ABSTRACT
Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.
Subject(s)
Brain Neoplasms , Glioblastoma , Mutation , Protein Kinase Inhibitors , Proto-Oncogene Proteins B-raf , Humans , Proto-Oncogene Proteins B-raf/genetics , Male , Adult , Glioblastoma/genetics , Glioblastoma/drug therapy , Glioblastoma/pathology , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Brain Neoplasms/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinase Kinases/geneticsABSTRACT
INTRODUCTION: Propylene glycol (PG) is usually considered safe, however, toxicity can develop with high doses or when used for prolonged periods of time. PG can be found in some medications as well as some food products. We report a case of likely PG toxicity that occurred after compulsive daily ingestion of large amounts of corn starch. CASE REPORT: Our patient initially presented to an outside hospital (OSH) via ambulance for altered mental status. Her mental status improved after her blood sugar of 25 was corrected. On admission to OSH Emergency Department her initial vital signs included a heart rate of 115 bpm, blood pressure 113/59 mm/hg, temperature 35.8C. Pertinent labs included: sodium 119 mEq/L, bicarbonate 9 mEq/L, anion gap 29 mEq/L, creatinine 2.5 mg/dL and lactic acid 20 mEq/L. On transfer to our hospital her repeat lactic acid was 20 mEq/L, osmolar gap was 20. Her PG level, which was drawn several hours after her initial presentation, was 11 mg/dL. Our patient noted that she ingested a 16 oz. package of corn starch mixed with baking soda approximately every 2 days. Given the concerns for PG she was underwent intermittent hemodialysis. PG and lactic acid levels improved, however, she ultimately died due to complications from her hospitalization. DISCUSSION: PG causes toxicity through metabolism to lactic acid. While there are small amounts in food products and medications, under the right circumstances, PG can accumulate and lead to significant toxicity.
Subject(s)
Starch , Zea mays , Compulsive Behavior , Eating , Female , Humans , Lactic Acid , Propylene Glycol/toxicitySubject(s)
Clonal Evolution , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/genetics , Preleukemia/genetics , Adult , Female , Humans , Living Donors , Male , Middle Aged , Preleukemia/drug therapy , Preleukemia/therapy , Transplantation Conditioning , Exome SequencingABSTRACT
OBJECTIVE: Cervical artificial disc replacement (C-ADR) was developed with the goal of preserving mobility of the cervical segment in patients with degenerative disc disease. So far, little is known about experiences with revision surgery and explantation of C-ADRs. Here, we report our experience with revision the third generation, Galileo-type disc prosthesis from a retrospective study of two institutions. PATIENTS AND METHODS: Between November 2008 and July 2016, 16 patients with prior implantation of C-ADR underwent removal of the Galileo-type disc prosthesis (Signus, Medizintechnik, Germany) due to a call back by industry. In 10 patients C-ADR was replaced with an alternative prosthesis, 6 patients received an ACDF. Duration of surgery, time to revision, surgical procedure, complication rate, neurological status, histological findings and outcome were examined in two institutions. RESULTS: The C-ADR was successfully revised in all patients. Surgery was performed through the same anterior approach as the initial access. Duration of the procedure varied between 43 and 80min. Access-related complications included irritation of the recurrent nerve in one patient and mal-positioning of the C-ADR in another patient. Follow up revealed two patients with permanent mild/moderate neurologic deficits, NDI (neck disability index) ranged between 10 and 42%. CONCLUSIONS: Anterior exposure of the cervical spine for explantation and revision of C-ADR performed through the initial approach has an overall complication rate of 18.75%. Replacements of the Galileo-type disc prosthesis with an alternative prosthesis or conversion to ACDF are both suitable surgical options without significant difference in outcome.
