Hybrid procedures as a combined endovascular and open approach for pararenal and thoracoabdominal aortic pathologies

OBJECTIVES: to report our experience with hybrid vascular procedures in patients with pararenal and thoracoabdominal aortic pathologies. METHODS: 68 patients were treated for thoracoabdominal aortic pathologies between October 1999 and February 2004; 19 patients (16 men; mean age 68, range 40-79) with high risk for open thoracoabdominal repair were considered to be candidates for combined endovascular and open repair. Aortic pathologies included five thoracoabdominal Crawford I aneurysms, one postdissection expanding aneurysm, three symptomatic plaque ruptures (Crawford IV), five combined thoracic descending and infrarenal aneurysms with a healthy visceral segment, three juxtarenal or para-anastomotic aneurysms, and two patients with simultaneous open aortic arch replacement and a rendezvous maneuver for thoracic endografting. Commercially available endografts were implanted with standardized endovascular techniques after revascularization of visceral and renal arteries. RESULTS: Technical success was 95%. One patient developed a proximal type I endoleak after chronic expanding type B dissection and currently is waiting conversion. Nine patients underwent elective, five emergency and five urgent (within 24 h) repair. 17 operations were performed simultaneously, and 2 as a staged procedure. Postoperative complications include two retroperitoneal hemorrhages, and one patient required long-term ventilation with preexisting subglottic tracheal stenosis. Thirty-day mortality was 17% (one multiple organ failure, one secondary rupture after open aortic arch repair, one myocardial infarction). Paraplegia or acute renal failure were not observed. Total survival rate was to 83% with a mean follow-up of 30 months. CONCLUSIONS: Midterm results of combined endovascular and open procedures in the thoracoabdominal aorta are encouraging in selected high risk patients. Staged interventions may reduce morbidity.     

Development of three parallel cytochrome P450 enzyme affinity detection systems coupled on-line to gradient high-performance liquid chromatography.

A high resolution screening (HRS) technology is described, in which gradient high-performance liquid chromatography (HPLC) is connected on-line to three parallel placed bioaffinity detection systems containing mammalian cytochromes P450 (P450s). The three so-called enzyme affinity detection (EAD) systems contained, respectively, liver microsomes from rats induced by beta-naphthoflavone (CYP1A activity), phenobarbital (CYP2B activity), and dexamethasone (CYP3A activity). Each P450-EAD system was optimized for enzyme, substrate, and organic modifier (isopropyl alcohol, methanol, and acetonitrile) in flow injection analysis mode. Characteristic P450 ligands were used to validate the P450-EAD systems. IC(50) values of the ligands were measured and found to be similar to those obtained with conventional microtiter plate reader assays. Detection limits (n = 3; signal-to-noise ratio = 3) of potent inhibitors ranged from 1 to 3 pmol for CYP1A activity, 4 to 17 pmol for CYP2B activity, and 4 to 15 pmol for CYP3A activity. The three optimized P450-EAD systems were subsequently coupled to gradient HPLC and used to screen compound mixtures for individual ligands. Finally, to increase analysis efficiency, a HRS system was constructed in which all three P450-EAD systems were coupled on-line and in parallel to gradient HPLC. The triple parallelized P450-EAD system was shown to enable rapid profiling of individual components in complex mixtures for inhibitory activity to three different P450s.     

Giving up driving in Alzheimer's disease—an integrative therapeutic approach

For patients with Alzheimer's disease (AD), a recommendation to stop operating a motor vehicle can be a serious event complicated by a loss of self-esteem and personal dignity. Patients are often reluctant to give up an activity so essential, both practically and symbolically, to independent living. We describe here a patient with moderately progressed AD who lacked insight of his need to cease driving. Through an integrative treatment approach, combining behavioral and psychodynamic modalities, we helped him to formulate effective ways of coping with his loss of access to independent transportation. We favor a psychotherapeutic strategy that combines behavioral and managerial measures with dynamic patient interaction, thereby developing the patient's insight of the need to give up driving while fostering his sense of autonomy.     

