Munchausen syndrome by proxy is a form of abuse in which an adult, usually the mother, deceives health workers by exaggerating, falsifying or directly inducing psychological or physical symptoms in the child victim for psychological gratification. In 2013, the American Academy of Pediatrics coined the term 'caregiver-fabricated illness in a child' to describe this form of child abuse. A 7-year-old girl had many encounters with health workers over a period of 4 years and presented with evolving clinical features including refractory seizures and red urine for which she was followed up as a case of acute intermittent porphyria. She was later discovered to be the victim of chronic monocrotophos organophosphate poisoning by her mother. If all medical staff who manage children are to avoid becoming inadvertent participants in medical child abuse, this case report is an important reminder that a high index of suspicion is warranted in cases which present a diagnostic dilemma and who respond unexpectedly to treatment.Abbreviations AIP: Acute intermittent porphyria; APSAC: American Professional Society on the Abuse of Children; ASM: anti-seizure medication; CFIC: caregiver-fabricated illness in a child; CT: computed tomography: DVT: deep vein thrombosis; EEG: electroencephalogram: ESR: erythrocyte sedimentation rate; HDW: high-dependency ward; ICU: intensive care unit; LFT: liver function test; MBP: Munchausen syndrome by proxy; NICU: neonatal intensive care unit; RFT: renal function test; TB: Tuberculosis; UTH-CH: University Teaching Hospitals Children's Hospital.

Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.

Cancer, developmental biology and tissue injury present multiple examples where groups of cells residing in close proximity communicate via paracrine factors. It is nearly impossible to dissect such cellular interactions in vivo and is quite challenging in vitro. The goal of this study is to utilize a reconfigurable microfluidic device in order to study paracrine signal exchange between groups of primary hepatocytes in vitro. Previously, we demonstrated that hepatocytes residing on protein spots containing collagen and hepatocyte growth factor (HGF) spots expressed epithelial (hepatic) phenotypes and also rescued them in neighboring hepatocytes on collagen spots that did not receive direct HGF stimulus. Herein, we designed a microfluidic device with parallel fluidic channels separated by retractable (reconfigurable) walls and employed this device to investigate interactions between groups of HGF-stimulated and unstimulated hepatocytes. Using a novel reconfigurable microfluidic device, we demonstrate that cultivation of HGF-containing protein spots upregulates the production of endogenous HGF in hepatocytes and that these HGF molecules diffuse over, causing phenotype enhancement in the recipient cells. We also show that selective treatment of the recipient hepatocytes with a c-met inhibitor (SU11274) diminishes the rescue effect, as gauged by the down-regulation of albumin and HGF expression. Our study is one of the first to demonstrate paracrine signaling via HGF in primary hepatocytes. More broadly, tools and methods described here may be used to study paracrine signaling in other types of cells and will have relevance for various fields of biomedical research from cancer to immunology.

Thrombolytic therapy, also known as clot busting drug, is a breakthrough treatment which has saved untold lives. It has been used in the clinical area to treat venous and arterial thromboembolic complaints which are a foremost cause of death. In 1761, Morgagni lead the way of thrombolytic therapy. Now day's different types of thrombolytic drugs are currently available in market: alteplase, anistreplase, urokinase, streptokinase, tenecteplase, and so forth. Thrombolytic therapy should be given with maintaining proper care in order to minimize the risk of clinically important bleeding as well as enhance the chances of successfully thrombolysis of clot. These cares include preinfusion care, during the infusion care, and postinfusion care. Besides proper knowledge of contraindication, evolutionary factor, and combination of drug is essential for successful thrombolytic therapy. In these review we discussed about these aspect of thrombolytic therapy.

