Treatment-Based Three-Dimensional Classification and Management of Anorectal Infections.

This article provides a current overview on clinical anatomy, pathophysiology, workup and surgical management of anorectal abscesses. Based on the three-dimensional nature of anorectal abscesses, a novel treatment-based classification is proposed. It examines the basis of a philosophic shift from simple drainage to concomitant definitive treatment of abscesses and their underlying primary fistulous trajectories. Complications are discussed specifically in this context.

Enhanced recovery protocol: implementation at a county institution with limited resources.

The benefits of an enhanced recovery protocol (ERP) in colorectal surgery have been well described; however, data on the implementation process is minimal, especially in a resource-limited institution. The purpose of this study was to evaluate outcomes during implementation of a physician-driven ERP at a public-funded institution. We retrospectively reviewed all elective colorectal surgery during a transition from standard care to an ERP (implemented via a standard order sheet). Data regarding use of care plan, length of stay (LOS), and rates of postoperative complications and readmission were recorded. One hundred eleven patients were included in the study; however, complete use of the ERP after its introduction occurred in a total of 50 patients for a compliance rate of 60 per cent (95% confidence interval [CI], 49 to 70). Late implementation of ERP diet, analgesics, and activity were the most common process errors. Full application of the ERP reduced mean LOS by 3 days (P=0.002), and there was a trend toward decreased postoperative morbidity without an increase in readmission rate (P=0.61). Full implementation of an ERP for colorectal surgery faces many challenges in a resource-limited county institution; however, when fully applied, the ERP safely reduced overall LOS, which is important in cost containment.

Exporting a technical skills evaluation technology to other sites.

BACKGROUND: The Objective Structured Assessment of Technical Skill (OSATS) is a multistation performance-based examination that assesses the technical skills of surgery residents. This study explores the implementation issues involved in remote administration of the OSATS focusing on feasibility and the psychometric properties of the examination. METHODS: An eight-station OSATS was administered to surgical residents in Los Angeles and Chicago. The University of Toronto and the local institutions shared responsibility for organization and administration of the examination. RESULTS: There was good reliability for both the checklist (alpha = 0.68 for LA, 0.73 for Chicago) and global rating forms (alpha = 0.82 for both sites). Both iterations also showed evidence of construct validity, with a significant effect of training year for the checklist and global rating forms at both sites (analysis of variance: F = 8.66 to 19.93, P <0.01). Despite some challenges, the model of central organization and peripheral delivery was effective for the administration of the examinations. CONCLUSIONS: Two iterations of the OSATS at remote sites demonstrated psychometric properties that are highly consistent with previously reported data suggesting that the examination is portable. Both faculty and residents indicated satisfaction with the examination experience. A model of central administration with peripheral delivery was feasible and effective.

The standardized vascular clinic: an alternative to the traditional ambulatory setting.

PURPOSE: To investigate the effectiveness of a standardized vascular clinic (SVC) in teaching diagnostic and management skills for common vascular problems, as compared with that of the traditional ambulatory setting. METHODS: Third-year medical students participating in the required surgical clerkship participated in this study. Students were randomly assigned to attend either a 4-hour SVC experience (group 1, n = 64) or a 4-hour traditional ambulatory experience (group 2, n = 60). Students completed a satisfaction rating scale and a preencounter and postencounter self-efficacy rating scale at the end of the experience. Student t tests were used to compare the groups in the areas of knowledge acquisition, problem solving, clinical skills and satisfaction with the encounter. Analysis of covariance was used to compare the change between pre and post self-efficacy ratings. RESULTS: Students in group 1 performed significantly higher than students in group 2 in the areas of problem solving, clinical skills, and student satisfaction. They also demonstrated a higher level of confidence in their vascular skills than students assigned to the traditional setting. CONCLUSION: The SVC may be more effective in teaching problem-solving and clinical skills. It also may promote more student satisfaction with the experience and confidence in clinical skills than the traditional ambulatory setting.

Tubulointerstitial nephritis due to a mutant polyomavirus BK virus strain, BKV(Cin), causing end-stage renal disease.

