Impact of mucositis on oral bioavailability and systemic exposure of ciprofloxacin Gram-negative infection prophylaxis in patients with haematological malignancies.

BACKGROUND: Patients with haematological malignancies frequently endure neutropenia and gastrointestinal (GI)-mucositis after high-dose chemotherapy. In these patients, ciprofloxacin is used for Gram-negative infection prophylaxis. OBJECTIVES: We investigate ciprofloxacin pharmacokinetics after oral administration in patients with haematological malignancies and explore the impact of GI-mucositis on oral bioavailability and clearance in order to assure adequate systemic exposure. METHODS: Adult haematological patients from two Dutch University Medical Centres received 500 mg twice daily oral ciprofloxacin for Gram-negative prophylaxis. The ciprofloxacin plasma concentrations were collected at various timepoints after oral ciprofloxacin administration and at various days after completion of chemotherapy. Data obtained after oral and intravenous ciprofloxacin administration in 28 healthy volunteers without mucositis served as a control group (391 samples). For haematological patients the degree of GI-mucositis was assessed using the Daily Gut Score (DGS), plasma citrulline and albumin. Data were analysed by non-linear mixed-effects modelling. RESULTS: In total, 250 blood samples were collected in 47 patients with a wide variety of haematological malignancies between 0-30 days after start of chemotherapy. Mucositis was generally mild [DGS median (IQR) 1 (1-1) and citrulline 16 µmol/L (12-23)]. The time to Cmax was slower in haematological patients compared with healthy volunteers although no association with the degree of mucositis (defined as DGS or citrulline) could be identified. Ciprofloxacin bioavailability and clearance were 60% and 33.2 L/h, respectively. CONCLUSIONS: This study supports oral dosing of ciprofloxacin as Gram-negative infection prophylaxis in haematological patients with mild-to-moderate mucositis capable of oral intake.

Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board.

Background: Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer. Patients and methods: Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated 'recommended' or 'for consideration' by WFO. Results: Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55-64 years. Receptor status was not found to affect concordance. Conclusion: Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited.

Self-expandable metal stents for malignant esophageal obstruction: a comparative study between extrinsic and intrinsic compression.

Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic.

AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.

We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul(-1)) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies.

Physical properties of cellulose nanocrystal/magnesium oxide/chitosan transparent composite films for packaging applications.

Hitherto unreported hybrid nanofillers (CNC:MgO) reinforced chitosan (CTS) based composite (CNC:MgO)/CTS films were synthesized using a solution-casting blend technique and synergistic effect of hybrid nanofiller in terms of properties enhancement were investigated. Optical microscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) technique, fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FESEM) were used to characterize the films. The hybrid nanofiller considerably changed the transparency and color of the CTS films. The tensile strengths of (3 wt%) CNC/CTS, (3 wt%) MgO/CTS, (1:1)(CNC:MgO)/CTS, (1:2)(CNC:MgO)/CTS and (2:1)(CNC:MgO)/CTS films were 27.49 %, 35.60 %, 91.62 %, 38.22 %, and 29.32 % higher than pristine CTS films respectively, while the water vapor permeation were 28.21 %, 30.77 %, 34.62 %, 38.46 %, and 37.44 % lower than pristine CTS film, respectively. Moreover, the CTS composite films exhibited an improvement in overall water barrier properties after incorporating hybrid nanofillers. Our observations suggest that chitosan-based hybrid nanofiller composite films are a good replacement for plastic-based packaging materials within the food industry.

Patients with Obesity Should be Recognised as a Special Patient Population During Drug Development of Antibacterial and Antifungal Agents; A Call to Action.

Individuals with obesity are at increased risk of developing infectious diseases. Timely administration of an effective dose of an antimicrobial agent is paramount to safeguard optimal therapy. For this purpose, special patient populations at risk for altered exposure such as renal or hepatic impairment are studied during drug development. Strikingly, there is no such evaluation in individuals with obesity despite a potential influence on exposure and a global obesity prevalence of 13 %. Optimal clinical decision making in patients with obesity is impossible without prior study of the drug of interest in this population. This statement is strengthened by an evaluation of 19 antimicrobial agents that showed tremendous variability in the influence of weight on clearance. In contrast to patient with renal or hepatic impairment who are mainly at risk of overexposure, individuals with obesity can be at risk of both under- and overexposure. Gaining knowledge on the influence of body weight on clearance during early phases of drug development may allow for optimisation of other phases of research, potentially increasing success rate of the drug, and can provide clinicians with vital information as soon as the drug reaches the market. Antimicrobial therapy should be tailored to obesity-related (patho)physiological changes and to reach this goal, obese individuals should be studied during drug development.

