Aspirin, Dipyridamole and Platelet Survival in Patients with Diabetes Mellitus

1982 ◽  
Vol 63 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Hilary Tindall ◽  
R. Colin Paton ◽  
George P. McNicol

1. Platelet survival in 27 insulin-dependent diabetic patients with severe retinopathy was studied in a double-blind cross-over trial using placebo, aspirin (990 mg/day) and a combination of dipyridamole (225 mg/day) with aspirin at two dosage levels (330 mg and 990 mg/day). 2. Twenty patients (group I) had 51Cr-labelled-platelet survival after treatment with placebo and the high-dose-aspirin/dipyridamole combination. The remaining seven patients (group II) had platelet-regeneration times measured after each of the four treatment periods. 3. Treatment of group I patients with the high-dose-aspirin/dipyridamole combination resulted in significant (P < 0·001) prolongation of platelet survival from 7·3 ± 0·2 (mean ± sem) days to 8·4 ± 0·1 days. 4. In group II patients, when compared with the mean placebo result of 7·2 ± 0·2 days, the mean aspirin-labelled-platelet-regeneration time was significantly (P < 0·01) longer only after high-dose-aspirin/dipyridamole (9·8 ± 0·5 days) but not after low-dose-aspirin/dipyridamole (8·3 ± 0·5 days) or aspirin alone (7·3 ± 0·3 days). 5. These results suggest that it may be premature to consider reducing the dose of aspirin in aspirin/dipyridamole combinations below 1 g/day when used as antithrombotic therapy.

Author(s):  
J.J.C. Jonker ◽  
den G.J.H. Ottolander

In 30 normal subjects (group I) and in 89 patients with angina pectoris we studied: the platelet survival time (PST), the platelet aggregation test I (PAT I) acc. to Breddin, the platelet aggregation ratio (PAR) acc. to Wu and Hoak and the Filtragometer log TA acc. to Hornstra. The patients were divided in two groups: 46 patients had already been treated for 6 months with Clofibrate (group II) and 43 patients with placebo (group III) in a double blind trial. The average PST (T½) was within the normal range (group I 99 hrs. group II 105,7 hrs.; group III 102,0 hrs.). About 20% of patients of group II and III had abnormally shortened T½. The PAT I was on average abnormal in group II and III (PAT I in group II 2,3; group III 2,7), but group II normalized after 12 months treatment (PAT I 1,85). The PAR was abnormal in group III, while group II was within the normal range (group I 0,87; group II 0,82; group III 0,69). The log TA results were abnormal in group II and III (group I 2, 45, group II 2,1; group III 2, 1), after 12 months treatment the patient group remained abnormal (group II 2,2; group III 2,1). We failed to find a correlation between the four platelet function tests, nor with these tests and basic laboratory values. The PAT I, the PAR and the Filtragometer seems to be valuable in the detection of abnormal platelet behavior in vitro, but it does not mean than an abnormal platelet survival in vivo occurs in the same individuals.


1981 ◽  
Author(s):  
H Tindall ◽  
R C Paton ◽  
G P McNicol

The effect of a combination of aspirin at 2 dosage levels (330mg/day and 1gm/day) and dipyridamole 225mg/day on platelet lifespan and some haemostatic variables was investigated in 30 insulin-dependent diabetic patients with retinopathy. Platelet regeneration time using a modification of the Stuart technique was measured in 40 normal controls and all patients before therapy commenced. Treatment was then allocated in a double-blind manner using a Latin square design and haemostatic variables were measured at the end of each treatment period. Platelet survival by the standard Na51Cr radioisotopic technique was performed twice during treatment. The post-aspirin platelet regeneration time in normal subjects was 9.98 ± 0.22 days (mean ± SEM) and in diabetic patients was significantly (p<0.001) shorter at 7.16 ± 0.18 days. A similar result of 7.37 ± 0.20 days was obtained in the diabetic patients by Na51cr platelet survival (analysed by γ function). The aspirin/dipyridamole combination (330mg/75mg tds) resulted in significant (p<0.001) lengthening of platelet survival to 8.46 ± 0.13 days (as estimated by Na51Cr method). The postaspirin platelet regeneration time was significantly prolonged (p<0.01) in this group (9.75 ± 0.52 days).Although the lower dose aspirin - dipyridamole combination (110mg/75mg tds) caused a prolongation in regeneration time (8.29 ± 0.45 days) this time was not significantly different from placebo, and was significantly (p<0.01) shorter than the time taken on the higher aspirin dosage. No significant changes in haemostatic function were observed. These results support the hypothesis that platelets may be involved in the microvascular complications of diabetes mellitus. Treatment with Igm aspirin +225mg dipyridamole/day significantly lengthened platelet survival suggesting that long term trials at this aspirin dosage level are justified.