A renal biopsy from a 36-year-old man with AIDS showed a severe tubulointerstitial nephritis with intranuclear inclusions in epithelial cells. Electron microscopy revealed the characteristic findings of a polyomavirus (PyV) infection, and immunofluorescence indicated the presence of BK virus (BKV) antigen. Inoculation of rhesus monkey kidney cell cultures both with urine and with buffy coat blood cells resulted in a cytopathic response which was subsequently confirmed to be due to BKV. Further characterization of the viral DNA from the kidney by PCR amplification and Southern blot analysis with PyV and strain-specific primers and probes indicated that the virus was closely related to the BK(Dun) strain but different in its apparent sequence arrangement. Subsequent cycle sequencing showed a dinucleotide mutation of TG-->AA which substitutes hydrophilic Gln for hydrophobic Leu in a sequence homologous to an origin DNA-binding domain of simian virus 40 T antigen. It is suggested that the mutation and a coding region rearrangement of this strain of BKV designated BKV(Cin) has the potential to alter viral DNA replication and enhance pathogenicity.

Activity of JC virus archetype and PML-type regulatory regions in glial cells.

Sequence variations are seen in the JC virus promoter/enhancer in virus taken from progressive multifocal leukoencephalopathy (PML) brains and it has been hypothesized that the variations arise in the host at some point in the development of PML. These rearrangements may be adaptations for enhanced growth in glial cells; if so, transcription or replication levels should differ between archetypal and rearranged PML-type promoters. The archetype and four PML-type promoters were analysed in human glial cells for early and late transcriptional activity in the absence or presence of virus T antigen, and for DNA replication. CAT reporter expression differed within a fivefold range and the archetype was intermediate in strength to the PML-type regulatory regions. The archetype differed from rearranged promoters in that the late promoter was less responsive to T antigen and the shift from early to late activity with T antigen was less pronounced. All five regulatory regions demonstrated similar levels of DNA replicating activity. Rearrangement of the archetype was not required for activity in glial cells, but the potential for differences in the regulation of the late capsid genes was found.

Selective management of hepatic adenomas.

Hepatic adenomas are uncommon hepatic neoplasms that may be identified after life-threatening hemorrhage, or as an incidental radiologic finding. The incidence of malignant transformation is unknown, and the correct treatment strategy is unclear. We examined our 10-year experience in the management of 12 patients with hepatic adenomas. Eleven adults (mean age of 37.6 years) and one 3-month-old were identified. Nine of 10 adult females (90%) were taking a hormonal preparation at the time of diagnosis. Four patients with tumor sizes of 1.0 to 4.0 cm were observed after cessation of oral contraceptives. Four patients with lesions of 5.5 to 13 cm underwent surgical resection. Three had malignant transformation, and two of the three had increased Alpha-fetoprotein levels. Four patients presented with acute hemorrhage and were treated initially by hepatic arterial embolization. We conclude that management of adenomas should be individualized based on their size and mode of presentation. Patients with lesions less than 5 cm and normal alpha-fetoprotein can be safely observed off oral contraceptives and followed by radiologic imaging. Lesions >5 cm should be considered for surgical resection due to the risk of malignancy. Hepatic arterial embolization is a new approach for acute hemorrhage.

Progressive multifocal leukoencephalopathy: clinical and laboratory observations on a viral induced demyelinating disease in the immunodeficient patient.

Progressive multifocal leukoencephalopathy is a viral-induced demyelinating disease of the central nervous system usually occurring in the immunocompromised individual. The incidence of progressive multifocal leukoencephalopathy has risen sharply over the past decade because of widespread human immunodeficiency virus infection leading to immunodeficiency. This increased incidence of progressive multifocal leukoencephalopathy may also be due to better recognition of its clinical signs, and more rapid and reliable laboratory diagnosis of JC virus, the etiologic agent. There have also been advances in the molecular detection of the JC virus and the identification of variations in the viral genome sequence that may affect its multiplication cycle in different tissues. Clinical and basic research have resulted in a better understanding of the pathogenesis of progressive multifocal leukoencephalopathy and have provided sufficient information to plan new approaches for treatment.

Brain and kidney of progressive multifocal leukoencephalopathy patients contain identical rearrangements of the JC virus promoter/enhancer.