Effect of carbon nanotube addition on the wear behavior of basalt/epoxy woven composites.

The effect of acid-treated carbon nanotube (CNT) addition on the wear and dynamic mechanical thermal properties of basalt/epoxy woven composites was investigated in this study. Basalt/CNT/epoxy composites were fabricated by impregnating woven basalt fibers into epoxy resin mixed with 1 wt% CNTs which were acid-treated. Wear and DMA (dynamic mechanical analyzer) tests were performed on basalt/epoxy composites and basalt/CNT/epoxy composites. The results showed that the addition of the acid-treated CNTs improved the wear properties of basalt/epoxy woven composites. Specifically, the friction coefficient of the basalt/epoxy composite was stabilized in the range of 0.5-0.6 while it fell in the range of 0.3-0.4 for basalt/CNT/epoxy composites. The wear volume loss of the basalt/CNT/epoxy composites was approximately 68% lower than that of the basalt/epoxy composites. The results also showed that the glass transition temperature of basalt/CNT/epoxy composites was higher than that of basalt/epoxy composites. The improvement of wear properties of basalt/epoxy composites by the addition of acid-treated CNTs was caused by the homogeneous load transfer between basalt fibers and epoxy matrix due to the reinforcement of CNTs.

Hydrophilicity and hydrophobicity consideration of organic surfactant compounds: Effect of alkyl chain length on corrosion protection.

Organic compounds have been recognized as one of the utmost operative corrosion protective measures. However, their usage and synthesis are allied with the consumption and release of malignant materials. More so, out of various manufactured and settled compounds, only a few are effective. Therefore, the high mandate is to design and formulate effective compounds based on literature outcomes. Literature outcomes suggest that surfactant molecules having alkyl substituent of neither too small nor too large act as effective aqueous phase corrosion inhibitors. The present review describes the effect of alkyl/hydrocarbon chain length on the corrosion inhibition potential of some series of surfactant molecules. Generally, an increase in the alkyl chain length favors inhibition performance due to enhancing the packing of surfactant molecules at the interface of metal and electrolyte, but a very high level of hydrophobicity disfavors the inhibition performance. Hydrophilicity and hydrophobicity can be suitably tailored by varying the number and size of the hydrocarbon chain. Organic compounds containing the hydrocarbon chain length of C12-C16 exhibit the best inhibition efficiency (%IE). The molecules become effective by adsorbing on the metal surface. They behave as mixed- and interface-type corrosion inhibitors.

Comparison of transnasal small-caliber vs. peroral conventional esophagogastroduodenoscopy for evaluating varices in unsedated cirrhotic patients.

BACKGROUND AND STUDY AIMS: We aimed to evaluate the accuracy of transnasal small-caliber esophagogastroduodenoscopy (TNSC-EGD) compared with peroral conventional EGD (POC-EGD) for evaluating varices in unsedated patients with liver cirrhosis. The success rate, safety, endoscopist satisfaction, and patient tolerability of TNSC-EGD were also addressed. PATIENTS AND METHODS: One hundred patients with liver cirrhosis participated in this randomized crossover trial, and 84 subjects completed both procedures. Of the 84 patients, 28 had marked bleeding diathesis (platelet count ≤ 50000/mm (3) and/or prothrombin time ≥ 1.7 INR). Endoscopists and patients answered questionnaires using a 100-mm visual analog scale about, respectively, their satisfaction and their tolerance of the procedure. RESULTS: The success rate of TNSC-EGD was comparable to that of POC-EGD (96% vs. 99%). Nasal mucosal hemorrhages induced by TNSC-EGD occurred in 5 patients (6%), but were easily controlled. Compared to the POC-EGD reference test, diagnostic accuracies of TNSC-EGD for detecting esophageal varices, gastric varices, and red color signs were 98%, 98%, and 96%, respectively. Concordance rates on grading esophageal varices and gastric varices were excellent at 93% (κ = 0.85) and 96% (κ = 0.87). Endoscopist satisfaction was not significantly different between TNSC-EGD and POC-EGD, whereas patient tolerance of TNSC-EGD was significantly greater than that of POC-EGD (79.0 ± 14.4 vs. 69.5 ± 16.1; P = 0.001). CONCLUSION: TNSC-EGD without sedation was found to be feasible, safe, and accurate for evaluating esophageal varices, gastric varices, and red color signs in patients with cirrhosis - even in those with marked bleeding diathesis. Furthermore, it was significantly better tolerated by patients, without altering endoscopist satisfaction. Our findings indicate that TNSC-EGD without sedation might be viewed as a potential alternative to POC-EGD for evaluation of varices.