Subject(s)
Cervical Vertebrae/surgery , Intervertebral Disc Degeneration/surgery , Outcome Assessment, Health Care , Prostheses and Implants/adverse effects , Reoperation/methods , Total Disc Replacement/methods , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Total Disc Replacement/adverse effectsABSTRACT
This study evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34(+) blood cells to pre-empt relapse in patients with CD34(+) myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). At a median of 169 days after HSCT, 20/59 prospectively screened patients experienced a decrease of CD34(+) donor chimerism to <80% and received four azacitidine cycles (75 mg/m(2)/day for 7 days) while in complete hematologic remission. A total of 16 patients (80%) responded with either increasing CD34(+) donor chimerism to ≥80% (n=10; 50%) or stabilization (n=6; 30%) in the absence of relapse. Stabilized patients and those with a later drop of CD34(+) donor chimerism to <80% after initial response were eligible for subsequent azacitidine cycles. A total of 11 patients (55%) received a median of 4 (range, 1-11) additional cycles. Eventually, hematologic relapse occurred in 13 patients (65%), but was delayed until a median of 231 days (range, 56-558) after initial decrease of CD34(+) donor chimerism to <80%. In conclusion, pre-emptive azacitidine treatment has an acceptable safety profile and can substantially prevent or delay hematologic relapse in patients with MDS or AML and MRD after allogeneic HSCT.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Adult , Aged , Antimetabolites, Antineoplastic/adverse effects , Azacitidine/adverse effects , Chimerism , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/mortality , Neoplasm, Residual/therapy , Recurrence , Time Factors , Transplantation, Homologous , Treatment Outcome , Young AdultABSTRACT
This case report describes the unilateral acute reduction of vision in the right eye of a 48-year-old woman. The patient was otherwise healthy but 2 days previously had suffered from dizziness and blurred vision. Secondary to this, the patient had already been under dental treatment for 1 week due to gingival swelling. At the first examination a macular branch retinal vein occlusion and Roth spots were found in the right eye by indirect ophthalmoscopy. The immediate diagnostic procedure identified aute amyeloid leukemia (AML) as the cause of the vascular pathology. The AML can be manifested in different ways and the retina is involved in approximately 50% of cases. Due to a secondary hyperviscosity syndrome, which is found in approx. 20% of acute leukaemias, symptomatic central vein occlusion or macular branch vein occlusion can occur. Ophthalmic symptoms can be the first and only signs to be detected. Therefore, ophthalmologists should also consider a systemic disease and initiate a clarification. A differential blood count is indispensable. The results usually improve by a rapidly arranged and suitable therapy. Ophthalmological follow-up examinations are imperative as an initiated chemotherapy can also produce ophthalmological side-effects.
Subject(s)
Gingival Hyperplasia/diagnosis , Gingival Hyperplasia/etiology , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/etiology , Vision Disorders/etiology , Diagnosis, Differential , Female , Humans , Middle Aged , Vision Disorders/diagnosisSubject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Bone Marrow Transplantation , Cyclophosphamide/therapeutic use , Graft vs Host Disease/prevention & control , Leukemia/therapy , Lymphoma/therapy , Adult , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Salvage Therapy , Siblings , Survival Rate , Tissue Donors , Treatment Outcome , Young AdultABSTRACT
In cases of unclear depression of conciousness, arrhythmia and symptoms of cardiac insufficiency inadvertent carbon monoxide intoxication should always be taken into consideration. Rapid diagnosis of acute carbon monoxide intoxication with mostly unspecific symptoms requires an immediate supply of high dose oxygen which enables a distinct reduction of mortality and long-term morbidity. Levels of carboxyhemoglobin, however, should not be used as a parameter to decide whether to supply normobaric or the more efficient hyperbaric oxygen. There is no sufficient coherence between carboxyhemoglobin blood levels and clinical symptoms. Increased carboxyhemoglobin concentrations help to diagnose acute carbon monoxide intoxication but do not allow conclusions to be drawn about possible long-term neuropsychiatric or cardiac consequences.
