Combined surgical and endovascular treatment of acute aortic dissection type A: preliminary results

BACKGROUND: The established treatment modality of acute Stanford type A dissection includes repair of the ascending aorta and various portions of the aortic arch, whereas the descending aorta is left untreated. We report a simultaneous approach of open repair of the ascending aorta with transluminal stent grafting of the descending aorta to minimize the consequences of an untreated descending aorta. METHODS: From April 2001 to February 2002, 8 consecutive patients (3 women [37.5%] and 5 men [62.5%]) with a mean age of 55.7 years (range, 45 to 70 years) were intended to be treated with the combined method of surgical repair of the ascending aorta and transluminal stent grafting into the descending aorta during the period of deep hypothermic circulatory arrest. Circulatory arrest time ranged between 30 and 67 minutes (average, 38.8 minutes). Specially designed Talent stent grafts (32 to 40 mm in diameter, length 13 cm) were inserted under direct vision and deployed with the proximal end at the origin of the left subclavian artery. RESULTS: Intraoperative stent graft placement was successful in 7 patients (87.5%). Because of severe kinking of the distal arch, stent insertion failed in 1 patient (12.5%). One patient with a history of preoperative stroke in the middle cerebral artery died because of intracerebral bleeding on postoperative day 2, resulting in an in-hospital mortality of 12.5%. Mean intensive care unit stay was 6.4 days (range, 2 to 21 days) and overall hospital stay was 18.2 days (range, 7 to 33 days). Completion computed tomographic scans revealed complete thrombosis of the false lumen in 2 patients and partial thrombosis in 4 patients. Follow-up was complete and ranged from 1 to 9 months (mean, 5.4 months). CONCLUSIONS: This preliminary study shows that combined surgical and endovascular treatment of acute type A dissection is feasible, and at least partial thrombosis of the false lumen can be achieved, potentially minimizing the risk of further dilatation or rupture. Additionally, the stent graft expands the otherwise sickle-shaped true lumen, thereby ameliorating distal aortic perfusion. Long-term results are warranted to demonstrate the effectiveness of this new combined treatment modality.     

Long-term Effects of Botulinum Toxin on Neuromuscular Function

Background: Recent reports indicate increased incidence of Clostridium botulinum infections, particularly among drug abusers and tissue allograft recipients. Botulinum toxin also has potential application in biochemical warfare. The neurotoxin-induced paralysis often requires mechanical ventilation with and without muscle relaxants. The authors investigated the long-term effects of botulinum toxin on muscle function, expression of nicotinic acetylcholine receptors (nAChRs), and their interaction with muscle relaxant, atracurium.

Methods: Rats (n = 30) were injected with varying doses (0.625, 2.5, and 10 U) of botulinum toxin into the tibialis muscle. Control animals (n = 9) received an equivalent volume of saline. At 128 days after injection, neuromuscular function, pharmacodynamics of atracurium, and nAChRs were evaluated.

Results: Nerve-evoked tensions, including tetanic tension and muscle mass, were decreased on the toxin-injected side in a dose-dependent manner relative to saline-injected controls as well as the contralateral side. Specific muscle tension and specific tetanic muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium was reduced, the ED50 was unchanged, and the ED90 was increased in the highest (10-U) dose of toxin group. The atracurium plasma concentration to maintain a steady state 50% paralysis was significantly reduced in the 10-U toxin group. The nAChR concentrations in the tibialis muscle were significantly increased in a dose-dependent manner in all experimental groups.     

Low birth weight,but not postnatal weight gain,aggravates the course of nephrotic syndrome

Clinical and animal studies have shown a higher risk of an aggravated course of renal disease in childhood after birth for babies small for gestational age (SGA). In addition relative “supernutrition” and fast weight gain in early infancy seem to support the development of later disease. In a retrospective analysis of 62 cases of idiopathic nephrotic syndrome treated between 1994 and 2004 at a university centre for paediatric nephrology, we related the course of disease to birth weight and to the weight gain in the first 2 years of life. Six children were born SGA (birth weight <−1.5 standard deviation score), and 56 were born as appropriate for gestational age (AGA). In all SGA children renal biopsy was performed, while only 55% of the AGA children underwent renal biopsy (P = 0.07), showing no difference in renal histology. In the SGA group, four of six patients developed steroid resistance (vs 12/56 AGA, P < 0.05). Of the SGA children, 83% needed antihypertensive treatment in the course of the disease compared to 39% of the AGA children (P = 0.07). The extent of weight gain between birth and 24 months of age did not influence the course of disease. In conclusion, we were able to find evidence for an aggravated course of idiopathic nephrotic syndrome in former SGA children. Independently of birth weight, weight gain in the first 2 years of life did not influence the course of disease.     

