Increase of Urinary 5-Hydroxyindoleacetic Acid Excretion but Not Serum Chromogranin a Following Over-The-Counter 5-Hydroxytryptophan Intake

BACKGROUND: 5-hydroxyindoleacetic acid (5-HIAA) excretion is commonly measured for biochemical detection of carcinoid tumours. A 77-year-old woman was referred for elevated 24 h urine 5-HIAA excretion (510 μmol/day; normal is less than 45 μmol/day) and serum chromogranin A (CgA) (72.1 U/L; normal is less than 18 U/L), both subsequently normalized after discontinuation of 5-hydroxytryptophan (5-HTP). 5-HTP, a precursor of serotonin, is not commonly listed as a substance that increases 5-HIAA levels in urine. The effect of 5-HTP on CgA has not been previously described.OBJECTIVES: To determine whether, and to what extent, oral 5-HTP increases urine 5-HIAA excretion and serum CgA levels in healthy volunteers.PATIENTS AND METHODS: A randomized, prospective, double-blind, placebo-controlled crossover study, with a four-day washout period, was performed in a general community setting. Eight healthy subjects aged 22 to 58 years were recruited by advertising. Bedtime ingestion of 5-HTP 100 mg/day was compared with placebo ingestion for 10 days. Twenty-four hour urine excretion of 5-HIAA and serum CgA were the main outcome measures.RESULTS: Median (range) urinary 5-HIAA excretion was 204 μmol/day (22 μmol/day to 459 μmol/day) during 5-HTP intake, compared with 18 μmol/day (12 μmol/day to 36 μmol/day) during placebo intake (P=0.017). 5-HTP did not affect clinical symptoms or serum CgA levels.CONCLUSIONS: Oral 5-HTP increases urinary 5-HIAA excretion with considerable interindividual variation. In a small number of subjects, oral 5-HTP did not affect serum CgA levels. Therefore, increased 5-HIAA levels with normal CgA levels may suggest 5-HTP ingestion. The use of over-the-counter 5-HTP should be excluded as the cause of increased urinary 5-HIAA levels before initiating diagnostic tests to search for a carcinoid tumour. 5-HTP should be added to popular references as a substance that may cause increased 5-HIAA excretion.

Download Full-text

Treatment of Lead-exposed Children

PEDIATRICS ◽

10.1542/peds.98.1.161a ◽

1996 ◽

Vol 98 (1) ◽

pp. 161-162

Author(s):

Steven M. Marcus

Keyword(s):

Lead Poisoning ◽

Lead Exposure ◽

Treatment Guidelines ◽

Clinical Symptoms ◽

Double Blind ◽

Developmental Abnormalities ◽

Lead Encephalopathy

I am writing in response to the recommendations in the statement "Treatment Guidelines for Lead Exposure in Children," by the Committee on Drugs, reported in the July 1995 issue of Pediatrics. The Committee did an admirable job in reviewing the various aspects of treating lead poisoning; however, there are several points that were made that need to be clarified. Although no one would argue that treatment is indicated for lead encephalopathy, there have been no studies, to my knowledge, of a double-blind, controlled nature, showing that treatment of lead poisoning, in the absence of clinical symptoms, is of any use in either reversing any neurologic or developmental abnormalities or, in fact, in prevention of such.

Download Full-text

Clinical Trial of Efficacy and Toxicity of Disoproxil Tenofovir Fumarate and Emtricitabine for Mild to Moderate SARS-CoV-2 Infections

10.1101/2021.09.28.21264242 ◽

2021 ◽

Author(s):

Aldo A M Lima ◽

Erico A G Arruda ◽

Roberto J Pires-Neto ◽

Melissa S Medeiros ◽

J Quirino-Filho ◽

...