Effects of silane modification and temperature on tensile and fractural behaviors of carbon nanotube/epoxy nanocomposites.

We investigated the effects of carbon nanotube (CNT) functionalization with silanes and temperature on the tensile and fractural characteristics of CNT/epoxy nanocomposites. Three groups of nanocomposites were fabricated using unmodified, oxidized and silanized CNTs, each at 0.1 wt%. Tensile and fractural tests were performed using the three nanocomposite samples at -30 degrees C, 20 degrees C, and 45 degrees C. Results showed that the tensile strength of silanized samples at -30 degrees C was about 89% and 241% higher, respectively, than at 20 degrees C and 45 degrees C. The elastic modulus of silanized CNT nanocomposite at -30 degrees C was about 52% and 871% higher, respectively, than at 20 degrees C and 45 degrees C. The fracture toughness of silanized samples was higher than those of unmodified and oxidized samples at all temperatures. However, fracture toughness decreased with decreasing temperature. Specifically, fracture toughness of silanized nanocomposites at -30 degrees C was about 76% and 117% lower, respectively, than those at 20 degrees C and 45 degrees C.

Silane treatment of carbon nanotubes and its effect on the tribological behavior of carbon nanotube/epoxy nanocomposites.

Functionalization of carbon nanotubes (CNTs) influences dispersion and interfacial strength in CNT-reinforced nanocomposites. In this study, multi-walled CNTs were functionalized via oxidation with a mixture of sulfuric acid (H2SO4) and nitric acid (HNO3). Then, the functionalized CNTs with oxidation were surface-modified using a coupling agent, 3-aminopropyltriethoxysilane. CNT/epoxy nanocomposites were fabricated using oxidized CNTs and silane-modified CNTs, respectively, to investigate the effect of silane treatment on the tribological behavior of CNT/epoxy nanocomposites. Wear tests were performed on oxidized and silanized CNT/epoxy nanocomposites, at three different sliding speeds. The results showed that the friction coefficient and wear rate of silanized CNT/epoxy nanocomposites were lower than those of oxidized CNT/epoxy nanocomposites, regardless of sliding speed. The improved tribological behavior of silanized CNT/epoxy nanocomposites occurred due to the improved dispersion of CNTs into the epoxy and improved adhesion with the epoxy.

Qualitative effects of fresh and dried plum ingredients on vacuum-packaged, sliced hams.

Boneless ham muscles (Semimembranosus+Adductor) were injected (20% w/w) with a curing brine containing no plum ingredient (control), fresh plum juice concentrate (FP), dried plum juice concentrate (DP), or spray dried plum powder (PP) at 2.5% or 5%. Hams were cooked, vacuum-packaged, stored at<4°C and evaluated at 2-week intervals over 10 week. Evaluations were performed on sliced product to determine cook loss, vacuum-package purge, Allo-Kramer shear force, 2-thiobarbituric acid-reactive substances (TBARS), proximate analysis, objective color, sensory panel color and sensory attributes. FP, DP and 2.5% PP increased (P<0.05) cook loss by 2% to 7% depending on treatment and level, but the highest cook loss (17.7%) was observed in hams with 5% PP. Shear force values increased as the level of plum ingredient increased (P<0.05) from 2.5% to 5%, and the highest shear values were observed in hams containing 5% FP. There were no differences (P>0.05) in lipid oxidation among treatments as determined by TBARS and sensory evaluation. FP and PP ham color was similar to the control, but DP had a more intense atypical color of cured ham. Minimal changes in physical, chemical and sensory properties were observed during storage of all treatments.

Antioxidant properties of plum concentrates and powder in precooked roast beef to reduce lipid oxidation.