Cardioprotective effects of the serine protease inhibitor aprotinin after regional ischemia and reperfusion on the beating heart

OBJECTIVE: Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal to preserve myocardium. However, reperfusion itself contributes to an additional myocardial injury (ie, reperfusion injury), which has been attributed to neutrophil infiltration with subsequent release of proteases and oxygen-derived radicals. We studied the effects of the serine protease inhibitor aprotinin (Trasylol) on myocardial ischemia and reperfusion in a rat model. METHODS: The effects of aprotinin (5000 and 20,000 U/kg) were examined in vivo in a rat model of regional myocardial ischemia (20 minutes) and long-term reperfusion (24 hours). Cardioprotecive effects were determined by means of measurement of creatine kinase and myeloperoxidase activity within the myocardium, as well as histochemical analysis. RESULTS: Aprotinin (20,000 U/kg) administrated 2 minutes before reperfusion significantly attenuated myocardial injury expressed as creatine kinase washout compared with that seen in vehicle-treated rats (65 +/- 25 vs 585 +/- 98 creatine kinase difference in units per 100 mg, P <.01). Administration of 5000 U/kg of the protease inhibitor resulted in partial inhibition of myocardial reperfusion injury. Moreover, cardiac myeloperoxidase activity in the ischemic myocardium, a marker of neutrophil accumulation, was significantly reduced after aprotinin treatment. Histologic analysis of the reperfused myocardium demonstrated reduced polymorphonuclear leukocyte infiltration and reduced tissue injury. Furthermore, aprotinin treatment resulted in decreased induction of cardiac myocyte apoptosis compared with that seen in vehicle-treated rats. CONCLUSIONS: Inhibition of serine proteases with aprotinin appears to be an effective means of preserving ischemic myocardium from reperfusion injury, even after 24 hours of reperfusion. Aprotinin might exert cardioprotection through inhibition of polymorphonuclear leukocyte-induced myocardial injury and inhibition of reperfusion-induced apoptosis of cardiac myocytes.     

The Well-being Model: A New Drug Interaction Model for Positive and Negative Effects

Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.

Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.

Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed.     

rt-PA Thrombolysis in Acute Thromboembolic Upper-Extremity Arterial Occlusion

Purpose: Retrospective analysis of the results of rt-PA thrombolysis in the treatment of acute thromboembolic occlusion of the upper limb. Methods: Of 55 patients with demonstrated acute embolic arterial occlusion, rt-PA thrombolysis was performed on 40 occlusions in 38 patients (23 women with a mean age of 62 years, range 32–85 years; 15 men with a mean age of 65 years, range 32–92 years) according to the following design: 6 mg rt-PA/hr for 30 min, 3 mg rt-PA/hr for the next 30 min, 1 mg rt-PA/hr for 7 hr, and 0.4 mg rt-PA/hr until the end of lysis. Onset of symptoms varied from 1 to 14 days. Included were three isolated upper-arm occlusions, nine combined brachial and forearm occlusions, and 28 forearm and hand artery occlusions. Results: The overall success rate was 55%. The lysis results for isolated upper arm, combined brachial and forearm occlusions, and forearm and hand artery occlusions were 100%, 66%, and 46%, respectively. In eight patients surgical embolectomy had to be performed after failed thrombolysis. No amputation was required in the follow-up period. No lethal complications occurred. Conclusions: Interventional rt-PA treatment of proximal upper-extremity arterial occlusions may be performed with comparable success rates to surgical embolectomy and without severe complications. For distal occlusions the results are inferior to the success rates obtained with surgery.     

A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia

INTRODUCTION: Benign prostatic hyperplasia (BPH) is associated with bothersome lower urinary tract symptoms (LUTS) and reduced patient quality of life (QoL). Phosphodiesterase (type) 5 (PDE5) inhibitors such as vardenafil are commonly used for the treatment of erectile dysfunction (ED), but have also been shown to improve the symptoms of BPH. This randomised, double-blind, placebo-controlled study investigated the effects of vardenafil on LUTS and QoL in men with BPH/LUTS, with or without concomitant ED. METHODS: Men aged 45-64 yr with BPH/LUTS and an International Prostate Symptom Score (IPSS) > or =12 were randomised to receive either 10mg vardenafil or placebo twice daily. LUTS were assessed with the use of two primary efficacy parameters, IPSS score and maximum urinary flow rate (Qmax), as well as postvoid residual (PVR) urine volume; ED was measured with the use of the erectile function (EF) domain score of the International Index of Erectile Function (IIEF-EF); and QoL was assessed with the Urolifetrade mark QoL-9 questionnaire. RESULTS: After 8 wk of treatment, there was a significant improvement in the IPSS total score in the vardenafil group compared with placebo (-5.9 and -3.6, respectively; p=0.0013). Nominally significant improvements in irritative and obstructive IPSS subscores (p=0.0017 and p=0.0081, respectively), EF (p=0.0001), and Urolife QoL-9 (p<0.0001) were also associated with vardenafil treatment. Qmax and PVR urine volume did not change significantly with treatment, although baseline values were already considered close to normal. Vardenafil was generally well tolerated, with most adverse events considered mild or moderate in severity. CONCLUSIONS: Vardenafil treatment significantly improved LUTS, EF, and QoL in men with BPH/LUTS. Vardenafil may be considered a promising treatment option for men with symptoms secondary to BPH.     

