optimal dose should be adapted to the degree of severity of hypercalcemia.

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