Timing of gangrene tissue debridement after autologous bone marrow cell implantation in patients with superficial femoral arterial occlusion: preliminary experiences.

AIM: Although implantation of bone marrow mononuclear cells (BMI) was shown to improve outcomes in patients with severe peripheral arterial occlusive disease (PAOD), little experience has been reported in patients with an arterial occlusion level above the knee, ischemic gangrene, and high cardiovascular risk. This study sought to investigate the timing of gangrene tissue debridement and the safety of BMI in these patients. METHODS: Six "no-option" PAOD patients were enrolled with an arterial occlusion level above the knee, ischemic gangrene, and 3 systemic diseases related to a high cardiovascular risk. The ischemic status was evaluated by measuring the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and wound healing after BMI. RESULTS: All patients safely underwent the procedures with intravenous general anesthesia by titrating propofol. Major lower extremity amputation, minor debridement amputation, and debridement surgery were performed in 2 (33.3%), 1 (16.7%), and 2 (33.3%) patients, respectively, 3.1 2.8 months after BMI. Compared to the amputation group (N=3), the salvage group (N=3) had a significantly higher baseline ABI (P=0.02) and a shorter distance between the gangrene site and arterial occlusion site (P=0.01). In the 3 patients who underwent debridement, ABI and TcPO2 significantly improved 1 month after BMI, and gangrenous tissues were debrided 3.8 ± 3.6 (range, 1~8) months after BMI with complete healing within 1 month. CONCLUSION: Autologous BMI therapy is safe in patients at high cardiovascular risk with an arterial occlusion level above the knee and ischemic gangrene. Effective predictors of BMI include the baseline ABI and distance to the ischemia. Gangrene tissue should be debrided at least 1 month after BMI.

Differential gene expression signature between primary and metastatic head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a world-wide malignancy. This study aimed to identify differential gene expression associated with the progression of disease from primary to metastatic HNSCC. Microdissection retrieved pure epithelial cells from paired primary tumours and cervical lymph node metastasis. cDNA microarray analysis and algorithm grouping identified differential mRNA expression of 301 genes. Quantitative reverse transcription-polymerase chain reaction analysis clarified the up-regulation of CCL19, CR2, EGR2, FUCA1, RGS1, and SELL, as well as the down-regulation of IGFBP6 and KLK8 in nodal metastasis compared to primary tumours. Immunohistochemistry confirmed the up-regulation of SELL and down-regulation of IGFBP6 in nodal metastasis relative to primary tumours. Interestingly, primary tumours exhibiting higher FUCA1 and SELL expression were associated with significantly worse patient survival. In OECM-1 HNSCC cells, inhibition of proliferation, migration, and anchorage-independent growth was noted following knockdown of SELL expression. In SAS HNSCC cells, expression of exogenous SELL resulted in increased invasion, anchorage-independent growth, and xenographic tumourigenesis in nude mice. Knockdown of FUCA1 and treatment with IGFBP6 inhibited the migration of OECM-1 cells. Knockdown of RGS1 inhibited the anchorage-independent growth of SAS cells. Our results provide a useful gene signature profile describing the factors underlying the metastasis of HNSCC to cervical lymph nodes, which may be beneficial for the treatment of HNSCC metastasis.

Neurotrophin-3 administration alters neurotrophin, neurotrophin receptor and nestin mRNA expression in rat dorsal root ganglia following axotomy.