2001 ◽  
Vol 19 (6) ◽  
pp. 1759-1767 ◽  
Author(s):  
Daniel Campos ◽  
Jose Rodrigues Pereira ◽  
Rick R. Reinhardt ◽  
Carlos Carracedo ◽  
Sergio Poli ◽  
...  

PURPOSE: The NK1-receptor antagonist MK-869 (L-754,030) has demonstrated antiemetic activity in humans receiving chemotherapy. Objectives of the present trial included the first assessment of oral MK-869 plus dexamethasone compared with a 5HT3 antagonist plus dexamethasone for prevention of acute and delayed emesis after high-dose cisplatin. Furthermore, the study sought to confirm that addition of MK-869 to a 5HT3 antagonist plus dexamethasone was more effective than just the 5HT3 antagonist plus dexamethasone for prevention of acute and delayed emesis. METHODS: This multicenter, double-blind, parallel-group trial in 351 cisplatin-naïve patients evaluated prevention of acute (0 to 24 hours) and delayed emesis (primary efficacy parameter; days 2 to 5) after cisplatin (≥70 mg/m2). Patients were randomized to four groups (I to IV) (n = number randomized; number evaluable): granisetron (10 μg/kg intravenously) pre-cisplatin followed by placebo on days 2 to 5 (group I) (n = 90; 90); granisetron and MK-869 (400 mg PO [by mouth]) pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group II) (n = 86; 84); MK-869 (400 mg PO) the evening before and pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group III) (n = 89; 88); or MK-869 (400 mg PO) pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group IV) (n = 86; 84). All patients also received dexamethasone (20 mg PO) before cisplatin. Additional medication was available to treat emesis or nausea at any time. RESULTS: In the acute period, 57%, 80%, 46%, and 43% of patients were without emesis in groups I, II, III, and IV, respectively (P < .01 for group II v group I). In the delayed period, the proportion of patients without emesis in groups I, II, III, and IV was 29%, 63%, 51%, and 57%, respectively (P < .01 for groups II, III, and IV v group I). The distribution of nausea scores in the delayed period was lower when comparing group II with group I (P < .05 for days 1 to 5 and days 2 to 5). One serious adverse event (dizziness) was rated as possibly related to MK-869. CONCLUSION: Once daily oral administration of MK-869 was effective in reducing delayed emesis and nausea after high-dose cisplatin. However, the combination of the 5HT3 antagonist plus dexamethasone was numerically superior to MK-869 plus dexamethasone in reducing acute emesis. Confirming and extending previous findings, the triple combination of a 5HT3 antagonist, MK-869, and dexamethasone provided the best control of acute emesis.


2014 ◽  
Vol 3;17 (3;5) ◽  
pp. 255-264
Author(s):  
Hala S. Abdel-Ghaffar

Background: Despite 30 years of clinical research, we still do not know the optimal dose of intrathecal morphine (ITM) when used alone. Objectives: A safety investigation and comparison of the analgesic efficacy of ITM 0.2 mg, 0.5 mg, and 1 mg in patients undergoing major abdominal cancer surgery. Study Design: A randomized, double-blind trial. Setting: Academic medical center. Methods: Ninety patients were randomly assigned to receive morphine intrathecally either 0.2 mg (Group I, ITM 0.2 mg, n = 30), 0.5 mg (Group II, ITM 0.5 mg, n = 30), or 1 mg (Group III, ITM 1 mg, n = 30) dissolved in 5 mL physiological saline before general anesthesia. Assessment parameters included hemodynamics, respiratory rate, peripheral arterial oxygenation, sedation score, pain severity, time of first analgesic request, total analgesic consumption, and side effects in the first 72 hours. Results: The mean time to first request for rescue analgesia was significantly prolonged in Group II (22.13 ± 5.21 hours, P < 0.001) and Group III (30.83 ± 4.89 h, P < 0.001), compared with Group I (0.50 ± 0.66 hours). The mean tramadol consumption dose was significantly reduced in Group II (383.33 ± 91.28 mg, P < 0.001) and Group III (300 ± 69.48 mg, P < 0.001) compared with Group I (770 ± 114.92 mg). Patients received 1 mg ITM showed lower VAS scores in the first 48 h postoperative (P < 0.04) compared with Group I and Group II. No significant differences were observed in the mean systolic and diastolic blood pressure values, respiratory rate, and peripheral arterial oxygen saturation between groups. Lower mean heart rate values were observed in Group III patients at 6 hours (P < 0.01) and 12 hours (P < 0.03) postoperative compared with Group I and Group II patients. Six patients (20%) in Group II and 8 (26.7%) in Group III exhibited pruritus compared with 2 patients (6.66%) in Group I (P < 0.01). No intergroup statistical differences were observed for other studied side effects. Limitations: This study is limited by its small sample size. Conclusion: One mg ITM provided superior analgesia for 48 hours postoperative compared with 0.2 mg and 0.5 mg ITM with a nonsignificant difference in the incidence of side effects. Further studies of larger sample size are recommended to confirm these findings. Key words: Anesthesia, analgesia, abdominal cancer, opioids, intrathecal, morphine


