Citations

Abstract Initial analysis of the Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of relapsed multiple myeloma patients showed significantly longer time to progression, higher response rate, and improved survival with single-agent bortezomib versus high-dose dexamethasone. In this updated analysis (median follow-up: 22 months), survival was assessed in both arms, and efficacy updated for the bortezomib arm. Median survival was 29.8 months for bortezomib versus 23.7 months for dexamethasone, a 6-month benefit, despite substantial crossover from dexamethasone to bortezomib. Overall and complete response rates with bortezomib were 43% and 9%, respectively; among responding patients, 56% improved response with longer therapy beyond initial response, leading to continued improvement in overall quality of response. Higher response quality (100% M-protein reduction) was associated with longer response duration; response duration was not associated with time to response. These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy. This study is registered at http://clinicaltrials.gov (Study ID NCT00048230).

AbstractMany congenital disorders of glycosylation (CDG) can be diagnosed by observing the extent of glycosylation of the abundant serum glycoprotein transferrin (Trf). Trf is an N‐glycosylated protein with two asparagine glycation sites. CDG types I are those genetic defects which occur prior to transfer of the complex oligosaccharide to the acceptor asparagine in the cotranslated polypeptide chain. CDG Ia constitutes by far the most frequent form of CDG and is the result of mutations in the phosphomannomutase gene. CDG Ia and the Ib subtype (Phosphomannoisomerase deficiency) result in low cellular mannose‐1‐phosphate levels, a required precursor for oligosaccharide assembly in the endoplasmic reticulum. The deficiency in oligosaccharides with branched mannose structures is thereafter expressed by the appearance of glycoproteins with unoccupied N‐glycosylation sites (hypoglycosylation). Currently, there have been at least 11 Type I defects, type Ia being by far the most frequently occurring. Most, if not all type I defects result in unoccupied N‐glycation sites. Hypoglycosylated Trf, also known as carbohydrate‐deficient Trf (CDT), can be detected using mass spectrometry (MS) to measure the masses of the serum Trf. The methods for sample preparation using affinity chromatography and MS analysis are described in this unit. Curr. Protoc. Hum. Genet. 54:17.4.1‐17.4.9 © 2007 by John Wiley & Sons, Inc.

SummaryThe continued expansion of newborn screening programmes to include additional conditions increases the responsibility of newborn screening laboratories to provide testing with the highest sensitivity and specificity to allow for identification of affected patients while minimizing the false‐positive rate. Some assays and analytes are particularly problematic. Over recent years, our laboratory tried to improve this situation by developing second‐tier tests to reduce false‐positive results in the screening for congenital adrenal hyperplasia (CAH), tyrosinaemia type I, methylmalonic acidaemias, homocystinuria, and maple syrup urine disease (MSUD). Beginning in 2004, this approach was applied to Mayo's newborn screening programme and resulted in a false‐positive rate of 0.09%, a positive predictive value of 41%, and a positive detection rate of 1 affected case in 1672 babies screened.

The coexistence of urologic malignancy (UM) and abdominal aortic aneurysm (AAA) is rare. Simultaneous treatment may increase morbidity, whereas staged operations delay necessary treatment. We reviewed our experience to develop guidelines for evaluation and management. Clinical data of all patients diagnosed between 1980 and 1998 with both AAA and UM, who also had staged or simultaneous surgical treatment were reviewed. Four thousand forty-seven patients underwent AAA repair during the study period at our institution. Of these, 18 (0.44%) patients, 16 men and two women (mean age: 74 years, range: 61 to 92) had UM. UM was discovered incidentally in nine patients with AAA with computed tomography (CT) scan (7) and ultrasonography (2). In one patient with AAA, hematuria raised the suspicion of UM. Eight patients were diagnosed with AAA during evaluation of UM by CT scan or ultrasound (7) or during laparotomy (1). Initial signs and symptoms included abdominal pain (33%), gross hematuria (33%), and urinary tract infections (17%), although 33% were asymptomatic. The AAA was symptomatic at first examination in three (17%) patients, 14 (78%) patients had hypertension, and two (11%) had renal insufficiency (overall mean serum creatinine: 1.6, range: 0.8 to 3.7). Mean AAA diameter was 5.8 cm (range: 3.8 to 8 cm). Aortography documented significant contralateral renal artery disease in two patients. Twelve patients underwent simultaneous AAA repair and resection of UM; the operations were staged in six (AAA repair first in 2, nephrectomy first in 4). One patient required emergent repair of a ruptured AAA three days after nephrectomy. UM was treated with nephrectomy in 17 patients, and with bilateral ureterectomy and cystectomy in one. A straight aortic graft was implanted in seven patients, a bifurcated graft in ten, and one had extra-anatomic reconstruction. Two patients required reconstruction of the contralateral renal artery. The 30-day mortality rate was 0% after staged and 6% after simultaneous repair (p= >0.1). Major perioperative complications occurred more frequently after simultaneous (42%) than after staged repair (33%), although the difference was not significant (p= >0.1). Two patients developed postoperative renal failure. Seventeen patients were followed for an average of 3.9 years (14 days to 10.8 years). Three (17%) patients died of recurrent cancer at 1, 10.7, and 10.8 years after surgery. Patients with resectable UM have satisfactory long-term survival, which justifies aggressive treatment of concomitant AAA. Aortography in these patients is suggested to exclude contralateral renal artery disease. Complications were frequent, but simultaneous repair did not increase morbidity or mortality significantly. The risk of AAA rupture after nephrectomy, need to correct contralateral renal artery disease at the time of nephrectomy, and disadvantage of delaying treatment of UM are compelling reasons to favor simultaneous treatment of AAA and UM.