This chapter about fibrinolytic, antiplatelet, and antithrombin treatment for acute ST-segment elevation (STE) myocardial infarction (MI) is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the chapter by Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with ischemic symptoms characteristic of acute MI of < or = 12 h in duration and persistent STE, we recommend that all undergo rapid evaluation for reperfusion (primary percutaneous coronary intervention [PCI] or fibrinolytic) therapy and have a reperfusion strategy implemented promptly after contact with the health-care system (Grade 1A). For patients with ischemic symptoms characteristic of acute MI of < or = 12 h in duration and persistent STE, we recommend administration of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over no fibrinolytic therapy (all Grade 1A). For patients with symptom duration < or = 6 h, we recommend the administration of alteplase or tenecteplase over streptokinase (both Grade 1A). We recommend aspirin over no aspirin therapy followed by indefinite therapy (Grade 1A); we also recommend clopidogrel in addition to aspirin for up to 28 days (Grade 1A). In addition to aspirin and other antiplatelet therapies, we recommend the use of antithrombin therapy (eg, unfractionated heparin (UFH), enoxaparin, or fondaparinux) over no antithrombin therapy (Grade 1A), including for those patients receiving fibrinolysis (and regardless of which lytic agent is administered), primary PCI, or patients not receiving reperfusion therapy.

Crosstalk is the coupling of energy between the elements of an ultrasonic transducer array. This coupling degrades the performance of transducers in applications such as medical imaging and therapeutics. In this paper, we present an experimental demonstration of guided interface waves in capacitive micromachined ultrasonic transducers (CMUTs). We compare the experimental results to finite element calculations using a commercial package (LS-DYNA) for a 1-D CMUT array operating in the conventional and collapsed modes. An element in the middle of the array was excited with a unipolar voltage pulse, and the displacements were measured using a laser interferometer along the center line of the array elements immersed in soybean oil. We repeated the measurements for an identical CMUT array covered with a 4.5-microm polydimethylsiloxane (PDMS) layer. The main crosstalk mechanism is the dispersive guided modes propagating in the fluid-solid interface. Although the transmitter element had a center frequency of 5.8 MHz with a 130% fractional bandwidth in the conventional operation, the dispersive guided mode was observed with the maximum amplitude at a frequency of 2.1 MHz, and had a cut-off frequency of 4 MHz. In the collapsed operation, the dispersive guided mode was observed with the maximum amplitude at a frequency of 4.0 MHz, and had a cut-off frequency of 10 MHz. Crosstalk level was lower in the collapsed operation (-39 dB) than in the conventional operation (-24.4 dB). The coverage of the PDMS did not significantly affect the crosstalk level, but reduced the phase velocity for both operation modes. Lamb wave modes, A0 and S0, were also observed with crosstalk levels of -40 dB and -65 dB, respectively. We observed excellent agreement between the finite element and the experimental results.

Thrombolytic drugs play a crucial role in the management of patients with acute myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial thrombosis, acute thrombosis of retinal vessel, extensive coronary emboli, and peripheral vascular thromboembolism. Recognition of the importance of fibrinolytic system in thrombus resolution has resulted in the development of different fibrinolytic agents. Now a days several newer plasminogen activators with different pharmacokinetic and pharmacodynamic properties have been developed to treat thrombotic disease, which are fibrin specific with prolonged half-life and can be administered as a single bolus.

This chapter about antithrombotic therapy for acute myocardial infarction (MI) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: For patients with ischemic symptoms characteristic of acute MI of < 12 h in duration, and ST-segment elevation or left bundle-branch block (of unknown duration) on the ECG, we recommend administration of any approved fibrinolytic agent (Grade 1A). We recommend the use of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over placebo (all Grade 1A). For patients with symptom duration < 6 h, we recommend the administration of alteplase over streptokinase (Grade 1A). For patients with known allergy or sensitivity to streptokinase, we recommend alteplase, reteplase, or tenecteplase (Grade 1A). For patients with acute posterior MI of < 12 h duration, we suggest fibrinolytic therapy (Grade 2C). In patients with any history of intracranial hemorrhage, closed head trauma, or ischemic stroke within past 3 months, we recommend against administration of fibrinolytic therapy (Grade 1C+). For patients with acute ST-segment elevation MI whether or not they receive fibrinolytic therapy, we recommend aspirin, 160 to 325 mg p.o., at initial evaluation by health-care personnel followed by indefinite therapy, 75 to 162 mg/d p.o. (both Grade 1A). In patients allergic to aspirin, we suggest use of clopidogrel as an alternative therapy to aspirin (Grade 2C). For patients receiving streptokinase, we suggest administration of either i.v. unfractionated heparin (UFH) [Grade 2C] or subcutaneous UFH (Grade 2A). For all patients at high risk of systemic or venous thromboembolism (anterior MI, pump failure, previous embolus, atrial fibrillation, or left ventricular thrombus), we recommend administration of IV UFH while receiving streptokinase (Grade 1C+).