Keyword(s):

Clinical Trial ◽

Vitamin C ◽

Respiratory Infection ◽

Clinical Symptoms ◽

Clinical Signs ◽

Signs And Symptoms ◽

Clinical Suspicion ◽

Pharmacological Intervention ◽

Controlled Clinical Trial ◽

Double Blind

This study aimed to evaluate the efficacy and toxicity of tenofovir (TDF) and TDF combined with emtricitabine (TDF/FTC) in patients with mild to moderate COVID-19 infections. We conducted a randomized, double-blind, placebo-controlled clinical trial in patients with clinical suspicion of mild to moderate respiratory infection caused by SARS-CoV-2 who were treated at an outpatient clinic. Patients were randomly recruited to take 10 days of TDF (300 mg/day), TDF (300 mg/day) combined with FTC (200 mg/day) or placebo Vitamin C (500 mg/day). The primary parameter was the score of symptoms and predictive signs of COVID-19, assessed on the seventh day of patient follow-up. From a total of 309 patients with clinical suspicion of SARS-CoV-2, 227 met the inclusion criteria and were randomly distributed into the following groups: (a) 75 (one did not initiate treatment) in the TDF group; (b) 74 in the TDF combined with FTC group; and (c) 77 in the Vitamin C group (placebo). Of the 226 patients, 139 (62%) were positive for SARS-CoV-2. Fever (37.8oC), ageusia or dysgeusia, anosmia or dysosmia, and two or more clinical symptoms or signs were significantly associated with SARS-CoV-2 infection. There was no significant change in clinical score based on clinical symptoms and signs between treatment groups. Patients with mild to moderate infection by SARS-CoV-2 had higher concentrations of G-CSF, IL-1β, IL-6 and TNF-α compared to patients without infection. Patients with mild to moderate respiratory infection, with fever (37.8oC), loss of smell, loss of taste and two or more symptoms, have a better prediction for the diagnosis of COVID-19. Patients with SARS-CoV-2 showed higher and more persistent proinflammatory cytokines profile compared to patients not infected with SARS-CoV-2. Pharmacological intervention with TDF or TDF combined with FTC did not change the clinical signs and symptoms score in mild to moderate respiratory infection in patients with SARS-CoV-2 compared to the Vitamin C group (placebo).

Download Full-text

The Effects of Propolis Extract Administration on HIV Patients Receiving ARV

The Indonesian Biomedical Journal ◽

10.18585/inabj.v13i1.1381 ◽

2021 ◽

Vol 13 (1) ◽

pp. 75-83

Author(s):

Erwin Astha Triyono ◽

Sarah Firdausa ◽

Heru Prasetyo ◽

Joni Susanto ◽

James Hutagalung ◽

...

Keyword(s):

Quality Of Life ◽

Placebo Group ◽

Clinical Symptoms ◽

Cd4 Count ◽

Controlled Clinical Trial ◽

Human Immune System ◽

Hiv Patients ◽

Double Blind ◽

Significant Difference

BACKGROUND: Human immunodeficiency virus (HIV) is an infectious disease that targets the human immune system by attacking cluster of differentiation (CD)4 cells. The use of propolis in HIV patients is expected to be safe and beneficial in terms of increasing endurance and immunity by its role in increasing CD4 level. This study aimed to analyze the influence of propolis supplementation in increasing the CD4 level in anti-retroviral (ARV)-treated HIV patients.METHODS: Double-blind randomized controlled clinical trial was conducted in 50 HIV patients who took regular ARV therapy. The subjects were divided into two groups, one group was treated with ARV and propolis, while another one was given ARV and placebo. The CD4 cell count was measured during pre-treatment, in the 3rd month, in the 6th month after treatment. The level of hemoglobin, leukocyte, and platelets were also measured. The SF-12 questionnaire was used to evaluate quality of life of the subject.RESULTS: Out of 50 subjects, 43 subjects completed the study, which were 19 subjects from the propolis group and 24 subjects from the placebo group. After 3-month of treatment, there was a statistically significant difference in the incrwase of CD 44 level in propolis group, while the increment was not significant in the placebo group. After 6-month treatment, the increase of CD4 level was occurred in both groups, propolis and placebo, however the increment was not statistically significant. The levels of hemoglobin, leukocyte, and platelets were not altered by the treatment and remained normal throughout the study. The quality of life was improved during the study; however, it was also not statistically significant. Mild adverse events occurred in 3 subjects which were relieved after the treatment stopped.CONCLUSION: Based on the result of this study, the administration of propolis on HIV patients receiving ARV bring significant difference in the increase of CD4 in propolis group from baseline to 3 month after the treatment. While in placebo group, this increment was not significant. At the end of study, CD4 count continued to rise up, however the increase was not statistically significant. There are no hemoglobin, leukocyte, platelets, and quality of life abnormalities. Therefore, it is necesary to do further research with a spesific CD4 count. However, it may be beneficial in relieving the clinical symptoms and quality of life of patient living with HIV.KEYWORDS: CD4, ARV, HIV, propolis

Download Full-text

A Single Administration of AZP-3601, a Novel, Long-Acting PTH Analog, Induces a Significant and Sustained Calcemic Response: Preliminary Data From a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.516 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A254-A254

Author(s):

Soraya Allas ◽

Michel Ovize ◽

Michael D Culler ◽

Clarisse Geraul ◽

Jeroen van de Wetering ◽

...

