B1tta/Drug-ACE huggingface dataset:
[Title]: Chlorproguanil-dapsone for treatment of drug-resistant falciparum malaria in Tanzania.
[Abstract]: BACKGROUND: Resistance to the affordable malaria treatments chloroquine and pyrimethamine-sulfadoxine is seriously impeding malaria control through treatment in east Africa. We did an open, alternate drug allocation study to assess the efficacy of chlorproguanil-dapsone in the treatment of falciparum malaria clinically resistant to pyrimethamine-sulfadoxine. METHODS: Children younger than 5 years with non-severe falciparum malaria, attending Muheza district hospital in Tanzania, were treated with the standard regimen of pyrimethamine-sulfadoxine. Patients whose clinical symptoms resolved but who remained parasitaemic 7 days after pyrimethamine-sulfadoxine were followed up for 1 month. Clinical malaria episodes were retreated with either single dose pyrimethamine-sulfadoxine or a 3-day regimen of chlorproguanil-dapsone. Those with parasitaemia after 7 days were treated with chlorproguanil-dapsone. Parasite DNA was collected on day 7 after first treatment with pyrimethamine-sulfadoxine and we looked for point mutations in the genes encoding dihydrofolate reductase (dhfr) and dyhydropteroate synthetase (dhps). FINDINGS: 360 children were enrolled and treated with pyrimethamine-sulfadoxine. On day 7, 192 (55%) of 348 had cleared parasitaemia. Of the remaining 156 parasitaemic children, 140 (90%) were followed up to day 28, and 92 (66%) of 140 developed clinical malaria. These 92 patients were alternately retreated with either pyrimethamine-sulfadoxine (46) or chlorproguanil-dapsone (46). 28 (61%) of 46 children retreated with pyrimethamine-sulfadoxine were still parasitaemic at day 7, compared with three (7%) of 44 [corrected] children retreated with chlorproguanil-dapsone. Resistance to pyrimethamine-sulfadoxine increased from 45% (156/348) at the first treatment to 61% (28/46) after retreatment. 83 of 85 parasite isolates collected after the first pyrimethamine-sulfadoxine treatment, and before and after the second treatments with pyrimethamine-sulfadoxine and chlorproguanil-dapsone showed triple-mutant dhfr alleles, associated with a variety of dhps mutations. INTERPRETATION: Most patients treated with pyrimethamine-sulfadoxine, who remain parasitaemic at day 7, develop new malaria symptoms within 1 month. Chlorproguanil-dapsone was a practicable therapy under these circumstances. Analysis of parasite dhfr and dhps before and after treatment supports the view that pyrimethamine-sulfadoxine resistance in this part of Africa is primarily due to parasites with three mutations in the dhfr domain.
[Drug-Disease]: chloroquine - malaria symptoms
[Title]: Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone.
[Abstract]: OBJECTIVE: The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) &gt; 90 mmHg on this medication given alone. METHODS: A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP &lt;/= 90 mmHg after 4 weeks of valsartan monotherapy. These patients continued the same treatment regimen for the next 4 weeks, but no further blood pressure reduction was observed. The remaining patients were randomized to either the valsartan-hydrochlorothiazide or the valsartan-benazepril combination. RESULTS: The two combinations induced an additional significant BP reduction, which was of similar magnitude for diastolic BP (-4.5 during valsartan-hydrochlorothiazide treatment and -3.3 mmHg during valsartan-benazepril treatment), but of greater magnitude for systolic BP during valsartan-hydrochlorothiazide (-6.77 mmHg) than during valsartan-benazepril co-administration (-3.2 mmHg). At the end of the trial, the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy. Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated. CONCLUSION: These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor, with the diuretic-containing combination tending to being more effective in controlling systolic BP.
[Drug-Disease]: benazepril - hypertension
[Title]: Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone.
[Abstract]: OBJECTIVE: The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) &gt; 90 mmHg on this medication given alone. METHODS: A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP &lt;/= 90 mmHg after 4 weeks of valsartan monotherapy. These patients continued the same treatment regimen for the next 4 weeks, but no further blood pressure reduction was observed. The remaining patients were randomized to either the valsartan-hydrochlorothiazide or the valsartan-benazepril combination. RESULTS: The two combinations induced an additional significant BP reduction, which was of similar magnitude for diastolic BP (-4.5 during valsartan-hydrochlorothiazide treatment and -3.3 mmHg during valsartan-benazepril treatment), but of greater magnitude for systolic BP during valsartan-hydrochlorothiazide (-6.77 mmHg) than during valsartan-benazepril co-administration (-3.2 mmHg). At the end of the trial, the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy. Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated. CONCLUSION: These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor, with the diuretic-containing combination tending to being more effective in controlling systolic BP.
