Does routine stress-thallium cardiac scanning reduce postoperative cardiac complications?

OBJECTIVE: Prophylactic cardiac revascularization in patients with ischemic myocardium could reduce postoperative cardiac complications after aortic reconstruction. However, the effectiveness of this approach has not been documented. SUMMARY BACKGROUND DATA: Stress-thallium scanning can identify patients with ischemic myocardium. Morbidity and mortality after aortic reconstruction appears to be largely caused by co-existent coronary artery disease, and patients who have had recent cardiac revascularization have few postoperative cardiac complications. METHODS: Preoperative stress-thallium scanning was evaluated prospectively in 146 patients undergoing aortic reconstruction. Patients with positive studies underwent coronary arteriography and cardiac revascularization, when appropriate. Postoperative cardiac complications and long-term survival in these patients were compared with results from 172 similar patients undergoing aortic reconstruction without stress-thallium scanning. Results also were analyzed to determine predictors of postoperative cardiac events. RESULTS: Forty-one per cent of patients undergoing stress-thallium testing underwent coronary arteriography, and 11.6% had cardiac revascularization. In contrast, 14.7% of patients treated without stress-thallium testing had coronary arteriography, and 4.1% had revascularization (p < 0.01). Despite this, cardiac mortality, serious cardiac complications, and long-term cardiac mortality were similar in both groups. Only advanced age and intraoperative complications (but not a positive stress-thallium test) predicted postoperative cardiac events. CONCLUSIONS: Preoperative stress-thallium testing confirmed a high incidence of significant coronary artery disease in patients undergoing aortic reconstruction, but prophylactic cardiac intervention does not reduce operative or long-term mortality. Thus, the risk and expense of routine stress-thallium testing and subsequent cardiac revascularization cannot be justified.     

Efficacy of the customized employment supports (CES) model of vocational rehabilitation for unemployed methadone patients: preliminary results

This article presents initial efficacy data for an innovative vocational rehabilitation model designed for methadone-maintained patients--the Customized Employment Supports (CES) model. In this model, a CES counselor works intensively with a small caseload of patients in order to overcome the vocational as well as nonvocational barriers that hinder their employment, with the goal of attaining rapid placement in competitive employment. The CES model was implemented at two Manhattan methadone treatment programs as part of a randomized clinical trial comparing the model's employment outcomes with those of standard vocational counseling. The study tested the hypothesis that patients in the experimental group will have better employment outcomes than those in the comparison group. The data were collected from May 2001 through September 2003. The sample consisted of the first 121 patients who had completed their 6-month follow-up interviews. The preliminary results supported the hypothesis for two indices of paid employment, i.e., the CES group was more likely to obtain both competitive employment and informal paid employment. The clinical trial is continuing.     

Mesenteric venous thrombosis

Sixteen patients with mesenteric venous thrombosis were reviewed retrospectively during a period from 1983 to 1987. Twelve patients had progressive abdominal pain, three had gastrointestinal bleeding, and one had general malaise. Seven of these 16 patients had previous deep-vein thrombosis. After negative routine gastrointestinal and hepatobiliary evaluation, 11 patients underwent an infusion computerized tomographic scan. Of these, 10 had superior mesenteric vein thrombosis; three of these 10 patients had portal vein thrombosis. Selective arteriography was done in two patients because of gastrointestinal bleeding, and a diagnosis of mesenteric vein thrombosis was made on the venous phase of the examination. The remaining four patients developed acute abdominal symptoms requiring surgical exploration, at which time mesenteric venous thrombosis was discovered. An identifiable coagulopathy was detected in nine patients (protein C deficiency in six, protein S deficiency in two, and factor IX deficiency treated with factor IX concentrate in one). No case of congenital antithrombin-III deficiency was identified. Six of these nine patients had a past history of deep venous thrombosis. Of five patients who underwent surgical exploration, all required bowel resection. In follow-up, two patients died of intestinal necrosis and a third died of associated pancreatic cancer. Thirteen patients were discharged from the hospital. Treatment of coagulopathy was by heparin in three patients and sodium warfarin (Coumadin) in four patients. Long-term anticoagulation was not instituted because of gastrointestinal bleeding in three and cirrhosis in three patients. Mesenteric venous thrombosis can occur without gangrenous bowel. Diagnosis should be suspected when acute abdominal symptoms develop in patients with prior thrombotic episodes and a coagulopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

The value of power frequency spectrum analysis in the identification of aortoiliac artery disease