Keyword(s):

Serum Calcium ◽

Clinical Symptoms ◽

Phase 1 ◽

High Dose ◽

Single Administration ◽

Double Blind ◽

Double Blind Placebo ◽

Healthy Humans ◽

Dose Dependent

Abstract Hypoparathyroidism is a rare disease characterized by a deficiency in parathyroid hormone (PTH) that results in hypocalcemia and hyperphosphatemia. Current treatment approaches, including high dose oral calcium and active vitamin D, as well as recombinant human PTH (1–84), do not provide adequate or consistent control of either serum calcium or clinical symptoms over a full 24-hour period. AZP-3601 is a novel 36 amino-acid PTH analog that has been designed to potently bind to the R0 conformation of the PTH1 receptor, which results in prolonged signaling responses in vitro and prolonged calcemic responses in animals despite having a short circulating half-life. A Phase 1 double-blind, placebo-controlled, single and multiple ascending dose study is being conducted to evaluate the safety, tolerability and pharmacodynamics of AZP-3601 in healthy adults. Here we report data from the first cohorts of the single ascending dose portion of the study. Sequential cohorts of 4 (cohort 1) to 8 (cohort 2 to 4) healthy male subjects aged 18–60 years, with a body mass index of 19–28 kg/m2, were assigned to receive 5, 10, 20 or 40μg of AZP-3601 or placebo at a ratio of 3:1. The study drug was administered in the morning by subcutaneous injection in the abdominal wall and was well tolerated with no remarkable adverse events. As compared with placebo controls, AZP-3601 treatment produced a clear, dose-dependent increase in mean albumin-adjusted serum calcium values from baseline. The normal physiological diurnal variation of albumin-adjusted serum calcium was gradually attenuated with 5 and 10μg AZP-3601, and was completely eliminated with 20μg. With the dose of 40μg AZP-3601, mean albumin-adjusted serum calcium values were significantly increased but stayed within normal laboratory range and remained elevated through at least 24 hours post-administration. We observed a dose-dependent decrease in mean endogenous serum PTH that was significantly correlated with the concomitant increase in mean serum calcium. These data provide initial evidence of the pharmacodynamic effect of AZP-3601 in healthy humans characterized by a sustained calcemic response for at least 24 hours following a single administration.

Download Full-text

Indolent Neuroendocrine Tumor Involving the Bone Marrow

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-0488-intitb ◽

2003 ◽

Vol 127 (4) ◽

pp. 488-491

Author(s):

Ellen Schlette ◽

L. Jeffrey Medeiros ◽

Miloslav Beran ◽

Carlos E. Bueso-Ramos

Keyword(s):

Bone Marrow ◽

Neuroendocrine Tumor ◽

Bone Marrow Biopsy ◽

Clinical Symptoms ◽

Eosinophilic Cytoplasm ◽

Hydroxyindoleacetic Acid ◽

History Of ◽

Cardiac Valve Disease ◽

Immunohistochemical Studies

Abstract We report a unique case of a patient with a neuroendocrine tumor localized to the bone marrow. The patient had a history of hairy cell leukemia, and the neuroendocrine tumor was detected in a bone marrow biopsy specimen obtained to assess response to 2-chlorodeoxyadenosine therapy. The neuroendocrine tumor was present as nodules that replaced approximately 15% of the bone marrow medullary space and was composed of round cells with fine chromatin, indistinct nucleoli, and relatively abundant, granular, eosinophilic cytoplasm. Histochemical stains showed cytoplasmic reactivity with Grimelius and Fontana-Masson stains, and immunohistochemical studies showed positivity for keratin and chromogranin. The histologic, cytochemical, and immunohistochemical features resembled a carcinoid tumor, and metastasis to the bone marrow was considered initially. The patient was asymptomatic without diarrhea, flushing, or cardiac valve disease. Serotonin production, assessed by the measurement of serum 5-hydroxyindoleacetic acid and substance P levels, was normal. Extensive clinical and radiologic work-up and endoscopy of the gastrointestinal tract to detect a primary site other than the bone marrow were negative. Follow-up bone marrow biopsy 7 years after the initial diagnosis was positive for persistent neuroendocrine tumor. The patient has not received any therapy specific for the neuroendocrine tumor and has had no clinical symptoms or evidence of progression after 9 years of clinical follow-up. We suggest that this neuroendocrine tumor may have arisen in the bone marrow.