In the months following transection of adult rat peripheral nerve some sensory neurons undergo apoptosis. Two weeks after sciatic nerve transection some neurons in the L4 and L5 dorsal root ganglia begin to show immunoreactivity for nestin, a filament protein expressed by neuronal precursors and immature neurons, which is stimulated by neurotrophin-3 (NT-3) administration. The aim of this study was to examine whether NT-3 administration could be compensating for decreased production of neurotrophins or their receptors after axotomy, and to determine the effect on nestin synthesis. The levels of mRNA in the ipsilateral and contralateral L4 and L5 dorsal root ganglia were analyzed using real-time polymerase chain reaction, 1 day, 1, 2 and 4 weeks after unilateral sciatic nerve transection and NT-3 or vehicle administration via s.c. micro-osmotic pumps. In situ hybridization was used to identify which cells and neurons expressed mRNAs of interest, and the expression of full-length trkC and p75NTR protein was investigated using immunohistochemistry. Systemic NT-3 treatment increased the expression of brain-derived neurotrophic factor, nestin, trkA, trkB and trkC mRNA in ipsilateral ganglia compared with vehicle-treated animals. Some satellite cells surrounding neurons expressed trkA and trkC mRNA and trkC immunoreactivity. NT-3 administration did not affect neurotrophin mRNA levels in the contralateral ganglia, but decreased the expression of trkA mRNA and increased the expression of trkB mRNA and p75NTR mRNA and protein. These data suggest that systemically administered NT-3 may counteract the decrease, or even increase, neurotrophin responsiveness in both ipsi- and contralateral ganglia after nerve injury.

Amphetamine-related acute myocardial infarction due to coronary artery spasm.

A 27-year-old man developed acute myocardial infarction after intravenous amphetamine use. A coronary angiogram showed plaques in the mid-portion of the left anterior descending artery which developed coronary artery spasm after administration of intracoronary ergonovine. The findings in this case suggest that these coronary artery plaques played a role in the endothelial dysfunction resulting from amphetamine use, and that induction of coronary arterial spasm was the likely mechanism of amphetamine-related acute myocardial infarction.

Profile of adult rat sensory neuron loss, apoptosis and replacement after sciatic nerve crush.

Following permanent transection of the adult rat sciatic nerve, sensory neuron apoptosis in the contributing L4 and L5 dorsal root ganglia can be observed for at least 6 months afterwards. To establish the profile of any sensory neuron apoptosis and loss over time when axonal regeneration is allowed, serial sections of L4 and L5 ganglia were examined and the neurons counted using a stereological technique 1, 2 and 3 months after crushing the right sciatic nerve at mid-thigh level. Our results show that an identical degree of sensory neuron loss and apoptosis occurs 1 month after crush as at 1 month after permanent transection. However, at 3 months no neurons undergoing apoptosis could be observed and no significant loss could be detected in the ipsilateral ganglia when compared to unoperated controls. One explanation was a neuronal replacement mechanism, which was investigated by administering bromodeoxyuridine to rats for 1 month after sciatic nerve transection or crush, prior to detection using immunohistochemistry on sections of their ganglia after 2 months. The presence of bromodeoxyuridine in the nuclei of occasional cells that would be counted as neurons on the basis of size and morphology indicates that a process of apparent neurogenesis may underlie the profile of sensory neuron loss after axotomy.

Guidewire-induced dissection of the right coronary artery and adjacent aortic wall during percutaneous coronary angioplasty.

We describe two patients in whom right coronary artery dissection and retrograde dissection of the sinus of Valsalva occurred during guidewire advancement for percutaneous coronary angioplasty Both patients were treated successfully by coronary stenting. These cases illustrate that contrast medium injection can detect early complications during guidewire advancement for coronary intervention.

Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure.

Fifteen elderly patients with normal left ventricular (LV) systolic function and New York Heart Association functional class II-III were studied. The effect of verapamil on LV diastolic function was assessed by congestive heart failure (CHF) score, treadmill exercise test, and Doppler echocardiography at baseline, and after each three-month treatment period (placebo or verapamil 120 mg once daily), separated by a one-week washout period before crossover. Blood pressure, heart rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo or verapamil. Verapamil treatment significantly improved CHF score at 3 months (3.5 +/- 0.5, p<0.05) compared with baseline (5.6 +/- 0.5) or placebo (5.5 +/- 0.5). The exercise time was similar at baseline (7.4 +/- 1.2 min) and after placebo (7.4 +/- 1.3 min) treatment but significantly (p<0.05) increased after verapamil (8.3 +/- 1.2 min) treatment. The ratio of mitral A wave duration/pulmonary venous atrial systolic reversal duration increased after verapamil (1.11 +/- 0.08) treatment compared with placebo (0.91 +/- 0.07, p<0.05) and baseline (0.89 +/- 0.08) which had similar durations. The isovolumic relaxation time was significantly (p<0.05) decreased from 84 +/- 12 ms at baseline and 86 +/- 13 ms with placebo to 73 +/- 9 ms with verapamil. The results of this study suggest that in elderly patients with Doppler evidence of diastolic dysfunction as the cause of CHF, three months treatment with verapamil can improve CHF, increase exercise tolerance and improve LV diastolic function.