2012 ◽  
Vol 2 (2) ◽  
pp. 89-92
Author(s):  
Sharmistha Dey ◽  
Kanta Das ◽  
Shamse Ara Begum ◽  
Akhtar Uddin Ahmed ◽  
Abu Saleh Mohiuddin

Objectives: This study was performed to find out the extent and nature of arterial flow abnormality in diabetic patients with peripheral neuropathy compared to diabetic patients without neuropathy, using duplex colour Doppler technique. Materials and method: This cross sectional study was performed on diabetic subjects in the Department of Radiology and Imaging, BIRDEM from July 2008’ to May 2009. Patients were referred from Department of neurology and preventive foot care OPD, BIRDEM, for colour Doppler imaging of lower limb arteries. Total 88 consecutive diabetic patients were included in this study. Out of them 48 were diagnosed cases of diabetic neuropathy (group I) and 40 were diabetic without neuropathy (Group II). In all patients the Ankle Brachial Index (ABI) and Pulsatility Index (PI) were recorded on both left and right lower limb arteries, by using duplex colour Doppler technique. Total no. of patients were 88. 48 had neuropathy. They were 27-57 yrs of age. Result: Unpaired‘t’ test was used to find out relationship between the variables.P value <o.o5 was considered as statistically significant. The mean ABI was 1.44±0.07, ranged from 1.30 to 1.59 in group I (diabetic neuropathy) and 1.17±0.06, ranged from 1.05 to 1.26 in group II (diabetic without neuropathy). The mean ABI difference was found statistically significant (p<0.05) between group I and group II. The mean PI was 3.0±0.69, ranged from 1.18 to 3.68 and 7.97±2.29,ranged from 5.50 to 13.0 in group I (diabetic neuropathy) and group II (diabetic without neuropathy) respectively. The mean PI difference was found statistically significant (p<0.05) between group I (diabetic neuropathy) and group II (diabetic without neuropathy). Conclusion: In this study it was observed that Pulsatility Index (PI) decreased and Ankle Brachial Index (ABI) increased in diabetic neuropathic group. There was significant difference of Pulsatility Index (PI) and Ankle Brachial Index (ABI) found between diabetic subjects with and without neuropathy. So, from the finding of the present work, it can be said that diabetic neuropathy affect the arterial flow detected by non invasive duplex colour Doppler imaging may help in proper patient management and may prevent neuropathic arterial complications. But for any definine conclusion, bigger appropriate study should be done.DOI: http://dx.doi.org/10.3329/birdem.v2i2.12309 (Birdem Med J 2012; 2(2): 89-92)


Author(s):  
Laily Indrayanti ◽  
Harjo Mulyono

Lactic acid is an intermediate product of carbohydrate metabolism. Increment of plasma lactic acid level usually correlated withaerobic metabolism defect which caused by hypoperfusion or hypoxia, that can be happened in DM (Diabetes Mellitus) patients. DiabetesMellitus is a risk factor of lactic acidosis. Determination of glycated Hb (HbA1c) is a parameter to monitor the blood glucose. The aimof this study is to compare the mean lactic acid level between uncontrolled and controlled DM) patients and their correlation betweenlactic acid and HbA1c level. The research carried out by cross sectional study which was done at the Clinical Pathology Laboratory ofSardjito Hospital between September–October 2007. Inclusion criteria of samples were diabetic patients who had HbA1c examination.Statistical analysis was done by independent t test and Pearson correlation test. Twenty one patients were included in this research.They were divided into two (2) groups, group I are those who had HbA1c ≤ 7%, they consist of 10 patients, group II are patients whohad HbA1c ≥ 7.1%, they consist 11 patients. The mean of lactic acid of group I was 1.85 mmol/L and group II was 1.74 mmol/L (p = 0.574). There wasn’t any significant correlation between HbA1c level and lactic acid. (r = -0.179, p = 0.437). The mean of lacticacid level in uncontrolled DM was lower than the controlled one but not significant, and there was no significant correlation betweenHbA1c level and lactic acid. It is suggested to continue this study but with larger sample to know the correlation between lactic acid andHbA1c in DM patients who had metformin therapy.


