Incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy for prostate cancer

PURPOSE: During radical prostatectomy for prostate cancer tumor at the surgical margin is a relatively frequent finding. We summarize the literature on the incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy. MATERIALS AND METHODS: The literature was reviewed for data on positive margins during radical prostatectomy for prostate cancer. RESULTS: Positive surgical margins may result from artifacts induced by tissue processing, incising inadvertently into the prostate or incising into extraprostatic tumor that has extended beyond the limits of resection. Patients with 10 ng./ml. or greater preoperative prostate specific antigen, biopsy Gleason score 7, multiple positive biopsies, or clinical stage T2b, T2c or T3 cancer have a higher risk of positive margins. Preoperative endorectal magnetic resonance imaging may be useful in staging a select group of patients. Neoadjuvant androgen deprivation reduces the incidence of positive margins but does not appear to delay progression or improve survival. The surgical approach, retropubic or perineal, may influence the location and etiology of positive margins. In general, nerve and bladder neck sparing procedures do not compromise tumor removal in appropriately selected patients. Positive margins increase the risk of progression and correlate with decreased cancer specific and overall survival. There is no consensus on the management of positive margins. External beam radiation and androgen deprivation may be administered as adjuvant therapy or at the time of recurrence. CONCLUSIONS: Tumor at the specimen edge is an adverse prognostic factor. With appropriate patient selection and meticulous surgical technique some positive margins can be prevented. Controlled prospective randomized studies of postoperative therapy are needed before definitive recommendations can be made for treating positive margins.     

Evaluation of fine needle capillary sampling in superficial and deep-seated lesions. An analysis of 670 cases

The gene rafY from the plasmid pRSD2, which enables Escherichia coli to grow on raffinose, was transferred into expression plasmid pUSL77. The protein was expressed in the porin-deficient Escherichia coli strain KS26 and was isolated and purified to homogeneity. The pure protein was reconstituted into lipid bilayer membranes. It formed an ion-permeable channel with a single-channel conductance of 2.9 nS of the open state in 1 M KCl, which is approximately twice of that of the general diffusion pores OmpF and OmpC of E. coli outer membrane. At lower pH the channel exhibited rapid flickering between three substates of the open channel. The RafY channel appears to be wide and water filled and has a small selectivity for cations over anions. Although RafY is part of an uptake and fermentation system for raffinose it does not contain a binding site for carbohydrates. Our results suggest that RafY is a general diffusion pore with a diameter, larger than that of the general diffusion porins OmpF and OmpC, that allows the diffusion of high-molecular-mass carbohydrates through the outer membrane.     

Motifs involved in interchain binding at the tail-end of spectrin

Segments 20-22 of alpha-spectrin and 1-3 of beta-spectrin are required for high avidity interchain binding at the tail-end of the molecule. Here, sequence analysis guided by the crystal structure of spectrin's repeating segments was used to redefine the boundaries of a repetitive beta segment that is critical for interchain binding and demonstrate the contribution of non-repetitive spectrin segments in high avidity interchain binding. Our results show that several motifs together are required for high avidity binding, indicating that interchain binding at the tail-end of the spectrin molecule depends on the long distance coordination of several different elements. We also explored the role of unusual motifs contained in beta segments involved in interchain binding. A row of basic residues and a row of small hydrophobic residues were found not to be required for interchain binding, suggesting that their conservation among species reflects functions unrelated to interchain binding. The octamer between segments beta 2 and beta 3 that maintains a specific register between true binding sites was found to have an indirect role in interchain binding by stabilizing neighboring segments. A 5-residue domain in segment beta 2 (EKPPK) was required for interchain binding because it sustains normal helix-helix interactions within segments beta 2.     

Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura: report of seven patients and a meta-analysis

We present the results of a meta-analysis using clinical data obtained from seven of our patients and 24 previously reported patients with idiopathic thrombocytopenic purpura complicated by intracranial hemorrhage. Twenty-four had an intracerebral hemorrhage (ICH) and seven had a subdural hematoma (SDH). Mean age of the patients with ICH was significantly younger than those with SDH. The mortality rate of ICH associated with ITP was similar to that of spontaneous ICH. All seven patients with SDH improved without sequelae.     