The kidneys of six progressive multifocal leukoencephalopathy (PML) patients were examined by PCR amplification for the presence of JC virus. Amplification of three different areas of the viral genome from multiple samples of each kidney revealed three that were positive for the virus. The use of a PCR-based typing assay on all tissue samples, and cloned sequences from the viral coding region from each positive kidney showed that the same viral genome was present in the kidney as in the brain of the patient. Regulatory region clones all had the archetypal promoter/enhancer structure. However, when PCR fragments from the regulatory region were digested with a restriction enzyme which cuts in region D, the region most often deleted in PML-type promoters, a low level of undigested DNA remained. This DNA refractory to digestion had a rearranged sequence identical to that of the unique rearranged promoter in the brain of each patient.

Type-specific amplification of viral DNA using touchdown and hot start PCR.

Two types of JC virus (JCV) are found in infected brain and kidney tissues. A highly reliable PCR assay to determine viral type in tissue is presented. This type-specific system is analogous to allele-specific PCR used to detect point mutations in cellular genes. Specific amplification of two fragments, using four pairs of type-specific primers, is based on a single nucleotide difference at the 3'-ends of the primers. A combination of three conditions in the PCR reaction was required for specificity: 'hot start', a ramped ('touchdown') cycle profile, and a slightly lowered molar concentration of the specific primers and dNTPs. Efficient yield of PCR product is not lost under these conditions, and even the least selective mismatches (C:A and T:G) provided specific amplification. Type-specific restriction enzyme sites within the amplified fragments confirm type designation.

Human polyomavirus JC promoter/enhancer rearrangement patterns from progressive multifocal leukoencephalopathy brain are unique derivatives of a single archetypal structure.

We have compared the promoter/enhancer structure of human polyomavirus JC (JCV) isolates from 11 progressive multifocal leukoencephalopathy brains. The duplications and deletions of the regulatory region were different in each patient, and usually only one sequence was found in each. The sites of strand breakage in the promoter were not random; four or five preferred sites or areas exist. Alignment of the JCV prototype Mad-1 regulatory region with the unduplicated archetypal structure defines six blocks of sequence, A to F. The preferred sites of strand breaks delineate these regions, although Mad-1 is an unusual promoter containing a break site not observed in other isolates, and an additional site is targeted in several promoters. Region A, containing the TATA box, and the first half of region C, containing several enhancer elements, and region E are consistently retained. Region B, the 23 bp insertion in the archetypal structure (relative to Mad-1) was also retained in all 11 isolates. Region D, the 66 bp insertion, was retained in isolates from three patients. Regions A and D were never duplicated, whereas regions C and E usually were duplicated or triplicated. Variation in the exact point of breakage within the preferred sites, alternative use of the sites in individual promoters and occasional short deletions at other sites result in sequences that are unique in each case. At the same time, the limited choice of break sites and the characteristic fates of the regions themselves result in three broad patterns of repeat sequences. The patterns do not correspond to the viral genotypes 1 and 2 defined by coding region base changes, and do not appear to be a stable feature of the virus. Rather, rearrangements appear to be generated in the host from a basic archetypal sequence.

Two major types of JC virus defined in progressive multifocal leukoencephalopathy brain by early and late coding region DNA sequences.

A 610-bp region of the JC virus (JCV) genome sequenced from brains of 11 progressive multifocal leukoencephalopathy (PML) patients contains 20 sites of point mutations that allow reliable classification of JCV isolates into two types. These type-determining sites were located in the region extending from position 2131 in the VP1 gene, through the intergenic region, to position 2740 in the T antigen gene. At these 20 sites the presence of different nucleotides creates two distinct patterns of substitution, with six isolates having the Type 1 pattern and five having the Type 2 pattern. Only four of the 11 isolates had 'crossovers' to the opposite type consensus DNA sequence at a small number of sites, indicating a very high type specificity. Additionally, three type-determining sites occur in the non-coding region to the left of the origin of replication. Other mutations occurred at random sites, making each strain unique, although one strain, 105, is identical to the Type 1 consensus. The JCV prototype strain Mad-1 was found to be Type 1 and differs from the consensus sequence at five sites. The other previously sequenced JCV strain, GS/B, is Type 2. At three sites out of five in the T antigen C terminus there is a type-specific amino acid substitution; however, none of the type-determining mutations in the VP1 gene cause an amino acid substitution. Comparison of each type's consensus DNA sequence to that of BK virus suggests that Type 2 represents the ancestral JCV sequence from which Type 1 diverged during human evolution.