The therapeutic approach to patients with acute ST-segment elevation myocardial infarction (STEMI) has advanced rapidly over the past decade. Intravenous fibrinolytic therapy remains the most common form of reperfusion therapy worldwide, since fibrinolytics are associated with a dramatic reduction in mortality rates. However, primary percutaneous coronary intervention (PCI) is associated with improved outcomes and less bleeding complications compared with fibrinolytic therapy, but it is not widely available. Adjunctive therapies with intracoronary stents, glycoprotein (GP) IIb/IIIa inhibitors, and more potent antithrombin agents have shown great promise for the initial treatment of STEMI and have stimulated further investigation of combined pharmacological/mechanical reperfusion strategies that may be synergistic. Although the optimal combination of fibrinolytics, antiplatelet agents, antithrombins, and mechanical reperfusion at hospitals with and without primary PCI facilities remains elusive, results from recent studies suggest that such a combined approach may facilitate transfer of patients with STEMI from a referral hospital to an invasive hospital for definitive primary PCI after administration of a potent pharmacologic regimen designed to enhance early infarct-related artery reperfusion. Thus, as the reperfusion era continues to evolve, the ideal treatment strategy for patients with STEMI is being redefined to integrate pharmacologic and mechanical approaches to reperfusion.

Forty years ago, after the establishment of coronary care units, a significant decrease in mortality of acute myocardial infarction was noted. Twenty years ago, the break-through of thrombolysis realized once again a significant decrease in mortality. In this study we compare, in a rather small community hospital, the mortality and safety of thrombolytic therapy in acute myocardial infarction with a more conventional, conservative medical therapy. We examined all cases of acute myocardial infarction between 1978 up to 1998 inclusive, concerning treatment and mortality rate after a six month period. To be included in the study, acute myocardial infarction had to fulfill particular inclusion criteria. A total of 1863 cases of acute myocardial infarction were included. The mortality rate of patients with acute myocardial infarction treated with thrombolytic agents was strikingly lower and statistically very significantly different (p < 0.001) in comparison with the mortality rate of patients treated with heparin or coumarine derivatives. The mortality rate dropped from 10.57% in the coumarine group and from 14.95% in the heparin group to 5.41% in the alteplase group, to 4.95% in the anistreplase group and 4.00% in the streptokinase subgroup. The complications directly connected to the treatment did not seem to be different between the five groups, and they were also not more frequent by using thrombolytic agents. In the last 20 years, better preventive measures (life habits, diet, medication) and trials to better control the risk factors have not influenced greatly the average amount of cholesterol in patients with an acute myocardial infarction. Also the percentage of patients with high blood pressure has hardly decreased over the last 20 years. The mortality associated with acute myocardial infarction has decreased significantly with the use of thrombolytics. In most cases, thrombolytics are administered routinely and safely. In this way, they are the first choice therapy for myocardial infarction in smaller hospitals. To obtain excellent coronary patency, thrombolytic agents with a long half-life and with PAI-1 resistance are required in the future. The current measures and medical therapies seem to be insufficient to control the risk factors for coronary atherosclerosis.