Download Full-text

Effects of curcumin-piperine co-supplementation on clinical signs, duration, severity, and inflammatory factors in patients with COVID-19: a structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-020-04924-9 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Mahsa Miryan ◽

Mohammad Bagherniya ◽

Amirhossein Sahebkar ◽

Davood Soleimani ◽

Mohammad Hossein Rouhani ◽

...

Keyword(s):

Clinical Trial ◽

Sample Size ◽

Inflammatory Mediators ◽

Disease Duration ◽

Clinical Symptoms ◽

Clinical Signs ◽

Inflammatory Factors ◽

Double Blind ◽

Full Protocol ◽

To Receive

Abstract Objectives This study aims to investigate the efficacy of curcumin-piperine co-supplementation on disease duration, severity and clinical symptoms, and inflammatory mediators in patients with coronavirus (COVID-19). Trial design This is a randomized, placebo-controlled, double-blind, parallel arm clinical trial. Participants All patients aged 20-75 years with the diagnosis of Covid-19 based on the PCR test. The exclusion criteria will include an age less than 20 and more than 75 years, current use of warfarin or other anticoagulant drugs, and the presence of sensitivity to herbal products such as turmeric and pepper. This study will be conducted in academic hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. Intervention and comparator Fifty outpatients will be randomly allocated in a ratio of 1:1 to receive a capsule of curcumin-piperine containing 500 mg curcumin plus 5 mg piperine or matching placebo containing 505 mg maltodextrin twice a daily, after lunch and dinner, over a period of 2 weeks. Similarly, 50 inpatients who are admitted to hospital wards excluding intensive care unit (ICU) will be randomly assigned in a ratio of 1:1 to receive a capsule curcumin-piperine or matching placebo (provided by the Sami Labs company) twice a daily, after lunch and dinner, over a period of 2 weeks. Main outcomes The main outcomes of this study are the efficacy of curcumin-piperine on coronavirus disease’s clinical symptoms, duration, severity, and inflammatory mediators after 2 weeks of curcumin-piperine co-supplementation. Randomisation Randomization sequences will be generated with the use of a random-number table with a permuted block design (block size of 4) and stratification according to the gender variable (male vs. female). These sequences will be prepared by an independent statistician and will be kept in opaque, sealed, numbered envelopes which will be opened only at the time of enrollment. The allocation ratio in intervention and control groups is 1:1. Researchers and all patients will be unaware of the study-group assignment until the completion of data analyses. Blinding (masking) This study is a double-blind clinical trial (participant, researcher). The curcumin-piperine and placebo supplements are packaged in similar numbered drug containers, and the researcher and all patients will be unaware of the study assignment until the end of the study. Numbers to be randomised (sample size) The calculated total sample size is 100 patients, with 25 patients in each group. Trial Status The protocol is Version 2.0, May 24, 2020. Recruitment began May 4, 2020, and is anticipated to be completed by April 19, 2021. Trial registration This trial has been registered by the title of “Effect of curcumin-piperine co-supplementation on disease duration, severity and clinical signs, and inflammatory factors in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial study” in the Iranian Registry of Clinical Trials (IRCT) with code “IRCT20121216011763N46”, https://www.irct.ir/trial/47529. The registration date is May 4, 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Download Full-text

PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression—A Randomized Controlled Trial

Nutrients ◽

10.3390/nu12113422 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3422

Author(s):

Eva Z. Reininghaus ◽

Martina Platzer ◽

Alexandra Kohlhammer-Dohr ◽

Carlo Hamm ◽

Sabrina Mörkl ◽

...