Augmentation of mechanical properties in osteoporotic vertebral bones – a biomechanical investigation of vertebroplasty efficacy with different bone cements

Recent clinical trials have reported favorable early results for transpedicular vertebral cement reinforcement of osteoporotic vertebral insufficiencies. There is, however, a lack of basic data on the application, safety and biomechanical efficacy of materials such as polymethyl-methacrylate (PMMA) and calciumphospate (CaP) cements. The present study analyzed 33 vertebral pairs from five human cadaver spines. Thirty-nine vertebrae were osteoporotic (bone mineral density < 0.75 g/cm2), 27 showed nearly normal values. The cranial vertebra of each pair was augmented with either PMMA (Palacos E-Flow) or experimental brushite cement (EBC), with the caudal vertebra as a control. PMMA and EBC were easy to inject, and vertebral fillings of 20-50% were achieved. The maximal possible filling was inversely correlated to the bone mineral density (BMD) values. Cement extrusion into the spinal canal was observed in 12% of cases. All specimens were subjected to axial compression tests in a displacement-controlled mode. From load-displacement curves, the stiffness, S, and the maximal force before failure, Fmax, were determined. Compared with the native control vertebrae, a statistically significant increase in vertebral stiffness and Fmax was observed by the augmentation. With PMMA the stiffness increased by 174% (P = 0.018) and Fmax by 195% (P = 0.001); the corresponding augmentation with EBC was 120% (P = 0.03) and 113% (P = 0.002). The lower the initial BMD, the more pronounced was the augmentation effect. Both PMMA and EBC augmentation reliably and significantly raised the stiffness and maximal tolerable force until failure in osteoporotic vertebral bodies. In non-porotic specimens, no significant increase was achieved.     

Ultrasonographic findings of the axillary part of the brachial plexus

In this prospective study we sought to determine anatomic variations of the main brachial plexus nerves in the axilla and upper arm via high-resolution ultrasonography (US) examination. Positions of nerves were studied via US in three sectional levels of the upper arm in 69 healthy volunteers (31 men and 38 women, median age 28 yr). Analysis was done by subdividing the US picture into eight pie-chart sectors and matching sectors for the position of the ulnar, radial, and median nerves. Shortly after the nerves pass the pectoralis minor muscle, they begin to diverge. At the middle level 9%-13%, and at the distal level, 30%-81% of the nerves are not seen together with the artery in the US picture. At the usual level of axillary block approach, we found the ulnar nerve in the posterior medial position in 59% of the volunteers. The other two nerves had two peaks in distribution: the radial nerve in posterior lateral (38%) and anterior lateral (20%) position, and the median nerve in anterior medial (30%) and posterior medial (26%) position. Applying light pressure distally can displace nerves to the side, especially when they are positioned anterior to the axillary artery. We conclude that an axillary block should be attempted as proximal as possible to the axilla. IMPLICATIONS: This prospective ultrasonography study demonstrates significant anatomic variations of the main brachial plexus nerves in the axilla and upper arm, which may increase the difficulty in identifying neural structures. Applying light pressure on the plexus can move nerves to the side, especially when they are positioned anterior to the axillary artery.     

Pathological Processing Techniques and Final Diagnosis of Breast Cancer Sentinel Lymph Nodes

Background

Recommendations for intraoperative and postoperative breast sentinel lymph node (SLN) processing differ widely. Micrometastases and isolated tumor cells (ITC) have recently been proposed as prognostically and therapeutically relevant. We compared 3 SLN protocols with regard to intraoperative and postoperative diagnosis.

Materials and Methods

SLN in cohort I (270 patients) were intraoperatively assessed by stereomicroscopy. Intraoperative frozen section (IFS) was used only in stereomicroscopically suspicious SLN. In cohort II (197 patients), all SLN were examined with only 1 IFS. Final SLN workup in cohorts I and II consisted of complete step sectioning with immunohistochemistry. In cohort III (268 patients) 2 or more IFS were performed followed by 3 step sections and immunohistochemistry.

Results

pN1 stages were significantly higher in cohorts I and II (33.3% and 34.0% respectively) than in cohort III (24.6%). Intraoperative false negativity for the detection of metastases (pN1) ranged from 54.4% (cohort I) and 35.8% (cohort II) to 21.2% (cohort III). In contrast, ITC were detected significantly more frequently in cohort I (9.3%) and cohort II (14.7%) than in cohort III (1.9%).

Conclusions

Higher rates of SLN metastases and ITC in cohort I/II compared to cohort III suggest that IFS may result in tissue loss thus increasing the risk of missing metastases. Sparse IFS but complete postoperative SLN workup with step sectioning and immunohistochemistry provides more accurate information regarding minimal disease in SLN, but often results in delayed axillary lymph node dissection. This is important for preoperative patient information and recommendations in SLN processing protocols.