Subject(s)
Carbon Monoxide Poisoning/blood , Carbon Monoxide Poisoning/therapy , Carboxyhemoglobin/analysis , Carbon Monoxide Poisoning/psychology , Humans , Hyperbaric Oxygenation , Mental Disorders/etiology , Mental Disorders/psychology , Monitoring, Physiologic , Predictive Value of Tests , Severity of Illness Index , Treatment OutcomeABSTRACT
Before elective surgery, it is mandatory that a precise history be taken to detect increased hemorrhagic diathesis and that thrombocytes, Quick/INR, and aPTT be determined. If pathological levels are found, further laboratory tests are necessary after frequent causes (e.g., liver cirrhosis) have been excluded. Single-factor analysis for the von Willebrand's factor antigen and if necessary further tests to check for von Willebrand's syndrome (multimeric analysis) as well as platelet function tests should be performed.Dysfibrinogenemia is a rare coagulation disorder, which causes elevated INR. It shows a wide spectrum of clinical manifestations including thrombophilia, excessive bleeding, and even asymptomatic cases. We present a 72-year-old patient with asymptomatic dysfibrinogenemia who needed hip replacement due to arthrosis. Lowered fibrinogen levels were substituted prior to operation and the clinical course afterwards was uneventful under additional prophylactic anticoagulation in order to prevent thrombosis. The case report illustrates the interdisciplinary teamwork which is very important in the management of patients with coagulation disorders.
Subject(s)
Afibrinogenemia/complications , Afibrinogenemia/therapy , Anticoagulants/administration & dosage , Arthroplasty, Replacement, Hip/adverse effects , Premedication/methods , Thrombosis/etiology , Thrombosis/prevention & control , Afibrinogenemia/diagnosis , Aged , Female , Humans , Perioperative Care/methods , Rare Diseases/prevention & control , Treatment OutcomeSubject(s)
Anesthetics , Conscious Sedation/methods , Endoscopy, Gastrointestinal/methods , Hypnotics and Sedatives , Anesthetics/adverse effects , Drug Therapy, Combination , Evidence-Based Medicine , Humans , Hypnotics and Sedatives/adverse effects , Patient Care Team , Quality Assurance, Health Care , Risk AssessmentABSTRACT
After a problem-free induction of anaesthesia for an elective aortocoronary bypass operation in a 64-year-old female patient, recurrent ventilation problems occurred. An externally intact but internally damaged anaesthesia tube caused an expiratory stenosis of varying extent. Based on this case, the safety of the algorithms for difficult ventilation, the knowledge necessary for a possible differential diagnosis, the necessity for knowledge on the alarm procedure of the anaesthesia apparatus, as well as strategies for risk reduction will be discussed.
Subject(s)
Anesthesia/adverse effects , Anesthesiology/instrumentation , Intraoperative Complications/etiology , Air Pressure , Algorithms , Apnea/etiology , Carbon Dioxide/analysis , Carbon Dioxide/metabolism , Coronary Artery Bypass , Equipment Failure , Equipment Safety , Female , Humans , Middle Aged , Positive-Pressure Respiration , Respiration, Artificial/instrumentation , Risk Reduction BehaviorABSTRACT
We report about a 19 years old man, suffering from an cardiac arrest (ventricular fibrillation) caused by an ecstasy intoxication. A supraventricular tachycardia was recorded on day three after resuscitation. No pathological findings were demonstrated by coronary angiography. An slow- fast- av -nodal- reentry- tachycardia (AVNRT) was detected and successfully treated by electrical ablation of the slow pathway during electrophysiological mapping. No severe neurological deficits were found in discharge from hospital.