Keyword(s):

Gut Microbiota ◽

Clinical Symptoms ◽

Psychiatric Symptoms ◽

Controlled Trial ◽

Intervention Group ◽

Double Blind ◽

16S Rrna Analysis ◽

Brain Functions ◽

Β Diversity ◽

Probiotic Treatment

Gut microbiota are suspected to affect brain functions and behavior as well as lowering inflammation status. Therefore, an effect on depression has already been suggested by recent research. The aim of this randomized double-blind controlled trial was to evaluate the effect of probiotic treatment in depressed individuals. Within inpatient care, 82 currently depressed individuals were randomly assigned to either receive a multistrain probiotic plus biotin treatment or biotin plus placebo for 28 days. Clinical symptoms as well as gut microbiome were analyzed at the begin of the study, after one and after four weeks. After 16S rRNA analysis, microbiome samples were bioinformatically explored using QIIME, SPSS, R and Piphillin. Both groups improved significantly regarding psychiatric symptoms. Ruminococcus gauvreauii and Coprococcus 3 were more abundant and β-diversity was higher in the probiotics group after 28 days. KEGG-analysis showed elevated inflammation-regulatory and metabolic pathways in the intervention group. The elevated abundance of potentially beneficial bacteria after probiotic treatment allows speculations on the functionality of probiotic treatment in depressed individuals. Furthermore, the finding of upregulated vitamin B6 and B7 synthesis underlines the connection between the quality of diet, gut microbiota and mental health through the regulation of metabolic functions, anti-inflammatory and anti-apoptotic properties. Concluding, four-week probiotic plus biotin supplementation, in inpatient individuals with a major depressive disorder diagnosis, showed an overall beneficial effect of clinical treatment. However, probiotic intervention compared to placebo only differed in microbial diversity profile, not in clinical outcome measures.

Download Full-text

On the pharmacological effects of two lidocaine concentrations tested on spontaneous and evoked pain in human painful neuroma: A new clinical model of neuropathic pain

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2013.07.012 ◽

2013 ◽

Vol 4 (4) ◽

pp. 258

Author(s):

Adriana Miclescu ◽

Björn Hägglöf ◽

Martin Schmelz ◽

Torsten Gordh

Keyword(s):

Neuropathic Pain ◽

Clinical Symptoms ◽

Control Level ◽

New Drugs ◽

Spontaneous Pain ◽

Double Blind ◽

Clinical Model ◽

Analgesic Effects ◽

Proposed Model ◽

Before And After

AbstractAimsSpontaneous and evoked pains are key symptoms of patients with neuropathic pain and there is a current discussion on the predictive value of evoked pain read outs for the reduction of spontaneous pain. Here we describe a new clinical model of neuropathic pain that may be useful for evaluation of new drugs. We also report the effects of lidocaine in this model as reference values.MethodsIn a randomized double-blind experiment, the analgesic effects of local lidocaine were investigated separately for spontaneous pain and for stimulus-evoked allodynia and hyperalgesia in sixteen patients with painful neuromas after traumatic nerve injuries in the upper extremities. The patterns of sensory changes were compared before and after treatment with lidocaine (0.1% or 0.5%, 1 ml), with 1–2 weeks interval, injected close to the neuroma. Spontaneous and evoked pains were assessed using a visual analogue scale (VAS) and quantitative/qualitative sensory testing.ResultsLidocaine dose-dependently reduced spontaneous and evoked pain scores by more than 90% with maximum effects between 1 and 5 min for evoked pain and between 3 and 15 min for spontaneous pain. While evoked pain normalized rapidly reaching about 50% of the control level 20 minutes after the injection spontaneous pain levels were lower than 25% at this time. Moreover, in 4 patients the reduction of ongoing pain lasted 24 h whereas evoked pain had returned to baseline levels in all the patients after 1 h.ConclusionDifferential analgesic effects of local lidocaine on spontaneous and evoked pain suggest that different mechanism underlie these two key clinical symptoms. Thus, clinical trials assessing localized traumatic neuropathic pain should investigate both aspects of pain separately with the proposed model allowing testing of new drugs systemically or locally administered.