[Drug-Disease]: Valsartan - hypertension
[Title]: Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone.
[Abstract]: OBJECTIVE: The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) &gt; 90 mmHg on this medication given alone. METHODS: A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP &lt;/= 90 mmHg after 4 weeks of valsartan monotherapy. These patients continued the same treatment regimen for the next 4 weeks, but no further blood pressure reduction was observed. The remaining patients were randomized to either the valsartan-hydrochlorothiazide or the valsartan-benazepril combination. RESULTS: The two combinations induced an additional significant BP reduction, which was of similar magnitude for diastolic BP (-4.5 during valsartan-hydrochlorothiazide treatment and -3.3 mmHg during valsartan-benazepril treatment), but of greater magnitude for systolic BP during valsartan-hydrochlorothiazide (-6.77 mmHg) than during valsartan-benazepril co-administration (-3.2 mmHg). At the end of the trial, the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy. Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated. CONCLUSION: These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor, with the diuretic-containing combination tending to being more effective in controlling systolic BP.
[Drug-Disease]: hydrochlorothiazide - hypertension
[Title]: Comparison of gallamine with d-tubocurarine effects on fasciculations after succinylcholine.
[Abstract]: Administration of either gallamine or d-tubocurarine before injecting succinylcholine diminished both the incidence and intensity of muscle fasciculations. Gallamine was more efficient than curare in this respect, 30 mg./70kg. almost entirely preventing fasciculations.
[Drug-Disease]: Gallamine - fasciculations
[Title]: Comparison of gallamine with d-tubocurarine effects on fasciculations after succinylcholine.
[Abstract]: Administration of either gallamine or d-tubocurarine before injecting succinylcholine diminished both the incidence and intensity of muscle fasciculations. Gallamine was more efficient than curare in this respect, 30 mg./70kg. almost entirely preventing fasciculations.
[Drug-Disease]: d-tubocurarine - fasciculations
[Title]: Phase II study of high-dose paclitaxel and carboplatin in previously untreated, unresectable non-small cell lung cancer.
[Abstract]: INTRODUCTION: This phase II study was designed to assess the activity and tolerability of the carboplatin-paclitaxel combination, given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. PATIENTS AND METHODS: Sixty patients (15 stage IIIb and 45 stage IV) received paclitaxel 225 mg/ml on day 1, followed by carboplatin AUC 6 mg/ml per minute (Calvert formula) every 3 weeks. Paclitaxel was administered as a 3-h intravenous infusion followed by carboplatin over 30 min, on completion of paclitaxel administration. RESULTS: The combination showed a good safety profile with Grade 4 neutropenia occurring in 31% of patients without any serious infectious episodes requiring hospitalization. Moderate to severe anemia and thrombocytopenia seldom occurred. Sensorimotor peripheral neuropathy (Grade 2-3) and myalgia (Grade 3-4) were documented in 34 and 20% of the patients, respectively. Among 59 evaluable patients, there was one complete response and 26 partial responses for an overall response rate of 46% (95% C.I.: 34-59%). With a minimum follow-up duration of 16.5 months, the median overall survival time is 52 weeks and the 1-year survival rate is 50%. Median duration of response is 20 weeks (range: 4-52) and progression-free survival is 22 weeks (range: 5-77). CONCLUSION: In advanced NSCLC, the combination carboplatin-paclitaxel at doses of AUC 6 mg/ml per minute and 225 mg/ml every 3 weeks, is both active and relatively well-tolerated.
[Drug-Disease]: carboplatin - NSCLC
[Title]: Phase II study of high-dose paclitaxel and carboplatin in previously untreated, unresectable non-small cell lung cancer.
[Abstract]: INTRODUCTION: This phase II study was designed to assess the activity and tolerability of the carboplatin-paclitaxel combination, given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. PATIENTS AND METHODS: Sixty patients (15 stage IIIb and 45 stage IV) received paclitaxel 225 mg/ml on day 1, followed by carboplatin AUC 6 mg/ml per minute (Calvert formula) every 3 weeks. Paclitaxel was administered as a 3-h intravenous infusion followed by carboplatin over 30 min, on completion of paclitaxel administration. RESULTS: The combination showed a good safety profile with Grade 4 neutropenia occurring in 31% of patients without any serious infectious episodes requiring hospitalization. Moderate to severe anemia and thrombocytopenia seldom occurred. Sensorimotor peripheral neuropathy (Grade 2-3) and myalgia (Grade 3-4) were documented in 34 and 20% of the patients, respectively. Among 59 evaluable patients, there was one complete response and 26 partial responses for an overall response rate of 46% (95% C.I.: 34-59%). With a minimum follow-up duration of 16.5 months, the median overall survival time is 52 weeks and the 1-year survival rate is 50%. Median duration of response is 20 weeks (range: 4-52) and progression-free survival is 22 weeks (range: 5-77). CONCLUSION: In advanced NSCLC, the combination carboplatin-paclitaxel at doses of AUC 6 mg/ml per minute and 225 mg/ml every 3 weeks, is both active and relatively well-tolerated.