Prediction and localization of significant proximal occlusive disease in the lower extremities, whether in isolation or in combination with significant distal disease, still represent major problems to the noninvasive vascular laboratory. Power frequency spectrum analysis (PFSA) was done on continuous-wave Doppler signals in the common femoral artery of 86 limbs in 50 patients before and after postocclusive reactive hyperemia testing in an effort to differentiate hemodynamically significant from insignificant proximal occlusive disease, whether in isolation or in combination with hemodynamically significant distal disease. Limbs were assigned to four different categories according to their angiographic findings. With the use of a bandwidth at 50% peak amplitude (f50%) of 2000 Hz as the cut-off point between a positive and a negative examination, the test was 93% sensitive, 90% specific, and 92% accurate in distinguishing hemodynamically significant proximal lesions from hemodynamically insignificant lesions, regardless of distal disease. In addition, there exists a small group with significant disease at or close to the site of Doppler sampling, which produces f50% values of more than 3000 Hz. Diagnosis in this subgroup was much like that in carotid disorders. Finally, the predictive accuracy of standard noninvasive Doppler/segmental pressure measurement was compared with results of PFSA. In most patients, standard measurements were comparable; however, in the subgroup with hemodynamically significant proximal and distal disease, the PFSA technique accurately predicted hemodynamically significant proximal diseases in 93% of patients, where combined pressure/Doppler testing had an accuracy of only 61%. In all, spectrum analysis of common femoral artery velocity signals can greatly aid in determining the presence or absence of significant proximal disease in all situations.     

Prostate Artery Embolization in Patients with Prostate Volumes of 80 mL or More: A Single-Institution Retrospective Experience of 93 Patients

Purpose

To evaluate the safety and efficacy of prostate artery embolization (PAE) for the treatment of benign prostatic hyperplasia for prostates ≥ 80 mL.

The LpoA activator is required to stimulate the peptidoglycan polymerase activity of its cognate cell wall synthase PBP1a

A cell wall made of the heteropolymer peptidoglycan (PG) surrounds most bacterial cells. This essential surface layer is required to prevent lysis from internal osmotic pressure. The class A penicillin-binding proteins (aPBPs) play key roles in building the PG network. These bifunctional enzymes possess both PG glycosyltransferase (PGT) and transpeptidase (TP) activity to polymerize the wall glycans and cross-link them, respectively. In Escherichia coli and other gram-negative bacteria, aPBP function is dependent on outer membrane lipoproteins. The lipoprotein LpoA activates PBP1a and LpoB promotes PBP1b activity. In a purified system, the major effect of LpoA on PBP1a is TP stimulation. However, the relevance of this activation to the cellular function of LpoA has remained unclear. To better understand why PBP1a requires LpoA for its activity in cells, we identified variants of PBP1a from E. coli and Pseudomonas aeruginosa that function in the absence of the lipoprotein. The changes resulting in LpoA bypass map to the PGT domain and the linker region between the two catalytic domains. Purification of the E. coli variants showed that they are hyperactivated for PGT but not TP activity. Furthermore, in vivo analysis found that LpoA is necessary for the glycan synthesis activity of PBP1a in cells. Thus, our results reveal that LpoA exerts a much greater control over the cellular activity of PBP1a than previously appreciated. It not only modulates PG cross-linking but is also required for its cognate synthase to make PG glycans in the first place.