Download Full-text

Bioavailability of isoflavone phytoestrogens in postmenopausal women consuming soya milk fermented with probiotic bifidobacteria

British Journal Of Nutrition ◽

10.1079/bjn20041299 ◽

2005 ◽

Vol 93 (6) ◽

pp. 867-877 ◽

Cited By ~ 41

Author(s):

Dimitri Tsangalis ◽

Gisela Wilcox ◽

Nagendra P. Shah ◽

Lily Stojanovska

Keyword(s):

Postmenopausal Women ◽

Dosage Level ◽

Protein Isolate ◽

Soya Protein ◽

Interindividual Variation ◽

Double Blind ◽

Soya Milk ◽

Percentage Recovery ◽

Supplementation Period ◽

Double Blind Crossover Study

We investigated the effects of consuming an isoflavone aglycone-enriched soya milk containing viable bifidobacteria on urinary isoflavone excretion and percentage recovery. Sixteen postmenopausal women were randomly divided into two groups to consume either fermented or non-fermented soya milk. Each group participated in a double-blind, crossover study with three 14 d supplementation periods, separated by a 14 d washout. Subjects ingested three daily dosages of isoflavone via the soya milk and collected four 24 h pooled urine specimens per supplementation period. Soya milks were prepared with soya protein isolate and soya germ, followed by fermentation with bifidobacteria. Isoflavone levels were quantified using HPLC. Non-fermented soya milks at 20, 40 and 80 mg isoflavone/200 ml contained 10 %, 9 % and 7 % aglycone, respectively, with their fermented counterparts containing 69 %, 57 % and 36 % aglycone (P<0·001). A trend to a greater percentage urinary recovery of daidzein and glycitein was observed among women consuming fermented soya milk at a dosage of 40 mg isoflavone (P=0·13). A distinct linear dose response for the fermented soya milk group (R2=0·9993) compared with the non-fermented group (R2=0·8865) suggested less interindividual variation in isoflavone absorption. However, total urinary isoflavone excretion was similar for both groups (P>0·05), with urinary isoflavone recovery at approximately 31 %. Increasing the isoflavone dosage correlated positively with its urinary excretion, but urinary percentage recovery of isoflavone was inversely related to dosage level. Hence, a modest dosage ranging from 20 to 30 mg/d may provide the most bioavailable source of isoflavone, regardless of whether it is via an aglycone-rich fermented soya milk or a glucoside-rich soya milk.

Download Full-text

RESTING MYOCARDIAL ISCHEMIA AFTER INTRAVENOUS INFUSION OF BM 13.177, A THROMBOXANE RECEPTOR ANTAGONIST

10.1055/s-0038-1643466 ◽

1987 ◽

Author(s):

W Terres ◽

W Kupper ◽

C Hamm ◽

W Bleifeld

Keyword(s):

Myocardial Ischemia ◽

Receptor Antagonist ◽

Clinical Symptoms ◽

Ex Vivo ◽

Controlled Trial ◽

Double Blind ◽

Thromboxane Receptor ◽

Exertional Angina ◽

Thromboxane Receptors ◽

Thromboxane Receptor Antagonist

We conducted a double blind placebo controlled trial of BM 13.177, a thromboxane receptor antagonist, given intravenously in patients (PTS) with stenoses >70 % of the left anterior descending coronary artery and stable exertional angina pectoris (AP). The study had to be stopped after enrollment of 8 PTS, because 2 had developed resting AP after initiation of the study medication. Both proved to belong to the 4 PTS who had received BM 13.177 (12.5 mg/min). While in one PT, AP was mild, transient and associated with only slight decreases in coronary sinus blood flow (CSBF) and myocardial lactate extraction (MLE), in the other, AP was severe and persisted for 30 minutes in spite of antianginal therapy. Severe clinical symptoms in this PT were associated with a marked fall in MLE from +24 to -121 %. Two PTS under BM 13.177 and 4 on placebo underwent supraventricular stimulation. For both groups, no change in clinical symptoms, CSBF or MLE occured in comparison to a former control stimulation without medication. BM 13.177 led to an inhibition of ex vivo platelet aggregation induced by collagen 1 pg/ml (mean reduction in rate of aggregation by 41 %, p< 0.05), while aggregation was not influenced with collagen 5 μg/ml or ADP. This effect of BM on platelets is explained by its thromboxane receptor blocking properties. The induction of resting myocardial ischemia, however, in 2 of 4 PTS with formerly stable exertional AP may have been the result of either a coronary steal mechanism or an intrinsic stimulation of vascular thromboxane receptors, followed by coronary vasoconstriction.

Download Full-text