Subject(s)
Hallucinogens/poisoning , Heart Arrest/chemically induced , N-Methyl-3,4-methylenedioxyamphetamine/poisoning , Adult , Cardiopulmonary Resuscitation , Coronary Angiography , Electrocardiography , Electrophysiology , Emergency Medical Services , Humans , Male , Tachycardia, Sinoatrial Nodal Reentry/physiopathology , Ventricular Fibrillation/chemically inducedABSTRACT
Due to the growing number of high-risk patients, the increasing proportion of geriatric patients and the expansion of surgical and invasive-diagnostic procedures, medical stuff in hospitals are confronted with a rising number of emergency situations. Nearly 50% are of cardio-circulatory origin and occur during surgical interventions or immediately afterwards. Another cause of life-threatening complications are side-effects of orally or intravenously administered agents, especially after treatment with antibiotics, anaesthetics, analgetics and sedatives. Due to a lack of emergency training and management in most hospitals, the survival rate after cardiopulmonary resuscitation in general wards lies between just two and 35%. Thus it seems necessary to perform special training in CPR procedures and emergency management at regular intervals for the entire medical stuff. In addition, a special infrastructure for giving sufficient treatment in emergencies has to be established (emergency team, emergency telephone number, intra-hospital emergency car). The second part of this review presents current diagnostic and therapeutic strategies for the most common emergency situations, e.g. anaphylaxis, myocardial infarction, pulmonary embolism, gastrointestinal bleeding, and heparin-induced thrombocytopenia (HIT).
Subject(s)
Critical Illness/therapy , Emergency Medicine/education , Inservice Training , Medical Staff, Hospital/education , Cardiopulmonary Resuscitation/education , Cardiopulmonary Resuscitation/methods , Critical Care/methods , Curriculum , Emergency Service, Hospital , Germany , HumansABSTRACT
The differential-diagnostic strategy and the order of precedence of most diverse radiologic diagnostic procedures are discussed based on a case of retroperitoneal bleeding. Apart from iatrogen-caused bleedings, the therapeutic anticoagulant therapy in the context of the patient's disease, haemodialysis or a rare, spontaneously-occurring retroperitoneal bleeding play a substantial role. In the order of precedence of radiologic diagnostic procedures for fast diagnosis of a retroperitoneal haematoma, the abdomen CT-scan is the preferred method.
Subject(s)
Hemorrhage/etiology , Patient Care Team , Retroperitoneal Space , Aged , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Biopsy, Needle/adverse effects , Diagnosis, Differential , Enoxaparin/adverse effects , Enoxaparin/therapeutic use , Female , Glomerulonephritis/pathology , Hematoma/diagnostic imaging , Hematoma/etiology , Hemorrhage/diagnostic imaging , Humans , Immune Complex Diseases/pathology , Kidney/pathology , Radiography , Retroperitoneal Space/diagnostic imaging , Risk Factors , Venous Thrombosis/complications , Venous Thrombosis/drug therapyABSTRACT
Herpes simplex infections are potentially a life-threatening situation for immunocompromised as well as critically ill patients. The correct diagnosis is made more difficult in comatose patients by the fact that the characteristic symptom of extreme pain cannot be registered. The clinical dermatological findings (polycyclic configuration, easily bleeding ulcers) are thus especially important in patients under intensive care conditions. As examples, the cases of 3 critically ill patients (subarachnoid bleeding or head injury) developing therapy-resistant, flat sacral or perioral skin ulcers with peripheral blisters are presented. Herpes simplex virus was confirmed immunohistologically and in the smear test. All patients subsequently died. These cases emphasize that patients in the intensive care unit are in danger of developing a chronic persistent Herpes simplex infection due to latent immunosuppression. Chronic persistent Herpes infections may be underrated in intensive therapy, and must always be ruled out in case of therapy-resistant erosions or ulcerations.