Nefopam, a Nonsedative Benzoxazocine Analgesic, Selectively Reduces the Shivering Threshold in Unanesthetized Subjects

Background: The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. The authors evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering.

Methods: Nine volunteers were studied on three randomly assigned days: (1) control (saline), (2) nefopam at a target plasma concentration of 35 ng/ml (low dose), and (3) nefopam at a target concentration of 70 ng/ml (high dose, approximately 20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. The authors determined the thresholds (triggering core temperature at a designated skin temperature of 34[degrees]C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response.

Results: Nefopam did not significantly modify the slopes for sweating (0.0 +/- 4.9[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = 0.73 +/- 0.32) or vasoconstriction (-3.6 +/- 5.0[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = -0.47 +/- 0.41). In contrast, nefopam significantly reduced the slope of shivering (-16.8 +/- 9.3[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = 0.92 +/- 0.06). Therefore, high-dose nefopam reduced the shivering threshold by 0.9 +/- 0.4[degrees]C (P < 0.001) without any discernible effect on the sweating or vasoconstriction thresholds.     

Compulsive respiratory stereotypies in children with autistic features: Polygraphic recording and treatment with fenfluramine

Syncopes due to compulsive respiratory stereotypies were studied in eight patients with autistic features. Most had been referred for episodes thought to be intractable epileptic seizures. Polygraphic recording showed two types of syncope, one induced by prolonged apnea and the other by a prolonged Valsalva maneuver. Fenfluramine, 1.5–3 mg/kg per day, was given in an open trial. In four of five cases with frequent Valsalva maneuvers, respiratory stereotypies and syncopes were suppressed for 2–18 months. Patients with periodic apneas were more severely retarded and had less clear benefit. Side effects consisted of dose-dependent sedation and mild weight loss which stabilized without interrupting treatment. We suggest that these syncopes are volitional and may be associated with pleasant sensations. A double-blind placebo-controlled trial of fenfluramine seems warranted in such patients.     

Familial amyloidotic polyneuropathy: long-term follow-up of abdominal fat tissue aspirate in patients with and without liver transplantation.

To estimate the evolution of amyloid in tissue, we studied abdominal fat aspirates of cases with familial amyloidotic polyneuropathy (FAP) longitudinally at regular intervals between 1994 and 2006. In 22 cases (13 carriers and nine patients) not yet transplanted median follow-up was 3.3 years (range 0.4-11.3). We found a significant increase in the amyloid grade of fat tissue from 2+ to 4+ and from 0 to 4+ in two of three subjects with follow-ups of >7 years, after 7 and 11 years, respectively. All other subjects remained negative or did not show a significant change. In 11 liver transplant patients, follow-up with fat aspirate was available with a median duration of 3.1 years (range 1.0-10.1). A comparison was made with cardiac amyloid as judged by the cardiac septum diameter and the serum NT-ProBNP (N-terminal pro-B-type natriuretic peptide) level. No stable increase of amyloid in fat was seen in any patient. A stable decrease of amyloid grade was seen in one patient 5 years after transplantation. In contrast, the cardiac septum diameter increased >or=4 mm in six of the 11 transplant patients. Our study shows the diagnostic utility of a regularly repeated fat aspirate in carriers at risk for the development of ATTR amyloidosis. Evolution of amyloid deposition in fat tissue is very gradual. After liver transplantation, amyloid deposition in fat tissue seems to stabilize and may even decrease in the long term, whereas amyloid deposition in cardiac tissue appears to be progressive.     