2020 ◽  
Vol 26 (2) ◽  
pp. 127-135 ◽  
Author(s):  
David I. Sandberg ◽  
Natasha Kharas ◽  
Bangning Yu ◽  
Christopher F. Janssen ◽  
Amanda Trimble ◽  
...  

OBJECTIVEChemotherapy infusions directly into the fourth ventricle may play a role in treating malignant fourth-ventricular tumors. This study tested the safety and pharmacokinetics of short-term and long-term administration of MTX110 (soluble panobinostat; Midatech Pharma) into the fourth ventricle of nonhuman primates.METHODSFour rhesus macaque monkeys underwent posterior fossa craniectomy and catheter insertion into the fourth ventricle. In group I (n = 2), catheters were externalized and lumbar drain catheters were placed simultaneously to assess CSF distribution after short-term infusions. MTX110 (0.5 ml of 300 μM panobinostat solution) was infused into the fourth ventricle daily for 5 consecutive days. Serial CSF and serum panobinostat levels were measured. In group II (n = 2), fourth-ventricle catheters were connected to a subcutaneously placed port for subsequent long-term infusions. Four cycles of MTX110, each consisting of 5 daily infusions (0.5 ml of 300 μM panobinostat solution), were administered over 8 weeks. Animals underwent detailed neurological evaluations, MRI scans, and postmortem histological analyses.RESULTSNo neurological deficits occurred after intraventricular MTX110 infusions. MRI scans showed catheter placement within the fourth ventricle in all 4 animals, with extension to the cerebral aqueduct in 1 animal and into the third ventricle in 1 animal. There were no MRI signal changes in the brainstem, cerebellum, or elsewhere in the brains of any of the animals. Histologically, normal brain cytoarchitecture was preserved with only focal mild postsurgical changes in all animals. Panobinostat was undetectable in serum samples collected 2 and 4 hours after infusions in all samples in both groups. In group I, the mean peak panobinostat level in the fourth-ventricle CSF (6242 ng/ml) was significantly higher than that in the lumbar CSF (9 ng/ml; p < 0.0001). In group II, the mean peak CSF panobinostat level (11,042 ng/ml) was significantly higher than the mean trough CSF panobinostat level (33 ng/ml; p < 0.0001).CONCLUSIONSMTX110 can be safely infused into the fourth ventricle in nonhuman primates at supratherapeutic doses. Postinfusion CSF panobinostat levels peak immediately in the fourth ventricle and then rapidly decrease over 24 hours. Panobinostat is detectable at low levels in CSF measured from the lumbar cistern up to 4 hours after infusions. These results will provide background data for a pilot clinical trial in patients with recurrent medulloblastoma.


2020 ◽  
Vol 9 (11) ◽  
pp. 3689
Author(s):  
Woong Chol Kang ◽  
Minsu Kim ◽  
Sang Min Park ◽  
Byeong-Keuk Kim ◽  
Byoung-Kwon Lee ◽  
...  

This study aimed to evaluate the efficacy of pitavastatin pretreatment on contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) after a coronary procedure. This was a prospective, randomized, double-blinded, placebo-controlled, multicenter clinical trial. All consecutive 70 patients with CKD (eGFR < 60 mL/min/1.73 m2) were enrolled and randomized into two groups. Group I consisted of patients who were treated with statins (pitavastatin 4 mg/day) for seven days before and three days after the procedure (n = 37, 52.9%), and group II consisted of patients who were treated with a placebo (n = 33, 47.1%). The primary endpoint was the incidence of CIN, and the secondary endpoints were the change in serum creatinine (∆sCr) level and estimated glomerular filtration rate (∆eGFR) after the procedure. The mean age of the patients (males, 74%) was 70.4 ± 9.0 years. After the coronary procedure, the incidence of CIN was lower in group I than in group II, but the difference was not significant (5.4% vs. 9.1%, p = 0.661). The maximal ∆sCr was lower and the maximal ∆eGFR was higher in group I than in group II, but the difference was not significant (−0.11 ± 0.53 mg/dL and −0.04 ± 0.33 mg/dL, p = 0.678; 4.3 ± 11.2 mL/min/1.73 m2 and −2.9 ± 20.4 mL/min/1.73 m2, p = 0.161, respectively). This study showed the possibility of a clinical benefit of pretreatment with a high dose of pitavastatin for the prevention of CIN in patients with CKD after coronary procedure (ClinicalTrials.gov Identifier: NCT01871792).