[Drug-Disease]: paclitaxel - NSCLC
[Title]: Pilot study of sequential vinorelbine and cisplatin followed by docetaxel for selected IIIB and stage IV non-small cell lung cancer.
[Abstract]: UNLABELLED: Vinorelbine, cisplatin and docetaxel are known to be efficacious in non-small cell lung cancer (NSCLC). This limited institution pilot study evaluated the novel strategy of sequencing active first line agents prior to progression. The primary objective of this study was to assess the toxicity profile in anticipation of a larger cooperative group standard phase II study. Patients with selected stage IIIB and IV NSCLC, Southwest Oncology Group (SWOG) performance status (PS) of 1 or less and measurable or evaluable disease were eligible. Treatment was cisplatin 100 mg/m(2) day 1 and 29, vinorelbine 25 mg/m(2) weekly for 8 weeks, followed by docetaxel 100 mg/m(2) every 21 days for four cycles if no progression. If grade IV neutropenia developed, G-CSF 5 mcg/kg/day was used in subsequent cycles. Of 18 eligible patients, 17 patients had stage IV disease with a median age of 66 years (range 48-80). Eight patients had a SWOG PS of 1, 10 had a PS of zero. Six of eighteen patients received all 8 weeks of vinorelbine/cisplatin and six of eight patients who went on to receive docetaxel received all four planned cycles; only two patients overall received all planned therapy. One grade III/IV event each of cardiotoxicity (myocardial infarction), renal toxicity (acute renal failure), anemia and thrombocytopenia occurred with vinorelbine and cisplatin, and 2 Grade IV hypersensitivity reactions, manifested by severe back pain with docetaxel occurred. Three deaths occurred during the study, all during treatment with vinorelbine and cisplatin: one due to neutropenic sepsis; one from a pulmonary embolism; and one secondary to severe hypoglycemia in a diabetic patient. Of the 16 patients evaluable for response after vinorelbine/cisplatin, there were two complete responses (12.5%) and three partial responses (19%) for an overall response rate of 31% (95% CI 8-58). One additional patient who received docetaxel experienced a partial response. Two patients remain alive (21+ and 18+ months, respectively). The 1-year survival was 44%. CONCLUSION: This sequence, as defined, was tolerated marginally well in patients with advanced NSCLC. Granulocytopenia was the major toxicity requiring dose adjustments throughout the sequence. Based on response rates and tolerability that were somewhat comparable to other regimens in this disease setting, a modified version of this program, adjusted to decrease the incidence of grade III and IV toxicity, was selected as one arm of a recent randomized phase II trial in the Southwest Oncology Group (SWOG), S9806, evaluating sequential therapy in advanced NSCLC.
[Drug-Disease]: vinorelbine - NSCLC
[Title]: Pilot study of sequential vinorelbine and cisplatin followed by docetaxel for selected IIIB and stage IV non-small cell lung cancer.
[Abstract]: UNLABELLED: Vinorelbine, cisplatin and docetaxel are known to be efficacious in non-small cell lung cancer (NSCLC). This limited institution pilot study evaluated the novel strategy of sequencing active first line agents prior to progression. The primary objective of this study was to assess the toxicity profile in anticipation of a larger cooperative group standard phase II study. Patients with selected stage IIIB and IV NSCLC, Southwest Oncology Group (SWOG) performance status (PS) of 1 or less and measurable or evaluable disease were eligible. Treatment was cisplatin 100 mg/m(2) day 1 and 29, vinorelbine 25 mg/m(2) weekly for 8 weeks, followed by docetaxel 100 mg/m(2) every 21 days for four cycles if no progression. If grade IV neutropenia developed, G-CSF 5 mcg/kg/day was used in subsequent cycles. Of 18 eligible patients, 17 patients had stage IV disease with a median age of 66 years (range 48-80). Eight patients had a SWOG PS of 1, 10 had a PS of zero. Six of eighteen patients received all 8 weeks of vinorelbine/cisplatin and six of eight patients who went on to receive docetaxel received all four planned cycles; only two patients overall received all planned therapy. One grade III/IV event each of cardiotoxicity (myocardial infarction), renal toxicity (acute renal failure), anemia and thrombocytopenia occurred with vinorelbine and cisplatin, and 2 Grade IV hypersensitivity reactions, manifested by severe back pain with docetaxel occurred. Three deaths occurred during the study, all during treatment with vinorelbine and cisplatin: one due to neutropenic sepsis; one from a pulmonary embolism; and one secondary to severe hypoglycemia in a diabetic patient. Of the 16 patients evaluable for response after vinorelbine/cisplatin, there were two complete responses (12.5%) and three partial responses (19%) for an overall response rate of 31% (95% CI 8-58). One additional patient who received docetaxel experienced a partial response. Two patients remain alive (21+ and 18+ months, respectively). The 1-year survival was 44%. CONCLUSION: This sequence, as defined, was tolerated marginally well in patients with advanced NSCLC. Granulocytopenia was the major toxicity requiring dose adjustments throughout the sequence. Based on response rates and tolerability that were somewhat comparable to other regimens in this disease setting, a modified version of this program, adjusted to decrease the incidence of grade III and IV toxicity, was selected as one arm of a recent randomized phase II trial in the Southwest Oncology Group (SWOG), S9806, evaluating sequential therapy in advanced NSCLC.