The value of pretreatment clinical and biochemical parameters in patients with newly diagnosed untreated prostate carcinoma and no indications for bone metastases on the bone scintigram

Between 10% and 25% of patients with newly diagnosed prostate cancer without bone metastases at the time of diagnosis will develop metastases during follow-up. To determine the value of clinical and biochemical parameters for assessment of prognosis at the time of diagnosis, a retrospective study was performed in 124 consecutive patients with newly diagnosed prostate cancer without bone metastases. The mean follow-up was 41 months, during which time 36 patients died and 15 patients developed metastases. Bone scans were classified from 0 (=normal) through 2 (=abnormal, but not typical for metastases) and were correlated with age, alkaline phosphatase (AP), prostate-specific antigen (PSA), tumour grade, T-stage and N-stage. In patients with a class 2 scan, additional roentgenograms and follow-up were used to exclude metastases at initial stage. All parameters, including therapy, were finally correlated with the development of metastases and survival. For survival 38 patients with proven metastases were used as controls. For all parameters tested, no statistically significant differences were found between the three bone scan classifications. The interval between diagnosis and the development of metastases ranged from 12 to 72 months. For the risk of development of metastases only PSA was found to be a significant correlate (P=0.0075). However, when tumour stages were clustered in limited disease (T0–2) and extensive disease (T3–4), the incidence of metastases was significantly higher in patients with extensive disease than in those with limited disease (P=0.0021). Finally, age, PSA and Anderson classification were found to be significant correlates of survival, but in stepwise analysis PSA was selected as the most prognostic variable (P<0.0001). In contrast with a typical pattern of metastases on bone scintigraphy, an abnormal scan (class 1 and 2) at the time of diagnosis is not a poor prognostic parameter of the risk of death. In conclusion, in patients with prostate cancer without bone metastases at the time of diagnosis, pretreatment PSA and tumour stage can be used for the assessment of risk of development of metastases during follow-up and survival. For this purpose, tumour stage should be clustered in limited and extensive disease. Received 14 April and in revised form 9 June 1997     

Comparison of dobutamine stress echocardiography and technetium-99m sestamibi single-photon emission tomography for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy

Stress echocardiography has been considered an accurate method for the diagnosis of coronary artery disease in hypertensive patients and in patients with left ventricular hypertrophy. In contrast, the specificity of myocardial perfusion scintigraphy in these patients has been questioned. The aim of this study was to compare the accuracy of these two imaging modalities in conjunction with dobutamine stress test for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy. Dobutamine (up to 40 μg kg^–1min^–1) stress echocardiography in conjunction with sestamibi (MIBI) single-photon emission tomography (SPET) was performed in 84 patients with the diagnosis of systemic hypertension who had been referred for evaluation of myocardial ischaemia. Ischaemia was defined as new or worsened wall motion abnormalities at echocardiography and reversible perfusion defects at SPET. Significant coronary artery disease (≥50% luminal diameter stenosis) was detected in 66 patients (79%). The sensitivity, specificity and accuracy of the ischaemic pattern at echocardiography for the diagnosis of coronary artery disease were 73% (CI 63%–82%), 83% (CI 75%–91%) and 75% (CI 66%–84%), those for MIBI were 67% (CI 57%–77%), 83% (CI 75%–91%) and 70% (CI 60%–80%) respectively (P = NS vs echocardiography). Significant stenosis was detected in 123 (49%) of the 252 analysed coronary arteries. The sensitivity, specificity and accuracy of echocardiography for the regional diagnosis of coronary artery disease were 63% (CI 56%–69%), 90% (CI 86%–94%) and 77% (CI 72%–82%). Those for MIBI were 58% (CI 51%–64%), 91% (CI 87%–94%) and 75% (CI 69%–80) respectively (P = NS vs echocardiography). Left ventricular hypertrophy was detected in 59 patients (70%) by echocardiography and did not influence the overall or regional specificity of echocardiography or MIBI SPET. It is concluded that in hypertensive patients, dobutamine stress echocardiography and MIBI SPET have a comparable accuracy for the overall and regional diagnosis of coronary artery disease. Hypertensive patients with or without left ventricular hypertrophy should not be considered unsuitable candidates for stress myocardial perfusion scintigraphy. Received 10 July and in revised form 19 September 1997