Subject(s)
Critical Care , Herpes Simplex/pathology , Skin Ulcer/pathology , Acyclovir/therapeutic use , Aged , Craniocerebral Trauma/complications , Critical Illness , Fatal Outcome , Female , Herpes Simplex/diagnosis , Herpes Simplex/drug therapy , Humans , Immunohistochemistry , Immunosuppression Therapy/adverse effects , Male , Reverse Transcriptase Polymerase Chain Reaction , Skin/pathology , Skin Ulcer/drug therapy , Subarachnoid Hemorrhage, Traumatic/complicationsABSTRACT
OBJECTIVE: Iatrogenic tracheobronchial ruptures are seldom but severe complications after intubation or bronchoscopy. Therefore, we evaluated the reasons, the subsequent therapy and the outcome of patients with tracheal rupture, who were admitted to our hospital. METHODS: In a retrospective study we examined 19 patients (15 women, four men; 43-87 years) treated for acute tracheobronchial lesions. Eleven (58%) patients had a tracheobronchial rupture by single-lumen tube, four (21%) by double-lumen tube and two patients (10%) by tracheal cannula. A total of 47% of whom were carried out under emergency conditions. Two patients had a rupture due to a stiff bronchoscopy. Mean symptoms were mediastinal and subcutaneous emphysema. Two emergency collar incisions had been done. RESULTS: The localization of ruptures was in all cases in the paries membranaceus, length: 1-7 cm (mean: 4.8 cm). The interval between the onset of symptoms and the diagnose differed widely (up to 72 h), nine (47%) diagnoses were made during intubation/bronchoscopy. One patient, with a small tear (1 cm) was treated conservatively with fibrin-glue. The other 18 patients had surgical repair through a thoracotomy. The postoperative mortality was determined with 42%, which was not dependent on the rupture but basically by the underlying diseases requiring intubation. CONCLUSIONS: Iatrogenic tracheal rupture is a dangerous complication with potentially high postoperative mortality, mostly influenced by the underlying disease. Early surgical repair must be the preferred treatment.
Subject(s)
Bronchi/injuries , Iatrogenic Disease , Rupture/etiology , Trachea/injuries , Adult , Aged , Aged, 80 and over , Bronchi/surgery , Bronchoscopy/adverse effects , Female , Follow-Up Studies , Germany/epidemiology , Humans , Iatrogenic Disease/epidemiology , Intubation, Intratracheal/adverse effects , Male , Middle Aged , Radiography , Reoperation , Retrospective Studies , Risk Factors , Rupture/surgery , Thoracotomy , Trachea/diagnostic imaging , Trachea/surgery , Tracheostomy/adverse effects , Treatment OutcomeABSTRACT
The object of this study was to determine if the resting muscle activity of TMD patients with measured hyperactivity (EMGave > 2.0 microvolts) could be reduced by the application of ULF-TENS (Ultra-Low-Frequency-Transcutaneous Electrical Neural Stimulation) [(BioTENS) BioResearch, Inc. Milwaukee, WI]. Twenty-nine patients with resting muscle hyperactivity and ten without resting muscle hyperactivity were selected from a series of 124 consecutively diagnosed TMD patients. Electromyographic records were taken bilaterally (with the mandible at rest) from the superficial masseter, anterior temporalis, anterior digastric, and posterior temporalis muscles before and after the application of ULF-TENS. The EMG data were averaged. For the 85 muscles that were found initially to exceed the usual cutoff of 2.0 microvolts, means and standard deviations were calculated. The "before TENS" levels were: mean = 3.353 +/- 1.44227 and the "after TENS" values were: mean = 1.844 +/- 0.92421. Using a student t-test, we found the difference between the before and after levels significant (p < .0005). Additionally, means and standard deviations were calculated for each muscle (Ta, Mm, etc.) separately and also found to be significantly different (before Vs after TENS). In these "hyperactive" patients, the nonhyperactive muscles were also pooled, the means calculated before (mean = 1.21 +/- 0.456) and after (mean = 1.00 +/- 0.345) TENS and found to be significantly different (p < 0.01). For the ten patients exhibiting no muscle exceeding the 2.0 microvolt cutoff (mean = 1.08 +/- 0.415), no significant change (in levels) was observed after ULF-TENS (mean = 0.96 +/- 0.359; p > 0.88); however, when we calculated the "paired difference," we found a significant reduction, albeit very slight, in these patients' muscles, too. We conclude that ULF-TENS has an activity-reducing effect on the resting EMG levels of both hyperactive and relaxed muscles. It also appears that while the > 2.0 microvolt cutoff is useful for identifying patients that are hyperactive at rest, it does not identify complete relaxation of masticatory muscles.