Relationship between dobutamine echocardiography and the elevation of cardiac troponin I in patients with acute coronary syndromes.

An elevated cardiac troponin I (cTnI) and a positive dobutamine echocardiography are powerful predictors for future cardiac events in patients with coronary artery disease. Investigating their correlation also should be helpful in understanding their clinical usefulness in evaluating patients with acute coronary syndromes (ACS). Dobutamine echocardiography and a blood sampling for cTnI were performed on 117 patients with ACS 70 +/- 2 hours after arriving at the hospital. CTnI was considered elevated when its value was greater than 2.0 ng/ml. Dobutamine echocardiography was positive in 86 (73.5%) patients, and cTnI was elevated in 37 (31.6%). The occurrence of positive dobutamine echocardiography in patients with elevated cTnI was significantly higher than in those with normal cTnI (86.5% vs. 67.5%, P = 0.042). More patients in the elevated cTnI group developed myocardial ischemia before or at the stage of dobutamine 20 microg/kg/min (43.2% vs. 15%, P = 0.002). When compared with patients with normal cTnI, patients with elevated cTnI had a lower ischemic threshold during dobutamine echocardiography, and more frequently had baseline echocardiographic wall-motion abnormalities, a history of myocardial infarction, and a positive dobutamine echocardiography. Using multivariate analysis, we found that only a lower dobutamine echocardiography ischemic threshold (P = 0.0008) and baseline wall-motion abnormalities (P = 0.0004) were associated independently with the elevation of cTnI. Our results suggest that in patients with ACS, dobutamine echocardiography can offer information regarding wall-motion abnormalities and ischemic threshold, which are suggested to have a clinical value similar to elevated cTnI.

Short- and long-term prognostic value of cardiac troponin I and dobutamine echocardiography in patients with stabilized acute coronary syndromes.

BACKGROUND: This study investigated the short- and long-term prognostic values of cardiac troponin I (cTnI) and dobutamine echocardiography (DE) in patients with acute coronary syndrome (ACS) who stabilized after medical treatment. METHODS AND RESULTS: 171 consecutive patients of ACS accepted blood sampling for cTnI at the emergency department and DE at 4.9+/-0.6 days after admission. The prognostic values of cTnI, DE, and combined cTnI and DE were separately investigated at follow up periods of 30 days, 1 year and 3 years for hard events (cardiac death and non-fatal myocardial infarction) and all spontaneous events. CTnI was elevated in 55 (32%) patients and DE was positive in 114 (67%) patients. Elevated cTnI with positive DE were found in 44 (26%) patients. Within 30 days, the combination of elevated cTnI and positive DE provided more accurate prognostic information than each test result alone, and was the only independent predictor for both hard (p=0.014) and all events (p=0.012). After 1 year, cTnI alone had no prognostic value. The combination of an elevated cTnI level and a positive DE only had a prognostic value for all events (p=0.015). However, DE was an independent predictor for both hard (p=0.006) and all events (p=0.002). Neither cTnI alone nor cTnI combined with DE had a significant 3-year prognostic value. However, DE maintained its prognostic value and was still an independent predictor after 3 years for both hard (p=0.024) and all events (p=0.004). CONCLUSIONS: For patients with stabilized ACS, the diagnostic finding of elevated cTnI combined with a positive DE has a better short-term prognostic value than each test alone. However, DE alone has a better long-term prognostic value.

Coronary vasospasm inducing dynamic left ventricular outflow tract obstruction.