The peptidoglycan (PG) cell wall is an essential structure surrounding most bacterial cells. It provides them with their characteristic shape and protects their cytoplasmic membrane from osmotic lysis. PG is composed of glycan strands with a repeating unit of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) connected by a β-1 to -4 linkage (1). A peptide stem is attached to the MurNAc sugars of the polymer and is used to form cross-links between adjacent glycans, generating an interconnected matrix that encases the cell (1). Many of our best antibiotics, including penicillin and related β-lactam drugs, target the assembly of this structure (2). Thus, in addition to addressing a fundamental biological problem, understanding the molecular mechanisms underlying PG biogenesis and its regulation also promises to aid the development of novel antibacterial therapies.PG is built from a lipid-linked precursor called lipid II, which consists of a disaccharide-peptide monomer unit attached to an undecaprenol lipid via a pyrophosphate linkage (1). Once the lipid II precursor has been synthesized and transported to the outer face of the cytoplasmic membrane, it is polymerized and cross-linked into the PG matrix by enzymes with PG glycosyltransferase (PGTase) and transpeptidase (TPase) activity, respectively (1). There are two main types of PG synthases. The most well studied of the two are the class A penicillin-binding proteins (aPBPs), which have a large extracytoplasmic domain with both PGTase and TPase subdomains (3). The second type of synthase was discovered more recently and is formed by a SEDS (shape, elongation, division, sporulation) family PGTase in complex with a monofunctional, class B PBP (bPBP) with TPase activity (4–7). Although it remains a matter of debate how these two types of synthases work together to build the PG layer, the SEDS-bPBP complexes are known to be the essential enzymes of the cell elongation and division machineries in most bacteria (4, 5, 7). The aPBPs, on the other hand, are thought to play critical roles in maintaining the integrity of the PG matrix (5, 8–10).In Escherichia coli, the aPBP-type synthases PBP1a and PBP1b form a synthetic lethal pair (11, 12). Mutants inactivated for either enzyme alone are viable, whereas the simultaneous loss of both of their activities results in rapid cell lysis. In E. coli and other gram-negative bacteria, aPBP function requires interaction with outer membrane lipoproteins (13–17). LpoA is the activator for PBP1a, and this pairing is widely conserved among the gamma-proteobacteria (13, 14). In contrast, the LpoB activator of PBP1b has a more limited phylogenetic distribution with the unrelated LpoP protein substituting for it in Pseudomonas aeruginosa and many other members of the gamma-proteobacteria (13, 14, 17). In purified systems, the lipoproteins activate both the PGT and TP activities of their cognate synthases (13, 14, 18–20). However, LpoB and LpoP have a much more profound effect on the PG polymerase activity of their cognate PBP1b proteins than on cross-linking (18–20). In contrast, the major effect of LpoA on PBP1a is the stimulation of TPase activity (19). Unlike LpoB, the effect of LpoA on the PGTase activity of its cognate synthase is completely abolished by the inhibition of TP activity with β-lactams (19). Based on these biochemical results, the primary function of LpoB and LpoP is thought to be the activation of the PGTase activity of PBP1b, and the major function of LpoA is thought to be the activation of the TPase activity of PBP1a (1).To investigate the physiological significance of the activation of PBP1b by LpoB in cells, we previously identified E. coli PBP1b variants that bypassed the requirement for LpoB activation in vivo (21). The amino acid substitutions resulting in LpoB bypass activity mapped either to the PGTase domain or clustered in the interdomain linker region near the LpoB-binding domain (UB2H domain) of the PBP1b structure (Fig. 1A). Purified PBP1b variants with these changes had enhanced PGTase activity. Notably, variants of P. aeruginosa PBP1b that bypass the requirement for LpoP activation map to a similar region in the modeled structure of this enzyme (Fig. 1A) (17). The observation that PBP1b variants with elevated PGTase activity bypass the lipoprotein requirement for cellular function provides strong support for the in vivo activity of LpoB and LpoP being the activation of PG polymerization by PBP1b.Open in a separate windowFig. 1.PBP structures and locations of activator bypass substitutions. Shown is the structure of E. coli PBP1b (PDB ID code 3VMA) (35) (A) and model structures of P. aeruginosa PBP1b (A), E. coli PBP1a (B), and P. aeruginosa PBP1a (B) made using i-Tasser. The PBP1a structures were based on the structure from Acinetobacter baumannii (PDB ID code 3UDF) (37). The different domains of the PBPs are color-coded. The locations of the previously identified LpoB/LpoP bypass mutations in PBP1b (17) (A) are indicated on the structures as are the LpoA bypass substitutions in PBP1a identified in this report (B).Although the effect of LpoA on PBP1a activity has been extensively studied in vitro, the role of LpoA in the activation of its cognate PBP in cells has remained unclear. There are many reasons to believe that LpoA may have a distinct function from that of LpoB and act on its target PBP in a different way. The two lipoproteins are structurally and evolutionarily divergent (14, 18, 22–24). They also bind different accessory domains on their cognate aPBP and stimulate different PG synthetic activities in vitro (Fig. 1B) (14, 19). Therefore, to learn more about the cellular role of LpoA, we selected for variants of PBP1a that can function in the absence of the activator in both E. coli and P. aeruginosa. Similar to the PBP1b bypass variants (21), PBP1a bypass variants have amino acid substitutions that cluster in the interdomain linker region of PBP1a and hyperactivate its PGTase activity. Thus, this domain appears to play a conserved role in modulating the synthesis of glycan strands by different types of gram-negative aPBP enzymes. Using an in vivo assay for PGTase activity (5, 25, 26), we further showed that PBP1a requires LpoA to promote PG polymerization in cells. Thus, our results reveal that LpoA exerts a much greater control over the cellular activity of PBP1a than previously appreciated. It not only modulates PG cross-linking but is also required to activate PG polymerization by its cognate synthase. Furthermore, based on the similar locations of the lipoprotein bypass substitutions, our findings suggest that LpoA and LpoB regulate the cellular activity of their cognate aPBPs in a fundamentally similar way despite differences in their structure and in vitro behavior.