Boneless beef roasts (Semimembranosus+Adductor) were injected (20%) with a brine containing (1) no plum ingredient (control), (2) 2.5 or 5% fresh plum juice concentrate (FP), (3) 2.5 or 5% dried plum juice concentrate (DP), or (4) 2.5 or 5% spray dried plum powder (PP). Whole roasts were cooked, vacuum-packaged and stored at <4.0°C for 10wk. At 2wk intervals, evaluations were performed on sliced product to determine vacuum-packaged purge, Allo-Kramer shear force, lipid oxidation (TBARS), color space values, and sensory attributes. All plum ingredients reduced TBARS values and had minimal effects on tenderness, sensory characteristics, color and appearance. Small changes in purge, color values, TBARS and some sensory properties were found during storage. These results indicate that 2.5% FP or DP could be incorporated into precooked beef roasts to reduce lipid oxidation and potentially, warmed-over flavor (WOF).

Prevalence of sexual dysfunctions and other sexual disorders in adults with attention-deficit/hyperactivity disorder compared to the general population.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and/or hyperactivity and impulsivity that lead to dysfunctioning in daily life. One of the affected areas of life that has so far not been studied in ADHD is sexual functioning. The goal of this study was to assess prevalence of sexual dysfunctions and other sexual disorders among adults with ADHD. A total of n = 136 adult patients treated in a Dutch outpatient ADHD clinic filled out two questionnaires to screen for sexual dysfunctions and other sexual disorders. We compared the prevalence of sexual dysfunctions and other sexual disorders in our ADHD patient population to results from two large surveys among the general Dutch population. We found that 39% of the male and 43% of the female ADHD patients had symptoms of a sexual dysfunction, and 17% of the male and 5% of the female ADHD patients had symptoms of any other sexual disorder. Only one male patient had received a diagnosis of a sexual disorder at this clinic prior to study participation. In conclusion, sexual dysfunctions and other sexual disorders are highly prevalent in adults with ADHD. Screening for sexual disorders should be therefore standard procedure during diagnostic assessment.

[A patient with severe digoxin toxicity]. / Een patiënt met ernstige digoxine-intoxicatie.

BACKGROUND: Digoxin is a cardiac glycoside that is frequently prescribed in atrial fibrillation and heart failure. Symptoms such as nausea, hyperkalaemia, cardiac arrhythmias and cardiac arrest are seen in digoxin toxicity. The treatment focuses on reduction of digoxin absorption, prevention of hypokalaemia and hyperkalaemia, treatment of symptoms and, in severe toxicity, administration of digoxin antibodies. CASE DESCRIPTION: A 73-year-old man with a history of extensive cardiac disease was seen 45 minutes after ingesting 20 mg of digoxin. The patient developed ventricular fibrillation within 3 hours of ingestion, before arrival of the digoxin antibodies. The patient passed away despite resuscitation and administration of an insufficient amount of digoxin antibodies. CONCLUSION: The national supply of digoxin antibodies in the Netherlands proved to be too limited for the treatment of a patient with severe digoxin toxicity. An increase in the supply, and central storage, of digoxin antibodies could promote faster administration of an adequate amount of the antibodies. Timely transportation to an extra corporeal membrane oxygenation centre should also be considered.

Incomplete discoid glenoid labrum combined with a ganglion cyst of the spinoglenoid notch.

In a 41-year-old man, right-sided infraspinatus muscle weakness was associated with compression of the suprascapular nerve caused by a spinoglenoid ganglion cyst. The lesion was confirmed using electromyography and MRI. In addition, arthroscopy showed an incomplete discoid labrum. The free inner edge of the labrum was removed as in a meniscectomy of a discoid meniscus in the knee joint. Arthroscopic decompression of the cyst was performed through a juxtaglenoid capsulotomy which was left open. Neurological function recovered completely.

c-Myc and cyclin D3 (CcnD3) genes are independent targets for glucocorticoid inhibition of lymphoid cell proliferation.