Unequivocal evidence exists that reperfusion therapy, when given within 12 hours after onset of symptoms, saves the lives of patients with acute myocardial infarction (MI). As a result, the routine use of such treatment has increased rapidly since the mid-1980s but the rates of utilisation have been relatively static over the last decade at approximately 50% of patients with acute MI. The major question arising in this respect is: is the benefit of reperfusion therapy, which is achieved during the acute phase in evolving MI, maintained on the long term? The main thrombolytic agents currently in use are streptokinase, alteplase, anistreplase, urokinase and reteplase. Other studies compared coronary angioplasty with thrombolytic therapy and investigated the effect of an additional angioplasty procedure after failed thrombolytic therapy. Furthermore, several studies have been performed to investigate the effect of initiation of reperfusion therapy before hospital admission. It is generally agreed that, in particular, patients receiving early treatment within 6 hours from onset of symptoms and patients with ST elevation benefit most from thrombolytic therapy. One would theoretically expect that infarct size reduction achieved by reperfusion therapy would also have a beneficial effect on the survival, not only during the hospital stay but also afterwards, resulting in diverging survival curves between patients who received reperfusion therapy and those who did not. However, the survival curves run perfectly parallel after hospital discharge from 1 year up to year 10 in most studies. The explanation for a lack of extra benefit may be a net result of combining the results of several subgroups. For example, thrombolytic therapy results in more frequent reinfarction especially in the first year, or patients with low left ventricular ejection fraction could survive the hospital phase because of effective thrombolytic therapy, but they survive at high risk. Although several trials suggest that primary percutaneous transluminal coronary angioplasty may be more beneficial than thrombolytic therapy in acute MI, these data should be interpreted cautiously unless confirmed by larger studies with long term results. In addition, evidence exists to suggest that administration of fibrinolytic treatment, under certain conditions, before hospital admission may lead to further improvement of a patient's prognosis. Again, further investigation is warranted. The conclusion is that clear evidence exists that the early improved survival after thrombolytic therapy has been shown to be maintained beyond a decade. However, the expected theorectical additional benefit of reperfusion therapy after hospital discharge has not been observed.

The treatment of acute myocardial infarction (MI) constitutes a significant problem in remote geographical areas of Greece. Furthermore, thrombolysis, the treatment of choice in the early phase of acute MI, requires the supervision of an expert. We have used thrombolytic treatment, using telemedicine, in remote medical centres. The Onassis Cardiac Surgery Centre was linked to six remote Aegean islands via telemedicine systems which permitted the transmission of 12-lead electrocardiograms (ECGs). The thrombolytic agent anistreplase was administered to patients with acute MI. Supervision, including consultation for treatment of complications, was achieved using the telemedicine system. One hundred and fifty-two ECGs were transmitted during 24 months, of which 108 (71%) indicated specific treatment of a cardiac condition. Ten cases were diagnosed as having acute MI and eight of these were treated with anistreplase. All patients survived acute MI and complications were treated locally. The application of thrombolytic treatment in acute MI is feasible in remote areas, with the use of a telemedicine system.

Incorporation of surfactant into polymerizing fibrin causes loss of surface activity and marked retardation of clot lysis by plasmin (Günther and colleagues, Am. J. Physiol. 1994;267:L618-L624). We compared the efficacy of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), activated anisoylated streptokinase-plasminogen activator complex (APSAC), and plasmin to dissolve surfactant-incorporating fibrin. Alveofact was employed as a natural surfactant source, and plasminogen was coincorporated into the fibrin matrix at a physiologic ratio to fibrin. Fibrinolysis was quantified by the release of tracer from (125)I-labeled fibrin, and the pattern of split products was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In addition, we investigated the fibrinolysis-related restoration of surface activity by measurement in the pulsating bubble surfactometer. Concentrations of all fibrinolytic agents were chosen to effect approximately 40% lysis of clot material in the absence of surfactant (control). When incorporated into the fibrin matrix, but not when admixed after clot formation, surfactant inhibited the cleavage of fibrin by all fibrinolytic agents in a dose-dependent manner. Interestingly, t-PA and u-PA were significantly less inhibited than was plasmin or APSAC. The pattern of arising fibrin scission products was identical for all fibrinolytic approaches and was independent of surfactant incorporation. Adsorption and minimum surface tension-lowering properties of Alveofact were almost completely lost upon incorporation into fibrin, but surface activity was fully restored upon sustained clot lysis with all fibrinolytic agents. We conclude that the fibrinolytic capacity of all agents investigated is markedly inhibited by surfactant incorporation in fibrin, but this inhibition is significantly less pronounced in the agents employing preincorporated plasminogen (t-PA and u-PA), as compared with plasmin and APSAC. The plasminogen activators may thus proffer to "rescue" pulmonary surfactant function by induction of fibrinolysis in the alveolar compartment.