As endografting technology advances, anatomical constraints limiting access and deployment have become less of a burden. While unsuitable candidates for endografting exist, these patients are becoming less frequent. To broaden the applicability of endovascular abdominal aortic aneurysm repair (EVAR), we have modified the bifurcated AneuRx™ device into a unilimb modular prosthesis, by placing an aortic extender cuff across the flow divider, thus excluding its contralateral limb. This technique was used with success in 3 groups of patients: with occlusion of 1 iliac artery, with a nontraversable iliac stenosis, or with a small calcific aortic bifurcation. In these patients, anatomy can make it difficult, if not impossible, to place a bifurcated stent graft. Whether as a planned preoperative procedure or as a ‘bail-out’ maneuver, this procedure has been successful in avoiding open surgical conversion.

Previous results following subfascial endoscopic perforator vein surgery were reported to be worse in post-thrombotic syndrome than in limbs with primary valvular incompetence. This report comprises a larger patient cohort with longer follow-up. The goal of this study was to determine if subfascial endoscopic perforator vein surgery is justified in patients with postthrombotic venous insufficiency. The clinical data of 91 consecutive patients who underwent subfascial endoscopic perforator vein surgery with or without superficial reflux ablation over a 7-year period from May 1993 to June 2000 were retrospectively analyzed. Fifty-four females and 37 males (median age, 53 years; range, 20-77) underwent 103 subfascial endoscopic perforator vein surgery procedures. Forty-two limbs were classified as C6 (active ulcer), 34 as C5 (healed ulcer), and 24 as C4 (lipodermatosclerosis). Thirty procedures were performed in post-thrombotic limbs. Concomitant superficial reflux ablation was performed in 74 limbs (72%); saphenous vein stripping had been previously performed in 29 (28%). Deep venous incompetence was present in 89% of limbs; 13% had venous outflow obstruction on plethysmography. Cumulative ulcer healing in post-thrombotic limbs was not significantly different from limbs with primary valvular incompetence; 30-, 60-, and 90-day healing rates were 44%, 72%, and 72% vs 39%, 70%, and 87%, respectively (p = 0.35). On univariate analysis, the presence of ulcer greater than 2 cm in diameter was associated with delayed ulcer healing (p = 0.02). Cumulative ulcer recurrence in all limbs was 4%, 20%, and 27% at 1, 3, and 5 years, respectively. Ulcer recurrence in post-thrombotic limbs was higher than in limbs with primary valvular incompetence at 1, 3, and 5 years; 16%, 47%, and 56% vs 0%, 8%, and 15%, respectively (p = 0.001). Recurrent ulcers were small, superficial, and easier to heal. Clinical improvement was significant even in post-thrombotic limbs; median clinical score decreased from 9.5 to 3 (p=0.001), and median outcome score was +2 (mean 1.9; range, -I to 3). Median clinical score in patients with primary valvular incompetence improved from 6 to 1.5 (p = 0.0001). Subfascial endoscopic perforator vein surgery with superficial reflux ablation promoted ulcer healing, improved clinical outcome, and resulted in a low long-term ulcer recurrence rate in limbs with primary valvular incompetence. Despite good clinical outcome in post-thrombotic limbs, ulcer recurrence was high. These results imply that the role of subfascial endoscopic perforator vein surgery with superficial reflux ablation in patients with post-thrombotic limbs continues to be controversial.