Glucocorticoids inhibit the expression of critical cell cycle-regulatory genes. The G1 cyclin gene CcnD3, which encodes cyclin D3, is inhibited by dexamethasone in P1798 murine T lymphoma cells. Glucocorticoids also inhibit expression of the catalytic partner of cyclin D3, Cdk4. Inhibition of these two genes results in a decrease in the ability to phosphorylate the Rb-1 tumor suppressor gene product. Stable transformation with SV40 T antigen expression vectors prevents glucocorticoid-mediated cell cycle arrest, which is consistent with the conclusion that glucocorticoids inhibit Rb-1 phosphorylation. Overexpression of cyclin D3 suffices to restore Rb-kinase activity in glucocorticoid-treated cells. Nevertheless, overexpression of cyclin D3 does not prevent glucocorticoid inhibition of cell proliferation. Cells transformed with Cdk4 expression vectors, with or without cyclin D3 expression vectors, also undergo G0 arrest in the presence of dexamethasone. Glucocorticoids inhibit c-Myc expression in lymphoid cells, and transient expression of c-Myc protein attenuates the lytic response in glucocorticoid-treated human leukemia cells (R. Thulasi, D. V. Harbour, and E. B. Thompson, J. Biol. Chem., 268: 18306-16312, 1993). However, P1798 cells stably transfected with c-Myc expression vectors are sensitive to glucocorticoid-mediated G0 arrest. Such transformants withdraw from the cell cycle when treated with dexamethasone. P1798 cells were transformed so as to express both c-Myc protein and cyclin D3 in the presence of glucocorticoids. These Myc/D3 cells continue to proliferate in the presence of dexamethasone, and virtually all of these cells are capable of entering S phase in the presence of the steroid. Rapid apoptotic cell death occurs when wild-type P1798 cells are treated with dexamethasone in serum-free medium. Myc-transformed and cyclin D3-transformed cells also die rapidly when treated with glucocorticoids in the absence of serum. T antigen transformants are resistant to glucocorticoid-mediated apoptosis in serum-free medium. Double transformants that express both cyclin D3 and c-Myc are also resistant to apoptosis in the presence of dexamethasone. We conclude that inhibition of both CcnD3 and c-Myc genes is critical to glucocorticoid-mediated G0 arrest. Furthermore, those genes that convey resistance to growth arrest also convey resistance to cell death.

Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa.

Helicobacter pylori causes type B gastritis. It shows strong association with the development of gastric carcinoma. A plausible hypothesis for the missing link between H. pylori infection and gastric carcinogenesis involves oxygen free radical-induced DNA damage. To test this hypothesis, we compared the amount of 9-hydroxydeoxyguanosine, a marker for oxygen free radical-induced DNA damage, in the DNA of human gastric mucosa with and without H. pylori infection. Gastric antral biopsies were taken from pediatric patients and volunteers to select H. pylori-positive and H. pylori-negative specimens. The 8-hydroxydeoxyguanosine content of the gastric mucosal DNA was measured after H. pylori-positive and H. pylori-negative volunteers were identified. The increased level of oxidative DNA damage suggests the mechanistic link between H. pylori infection and gastric carcinoma.

Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning.

OBJECTIVES: This study investigated the effect of prolonged cardiac arrest and subsequent cardiopulmonary resuscitation on left ventricular systolic and diastolic function. BACKGROUND: Cardiac arrest from ventricular fibrillation results in cessation of forward blood flow, including myocardial blood flow. During cardiopulmonary resuscitation, myocardial blood flow remains suboptimal. Once the heart is defibrillated and successful resuscitation achieved, reversible myocardial dysfunction, or "stunning," may occur. The magnitude and time course of myocardial stunning from cardiac arrest is unknown. METHODS: Twenty-eight domestic swine (26 +/- 1 kg) were studied with both invasive and noninvasive measurements of ventricular function before and after 10 or 15 min of untreated cardiac arrest. Contrast left ventriculograms, ventricular pressures, cardiac output, isovolumetric relaxation time (tau) and transthoracic Doppler-echocardiographic studies were obtained. RESULTS: Twenty-three of 28 animals were successfully resuscitated and postresuscitation data obtained. Left ventricular ejection fraction showed a significant reduction 30 min after resuscitation (p < 0.05). Regional wall motion analysis revealed diffuse, global left ventricular systolic dysfunction. Left ventricular end-diastolic pressure increased significantly in the postresuscitation period (p < 0.05). Isovolumetric relaxation time (tau) was significantly increased over baseline by 2 h after resuscitation (p < 0.05). Similar findings were noted with the Doppler-echocardiographic analysis, including a reduction in fractional shortening (p < 0.05), a reduction in mitral valve deceleration time (p < 0.05) and an increase in left ventricular isovolumetric relaxation time at 5 h after resuscitation (p < 0.05> By 24 h, these invasive and noninvasive variables of systolic and diastolic left ventricular function had begun to improve. At 48 h, all measures of left ventricular function had returned to baseline levels. CONCLUSIONS: Myocardial systolic and diastolic dysfunction is severe after 10 to 15 min of untreated cardiac arrest and successful resuscitation. Full recovery of this postresuscitation myocardial stunning is seen by 48 h in this experimental model of ventricular fibrillation cardiac arrest.