Retail yield and fabrication times for veal as influenced by purchasing options and merchandising styles

Twenty-nine selected styles of subprimals or sections of veal were obtained from a commercial facility to assist in the development of a support program for retailers. They were fabricated into bone-in or boneless retail cuts and associated components by trained meat cutters. Each style selected (n = 6) was used to generate mean retail yields and labor requirements, which were calculated from wholesale and retail weights and processing times. Means and standard errors for veal ribs consisting of five different styles (n = 30) concluded that style #2, 7-rib 4 (10 cm) x 4 (10 cm), had the lowest percentage of total retail yield (P < .05) owing to the greatest percentage of bone. Furthermore, rib style #2 required the longest total processing time (P < .05). Rib styles #3, 7-rib chop-ready, and #5, 6-rib chop ready, yielded the greatest percentage of total retail yield and also had the shortest total processing time (P < .05). Within veal loins, style #2, 4 (10 cm) x 4 (10 cm) loin kidney fat in, had the greatest percentage fat (P < .05). Loin styles #2 and #3, 4 (10 cm) x 4 (10 cm) loin special trimmed, generated more lean and fat trimmings and bone, resulting in lower percentage of total retail yields than loin style #1, 0 (0 cm) x 1 (2.5 cm) loin special trimmed (P < .05). Results indicated that bone-in subprimals and sections required more processing time if fabricated into a boneless end point. In addition, as the number of different retail cuts increased, processing times also increased.     

ISIS 4: clinical controversy regarding magnesium infusion, thrombolytic therapy, and acute myocardial infarction

Magnesium (Mg) infusions over 24 hours were given to patients with suspected acute myocardial infarction (AMI) at least 2 hours after thrombolysis. Patients showed no benefit and even some increased risk in contrast to reduction in mortality obtained by Mg therapy in smaller trials. Results of all of the studies were pooled and statistically analyzed, according to a fixed-effects model that is inappropriate for studies of different protocols. The panel concluded that further study of Mg in AMI is not needed. This conclusion has been questioned.     

Fast and one-step folding of closely and distantly related homologous proteins of a four-helix bundle family

Bovine acyl-coenzyme A binding protein is a four-helix bundle protein belonging to a group of homologous eukaryote proteins that binds medium and long-chain acyl-coenzyme A esters with a very high affinity. The three-dimensional structure of both the free and the ligated protein together with the folding kinetics have been described in detail for the bovine protein and with four new sequences reported here, a total of 16 closely related sequences ranging from yeasts and plants to human are known. The kinetics of folding and unfolding in different concentrations of guanidine hydrochloride together with equilibrium unfolding have been measured for bovine, rat and yeast acyl-coenzyme A binding protein. The bovine and rat sequences are closely related whereas the yeast is more distantly related to these. In addition to the three natural variants, kinetics of a bovine mutant protein, Tyr31 --> Asn, have been studied. Both the folding and unfolding rates in water of the yeast protein are 15 times faster than those of bovine. The folding rates in water of the two mammalian forms, rat and bovine, are similar, though still significantly different. A faster unfolding rate both for rat and the bovine mutant protein results from a lower stability of the native states of these. These hydrophobic regions, mini cores, have been identified in the three-dimensional structure of the bovine protein and found to be formed primarily by residues that have been conserved throughout the entire eukaryote evolution from yeasts to both plants and mammals as seen in the sample of 16 sequences. The conserved residues are found to stabilize helix-helix interactions and serve specific functional purposes for ligand binding. The fast one-step folding mechanism of ACBP has been shown to be a feature that seems to be maintained throughout evolution despite numerous differences in sequence and even dramatic differences in folding kinetics and protein stability. The protein study raises the question to what extent does the conserved hydrophobic residues provide a scaffold for an efficient one-step folding mechanism.     

Cyclic voltammetry on electrode surfaces covered with porous layers: An analysis of electron transfer kinetics at single-walled carbon nanotube modified electrodes

Cyclic voltammetry is recorded of the oxidation of ferrocyanide on a glassy carbon electrode modified with multiple layers of single-walled carbon nanotubes. The current response is interpreted in terms of semi-infinite planar diffusion towards the macro-electrode surface and in terms of oxidation of the electroactive species trapped in pockets in between the nanotubes. A thin layer model is used to illustrate the effects of diffusion within a porous layer. It is found that a semi-infinite planar diffusion model alone is not appropriate for interpreting the kinetics of the electron transfer at this electrode surface. In particular, caution should be exercised in respect of comparing voltammetric peak-to-peak potential separations between naked electrodes and nanotube-modified electrodes for the inference of electrocatalysis via electron transfer via the nanotubes.