In situ lesser saphenous vein (LSV) graft has been advocated in cases where the greater saphenous vein is not available and the target arteries are confined to the lower leg. This is often the case of diabetic patients, whose occlusive disease pattern typically affects the tibioperoneal vessels, sparing the femoropopliteal segment. The in situ technique offers the potential advantages of decreasing surgical trauma to the vein and its vasa vasorum, better size-matching between vein and artery at the anastomoses, and improving hemodynamics. The authors reviewed the use of in situ LSV graft with attention to its indications and technical requirements. A 73-and a 76-year-old man presented with critical limb ischemia. Both had a history of diabetes, chronic renal failure, and previous use of the greater saphenous veins for coronary or peripheral bypasses. Both had good femoropopliteal inflow and tibioperoneal disease with single runoff through the distal peroneal and common plantar arteries, respectively. Venous mapping showed diminutive veins, with exception of an adequate ipsilateral lesser saphenous vein. The patients were placed in prone position for a posterior approach. The lesser saphenous veins were exposed through a longitudinal incision. Proximal anastomosis was based on the popliteal artery, exposed through the same incision. A successful in situ lesser saphenous vein bypass was performed by using the common plantar and the distal peroneal artery as target vessels. Both bypasses were patent at 24 and 18-months' follow-up, respectively. Selection criteria for in situ LSV bypass are patent femoral arteries; accessible target vessels in prone position through a medial, posterior, or lateral approach; and adequate LSV in diameter and length. In the authors' experience, in situ LSV bypass is a safe and simple option that offers successful distal revascularization.

The purpose of this study was to examine the technical aspects of intraoperative duplex ultrasound (DUS) following carotid endarterectomy (CEA), suggest criteria to differentiate significant lesions requiring immediate surgical revision from normal or benign defects, and evaluate how frequently intraoperative DUS provides useful or unsuspected information. A retrospective study was performed on all patients who had both CEA and intraoperative carotid DUS between January 1,1990. and January 1,1995. A total of 155 DUS examinations were performed in 149 patients. Findings were grouped into three categories: normal; minor/insignificant lesions; and hemodynamically significant lesions based on the presence or absence of elevated peak systolic velocities, visible stenosis/thrombus, or intimal flap/dissection. Postoperative status was correlated with intraoperative DUS findings. Ninety-one (59%) examinations performed on 87 patients produced normal findings. Forty-seven (30%) examinations performed on 45 patients showed minor abnormalities consisting of insignificant residual plaque, residual external carotid artery stenoses, small intimal flaps, elevated velocities with no associated anatomic lesion, or an arterial kink. Fourteen patients (9%) had significant findings requiring immediate surgical revision. These consisted of large intimal flaps or dissection in six patients, marked residual plaque and significant stenosis in five patients, thrombus in two patients, and a kink in one patient. Three additional patients ( 2 %) had significant findings but were not revised for various reasons. No significant difference was identified in morbidity or mortality rates between those patients with normal findings, those patients with minor technical defects, and those patients with significant abnormalities undergoing immediate surgical revision. However, two of three patients who had significant abnormalities within the common carotid artery that were not revised suffered perioperative ipsilateral strokes. Intraoperative DUS is a safe and accurate method to assess the technical adequacy of CEA. Intraoperative DUS showed significant lesions in 11% of patients. Identification and immediate repair of significant technical defects may decrease perioperative complication rate and long-term restenosis rate.

Studies of the immunohistochemical profiles and clinical course of desmoplastic melanoma have produced conflicting results. We identified 28 cases of desmoplastic melanoma after a search of our files for spindle cell neoplasms of the head and neck from 1960 through 1995. The 17 male (61%) and 11 female (39%) patients averaged 65 years of age. The cheek was the most common location (12 cases, 43%). The average length of follow-up was 5 years. Overall 5-year survival rate was 46%. Melan A and tyrosinase positivity (P = 0.0195), smooth muscle actin positivity (P = 0.0328), tumor size (P = 0.0297), and tumor thickness (P = 0.0419) were significantly associated with local progression-free survival. No histologic or immunohistochemical marker was associated with overall or metastasis-free survival.

The goals of this study were to evaluate the validity of the visual analogue scale (VAS) for young children and to compare a newly developed method of teaching children to use a VAS with one used in our previous studies. It was hypothesized that the new method would increase the number of children who understand the VAS and correctly mark their responses on the VAS line. The association between child's age and ability to understand the VAS was also evaluated. One hundred-six children with a laceration requiring sutures and receiving a lidocaine injection for local anesthesia participated in the study. They ranged in age from 5 to 14 years. Two outcome measures were used to assess the baseline and lidocaine injection pain: a 5-point Likert scale and a VAS. A calibration study was used to determine whether the subjects were able to use the VAS to make proportional judgments about their perceptions. Teaching method had no effect on the number of subjects who could correctly mark their responses on the VAS line, nor did it significantly increase the number of subjects who could understand the concept of the VAS. Subjects who were able to understand the VAS were significantly older (mean = 9.8 years, SD = 2.8) than those who did not (mean = 8.2 years, SD = 2.5). Overall, only about one third of the subjects were able to correctly mark the VAS and understand the concept of the VAS. Other measures of pain that are better understood by young children may be more valid indicators of pain than the VAS.