In a number of cases, thrombolytic therapy fails to re-open occluded blood vessels, possibly due to the occurrence of thrombi resistant to lysis. We investigated in vitro how the lysis of hardly lysable model thrombi depends on the choice of the plasminogen activator (PA) and is accelerated by ultrasonic irradiation. Lysis of compacted crosslinked human plasma clots was measured after addition of nine different PAs to the surrounding plasma and the effect of 3 MHz ultrasound on the speed of lysis was assessed. Fibrin-specific PAs showed bell-shaped dose-response curves of varying width and height. PAs with improved fibrin-specificity (staphylokinase, the TNK variant of tissue-type PA [tPA], and the PA from the saliva of the Desmodus rotundus bat) induced rapid lysis in concentration ranges (80-, 260-, and 3,500-fold ranges, respectively) much wider than that for tPA (a 35-fold range). However, in terms of speed of lysis, these three PAs exceeded tPA only slightly. Reteplase and single-chain urokinase were comparable to tPA, whereas two-chain urokinase, anistreplase, and streptokinase were inferior to tPA. In the case of fibrin-specific PAs, ultrasonic treatment accelerated lysis about 1.5-fold. For streptokinase no acceleration was observed. The effect of ultrasound correlated with the presence of plasminogen in the outer plasma, suggesting that it was mediated by facilitating the transport of plasminogen to the surface of the clot. In conclusion, PAs with improved fibrin-specificity induce rapid lysis of plasminogen-poor compacted plasma clots in much wider concentration ranges than tPA. This offers a possibility of using single-or double-bolus administration regimens for such PAs. However, it is not likely that administration of these PAs will directly cause a dramatic increase in the rate of re-opening of the occluded arteries since they are only moderately superior to tPA in terms of maximal speed of lysis. Application of high-frequency ultrasound as an adjunct to thrombolytic therapy may increase the treatment efficiency, particularly in conjunction with fibrin-specific PAs.

This study sought to assess the rate of acute Thrombolysis In Myocardial Infarction (TIMI) trial grade 3 patency that can be achieved with the combination of prehospital thrombolysis and standby rescue angioplasty in acute myocardial infarction. No large angiographic study has been performed after prehospital thrombolysis to determine the 90-minute TIMI 3 patency rate in the infarct-related artery. Hospital outcome and artery patency were compared to 170 matched patients treated with primary angioplasty. Prehospital thrombolysis was applied 151+/-61 minutes after the onset of pain in 170 patients (56+/-12 years, 86% men), using recombinant tissue-type plasminogen activator, streptokinase, or eminase. Emergency 90-minute angiography was performed in every case. All patients in whom thrombolysis failed underwent rescue angioplasty. After thrombolysis alone, TIMI grade 3 flow in the infarct-related artery was observed in 108 patients (64%), TIMI grade 2 in 12 (7%), and TIMI grade 0 or 1 in 50 (29%). Rescue angioplasty was successful in 47 of 50 attempts. Overall, TIMI 3 patency was achieved in 91%, and additionally TIMI 2 flow in 7% of patients, an average of 113+/-39 minutes after thrombolysis and 55+19 minutes after admission. Therefore, < 2 hours after thrombolysis, only 2% of patients had persistent occlusion (TIMI 0 or 1) of the infarct-related artery. In-hospital mortality was 4% overall (7 of 170), and 3% in the 155 patients in whom TIMI 3 was obtained during the acute phase. Severe hemorrhagic complications occurred in 14 patients (8%) with 2 fatal cerebral hemorrhages (7% of patients required transfusions). The matched comparison with primary PTCA showed no significant difference in hospital outcome. Combined prehospital thrombolysis, 90-minute angiography, and rescue angioplasty yield a high rate of acute TIMI 3 patency rate early after thrombolysis and hospital admission. A randomized, prospective comparison between these 2 reperfusion strategies may be now warranted.

Thrombolytic therapy in patients with acute coronary syndrome is not so widely used compared to coronary intervention, such as PTCA or stenting in Japan. This is probably because of the facts that the narrowing of the coronary artery is not completely restored after the thrombolytic therapy and that the coronary intervention is frequently necessary inspite of the administration of the thrombolytic agent. However, the thrombolytic therapy can be easily done in the peracute stage of myocardial infarction, and improvement of the prognosis of the affected patient may be possible. In this paper, the concepts as well as the effect of thrombolytic therapy and the characteristics of newly developed thrombolytic drugs are discussed.