An 80-year-old man was admitted to the emergency department of our institution due to acute, anterior-wall myocardial infarction and cardiogenic shock. Two-dimensional echocardiography revealed systolic anterior motion of the mitral leaflets with severe left ventricular outflow tract obstruction. Although coronary angiography showed normal coronary arteries, an ergonovine provocation test induced diffuse coronary constriction of the left coronary artery, with chest pain, and ST-T changes seen on the electrocardiogram. These clinical signs caused us to suspect coronary spasm. The present case serves as a reminder that coronary vasospasm may be a factor in the development of dynamic left ventricular outflow tract obstruction. Early detection and intensive efforts to relieve vasospasm, including emergency coronary angiography and intracoronary injection of nitroglycerin, are essential.

Recurrent cerebral embolism and impending detachment of a previous nonmobile left atrial thrombus following initiation of anticoagulant therapy in a patient with nonvalvular atrial fibrillation.

A 65-year-old female with nonvalvular atrial fibrillation who presented with a transient ischemic attack was admitted to our hospital. Transesophageal echocardiography (TEE) revealed a nonmobile thrombus attached to the wall of the left atrial appendage. She suffered from a new episode of syncope on the 8th day following initiation of anticoagulant therapy. Follow-up TEE indicated not only that the left atrial (LA) thrombus decreased in size but also that the previous nonmobile thrombus became mobile and showed impending detachment. Urgent surgery was subsequently performed to remove the LA thrombus, and the patient recovered uneventfully. In conclusion, anticoagulant therapy may precipitate partial fragmentation or partial detachment of LA thrombus.

Coronary artery spasm-induced paroxysmal atrial fibrillation--a case report.

Paroxysmal atrial fibrillation is described in a patient that was consistent with the clinical history developed after induction of coronary artery spasm. The mechanism appeared to be sinus node artery spasm inducing sinus node ischemia. Coronary artery spasm can be a cause of paroxysmal atrial fibrillation.

Pulsation, systolic thrill and murmur in femoral veins secondary to severe tricuspid regurgitation.

We report on a case of pulsatile femoral veins with a systolic thrill and murmur in a 26-year-old patient who exhibited severe tricuspid regurgitation. The pulsatile nature of the veins may result from the 'ventricularization' of venous pressure with each pressure pulse. The observed systolic thrill and murmur may be due to the systolic reversal of substantial regurgitant flow in the venous system of the lower limbs. This case also demonstrates that severe tricuspid regurgitation can have far-reaching manifestations.

Effects of verapamil in normal elderly individuals with left ventricular diastolic dysfunction.

Treatment with oral verapamil for 3 to 4 days has been found to enhance left ventricular (LV) diastolic filling in elderly subjects as assessed by radionuclide angiography. However, there are no Doppler echocardiographic studies to assess the long-term effect of verapamil in normal elderly subjects. Thirteen healthy elderly subjects (mean age, 64 +/- 7 years; 8 men and 5 women) with LV diastolic dysfunction underwent this placebo-controlled cross-over trial. The effect of verapamil on LV diastolic function was assessed by treadmill exercise test and Doppler echocardiography at baseline, and after each 3-month treatment period (placebo or verapamil 120 mg once daily), separated by a 1-week washout period before cross-over. Blood pressure, heart rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo or verapamil. The exercise time was similar at baseline (11.4 +/- 2.4 min) and after placebo treatment (11.4 +/- 2.3 min) but significantly increased (P < 0.05) after verapamil treatment (12.3 +/- 2.0 min). The ratio of mitral A wave duration/pulmonary venous atrial systolic reversal duration increased after verapamil treatment (1.12 +/- 0.08) compared to placebo (0.93 +/- 0.06, P < 0.05) and baseline (0.89 +/- 0.09), which had similar durations. The isovolumic relaxation time (IVRT) was significantly decreased (P < 0.05) from 85 +/- 13 msec at baseline and 87 +/- 13 msec with placebo to 73 +/- 9 msec with verapamil. The results of this study suggest that in normal elderly patients with Doppler evidence of diastolic dysfunction, 3 months treatment with verapamil can increase exercise tolerance and improve LV diastolic function.