Subject(s)
Electromyography , Facial Nerve/physiopathology , Muscle Relaxation , Temporomandibular Joint Disorders/therapy , Transcutaneous Electric Nerve Stimulation/methods , Trigeminal Nerve/physiopathology , Adult , Female , Humans , Male , Masticatory Muscles/physiopathology , Middle Aged , Temporomandibular Joint Disorders/physiopathology , Treatment OutcomeABSTRACT
Tachyzoite endodyogeny is characterized by a three phase cell cycle comprised of major G1 and S phases with mitosis following immediately upon the conclusion of DNA replication. Cytokinesis, which begins with the formation of daughter apical complexes, initiates in late S phase and overlaps mitosis. There is no evidence to support an extended G2 period in these parasites. In all strains, parasites with a 2 N DNA content are a relatively small subpopulation and when tachyzoites expressing a fluorescent nuclear marker (green-fluorescent-protein fused to proliferating-cell-nuclear-antigen) were observed by time-lapse microscopy, there appeared to be little delay between S phase and mitosis. Measurements of the DNA content of RH parasites by flow cytometry demonstrated that the G1 and S periods were approximately 60 and approximately 30% of a single division cycle, although these phases were longer in strains that display a slower growth rate. The overall length of S phase was determined by [3H]-thymidine autoradiography using transgenic parasites expressing herpes simplex thymidine kinase and validated by Northern analysis of S phase specific genes during synchronous growth. The fraction of S phase parasites by flow cytometry paralleled autoradiography, however, within S phase, the distribution of parasites was bimodal in all strains examined. Parasites containing a 1-1.7 N DNA complement were a small fraction when compared to the major S phase population which contained a near-diploid ( approximately 1.8 N) complement, suggesting parasites in late S phase have a slower rate of DNA replication. In lieu of a short or missing G2, where checkpoints are thought to operate in other eukaryotes, the bimodal replication of tachyzoite chromosomes may represent a distinct premitotic checkpoint associated with endodyogeny.
Subject(s)
Cell Cycle/physiology , Toxoplasma/growth & development , Animals , Cell Division , DNA, Protozoan/analysis , Flow Cytometry , Fluorescent Antibody Technique , G1 Phase , G2 Phase , Gene Expression , Mitosis , Proliferating Cell Nuclear Antigen/analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , S Phase , Toxoplasma/cytology , Toxoplasma/geneticsABSTRACT
beta 1-adrenoceptors play a pivotal role in regulating contractility and heart rate in the human heart. Recently, a polymorphism of the beta 1-adrenoceptor has been detected: at amino acid position 389 either Gly or Arg has been found with the Gly389 exhibiting reduced responsiveness upon agonist-induced stimulation in vitro. In order to find out whether the Gly389 polymorphism exhibits blunted responsiveness also in vivo we studied, in healthy volunteers, the effects of exercise on heart rate and heart rate-corrected duration of electromechanical systole (QS2c as a measure of inotropism) which, in humans, is mediated by beta 1-adrenoceptors stimulation. Twenty-four healthy volunteers (12 female, 12 male) homozygous for the Gly389 or Arg389 exercised on a bicycle in supine position (25, 50, 75 and 100 W for 5 min each), and heart rate and QS2c were assessed; in addition, plasma renin activity (PRA) was determined which is also regulated by beta 1-adrenoceptors in humans. Exercise caused work-load dependent increases in heart rate and PRA, and shortening of QS2c; however, these changes were not significantly different between the Gly389 and Arg389 polymorphism. Thus, these three beta 1-adrenoceptor responses did not differ between volunteers with the Arg389 versus the Gly389 polymorphism. Intragroup analysis, however, revealed that exercise induced increase in heart rate and shortening of QS2c were higher in female than in male volunteers. In conclusion, our data do not support the idea that the reduced responsiveness of Gly389 against agonist-induced stimulation observed in vitro is of major functional importance in vivo.