2012 ◽  
Vol 5 (1) ◽  
pp. 37-43
Author(s):  
ABMM Alam ◽  
M Moniruzzaman ◽  
MB Alam ◽  
N Islam ◽  
F Khatoon ◽  
...  

Background: CIN has gained increased attention in the clinical setting, particularly during cardiac intervention but also in many other radiological procedures in which iodinated contrast media are used. There is at present good clinical evidence from well-controlled randomized studies that CIN is a common cause of acute renal dysfunction.Methodology: This was a prospective study conducted among the patients who underwent coronary angiography and percutaneous coronary intervention in the Department of Cardiology, Dhaka Medical College Hospital during January 2010 to December 2010. A total of 111 patients age range from 25 to 75 years were included in the study. Serum creatinine level at baseline and at the end of 48 hours was done in all these patients. Study population was divided into two groups according to development of acute kidney injury (AKI). Group-I = AKI, Group II = Not developed AKI. Results: AKI developed 11.7% of the study patient. DM and Preexisting renal insufficiency were significantly higher in group I patients. HTN was (61.5% Vs 44.9%) higher in group I but not significantly. History of ACE inhibitor/ARB, NSAID intake and LVEF <40% were significantly higher in group I patients. The mean±SD volume of CM (Contrast Media) were 156.9±44.8 ml and 115.4±30.0 ml in group I and group II respectively, which was significant. The mean±SD of serum creatinine after 48-72 hours of CAG/PCI was 1.4±0.37 mg/dl and 1.1±0.2 mg/dl in group I and group II respectively. The serum creatinine level increased significantly (p<0.05) after 48-72 hours of CAG/PCI in group I. In group II, S. creatinine level increased but not significant (p>0.05). Impaired renal function was found 76.9% and 2.0% in group I and group II respectively. DM, HTN, preexisting renal insufficiency, ACE inhibitor/ARB, NSAIDs, contrast volume (>150 ml), eGFR (<60 ml/min/ 1.73m2) and LVEF (<40%) are significantly (p0.05) associated for CIN development.Conclusion: CIN is an iatrogenic but preventable disorder results from the administration of contract media. Although rare in the general population, CIN occurs frequently in patients with underlying renal dysfunction and diabetes. In patients with pre angiographic normal renal function, the prevalence is low but in pre-existing renal impairment it may pose a serious threat. Thus risk factors are synergistic in their ability to predispose to the development of CIN. A careful risk-benefit analysis must always be performed prior to the administration of contrast media to patients at risk for CIN. DOI: http://dx.doi.org/10.3329/cardio.v5i1.12227 Cardiovasc. j. 2012; 5(1): 37-43


2019 ◽  
Vol 2 (3) ◽  
pp. 137-141
Author(s):  
Padma Raj Dhungana ◽  
Rajesh Adhikari ◽  
Prem Raj Pageni ◽  
Apsara Koirala ◽  
Anand Nepal

Background: Labor is a naturally occurring physiological process associated with uterine contractions, effacement, dilatation of cervix and descent of presenting part. Drotaverine hydrochloride is a non-anticholinergic isoquinoline derivative which acts by elevating intracellular cyclic Adenosine Mono Phosphate (cAMP) and cyclic Guanosine Mono Phosphate (cGMP) promoting smooth muscle relaxation. Materials and Method: This was a hospital based prospective study on effectiveness of Drotaverine Hydrochloride on enhancing dilatation of cervix and acceleration of active phase of labor. The sample size was 100. Fifty cases of women in active phase of labor received injection drotaverine hydrochloride 40 mg (group i) and fifty cases of women did not receive any drug (group ii) among those at term with singleton pregnancy and vertex presentation. Variables like maternal age, interval between administration of drug and delivery, mode of delivery, apgar score at 5 minutes, NCU (Neonatal Care Unit) admission and neonatal outcomes were recorded. Data analysis was done with the help of SPSS program. Results: The mean interval between drug administration to delivery in primipara and multipara in group i was 3.05 hours and 2.31 hours while in group ii was 4.5 hours and 3.75 hours respectively. The mean interval between drug administration and delivery was shorter in both groups of multipara. In group i, 96% had normal delivery and 4 % had vacuum delivery and in group ii 90% and 10% had normal delivery and vacuum delivery respectively. None of the participants had caeserian section. There were no perinatal mortalities. Conclusion: The administration of drug Drotaverine Hydrochloride is effective in shortening duration of labor with favorable feto-maternal outcome.  


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