[Drug-Disease]: cisplatin - NSCLC
[Title]: Outcome of renal transplantation in hepatitis B surface antigen-positive patients after introduction of lamivudine.
[Abstract]: BACKGROUND: In end-stage renal disease patients with hepatitis B surface antigen (HBsAg), the risk of hepatic dysfunction after immunosuppression represents a large barrier in renal transplantation. Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. We retrospectively investigated the outcome of HBsAg-positive renal transplantation recipients after lamivudine had become available. METHODS: From July 1994 to August 2000, seventeen HBsAg-positive patients (M:F=15:2) received renal allografts (13:4=living:cadaveric donors). Liver function tests at the time of transplantation were normal in all patients. Pre-transplant liver biopsies performed in 15 patients demonstrated minimal inflammatory histology, except in three patients showing pathological and clinical signs of active hepatitis. Lamivudine was started pre-operatively in these three subjects. Another seven patients were treated with lamivudine for post-operative hepatic dysfunction. The remaining seven patients did not develop hepatic dysfunction after transplantation. RESULTS: Lamivudine was initially effective in decreasing serum HBV DNA titres, and in normalizing hepatic enzymes. Lamivudine was well tolerated without significant side effects for 35.5+/-8.9 months after initiation of treatment. HBV DNA became negative in nine patients but remained positive in one patient. Among the nine patients with initial negative conversion of HBV DNA, two developed transient positive conversion of HBV DNA and two demonstrated persistent positive conversion. Among the patients with normal liver histology in the pre-transplant period, 41.6% (5/12) developed liver pathology progression after immunosuppression. All 17 patients had functioning grafts, except for one patient who developed relapsed IgA nephropathy. CONCLUSIONS: Our data showed relatively favourable outcomes in hepatitis B-positive renal transplant recipients receiving lamivudine treatment, even though two patients developed lamivudine resistance.
[Drug-Disease]: lamivudine - hepatitis B
[Title]: Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment.
[Abstract]: Bisphosphonates are potent inhibitors of osteoclastic activity and reduce the disease-related skeletal complications when they are used in combination with chemotherapy in patients with multiple myeloma (MM). Pamidronate also inhibits apoptosis of primary osteoblastic cells and probably induces apoptosis on human MM cells and osteoclasts. It has been reported that interferon-alpha (IFN-alpha) decreases bone resorption and that low doses of IFN-alpha result in a significant increase in serum osteocalcin (OSC). The aim of this study was to determine the effects of pamidronate treatment on biochemical markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], bone formation [bone alkaline phosphatase (BAP) and OSC], disease activity [beta2-microglobulin, CRP, paraprotein], and interleukin-6 (IL-6) in patients with MM in plateau phase under IFN-alpha maintenance. The above parameters were evaluated in 28 patients (13 M, 15 F, median age 70 years) during maintenance treatment, before the addition of pamidronate and after 1, 3, 6, 9, 12, and 14 months of the combined therapy. The addition of pamidronate to maintenance treatment resulted in a significant reduction of NTx, IL-6, beta2-microglobulin, CRP from the 3rd month and paraprotein from the 6th month of treatment, whereas BAP and OSC were significantly increased from the 6th month. These changes continued during the 14-month follow-up of the combined treatment. Multivariate analysis showed a significant negative correlation between changes of BAP and OSC and the patients' age. The greater increase of the bone formation markers was observed in younger patients. These results suggest that, in addition to the inhibition of osteoclastic activity, pamidronate in combination with IFN-alpha was shown to induce bone formation in patients with MM in the plateau phase.
[Drug-Disease]: pamidronate - multiple myeloma