Spontaneous coronary artery spasm during coronary angiography in a patient with exercise-induced ST segment elevation.

We describe a patient with a history of early morning chest pain who developed ST segment elevation during a treadmill exercise test. Severe coronary artery stenosis was identified initially and was relieved after intracoronary administration of nitroglycerin. A history of vasospastic angina in this patient facilitated prompt diagnosis.

Usefulness of head-up tilt test in the evaluation and management of unexplained syncope or pre-syncope.

This study included 87 consecutive patients with unexplained syncope or pre-syncope who had undergone the head-up tilt (HUT) test with concomitant isoproterenol infusion. A positive response was defined as development of syncope or pre-syncope in association with substantial hypotension (decline of systolic blood pressure > or = 20 mmHg). Coronary artery spasm was suggested from the clinical symptoms and electrocardiographic findings in 1 patient (1/87= 1.1%). Intolerance to isoproterenol infusion was noted in 8 cases (8/87 = 9%). Of the 78 patients who completed the study, 73 showed positive responses (73/78 = 94%). (baseline systolic blood pressure = 125 +/- 23 mmHg endpoint systolic blood pressure = 76 +/- 11 mmHg, p < 0.05; baseline heart rate = 73 +/- 14 beats per minute vs endpoint HR = 80 +/- 24 beats per minute, p < 0.05). In 73 patients who showed positive responses, the systolic blood pressure (SBP) and heart rate (HR) returned to a safe level at 2 minutes when the patients were returned to a supine position (post-study 2 minutes SBP = 124 +/- 18 mmHg vs baseline SBP 125 +/- 23 mmHg, p = NS; post-study 2 minutes HR = 82 +/- 18 beats per minute vs baseline HR = 73 +/- 14 beats per minute, p < 0.05). All 73 patients with a positive HUT test received Atenolol therapy (50 mg daily). Only 35 of these 73 patients took Atenolol regularly and had a repeat HUT test. After atenolol therapy, persistent positive responses were observed in 19 cases (19/35 = 54%) and negative responses were noted in 16 cases (16/35 = 46%). The mean dosage of isoproterenol needed to provoke a positive HUT test in 19 patients who had received Atenolol therapy and had a positive repeat HUT test was 2.3 +/- 1.2 microg/min at baseline and 3.5 +/- 0.9 microg/min for post-Atenolol therapy (p < 0.001). Sixteen patients with a negative repeat HUT test were treated continuously with Atenolol and followed for a mean period of 13 +/- 11 months (range, 1-34 months). All 16 patients were free of syncope or pre-syncope during the period of follow up. In conclusion, the HUT test is mostly well tolerated and safe, even though the test has a low rate of adverse effects. Atenolol is effective for the prevention of provoked or spontaneous recurrent syncope or pre-syncope.

Isolated right atrial tear following blunt chest trauma: report of three cases.

Blunt chest trauma causing isolated right atrial tear and cardiac tamponade in three patients is reported. All three patients presented with hypotension, elevated central venous pressure and altered consciousness. Echocardiographic examination demonstrated pericardial effusion in all three cases. All three patients underwent operation with a median sternotomy approach without using cardiopulmonary bypass. At operation, two patients had one tear in the right atrium, the other had two tears in the right atrium. All three patients recovered uneventfully. Early use of echocardiography to detect the presence of hemopericardium and cardiac tamponade in patients with suspected atrial rupture following blunt chest trauma is advocated.

Large right atrial thrombus with pulmonary embolism.

We present the cases of two patients, aged 67 and 77 years, who were admitted for the evaluation of rapidly progressive dyspnea and syncope, respectively. Both patients developed large right atrial thrombi with pulmonary embolism. The first patient received recombinant tissue plasminogen activator and survived with an uneventful result, whereas the second patient received operative thrombectomy followed by intravenous heparin and died 15 days later of pulmonary infarction with pulseless electrical activity. Data from these limited experiences suggest that thrombolytic therapy might be considered in patients with right heart thrombi with pulmonary embolism.